Avanafil instructions for use, how to take?

This page is an instruction manual for the use of avanafil and all generics based on it presented in the GENERICS catalog: Avana, Avaforce, Top Avana, Super Avana, and others. They all share the same active ingredient — avanafil. The mechanism of action, dosages, contraindications, and interactions are identical for all these drugs.

What is avanafil

Avanafil is an active ingredient from the group of fourth-generation PDE-5 inhibitors. The original drug Stendra® was approved by the FDA on April 27, 2012 — exactly nine years after the first three PDE-5 inhibitors (sildenafil, vardenafil, tadalafil), becoming "the first new prescription drug for the treatment of ED in nearly a decade," according to the wording of the FDA press release.[1] In Europe, the drug is registered under the name Spedra® (EMA, June 2013). The molecule was developed by the Japanese company Mitsubishi Tanabe Pharma and licensed by the American company Vivus Inc.

Avanafil was created with a specific goal: to eliminate the main practical drawback of the "classic trio" — the need to take a pill 30–60 minutes before intimacy. Thanks to its unique pharmacokinetic profile, avanafil reaches its peak blood concentration in about 30–45 minutes, and the clinical effect in some men occurs as early as 15 minutes after administration. It is the only approved PDE-5 inhibitor whose official instructions state a minimum administration time before intercourse of "from 15 minutes."[2]

In addition to speed, avanafil stands out for having the highest selectivity for PDE-5 among all approved drugs of its class: its affinity for PDE-5 exceeds its affinity for PDE-6 by more than 100 times, and for PDE-11 by more than 10,000 times. This explains the virtually complete absence of color vision disturbances and back pain — side effects that are characteristic of other molecules in the class to varying degrees.

Avanafil generics contain the same molecule in the same dosage, are manufactured according to GMP standards, and are significantly cheaper than the original.

How avanafil works

The mechanism of action of avanafil is identical to other PDE-5 inhibitors. Upon sexual arousal, nerve endings release nitric oxide (NO), which triggers the synthesis of cyclic guanosine monophosphate (cGMP). cGMP relaxes the smooth muscles of the blood vessels of the corpora cavernosa, which causes an influx of blood and forms an erection. The PDE-5 enzyme constantly destroys cGMP, limiting the erection. Avanafil blocks PDE-5, preventing cGMP from being destroyed prematurely.

Diagram: during sexual arousal, nitric oxide is produced → triggers cGMP synthesis → relaxes blood vessels → erection. The PDE-5 enzyme destroys cGMP and dampens the process. Avanafil blocks PDE-5, preventing cGMP from being destroyed prematurely.

An erection occurs only during sexual arousal — the drug does not replace or create it.

How does avanafil fundamentally differ from the "first generation" at the molecular level? The structure of the molecule is designed in such a way that it interacts with regions of the active center of PDE-5 that are atypical for other isoforms. Due to this, both high potency (IC₅₀ ~5.2 nM) and unprecedented selectivity for the class are achieved simultaneously:

• PDE-6 (retina, responsible for color vision) — more than 100-fold selectivity for PDE-5. For comparison: sildenafil has only ~16-fold, vardenafil ~21-fold.
• PDE-11 (muscle tissue, testicles) — more than 10,000-fold. Tadalafil: ~25-fold — this explains the back pain when taking tadalafil.
• PDE-1 (heart, blood vessels) — more than 10,000-fold. Sildenafil: ~380-fold.

In practical terms, this means: no color vision disturbances were recorded during the use of avanafil in clinical trials, even at a dose of 200 mg, and back pain and myalgia occurred in less than 2% of patients.[3]

Dosages

Avanafil is officially approved in three dosages: 50, 100, and 200 mg.

• 50 mg — reduced dose

It is used when it is necessary to reduce the dose for tolerability reasons, as well as for patients taking moderate CYP3A4 inhibitors. The starting dose according to the "minimum" scenario is 30 minutes before intercourse.

• 100 mg — recommended starting dose

This is the dose most patients start with. It can be taken as early as 15 minutes before intimacy. If 100 mg is insufficient, the dose can be increased to 200 mg.

