Viagra ( Sildenafil )

What dose of Cialis should I take

Drinking alcohol with any dosage of Cialis can also decrease its effectiveness, making it harder to achieve an erection.

Cialis dosage

Cialis is also used as a single medication to treat ED and BPH in males who have both conditions.

Cialis comes as oral tablets that are available in several strengths. The active drug in Cialis is tadalafil, which is classified as a phosphodiesterase-5 (PDE5) inhibitor.

Tadalafil is available as a generic medication. A generic drug is an exact copy of the active drug in a brand-name medication. A generic is considered to be as safe and effective as the original drug. Generics also tend to cost less than brand-name drugs.

For details about the dosage of Cialis, including its form, strengths, and how to take the drug, keep reading. For a comprehensive look at Cialis, see this article.

* Sex and gender exist on spectrums. Use of the term “male” in this article refers to sex assigned at birth.

This article describes typical dosages for Cialis provided by the drug’s manufacturer. When taking Cialis, always follow the dosage prescribed by your doctor.

Below you’ll find information about dosage instructions and dosage options for Cialis.

Cialis form and strengths (2.5 mg, 5 mg, 10 mg, 20 mg)

Cialis comes as oral tablets that are available in four strengths: 2.5 milligrams (mg), 5 mg, 10 mg, and 20 mg.

Recommended dosage for Cialis

Typically, your doctor will have you start taking a low dosage of Cialis. Then they’ll adjust it over time to reach the amount that’s right for you. Your doctor will ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Whichever condition Cialis is used to treat, the recommended maximum dose per day is 20 mg. This is the highest dosage that a doctor may prescribe.

Dosage for erectile dysfunction (ED)

For treating erectile dysfunction (ED), Cialis may be used daily or on occasion.

Cialis ED dosage for daily use

For treating ED, the Cialis dosage for daily use is 2.5 mg once per day. You do not have to take Cialis at any specific time before sexual activity when it’s prescribed in this way. You can take your dose at any time of day. But you should try and take it at the same time every day. This helps make sure there’s enough medication in your body for Cialis to be effective.

Your doctor may increase your dose to 5 mg if the 2.5 mg-dose doesn’t work well for you.

Cialis ED dosage for occasional use

The normal dosage of Cialis for occasional use in treating ED is 10 mg taken before sexual activity. If you have side effects with the 10-mg dose, your doctor may prescribe a 5-mg dose. If the 10-mg dose doesn’t work for you, they may increase your treatment to the maximum dosage of 20 mg once per day.

When taken for occasional use to treat ED, the effects of Cialis have been shown to last up to 36 hours.

Regardless of the dose prescribed, you should not take more than one Cialis tablet per day.

Dosage for benign prostatic hyperplasia (BPH)

For treating benign prostatic hyperplasia (BPH), the recommended Cialis dosage is 5 mg taken once per day.

Dosage for ED and BPH

For use as a single medication to treat both ED and BPH, the recommended Cialis dosage is 5 mg taken once per day. You don’t have to take Cialis at any specific time before sexual activity when it’s prescribed in this way. You can take your dose at any time of day. But you should try and take it at the same time every day. This helps make sure there’s enough medication in your body for Cialis to be effective.

Long-term use

Doctors recommend using Cialis as a long-term treatment, even if you take it only on occasion to treat ED. If you and your doctor determine that Cialis is safe and effective for you, you’ll likely take it long term.

Below are some answers to frequently asked questions about Cialis dosages.

Is a 40-mg dose of Cialis safe to take?

No, 40 milligrams (mg) is not a safe dose of Cialis to take. The maximum recommended dosage of Cialis is 20 mg once per day. Taking a dose of Cialis that’s higher than recommended could increase your risk for side effects. These can include serious side effects such as drops in blood pressure or priapism (a painful erection that won’t go away).

It’s important to not take more Cialis than the dose your doctor recommends. You should take Cialis exactly as it’s prescribed for you. If you have other questions about Cialis doses, talk with your doctor or pharmacist.

What’s the Cialis dosage for someone who’s 70 years old?

Cialis dosages for someone who is age 70 years (and older adults in general) are the same as those for other adults. Details about these dosages are in the “Cialis dosage” section above.

Older adults may be more sensitive to the effects of Cialis. Because of this, your doctor may decide to prescribe a lower dose than usual when you start taking Cialis. Then, if needed, they can adjust it over time to reach the amount that’s right for you.

If you have additional questions about the use of Cialis in older adults, talk with your doctor or pharmacist.

It’s important that you do not use more Cialis than your doctor prescribes. For some medications, taking more than the recommended amount may lead to side effects or overdose.

If you take more than the recommended amount of Cialis

Call your doctor right away if you believe you’ve taken too much Cialis. Another option is to call the American Association of Poison Control Centers at 800-222-1222 or use its online tool. If you have severe symptoms, immediately call 911 or your local emergency number, or go to the nearest emergency room.

The Cialis dosage your doctor prescribes will depend on several factors. These include:

  • the type and severity of the condition you’re using Cialis to treat
  • how often you take Cialis
  • your age
  • other medications you may take
  • side effects that you may have from taking Cialis
  • how well the medication is working for you, if used to treat erectile dysfunction (ED)

Other medical conditions you have can also affect your Cialis dosage.

Dosage adjustments

If you have kidney or liver problems, your doctor may adjust your Cialis dosage. If the kidney or liver problems are mild or moderate, you’ll likely need a lower dose of the drug than usual. Keep in mind that if you have severe liver problems, you should not use Cialis. The drug is also not recommended for daily use if you have severe kidney problems.

Your doctor can determine the severity of your kidney or liver problems and whether Cialis is a safe medication for you to take. Talk with your doctor or pharmacist if you have questions about Cialis dosage adjustments.

Cialis comes as oral tablets. You can take them with or without food.

If you take Cialis for occasional use to treat erectile dysfunction (ED), you should take your dose before sexual activity. When taken for occasional use to treat ED, the effects of Cialis have been shown to last up to 36 hours.

If you take Cialis daily for ED, benign prostatic hyperplasia (BPH), or both ED and BPH, you can take your dose at any time of day. But you should try and take your dose at the same time every day.

You should not take more than one dose of Cialis per day. Be sure not to take more of the drug than your doctor prescribes for you. Doing so may lead to serious side effects from Cialis.

If you have questions about how to take Cialis, talk with your doctor or pharmacist.

If you forget to take a once-daily dose of Cialis, try to take it as soon as you remember. But keep in mind that you should not take more than one Cialis dose per day. So if you missed a dose yesterday, skip that dose and take your next scheduled dose of Cialis.

It’s important that you do not take more Cialis than your doctor prescribes for you. Doing so may lead to serious side effects from the drug.

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm or timer on your phone or downloading a reminder app. A kitchen timer can work, too.

The dosages in this article are typical dosages provided by the drug manufacturer. If your doctor recommends Cialis for you, they will prescribe the proper dosage for you. Always follow the dosage that your doctor prescribes for you.

As with any drug, never change your dosage of Cialis without your doctor’s recommendation. If you have questions about the dosage of Cialis that’s right for you, talk with your doctor.

Besides learning about dosage, you may want other information about Cialis. These additional articles might be helpful:

  • More about Cialis. For information about other aspects of Cialis, refer to this article.
  • Drug comparison. To find out how Cialis compares with Viagra, Levitra, and Stendra, read this article.
  • Details about your condition. For details about your condition, visit our men’s health hub. You can also see our lists of erectile dysfunction articles and prostate articles.

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Last medically reviewed on July 16, 2021

How we reviewed this article:

Medical News Today has strict sourcing guidelines and draws only from peer-reviewed studies, academic research institutions, and medical journals and associations. We avoid using tertiary references. We link primary sources — including studies, scientific references, and statistics — within each article and also list them in the resources section at the bottom of our articles. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.

What dose of Cialis should I take?

Tadalafil is an Erectile Dysfunction (ED) treatment used by men who have difficulty in achieving and maintaining an erection. It is the generic (non-branded) version of Cialis, which means they both contain the same active ingredient (tadalafil), and are as good as each other. Tadalafil is commonly referred to as “generic Cialis”. Cialis and tadalafil are the same, and work in the same way. Tadalafil tablets are available in 4 different strengths, 2.5mg, 5mg, 10mg and 20mg. Tadalafil 2.5mg and 5mg are taken daily and provide a continuous effect. Tadalafil 10mg and 20mg are taken when required. If you are taking the 10mg and 20mg strength, you should take one tablet around 30 minutes before sexual activity. The effects of tadalafil can last for up to 36 hours.

The weekend pill

Tadalafil 20mg and 10mg are commonly referred to as “the weekend pill”. This is because they have a long-lasting effect of up to 36 hours. This means you can take a tablet on a Friday night, and it can still be effective until Sunday morning.

How Cialis works

Tadalafil works by increasing blood flow to the penis when you are sexually stimulated. The increase in blood flow helps to get and keep an erection. You should take one tablet around half an hour before sex. Tadalafil peaks at around the 2 hour mark, so you may wish to take a tablet slightly earlier, as tadalafil is most effective after 2 hours. Tablets can be taken with a glass of water. You don’t need to worry about taking these pills on an empty stomach. Unlike Viagra, food does not affect the absorption of tadalafil.

Cialis starting dose

  • Take one tablet at a time
  • Take a tablet around half an hour before you plan to have sex
  • Avoid drinking alcohol with tadalafil as this can negatively affect your ability to get erection. Alcohol may increase the chances of experiencing common side effects such as headaches.
  • Do not take more than one tablet in a 24 hour period

Tadalafil tablets, will only work when you are sexually aroused, and treatment alone (or any other type of ED tablets) will not increase sexual desire (libido). If you are experiencing a loss of sexual drive, you should see your doctor as there may be an underlying health condition causing ED. The effects of tadalafil 10mg tablets can last for up to 36 hours, and within this timeframe, you should be able to get an erection when you are sexually stimulated.

The starting dose of Cialis did not work for me. What should I do?

If tadalafil 10mg is not working, there are a few things you can do:

  • Try taking a tablet another 7 times. According to UK national guidelines, you should try taking ED tablets on 8 separate occasions, before increasing the dose or trying another treatment. It can take time for you to get used to the idea of using a tablet to help with ED
  • Speak to your doctor or pharmacist about increasing the strength to tadalafil 20mg
  • Consider using a different ED tablet such as sildenafil or vardenafil

Can I take two Cialis 10mg tablets?

You can safely take two tadalafil 10mg tablets to give you 20mg. You should only do this if your doctor of pharmacist has prescribed you with tadalafil 20mg. The maximum dose of tadalafil that you should take is 20mg within a 24 hour period.

Taking the higher dose of Cialis

You doctor or pharmacist may prescribe tadalafil 20mg initially, although it’s more common to start with tadalafil 10mg and work your way up to 20mg if you have limited success. This lowers the chances of experiencing side effects.

Tadalafil 20mg tablets are taken in the same way as the lower strength 10mg tablets, 30 minutes before sex. There is not too much of a difference between tadalafil 20mg and 10mg. However, clinical trials have shown the 20mg dose to be around 10% more effective than the 10mg dose.

The effects of tadalafil 20mg do not last longer than the 10mg strength, but they may be stronger. This can increase the chances of experiencing side effects.

Common side effects of tadalafil include headaches, facial flushing, indigestion, muscle pain and a stuffy nose. Not everyone experiences side effects, however, the chances increase if you take tadalafil 20mg.

The higher dose of Cialis did not work for me. What should I do?

If the 20mg tablets are not effective, you should speak to your doctor or pharmacist. As is the case with all ED tablets, you should try taking these pills on 8 separate occasions, before trying another ED medication.

If you have followed this advice, and still find tadalafil tablets to be ineffective, you may wish to speak to your doctor or pharmacist about trying an alternative ED treatment.

Most alternative ED tablets belong to the same class of drugs, known as PDE5 inhibitors. This means that they will act in the same way. In certain instances, counselling may be helpful, especially if ED is caused by anxiety. You should speak to a healthcare professional to find our if your ED is psychological, or physical.

Cialis overdose

You should not take more than 20mg of tadalafil within a 24 hour period. This is because 20mg is the highest licensed dose to treat ED. Taking more than 20mg can increase the likelihood of experiencing serious side effects, such as a drop in blood pressure, which can cause headache and dizziness. It can also increase the chances of experiencing other potentially harmful side effects such as priapism.

Can I take Cialis as a daily dose?

Tadalafil 10mg and 20mg are safe to take daily for most men. You should check this with your doctor or pharmacist to make sure. Tadalafil tablets are also available in lower strengths, 2.5mg and 5mg. These tablets are also known as “tadalafil daily”. The 2.5mg and 5mg strength are usually more appropriate to be taken every day, as the dose is smaller, resulting in a lower chance of experiencing side effects.

Tadalafil or sildenafil, which one should I choose?

No ED treatment can make you last longer in bed, however, tadalafil has an advantage over sildenafil as it has a longer duration of action. This means that you can benefit from more sexual encounters within a longer time frame (up to 36 hours). Sildenafil has a shorter duration of action, with the effects lasting up to 4 hours. Tadalafil tablets also work faster than sildenafil, and can take up to 30 minutes to kick in as opposed to sildenafil, which takes 1 hour to kick in. Tadalafil can also be taken after a meal as food does not affect absorption, unlike sildenafil, where the onset of action can be delayed by food.

Having said this, these points are theoretical and ultimately, it comes down to personal preference and what you find suits you. Individuals are likely to experience different responses to different ED tablets, and there is no correct answer for what treatment is best. You may prefer tadalafil or sildenafil, depending on your response to treatment.

So, what dose of Cialis should I take?

Studies have shown that tadalafil is an effective treatment for erectile dysfunction, allowing patients of all ages to regain a satisfactory sex life. The 10mg strength is usually prescribed if you are taking tadalafil tablets for the first time, and the strength is generally only increased if need be. Both the 10mg and 20mg dose take around 30 minutes to kick in, with the effects lasting for up to 36 hours. If you engage in sexual activity more than 3 times a week, you may wish to explore the daily dose of tadalafil. It has a continuous effect and allows you to enjoy a spontaneous sex life.

It is important to note that these pills are not recreational drugs and are only for use if you are experiencing ED. Certain types of cardiovascular disease, heart disease and other health conditions may mean that ED medication is not appropriate. You can speak to your GP about alternative ED treatments such as penile implants or penis pumps.

Whilst all of our content is written and reviewed by healthcare professionals, it is not intended to be substituted for or used as medical advice. If you have any questions or concerns about your health, please speak to your doctor.

Cialis Dosage Guide

Cialis is a popular and effective treatment for erectile dysfunction that contains tadalafil. When taken at least 30 minutes before sex, it helps you achieve and keep a strong erection so you can have a normal, healthy sex life.

