TADALAFIL
Clinical safety rating: safe
Animal studies have demonstrated safety
Inhibitor of phosphodiesterase type 5 (PDE5), enhancing cyclic guanosine monophosphate (cGMP)-mediated relaxation of smooth muscle in the corpus cavernosum and pulmonary vasculature.
| Metabolism | Primarily metabolized by CYP3A4; minor contribution from CYP3A5 and CYP2C9. |
| Excretion | Primarily hepatic metabolism (CYP3A4); 36% excreted in urine (mainly metabolites), 61% in feces (mainly metabolites), <0.1% unchanged in urine. |
| Half-life | Terminal elimination half-life is 17.5 hours in healthy subjects; supports once-daily dosing and prolonged effect (up to 36 hours for erectile function). |
| Protein binding | 94% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 63 L (0.9 L/kg for 70 kg adult); indicates distribution into tissues beyond plasma volume. |
| Bioavailability | Oral bioavailability is 80% (dose-independent). |
| Onset of Action | Oral: 16 minutes (first signs of erection with sexual stimulation); median time to erection sufficient for intercourse is 30 minutes. |
| Duration of Action | Up to 36 hours (ability to achieve and maintain erection); peak effect at 2-6 hours, with clinically meaningful effect persisting for 24-36 hours. |
| Molecular Weight | 389.406 |
Erectile dysfunction: 10-20 mg orally as needed, 30-60 minutes before sexual activity; maximum 1 dose per day. Benign prostatic hyperplasia: 5 mg orally once daily. Pulmonary arterial hypertension: 40 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | Creatinine clearance (CrCl) 30-50 mL/min: no adjustment for as-needed use; for daily use, reduce dose to 5 mg once daily. CrCl <30 mL/min: not recommended. Hemodialysis: not recommended. |
| Liver impairment | Child-Pugh class A and B: no adjustment necessary; monitor for adverse effects. Child-Pugh class C: not recommended due to increased exposure. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required for age alone. Consider dose adjustment for renal impairment as indicated. |
| 1st trimester | Limited data; tadalafil is not recommended in pregnancy due to potential fetal risk. Animal studies have shown developmental toxicity at high doses. |
| 2nd trimester | Not recommended; avoid use unless benefit clearly outweighs risk. |
| 3rd trimester | Not recommended; use only if clearly needed. Monitor for adverse effects on uterine contractility. |
Clinical note
Nitrates can cause severe hypotension Can cause priapism and back pain.
| Placental transfer | Tadalafil crosses the placenta in animals. In humans, limited data suggest transfer occurs; however, the extent and clinical significance are not well defined. |
| Breastfeeding | Tadalafil is excreted into breast milk in very small amounts, but no adverse effects have been reported in nursing infants. However, due to potential for vasodilation and unknown long-term effects, caution is advised. The manufacturer recommends discontinuing breastfeeding or the drug, considering the importance of the drug to the mother. |
■ FDA Black Box Warning
Not recommended in patients with unstable angina or uncontrolled hypertension. Risk of priapism and vision loss.
| Common Effects | BPH |
| Serious Effects |
Concurrent use of any nitrate (e.g., nitroglycerin, isosorbide dinitrate) due to risk of severe hypotension.Use in patients with unstable angina, severe heart failure (NYHA class II-IV), uncontrolled arrhythmias, or recent stroke or myocardial infarction (within the last 3 months).Hypersensitivity to tadalafil or any component of the formulation.Use in patients with severe hepatic impairment (Child-Pugh class C).
| Precautions | Concomitant nitrates (absolute contraindication), hypotension risk, priapism, sudden hearing loss, non-arteritic anterior ischemic optic neuropathy (NAION), use with strong CYP3A4 inhibitors requiring dose adjustment. |
| Food/Dietary |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category B. In animal studies, no teratogenicity or fetal harm observed at doses up to 18 mg/kg/day in rats and 30 mg/kg/day in mice. No adequate controlled studies in pregnant women; use only if clearly needed. |
| Fetal Monitoring | No specific monitoring required; standard prenatal care. Monitor for maternal hypotension due to vasodilation, especially if used with nitrates. |
| Fertility Effects | In animal studies, no impairment of fertility at doses up to 400 mg/kg/day in rats. Human data limited; no adverse effects on spermatogenesis reported. |
| No significant food interactions. High-fat meals may delay absorption but do not affect efficacy. Grapefruit juice may slightly increase tadalafil levels; avoid excessive consumption. |
| Clinical Pearls | Tadalafil has a longer half-life (17.5 h) than sildenafil, allowing once-daily dosing for ED and BPH. Avoid use with nitrates due to risk of severe hypotension. Use with caution in patients with severe renal or hepatic impairment. Contraindicated in patients taking guanylate cyclase stimulators (e.g., riociguat). |
| Patient Advice | Take tadalafil at least 30 minutes before sexual activity for ED; effect lasts up to 36 hours. · For BPH, take once daily at approximately the same time each day. · Do not take with nitrates for chest pain or recreational drugs called 'poppers'. · Seek immediate medical help if you have a sudden decrease or loss of vision or hearing. · Avoid alcohol in excess as it may increase the risk of dizziness and hypotension. |