• 200 mg — maximum dose

It is used in case of insufficient response to 100 mg. In a long-term study, 65% of men who did not respond to 100 mg responded to 200 mg.[4] It can also be taken 15 minutes before intercourse.

The maximum frequency of administration is once a day. Avanafil is taken "on demand" — it is not intended for a daily regimen.

How to take

Time of administration

The key practical advantage of avanafil over other PDE-5 inhibitors: doses of 100 and 200 mg are officially allowed to be taken 15 minutes before planned sexual activity (50 mg — 30 minutes before). The median Tmax on an empty stomach is 30–45 minutes; in phase 3 clinical trials, about two-thirds of attempts made up to 15 minutes after administration were successful.[5] This does not mean that the effect is guaranteed to occur in 15 minutes for everyone — Tmax is individual, and the recommended "window" of 15–30 minutes provides a greater margin of reliability.

Do not chew the tablet, swallow it with water (~200 ml).

Important: grapefruit juice inhibits CYP3A4 in the intestine and increases the concentration of avanafil. Wash down only with water.

Influence of food

A high-fat meal delays the achievement of peak concentration by an average of 1.1–1.25 hours, but does not change the overall exposure (AUC). This means that avanafil can be taken after any meal — it will still work, just slightly slower. For maximum onset speed, take it on an empty stomach or after a light snack. The positioning of "can be taken with food" is a clinical reality for standard use, but if you want to utilize the main advantage of avanafil (a fast start), it is better to avoid a heavy, fatty dinner.[6]

Alcohol

In a special pharmacodynamic study, avanafil (200 mg) + alcohol (0.5 g/kg, ~3 units, blood level 0.057%) led to an additional decrease in systolic/diastolic pressure by 3.5/4.5 mmHg and an increase in heart rate by 9.3 bpm compared to alcohol without avanafil. No cases of orthostatic hypotension were recorded. Practical conclusion: moderate doses of alcohol (~3 units = approximately 2 glasses of wine) during a single dose of avanafil are clinically acceptable for most healthy men. With a significant amount of alcohol (>3 units), the FDA warns of the risk of orthostatic phenomena — dizziness, tachycardia, and drop in blood pressure when standing up.[6]

Efficacy

Avanafil has undergone three key randomized, double-blind, placebo-controlled phase-3 studies involving 1,267 men: in the general ED population, in patients with diabetes mellitus, and in men after nerve-sparing radical prostatectomy.

General population

In a key phase-3 RCT in 646 men with mild-to-severe ED, avanafil 50, 100, and 200 mg significantly improved all primary endpoints compared to placebo (IIEF-EF scale, SEP2, SEP3). The data on the time of administration before the attempt are indicative: out of 300 intercourse attempts made less than 15 minutes after taking avanafil, 64–71% were successful — compared to 27% in the placebo group. Similar efficacy was observed in attempts made more than 6 hours after dosing.[5]

In diabetes mellitus

In the REVIVE-Diabetes study in 390 men with ED and type 1 or 2 diabetes, avanafil 100 and 200 mg significantly exceeded placebo in all primary outcomes. SEP3 (successful intercourse) increased from 8% to 34% (100 mg) and to 40% (200 mg) — compared to an increase from 10% to 20% in the placebo group. Efficacy was registered even in attempts made less than 15 minutes after administration.[7]

After nerve-sparing radical prostatectomy

In a phase-3 study in 298 men after bilateral nerve-sparing prostatectomy, avanafil 100 and 200 mg significantly improved all three primary endpoints (SEP2, SEP3, IIEF-EF) compared to placebo. A rapid onset of action and maintenance of effect were noted for all intervals between administration and attempt — from "less than 15 minutes" to "more than 6 hours."[8]

Long-term use

In an open-label, 52-week extension of two phase-3 studies (712 patients), the proportion of successful SEP2 attempts increased from 44% to 83% (100 mg), and SEP3 — from 13% to 68%. The mean IIEF-EF score improved from 13.6 to 22.2. Less than 3% of patients discontinued treatment due to adverse events.[4]

Important: avanafil eliminates the symptom, but not the cause of ED. The drug is less effective in cases of complete damage to nerve bundles, severe atherosclerosis, and decompensated systemic diseases.

