Avanafil (Stendra/Spedra) Contraindications: What Not to Mix and When to Avoid

Quick note on intent: You clicked to learn when avanafil is a bad idea. This page gives you the specific no-go combinations, health situations where it’s unsafe, and the practical steps to stay out of trouble. Expect clear rules, not vague warnings.

• Absolute no-go: nitrates (e.g., GTN spray), nitric oxide donors (poppers), and guanylate cyclase stimulators like riociguat. These combos can crash blood pressure.
• Common tripwires: strong CYP3A4 inhibitors (e.g., ritonavir, ketoconazole) and unstable heart disease. In some cases, avanafil is simply not an option.
• Timing matters: if you took avanafil, avoid nitrates for at least 12 hours; do not self-experiment. If you need emergency chest pain meds, tell clinicians immediately.
• Liver and kidney disease: severe liver disease-don’t use; serious kidney problems-doctor-led decision only. Dosing may need to be lower or avoided.
• Alternatives exist if you can’t take avanafil: different ED treatments, cardiac clearance first, and simple lifestyle fixes that actually help.

If you only remember one phrase, make it this: avanafil contraindications.

What makes avanafil unsafe: the red lines and the gray areas

Avanafil is a fast-acting PDE5 inhibitor for erectile dysfunction. In the US it’s sold as Stendra; in the UK/EU it’s Spedra. Most men tolerate it well. The danger comes from very specific drug combinations and certain heart and eye conditions. The stakes are high because mixing it with the wrong drug can drop your blood pressure so low you pass out or worse.

Let’s sort things into two buckets: absolute contraindications (do not use), and strong precautions/“functionally contraindicated” situations (avoid unless a specialist says otherwise).

Absolute contraindications (do not use) - backed by regulator labeling (FDA Prescribing Information for Stendra, EMA SmPC for Spedra, and the BNF):

• Any nitrate therapy in any form: nitroglycerin/GTN spray or tablets, isosorbide dinitrate/mononitrate, nitrate patches or ointments. This includes as-needed GTN that many people with angina carry.
• Nitric oxide donors such as “poppers” (amyl/butyl nitrite). Same blood pressure crash problem.
• Guanylate cyclase stimulators, especially riociguat (used for pulmonary hypertension). Additive vasodilation can be dangerous.
• Known hypersensitivity to avanafil or any component of the tablet.
• Strong CYP3A4 inhibitors: examples include ritonavir or cobicistat-boosted HIV regimens, ketoconazole/itraconazole (systemic), certain antivirals, and sometimes clarithromycin. With these, blood levels of avanafil can spike; most labels say don’t co-prescribe.

“Functionally contraindicated” or avoid unless a specialist clears it - these aren’t always line-by-line contraindications in every label, but major guidelines and the BNF treat them as hard stops pending medical review:

• Unstable cardiovascular disease: unstable angina, decompensated heart failure, severe valvular disease, or serious arrhythmias not under control.
• Recent major cardiac events: a recent heart attack or stroke (many guidelines use the past 6 months as a rule of thumb; your cardiologist may tailor this).
• Severe hypotension (e.g., blood pressure under ~90/50 mmHg) or uncontrolled hypertension. Get blood pressure under control first.
• Severe hepatic impairment (Child-Pugh C): avoid. With moderate impairment, lower dosing may be required and some prescribers still avoid.
• Severe renal impairment: labels vary, but prescribers often avoid or cap dosing; specialist input recommended if eGFR is very low or you’re on dialysis.
• History of non-arteritic anterior ischemic optic neuropathy (NAION) or “crowded” optic discs: risk of sudden vision loss; most prescribers avoid PDE5 inhibitors in this group.
• Retinitis pigmentosa: theoretical retinal risk; most labels advise against or caution.
• Condition where sex itself poses a risk: if your doctor says sexual activity isn’t safe for now, ED pills must wait.

Important cautions (not absolute, but treat with respect):

• Alpha-blockers (for blood pressure or prostate): if you’re stable on an alpha-blocker, you can sometimes use avanafil at a low dose with careful timing and monitoring to avoid dizziness or fainting.
• Moderate CYP3A4 inhibitors (e.g., erythromycin, verapamil, diltiazem, fluconazole, grapefruit juice): your clinician may cap avanafil at 50 mg and set longer spacing.
• Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin, St John’s wort): avanafil may do little. Not dangerous, but it can be a waste of time and money.

