PDE5 Inhibitor Safety: Interactions, Contraindications and Emergencies

What counts as a nitrate

• Nitroglycerin in every form — sublingual tablets, spray, patches, ointment, intravenous.
• Isosorbide mononitrate and isosorbide dinitrate, often taken daily for angina.
• Amyl nitrite and butyl nitrite — 'poppers'. These are sold recreationally and are chemically nitrates.
• Riociguat (Adempas), a guanylate cyclase stimulator used in pulmonary hypertension, is separately contraindicated for the same reason.

Alpha-blockers

Tamsulosin, alfuzosin, doxazosin, terazosin — used for prostate symptoms and sometimes blood pressure. Both drug classes lower blood pressure. The standard approach is to be stable on the alpha-blocker first, start the PDE5 inhibitor at the lowest dose, and separate the two doses by several hours.

Strong CYP3A4 inhibitors

Ritonavir and other protease inhibitors, ketoconazole, itraconazole, clarithromycin, and grapefruit juice in quantity. These raise PDE5 inhibitor levels substantially and usually require a reduced dose and limited frequency.

CYP3A4 inducers

Rifampicin, carbamazepine, phenytoin and St John's wort reduce levels and may make the medication less effective.

Other antihypertensives

Generally compatible, with a modest additive blood-pressure effect. Worth knowing about if you are prone to dizziness.

Liver or kidney impairment

Severe impairment requires a lower starting dose. Daily tadalafil is generally not recommended in severe renal impairment.

Alcohol

Both lower blood pressure. Moderate intake is usually fine; heavy drinking increases dizziness and impairs erections independently.

• Anyone taking nitrates in any form, or riociguat.
• Anyone with a recent heart attack, stroke or life-threatening arrhythmia — typically within about six months, pending assessment.
• Unstable angina, or angina occurring during sexual activity.
• Uncontrolled hypertension, or significant low blood pressure.
• Severe heart failure that is not stable.
• Previous non-arteritic anterior ischaemic optic neuropathy (NAION) in either eye.
• Hereditary degenerative retinal disorders such as retinitis pigmentosa.
• Severe liver impairment, without specialist advice.
• Anyone with a condition predisposing to priapism — sickle cell disease, multiple myeloma or leukaemia — needs individual assessment.
• For vardenafil specifically: congenital long QT syndrome, or treatment with class IA or class III antiarrhythmics.

• Sudden loss of vision in one or both eyes — stop the medication and seek care immediately.
• Sudden hearing loss, ringing or dizziness — the same.
• Chest pain, jaw or arm pain, or severe breathlessness during or after sex — call emergency services and tell them what you have taken.
• Fainting or near-fainting, particularly with an alpha-blocker.
• A severe rash or facial swelling — allergic reactions are rare but possible.

• ✓Tell every prescriber and pharmacist that you take an ED medication — including dentists and emergency staff.
• ✓Carry a note or use your phone's medical ID if you take tadalafil, given the 48-hour nitrate window.
• ✓Never take a dose obtained from someone else. Their prescription reflects their health, not yours.
• ✓Never double a dose that did not work. Discuss it instead.
• ✓Do not combine an ED tablet with an injectable treatment unless a specialist has told you to.
• ✓Be honest about recreational drug use, especially poppers.