Side effects

Avanafil demonstrates one of the most favorable tolerability profiles among all PDE-5 inhibitors. The rate of treatment discontinuation due to adverse events in studies was less than 3% — comparable to placebo.

Common (≥2% of patients)

Headache, flushing (redness of the face), nasal congestion, nasopharyngitis, back pain (frequency is close to placebo — significantly lower than with tadalafil). All of these reactions are dose-dependent and short-lived.

What is fundamentally ABSENT in avanafil

In clinical phase-3 studies, no cases of color vision impairment were registered at all three doses (50, 100, 200 mg). This is a direct consequence of the high selectivity of avanafil for PDE-5 relative to PDE-6 of the retina. Back pain and myalgia occurred in less than 2% of patients — also significantly less frequently than with tadalafil. Avanafil does not cause QT interval prolongation — unlike vardenafil.[3]

Uncommon (0.1–1%)

Dizziness, dyspepsia, nausea, skin rash.

Rare but serious (<0.1%)

• Priapism — a painful erection lasting more than 4 hours. Requires immediate medical attention. If delayed, irreversible tissue damage can occur.
• NAION (non-arteritic anterior ischemic optic neuropathy) — a sudden loss of vision, described as a class effect of PDE-5 inhibitors.
• Sudden hearing loss — isolated post-marketing cases.

Comparison with other molecules: among all approved PDE-5 inhibitors, avanafil has the cleanest side effect profile — no color vision disturbances (as with sildenafil/vardenafil), no characteristic back pain (as with tadalafil), no QT prolongation (as with vardenafil). The trade-off for this is a slightly less extensive evidence base due to the relatively young age of the molecule.

Contraindications

Absolute

• Nitrates in any form — nitroglycerin, isosorbide dinitrate/mononitrate, nitro spray. Concomitant use causes a dangerous drop in blood pressure. This is an absolute contraindication for the entire class of PDE-5 inhibitors.
• Strong CYP3A4 inhibitors — ketoconazole, itraconazole, ritonavir, atazanavir, clarithromycin, indinavir, nelfinavir, saquinavir. Avanafil is contraindicated in combination with all strong CYP3A4 inhibitors (for sildenafil and tadalafil, the dose is reduced in this case, rather than the drug being discontinued — this is a specificity of avanafil associated with a very high fold increase in AUC: ketoconazole increases the AUC of avanafil by 13 times).
• Riociguat (Adempas®) — concomitant use is contraindicated.
• Severe cardiovascular conditions in which sexual activity is contraindicated: unstable angina, myocardial infarction or stroke less than 6 months ago, severe heart failure, uncontrolled arrhythmias, severe hypotension (<90/50 mmHg) or hypertension (>170/110 mmHg).
• Loss of vision in one eye due to a history of NAION.
• Hypersensitivity to avanafil.
• Age under 18 years.

Relative (require caution)

• Moderate CYP3A4 inhibitors (erythromycin, amprenavir, diltiazem, fluconazole, verapamil) — maximum dose of 50 mg in 24 hours.
• Controlled hypertension, stable CAD — after assessment of cardiovascular risk.
• Anatomical deformities of the penis (Peyronie's disease) — risk of priapism.
• Sickle cell anemia, leukemia, multiple myeloma — risk of priapism.
• Retinitis pigmentosa.
• Moderate hepatic impairment (Child-Pugh B) — data are limited, use caution.
• Severe renal impairment (CrCl <30 ml/min) and hemodialysis — data are limited, not recommended.

Drug interactions

Absolute contraindications for concomitant use

• Nitrates. After taking avanafil, nitrates must not be used for at least 24 hours (with T½ ~5 hours — similar to sildenafil and vardenafil; tadalafil has a longer interval: 48 hours).
• Strong CYP3A4 inhibitors. Ketoconazole (400 mg/day) increases the AUC of avanafil by 13 times, Cmax by 3 times, and prolongs T½. This is the most stringent limitation of avanafil compared to other molecules of the class (tadalafil and vardenafil simply have reduced dose limits when taken concomitantly with ritonavir). Full list: ketoconazole, itraconazole, ritonavir, atazanavir, clarithromycin, indinavir, nelfinavir, saquinavir.
• Riociguat — contraindicated.