Why nitrates and avanafil can’t mix: Avanafil lowers blood pressure modestly on its own (class effect; PDE5 inhibitors often knock systolic by roughly 8-10 mmHg at peak). Nitrates also widen blood vessels. Together, the fall in pressure can be dramatic and unpredictable. That’s why the label says it’s an absolute “don’t”. The same logic applies to poppers and to riociguat.

Citations: FDA Stendra label (2024 update), EMA Spedra SmPC, BNF (UK) 2024-2025; AHA statements on sexual activity and heart disease.

How to screen yourself: simple checks, timing rules, and what to do if you slip up

If a doctor or pharmacist isn’t right in front of you, use this simple set of checks. It won’t replace medical advice, but it will keep you out of most trouble.

1) Quick yes/no screen

• Do you carry or use any nitrate, like a GTN spray or tablets for chest pain? - If yes, avanafil is not for you.
• Do you use poppers? - Don’t mix with avanafil. If you won’t stop, don’t start avanafil.
• Are you on riociguat (for pulmonary hypertension)? - Avanafil is off the table.
• Are you on a ritonavir- or cobicistat-boosted HIV regimen, or strong azole antifungals? - Avoid avanafil; ask your clinic for options.
• Has a doctor told you sex is not safe for now due to your heart? - Don’t use avanafil yet.
• Do you have severe liver disease, very low blood pressure, or a history of sudden vision loss (NAION)? - You need a specialist discussion before any PDE5 inhibitor.

2) The nitrate timing rule (if you already took avanafil)

If you’ve taken avanafil and then develop chest pain, do not use your nitrate spray. Call emergency services and tell them exactly when you took avanafil. Clinicians will treat without nitrates first. Labels and cardiology guidance use these washout windows:

These are minimums, not DIY rules. Only trained clinicians should weigh up nitrates after those times because blood pressure responses vary person to person.

3) The alpha-blocker trick

If you take an alpha-blocker (doxazosin, tamsulosin, alfuzosin), make sure your dose has been stable and your blood pressure is steady. Start avanafil low (often 50 mg in the UK), separate doses by several hours, and stand up slowly. If you get lightheaded, stop and call your prescriber.

4) The CYP3A4 check

• Strong inhibitors: ritonavir/cobicistat boosters, ketoconazole, itraconazole - don’t combine with avanafil.
• Moderate inhibitors: erythromycin, clarithromycin, verapamil, diltiazem, fluconazole, grapefruit juice - you may need to cap avanafil at 50 mg no more than once daily, or avoid.
• Inducers: rifampicin, carbamazepine, phenytoin, St John’s wort - avanafil may underperform; consider different ED strategies.

5) Eye and ear red flags

• Sudden drop in vision in one or both eyes? Stop avanafil; seek urgent eye care (risk of NAION).
• Sudden hearing loss, ringing, or dizziness? Stop and get urgent medical help.

6) Heart and blood pressure sanity check

• If you get breathless walking up one flight of stairs, or chest pain with light activity, get heart review first.
• If your blood pressure is rarely above 90/50 mmHg, this drug isn’t a safe starting point.

Accidentally mixed? Here’s what to do

• Took avanafil and then a nitrate (or poppers)? Sit or lie down. Call emergency services. Tell them exactly what you took and when.
• Feeling faint, sweaty, or confused after a mix? Same plan-get help, don’t try to “walk it off”.
• Chest pain after avanafil: avoid nitrates and seek urgent care; other non-nitrate treatments exist in the ambulance/hospital.

Why this matters: In controlled studies, PDE5 inhibitors plus nitrates produced large additional drops in blood pressure vs either alone. Labels reflect that evidence, and emergency teams follow strict protocols.

If avanafil isn’t for you: safer paths, swaps, and real-life workarounds

Plenty of men can’t take avanafil because of heart meds or health history. The good news: there are workable options. Some are pills with different timing; others skip the blood pressure pathway altogether.

1) Non-PDE5 options that dodge the nitrate clash

• Vacuum erection devices (VEDs): drug-free, safe with nitrates, and increasingly discreet. Add a constriction ring to maintain the erection. Many NHS clinics still recommend them when pills aren’t suitable.
• Alprostadil (injection or urethral suppository): works locally on penile tissue. No nitrate conflict. Training helps-and most men find the injection easier than they fear.
• Psychosexual therapy: performance anxiety is common and can tank response to meds. A few targeted sessions can change outcomes more than dose tweaks.