But Cialis comes in a variety of different dosages. Smaller dosages of Cialis oral tablets, 2.5mg and 5mg, are perfect for daily use. If you have sex on a regular basis, then Cialis daily is a good option for you. Larger dosages of Cialis, on the other hand, such as the 10mg and 20mg oral tablets, are better for those who have sex less frequently (fewer than 2 – 3 times per week).

To help you find the right dosage of Cialis for you, we’ve compiled this useful guide. It looks at the recommended dosage per person, how often you should take Cialis for best results, what happens if you take more than one tablet of Cialis, and more.

General dose information

Cialis comes in four different dosages:

The smaller dosages of 2.5mg and 5mg are known as the Cialis Once Daily Tablet. These are prescribed to men who are looking to have spontaneous sex and do not wish to plan their intercourse. These tablets are taken once a day, every day.

The 10mg and 20mg dosages of Cialis, on the other hand, are known as “the weekend pill”. They last for 36 hours and are prescribed to men who have sex less regularly. Regular Cialis is not taken every day. Instead, it is taken as required allowing you to participate in sexual activity at any point during a 36-hour period, hence its nickname “the weekend pill”.

Each dosage of Cialis should be taken at least 30 minutes before sex, but it may take longer to take effect depending on the person.

If you need more information on this treatment and how it works, then read our ‘what is Cialis?’ guide.

How to use Cialis and how often should it be taken?

The correct usage of Cialis depends on the type of Cialis you’re taking and the frequency with which you have sex.

The 2.5mg and 5mg dosage tablets of Cialis should be taken once daily at the same time each day, one tablet per day. Avoid skipping doses of Cialis, and never take more than one tablet per day, even if you have missed a day.

The 10mg and 20mg dosage tablets of Cialis should be taken as required, at least 30 minutes before sex. They can help to get a better erection for up to 36 hours, so you should not take more than one Cialis tablet in 36 hours. While Cialis can be taken with food, it should not be taken with excessive alcohol as this can make it less effective.

Your doctor may change your prescription depending on the severity of your erectile dysfunction.

Using Cialis with food

Unlike Viagra or sildenafil, Cialis can be taken with or without food. It can be taken after a meal, or on an empty stomach.

Some studies suggest that you should not eat grapefruit or drink grapefruit juice while taking Cialis unless approved by your doctor. This is because this may increase the risk of Cialis’ side effects occurring. If you are unsure, always speak with your doctor first.

The recommended dosage of Cialis

The recommended dosage of Cialis depends on how often you have sex, how serious your ED is, and the type of Cialis your doctor has prescribed you.

If you have sex regularly (at least twice a week), most doctors will start you on the 2.5mg dosage for Cialis Daily. If you have sex more often than this, or you find it is not as effective as you hoped, your doctor might increase your dosage to Cialis 5mg.

If you have sex less frequently than twice a week, your doctor will likely start you on 10mg for Cialis on demand. If the 10mg dosage of Cialis does not work as expected, your doctor might increase your dosage to 20mg instead.

It also depends on your lifestyle and the spontaneity at which you want to enjoy sexual activity. For instance, the Once Daily tablet will allow you to participate in sexual activity any time any day.

Rather than trying to gauge the dosage for yourself the best course of action is to speak to a qualified physician. The Independent Pharmacy provides a free consultation with a qualified UK GP before you buy Cialis from us.

Storing and handling Cialis

Cialis should be stored at room temperature out of direct sunlight. This ensures that your Cialis stays effective at treating your erectile dysfunction. Always keep Cialis out of reach of children.

Cialis and Viagra dosages compared

Cialis and Viagra are both effective treatments for impotence. However, each comes in different dosages and work in different ways.

Whereas Cialis comes in 4 doses, Viagra comes in the following 3 dosages:

The recommended dosage of Viagra is 50mg, at least one hour before sex. However, you can generally take Viagra anywhere between 30 minutes and four hours before sex. The effects of Viagra’s dosages last for around four hours, although this may vary depending on the user.

For more information on the difference between Viagra and Cialis, read our Cialis vs Viagra comparison guide here.

Cialis and alcohol

While you can drink while taking any dosage of Cialis, it is not recommended. Drinking excessive amounts of alcohol can increase your heart rate and reduce your blood pressure. This can increase the risk of experiencing Cialis’ side effects, such as dizziness or headaches.

Drinking alcohol with any dosage of Cialis can also decrease its effectiveness, making it harder to achieve an erection.

What happens if you take more than one Cialis tablet?

You should never take more than one Cialis tablet at a time. The maximum recommended dose for 2.5mg and 5mg Cialis tablets is once per 24 hours, and once per 36 hours for 10mg and 20mg Cialis tablets.

If you exceed the maximum recommended dose of Cialis, you put yourself at serious risk. It is more likely you will experience the more severe side effects of Cialis. As a result, you will require immediate medical attention.

Visit this page for more information on Cialis side effects.

How to take Cialis for best results

To get the best results from your Cialis dosage of 10mg and 20mg tablets, it is recommended that you give it enough time to take effect. As results of Cialis are not instant, you should take it no less than 30 minutes before sex, or even longer if possible.

That said, you should also expect to take it slow. Don’t rush yourself into sex — let yourself become naturally aroused and take time getting into the mood.

Another way to get the best results from your dosage of Cialis is by avoiding alcohol. Alcohol makes it more difficult to get an erection and increases the risk of side effects occurring.

Avoiding mixing any dosage of Cialis with nitrates, such as isosorbide mononitrate or GTN spray. These can cause a significant drop in blood pressure, which at best decreases the effectiveness of Cialis and at worst can cause serious health issues.

For more general advice on erectile dysfunction, read our ED advice guides here.

Summary

Cialis comes in a range of four dosages, each of which is prescribed according to your unique situation and requirements.

If you need to get an erection at least twice a week, Cialis daily tablets of 2.5mg and 5mg are for you. If you have sex less regularly, then the higher dosages of 10mg and 20mg Cialis on demand are a better option.

The advice above should give you a good idea of what Cialis dosage is right for you. If you feel like Cialis is the right option for your ED treatment, The Independent Pharmacy sells both Cialis Once Daily tablets and Cialis 10mg and 20mg tablets.

Simply complete our free online consultation for our in-house UK doctors to approve. Once you’ve approved, we’ll dispatch your Cialis to you within the next few working days in plain packaging for your discretion.

Sources

Should you take a daily erectile dysfunction pill?

The drug Cialis is popular because you can take it every day. But should you?

Tadalafil (Cialis) is one of the most popular erectile dysfunction (ED) drugs. Its major appeal? The drug comes in low-dose versions that can be taken daily. This means you can have sex at any time, rather than needing to take a pill from time to time as needed like other ED brands.

The starting dose for daily-use Cialis is 2.5 milligrams (mg). If that doesn’t work, you can increase your daily dose up to 5 mg. But is this the right approach for you—or are you better off with traditional ED drugs like Viagra, Levitra, or even the nondaily version of Cialis? If you are contemplating Cialis for daily use, consider these questions and then discuss it with your doctor:

  • How often do you have sex? If it’s two or more times a week, a daily pill might be a reasonable choice, since the drug continually circulates in your bloodstream.
  • How important is spontaneity? A daily pill clears the path for sex at any time—if the drug works for you. (Remember, just like other ED drugs, it may not work for everyone). On the other hand, the 36-hour window offered by the nondaily version of Cialis might offer enough spontaneity.
  • Have side effects of your current ED pill been bothering you? Taking a daily low-dose pill may reduce side effects, though it may reduce effectiveness as well. In studies, the most common daily pill side effects were headache, muscle pain, indigestion, and back pain.
  • How much alcohol do you drink? Men taking Cialis for daily use can experience a worrisome drop in blood pressure if they drink too much.
  • What other medications do you take? Ask your doctor if any medications or supplements you take might interact with a daily erectile dysfunction pill, including blood pressure drugs, antifungal drugs, and HIV drugs. Also, men taking nitrate medications are advised not to take any ED drugs.
  • How important is cost? While the manufacturer suggests that a 30-day supply of daily Cialis should cost about the same as eight pills of 36-hour Cialis a month, there’s no way to enforce this. Check your insurance policy and local pharmacies for price information.

By Matthew Solan
Executive Editor, Harvard Men’s Health Watch

Image: yacobchuk/Getty Images

Disclaimer:

As a service to our readers, Harvard Health Publishing provides access to our library of archived content. Please note the date of last review or update on all articles.

No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician.

Cialis

Cialis is a prescription medicine used to treat the symptoms of erectile dysfunction. Cialis may be used alone or with other medications.

Cialis belongs to a class of drugs called Phosphodiesterase-5 Enzyme Inhibitors.

It is not known if Cialis is safe and effective in children.

What are the possible side effects of Cialis?

Cialis may cause serious side effects including:

  • chest pain,
  • pain spreading to the jaw or shoulder,
  • nausea,
  • sweating,
  • vision changes,
  • sudden vision loss,
  • ringing in your ears,
  • sudden hearing loss, and
  • an erection that is painful or lasts longer than 4 hours

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Cialis include:

  • headache,
  • flushing (warmth, redness or tingly feeling),
  • nausea,
  • upset stomach,
  • runny or stuffy nose,
  • muscle pain,
  • back pain, and
  • pain in your arms or legs

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Cialis. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

DESCRIPTION

CIALIS (tadalafil) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Tadalafil has the empirical formula C22H19N3O4 representing a molecular weight of 389.41. The structural formula is:

The chemical designation is pyrazino[1′;,2′;:1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-. It is a crystalline solid that is practically insoluble in water and very slightly soluble in ethanol.

CIALIS is available as almond-shaped tablets for oral administration. Each tablet contains 2.5, 5, 10, or 20 mg of tadalafil and the following inactive ingredients: croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, talc, titanium dioxide, and triacetin.

INDICATIONS

Erectile Dysfunction

CIALIS® is indicated for the treatment of erectile dysfunction (ED).

Benign Prostatic Hyperplasia

CIALIS is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).

Erectile Dysfunction And Benign Prostatic Hyperplasia

CIALIS is indicated for the treatment of ED and the signs and symptoms of BPH (ED/BPH).

Limitation Of Use

If CIALIS is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks because the incremental benefit of CIALIS decreases from 4 weeks until 26 weeks, and the incremental benefit of CIALIS beyond 26 weeks is unknown [see Clinical Studies].

DOSAGE AND ADMINISTRATION

Do not split CIALIS tablets; entire dose should be taken.

CIALIS For Use As Needed For Erectile Dysfunction

  • The recommended starting dose of CIALIS for use as needed in most patients is 10 mg, taken prior to anticipated sexual activity.
  • The dose may be increased to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. The maximum recommended dosing frequency is once per day in most patients.
  • CIALIS for use as needed was shown to improve erectile function compared to placebo up to 36 hours following dosing. Therefore, when advising patients on optimal use of CIALIS, this should be taken into consideration.

CIALIS For Once Daily Use For Erectile Dysfunction

  • The recommended starting dose of CIALIS for once daily use is 2.5 mg, taken at approximately the same time every day, without regard to timing of sexual activity.
  • The CIALIS dose for once daily use may be increased to 5 mg, based on individual efficacy and tolerability.

CIALIS For Once Daily Use For Benign Prostatic Hyperplasia

  • The recommended dose of CIALIS for once daily use is 5 mg, taken at approximately the same time every day.
  • When therapy for BPH is initiated with CIALIS and finasteride, the recommended dose of CIALIS for once daily use is 5 mg, taken at approximately the same time every day for up to 26 weeks.

CIALIS For Once Daily Use For Erectile Dysfunction And Benign Prostatic Hyperplasia

The recommended dose of CIALIS for once daily use is 5 mg, taken at approximately the same time every day, without regard to timing of sexual activity.

Use With Food

CIALIS may be taken without regard to food.

Use In Specific Populations

Renal Impairment
  • Creatinine clearance 30 to 50 mL/min: A starting dose of 5 mg not more than once per day is recommended, and the maximum dose is 10 mg not more than once in every 48 hours.
  • Creatinine clearance less than 30 mL/min or on hemodialysis: The maximum dose is 5 mg not more than once in every 72 hours [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Erectile Dysfunction
Benign Prostatic Hyperplasia And Erectile Dysfunction/Benign Prostatic Hyperplasia
  • Creatinine clearance 30 to 50 mL/min: A starting dose of 2.5 mg is recommended. An increase to 5 mg may be considered based on individual response.
  • Creatinine clearance less than 30 mL/min or on hemodialysis: CIALIS for once daily use is not recommended [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Hepatic Impairment
  • Mild or moderate (Child Pugh Class A or B): The dose should not exceed 10 mg once per day. The use of CIALIS once per day has not been extensively evaluated in patients with hepatic impairment and therefore, caution is advised.
  • Severe (Child Pugh Class C): The use of CIALIS is not recommended [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
  • Mild or moderate (Child Pugh Class A or B): CIALIS for once daily use has not been extensively evaluated in patients with hepatic impairment. Therefore, caution is advised if CIALIS for once daily use is prescribed to these patients.
  • Severe (Child Pugh Class C): The use of CIALIS is not recommended [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].

Concomitant Medications

Nitrates

Concomitant use of nitrates in any form is contraindicated [see CONTRAINDICATIONS].

Alpha-Blockers

ED — When CIALIS is coadministered with an alpha-blocker in patients being treated for ED, patients should be stable on alpha-blocker therapy prior to initiating treatment, and CIALIS should be initiated at the lowest recommended dose [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].

BPH — CIALIS is not recommended for use in combination with alpha-blockers for the treatment of BPH [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].

CYP3A4 Inhibitors

CIALIS for Use as Needed — For patients taking concomitant potent inhibitors of CYP3A4, such as ketoconazole or ritonavir, the maximum recommended dose of CIALIS is 10 mg, not to exceed once every 72 hours [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].

CIALIS for Once Daily Use — For patients taking concomitant potent inhibitors of CYP3A4, such as ketoconazole or ritonavir, the maximum recommended dose is 2.5 mg [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].

HOW SUPPLIED

Dosage Forms And Strengths

Four strengths of almond-shaped tablets are available in different sizes and different shades of yellow:

2.5 mg tablets debossed with “C 2½”
5 mg tablets debossed with “C 5”
10 mg tablets debossed with “C 10”
20 mg tablets debossed with “C 20”

Storage And Handling

CIALIS (tadalafil) is supplied as follows:

Four strengths of almond-shaped tablets are available in different sizes and different shades of yellow, and supplied in the following package sizes:

Blisters of 2 x 15 NDC 0002-4465-34

Bottles of 30 NDC 0002-4462-30
Blisters of 2 x 15 NDC 0002-4462-34

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Marketed by: Lilly USA, LLC Indianapolis, IN 46285, USA www.cialis.com. Revised: Feb 2018

QUESTION

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Tadalafil was administered to over 9000 men during clinical trials worldwide. In trials of CIALIS for once daily use, a total of 1434, 905, and 115 were treated for at least 6 months, 1 year, and 2 years, respectively. For CIALIS for use as needed, over 1300 and 1000 subjects were treated for at least 6 months and 1 year, respectively.

