Avanafil

Before taking avanafil,

• tell your doctor and pharmacist if you are allergic to avanafil, any other medications, or any of the ingredients in avanafil tablets. Ask your pharmacist or check the patient information for a list of the ingredients.
• do not take avanafil if you are taking or have recently taken riociguat (Adempas) or nitrates such as isosorbide dinitrate (Dilatrate-SR, Isordil, in BiDil), isosorbide mononitrate (Monoket), and nitroglycerin (Minitran, Nitro-Dur, Nitromist, Nitrostat, others). Nitrates come as tablets, sublingual (under the tongue) tablets, sprays, patches, pastes, and ointments. Ask your doctor if you are not sure if any of your medications contain nitrates.
• do not take street drugs containing nitrates such as amyl nitrate and butyl nitrate ('poppers') while taking avanafil.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: alpha blockers such as alfuzosin (Uroxatral), doxazosin (Cardura), prazosin (Minipress), tamsulosin (Flomax, in Jalyn), silodosin (Rapaflo), and terazosin; certain antifungal medications such as fluconazole (Diflucan), itraconazole (Onmel, Sporanox), and ketoconazole (Nizoral); aprepitant (Emend); clarithromycin (Biaxin, in Prevpac); diltiazem (Cardizem, Cartia, Tiazac); erythromycin (E.E.S, E-Mycin, Erythrocin); HIV protease inhibitors such as atazanavir (Reyataz, in Evotaz), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), and saquinavir (Invirase); other medications or treatments for erectile dysfunction; medications for high blood pressure; nefazodone; verapamil (Calan, Covera, Verelan, others); and telithromycin (Ketek). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with avanafil, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor if you have ever been advised by a doctor to avoid sexual activity for medical reasons, if you have had heart surgery within the past 6 months and if you have ever had an erection that lasted longer than 4 hours. Also tell your doctor if you have or have ever had a condition that affects the shape of the penis such as angulation, cavernosal fibrosis, or Peyronie's disease; a heart attack; a stroke; an irregular heartbeat; a blocked artery; angina (chest pain); high or low blood pressure; heart failure; blood cell problems such as sickle cell anemia (a disease of the red blood cells), multiple myeloma (cancer of the plasma cells), or leukemia (cancer of the white blood cells); ulcers; bleeding problems; or liver or kidney disease. Also tell your doctor if you have or have ever had retinitis pigmentosa (a rare inherited eye disease) or if you have ever had severe vision loss, especially if you were told that the vision loss was caused by a blockage of blood flow to the nerves that help you see.
• you should know that avanafil is only for use in males. Women should not take avanafil, especially if they are or may become pregnant or are breastfeeding. If a pregnant woman takes avanafil, she should call her doctor.
• talk to your doctor about the safe use of alcoholic beverages during your treatment with avanafil. If you drink a large amount of alcohol (more than three glasses of wine or three shots of whiskey) while you are taking avanafil you are more likely to experience certain side effects of avanafil such as dizziness, headache, fast heartbeat, and low blood pressure.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking avanafil.
• you should know that sexual activity may be a strain on your heart, especially if you have heart disease. If you have chest pain, dizziness, or nausea during sexual activity, call your doctor immediately and avoid sexual activity until your doctor tells you otherwise.
• tell all your healthcare providers that you are taking avanafil. If you ever need emergency medical treatment for a heart problem, the healthcare providers who treat you will need to know when you last took avanafil.

The breakdown and elimination of avanafil from the body may be decreased by several drugs, leading to increased blood levels of avanafil and possible toxicity. Ketoconazole (Nizoral), itraconazole (Sporanox), indinavir (Crixivan) and ritonavir (Norvir), atazanavir (Reyataz), clarithromycin (Biaxin), nelfinavir (Viracept), saquinavir (Invirase), telithromycin (Ketek) profoundly increase blood levels of avanafil and should not be combined with avanafil.

The dose of avanafil should not exceed 50 mg daily when combined with erythromycin, amprenavir (Agenerase), aprepitant (Emend), diltiazem (Cardizem), fluconazole (Diflucan), fosamprenavir (Lexiva), and verapamil (Calan) because these drug moderately increase blood levels of avanafil.

