Stendra Side Effects Center

Last updated on RxList: 7/18/2021
Stendra Side Effects Center

Medical Editor: John Cunha, DO, FACOEP

What Is Stendra?

Stendra (avanafil) is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction.

What Are Side Effects of Stendra?

Common side effects of Stendra include:

Stendra may uncommonly cause:

  • an erection that will not go away (priapism),
  • sudden loss of vision in one or both eyes, and/or
  • sudden hearing decrease or hearing loss.

Dosage for Stendra

For most patients, the starting dose is 100 mg taken approximately 30 minutes before sexual activity, on an as needed basis. Stendra should not be taken more than once per day. The dose may be increased to 200 mg or decreased to 50 mg based on efficacy and/or tolerability, however, it is best to use the lowest beneficial dose.

What Drugs, Substances, or Supplements Interact with Stendra?

Stendra may interact with nitrates, alpha blockers, antihypertensives, alcohol, ketoconazole, ritonavir, antibiotics, and amlodipine. Tell your doctor all medications you use.

Stendra During Pregnancy and Breastfeeding

Stendra is not indicated for use in women. There are no adequate and well-controlled studies of Stendra in pregnant women. Consult your doctor before breastfeeding.

Additional Information

Our Stendra Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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.

QUESTION

Erectile dysfunction (ED) is… See Answer
Stendra Consumer Information

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;
  • 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.

Read the entire detailed patient monograph for Stendra (Avanafil)

SLIDESHOW

Erectile Dysfunction (ED) Causes and Treatment See Slideshow
Stendra Professional Information

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.

STENDRA was administered to 2215 men during clinical trials. In trials of STENDRA for use as needed, a total of 493 patients were exposed for greater than or equal to 6 months, and 153 patients were treated for greater than or equal to 12 months.

In three randomized, double-blind, placebo-controlled trials lasting up to 3 months in duration, the mean age of patients was 56.4 years (range from 23 to 88 years). 83.9% of patients were White, 13.8% were Black, 1.4% Asian, and < 1% Hispanic. 41.1% were current or previous smokers. 30.6% had diabetes mellitus.

The discontinuation rate due to adverse reactions for patients treated with STENDRA 50 mg, 100 mg, or 200 mg was 1.4%, 2.0%, and 2.0%, respectively, compared to 1.7% for placebo-treated patients.

Table 1 presents the adverse reactions reported when STENDRA was taken as recommended (on an as-needed basis) from these 3 clinical trials.

Table 1: Adverse Reactions Reported by Greater Than or Equal to 2% of Patients Treated with STENDRA From 3 Placebo-Controlled Clinical Trials Lasting 3 Months for STENDRA Use as Needed

Adverse
Reaction
Placebo
(N = 349)
STENDRA
50 mg
(N = 217)
STENDRA
100 mg
(N = 349)
STENDRA
200 mg
(N = 352)
Headache 1.7% 5.1% 6.9% 10.5%
Flushing 0.0% 3.2% 4.3% 4.0%
Nasal
congestion
1.1% 1.8% 2.9% 2.0%
Nasopharyngitis 2.9% 0.9% 2.6% 3.4%
Back pain 1.1% 3.2% 2.0% 1.1%

Adverse reactions reported by greater than or equal to 1%, but less than 2% of patients in any STENDRA dose group, and greater than placebo included: upper respiratory infection (URI), bronchitis, influenza, sinusitis, sinus congestion, hypertension, dyspepsia, nausea, constipation, and rash.

In an open-label, long-term extension study of two of these randomized, double-blind, placebo-controlled trials, the total duration of treatment was up to 52 weeks. Among the 712 patients who participated in this open-label extension study, the mean age of the population was 56.4 years (range from 23 to 88 years). The discontinuation rate due to adverse reactions for patients treated with STENDRA (50 mg, 100 mg, or 200 mg) was 2.8%.

In this extension trial, all eligible patients were initially assigned to STENDRA 100 mg. At any point during the trial, patients could request to have their dose of STENDRA increased to 200 mg or decreased to 50 mg based on their individual response to treatment. In total, 536 (approximately 75%) patients increased their dose to 200 mg and 5 (less than 1%) patients reduced their dose to 50 mg.

Table 2 presents the adverse reactions reported when STENDRA was taken as recommended (on an as-needed basis) in this open-label extension trial.

Table 2: Adverse Reactions Reported by Greater Than or Equal to 2% of Patients Treated With STENDRA in an Open-Label Extension Trial

Adverse Reaction STENDRA
(N = 711)
Headache 5.6%
Flushing 3.5%
Nasopharyngitis 3.4%
Nasal congestion 2.1%

Adverse reactions reported by greater than or equal to 1%, but less than 2% of patients in the open-label extension study included: upper respiratory infection (URI), influenza, sinusitis, bronchitis, dizziness, back pain, arthralgia, hypertension, and diarrhea.