CIALIS For Use As Needed For ED

In eight primary placebo-controlled clinical studies of 12 weeks duration, mean age was 59 years (range 22 to 88) and the discontinuation rate due to adverse events in patients treated with tadalafil 10 or 20 mg was 3.1%, compared to 1.4% in placebo treated patients.

When taken as recommended in the placebo-controlled clinical trials, the following adverse reactions were reported (see Table 1) for CIALIS for use as needed:

Table 1: Treatment-Emergent Adverse Reactions Reported by ≥2% of Patients Treated with CIALIS (10 or 20 mg) and More Frequent on Drug than Placebo in the Eight Primary Placebo-Controlled Clinical Studies (Including a Study in Patients with Diabetes) for CIALIS for Use as Needed for ED

Adverse Reaction Placebo
(N=476)
Tadalafil 5 mg
(N=151)
Tadalafil 10 mg
(N=394)
Tadalafil 20 mg
(N=635)
Headache 5% 11% 11% 15%
Dyspepsia 1% 4% 8% 10%
Back pain 3% 3% 5% 6%
Myalgia 1% 1% 4% 3%
Nasal congestion 1% 2% 3% 3%
Flushing a 1% 2% 3% 3%
Pain in limb 1% 1% 3% 3%
a The term flushing includes: facial flushing and flushing
CIALIS For Once Daily Use For ED

In three placebo-controlled clinical trials of 12 or 24 weeks duration, mean age was 58 years (range 21 to 82) and the discontinuation rate due to adverse events in patients treated with tadalafil was 4.1%, compared to 2.8% in placebo-treated patients.

The following adverse reactions were reported (see Table 2) in clinical trials of 12 weeks duration:

Table 2: Treatment-Emergent Adverse Reactions Reported by ≥2% of Patients Treated with CIALIS for Once Daily Use (2.5 or 5 mg) and More Frequent on Drug than Placebo in the Three Primary Placebo-Controlled Phase 3 Studies of 12 weeks Treatment Duration (Including a Study in Patients with Diabetes) for CIALIS for Once Daily Use for ED

Adverse Reaction Placebo
(N=248)
Tadalafil 2.5 mg
(N=196)
Tadalafil 5 mg
(N=304)
Headache 5% 3% 6%
Dyspepsia 2% 4% 5%
Nasopharyngitis 4% 4% 3%
Back pain 1% 3% 3%
Upper respiratory tract infection 1% 3% 3%
Flushing 1% 1% 3%
Myalgia 1% 2% 2%
Cough 0% 4% 2%
Diarrhea 0% 1% 2%
Nasal congestion 0% 2% 2%
Pain in extremity 0% 1% 2%
Urinary tract infection 0% 2% 0%
Gastroesophageal reflux disease 0% 2% 1%
Abdominal pain 0% 2% 1%

The following adverse reactions were reported (see Table 3) over 24 weeks treatment duration in one placebo-controlled clinical study:

Table 3: Treatment-Emergent Adverse Reactions Reported by ≥2% of Patients Treated with CIALIS for Once Daily Use (2.5 or 5 mg) and More Frequent on Drug than Placebo in One Placebo-Controlled Clinical Study of 24 Weeks Treatment Duration for CIALIS for Once Daily Use for ED

Adverse Reaction Placebo
(N=94)
Tadalafil 2.5 mg
(N=96)
Tadalafil 5 mg
(N=97)
Nasopharyngitis 5% 6% 6%
Gastroenteritis 2% 3% 5%
Back pain 3% 5% 2%
Upper respiratory tract infection 0% 3% 4%
Dyspepsia 1% 4% 1%
Gastroesophageal reflux disease 0% 3% 2%
Myalgia 2% 4% 1%
Hypertension 0% 1% 3%
Nasal congestion 0% 0% 4%
CIALIS For Once Daily Use For BPH And For ED And BPH

In three placebo-controlled clinical trials of 12 weeks duration, two in patients with BPH and one in patients with ED and BPH, the mean age was 63 years (range 44 to 93) and the discontinuation rate due to adverse events in patients treated with tadalafil was 3.6% compared to 1.6% in placebo-treated patients. Adverse reactions leading to discontinuation reported by at least 2 patients treated with tadalafil included headache, upper abdominal pain, and myalgia. The following adverse reactions were reported (see Table 4).

Table 4: Treatment-Emergent Adverse Reactions Reported by ≥1% of Patients Treated with CIALIS for Once Daily Use (5 mg) and More Frequent on Drug than Placebo in Three Placebo-Controlled Clinical Studies of 12 Weeks Treatment Duration, including Two Studies for CIALIS for Once Daily Use for BPH and One Study for ED and BPH

Adverse Reaction Placebo
(N=576)
Tadalafil 5 mg
(N=581)
Headache 2.3% 4.1%
Dyspepsia 0.2% 2.4%
Back pain 1.4% 2.4%
Nasopharyngitis 1.6% 2.1%
Diarrhea 1.0% 1.4%
Pain in extremity 0.0% 1.4%
Myalgia 0.3% 1.2%
Dizziness 0.5% 1.0%

Across placebo-controlled studies with CIALIS for use as needed for ED, diarrhea was reported more frequently in patients 65 years of age and older who were treated with CIALIS (2.5% of patients) [see Use In Specific Populations].

Across all studies with any CIALIS dose, reports of changes in color vision were rare (

Body as a Whole – asthenia, face edema, fatigue, pain, peripheral edema

Digestive – abnormal liver function tests, dry mouth, dysphagia, esophagitis, gastritis, GGTP increased, loose stools, nausea, upper abdominal pain, vomiting, gastroesophageal reflux disease, hemorrhoidal hemorrhage, rectal hemorrhage

Nervous – dizziness, hypesthesia, insomnia, paresthesia, somnolence, vertigo

Renal and Urinary – renal impairment

Skin and Appendages – pruritus, rash, sweating

Ophthalmologic – blurred vision, changes in color vision, conjunctivitis (including conjunctival hyperemia), eye pain, lacrimation increase, swelling of eyelids

Otologic – sudden decrease or loss of hearing, tinnitus

Urogenital – erection increased, spontaneous penile erection

Postmarketing Experience

The following adverse reactions have been identified during post approval use of CIALIS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion either due to their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors.

Cardiovascular And Cerebrovascular

Serious cardiovascular events, including myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations, and tachycardia, have been reported postmarketing in temporal association with the use of tadalafil. Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of CIALIS without sexual activity. Others were reported to have occurred hours to days after the use of CIALIS and sexual activity. It is not possible to determine whether these events are related directly to CIALIS, to sexual activity, to the patient’s underlying cardiovascular disease, to a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONS].

Body As A Whole – hypersensitivity reactions including urticaria, Stevens-Johnson syndrome, and exfoliative dermatitis

Nervous – migraine, seizure and seizure recurrence, transient global amnesia
Ophthalmologic – visual field defect, retinal vein occlusion, retinal artery occlusion Non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported rarely postmarketing in temporal association with the use of PDE5 inhibitors, including CIALIS. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking [see WARNINGS AND PRECAUTIONS].

Otologic – Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including CIALIS. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of CIALIS, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors [see WARNINGS AND PRECAUTIONS].

Urogenital – priapism [see WARNINGS AND PRECAUTIONS].

DRUG INTERACTIONS

Potential For Pharmacodynamic Interactions With CIALIS

Nitrates

Administration of CIALIS to patients who are using any form of organic nitrate, is contraindicated. In clinical pharmacology studies, CIALIS was shown to potentiate the hypotensive effect of nitrates. In a patient who has taken CIALIS, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last dose of CIALIS before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring [see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and CLINICAL PHARMACOLOGY].

Alpha-Blockers

Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including CIALIS, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. Clinical pharmacology studies have been conducted with coadministration of tadalafil with doxazosin, tamsulosin or alfuzosin. [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY].

Antihypertensives

PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. Clinical pharmacology studies were conducted to assess the effect of tadalafil on the potentiation of the blood-pressure-lowering effects of selected antihypertensive medications (amlodipine, angiotensin II receptor blockers, bendrofluazide, enalapril, and metoprolol). Small reductions in blood pressure occurred following coadministration of tadalafil with these agents compared with placebo. [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Alcohol

Both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Substantial consumption of alcohol (e.g., 5 units or greater) in combination with CIALIS can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Tadalafil did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations. [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Potential For Other Drugs To Affect CIALIS

Antacids

Simultaneous administration of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduced the apparent rate of absorption of tadalafil without altering exposure (AUC) to tadalafil.

H2 Antagonists (e.g. Nizatidine)

An increase in gastric pH resulting from administration of nizatidine had no significant effect on pharmacokinetics.

Cytochrome P450 Inhibitors

CIALIS is a substrate of and predominantly metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase tadalafil exposure.

Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20 mg single-dose exposure (AUC) by 312% and Cmax by 22%, relative to the values for tadalafil 20 mg alone. Ketoconazole (200 mg daily) increased tadalafil 10-mg single-dose exposure (AUC) by 107% and Cmax by 15%, relative to the values for tadalafil 10 mg alone [see DOSAGE AND ADMINISTRATION].

Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure.

Ritonavir (500 mg or 600 mg twice daily at steady state), an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil 20-mg single-dose exposure (AUC) by 32% with a 30% reduction in Cmax, relative to the values for tadalafil 20 mg alone. Ritonavir (200 mg twice daily), increased tadalafil 20-mg single-dose exposure (AUC) by 124% with no change in Cmax, relative to the values for tadalafil 20 mg alone. Although specific interactions have not been studied, other HIV protease inhibitors would likely increase tadalafil exposure [see DOSAGE AND ADMINISTRATION].

Cytochrome P450 Inducers

Studies have shown that drugs that induce CYP3A4 can decrease tadalafil exposure.

Rifampin (600 mg daily), a CYP3A4 inducer, reduced tadalafil 10-mg single-dose exposure (AUC) by 88% and Cmax by 46%, relative to the values for tadalafil 10 mg alone. Although specific interactions have not been studied, other CYP3A4 inducers, such as carbamazepine, phenytoin, and phenobarbital, would likely decrease tadalafil exposure. No dose adjustment is warranted. The reduced exposure of tadalafil with the coadministration of rifampin or other CYP3A4 inducers can be anticipated to decrease the efficacy of CIALIS for once daily use; the magnitude of decreased efficacy is unknown.

Potential For CIALIS To Affect Other Drugs

Aspirin

Tadalafil did not potentiate the increase in bleeding time caused by aspirin.

Cytochrome P450 Substrates

CIALIS is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms. Studies have shown that tadalafil does not inhibit or induce P450 isoforms CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1.

Tadalafil had no significant effect on the pharmacokinetics of theophylline. When tadalafil was administered to subjects taking theophylline, a small augmentation (3 beats per minute) of the increase in heart rate associated with theophylline was observed.

Tadalafil had no significant effect on exposure (AUC) to S-warfarin or R-warfarin, nor did tadalafil affect changes in prothrombin time induced by warfarin.

Tadalafil had no significant effect on exposure (AUC) to midazolam or lovastatin.

P-glycoprotein (e.g. Digoxin)

Coadministration of tadalafil (40 mg once per day) for 10 days did not have a significant effect on the steady-state pharmacokinetics of digoxin (0.25 mg/day) in healthy subjects.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Evaluation of erectile dysfunction and BPH should include an appropriate medical assessment to identify potential underlying causes, as well as treatment options.

Before prescribing CIALIS, it is important to note the following:

Cardiovascular

Physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Therefore, treatments for erectile dysfunction, including CIALIS, should not be used in men for whom sexual activity is inadvisable as a result of their underlying cardiovascular status. Patients who experience symptoms upon initiation of sexual activity should be advised to refrain from further sexual activity and seek immediate medical attention.

Physicians should discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of CIALIS. In such a patient, who has taken CIALIS, where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of CIALIS before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring. Therefore, patients who experience anginal chest pain after taking CIALIS should seek immediate medical attention. [see CONTRAINDICATIONS and PATIENT INFORMATION].

Patients with left ventricular outflow obstruction, (e.g., aortic stenosis and idiopathic hypertrophic subaortic stenosis) can be sensitive to the action of vasodilators, including PDE5 inhibitors.

The following groups of patients with cardiovascular disease were not included in clinical safety and efficacy trials for CIALIS, and therefore until further information is available, CIALIS is not recommended for the following groups of patients:

  • myocardial infarction within the last 90 days
  • unstable angina or angina occurring during sexual intercourse
  • New York Heart Association Class 2 or greater heart failure in the last 6 months
  • uncontrolled arrhythmias, hypotension (
  • stroke within the last 6 months.

As with other PDE5 inhibitors, tadalafil has mild systemic vasodilatory properties that may result in transient decreases in blood pressure. In a clinical pharmacology study, tadalafil 20 mg resulted in a mean maximal decrease in supine blood pressure, relative to placebo, of 1.6/0.8 mm Hg in healthy subjects [see CLINICAL PHARMACOLOGY]. While this effect should not be of consequence in most patients, prior to prescribing CIALIS, physicians should carefully consider whether their patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. Patients with severely impaired autonomic control of blood pressure may be particularly sensitive to the actions of vasodilators, including PDE5 inhibitors.

Potential For Drug Interactions When Taking CIALIS For Once Daily Use

Physicians should be aware that CIALIS for once daily use provides continuous plasma tadalafil levels and should consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha-blockers, anti-hypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol [see DRUG INTERACTIONS].

Prolonged Erection

There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention.

CIALIS should be used with caution in patients who have conditions that might predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease).

Effects On The Eye

Physicians should advise patients to stop use of all phosphodiesterase type 5 (PDE5) inhibitors, including CIALIS, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition and a cause of decreased vision, including permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Based on published literature, the annual incidence of NAION is 2.5-11.8 cases per 100,000 in males aged ≥50.

An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies.

Neither the rare postmarketing reports, nor the association of PDE5 inhibitor use and NAION in the observational studies, substantiate a causal relationship between PDE5 inhibitor use and NAION [see ADVERSE REACTIONS].