Avanafil exaggerates the increases in heart rate and lowering of blood pressure caused by nitrates, for example, nitroglycerin, isosorbide dinitrate (Isordil), isosorbide mononitrate (Imdur, Ismo, Monoket), and nitroglycerin (Nitro-Dur, Transderm-Nitro) that are used primarily for treating heart pain (angina). In patients who take nitrates for angina, avanafil could cause heart pain or possibly even a heart attack by exaggerating the increase in heart rate and the lowering of blood pressure. Therefore, avanafil should not be used with nitrates. If nitrates must be administered to a patient who has taken avanafil, at least 12 hours should elapse after the last dose of avanafil before administering the nitrates. Avanafil also exaggerates the blood pressure lowering effects of some alpha-blocking drugs for example, terazosin (Hytrin) that primarily are used for treating high blood pressure or enlargement of the prostate. Individuals who take these alpha-blockers should be on a stable dose of the alpha-blocker before avanafil is started. In such situations, avanafil should be started at the 50 mg dose. If the patient is already taking avanafil, the alpha-blocker should be started at the lowest dose.

Avanafil and alcohol both lower blood pressure. Therefore, combining avanafil with alcohol may cause excessive drops in blood pressure and cause dizziness, headaches, and increased heart rate.

Avanafil should not be combined with other PDE5 inhibitors used for treating impotence, for example, vardenafil (Levitra) or sildenafil (Viagra, Revatio).

Tablets: 50, 100 and 200 mg.

Avanafil should be stored at room temperature between 20 C and 25 C (68 F and 77 F).

STENDRA®
(sten-druh)
(avanafil) Tablets

Read this Patient Information before you start taking STENDRA and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is the most important information I should know about STENDRA?

STENDRA can cause your blood pressure to drop suddenly to an unsafe level if it is taken with certain other medicines. Do not take STENDRA if you take any medicines called “nitrates.” Nitrates are used to treat chest pain (angina). A sudden drop in blood pressure can cause you to feel dizzy, faint, or have a heart attack or stroke.

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

• riociguat (Adempas®) a medicine that treats pulmonary arterial hypertension and chronic-thromboembolic pulmonary hypertension

Ask your healthcare provider or pharmacist if any of your medicines are nitrates or guanylate cyclase stimulators, such as riociguat.

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

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 if your heart is already weak from a heart attack or heart disease.

What is STENDRA?

STENDRA is a prescription medicine used to treat erectile dysfunction (ED).

STENDRA is not for use in women or children.

It is not known if STENDRA is safe and effective in women or children under 18 years of age.

Who should not take STENDRA?

Do not take STENDRA if you:

• take medicines called “nitrates”
• use street drugs called “poppers” such as amyl nitrate and butyl nitrate
• are allergic to avanafil or any of the ingredients in STENDRA. See the end of this leaflet for a complete list of ingredients in STENDRA.

What should I tell my healthcare provider before taking STENDRA?

Before you take STENDRA, tell your healthcare provider if you:

• have or have had heart problems such as a heart attack, irregular heartbeat, angina, or heart failure
• have had heart surgery within the last 6 months
• have had a stroke
• have low blood pressure, or high blood pressure that is not controlled
• have a deformed penis shape
• have had an erection that lasted for more than 4 hours
• have problems with your blood cells such as sickle cell anemia, multiple myeloma, or leukemia
• have retinitis pigmentosa, a rare genetic (runs in families) eye disease
• have ever had severe vision loss, including an eye problem called non-arteritic anterior ischemic optic neuropathy (NAION)
• have bleeding problems
• have or have had stomach ulcers
• have liver problems
• have kidney problems or are having kidney dialysis
• have any other medical conditions

