Safety
Food, alcohol, grapefruit, and other drugs
A PDE5 inhibitor fails in ordinary life for ordinary reasons: a heavy dinner, a third drink, or a medicine that blocks the enzyme which clears the drug. This page separates absorption effects from true contraindications.
High-fat meals
Sildenafil may be taken with or without food. With a high-fat meal, the mean time to peak blood level is delayed about 60 minutes and the mean peak falls about 29 percent. The practical result is a dose that feels late and weak. A lighter meal, or taking the dose further ahead of a heavy dinner, is the adjustment people discuss. It is not a requirement to fast for safety.
Tadalafil’s label says to take it without regard to food. Avanafil may be taken with or without food. Levitra may be taken with or without food. Staxyn, the dissolving vardenafil tablet, is taken without liquid. If food timing is the main problem with sildenafil, that is a reason to talk about a different drug, not a reason to take a second sildenafil tablet.
Alcohol
Alcohol makes erectile dysfunction worse on its own, so a drink can cancel the benefit you are trying to measure. It also adds to dizziness and low blood pressure. Avanafil’s label specifically warns that substantial alcohol, more than about 3 units, may lead to hypotension, with a faster heart rate, dizziness, or headache. Tadalafil labeling likewise warns that alcohol potentiates blood-pressure lowering. “A unit” is not an invitation to calculate a personal maximum. Less alcohol makes both the erection and the blood pressure easier to predict.
Grapefruit and CYP3A4
Sildenafil, tadalafil, vardenafil, and avanafil are all cleared largely by CYP3A4 in the liver and gut. Grapefruit juice inhibits that enzyme in the intestinal wall and can raise exposure to drugs that use it. The effect of grapefruit is variable and lasts longer than the glass, because the enzyme has to be replaced. The clean consumer instruction is to ask the pharmacist before you combine grapefruit with a standing PDE5 prescription, and not to use grapefruit to “boost” a dose.
Stronger inhibitors than grapefruit are already written into the dose caps:
- Sildenafil. Consider 25 mg with ketoconazole, itraconazole, saquinavir, or erythromycin. With ritonavir, do not exceed 25 mg in 48 hours.
- Tadalafil. With potent inhibitors, as-needed use is capped at 10 mg no more than every 72 hours, and once-daily use at 2.5 mg.
- Vardenafil. Inhibitor-specific caps, including a very low dose with cobicistat.
- Avanafil. Do not use with strong inhibitors. Moderate inhibitors: maximum 50 mg in 24 hours.
The list of strong inhibitors includes some HIV medicines, some hepatitis C regimens, clarithromycin, and older azole antifungals. Rifampin does the opposite: it induces CYP3A4 and can make tadalafil much less effective. Do not change the ED dose to compensate. Tell the prescriber.
Alpha-blockers and other blood-pressure drugs
Alpha-blockers (tamsulosin, alfuzosin, silodosin, doxazosin, terazosin, prazosin) and PDE5 inhibitors both relax vascular smooth muscle. Together they can cause symptomatic hypotension: dizziness, lightheadedness, fainting. Labels share a sequence. Be stable on the alpha-blocker first. Start the PDE5 inhibitor at its lowest recommended dose. For sildenafil that starting dose is 25 mg. For vardenafil it is 5 mg. For avanafil it is 50 mg. For as-needed tadalafil it is the lowest recommended dose. Once-daily tadalafil for prostate symptoms is not recommended with alpha-blockers at all.
Other antihypertensives can add a smaller effect. The prescriber needs the whole list, including “as needed” prostate samples from a previous clinician.
What not to stack
Do not combine two PDE5 inhibitors. Do not add an herbal male-enhancement product, because FDA testing has repeatedly found undeclared sildenafil, tadalafil, or analogues in those bottles. That is a double dose you cannot see. See unregulated supplements.
Sources
- Clinical pharmacology sections of the four U.S. labels, especially sildenafil food data and the CYP3A4 dose modifications.