Physicians should consider whether their patients with underlying NAION risk factors could be adversely affected by use of PDE5 inhibitors. Individuals who have already experienced NAION are at increased risk of NAION recurrence. Therefore, PDE5 inhibitors, including CIALIS, should be used with caution in these patients and only when the anticipated benefits outweigh the risks. Individuals with “crowded” optic disc are also considered at greater risk for NAION compared to the general population; however, evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including CIALIS, for this uncommon condition.

Patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, were not included in the clinical trials, and use in these patients is not recommended.

Sudden Hearing Loss

Physicians should advise patients to stop taking PDE5 inhibitors, including CIALIS, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including CIALIS. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see ADVERSE REACTIONS].

Alpha-blockers And Antihypertensives

Physicians should discuss with patients the potential for CIALIS to augment the blood-pressure-lowering effect of alpha-blockers and antihypertensive medications [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].

Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including CIALIS, and alpha-adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. In some patients, concomitant use of these two drug classes can lower blood pressure significantly [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY], which may lead to symptomatic hypotension (e.g., fainting). Consideration should be given to the following:

ED
  • Patients should be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor. Patients who demonstrate hemodynamic instability on alpha-blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of PDE5 inhibitors.
  • In those patients who are stable on alpha-blocker therapy, PDE5 inhibitors should be initiated at the lowest recommended dose.
  • In those patients already taking an optimized dose of PDE5 inhibitor, alpha-blocker therapy should be initiated at the lowest dose. Stepwise increase in alpha-blocker dose may be associated with further lowering of blood pressure when taking a PDE5 inhibitor.
  • Safety of combined use of PDE5 inhibitors and alpha-blockers may be affected by other variables, including intravascular volume depletion and other antihypertensive drugs. [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS].
BPH
  • The efficacy of the coadministration of an alpha-blocker and CIALIS for the treatment of BPH has not been adequately studied, and due to the potential vasodilatory effects of combined use resulting in blood pressure lowering, the combination of CIALIS and alpha-blockers is not recommended for the treatment of BPH. [see DOSAGE AND ADMINISTRATION, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].
  • Patients on alpha-blocker therapy for BPH should discontinue their alpha-blocker at least one day prior to starting CIALIS for once daily use for the treatment of BPH.

Renal Impairment

CIALIS For Use As Needed

CIALIS should be limited to 5 mg not more than once in every 72 hours in patients with creatinine clearance less than 30 mL/min or end-stage renal disease on hemodialysis. The starting dose of CIALIS in patients with creatinine clearance 30 – 50 mL/min should be 5 mg not more than once per day, and the maximum dose should be limited to 10 mg not more than once in every 48 hours. [see Use In Specific Populations].

CIALIS For Once Daily Use

Due to increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis, CIALIS for once daily use is not recommended in patients with creatinine clearance less than 30 mL/min [see Use In Specific Populations].

Due to increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis, CIALIS for once daily use is not recommended in patients with creatinine clearance less than 30 mL/min. In patients with creatinine clearance 30 – 50 mL/min, start dosing at 2.5 mg once daily, and increase the dose to 5 mg once daily based upon individual response [see DOSAGE AND ADMINISTRATION, Use In Specific Populations, and CLINICAL PHARMACOLOGY].

Hepatic Impairment

CIALIS For Use As Needed

In patients with mild or moderate hepatic impairment, the dose of CIALIS should not exceed 10 mg. Because of insufficient information in patients with severe hepatic impairment, use of CIALIS in this group is not recommended [see Use In Specific Populations].

CIALIS For Once Daily Use

CIALIS for once daily use has not been extensively evaluated in patients with mild or moderate hepatic impairment. Therefore, caution is advised if CIALIS for once daily use is prescribed to these patients. Because of insufficient information in patients with severe hepatic impairment, use of CIALIS in this group is not recommended [see Use In Specific Populations].

Alcohol

Patients should be made aware that both alcohol and CIALIS, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Therefore, physicians should inform patients that substantial consumption of alcohol (e.g., 5 units or greater) in combination with CIALIS can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache [see CLINICAL PHARMACOLOGY].

Concomitant Use Of Potent Inhibitors Of Cytochrome P450 3A4 (CYP3A4)

CIALIS is metabolized predominantly by CYP3A4 in the liver. The dose of CIALIS for use as needed should be limited to 10 mg no more than once every 72 hours in patients taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, and itraconazole [see DRUG INTERACTIONS]. In patients taking potent inhibitors of CYP3A4 and CIALIS for once daily use, the maximum recommended dose is 2.5 mg [see DOSAGE AND ADMINISTRATION].

Combination With Other PDE5 Inhibitors Or Erectile Dysfunction Therapies

The safety and efficacy of combinations of CIALIS and other PDE5 inhibitors or treatments for erectile dysfunction have not been studied. Inform patients not to take CIALIS with other PDE5 inhibitors, including ADCIRCA.

Effects On Bleeding

Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in platelets. When administered in combination with aspirin, tadalafil 20 mg did not prolong bleeding time, relative to aspirin alone. CIALIS has not been administered to patients with bleeding disorders or significant active peptic ulceration. Although CIALIS has not been shown to increase bleeding times in healthy subjects, use in patients with bleeding disorders or significant active peptic ulceration should be based upon a careful risk-benefit assessment and caution.

Counseling Patients About Sexually Transmitted Diseases

The use of CIALIS offers no protection against sexually transmitted diseases. Counseling patients about the protective measures necessary to guard against sexually transmitted diseases, including Human Immunodeficiency Virus (HIV) should be considered.

Consideration Of Other Urological Conditions Prior To Initiating Treatment For BPH

Prior to initiating treatment with CIALIS for BPH, consideration should be given to other urological conditions that may cause similar symptoms. In addition, prostate cancer and BPH may coexist.

Patient Counseling Information

“See FDA-approved patient labeling (PATIENT INFORMATION)

Nitrates

Physicians should discuss with patients the contraindication of CIALIS with regular and/or intermittent use of organic nitrates. Patients should be counseled that concomitant use of CIALIS with nitrates could cause blood pressure to suddenly drop to an unsafe level, resulting in dizziness, syncope, or even heart attack or stroke.

Physicians should discuss with patients the appropriate action in the event that they experience anginal chest pain requiring nitroglycerin following intake of CIALIS. In such a patient, who has taken CIALIS, where nitrate administration is deemed medically necessary for a life-threatening situation, at least 48 hours should have elapsed after the last dose of CIALIS before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring. Therefore, patients who experience anginal chest pain after taking CIALIS should seek immediate medical attention [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Guanylate Cyclase (GC) Stimulators

Physicians should discuss with patients the contraindication of CIALIS with any use of a GC stimulator, such as riociguat, for pulmonary arterial hypertension. Patients should be counseled that the concomitant use of CIALIS with GC stimulators may cause blood pressure to drop to an unsafe level.

Cardiovascular Considerations

Physicians should consider the potential cardiac risk of sexual activity in patients with preexisting cardiovascular disease. Physicians should advise patients who experience symptoms upon initiation of sexual activity to refrain from further sexual activity and seek immediate medical attention [see WARNINGS AND PRECAUTIONS].

Concomitant Use With Drugs Which Lower Blood Pressure

Physicians should discuss with patients the potential for CIALIS to augment the blood-pressure-lowering effect of alpha-blockers, and antihypertensive medications [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].

Potential For Drug Interactions When Taking CIALIS For Once Daily Use

Physicians should discuss with patients the clinical implications of continuous exposure to tadalafil when prescribing CIALIS for once daily use, especially the potential for interactions with medications (e.g., nitrates, alpha-blockers, antihypertensives and potent inhibitors of cytochrome P450 3A4) and with substantial consumption of alcohol. [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, CLINICAL PHARMACOLOGY, and Clinical Studies].

Priapism

There have been rare reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Physicians should advise patients who have an erection lasting greater than 4 hours, whether painful or not, to seek emergency medical attention.

Sudden Loss Of Vision

Physicians should advise patients to stop use of all PDE5 inhibitors, including CIALIS, and seek medical attention in the event of a sudden loss of vision in one or both eyes. Such an event may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision, including possible permanent loss of vision, that has been reported rarely postmarketing in temporal association with the use of all PDE5 inhibitors. Physicians should discuss with patients the increased risk of NAION in individuals who have already experienced NAION in one eye. Physicians should also discuss with patients the increased risk of NAION among the general population in patients with a “crowded” optic disc, although evidence is insufficient to support screening of prospective users of PDE5 inhibitors, including CIALIS, for this uncommon condition [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Sudden Hearing Loss

Physicians should advise patients to stop taking PDE5 inhibitors, including CIALIS, and seek prompt medical attention in the event of sudden decrease or loss of hearing. These events, which may be accompanied by tinnitus and dizziness, have been reported in temporal association to the intake of PDE5 inhibitors, including CIALIS. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see ADVERSE REACTIONS].

Alcohol

Patients should be made aware that both alcohol and CIALIS, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Therefore, physicians should inform patients that substantial consumption of alcohol (e.g., 5 units or greater) in combination with CIALIS can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache [see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, and CLINICAL PHARMACOLOGY].

Sexually Transmitted Disease

The use of CIALIS offers no protection against sexually transmitted diseases. Counseling of patients about the protective measures necessary to guard against sexually transmitted diseases, including Human Immunodeficiency Virus (HIV) should be considered.

Recommended Administration

Physicians should instruct patients on the appropriate administration of CIALIS to allow optimal use.

For CIALIS for use as needed in men with ED, patients should be instructed to take one tablet at least 30 minutes before anticipated sexual activity. In most patients, the ability to have sexual intercourse is improved for up to 36 hours.

For CIALIS for once daily use in men with ED or ED/BPH, patients should be instructed to take one tablet at approximately the same time every day without regard for the timing of sexual activity. Cialis is effective at improving erectile function over the course of therapy.

For CIALIS for once daily use in men with BPH, patients should be instructed to take one tablet at approximately the same time every day.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Tadalafil was not carcinogenic to rats or mice when administered daily for 2 years at doses up to 400 mg/kg/day. Systemic drug exposures, as measured by AUC of unbound tadalafil, were approximately 10-fold for mice, and 14-and 26-fold for male and female rats, respectively, the exposures in human males given Maximum Recommended Human Dose (MRHD) of 20 mg.

Mutagenesis

Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells. Tadalafil was not clastogenic in the in vitro chromosomal aberration test in human lymphocytes or the in vivo rat micronucleus assays.

Impairment Of Fertility

There were no effects on fertility, reproductive performance or reproductive organ morphology in male or female rats given oral doses of tadalafil up to 400 mg/kg/day, a dose producing AUCs for unbound tadalafil of 14-fold for males or 26-fold for females the exposures observed in human males given the MRHD of 20 mg. In beagle dogs given tadalafil daily for 3 to 12 months, there was treatment-related non-reversible degeneration and atrophy of the seminiferous tubular epithelium in the testes in 20-100% of the dogs that resulted in a decrease in spermatogenesis in 40-75% of the dogs at doses of ≥10 mg/kg/day. Systemic exposure (based on AUC) at no-observed-adverse-effectlevel (NOAEL) (10 mg/kg/day) for unbound tadalafil was similar to that expected in humans at the MRHD of 20 mg.

There were no treatment-related testicular findings in rats or mice treated with doses up to 400 mg/kg/day for 2 years.

Use In Specific Populations

Pregnancy

Risk Summary

CIALIS (tadalafil) is not indicated for use in females.

There are no data with the use of CIALIS in pregnant women to inform any drug-associated risks for adverse developmental outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats or mice during organogenesis at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg/day (see Data).

Data

Animal reproduction studies showed no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given orally to pregnant rats or mice at exposures up to 11 times the maximum recommended human dose (MRHD) of 20 mg/day during organogenesis. In a prenatal/postnatal developmental study in rats, postnatal pup survival decreased following maternal exposure to tadalafil doses greater than 10 times the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 16 times the MRHD based on AUC. Surviving offspring had normal development and reproductive performance.

In another rat prenatal and postnatal development study at doses of 60, 200, and 1000 mg/kg, a reduction in postnatal survival of pups was observed. The no observed effect level (NOEL) for maternal toxicity was 200 mg/kg/day and for developmental toxicity was 30 mg/kg/day. This gives approximately 16 and 10 fold exposure multiples, respectively, of the human AUC for the MRHD of 20 mg.

Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats.

Lactation

Risk Summary

CIALIS is not indicated for use in females.

There is no information on the presence of tadalafil and/or metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Tadalafil and/or its metabolites are present in the milk of lactating rats at concentrations approximately 2.4-fold greater than found in the plasma.

Females And Males Of Reproductive Potential

Infertility

Based on the data from 3 studies in adult males, tadalafil decreased sperm concentrations in the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. There was no adverse effect of tadalafil 10 mg or 20 mg on mean concentrations of testosterone, luteinizing hormone or follicle stimulating hormone. The clinical significance of the decreased sperm concentrations in the two studies is unknown. There have been no studies evaluating the effect of tadalafil on fertility in men [see CLINICAL PHARMACOLOGY].

Based on studies in animals, a decrease in spermatogenesis was observed in dogs, but not in rats [see Nonclinical Toxicology].

Pediatric Use

CIALIS is not indicated for use in pediatric patients. Safety and efficacy in patients below the age of 18 years have not been established.

A randomized, double-blind, placebo-controlled trial in pediatric patients (7 to 14 years of age) with Duchenne muscular dystrophy, who received CIALIS 0.3 mg/kg, CIALIS 0.6 mg/kg, or placebo daily for 48 weeks failed to demonstrate any benefit of treatment with CIALIS on a range of assessments of muscle strength and performance.

Juvenile Animal Study

No adverse effects were observed in a study in which tadalafil was administered orally at doses of 60, 200, and 1000 mg/kg/day to juvenile rats on postnatal days 14 to 90. The highest plasma tadalafil exposures (AUC) achieved were approximately 10-fold that observed at the MRHD.

Geriatric Use

Of the total number of subjects in ED clinical studies of tadalafil, approximately 19 percent were 65 and over, while approximately 2 percent were 75 and over. Of the total number of subjects in BPH clinical studies of tadalafil (including the ED/BPH study), approximately 40 percent were over 65, while approximately 10 percent were 75 and over. In these clinical trials, no overall differences in efficacy or safety were observed between older (>65 and ≥75 years of age) and younger subjects (≤65 years of age). However, in placebo-controlled studies with CIALIS for use as needed for ED, diarrhea was reported more frequently in patients 65 years of age and older who were treated with CIALIS (2.5% of patients) [see ADVERSE REACTIONS]. No dose adjustment is warranted based on age alone. However, a greater sensitivity to medications in some older individuals should be considered. [see CLINICAL PHARMACOLOGY].