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

STENDRA may affect the way other medicines work, and other medicines may affect the way STENDRA works causing side effects. 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 STENDRA?)
• medicines called guanylate cyclose stimulators, such a riociguat (see What is the most important information I should know about STENDRA?)
• medicines called HIV protease inhibitors, such as ritonavir (Norvir), indinavir (Crixivan), saquinavir (Fortavase or Invirase) or atazanir (Reyataz)
• some types of oral antifungal medicines, such as ketoconazole (Nizoral), and itraconozale (Sporonox)
• some types of antibiotics, such as clarithromycin (Biaxin), telithromycin (Ketek), or erythromycin
• medicines called alpha blockers. These include Hytrin (terazosin), Flomax (tamsulosin HCl), Cardura (doxazosin), Minipress (prazosin HCl), Uroxatral (alfuzosin HCl), Jalyn (dutasteride and tamsulosin HCl), or Rapaflo (silodosin). Alpha-blockers are sometimes prescribed for prostate problems or high blood pressure. In some patients, the use of STENDRA with alpha-blockers can lead to a drop in blood pressure or to fainting.
• other medicines that treat high blood pressure
• other medicines or treatments for ED Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

How should I take STENDRA?

• Take STENDRA exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much STENDRA to take and when to take it.
• Take STENDRA 100 mg or 200 mg as early as approximately 15 minutes before sexual activity.
• Take STENDRA 50 mg as early as approximately 30 minutes before sexual activity
• Do not take STENDRA more than 1 time a day.
• Your healthcare provider may change your dose if needed.
• You should take the lowest dose of STENDRA that works for you. You and your healthcare provider should decide about the lowest dose of STENDRA that works for you.
• STENDRA may be taken with or without food.
• Do not drink too much alcohol when taking STENDRA (for example, 3 glasses of wine, or 3 shots of whiskey). Drinking too much alcohol when taking STENDRA can increase your chances of getting a headache or getting dizzy, increasing your heart rate, or lowering your blood pressure.

What are the possible side effects of STENDRA?

The most common side effects of STENDRA are:

• headache
• flushing
• stuffy or runny nose
• sore throat
• back pain

STENDRA may uncommonly cause:

• an erection that will not go away (priapism). If you have an erection that lasts more than 4 hours, get medical help right away.
• sudden vision loss in 1 or both eyes. Sudden vision loss in 1 or both eyes can be a sign of a serious eye problem called non-arteritic anterior ischemic optic neuropathy (NAION). It is uncertain whether PDE5 inhibitors directly cause vision loss. Stop taking STENDRA and call your healthcare provider right away if you have sudden vision loss in 1 or both eyes.
• sudden hearing decrease or hearing loss. Some people may also have ringing in their ears (tinnitus) or dizziness.

Tell your healthcare provider if you have any side effect that bothers you or does not go away.

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

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

How should I store STENDRA?

• Store STENDRA at 68°F to 77°F (20°C to 25°C).
• Keep STENDRA out of the light.

Keep STENDRA and all medicines out of the reach of children

General information about the safe and effective use of STENDRA.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use STENDRA for a condition for which it was not prescribed. Do not give STENDRA to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about STENDRA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about STENDRA that is written for health professionals.

For more information, go to www.STENDRA.com or call 1-844-458-4887.

What are the ingredients in STENDRA?

Active ingredient: avanafil

Inactive ingredients: mannitol, fumaric acid, hydroxypropylcellulose, low substituted hydroxypropylcellulose, calcium carbonate, magnesium stearate, and ferric oxide yellow

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

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medicines called nitrates such as isosorbide dinitrate (Isordil), isosorbide mononitrate (Imdur, ISMO), and nitroglycerin (Nitro-BID, Nitro-Dur, Nitroquick, Nitrostat)
• medicines called HIV protease inhibitors, such as ritonavir (Norvir), indinavir (Crixivan), saquinavir (Fortavase or Invirase), fosamprenavir (Lexiva), atazanir (Reyataz), or nelfinavir (Viracept)
• some types of oral antifungal medicines, such as ketoconazole (Nizoral), fluconazole (Diflucan), and itraconozale (Sporonox)
• some types of antibiotics, such as clarithromycin (Biaxin), telithromycin (Ketek), or erythromycin
• medicines called alpha blockers. These include Hytrin (terazosin), Flomax (tamsulosin), Cardura (doxazosin), Minipress (prazosin), Uroxatral (alfuzosin), Jalyn (dutasteride and tamsulosin), or Rapaflo (silodosin). Alpha-blockers are sometimes prescribed for prostate problems or high blood pressure. In some patients, the use of avanafil with alpha-blockers can lead to a drop in blood pressure or to fainting.
• amlodipine (Norvasc), diltiazem (Cardizem, Dilacor, Tiazac), and verapamil (Calan, Covera, Isoptin, Verelan)
• nefazodone
• aprepitant (Emend)
• other medicines that treat high blood pressure
• other medicines or treatments for erectile dysfunction

