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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Nitrates can cause severe hypotension Can cause priapism and back pain.
| Breastfeeding | Excretion into human milk unknown; but based on molecular weight, expected to be minimal. M/P ratio not available. Caution advised due to potential adverse effects in nursing infants. |
| 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 |
■ 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 |
Concomitant use with nitrates or nitric oxide donors, hypersensitivity to tadalafil, use in patients with severe hepatic impairment (Child-Pugh class C), use with guanylate cyclase stimulators (e.g., riociguat).
| 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. |
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| 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. |