Require dose adjustment

• Moderate CYP3A4 inhibitors (erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, verapamil) — maximum 50 mg in 24 hours.
• Alpha-blockers (tamsulosin, doxazosin) — additive hypotensive effect. With a stable dose of alpha-blocker, the maximum dose of avanafil is 50 mg. Start carefully, and reduce the dose further if necessary.
• Significant amounts of alcohol (>3 units) — enhanced hypotensive effect, risk of orthostatic phenomena.

Moderate interactions

Grapefruit juice — inhibits intestinal CYP3A4, avoid. CYP3A4 inducers (rifampicin, carbamazepine, St. John's wort) — reduce the AUC of avanafil, the effect may weaken.

No significant interactions

Warfarin, digoxin, omeprazole, rosiglitazone — no clinically significant interactions were identified.

Be sure to inform your doctor about taking any antifungal, antibacterial, antiretroviral (HIV), and cardiac drugs — they are most often CYP3A4 inhibitors.

Special patient groups

Elderly men (65+)

In population pharmacokinetic studies in healthy men aged 65–80 years, the AUC of avanafil was slightly higher than in younger men. The official instructions state that no initial dose adjustment is required; however, it is recommended to exercise usual caution when selecting a dose in elderly patients, taking into account concomitant therapy.

Diabetes mellitus

Avanafil is effective in diabetic ED — this has been confirmed in a special phase-3 RCT. A particular plus for this group: no color vision disturbances (diabetics often have concomitant diabetic retinopathy), and minimal musculoskeletal side effects. The starting dose is 100 mg, if necessary — 200 mg.

After prostate surgery

Avanafil has shown efficacy after nerve-sparing prostatectomy. As with all PDE-5 inhibitors, the result depends on the degree of preservation of the nerve bundles. In cases of complete neuronal damage, efficacy is limited.

Impaired liver function

Mild (Child-Pugh A) — no adjustment is needed. Moderate (Child-Pugh B) — data are limited, caution is recommended. Severe (Child-Pugh C) — not recommended.

Impaired renal function

Mild and moderate — no adjustment is needed. Severe (CrCl <30 ml/min) and hemodialysis — data are lacking, not recommended.

Cardiovascular diseases

Controlled hypertension and stable CAD are not absolute contraindications. At a dose of 200 mg, avanafil caused a temporary decrease in systolic pressure by an average of 8.0 mmHg and diastolic by 3.3 mmHg in healthy volunteers — a moderate effect typical of the class. The decision is made jointly with a cardiologist.

What to do if...

...the drug did not work

Common reasons:

• Taking it after a very fatty meal — Tmax can shift by 1–1.5 hours. For avanafil, with its fast profile, this is especially critical: a fatty dinner "negates" the main advantage of the molecule.
• Insufficient sexual arousal — the drug only enhances the vascular response.
• Psychological anxiety during the first use.
• Taking CYP3A4 inhibitor drugs that the doctor did not know about — they can impair absorption.

If 100 mg is not enough, try 200 mg. If both options are ineffective after several attempts, consult a doctor.

...side effects have occurred

• Headache, redness, nasal congestion — short-term, pass on their own. Next time you take it, try reducing the dose.
• A sharp drop in blood pressure (dizziness when standing up) — lie down, raise your legs, drink water. In case of severe symptoms, call an ambulance.
• Chest pain — call an ambulance immediately. Do not take nitroglycerin: the safety interval after avanafil is at least 24 hours. Be sure to inform the medical staff about taking avanafil.

...the erection does not go away (priapism)

A painful erection lasting more than 2–3 hours after the end of intercourse is an emergency. Contact an emergency room or call an ambulance immediately. Treatment in the first 4–6 hours helps prevent irreversible damage. This is a rare complication (<0.1%).

...an excessive dose has been taken (overdose)

There is no specific antidote. Symptoms include an increase in common side effects. Lie down, and in case of a pronounced decrease in pressure, call an ambulance. Do not take nitrates under any circumstances. Dialysis is ineffective.

Storage conditions

Store at a temperature not exceeding 30°C, in a dry place protected from direct sunlight. Keep out of reach of children. The shelf life is indicated on the package, usually 2–3 years.