This is not a complete list of avanafil drug interactions. Ask your doctor or pharmacist for more information.

Take avanafil exactly as prescribed. Your healthcare provider will tell you how much avanafil to take and when to take it.

Avanafil comes in tablet form and is taken typically once a day, on an as needed basis. Avanafil can be taken with or without food.

Take avanafil about 30 minutes before sexual activity. Some men may achieve an erection in approximately 15 minutes, and therefore, may be taken 15 minutes before sexual activity.

Do not take more avanafil than 1 time a day.

Do not drink too much alcohol when taking avanafil (for example, 3 glasses of wine, or 3 shots of whiskey). Drinking too much alcohol when taking avanafil can increase your chances of getting a headache or getting dizzy, increasing your heart rate, or lowering your blood pressure.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using avanafil and get emergency medical help if you have sudden vision loss.

During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of avanafil.

Stop using avanafil and call your doctor at once if you have:

• vision changes, sudden vision loss;

• ringing in your ears, or sudden hearing loss;

• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• pain, swelling, warmth, or redness in one or both legs;

• shortness of breath, swelling in your hands or feet;

• a light-headed feeling, like you might pass out; or

• penis erection that is painful or lasts 4 hours or longer.

Common side effects may include:

• headache;

• flushing (warmth, redness, or tingly feeling);

• cold symptoms such as runny or stuffy nose, sore throat; or

• back pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Erectile Dysfunction (ED)

To facilitate attainment of a sexually functional erection in men with ED (impotence).1 2 3 4 5 7 10

Some experts recommend a selective PDE type 5 inhibitor as first-line therapy for ED unless contraindicated.6 8 12 13 15 Evidence currently insufficient to establish superiority of one selective PDE type 5 inhibitor over another.8

Effective for ED only in the presence of adequate sexual stimulation.1

Metabolized principally by CYP3A4; CYP2C appears to play a minor role.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased avanafil exposure) and increased risk of PDE type 5 inhibitor-associated adverse effects (e.g., hypotension, syncope, visual changes, priapism).1 47 48 200 Do not use concomitantly with potent CYP3A4 inhibitors; reduce avanafil dose when used concomitantly with moderate CYP3A4 inhibitors.1 (See Specific Drugs and Foods under Interactions.)

Inducers of CYP: Potential pharmacokinetic interaction (decreased avanafil exposure) and possible decreased efficacy of avanafil.17 Drug interaction studies with CYP inducers not performed to date;1 concomitant use with CYP inducers not recommended.1

Specific Drugs and Foods

• Selective inhibitor of PDE, with high selectivity for PDE type 5, the principal isoenzyme involved in the metabolism of cGMP to GMP in the corpora cavernosa of the penis.1 2 3 7 In vitro, avanafil does not substantially inhibit other PDE isoenzymes.1 2 3 7

• Enhances the effect of nitric oxide by inhibiting PDE type 5-mediated hydrolysis of cGMP, resulting in vascular relaxation.1

• Potentiates accumulation of cGMP only when cGMP production in the penis is increased by sexual arousal; no effect on erectile function in the absence of sexual stimulation.1

• Although pharmacologically related to other PDE type 5 inhibitors, avanafil generally has a faster onset compared with sildenafil, vardenafil, or tadalafil.2 3 7

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Take avanafil before sex when you were told by your doctor. If you are not sure when to take this medicine, talk with your doctor.

What do I do if I miss a dose?

