Sildenafil and tadalafil are usually well tolerated, but they belong to a class, the PDE5 inhibitors, that relaxes blood vessels, and that is where their important interactions come from. Some combinations are never prescribed. Others change the dose, the medication, or the advice a clinician gives. The list below follows the sildenafil and tadalafil labels and MedlinePlus. It isn't a screening tool: the intake asks about everything you take and every condition you have, and a US-licensed clinician decides what is appropriate for you.
The short answer
Never with nitrates or riociguat. Tell your clinician about alpha-blockers and any blood pressure medication, antifungal, antibiotic, HIV or seizure medication, any other product for erections, and how much you drink. Chest pain, fainting, a sudden change in vision or hearing, or an erection lasting more than 4 hours mean stop and get care.
Nitrates: the combination that is never prescribed
Nitrates are the chest-pain medications: nitroglycerin tablets, sprays, ointments and patches, isosorbide mononitrate and isosorbide dinitrate. Recreational "poppers" such as amyl nitrite and butyl nitrite are nitrates too. PDE5 inhibitors and nitrates both widen blood vessels, and together they can drop blood pressure suddenly and severely. Both labels list nitrates as a contraindication, with no dose that makes the combination acceptable.
The timing cuts both ways. If you take sildenafil or tadalafil and then develop chest pain, tell emergency staff what you took and when: the tadalafil label says at least 48 hours should pass after a dose before a nitrate is even considered.
Riociguat
Riociguat (Adempas), a medication for pulmonary hypertension, is a contraindication on both labels for the same reason as nitrates: it works on the same pathway, and the combination can cause a dangerous drop in blood pressure.
Alpha-blockers and other blood pressure medications
Alpha-blockers are prescribed for prostate symptoms and for high blood pressure: alfuzosin, doxazosin, prazosin, silodosin, tamsulosin and terazosin. Taken with a PDE5 inhibitor they can lower blood pressure further, with dizziness or fainting on standing. The labels' approach is sequencing: a man should be stable on his alpha-blocker before a PDE5 inhibitor is started, and the PDE5 inhibitor is started at its lowest dose. Other blood pressure medications add a smaller drop; most men take them together without trouble, but your clinician needs the list to set the dose.
Medications that raise sildenafil or tadalafil levels
Both medications are broken down by the liver enzyme CYP3A4. Medications that block it raise sildenafil and tadalafil levels, which raises the chance of side effects: the antifungals ketoconazole and itraconazole, the antibiotics clarithromycin and erythromycin, and ritonavir and other HIV protease inhibitors. The labels respond with lower doses or longer intervals between doses, and that adjustment is the clinician's to make. Medications that speed CYP3A4 up, such as rifampin and some seizure medications, can lower levels instead. MedlinePlus lists grapefruit and grapefruit juice as something to talk with your doctor about for both medications.
Alcohol
Alcohol also widens blood vessels. The tadalafil label notes that substantial alcohol, 5 units or more, taken with tadalafil may lead to low blood pressure, with dizziness, headache and a faster heart rate on standing, and MedlinePlus advises asking your doctor about alcohol with either medication. Moderate drinking is the safer side of the line.
Other products for erections
Sildenafil and tadalafil are not combined with each other or with any other PDE5 inhibitor, and neither is taken more than once a day. Supplements sold for sexual performance are a particular problem: some contain undeclared sildenafil or tadalafil, so taking one alongside a prescription doubles up without your knowing. Tell your clinician about every supplement, including nitric-oxide boosters such as L-arginine.
Conditions to tell your clinician about
None of these is an automatic no. They are the facts a clinician weighs when deciding whether a PDE5 inhibitor is appropriate, and at what dose:
- Heart disease, a recent heart attack or stroke, chest pain during sex, or an irregular heartbeat
- Low blood pressure, or high blood pressure that isn't controlled
- A history of sudden vision loss in one or both eyes, the eye condition retinitis pigmentosa, or NAION
- Sickle cell anemia, multiple myeloma or leukemia, which raise the risk of a prolonged erection
- Peyronie's disease or another physical deformity of the penis
- Kidney or liver disease, which can change the dose
- A bleeding problem or a stomach ulcer
- Hearing problems
Symptoms that mean stop and get care
Stop the medication and get care right away for chest pain, dizziness or nausea during sex; fainting; a sudden decrease or loss of vision in one or both eyes; a sudden decrease or loss of hearing, with or without ringing in the ears; or an erection that is painful or lasts longer than 4 hours, which is a medical emergency because it can damage the penis. Milder effects such as headache, flushing, a stuffy nose, indigestion and back pain are common and usually pass; mention them at your check-in so your clinician can adjust.
Bottom line: Nitrates and riociguat are never combined with sildenafil or tadalafil. Alpha-blockers, blood pressure medications, strong CYP3A4 inhibitors and alcohol change how these medications are prescribed, and supplements can hide a second PDE5 inhibitor. Give your clinician the whole list, and treat chest pain, fainting, a sudden change in vision or hearing, or an erection over 4 hours as reasons to stop and get care. For how the two medications differ, see sildenafil vs. tadalafil; for the once-daily option, see daily tadalafil.
