ENTADFI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENTADFI (ENTADFI).
Combination of a 5α-reductase inhibitor (finasteride) and a phosphodiesterase 5 inhibitor (tadalafil). Finasteride inhibits type II 5α-reductase, preventing conversion of testosterone to dihydrotestosterone, reducing prostate growth. Tadalafil inhibits PDE5, increasing cGMP in smooth muscle, causing relaxation of the prostate and bladder neck.
| Metabolism | Finasteride is metabolized primarily via CYP3A4. Tadalafil is metabolized mainly by CYP3A4. |
| Excretion | ENTADFI (finasteride 5 mg and tadalafil 5 mg) is a fixed-dose combination. Finasteride is excreted 57% in feces (as metabolites) and 39% in urine (<1% as unchanged). Tadalafil is excreted primarily as metabolites, with 61% in feces and 36% in urine; <0.001% of dose is excreted unchanged in urine. |
| Half-life | Finasteride: terminal half-life ~6-8 hours (range 4-12 h) in young adults, 8 hours in elderly. Tadalafil: terminal half-life ~17.5 hours (range 11-28 h), supporting once-daily dosing. |
| Protein binding | Finasteride: ~90% bound to plasma proteins (mainly albumin). Tadalafil: ~94% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Finasteride: Vd ≈ 76 L (approx 1.1 L/kg based on 70 kg). Tadalafil: Vd ≈ 63-77 L (approx 0.9-1.1 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Finasteride 5 mg: oral bioavailability ~63% (range 56-74%). Tadalafil 5 mg: oral bioavailability ~80% (relative to intravenous); absorption not affected by food. |
| Onset of Action | Finasteride 5 mg: clinical effect (reduction in prostate size, improvement in urinary symptoms) evident after 3-6 months of daily dosing. Tadalafil 5 mg: onset of effect for BPH symptoms within 1-2 weeks, with peak effect at 4-8 weeks. |
| Duration of Action | Finasteride: effect persists as long as therapy continues; after discontinuation, serum DHT returns to baseline within 14 days, but clinical improvement may persist for several months. Tadalafil 5 mg: improvement in BPH symptoms maintained with continuous daily dosing; after cessation, symptoms gradually return to baseline. |
| Molecular Weight | 372.55 |
5 mg orally once daily.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m²). |
| Liver impairment | Contraindicated in Child-Pugh class B and C hepatic impairment. No dose adjustment required for Child-Pugh class A. |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustment required; however, monitor for adverse effects due to potential age-related renal and hepatic decline. |
| 1st trimester | Contraindicated due to risk of fetal external genitalia abnormalities; finasteride inhibits conversion of testosterone to dihydrotestosterone, which is critical for male fetal development. |
| 2nd trimester | Contraindicated; continued risk of fetal harm, especially in male fetuses. |
| 3rd trimester | Contraindicated; risk persists throughout pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for ENTADFI (ENTADFI).
| Placental transfer | Finasteride crosses the placenta in animal studies and is expected to cross in humans based on its molecular weight and lipophilicity. |
| Breastfeeding | Finasteride is excreted in human breast milk in small amounts; however, data are limited. Due to potential for adverse effects in nursing infants, caution is advised. Avoid use in breastfeeding women unless benefit clearly outweighs risk. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
PregnancyWomen of childbearing potential not using effective contraceptionHypersensitivity to finasteride or any component of the formulation
| Precautions | Hypersensitivity reactions, Sudden decrease in hearing or tinnitus, Prostate cancer screening and monitoring, Cardiovascular risk with sexual activity, Contraindicated with organic nitrates and GC stimulators (e.g., riociguat), Risk of priapism, Hepatic impairment dose adjustment, Renal impairment dose adjustment, Use of alpha-blockers, Antihypertensive effects, Risk of hypotension with concomitant alcohol |
| Food/Dietary | Grapefruit juice may increase tadalafil plasma concentrations; avoid concurrent consumption. High-fat meals may delay tadalafil absorption but do not affect overall exposure. There are no significant food interactions with finasteride. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | ENTADFI (finasteride and tadalafil) is contraindicated in pregnancy. Finasteride is a 5α-reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone (DHT) and can cause abnormal development of external genitalia in male fetuses. First trimester exposure is associated with hypospadias and other genital malformations. There is no human data for second and third trimester; however, based on mechanism, risks persist throughout pregnancy. Tadalafil, a PDE5 inhibitor, is Pregnancy Category B; no fetal harm is known in animals, but human data are limited. |
| Fetal Monitoring | Before initiating ENTADFI, rule out pregnancy with a negative pregnancy test. Women of childbearing potential should use effective contraception. If inadvertently used during pregnancy, monitor fetal anatomy (especially genitalia in male fetuses) via ultrasound. No specific maternal monitoring required, but monitor for maternal adverse effects (e.g., hypotension, priapism, myalgia). |
| Fertility Effects | Finasteride reduces serum DHT and can decrease epididymal sperm count, sperm motility, and fertility in male rats. Human studies report decreased semen volume, total sperm count, and sperm motility; these effects are reversible upon discontinuation. Tadalafil does not impair spermatogenesis or sperm motility; may transiently decrease sperm concentration in some men. In females, no direct fertility effects are known, but androgen suppression may theoretically affect ovarian function. |
| Clinical Pearls | ENTADFI (finasteride and tadalafil fixed-dose combination) is used for benign prostatic hyperplasia (BPH). Finasteride reduces DHT, improving symptoms and reducing risk of acute urinary retention; tadalafil enhances smooth muscle relaxation via PDE5 inhibition. Monitor PSA levels during therapy (finasteride halves PSA). Assess cardiovascular status before initiating tadalafil; avoid concurrent nitrates. Caution in hepatic impairment (tadalafil exposure increased). Advise patients that therapeutic effect may take 3-6 months. |
| Patient Advice | Take ENTADFI at the same time daily with or without food. · Do not take more than one dose per day. · Avoid grapefruit juice as it may increase tadalafil levels. · Report sudden decrease in hearing or vision promptly. · Seek immediate medical help for erection lasting >4 hours. · Use contraception if partner is pregnant or may become pregnant (finasteride can cause fetal harm). · Do not donate blood during treatment and for 1 month after stopping. · Avoid alcohol excessively as it may increase risk of hypotension. |