Hepatic Impairment

In clinical pharmacology studies, tadalafil exposure (AUC) in subjects with mild or moderate hepatic impairment (Child-Pugh Class A or B) was comparable to exposure in healthy subjects when a dose of 10 mg was administered. There are no available data for doses higher than 10 mg of tadalafil in patients with hepatic impairment. Insufficient data are available for subjects with severe hepatic impairment (Child-Pugh Class C). [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Renal Impairment

In clinical pharmacology studies using single-dose tadalafil (5 to 10 mg), tadalafil exposure (AUC) doubled in subjects with creatinine clearance 30 to 80 mL/min. In subjects with end-stage renal disease on hemodialysis, there was a two-fold increase in Cmax and 2.7-to 4.8-fold increase in AUC following single-dose administration of 10 or 20 mg tadalafil. Exposure to total methylcatechol (unconjugated plus glucuronide) was 2-to 4-fold higher in subjects with renal impairment, compared to those with normal renal function. Hemodialysis (performed between 24 and 30 hours post-dose) contributed negligibly to tadalafil or metabolite elimination. In a clinical pharmacology study (N=28) at a dose of 10 mg, back pain was reported as a limiting adverse event in male patients with creatinine clearance 30 to 50 mL/min. At a dose of 5 mg, the incidence and severity of back pain was not significantly different than in the general population. In patients on hemodialysis taking 10-or 20-mg tadalafil, there were no reported cases of back pain. [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

OVERDOSE

Single doses up to 500 mg have been given to healthy subjects, and multiple daily doses up to 100 mg have been given to patients. Adverse events were similar to those seen at lower doses. In cases of overdose, standard supportive measures should be adopted as required. Hemodialysis contributes negligibly to tadalafil elimination.

CONTRAINDICATIONS

Nitrates

Administration of CIALIS to patients who are using any form of organic nitrate, either regularly and/or intermittently, is contraindicated. In clinical pharmacology studies, CIALIS was shown to potentiate the hypotensive effect of nitrates [see CLINICAL PHARMACOLOGY].

Hypersensitivity Reactions

CIALIS is contraindicated in patients with a known serious hypersensitivity to tadalafil (CIALIS or ADCIRCA®). Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis [see ADVERSE REACTIONS].

Concomitant Guanylate Cyclase (GC) Stimulators

Do not use CIALIS in patients who are using a GC stimulator, such as riociguat. PDE5 inhibitors, including CIALIS, may potentiate the hypotensive effects of GC stimulators.

CLINICAL PHARMACOLOGY

Mechanism Of Action

Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil inhibits PDE5. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation.

The effect of PDE5 inhibition on cGMP concentration in the corpus cavernosum and pulmonary arteries is also observed in the smooth muscle of the prostate, the bladder and their vascular supply. The mechanism for reducing BPH symptoms has not been established.

Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in the smooth muscle of the corpus cavernosum, prostate, and bladder as well as in vascular and visceral smooth muscle, skeletal muscle, urethra, platelets, kidney, lung, cerebellum, heart, liver, testis, seminal vesicle, and pancreas.

In vitro studies have shown that the effect of tadalafil is more potent on PDE5 than on other phosphodiesterases. These studies have shown that tadalafil is >10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, tadalafil is 700-fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Tadalafil is >9,000-fold more potent for PDE5 than for PDE8, PDE9, and PDE10. Tadalafil is 14-fold more potent for PDE5 than for PDE11A1 and 40-fold more potent for PDE5 than for PDE11A4, two of the four known forms of PDE11. PDE11 is an enzyme found in human prostate, testes, skeletal muscle and in other tissues (e.g., adrenal cortex). In vitro, tadalafil inhibits human recombinant PDE11A1 and, to a lesser degree, PDE11A4 activities at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined.

Pharmacodynamics

Effects On Blood Pressure

Tadalafil 20 mg administered to healthy male subjects produced no significant difference compared to placebo in supine systolic and diastolic blood pressure (difference in the mean maximal decrease of 1.6/0.8 mm Hg, respectively) and in standing systolic and diastolic blood pressure (difference in the mean maximal decrease of 0.2/4.6 mm Hg, respectively). In addition, there was no significant effect on heart rate.

Effects On Blood Pressure When Administered With Nitrates

In clinical pharmacology studies, tadalafil (5 to 20 mg) was shown to potentiate the hypotensive effect of nitrates. Therefore, the use of CIALIS in patients taking any form of nitrates is contraindicated [see CONTRAINDICATIONS].

A study was conducted to assess the degree of interaction between nitroglycerin and tadalafil, should nitroglycerin be required in an emergency situation after tadalafil was taken. This was a double-blind, placebo-controlled, crossover study in 150 male subjects at least 40 years of age (including subjects with diabetes mellitus and/or controlled hypertension) and receiving daily doses of tadalafil 20 mg or matching placebo for 7 days. Subjects were administered a single dose of 0.4 mg sublingual nitroglycerin (NTG) at pre-specified timepoints, following their last dose of tadalafil (2, 4, 8, 24, 48, 72, and 96 hours after tadalafil). The objective of the study was to determine when, after tadalafil dosing, no apparent blood pressure interaction was observed. In this study, a significant interaction between tadalafil and NTG was observed at each timepoint up to and including 24 hours. At 48 hours, by most hemodynamic measures, the interaction between tadalafil and NTG was not observed, although a few more tadalafil subjects compared to placebo experienced greater blood-pressure lowering at this timepoint. After 48 hours, the interaction was not detectable (see Figure 1).

Figure 1: Mean Maximal Change in Blood Pressure (Tadalafil Minus Placebo, Point Estimate with 90% CI) in Response to Sublingual Nitroglycerin at 2 (Supine Only), 4, 8, 24, 48, 72, and 96 Hours after the Last Dose of Tadalafil 20 mg or Placebo

Therefore, CIALIS administration with nitrates is contraindicated. In a patient who has taken CIALIS, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last dose of CIALIS before nitrate administration is considered. In such circumstances, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring [see CONTRAINDICATIONS].

Effect On Blood Pressure When Administered With Alpha-Blockers

Six randomized, double-blinded, crossover clinical pharmacology studies were conducted to investigate the potential interaction of tadalafil with alpha-blocker agents in healthy male subjects [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. In four studies, a single oral dose of tadalafil was administered to healthy male subjects taking daily (at least 7 days duration) an oral alpha-blocker. In two studies, a daily oral alpha-blocker (at least 7 days duration) was administered to healthy male subjects taking repeated daily doses of tadalafil.

Three clinical pharmacology studies were conducted with tadalafil and doxazosin, an alpha[1]adrenergic blocker.

In the first doxazosin study, a single oral dose of tadalafil 20 mg or placebo was administered in a 2-period, crossover design to healthy subjects taking oral doxazosin 8 mg daily (N=18 subjects). Doxazosin was administered at the same time as tadalafil or placebo after a minimum of seven days of doxazosin dosing (see Table 5 and Figure 2).

Table 5: Doxazosin (8 mg/day) Study 1: Mean Maximal Decrease (95% CI) in Systolic Blood Pressure

Placebo-subtracted mean maximal decrease in systolic blood pressure (mm Hg) Tadalafil 20 mg
Supine 3.6 (-1.5, 8.8)
Standing 9.8 (4.1, 15.5)

Figure 2: Doxazosin Study 1: Mean Change from Baseline in Systolic Blood Pressure

Blood pressure was measured manually at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after tadalafil or placebo administration. Outliers were defined as subjects with a standing systolic blood pressure of 30 mm Hg at one or more time points. There were nine and three outliers following administration of tadalafil 20 mg and placebo, respectively. Five and two subjects were outliers due to a decrease from baseline in standing systolic BP of >30 mm Hg, while five and one subject were outliers due to standing systolic BP

In the second doxazosin study, a single oral dose of tadalafil 20 mg was administered to healthy subjects taking oral doxazosin, either 4 or 8 mg daily. The study (N=72 subjects) was conducted in three parts, each a 3-period crossover.

In part A (N=24), subjects were titrated to doxazosin 4 mg administered daily at 8 a.m. Tadalafil was administered at either 8 a.m., 4 p.m., or 8 p.m. There was no placebo control.

In part B (N=24), subjects were titrated to doxazosin 4 mg administered daily at 8 p.m. Tadalafil was administered at either 8 a.m., 4 p.m., or 8 p.m. There was no placebo control.

In part C (N=24), subjects were titrated to doxazosin 8 mg administered daily at 8 a.m. In this part, tadalafil or placebo were administered at either 8 a.m. or 8 p.m.

The placebo-subtracted mean maximal decreases in systolic blood pressure over a 12-hour period after dosing in the placebo-controlled portion of the study (part C) are shown in Table 6 and Figure 3.

Table 6: Doxazosin (8 mg/day) Study 2 (Part C): Mean Maximal Decrease in Systolic Blood Pressure

Placebo-subtracted mean maximal decrease in systolic blood pressure (mm Hg) Tadalafil 20 mg at 8 a.m. Tadalafil 20 mg at 8 p.m.
Ambulatory Blood-Pressure Monitoring (ABPM) 7 8

Figure 3: Doxazosin Study 2 (Part C): Mean Change from Time-Matched Baseline in Systolic Blood Pressure

Blood pressure was measured by ABPM every 15 to 30 minutes for up to 36 hours after tadalafil or placebo. Subjects were categorized as outliers if one or more systolic blood pressure readings of 30 mm Hg from a time-matched baseline occurred during the analysis interval.

Of the 24 subjects in part C, 16 subjects were categorized as outliers following administration of tadalafil and 6 subjects were categorized as outliers following placebo during the 24-hour period after 8 a.m. dosing of tadalafil or placebo. Of these, 5 and 2 were outliers due to systolic BP 30 mm Hg following tadalafil and placebo, respectively.

During the 24-hour period after 8 p.m. dosing, 17 subjects were categorized as outliers following administration of tadalafil and 7 subjects following placebo. Of these, 10 and 2 subjects were outliers due to systolic BP 30 mm Hg, following tadalafil and placebo, respectively.

Some additional subjects in both the tadalafil and placebo groups were categorized as outliers in the period beyond 24 hours.

Severe adverse events potentially related to blood-pressure effects were assessed. In the study (N=72 subjects), 2 such events were reported following administration of tadalafil (symptomatic hypotension in one subject that began 10 hours after dosing and lasted approximately 1 hour, and dizziness in another subject that began 11 hours after dosing and lasted 2 minutes). No such events were reported following placebo. In the period prior to tadalafil dosing, one severe event (dizziness) was reported in a subject during the doxazosin run-in phase.

In the third doxazosin study, healthy subjects (N=45 treated; 37 completed) received 28 days of once per day dosing of tadalafil 5 mg or placebo in a two-period crossover design. After 7 days, doxazosin was initiated at 1 mg and titrated up to 4 mg daily over the last 21 days of each period (7 days on 1 mg; 7 days of 2 mg; 7 days of 4 mg doxazosin). The results are shown in Table 7.

Table 7: Doxazosin Study 3: Mean Maximal Decrease (95% CI) in Systolic Blood Pressure

Placebo-subtracted mean maximal decrease in systolic blood pressure Tadalafil 5 mg
Day 1 of 4 mg Doxazosin Supine 2.4 (-0.4, 5.2)
Standing -0.5 (-4.0, 3.1)
Day 7 of 4 mg Doxazosin Supine 2.8 (-0.1, 5.7)
Standing 1.1 (-2.9, 5.0)

Blood pressure was measured manually pre-dose at two time points (-30 and -15 minutes) and then at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours post dose on the first day of each doxazosin dose, (1 mg, 2 mg, 4 mg), as well as on the seventh day of 4 mg doxazosin administration.

Following the first dose of doxazosin 1 mg, there were no outliers on tadalafil 5 mg and one outlier on placebo due to a decrease from baseline in standing systolic BP of >30 mm Hg.

There were 2 outliers on tadalafil 5 mg and none on placebo following the first dose of doxazosin 2 mg due to a decrease from baseline in standing systolic BP of >30 mm Hg.

There were no outliers on tadalafil 5 mg and two on placebo following the first dose of doxazosin 4 mg due to a decrease from baseline in standing systolic BP of >30 mm Hg. There was one outlier on tadalafil 5 mg and three on placebo following the first dose of doxazosin 4 mg due to standing systolic BP 30 mm Hg in standing systolic blood pressure, and one subject on placebo had standing systolic blood pressure

Tamsulosin

In the first tamsulosin study, a single oral dose of tadalafil 10, 20 mg, or placebo was administered in a 3 period, crossover design to healthy subjects taking 0.4 mg once per day tamsulosin, a selective alpha[1A]adrenergic blocker (N=18 subjects). Tadalafil or placebo was administered 2 hours after tamsulosin following a minimum of seven days of tamsulosin dosing.

Table 8: Tamsulosin (0.4 mg/day) Study 1: Mean Maximal Decrease (95% CI) in Systolic Blood Pressure

Placebo-subtracted mean maximal decrease in systolic blood pressure (mm Hg) Tadalafil 10 mg Tadalafil 20 mg
Supine 3.2 (-2.3, 8.6) 3.2 (-2.3, 8.7)
Standing 1.7 (-4.7, 8.1) 2.3 (-4.1, 8.7)

Blood pressure was measured manually at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after tadalafil or placebo dosing. There were 2, 2, and 1 outliers (subjects with a decrease from baseline in standing systolic blood pressure of >30 mm Hg at one or more time points) following administration of tadalafil 10 mg, 20 mg, and placebo, respectively. There were no subjects with a standing systolic blood pressure

In the second tamsulosin study, healthy subjects (N=39 treated; and 35 completed) received 14 days of once per day dosing of tadalafil 5 mg or placebo in a two-period crossover design. Daily dosing of tamsulosin 0.4 mg was added for the last seven days of each period.

Table 9: Tamsulosin Study 2: Mean Maximal Decrease (95% CI) in Systolic Blood Pressure

Placebo-subtracted mean maximal decrease in systolic blood pressure Tadalafil 5 mg
Day 1 of 0.4 mg Tamsulosin Supine -0.1 (-2.2, 1.9)
Standing 0.9 (-1.4, 3.2)
Day 7 of 0.4 mg Tamsulosin Supine 1.2 (-1.2, 3.6)
Standing 1.2 (-1.0, 3.5)

Blood pressure was measured manually pre-dose at two time points (-30 and -15 minutes) and then at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours post dose on the first, sixth and seventh days of tamsulosin administration. There were no outliers (subjects with a decrease from baseline in standing systolic blood pressure of >30 mm Hg at one or more time points). One subject on placebo plus tamsulosin (Day 7) and one subject on tadalafil plus tamsulosin (Day 6) had standing systolic blood pressure

Alfuzosin

A single oral dose of tadalafil 20 mg or placebo was administered in a 2-period, crossover design to healthy subjects taking once-daily alfuzosin HCl 10 mg extended-release tablets, an alpha[1]-adrenergic blocker (N=17 completed subjects). Tadalafil or placebo was administered 4 hours after alfuzosin following a minimum of seven days of alfuzosin dosing.

