What are the contraindications for tadalafil (Cialis)?

Contraindications for Tadalafil

Tadalafil is absolutely contraindicated in patients using any form of nitrate therapy (requiring a 48-hour washout period), those taking guanylate cyclase stimulators, and patients with known serious hypersensitivity to the drug. 1

Absolute Contraindications

Nitrate Therapy (Most Critical)

• Any form of organic nitrate use—whether regular, intermittent, oral, sublingual, transdermal, or topical (including Nitro-BID ointment)—is an absolute contraindication to tadalafil. 2, 3, 1
• The mechanism involves tadalafil's inhibition of phosphodiesterase-5 (PDE5), which prevents degradation of cyclic GMP; when combined with nitrates, this causes markedly exaggerated and prolonged vasodilation leading to profound hypotension, myocardial infarction, and potentially death. 3, 4
• If a patient has taken tadalafil, at least 48 hours must elapse after the last dose before ANY nitrate therapy can be administered (compared to only 24 hours for shorter-acting PDE5 inhibitors like sildenafil or vardenafil). 2, 3, 4, 1
• This is a Class III (harm) recommendation from the ACC/AHA, meaning the intervention should never be performed. 3
• Even in life-threatening situations requiring nitrates, the 48-hour window should be respected, and nitrates should only be given under close medical supervision with hemodynamic monitoring. 1

Guanylate Cyclase Stimulators

• Concomitant use with GC stimulators (such as riociguat for pulmonary arterial hypertension) is absolutely contraindicated due to potentiation of hypotensive effects through the same cGMP pathway. 1

Hypersensitivity Reactions

• Tadalafil is contraindicated in patients with known serious hypersensitivity, including those with history of Stevens-Johnson syndrome or exfoliative dermatitis. 1

Relative Contraindications and High-Risk Conditions

Cardiovascular Disease Requiring Caution

• Cardiac disease, hypotension, poorly controlled blood pressure, or recent stroke (<6 months) represent contraindications per European Association of Urology guidelines. 2
• Patients with preexisting cardiovascular disease require careful assessment of cardiac risk before sexual activity and tadalafil use. 1, 5

Hepatic and Renal Insufficiency

• Significant hepatic or renal insufficiency is listed as a contraindication in EAU guidelines. 2

Anterior Ischemic Optic Neuropathy

• Contraindicated in patients who report sudden loss of vision due to anterior ischemic optic neuropathy after previous PDE5 inhibitor use. 2

Critical Drug Interactions Requiring Dose Adjustment

Alpha-Blockers

• While not absolutely contraindicated, caution is required when coadministering tadalafil with alpha-blockers (doxazosin, tamsulosin, alfuzosin) due to additive vasodilatory effects and blood pressure lowering. 1
• Combination should only be considered when patients are hemodynamically stable, using the lowest tadalafil dose, with close blood pressure monitoring. 5

Antihypertensive Medications

• Tadalafil acts as a mild systemic vasodilator and can augment blood pressure-lowering effects of antihypertensives (amlodipine, ARBs, bendrofluazide, enalapril, metoprolol). 1
• Small reductions in blood pressure occur but are generally not clinically significant in stable patients. 1, 6

CYP3A4 Inhibitors

• Strong CYP3A4 inhibitors increase tadalafil exposure and require dose adjustment, though this represents a dosing consideration rather than absolute contraindication. 1, 7

Common Clinical Pitfalls to Avoid

• Never assume topical nitrates (like Nitro-BID ointment) are safer—they carry the same absolute contraindication as all other nitrate formulations. 4
• Always ask patients presenting with chest pain about recent PDE5 inhibitor use before administering nitroglycerin. 4, 1
• Remember tadalafil's extended half-life (17.5 hours) and duration of effect (up to 36 hours) necessitates the longer 48-hour washout period compared to other PDE5 inhibitors. 4, 8
• Document carefully which PDE5 inhibitor and when it was last taken—this is critical for emergency situations where nitrates might be needed. 4

Alternative Anti-Ischemic Therapies When Tadalafil Precludes Nitrate Use

• Beta-blockers are recommended as first-line anti-ischemic therapy when nitrates are contraindicated due to recent tadalafil use. 3, 4
• Calcium channel blockers (non-dihydropyridine preferred) can be used for recurrent ischemia. 3, 4
• ACE inhibitors provide blood pressure control and cardioprotection. 3, 4