Why Avanafil Drug Interactions Matter

Avanafil (brand name Stendra) is an effective medication for erectile dysfunction, but like all drugs, it doesn't exist in a vacuum. The other medications you take, the supplements you use, and even what you eat and drink can all affect how Avanafil works in your body — and in some cases, create serious safety risks.

This guide covers every major interaction you should know about, from life-threatening combinations to moderate ones that may require a dose adjustment. Keep this as a reference, and always share your complete medication list with your doctor before starting Avanafil.

How Drug Interactions Work

Drug interactions happen in a few ways:

• Additive effects — Two drugs that do similar things amplify each other. Since Avanafil lowers blood pressure, combining it with other blood pressure-lowering drugs can drop your pressure too far.
• Metabolic interference — Your liver uses specific enzymes (especially CYP3A4) to break down Avanafil. If another drug blocks those enzymes, Avanafil builds up in your system to potentially dangerous levels.
• Competing mechanisms — Some drugs work through the same biochemical pathways as Avanafil, and combining them can create unpredictable or dangerous effects.

Not every interaction is equally dangerous. Some are absolute contraindications (never combine), while others just require caution or dose adjustments.

Medications That Interact With Avanafil

Contraindicated (Never Combine)

These combinations are strictly prohibited — they can cause life-threatening reactions:

Nitrates

This is the most critical interaction. Never take Avanafil if you use any form of nitrate medication.

• Nitroglycerin (Nitrostat, Nitro-Dur, Nitro-Bid) — used for chest pain (angina)
• Isosorbide Mononitrate (Imdur, Monoket)
• Isosorbide Dinitrate (Isordil, Dilatrate)
• Amyl nitrite or butyl nitrite — recreational "poppers"

Both Avanafil and nitrates lower blood pressure. Together, they can cause a sudden, severe, and potentially fatal drop in blood pressure. There is no safe waiting period or dose adjustment that makes this combination okay.

If you use nitrates for heart disease, your doctor will need to prescribe a different approach to managing your ED. See our guide on alternatives to Avanafil.

Riociguat (Adempas)

Riociguat is a guanylate cyclase stimulator used for pulmonary hypertension. It works through a pathway that overlaps with PDE5 inhibitors. Combining Avanafil with Riociguat can cause dangerous hypotension and is contraindicated.

Strong CYP3A4 Inhibitors

Your body relies on the CYP3A4 liver enzyme to metabolize Avanafil. Strong inhibitors of this enzyme prevent your body from breaking down Avanafil, causing it to build up to unsafe levels. Avanafil is contraindicated with:

• Ketoconazole (Nizoral) — antifungal
• Ritonavir (Norvir) — HIV protease inhibitor
• Itraconazole (Sporanox) — antifungal
• Clarithromycin (Biaxin) — antibiotic
• Atazanavir (Reyataz) — HIV medication
• Indinavir (Crixivan) — HIV medication
• Nefazodone — antidepressant
• Nelfinavir (Viracept) — HIV medication
• Saquinavir (Invirase) — HIV medication
• Telithromycin (Ketek) — antibiotic

Other PDE5 Inhibitors

Do not take Avanafil with other PDE5 inhibitors like Sildenafil (Viagra), Tadalafil (Cialis), or Vardenafil (Levitra). They all work through the same mechanism, and combining them increases the risk of severe side effects including dangerous drops in blood pressure and priapism.

Major Interactions (Use With Extreme Caution)

Alpha-Blockers

Alpha-blockers are used for high blood pressure and enlarged prostate (BPH). They include:

• Doxazosin (Cardura)
• Tamsulosin (Flomax)
• Alfuzosin (Uroxatral)

Both alpha-blockers and Avanafil lower blood pressure, so combining them increases the risk of dizziness, lightheadedness, and fainting. If you must take both:

• You should be stable on your alpha-blocker dose before starting Avanafil.
• Your doctor may start you on a lower Avanafil dose.
• Take them at different times of day when possible.