Table 10: Alfuzosin (10 mg/day) Study: Mean Maximal Decrease (95% CI) in Systolic Blood Pressure

Placebo-subtracted mean maximal decrease in systolic blood pressure (mm Hg) Tadalafil 20 mg
Supine 2.2 (-0.9,-5.2)
Standing 4.4 (-0.2, 8.9)

Blood pressure was measured manually at 1, 2, 3, 4, 6, 8, 10, 20, and 24 hours after tadalafil or placebo dosing. There was 1 outlier (subject with a standing systolic blood pressure 30 mm Hg at one or more time points. No severe adverse events potentially related to blood pressure effects were reported. No syncope was reported.

Effects On Blood Pressure When Administered With Antihypertensives

A study was conducted to assess the interaction of amlodipine (5 mg daily) and tadalafil 10 mg. There was no effect of tadalafil on amlodipine blood levels and no effect of amlodipine on tadalafil blood levels. The mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking amlodipine was 3/2 mm Hg, compared to placebo. In a similar study using tadalafil 20 mg, there were no clinically significant differences between tadalafil and placebo in subjects taking amlodipine.

Angiotensin II Receptor Blockers (with and without other antihypertensives)

A study was conducted to assess the interaction of angiotensin II receptor blockers and tadalafil 20 mg. Subjects in the study were taking any marketed angiotensin II receptor blocker, either alone, as a component of a combination product, or as part of a multiple antihypertensive regimen. Following dosing, ambulatory measurements of blood pressure revealed differences between tadalafil and placebo of 8/4 mm Hg in systolic/diastolic blood pressure.

A study was conducted to assess the interaction of bendrofluazide (2.5 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking bendrofluazide was 6/4 mm Hg, compared to placebo.

A study was conducted to assess the interaction of enalapril (10 to 20 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking enalapril was 4/1 mm Hg, compared to placebo.

A study was conducted to assess the interaction of sustained-release metoprolol (25 to 200 mg daily) and tadalafil 10 mg. Following dosing, the mean reduction in supine systolic/diastolic blood pressure due to tadalafil 10 mg in subjects taking metoprolol was 5/3 mm Hg, compared to placebo.

Effects On Blood Pressure When Administered With Alcohol

Alcohol and PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. The interaction of tadalafil with alcohol was evaluated in 3 clinical pharmacology studies. In 2 of these, alcohol was administered at a dose of 0.7 g/kg, which is equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male, and tadalafil was administered at a dose of 10 mg in one study and 20 mg in another. In both these studies, all patients imbibed the entire alcohol dose within 10 minutes of starting. In one of these two studies, blood alcohol levels of 0.08% were confirmed. In these two studies, more patients had clinically significant decreases in blood pressure on the combination of tadalafil and alcohol as compared to alcohol alone. Some subjects reported postural dizziness, and orthostatic hypotension was observed in some subjects. When tadalafil 20 mg was administered with a lower dose of alcohol (0.6 g/kg, which is equivalent to approximately 4 ounces of 80-proof vodka, administered in less than 10 minutes), orthostatic hypotension was not observed, dizziness occurred with similar frequency to alcohol alone, and the hypotensive effects of alcohol were not potentiated.

Tadalafil did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations.

Effects On Exercise Stress Testing

The effects of tadalafil on cardiac function, hemodynamics, and exercise tolerance were investigated in a single clinical pharmacology study. In this blinded crossover trial, 23 subjects with stable coronary artery disease and evidence of exercise-induced cardiac ischemia were enrolled. The primary endpoint was time to cardiac ischemia. The mean difference in total exercise time was 3 seconds (tadalafil 10 mg minus placebo), which represented no clinically meaningful difference. Further statistical analysis demonstrated that tadalafil was non-inferior to placebo with respect to time to ischemia. Of note, in this study, in some subjects who received tadalafil followed by sublingual nitroglycerin in the post-exercise period, clinically significant reductions in blood pressure were observed, consistent with the augmentation by tadalafil of the blood-pressure-lowering effects of nitrates.

Effects On Vision

Single oral doses of phosphodiesterase inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green), using the Farnsworth-Munsell 100-hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. In a study to assess the effects of a single dose of tadalafil 40 mg on vision (N=59), no effects were observed on visual acuity, intraocular pressure, or pupilometry. Across all clinical studies with CIALIS, reports of changes in color vision were rare (

Effects On Sperm Characteristics

Three studies were conducted in men to assess the potential effect on sperm characteristics of tadalafil 10 mg (one 6 month study) and 20 mg (one 6 month and one 9 month study) administered daily. There were no adverse effects on sperm morphology or sperm motility in any of the three studies. In the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months, results showed a decrease in mean sperm concentrations relative to placebo, although these differences were not clinically meaningful. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. In addition there was no adverse effect on mean concentrations of reproductive hormones, testosterone, luteinizing hormone or follicle stimulating hormone with either 10 or 20 mg of tadalafil compared to placebo.

Effects On Cardiac Electrophysiology

The effect of a single 100-mg dose of tadalafil on the QT interval was evaluated at the time of peak tadalafil concentration in a randomized, double-blinded, placebo, and active (intravenous ibutilide) -controlled crossover study in 90 healthy males aged 18 to 53 years. The mean change in QTc (Fridericia QT correction) for tadalafil, relative to placebo, was 3.5 milliseconds (two-sided 90% CI=1.9, 5.1). The mean change in QTc (Individual QT correction) for tadalafil, relative to placebo, was 2.8 milliseconds (two-sided 90% CI=1.2, 4.4). A 100-mg dose of tadalafil (5 times the highest recommended dose) was chosen because this dose yields exposures covering those observed upon coadministration of tadalafil with potent CYP3A4 inhibitors or those observed in renal impairment. In this study, the mean increase in heart rate associated with a 100-mg dose of tadalafil compared to placebo was 3.1 beats per minute.

Pharmacokinetics

Over a dose range of 2.5 to 20 mg, tadalafil exposure (AUC) increases proportionally with dose in healthy subjects. Steady-state plasma concentrations are attained within 5 days of once per day dosing and exposure is approximately 1.6-fold greater than after a single dose. Mean tadalafil concentrations measured after the administration of a single oral dose of 20 mg and single and once daily multiple doses of 5 mg, from a separate study, (see Figure 4) to healthy male subjects are depicted in Figure 4.

Figure 4: Plasma tadalafil concentrations (mean ± SD) following a single 20-mg tadalafil dose and single and once daily multiple doses of 5 mg

Absorption

After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined.

The rate and extent of absorption of tadalafil are not influenced by food; thus CIALIS may be taken with or without food.

Distribution

The mean apparent volume of distribution following oral administration is approximately 63 L, indicating that tadalafil is distributed into tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins.

Less than 0.0005% of the administered dose appeared in the semen of healthy subjects.

Metabolism

Tadalafil is predominantly metabolized by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. The major circulating metabolite is the methylcatechol glucuronide. Methylcatechol concentrations are less than 10% of glucuronide concentrations. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations.

Excretion

The mean oral clearance for tadalafil is 2.5 L/hr and the mean terminal half-life is 17.5 hours in healthy subjects. Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).

Geriatric

Healthy male elderly subjects (65 years or over) had a lower oral clearance of tadalafil, resulting in 25% higher exposure (AUC) with no effect on Cmax relative to that observed in healthy subjects 19 to 45 years of age. No dose adjustment is warranted based on age alone. However, greater sensitivity to medications in some older individuals should be considered [see Use In Specific Populations].

Patients With Diabetes Mellitus

In male patients with diabetes mellitus after a 10 mg tadalafil dose, exposure (AUC) was reduced approximately 19% and Cmax was 5% lower than that observed in healthy subjects. No dose adjustment is warranted.

Patients With BPH

In patients with BPH following single and multiple-doses of 20 mg tadalafil, no statistically significant differences in exposure (AUC and Cmax) were observed between elderly (70 to 85 years) and younger (≤60 years of age) subjects. No dose adjustment is warranted.

Animal Toxicology And/Or Pharmacology

Animal studies showed vascular inflammation in tadalafil-treated mice, rats, and dogs. In mice and rats, lymphoid necrosis and hemorrhage were seen in the spleen, thymus, and mesenteric lymph nodes at unbound tadalafil exposure of 2-to 33-fold above the human exposure (AUCs) at the MRHD of 20 mg. In dogs, an increased incidence of disseminated arteritis was observed in 1-and 6-month studies at unbound tadalafil exposure of 1-to 54-fold above the human exposure (AUC) at the MRHD of 20 mg. In a 12-month dog study, no disseminated arteritis was observed, but 2 dogs exhibited marked decreases in white blood cells (neutrophils) and moderate decreases in platelets with inflammatory signs at unbound tadalafil exposures of approximately 14-to 18-fold the human exposure at the MRHD of 20 mg. The abnormal blood-cell findings were reversible within 2 weeks after stopping treatment.

Clinical Studies

CIALIS For Use As Needed For ED

The efficacy and safety of tadalafil in the treatment of erectile dysfunction has been evaluated in 22 clinical trials of up to 24-weeks duration, involving over 4000 patients. CIALIS, when taken as needed up to once per day, was shown to be effective in improving erectile function in men with erectile dysfunction (ED).

CIALIS was studied in the general ED population in 7 randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design, primary efficacy and safety studies of 12-weeks duration. Two of these studies were conducted in the United States and 5 were conducted in centers outside the US. Additional efficacy and safety studies were performed in ED patients with diabetes mellitus and in patients who developed ED status post bilateral nerve-sparing radical prostatectomy.

In these 7 trials, CIALIS was taken as needed, at doses ranging from 2.5 to 20 mg, up to once per day. Patients were free to choose the time interval between dose administration and the time of sexual attempts. Food and alcohol intake were not restricted.

Several assessment tools were used to evaluate the effect of CIALIS on erectile function. The 3 primary outcome measures were the Erectile Function (EF) domain of the International Index of Erectile Function (IIEF) and Questions 2 and 3 from Sexual Encounter Profile (SEP). The IIEF is a 4-week recall questionnaire that was administered at the end of a treatment-free baseline period and subsequently at follow-up visits after randomization. The IIEF EF domain has a 30point total score, where higher scores reflect better erectile function. SEP is a diary in which patients recorded each sexual attempt made throughout the study. SEP Question 2 asks, “Were you able to insert your penis into the partner’s vagina?” SEP Question 3 asks, “Did your erection last long enough for you to have successful intercourse?” The overall percentage of successful attempts to insert the penis into the vagina (SEP2) and to maintain the erection for successful intercourse (SEP3) is derived for each patient.

Results In ED Population In US Trials

The 2 primary US efficacy and safety trials included a total of 402 men with erectile dysfunction, with a mean age of 59 years (range 27 to 87 years). The population was 78% White, 14% Black, 7% Hispanic, and 1% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease. Most (>90%) patients reported ED of at least 1-year duration. Study A was conducted primarily in academic centers. Study B was conducted primarily in community-based urology practices. In each of these 2 trials, CIALIS 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables (see Table 11). The treatment effect of CIALIS did not diminish over time.

Table 11: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in the Two Primary US Trials

Study A Study B
Placebo
(N=49)
CIALIS 20 mg
(N=146)
p-value Placebo
(N=48)
CIALIS 20 mg
(N=159)
p-value
EF Domain Score
Endpoint 13.5 19.5 13.6 22.5
Change from baseline -0.2 6.9 0.3 9.3
Insertion of Penis (SEP2)
Endpoint 39% 62% 43% 77%
Change from baseline 2% 26% 2% 32%
Maintenance of Erection (SEP3)
Endpoint 25% 50% 23% 64%
Change from baseline 5% 34% 4% 44%
Results In General ED Population In Trials Outside The US

The 5 primary efficacy and safety studies conducted in the general ED population outside the US included 1112 patients, with a mean age of 59 years (range 21 to 82 years). The population was 76% White, 1% Black, 3% Hispanic, and 20% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease. Most (90%) patients reported ED of at least 1-year duration. In these 5 trials, CIALIS 5, 10, and 20 mg showed clinically meaningful and statistically significant improvements in all 3 primary efficacy variables (see Tables 12, 13 and 14). The treatment effect of CIALIS did not diminish over time.

Table 12: Mean Endpoint and Change from Baseline for the EF Domain of the IIEF in the General ED Population in Five Primary Trials Outside the US

Placebo CIALIS 5 mg CIALIS 10 mg CIALIS 20 mg
Study C
Endpoint [Change from baseline] 15.0 [0.7] 17.9 [4.0] 20.0 [5.6]
p=. 006 p
Study D
Endpoint [Change from baseline] 14.4 [1.1] 17.5 [5.1] 20.6 [6.0]
p=. 002 p
Study E
Endpoint [Change from baseline] 18.1 [2.6] 22.6 [8.1] 25.0 [8.0]
p p
Study F a
Endpoint [Change from baseline] 12.7 [-1.6] 22.8 [6.8]
p
Study G
Endpoint [Change from baseline] 14.5 [-0.9] 21.2 [6.6] 23.3 [8.0]
p p
a Treatment duration in Study F was 6 months

Table 13: Mean Post-Baseline Success Rate and Change from Baseline for SEP Question 2 (“Were you able to insert your penis into the partner’s vagina?”) in the General ED Population in Five Pivotal Trials Outside the US

Placebo CIALIS 5 mg CIALIS 10 mg CIALIS 20 mg
Study C
Endpoint [Change from baseline] 49% [6%] 57% [15%] 73% [29%]
p=.063 p
Study D
Endpoint [Change from baseline] 46% [2%] 56% [18%] 68% [15%]
p=. 008 p
Study E
Endpoint [Change from baseline] 55% [10%] 77% [35%] 85% [35%]
p p
Study F a
Endpoint [Change from baseline] 42% [-8%] 81% [27%]
p
Study G
Endpoint [Change from baseline] 45% [-6%] 73% [21%] 76% [21%]
p p
a Treatment duration in Study F was 6 months

Table 14: Mean Post-Baseline Success Rate and Change from Baseline for SEP Question 3 (“Did your erection last long enough for you to have successful intercourse?”) in the General ED Population in Five Pivotal Trials Outside the US

Placebo CIALIS 5 mg CIALIS 10 mg CIALIS 20 mg
Study C
Endpoint [Change from baseline] 26% [4%] 38% [19%] 58% [32%]
p=. 040 p
Study D
Endpoint [Change from baseline] 28% [4%] 42% [24%] 51% [26%]
p p
Study E
Endpoint [Change from baseline] 43% [15%] 70% [48%] 78% [50%]
p p
Study F a
Endpoint [Change from baseline] 27% [1 %] 74% [40%]
p
Study G
Endpoint [Change from baseline] 32% [5%] 57% [33%] 62% [29%]
p p
a Treatment duration in Study F was 6 months

In addition, there were improvements in EF domain scores, success rates based upon SEP Questions 2 and 3, and patient-reported improvement in erections across patients with ED of all degrees of disease severity while taking CIALIS, compared to patients on placebo.

