Tadalafil
Tadalafil
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
| Parameter | Details |
| Absorption | Rapid oral absorption; peak plasma concentration in ~1–2 h. |
| Bioavailability | ~ 66 % after 10 mg dose; food slows absorption by ~30 % but does not reduce overall exposure. |
| Distribution | Protein binding ~70 % (primarily albumin). CNS penetration low. |
| Metabolism | Hepatic metabolism via CYP3A4/5 and CYP2C9; mainly forms 19‑hydroxy and 6‑/10‑oxid metabolites. |
| Elimination | Renal route (~ 35 %) and fecal excretion of metabolites. |
| Half‑life | ~ 17–20 h (supports once‑daily dosing). |
| Drug interactions | Strong CYP3A4 inhibitors ↑ plasma levels; CYP3A4 inducers ↓ exposure. Nitrates, salicylates, organophosphates contraindicated (both). |
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
| Indication | On‑Demand (ED) | Daily (ED/BPH) |
| Standard | 10 mg per sexual activity (minimum 2 h apart) | 5 mg once daily (anytime) or 2.5 mg twice daily |
| Light/Moderate | 5 mg as needed | 2.5 mg once daily |
| BPH separate | 5 mg twice daily | 2.5 mg once daily |
• 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.
--
• 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.