Generic Name

Tadalafil

Mechanism

• Selective PDE‑5 inhibition → prevents the breakdown of cyclic‑guanosine monophosphate (cGMP) in smooth muscle.
• Elevated cGMP → smooth‑muscle relaxation in the corpus cavernosum, pulmonary vasculature, and prostate/Bladder neck.
• Results in increased blood flow to the penis (ED), reduced prostate smooth‑muscle tone (BPH), and lower pulmonary arterial pressure (PAH).

The drug is non‑competitive and exhibits a long duration of action (≈ 36 h), allowing for flexible dosing.

Pharmacokinetics

Indications

1. Erectile Dysfunction (ED) – on‑demand or continuous therapy.
2. Benign Prostatic Hyperplasia (BPH) – improvements in urinary flow and symptoms.
3. BPH + ED – dual indication therapy.
4. Pulmonary Arterial Hypertension (PAH) – WHO Group 1; improves exercise capacity.

Contraindications

• Use with nitrates or nitric‑oxide donors – risk of severe hypotension.
• Severe hepatic impairment (Child‑Pugh class C) – contraindicated.
• Severe renal impairment (CrCl < 30 mL/min) – caution; dosing adjustment for BPH.
• Recent retinal or cerebral vascular events – not recommended.
• Concurrent use of POS (pulmonary arterial hypertension) with high‑dose nitrates – avoid.

Dosing

• Start lowest dose; titrate after 4 weeks if clinically necessary.
• For PAH, typical starting dose ≥ 2.5 mg once daily, escalation to 5 mg as tolerated.

Administration tips:
• Take with or without food; avoid high‑fat meals for rapid onset.
• Avoid alcohol; may enhance hypotensive effect.

Adverse Effects

Common (≥ 5 %)
• Headache
• Dyspepsia / abdominal pain
• Back pain
• Flushing
• Nasal congestion

Serious (≤ 1 %)
• Priapism (prolonged erection > 4 h)
• Angle‑closure glaucoma (rare)
• Severe hypotension (with nitrates)
• Visual disturbances (macular edema, central serous retinopathy)
• Transient ischaemic attack (TIA) / stroke (rare)

Monitoring

• Blood pressure before first dose in patients with hypertension or on nitrates.
• Liver function tests every 6 months in long‑term therapy or if hepatic dysfunction suspected.
• Renal function at baseline and annually (or sooner if CrCl ↓).
• Ophthalmologic exam when patients report visual changes.
• Cardiovascular assessment (ECG) in patients with unstable cardiac disease.

Clinical Pearls

• One‑day “day‑long” dosing: 5 mg daily maintains PDE‑5 inhibition throughout the day, providing spontaneous sexual activity without precise timing.
• Rapid onset vs. “cost‑efficient” dosing: 10 mg on‑demand yields faster response for ED but loses the convenience of once‐daily usage; consider patient lifestyle.
• CYP3A4 interactions: Patients on strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) should be monitored for increased plasma concentrations and adverse effects.
• BPH‑specific benefits: Tadalafil reduces prostate smooth‑muscle tone, thus improving Qmax by ~2 L/min and relieving LUTS (lower urinary tract symptoms) without the need for α‑blockers.
• Emergency when nitrate‑driven hypotension may occur: Ensure patients on nitrates avoid tadalafil; a *red‑flag* check in history or electronic alerts can prevent adverse drug events.
• Use in PAH: Even though tadalafil improves exercise capacity, it does not cure PAH; patients should remain under cardiology follow‑up with serial 6‑minute walk tests.

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• References (peer‑reviewed, up to 2024):
• Gauthier JJ, et al. *Pharmacologic Treatment of Erectile Dysfunction.* J Clin Pharmacol. 2023.
• American Urological Association Guidelines 2023.
• Pulmonary Arterial Hypertension Scientific Statement 2024.
• FDA label revision 2023.