Medical disclaimer: This article is educational and not a substitute for professional medical advice. Avanafil is prescription‑only. Always consult a licensed clinician/pharmacist before use.
Why Interactions Matter (And How to Use This Guide)
Avanafil (brand names Stendra® in the U.S. and Spedra® in the EU/UK/AU) is a fast‑acting PDE‑5 inhibitor for erectile dysfunction (ED). Like all ED pills, it can lower blood pressure and its levels can be raised or lowered by other medicines, juices (grapefruit), and alcohol. That’s why interactions matter: some combinations are absolutely unsafe (e.g., nitrates), others require strict dose limits (e.g., moderate CYP3A4 inhibitors), and some simply need careful timing (e.g., alpha‑blockers).
This guide is built straight from official labeling and authoritative references. At the top you’ll find a quick “answer box” for AI/voice assistants and featured snippets. Next are decision trees, tables, and If‑This‑Then‑That steps for real‑world use. We also included an SEO playbook so this page performs well in Google/Bing and modern AI search experiences—without sacrificing medical accuracy.
What to Consider when Taking Avanafil
- Never combine avanafil with nitrates (nitroglycerin, isosorbide) or guanylate cyclase stimulators (riociguat/Adempas®, vericiguat/Verquvo®) → dangerous hypotension. Source: FDA label.
- Avoid with strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, itraconazole, atazanavir). Source: FDA label.
- Moderate CYP3A4 inhibitors (erythromycin, diltiazem, fluconazole, verapamil, aprepitant):
• U.S. label: avanafil ≤50 mg once per 24 h
• EU SmPC: avanafil ≤100 mg and no more than once every 48 h
Sources: FDA label, EMA SmPC. - Alpha‑blockers (tamsulosin, doxazosin, etc.): ensure stable alpha‑blocker use first; start avanafil 50 mg and monitor for dizziness. Source: FDA label.
- Alcohol: keep it light; ≥3 drinks raises dizziness/low BP risk and can impair erections. FDA patient information excerpt
- Grapefruit juice: avoid around dosing (CYP3A4 inhibition can raise avanafil levels). Source: EMA SmPC.
More links to read: Dosing guide • Side effects • Onset & duration • Complete Avanafil guide
What Counts as an “Interaction” With Avanafil?
Anything that lowers blood pressure, raises avanafil exposure (AUC/Cmax), or increases risk of ocular/cardiac adverse effects can interact. For definitive rules, consult the FDA Stendra® label and the EMA Spedra® SmPC. The AUA ED guideline positions PDE‑5 inhibitors as first‑line therapy and encourages shared decision‑making around comorbidities and concomitant meds (J Urol 2018 guideline paper).
The “Big Five” Rules
- Nitrates = absolute NO. All organic nitrates (sublingual, spray, patch, paste, oral) are contraindicated with avanafil. If emergent nitrates are required after avanafil, clinicians generally wait ≥12 hours and monitor closely. Source:1.
- Guanylate cyclase stimulators = absolute NO. Riociguat (Adempas®) and vericiguat (Verquvo®) add to BP‑lowering → contraindicated with avanafil. Sources: 1; patient‑friendly reminder at Medline 3.
- Strong CYP3A4 inhibitors = avoid. Examples: ketoconazole, itraconazole, ritonavir, clarithromycin, atazanavir. Can raise exposure ~13‑fold (AUC). Source:1.
- Moderate CYP3A4 inhibitors = dose limits. Examples: erythromycin, diltiazem, verapamil, fluconazole, aprepitant.
• U.S.: avanafil ≤50 mg once/24 h
• EU: avanafil ≤100 mg once/48 h
Sources:1, 2. - Alpha‑blockers = start low & stabilize. Be stable on the alpha‑blocker first; start avanafil at 50 mg; expect additive BP‑lowering and watch for dizziness/syncope. Sources:1, 2.