The following events occurred in less than 1% of patients in the three placebo-controlled 3-month clinical trials and/or the open-label, long-term extension study lasting 12 months. A causal relationship to STENDRA is uncertain. Excluded from this list are those events that were minor, those with no plausible relation to drug use and reports too imprecise to be meaningful.

Body as a whole - edema peripheral, fatigue

Cardiovascular - angina, unstable angina, deep vein thrombosis, palpitations

Digestive - gastritis, gastroesophageal reflux disease, hypoglycemia, blood glucose increased, alanine aminotransferase increased, oropharyngeal pain, stomach discomfort, vomiting

Musculoskeletal - muscle spasms, musculoskeletal pain, myalgia, pain in extremity

Nervous - depression, insomnia, somnolence, vertigo

Respiratory - cough, dyspnea exertional, epistaxis, wheezing

Skin and Appendages -pruritus

Urogenital-balanitis, erection increased, hematuria, nephrolithiasis, pollakiuria, urinary tract infection

In an additional, randomized, double-blind, placebo-controlled study lasting up to 3 months in 298 men who had undergone bilateral nerve-sparing radical prostatectomy for prostate cancer, the mean age of patients was 58.4 years (range 40 – 70). Table 3 presents the adverse reactions reported in this additional study.

Table 3: Adverse Reactions Reported by Greater than or Equal to 2% of Patients Treated with STENDRA in a Placebo-Controlled Clinical Trial Lasting 3 Months in Patients Who Underwent Bilateral Nerve-Sparing Radical Prostatectomy

Adverse Reaction Placebo
(N = 100)
STENDRA
100 mg
(N = 99)
STENDRA
200 mg
(N = 99)
Headache 1.0% 8.1% 12.1%
Flushing 0.0% 5.1% 10.1%
Nasopharyngitis 0.0% 3.0% 5.1%
Upper respiratory infection 0.0% 2.0% 3.0%
Nasal congestion 1.0% 3.0% 1.0%
Back pain 1.0% 3.0% 2.0%
Electrocardiogram
abnormal
0.0% 1.0% 3.0%
Dizziness 0.0% 1.0% 2.0%

A randomized, double-blind, placebo-controlled 2 months study was conducted in 435 subjects with a mean age of 58.2 years (range 24 to 86 years) to determine the time to onset of effect of STENDRA, defined as the time to the first occurrence of an erection sufficient for sexual intercourse. Table 4 presents the adverse reactions occurring in ≥ 2% of subjects treated with STENDRA.

Table 4: Adverse Reactions Reported by ≥ 2% of Patients Treated with STENDRA in a Placebo-Controlled Clinical Trial Lasting 2 Months to Determine the Time to Onset of Effect (Study 3)

Adverse Reaction Placebo
(N = 143)
STENDRA
100 mg
(N = 146)
STENDRA
200 mg
(N = 146)
Headache 0.7% 1.4% 8.9%
Nasal congestion 0.0% 0.7% 4.1%
Gastroenteritis viral 0.0% 0.0% 2.1%

Across all trials with any STENDRA dose, 1 subject reported a change in color vision.

Postmarketing Experience

Ophthalmologic

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 phosphodiesterase type 5 (PDE5) inhibitors. Most, but not all, of these patients had underlying anatomic or vascular risk factors for developing 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 and PATIENT INFORMATION].

DRUG INTERACTIONS

Potential For Pharmacodynamic Interactions With STENDRA

Nitrates

Administration of STENDRA to patients who are using any form of organic nitrate, is contraindicated. In a clinical pharmacology trial, STENDRA was shown to potentiate the hypotensive effect of nitrates. In a patient who has taken STENDRA, where nitrate administration is deemed medically necessary in a lifethreatening situation, at least 12 hours should elapse after the last dose of STENDRA before nitrate administration is considered. In such circumstances, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring [seeCONTRAINDICATIONS, DOSAGE AND ADMINISTRATION, and CLINICAL PHARMACOLOGY].

Alpha-Blockers

Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including STENDRA, 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 leading to symptomatic hypotension (e.g., dizziness, lightheadedness, fainting) [see WARNINGS AND PRECAUTIONS, DOSAGE AND ADMINISTRATION, and CLINICAL PHARMACOLOGY].