• This medicine is taken on an as needed basis. Do not take more often than every 24 hours unless told to do so by your doctor.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Concerns related to adverse effects:

• Color discrimination: May cause dose-related impairment of color discrimination. Use caution in patients with retinitis pigmentosa; a minority have genetic disorders of retinal phosphodiesterases (no safety information available).

• Hearing loss: Sudden decrease or loss of hearing has been reported rarely; hearing changes may be accompanied by tinnitus and dizziness. A direct relationship between therapy and hearing loss has not been determined.

• Hypotension: Decreases in blood pressure may occur due to vasodilator effects; use with caution in patients with left ventricular outflow obstruction (aortic stenosis or hypertrophic obstructive cardiomyopathy); may be more sensitive to hypotensive actions. Concurrent use with alpha-adrenergic antagonist therapy may cause symptomatic hypotension; patients should be hemodynamically stable prior to initiating therapy at the lowest possible dose. Patients should avoid or limit concurrent substantial ethanol consumption as this may increase the risk of symptomatic hypotension.

• Priapism: Painful erection >6 hours in duration has been reported (rarely). Instruct patients to seek immediate medical attention if erection persists >4 hours. Use with caution in patients who have conditions which may predispose them to priapism (sickle cell anemia, multiple myeloma, leukemia).

• Vision loss: Vision loss may occur rarely and be a sign of nonarteritic anterior ischemic optic neuropathy (NAION). Instruct patients to seek medical assistance for sudden loss of vision in one or both eyes. Patients who have already experienced NAION are at an increased risk of recurrence. Other risk factors for NAION include low cup-to-disc ratio (“crowded disc”), coronary artery disease, diabetes, hypertension, hyperlipidemia, smoking, and >50 years of age. Use with caution in these patients only when the benefits outweigh the risks. Safety and efficacy were not studied in patients with known degenerative retinal disorders (eg, retinitis pigmentosa); use is not recommended.

Disease-related concerns:

• Anatomical penis deformation: Use with caution in patients with anatomical deformation of the penis (angulation, cavernosal fibrosis, or Peyronie's disease).

• Bleeding disorders: Use with caution in patients with bleeding disorders; safety and efficacy have not been established.

• Cardiovascular disease: Use is not recommended in patients with hypotension (<90/50 mm Hg); uncontrolled hypertension (>170/100 mm Hg); unstable angina or angina during intercourse; life-threatening arrhythmias, stroke, MI, or coronary revascularization within the last 6 months; cardiac failure or coronary artery disease causing unstable angina. Safety and efficacy have not been studied in these patients. Use caution in patients with left ventricular outflow obstruction (eg, aortic stenosis, hypertrophic cardiomyopathy with outflow tract obstruction). There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the cardiovascular status of their patients prior to initiating any treatment for erectile dysfunction.

• Hepatic impairment: Safety and efficacy have not been studied in patients with severe hepatic impairment (Child-Pugh class C); therefore, use in these patients is not recommended.

• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; safety and efficacy have not been established.

• Renal impairment: Safety and efficacy have not been studied in patients with severe renal impairment or end-stage renal disease requiring dialysis, therefore, use in these patients is not recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Nitrates: Use of avanafil is contraindicated in patients currently taking nitrate preparations. According to the manufacturer, when nitrate administration is deemed medically necessary in a life-threatening situation, may administer nitrates only if 12 hours has elapsed after avanafil use. Of note, the elimination half-life of avanafil is similar to that of sildenafil and vardenafil which both require 24 hours to elapse prior to administration of nitrates (ACCF/AHA [Anderson, 2013]; ACCF/AHA [O'Gara, 2013]).

Other warnings/precautions:

• Appropriate use: Potential underlying causes of erectile dysfunction should be evaluated prior to treatment.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience flushing, pharyngitis, back pain, rhinitis, or rhinorrhea. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), angina, tachycardia, abnormal heartbeat, severe dizziness, passing out, severe headache, severe nausea, severe vomiting, vision changes, eye pain, severe eye irritation, blindness, hearing impairment, tinnitus, or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Data not available.

Administration advice: Avanafil can be taken with or without food