2) Fix the “silent blockers” of erectile function

• Obstructive sleep apnoea: untreated OSA blunts erectile response. CPAP often improves ED within weeks.
• Low testosterone: if symptoms fit (low libido, low morning energy), check morning total testosterone twice. Treat if truly low; pills work better once hormones are steady.
• Metabolic syndrome: waist size, triglycerides, and HbA1c tell you a lot. Small changes (5-10% weight loss, consistent walking) can raise nitric oxide bioavailability and responsiveness.

3) If you’re on alpha-blockers or borderline BP

• Prioritise daytime hydration and slow position changes.
• Take avanafil at the lowest effective dose, and don’t stack alcohol on top-it potentiates hypotension.
• If dizziness persists, switch strategy rather than chasing doses.

4) When a different PDE5 might fit better

Be honest: all PDE5 inhibitors share the big “don’ts” (nitrates, riociguat). But their half-lives differ, which affects timing cautions and planning. If you struggle to time sex, tadalafil’s longer window helps; if you need a shorter nitrate restriction, avanafil has the shortest washout among the big four. This only matters if you don’t take nitrates at baseline.

5) Talking to your clinician (and what they’ll ask)

• Bring a full medication list, including GTN spray, inhalers, injections, and over-the-counter products like decongestants or herbal supplements.
• Share your worst blood pressure readings and any dizzy spells. That context changes starting dose or the plan entirely.
• Mention any vision/hearing episodes, even if they resolved.
• Set a goal beyond “stronger erections”: fewer side effects, better reliability, or nitrate compatibility. The plan flows from the goal.

Cheat-sheet checklist (print or screenshot)

• If you use nitrates or poppers → no avanafil, full stop.
• On riociguat → no avanafil.
• On strong CYP3A4 inhibitor (ritonavir/cobicistat, ketoconazole) → avoid avanafil.
• Unstable cardiac disease or recent MI/stroke → cardiology clearance first.
• Severe liver disease → avoid avanafil; discuss alternatives.
• Severe kidney disease → specialist advice before any PDE5.
• History of NAION/retinal disease → avoid; get ophthalmology/cardiology input.
• Alpha-blocker on board → stable first, then low-dose start with caution.
• If chest pain after taking avanafil → no nitrates; call emergency services.

Mini‑FAQ

• Can I drink alcohol with avanafil? Small amounts are usually fine, but alcohol increases dizziness and lowers blood pressure. Heavy drinking also blunts erections. Keep it light.
• Is grapefruit juice a problem? Yes, it can raise avanafil levels. Avoid on the day you use it.
• What if I have controlled heart disease? Many men with stable heart disease and good exercise tolerance can use a PDE5 inhibitor safely. Get your GP or cardiologist to sign off; they’ll often do a risk/fitness check.
• Can I take avanafil with tamsulosin? Sometimes, yes-if your blood pressure is stable. Start low, separate the doses by several hours, and watch for lightheadedness.
• What’s the usual starting dose? Many start at 100 mg 15-30 minutes before sex; some need 50 mg due to interactions or side effects; others may go to 200 mg if tolerated. Follow local labeling and your prescriber.
• Is avanafil safe with antihypertensives? Often yes, if blood pressure is well controlled. The exception is alpha‑blockers (caution) and the absolute exception is nitrates (do not use).

Next steps and troubleshooting

• You carry GTN spray or take nitrates: Skip avanafil. Ask about vacuum devices or alprostadil. If ED is new, screen for underlying heart disease-it’s often the first sign.
• You’re on ritonavir/cobicistat or strong azoles: Don’t mix. Your HIV or infectious disease team can advise on timing or alternatives not metabolised the same way.
• Blood pressure is low or you feel woozy on standing: Treat that first. Hydration, medication review, and slower position changes help. Only then reconsider ED treatment.
• No response to avanafil but no red flags: Try it on 4 separate occasions (good sleep, light meal, low alcohol), then consider dose adjustment. If still poor, switch class (e.g., to tadalafil) or move to VED/alprostadil.
• Vision/hearing scares: Stop the drug and get urgent medical care. Don’t retry until a specialist reviews.

Credibility note: The advice above aligns with 2024-2025 FDA/EMA labeling for avanafil, the British National Formulary, and cardiology guidance (including AHA statements) on sexual activity and cardiovascular risk. Labels change; your prescriber’s call always takes priority.