Therefore, in all 7 primary efficacy and safety studies, CIALIS showed statistically significant improvement in patients’ ability to achieve an erection sufficient for vaginal penetration and to maintain the erection long enough for successful intercourse, as measured by the IIEF questionnaire and by SEP diaries.

Efficacy Results In ED Patients With Diabetes Mellitus

CIALIS was shown to be effective in treating ED in patients with diabetes mellitus. Patients with diabetes were included in all 7 primary efficacy studies in the general ED population (N=235) and in one study that specifically assessed CIALIS in ED patients with type 1 or type 2 diabetes (N=216). In this randomized, placebo-controlled, double-blinded, parallel-arm design prospective trial, CIALIS demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary (see Table 15).

Table 15: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in ED Patients with Diabetes

Placebo
(N=71)
CIALIS 10 mg
(N=73)
CIALIS 20 mg
(N=72)
p-value
EF Domain Score
Endpoint [Change from baseline] 12.2 [0.1] 19.3 [6.4] 18.7 [7.3]
Insertion of Penis (SEP2)
Endpoint [Change from baseline] 30% [-4%] 57% [22%] 54% [23%]
Maintenance of Erection (SEP3)
Endpoint [Change from baseline] 20% [2%] 48% [28%] 42% [29%]
Efficacy Results In ED Patients Following Radical Prostatectomy

CIALIS was shown to be effective in treating patients who developed ED following bilateral nerve-sparing radical prostatectomy. In 1 randomized, placebo-controlled, double-blinded, parallel-arm design prospective trial in this population (N=303), CIALIS demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary (see Table 16).

Table 16: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a Study in Patients who Developed ED Following Bilateral Nerve-Sparing Radical Prostatectomy

Placebo
(N=102)
CIALIS 20 mg
(N=201)
p-value
EF Domain Score
Endpoint [Change from baseline] 13.3 [1.1] 17.7 [5.3]
Insertion of Penis (SEP2)
Endpoint [Change from baseline] 32% [2%] 54% [22%]
Maintenance of Erection (SEP3)
Endpoint [Change from baseline] 19% [4%] 41% [23%]
Results In Studies To Determine The Optimal Use Of CIALIS

Several studies were conducted with the objective of determining the optimal use of CIALIS in the treatment of ED. In one of these studies, the percentage of patients reporting successful erections within 30 minutes of dosing was determined. In this randomized, placebo-controlled, double-blinded trial, 223 patients were randomized to placebo, CIALIS 10, or 20 mg. Using a stopwatch, patients recorded the time following dosing at which a successful erection was obtained. A successful erection was defined as at least 1 erection in 4 attempts that led to successful intercourse. At or prior to 30 minutes, 35% (26/74), 38% (28/74), and 52% (39/75) of patients in the placebo, 10-, and 20-mg groups, respectively, reported successful erections as defined above.

Two studies were conducted to assess the efficacy of CIALIS at a given timepoint after dosing, specifically at 24 hours and at 36 hours after dosing.

In the first of these studies, 348 patients with ED were randomized to placebo or CIALIS 20 mg. Patients were encouraged to make 4 total attempts at intercourse; 2 attempts were to occur at 24 hours after dosing and 2 completely separate attempts were to occur at 36 hours after dosing. The results demonstrated a difference between the placebo group and the CIALIS group at each of the pre-specified timepoints. At the 24-hour timepoint, (more specifically, 22 to 26 hours), 53/144 (37%) patients reported at least 1 successful intercourse in the placebo group versus 84/138 (61%) in the CIALIS 20-mg group. At the 36-hour timepoint (more specifically, 33 to 39 hours), 49/133 (37%) of patients reported at least 1 successful intercourse in the placebo group versus 88/137 (64%) in the CIALIS 20-mg group.

In the second of these studies, a total of 483 patients were evenly randomized to 1 of 6 groups: 3 different dosing groups (placebo, CIALIS 10, or 20 mg) that were instructed to attempt intercourse at 2 different times (24 and 36 hours post-dosing). Patients were encouraged to make 4 separate attempts at their assigned dose and assigned timepoint. In this study, the results demonstrated a statistically significant difference between the placebo group and the CIALIS groups at each of the pre-specified timepoints. At the 24-hour timepoint, the mean, per patient percentage of attempts resulting in successful intercourse were 42, 56, and 67% for the placebo, CIALIS 10-, and 20-mg groups, respectively. At the 36-hour timepoint, the mean, per-patient percentage of attempts resulting in successful intercourse were 33, 56, and 62% for placebo, CIALIS 10-, and 20-mg groups, respectively.

CIALIS For Once Daily Use For ED

The efficacy and safety of CIALIS for once daily use in the treatment of erectile dysfunction has been evaluated in 2 clinical trials of 12-weeks duration and 1 clinical trial of 24-weeks duration, involving a total of 853 patients. CIALIS, when taken once daily, was shown to be effective in improving erectile function in men with erectile dysfunction (ED).

CIALIS was studied in the general ED population in 2 randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design, primary efficacy and safety studies of 12-and 24-weeks duration, respectively. One of these studies was conducted in the United States and one was conducted in centers outside the US. An additional efficacy and safety study was performed in ED patients with diabetes mellitus. CIALIS was taken once daily at doses ranging from 2.5 to 10 mg. Food and alcohol intake were not restricted. Timing of sexual activity was not restricted relative to when patients took Cialis.

Results In General ED Population

The primary US efficacy and safety trial included a total of 287 patients, with a mean age of 59 years (range 25 to 82 years). The population was 86% White, 6% Black, 6% Hispanic, and 2% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease. Most (>96%) patients reported ED of at least 1-year duration.

The primary efficacy and safety study conducted outside the US included 268 patients, with a mean age of 56 years (range 21 to 78 years). The population was 86% White, 3% Black, 0.4% Hispanic, and 10% of other ethnicities, and included patients with ED of various severities, etiologies (organic, psychogenic, mixed), and with multiple co-morbid conditions, including diabetes mellitus, hypertension, and other cardiovascular disease. Ninety-three percent of patients reported ED of at least 1-year duration.

In each of these trials, conducted without regard to the timing of dose and sexual intercourse, CIALIS demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary (see Table 17). When taken as directed, CIALIS was effective at improving erectile function.

In the 6 month double-blind study, the treatment effect of CIALIS did not diminish over time.

Table 17: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in the Two CIALIS for Once Daily Use Studies

Study H a Study I b
Placebo
(N=94)
CIALIS 2.5 mg
(N=96)
CIALIS 5 mg
(N=97)
p-value Placebo
(N=54)
CIALIS 5 mg
(N=109)
p-value
EF Domain Score
Endpoint 14.6 19.1 20.8 15.0 22.8
Change from baseline 1.2 6.1 c 7.0 c 0.9 9.7 c
Insertion of Penis (SEP2)
Endpoint 51% 65% 71% 52% 79%
Change from baseline 5% 24% c 26% c 11% 37% c
Maintenance of Erection (SEP3)
Endpoint 31% 50% 57% 37% 67%
Change from baseline 10% 31% c 35% c 13% 46% c
a Twenty-four-week study conducted in the US.
b Twelve-week study conducted outside the US.
c Statistically significantly different from placebo.
Efficacy Results In ED Patients With Diabetes Mellitus

CIALIS for once daily use was shown to be effective in treating ED in patients with diabetes mellitus. Patients with diabetes were included in both studies in the general ED population (N=79). A third randomized, multicenter, double-blinded, placebo-controlled, parallel-arm design trial included only ED patients with type 1 or type 2 diabetes (N=298). In this third trial, CIALIS demonstrated clinically meaningful and statistically significant improvement in erectile function, as measured by the EF domain of the IIEF questionnaire and Questions 2 and 3 of the SEP diary (see Table 18).

Table 18: Mean Endpoint and Change from Baseline for the Primary Efficacy Variables in a CIALIS for Once Daily Use Study in ED Patients with Diabetes

Placebo
(N=100)
CIALIS 2.5 mg
(N=100)
CIALIS 5 mg
(N=98)
p-value
EF Domain Score
Endpoint 14.7 18.3 17.2
Change from baseline 1.3 4.8 a 4.5 a
Insertion of Penis (SEP2)
Endpoint 43% 62% 61%
Change from baseline 5% 21% a 29% a
Maintenance of Erection (SEP3)
Endpoint 28% 46% 41%
Change from baseline 8% 26% a 25% a
a Statistically significantly different from placebo.

CIALIS 5 mg For Once Daily Use For Benign Prostatic Hyperplasia (BPH)

The efficacy and safety of CIALIS for once daily use for the treatment of the signs and symptoms of BPH was evaluated in 3 randomized, multinational, double-blinded, placebo-controlled, parallel-design, efficacy and safety studies of 12 weeks duration. Two of these studies were in men with BPH and one study was specific to men with both ED and BPH [see Clinical Studies]. The first study (Study J) randomized 1058 patients to receive either CIALIS 2.5 mg, 5 mg, 10 mg or 20 mg for once daily use or placebo. The second study (Study K) randomized 325 patients to receive either CIALIS 5 mg for once daily use or placebo. The full study population was 87% White, 2% Black, 11% other races; 15% was of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.

The primary efficacy endpoint in the two studies that evaluated the effect of CIALIS for the signs and symptoms of BPH was the International Prostate Symptom Score (IPSS), a four week recall questionnaire that was administered at the beginning and end of a placebo run-in period and subsequently at follow-up visits after randomization. The IPSS assesses the severity of irritative (frequency, urgency, nocturia) and obstructive symptoms (incomplete emptying, stopping and starting, weak stream, and pushing or straining), with scores ranging from 0 to 35; higher numeric scores representing greater severity. Maximum urinary flow rate (Qmax), an objective measure of urine flow, was assessed as a secondary efficacy endpoint in Study J and as a safety endpoint in Study K.

The results for BPH patients with moderate to severe symptoms and a mean age of 63.2 years (range 44 to 87) who received either CIALIS 5 mg for once daily use or placebo (N=748) in Studies J and K are shown in Table 19 and Figures 5 and 6, respectively.

In each of these 2 trials, CIALIS 5 mg for once daily use resulted in statistically significant improvement in the total IPSS compared to placebo. Mean total IPSS showed a decrease starting at the first scheduled observation (4 weeks) in Study K and remained decreased through 12 weeks.

Table 19: Mean IPSS Changes in BPH Patients in Two CIALIS for Once Daily Use Studies

Study J Study K
Placebo
(N=205)
CIALIS 5 mg
(N=205)
p-value Placebo
(N=164)
CIALIS 5 mg
(N=160)
p-value
Total Symptom Score (IPSS)
Baseline 17.1 17.3 16.6 17.1
Change from Baseline to Week 12 -2.2 -4.8 -3.6 -5.6 .004

Figure 5: Mean IPSS Changes in BPH Patients by Visit in Study J

Figure 6: Mean IPSS Changes in BPH Patients by Visit in Study K

In Study J, the effect of CIALIS 5 mg once daily on maximum urinary flow rate (Qmax) was evaluated as a secondary efficacy endpoint. Mean Qmax increased from baseline in both the treatment and placebo groups (CIALIS 5 mg: 1.6 mL/sec, placebo: 1.2 mL/sec); however, these changes were not significantly different between groups.

In Study K, the effect of CIALIS 5 mg once daily on Qmax was evaluated as a safety endpoint. Mean Qmax increased from baseline in both the treatment and placebo groups (CIALIS 5 mg: 1.6 mL/sec, placebo: 1.1 mL/sec); however, these changes were not significantly different between groups.

Efficacy Results In Patients With BPH Initiating CIALIS And Finasteride

CIALIS for once daily use initiated together with finasteride was shown to be effective in treating the signs and symptoms of BPH in men with an enlarged prostate (>30 cc) for up to 26 weeks. This additional double-blinded, parallel-design study of 26 weeks duration randomized 696 men to initiate either CIALIS 5 mg with finasteride 5 mg or placebo with finasteride 5 mg. The study population had a mean age of 64 years (range 46-86). Patients with multiple co-morbid conditions such as erectile dysfunction, diabetes mellitus, hypertension, and other cardiovascular disease were included.

CIALIS with finasteride demonstrated statistically significant improvement in the signs and symptoms of BPH compared to placebo with finasteride, as measured by the total IPSS at 12 weeks, the primary study endpoint (see Table 20). Key secondary endpoints demonstrated improvement in total IPSS starting at the first scheduled observation at week 4 (CIALIS -4.0, placebo -2.3: p<.001) and the score remained decreased through 26 weeks (CIALIS -5.5, placebo -4.5; p=.022). However, the magnitude of the treatment difference between placebo/finasteride and CIALIS/finasteride decreased from 1.7 points at Week 4 to 1.0 point at Week 26, as shown in Table 20 and in Figure 7. The incremental benefit of CIALIS beyond 26 weeks is unknown.

Table 20: Mean Total IPSS Changes in BPH Patients in a CIALIS for Once Daily Use Study Together with Finasteride

n Placebo and finasteride 5 mg
(N=350) a
n CIALIS 5mg and finasteride 5 mg
(N=345) a
Treatment difference p-value b
Total Symptom Score (IPSS)
Baseline c 349 17.4 344 17.1
Change from Baseline to Week 4 b 340 -2.3 330 -4.0 -1.7
Change from Baseline to Week 12 b 318 -3.8 317 -5.2 -1.4 .001
Change from Baseline to Week 26 b 295 -4.5 308 -5.5 -1.0 .022
a Overall ITT population.
b Mixed model for repeated measurements. Unadjusted mean.

Figure 7: Mean Total IPSS Changes By Visit in BPH Patients Taking CIALIS for Once Daily Use Together With Finasteride

In the 404 patients who had both ED and BPH at baseline, changes in erectile function were assessed as key secondary endpoints using the EF domain of the IIEF questionnaire. CIALIS with finasteride (N=203) was compared to placebo with finasteride (N=201). A statistically significant improvement from baseline (CIALIS/finasteride 13.7, placebo/finasteride 15.1) was observed at week 4 (CIALIS/finasteride 3.7, placebo/finasteride -1.1; p<.001), week 12 (CIALIS/finasteride 4.7, placebo/finasteride 0.6; p<.001), and week 26 (CIALIS/finasteride 4.7, placebo/finasteride 0.0; p<.001).