Moderate Interactions (Dose Adjustment May Be Needed)

Moderate CYP3A4 Inhibitors

These medications partially slow Avanafil metabolism. If you take any of them, your maximum Avanafil dose is 50 mg per day:

• Diltiazem (Cardizem) — calcium channel blocker for blood pressure
• Verapamil (Calan) — calcium channel blocker
• Fluconazole (Diflucan) — antifungal
• Erythromycin (Eryc) — antibiotic
• Fosamprenavir (Lexiva) — HIV medication
• Aprepitant (Emend) — anti-nausea medication

Antihypertensives

Blood pressure medications of all types can have additive effects with Avanafil. This includes:

• ACE inhibitors (Lisinopril, Enalapril)
• ARBs (Losartan, Valsartan)
• Beta-blockers (Metoprolol, Atenolol)
• Diuretics (Hydrochlorothiazide, Furosemide)

This doesn't mean you can't take Avanafil with blood pressure medication — most men with controlled hypertension can safely use it. But your doctor should monitor your blood pressure and may adjust your doses.

Amlodipine (Norvasc)

This calcium channel blocker specifically increases Avanafil exposure by about 22%. While not contraindicated, your doctor should be aware if you take Amlodipine so they can consider a lower Avanafil dose.

Supplements and OTC Medications to Watch

Don't assume that "natural" means safe to combine with Avanafil. Watch out for:

• Grapefruit juice — Inhibits CYP3A4, the same enzyme pathway as prescription drug interactions. Occasional small amounts are likely fine, but avoid drinking large quantities regularly.
• St. John's Wort — This herbal supplement induces CYP3A4, meaning it can speed up Avanafil metabolism and make the medication less effective.
• Yohimbe/Yohimbine — Sometimes marketed for ED, yohimbe can affect blood pressure unpredictably. Do not combine with Avanafil without medical guidance.
• Blood pressure supplements — Products containing CoQ10, fish oil, garlic extract, or magnesium may have mild blood pressure-lowering effects that add to Avanafil's.
• NSAIDs (Ibuprofen, Naproxen) — Generally safe with Avanafil, but both can occasionally affect blood pressure. No dose adjustment typically needed.

Food and Drink Interactions

Alcohol

Alcohol is one of the most commonly overlooked interactions. Both alcohol and Avanafil lower blood pressure, so combining them increases the risk of:

• Dizziness
• Lightheadedness
• Fainting
• Headache

A drink or two is unlikely to cause problems for most people, but heavy drinking significantly increases risks. Your doctor may advise limiting alcohol when using Avanafil.

Grapefruit

As mentioned above, grapefruit and grapefruit juice inhibit CYP3A4. This can increase Avanafil levels in your blood. Avoid consuming large amounts of grapefruit while taking Avanafil.

Food Generally

Avanafil can be taken with or without food. Heavy, high-fat meals may slightly delay absorption but don't significantly reduce effectiveness. This is a practical advantage over Sildenafil, which is more sensitive to food timing.

What to Tell Your Doctor

Before your doctor prescribes Avanafil, make sure they know about:

• Every medication you take — prescription, over-the-counter, and recreational. Don't leave anything out, even if it seems unrelated.
• All supplements and herbal products — including vitamins, protein powders, and herbal remedies.
• Any heart conditions — especially if you've had a heart attack, stroke, or arrhythmia, or if you take nitrates for chest pain.
• Blood pressure issues — both high and low blood pressure matter.
• Liver or kidney problems — these affect how your body processes Avanafil.
• History of priapism or penile conditions — sickle cell disease, multiple myeloma, leukemia, or Peyronie's disease can increase risks.
• Upcoming surgeries or procedures — your medical team needs to know about all medications, including Avanafil.

It's better to over-share than under-share. Your doctor can't help you avoid dangerous interactions if they don't know what you're taking.

Final Thoughts

Avanafil is generally safe when used as directed, but the interactions with nitrates and strong CYP3A4 inhibitors are serious and non-negotiable. Always be upfront with your doctor about everything you take, and don't start Avanafil without a thorough medication review.

For more information about Avanafil, explore our guides on what Avanafil is, side effects, and how to save money on your prescription. When you're ready to fill your prescription, Medfinder can help you find a pharmacy with Avanafil in stock.