Antihypertensives

PDE5 inhibitors, including STENDRA, are mild systemic vasodilators. A clinical pharmacology trial was conducted to assess the effect of STENDRA on the potentiation of the blood pressure-lowering effects of selected antihypertensive medications (amlodipine and enalapril). Additional reductions in blood pressure of 3 to 5 mmHg occurred following co-administration of a single 200 mg dose of STENDRA with these agents compared with placebo [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Alcohol

Both alcohol and PDE5 inhibitors, including STENDRA, act as vasodilators. When vasodilators are taken in combination, blood pressure-lowering effects of each individual compound may be increased. Substantial consumption of alcohol (e.g., greater than 3 units) in combination with STENDRA can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache [see Potential For Pharmacodynamic Interactions With STENDRA and CLINICAL PHARMACOLOGY].

Potential For Other Drugs To Affect STENDRA

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

Strong CYP3A4 Inhibitors

Ketoconazole (400 mg daily), a selective and strong inhibitor of CYP3A4, increased STENDRA 50 mg single-dose systemic exposure (AUC) and maximum concentration (Cmax) equal to 13-fold and 3-fold, respectively, and prolonged the half-life of avanafil to approximately 9 hours. Other potent inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir and telithromycin) would be expected to have similar effects. Do not use STENDRA in patients taking strong CYP3A4 inhibitors [see WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION].

HIV Protease inhibitor

Ritonavir (600 mg twice daily), a strong CYP3A4 inhibitor, which also inhibits CYP2C9, increased STENDRA 50 mg single-dose C and AUCequal to approximately 2-fold and 13-fold, and prolonged the half-life of avanafil to approximately 9 hours in healthy volunteers. Do not use STENDRA in patients taking ritonavir.

Moderate CYP 3A4 Inhibitors

Erythromycin (500 mg twice daily) increased STENDRA 200 mg single-dose Cmax and AUCequal to approximately 2-fold and 3-fold, respectively, and prolonged the half-life of avanafil to approximately 8 hours in healthy volunteers. Moderate CYP3A4 inhibitors (e.g., erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, and verapamil) would be expected to have similar effects. Consequently, the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours for patients taking concomitant moderate CYP3A4 inhibitors [see WARNINGS AND PRECAUTIONS and Potential For Other Drugs To Affect STENDRA].

Although specific interactions have not been studied, other CYP3A4 inhibitors, including grapefruit juice are likely to increase avanafil exposure.

Weak CYP3A4 Inhibitors

No in vivo drug-drug interaction studies with weak CYP3A4 inhibitors were conducted.

CYP3A4 Substrate

When administered with STENDRA 200 mg, amlodipine (5 mg daily) increased the Cmax and AUC of avanafil by approximately 22% and 70%, respectively. The half-life of STENDRA was prolonged to approximately 10 hrs. The Cmax and AUC of amlodipine decreased by approximately 9% and 4%, respectively [see DOSAGE AND ADMINISTRATION].

Cytochrome P450 Inducers

The potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated. The concomitant use of STENDRA and CYP inducers is not recommended.

Potential For STENDRA To Affect Other Drugs

In Vitro Studies

Avanafil had no effect on CYP1A1/2, 2A6, 2B6 and 2E1 (IC50 greater than 100 micromolar) and weak inhibitory effects toward other isoforms (CYP2C8, 2C9, 2C19, 2D6, 3A4). Major circulating metabolites of avanafil (M4 and M16) had no effect on CYPs 1A, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Avanafil and its metabolites (M4 and M16) are unlikely to cause clinically significant inhibition of CYPs 1A, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4.

In Vivo Studies

Warfarin

A single 200 mg dose of STENDRA did not alter the changes in PT or INR induced by warfarin, and did not affect collagen-induced platelet aggregation or the AUC or Cmax of R- or S-warfarin, a 2C9 substrate.

Desipramine

A single STENDRA 200 mg dose increased AUC and Cmax of a single 50 mg dose of desipramine, a CYP2D6 substrate, by 5.7% and 5.2%, respectively.

Omeprazole

A single STENDRA 200 mg dose increased AUC and Cmax of a single 40 mg dose of omeprazole, a CYP2C19 substrate, given once daily for 8 days by 5.9% and 8.6%, respectively.

Rosiglitazone

A single STENDRA 200 mg dose increased AUC by 2.0% and decreased Cmax by 14% of a single 8 mg dose of rosiglitazone, a CYP2C8 substrate.

Amlodipine

A single STENDRA 200 mg dose did not affect the pharmacokinetics of amlodipine (5 mg daily), a CYP3A4 substrate [see DOSAGE AND ADMINISTRATION].

Alcohol

A single oral dose of STENDRA 200 mg did not affect alcohol (0.5 g ethanol/kg) plasma concentrations [seeWARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Stendra (Avanafil)

© Stendra Patient Information is supplied by Cerner Multum, Inc. and Stendra Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Health Solutions From Our Sponsors