CIALIS 5 mg For Once Daily Use For ED And BPH

The efficacy and safety of CIALIS for once daily use for the treatment of ED, and the signs and symptoms of BPH, in patients with both conditions was evaluated in one placebo-controlled, multinational, double-blind, parallel-arm study which randomized 606 patients to receive either CIALIS 2.5 mg, 5 mg, for once daily use or placebo. ED severity ranged from mild to severe and BPH severity ranged from moderate to severe. The full study population had a mean age of 63 years (range 45 to 83) and was 93% White, 4% Black, 3% other races; 16% were of Hispanic ethnicity. Patients with multiple co-morbid conditions such as diabetes mellitus, hypertension, and other cardiovascular disease were included.

In this study, the co-primary endpoints were total IPSS and the Erectile Function (EF) domain score of the International Index of Erectile Function (IIEF). One of the key secondary endpoints in this study was Question 3 of the Sexual Encounter Profile diary (SEP3). Timing of sexual activity was not restricted relative to when patients took CIALIS.

The efficacy results for patients with both ED and BPH, who received either CIALIS 5 mg for once daily use or placebo (N=408) are shown in Tables 21 and 22 and Figure 8.

CIALIS 5 mg for once daily use resulted in statistically significant improvements in the total IPSS and in the EF domain of the IIEF questionnaire. CIALIS 5 mg for once daily use also resulted in statistically significant improvement in SEP3. CIALIS 2.5 mg did not result in statistically significant improvement in the total IPSS.

Table 21: Mean IPSS and IIEF EF Domain Changes in the CIALIS 5 mg for Once Daily Use Study in Patients with ED and BPH

Placebo CIALIS 5 mg p-value
Total Symptom Score (IPSS)
(N=193) (N=206)
Baseline 18.2 18.5
Change from Baseline to Week 12 -3.8 -6.1
EF Domain Score (IIEF EF)
(N=188) (N=202)
Baseline 15.6 16.5
Endpoint 17.6 22.9
Change from Baseline to Week 12 1.9 6.5

Table 22: Mean SEP Question 3 Changes in the CIALIS 5 mg for Once Daily Use Study in Patients with ED and BPH

Placebo
(N=187)
CIALIS 5 mg
(N=199)
p-value
Maintenance of Erection (SEP3)
Baseline 36% 43%
Endpoint 48% 72%
Change from Baseline to Week 12 12% 32%

CIALIS for once daily use resulted in improvement in the IPSS total score at the first scheduled observation (week 2) and throughout the 12 weeks of treatment (see Figure 8).

Figure 8: Mean IPSS Changes in ED/BPH Patients by Visit in Study L

In this study, the effect of CIALIS 5 mg once daily on Qmax was evaluated as a safety endpoint. Mean Qmax increased from baseline in both the treatment and placebo groups (CIALIS 5 mg: 1.6 mL/sec, placebo: 1.2 mL/sec); however, these changes were not significantly different between groups.

PATIENT INFORMATION

CIALIS®
(See-AL-iss)
(tadalafil) tablets

Read this important information before you start taking CIALIS and each time you get a refill. There may be new information. You may also find it helpful to share this information with your partner. Thisinformation does not take the place of talking with your healthcare provider. You and your healthcare provider should talk about CIALIS when you start taking it and at regular checkups. If you do notunderstand the information, or have questions, talk with your healthcare provider or pharmacist.

What Is The Most Important Information I Should Know About CIALIS?

CIALIS can cause your blood pressure to drop suddenly to an unsafe level if it is taken withcertain other medicines. You could get dizzy, faint, or have a heart attack or stroke. Never take CIALIS with any nitrate or guanylate cyclase stimulator medicines.

Do not take CIALIS if you take any medicines called “nitrates.” Nitrates are commonly used to treat angina. Angina is a symptom of heart disease and can cause pain in your chest, jaw, or down your arm.

  • Medicines called nitrates include nitroglycerin that is found in tablets, sprays, ointments,pastes, or patches. Nitrates can also be found in other medicines such as isosorbide dinitrate or isosorbide mononitrate. Some recreational drugs called “poppers” also contain nitrates,such as amyl nitrite and butyl nitrite.

Do not take CIALIS if you take medicines called guanylate cyclase stimulators which include:

Ask your healthcare provider or pharmacist if you are not sure if any of your medicines are nitrates or guanylate cyclase stimulators, such as riociguat.

Tell all of your healthcare providers that you take CIALIS. If you need emergency medical care for a heart problem, it will be important for your healthcare provider to know when you last took CIALIS.

After taking a single tablet, some of the active ingredient of CIALIS remains in your body formore than 2 days. The active ingredient can remain longer if you have problems with your kidneys orliver, or you are taking certain other medications (see “Can Other Medicines Affect CIALIS?”).

Stop sexual activity and get medical help right away if you get symptoms such as chest pain,dizziness, or nausea during sex. Sexual activity can put an extra strain on your heart, especially ifyour heart is already weak from a heart attack or heart disease.

See also “What Are The Possible Side Effects Of CIALIS?”

CIALIS is a prescription medicine taken by mouth for the treatment of:

ED is a condition where the penis does not fill with enough blood to harden and expand when a man is sexually excited, or when he cannot keep an erection. A man who has trouble getting or keeping an erection should see his healthcare provider for help if the condition bothers him. CIALIS helpsincrease blood flow to the penis and may help men with ED get and keep an erection satisfactory forsexual activity. Once a man has completed sexual activity, blood flow to his penis decreases, and hiserection goes away.

Some form of sexual stimulation is needed for an erection to happen with CIALIS.

  • cure ED
  • increase a man’s sexual desire
  • protect a man or his partner from sexually transmitted diseases, including HIV. Speak to yourhealthcare provider about ways to guard against sexually transmitted diseases.
  • serve as a male form of birth control

CIALIS is only for men over the age of 18, including men with diabetes or who have undergone prostatectomy.

CIALIS for the Treatment of Symptoms of BPH

BPH is a condition that happens in men, where the prostate gland enlarges which can cause urinary symptoms.

CIALIS for the Treatment of ED and Symptoms of BPH

ED and symptoms of BPH may happen in the same person and at the same time. Men who have both ED and symptoms of BPH may take CIALIS for the treatment of both conditions.

CIALIS must be used only under a healthcare provider’s care.

  • take any medicines called “nitrates”.
  • use recreational drugs called “poppers” like amyl nitrite and butyl nitrite. (See “What Is The Most Important Information I Should Know About CIALIS?”)
  • take any medicines called guanylate cyclase stimulators, such as riociguat.
  • are allergic to CIALIS or ADCIRCA®, or any of its ingredients. See the end of this leaflet for a complete list of ingredients in CIALIS. Symptoms of an allergic reaction may include:
    • rash
    • hives
    • swelling of the lips, tongue, or throat
    • difficulty breathing or swallowing

    Call your healthcare provider or get help right away if you have any of the symptoms of an allergic reaction listed above.

    What Should I Tell My Healthcare Provider Before Taking CIALIS?

    CIALIS is not right for everyone. Only your healthcare provider and you can decide if CIALIS is right for you. Before taking CIALIS, tell your healthcare provider about all your medical problems,including if you:

    • have heart problems such as angina, heart failure, irregular heartbeats, or have had a heartattack. Ask your healthcare provider if it is safe for you to have sexual activity. You should nottake CIALIS if your healthcare provider has told you not to have sexual activity because of yourhealth problems.
    • have pulmonary hypertension
    • have low blood pressure or have high blood pressure that is not controlled
    • have had a stroke
    • have liver problems
    • have kidney problems or require dialysis
    • have retinitis pigmentosa, a rare genetic (runs in families) eye disease
    • have ever had severe vision loss, including a condition called NAION
    • have stomach ulcers
    • have a bleeding problem
    • have a deformed penis shape or Peyronie’s disease
    • have had an erection that lasted more than 4 hours
    • have blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia

    Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. CIALIS and other medicines mayaffect each other. Always check with your healthcare provider before starting or stopping anymedicines. Especially tell your healthcare provider if you take any of the following*:

    • medicines called nitrates (see “What Is The Most Important Information I Should Know About CIALIS?”)
    • medicines called guanylate cyclase stimulators, such as riociguat (Adempas®), used to treat pulmonary hypertension
    • medicines called alpha blockers. These include Hytrin® (terazosin HCl), Flomax® (tamsulosin HCl), Cardura® (doxazosin mesylate), Minipress® (prazosin HCl), Uroxatral® (alfuzosin HCl), Jalyn® (dutasteride and tamsulosin HCl) or Rapaflo® (silodosin). Alpha-blockers are sometimesprescribed for prostate problems or high blood pressure. If CIALIS is taken with certain alpha blockers, your blood pressure could suddenly drop. You could get dizzy or faint.
    • other medicines to treat high blood pressure (hypertension)
    • medicines called HIV protease inhibitors, such as ritonavir (Norvir®, Kaletra®)
    • some types of oral antifungals such as ketoconazole (Nizoral®), itraconazole (Sporanox®)
    • some types of antibiotics such as clarithromycin (Biaxin®), telithromycin (Ketek®), erythromycin (several brand names exist. Please consult your healthcare provider to determine if you are taking this medicine).
    • other medicines or treatments for ED.
    • CIALIS is also marketed as ADCIRCA for the treatment of pulmonary arterial hypertension. Do not take both CIALIS and ADCIRCA. Do not take sildenafil citrate (Revatio®) with CIALIS.
    • Take CIALIS exactly as your healthcare provider prescribes it. Your healthcare provider willprescribe the dose that is right for you.
    • Some men can only take a low dose of CIALIS or may have to take it less often, because ofmedical conditions or medicines they take.
    • Do not change your dose or the way you take CIALIS without talking to your healthcare provider. Your healthcare provider may lower or raise your dose, depending on how your bodyreacts to CIALIS and your health condition.
    • CIALIS may be taken with or without meals.
    • If you take too much CIALIS, call your healthcare provider or emergency room right away.

    How Should I Take CIALIS for Symptoms of BPH?

    For symptoms of BPH, CIALIS is taken once daily.

    • Do not take CIALIS more than one time each day.
    • Take one CIALIS tablet every day at about the same time of day.
    • If you miss a dose, you may take it when you remember but do not take more than one dose per day.

    For ED, there are two ways to take CIALIS -either for use as needed OR for use once daily.

    • Do not take CIALIS more than one time each day.
    • Take one CIALIS tablet before you expect to have sexual activity. You may be able to have sexual activity at 30 minutes after taking CIALIS and up to 36 hours after taking it. You andyour healthcare provider should consider this in deciding when you should take CIALIS before sexual activity. Some form of sexual stimulation is needed for an erection to happen with CIALIS.
    • Your healthcare provider may change your dose of CIALIS depending on how you respond to the medicine, and on your health condition.

    CIALIS for once daily use is a lower dose you take every day.

    • Do not take CIALIS more than one time each day.
    • Take one CIALIS tablet every day at about the same time of day. You may attempt sexualactivity at any time between doses.
    • If you miss a dose, you may take it when you remember but do not take more than one dose per day.
    • Some form of sexual stimulation is needed for an erection to happen with CIALIS.
    • Your healthcare provider may change your dose of CIALIS depending on how you respond to the medicine, and on your health condition.

    How Should I Take CIALIS for Both ED and the Symptoms of BPH?

    For both ED and the symptoms of BPH, CIALIS is taken once daily.

    • Do not take CIALIS more than one time each day.
    • Take one CIALIS tablet every day at about the same time of day. You may attempt sexualactivity at any time between doses.
    • If you miss a dose, you may take it when you remember but do not take more than one dose per day.
    • Some form of sexual stimulation is needed for an erection to happen with CIALIS.

    What Should I Avoid While Taking CIALIS?

    • Do not use other ED medicines or ED treatments while taking CIALIS.
    • Do not drink too much alcohol when taking CIALIS (for example, 5 glasses of wine or 5 shotsof whiskey). Drinking too much alcohol can increase your chances of getting a headache orgetting dizzy, increasing your heart rate, or lowering your blood pressure.

    What Are The Possible Side Effects Of CIALIS?

    See “What Is The Most Important Information I Should Know About CIALIS?”

    The most common side effects with CIALIS are: headache, indigestion, back pain, muscle aches,flushing, and stuffy or runny nose. These side effects usually go away after a few hours. Men who getback pain and muscle aches usually get it 12 to 24 hours after taking CIALIS. Back pain and muscle aches usually go away within 2 days.

    Call your healthcare provider if you get any side effect that bothers you or one that does not go away.

    An erection that won’t go away (priapism). If you get an erection that lasts more than 4 hours, getmedical help right away. Priapism must be treated as soon as possible or lasting damage can happen to your penis, including the inability to have erections.

    Color vision changes, such as seeing a blue tinge (shade) to objects or having difficulty telling the difference between the colors blue and green.

    In rare instances, men taking PDE5 inhibitors (oral erectile dysfunction medicines, including CIALIS)reported a sudden decrease or loss of vision in one or both eyes. It is uncertain whether PDE5 inhibitors directly cause the vision loss. If you experience sudden decrease or loss of vision, stoptaking PDE5 inhibitors, including CIALIS, and call a healthcare provider right away.

    Sudden loss or decrease in hearing, sometimes with ringing in the ears and dizziness, has been rarely reported in people taking PDE5 inhibitors, including CIALIS. It is not possible to determine whether these events are related directly to the PDE5 inhibitors, to other diseases or medications, to other factors, or to a combination of factors. If you experience these symptoms, stop taking CIALISand contact a healthcare provider right away.

    These are not all the possible side effects of CIALIS. For more information, ask your healthcare provider or pharmacist.

    Store CIALIS at room temperature between 59° and 86°F (15° and 30°C).

    Keep CIALIS and all medicines out of the reach of children.

    Medicines are sometimes prescribed for conditions other than those described in patient information leaflets. Do not use CIALIS for a condition for which it was not prescribed. Do not give CIALIS to other people, even if they have the same symptoms that you have. It may harm them.

    This is a summary of the most important information about CIALIS. If you would like more information,talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about CIALIS that is written for health providers. For more information you can also visitwww.cialis.com, or call 1-877-CIALIS1 (1-877-242-5471).

    What Are The Ingredients In CIALIS?

    Inactive Ingredients: croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxide,lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, talc,titanium dioxide, and triacetin.

    This Patient Information has been approved by the U.S. Food and Drug Administration