Avanafil-based drugs in our catalog

All listed drugs contain avanafil as the active ingredient. This instruction manual applies to all of them.

Monotherapy avanafil drugs

• Avanafil — Avana 50 (50 mg), Avana 100 (100 mg), Avana 200 (200 mg) by Sunrise Remedies
• Avaforce 50 (50 mg), Avaforce 100 (100 mg), Avaforce 200 (200 mg) by Centurion Laboratories

Combination drugs (avanafil + dapoxetine)

If premature ejaculation is an issue in addition to ED, avanafil as a monotherapy cannot handle it. 2-in-1 combo drugs are available in the catalog:

• Super Avana — avanafil 100 mg + dapoxetine 60 mg
• Extra Super Avana — avanafil 200 mg + dapoxetine 60 mg
• Top Avana — avanafil 50 mg + dapoxetine 30 mg

The information on this page is for informational purposes only and does not replace consultation with a doctor. Before using any avanafil-based drug for the first time, consult a urologist or general practitioner — especially if you have cardiovascular diseases, are taking antifungal and antiretroviral drugs, or have chronic conditions.

Why is Avanafil better than Sildenafil and why hasn't it pushed it out of the market?

Avanafil objectively wins over sildenafil in several parameters: faster onset of action (15–30 min vs 30–60 min), virtually no color vision disturbances, and less dependence on fatty food (Tmax delay ~1 h vs a 29% decrease in Cmax for sildenafil). Why hasn't it pushed it out? Firstly, sildenafil has already become a generic with a very low price — the price advantage is huge. Secondly, sildenafil has 25+ years of clinical practice and thousands of studies, which builds trust among doctors. Thirdly, for most men, the increase in speed from 30 to 15 minutes is not a deciding factor. Avanafil is the choice for those for whom speed is truly critical or who experience adverse reactions to other molecules of the class.

Can I take Avanafil every day?

Officially, no — avanafil is intended for "on-demand" use, maximum once a day. For a daily regimen, tadalafil 2.5–5 mg was created — it has the corresponding FDA approval and an extensive clinical base specifically for this scheme.

Avanafil or Tadalafil, which to choose?

It depends on what is more important to you. Choose Avanafil if you need the maximum speed of onset of action (15–30 minutes), minimum side effects (no vision impairment, no back pain, no QT prolongation), and situational use. Choose Tadalafil if duration is important (up to 36 hours), daily regimen, or if you have symptoms of prostate adenoma (tadalafil 5 mg is the only approved drug for BPH). Avanafil is contraindicated when taken concomitantly with strong CYP3A4 inhibitors — tadalafil is acceptable in a reduced dose in this case. If you are not sure, start with 100 mg of avanafil and evaluate.

Sources

• [1] VIVUS Inc. Press Release: FDA approves STENDRA™ (avanafil) for the treatment of erectile dysfunction. April 27, 2012. Vivus.com
• [2] FDA Label — STENDRA® (avanafil) Tablets. Full Prescribing Information. 2022. FDA.gov (PDF)
• [3] Kotera J. et al. Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: implications for clinical safety and improved tolerability. The Journal of Sexual Medicine, 2012; 9(8): 2122–2129. PubMed: 22759639
• [4] Belkoff L.H. et al. An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction. International Journal of Clinical Practice, 2013; 67(4): 333–341. PubMed: 23521325
• [5] Goldstein I. et al. Avanafil for the treatment of erectile dysfunction: a multicenter, randomized, double-blind, placebo-controlled study. Mayo Clinic Proceedings, 2012; 87(9): 843–852. PMC: 3498142
• [6] FDA Label — STENDRA® (avanafil) Tablets. Clinical Pharmacology. Section on food and alcohol interactions. FDA.gov (PDF)
• [7] Goldstein I. et al. Avanafil for the Treatment of Erectile Dysfunction: A Multicenter, Randomized, Double-Blind Study in Men With Diabetes Mellitus. Mayo Clinic Proceedings, 2012; 87(9): 843–852. PMC: 3498142
• [8] Mulhall J.P. et al. A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy. The Journal of Urology, 2013; 189(6): 2229–2236. PubMed: 23219537

The sources describe the avanafil molecule and apply to all drugs based on it — both the original Stendra®/Spedra® and generics.