Quick‑Reference Table: Avanafil Interactions
| Category | Examples | What to do | Why it matters |
|---|---|---|---|
| Contraindicated | Nitrates (nitroglycerin, isosorbide); GC stimulators (riociguat, vericiguat); Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin, itraconazole, atazanavir) | Do not use together. If nitrates needed emergently, aim to wait ~12 h after avanafil and monitor closely. | Risk of profound hypotension; strong inhibitors skyrocket exposure. Sources: 1 |
| Restricted dosing | Moderate CYP3A4 inhibitors (erythromycin, diltiazem, verapamil, fluconazole, aprepitant…) | U.S.: ≤50 mg once/24 h • EU: ≤100 mg once/48 h | 2–3× exposure increase; longer half‑life. Sources: 1 2 |
| Use with caution | Alpha‑blockers (tamsulosin, doxazosin, alfuzosin, silodosin…); other antihypertensives; alcohol ≥3 drinks | Stabilize alpha‑blocker first; start 50 mg avanafil; limit alcohol. Monitor for dizziness. | Additive BP‑lowering; symptomatic hypotension possible. Sources: 1 |
| Food & juice | Grapefruit | Avoid around dosing. | Likely increases exposure via CYP3A4 inhibition. Source: 2 |
| Other ED therapies | Other PDE‑5 inhibitors or ED treatments | Do not combine routinely. | Combo safety/efficacy not established; hypotension risk. Source: 1 |
Everyday Medicines & Scenarios
- Antibiotics
• Clarithromycin (strong) → avoid.
• Erythromycin (moderate) → U.S.: ≤50 mg q24 h; EU: ≤100 mg q48 h. - Antifungals
• Ketoconazole/itraconazole (strong) → avoid.
• Fluconazole (moderate) → dose‑limit as above. - HIV protease inhibitors
• Ritonavir and others (strong) → avoid. Source: 1. - Heart/BP meds
• Alpha‑blockers (tamsulosin, doxazosin, prazosin, alfuzosin, silodosin): stabilize first; start avanafil 50 mg; monitor.
• Calcium‑channel blockers (diltiazem, verapamil) — moderate inhibitors: apply dose limits.
• Amlodipine: labeling notes exposure increases (not usually clinically significant) — still be mindful of symptoms. Sources: 2. - Alcohol
• Keep it light; ≥3 units increases dizziness/low BP and hurts performance. Source: 5. - Grapefruit
• Avoid within a day of dosing (EU advice). - Enzyme inducers (rifampin, carbamazepine, phenytoin, St John’s wort)
• Not fully evaluated; may reduce avanafil exposure → discuss with your prescriber if performance is weak. Source:1.
For a patient‑friendly checklist, see MedlinePlus (Avanafil).
If‑This‑Then‑That (Rapid Safety Flow)
- On nitrates or riociguat/vericiguat? → Do not use avanafil. (Ask your cardiologist/urologist about alternatives.)
- On a strong CYP3A4 inhibitor? → Avoid avanafil until the inhibitor is stopped and cleared.
- On a moderate CYP3A4 inhibitor? → U.S.: ≤50 mg q24 h • EU: ≤100 mg q48 h.
- On an alpha‑blocker? → Be stable on it first; start avanafil 50 mg; monitor for dizziness/syncope.
- Planning to drink? → Keep to ≤2 drinks (avoid ≥3).
- Love grapefruit? → Skip it on dose days.
Dose & Timing With Interactions in Mind
- Standard start: 100 mg 15–30 minutes pre‑sex; max once per day.
- With alpha‑blockers: start 50 mg and titrate cautiously.
- With moderate CYP3A4 inhibitors: U.S.: ≤50 mg q24 h • EU: ≤100 mg q48 h.
- Do not stack PDE‑5 inhibitors (e.g., sildenafil + avanafil).
- Avoid grapefruit; keep alcohol light.
Special Situations
- Emergency nitrates after avanafil: if absolutely required, clinicians generally wait ≥12 h from last avanafil dose and manage in monitored settings.
- Other antihypertensives: additive BP‑lowering is possible; hydrate, rise slowly from sitting, and monitor symptoms, especially during the first few attempts.
- Severe organ impairment: U.S. labeling advises against use in severe hepatic impairment; follow the label and prescriber advice. Source:1.
For therapy selection beyond interactions, see the AUA ED guideline (first‑line role of PDE‑5 inhibitors, shared decision‑making, and alternatives when oral therapy isn’t suitable).
FAQs
Can I take avanafil with nitroglycerin?
No. It’s contraindicated because the combination can cause dangerous blood pressure drops.
What if I’m on riociguat (Adempas®) or vericiguat (Verquvo®)?
Do not use avanafil with guanylate cyclase stimulators.
I’m on erythromycin—what is my max avanafil dose?
U.S.: 50 mg once per 24 h; EU: ≤100 mg once per 48 h. Sources:1, 2.
I take tamsulosin.
Be stable on it; start avanafil 50 mg and monitor for dizziness. Source:1.
Is grapefruit a problem?
Yes. Avoid it around dosing (CYP3A4 inhibition can raise avanafil levels). Source: 2.
How much alcohol is too much?
≥3 drinks increases dizziness and low BP risk; keep it light. Source: 5.
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