Tadalafil

• Erectile dysfunction
• Benign prostatic hyperplasia (BPH)
• Pulmonary arterial hypertension
• Combined ED and BPH treatment

Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor used for the treatment of erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension. Distinguished by its prolonged duration of action (up to 36 hours), it offers unique dosing flexibility including daily dosing options that allow for spontaneity in intimate relationships.

Mechanism of Action

Tadalafil selectively inhibits phosphodiesterase type 5 (PDE5), the enzyme responsible for degrading cyclic guanosine monophosphate (cGMP) in the corpus cavernosum, prostatic smooth muscle, and pulmonary vasculature. Sexual stimulation causes local release of nitric oxide, which activates guanylate cyclase to produce cGMP. By inhibiting PDE5, tadalafil allows cGMP to accumulate, enhancing smooth muscle relaxation and blood flow.

In erectile dysfunction, this mechanism promotes penile erection in response to sexual stimulation. In benign prostatic hyperplasia, smooth muscle relaxation in the prostate and bladder improves urinary symptoms. In pulmonary arterial hypertension, pulmonary vasodilation reduces pulmonary vascular resistance and improves exercise capacity.

Available Formulations

Tadalafil is available under different brand names for different indications. Cialis is available as tablets in 2.5 mg, 5 mg, 10 mg, and 20 mg strengths for erectile dysfunction and BPH. Adcirca is available as 20 mg tablets specifically for pulmonary arterial hypertension. Generic tadalafil is now available for all indications. The same molecule is used across all products, but FDA-approved labeling and dosing differ by indication.

FDA-Approved Indications

Tadalafil is FDA-approved for erectile dysfunction in adult males, signs and symptoms of benign prostatic hyperplasia, the combination of erectile dysfunction and BPH, and pulmonary arterial hypertension (WHO Group 1) to improve exercise ability in adults. The ability to treat both ED and BPH with a single medication is particularly valuable for patients with both conditions.

Dosing Guidelines

For erectile dysfunction (as needed): Start at 10 mg prior to anticipated sexual activity; may adjust to 20 mg or decrease to 5 mg based on efficacy and tolerability. For erectile dysfunction (daily): 2.5 mg once daily at approximately the same time, may increase to 5 mg daily. For BPH: 5 mg once daily at approximately the same time. For ED and BPH combined: 5 mg once daily. For pulmonary arterial hypertension: 40 mg (two 20 mg tablets) once daily.

Duration of Action

Tadalafil's extended duration of action (up to 36 hours) distinguishes it from other PDE5 inhibitors. This prolonged effect allows for greater spontaneity and has led to its nickname "the weekend pill." The daily dosing option maintains steady plasma levels, eliminating the need to time medication with anticipated sexual activity.

Important Safety Considerations

All PDE5 inhibitors are contraindicated with nitrates due to severe hypotensive effects that can be life-threatening. The interaction can occur for up to 48 hours after tadalafil use due to its long half-life. Caution is advised with alpha-blockers due to additive hypotension. Tadalafil is contraindicated in patients with severe hepatic impairment and is not recommended with CrCl less than 30 mL/min for daily dosing. Vision loss (NAION) and hearing loss have been reported rarely.

Drug Interactions

Nitrates and nitric oxide donors are absolutely contraindicated. Alpha-blockers may cause additive hypotension; patients should be stable on alpha-blocker therapy before adding tadalafil. Strong CYP3A4 inhibitors (ketoconazole, ritonavir) significantly increase tadalafil levels; dose adjustment may be needed. CYP3A4 inducers (rifampin) may decrease tadalafil efficacy. Alcohol can increase the risk of orthostatic hypotension.

Special Populations

Dose adjustment is required in renal and hepatic impairment depending on severity and indication. For mild to moderate hepatic impairment, doses should not exceed 10 mg for as-needed use. Tadalafil is not indicated for use in women. In patients over 65 years, no dose adjustment is needed based on age alone, but they may be more sensitive to hypotensive effects. Patients with cardiovascular disease should discuss with their physician whether sexual activity is appropriate.

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