GENAPAX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GENAPAX (GENAPAX).
Gepirone is a 5-HT1A receptor partial agonist, enhancing serotonergic neurotransmission in brain regions implicated in mood regulation.
| Metabolism | Primarily via CYP3A4; also minor routes via CYP2D6 and aldehyde oxidase. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 80%); biliary/fecal elimination accounts for 15%; the remainder is metabolized. |
| Half-life | Terminal elimination half-life: 18-24 hours in adults with normal renal function, prolonged to >40 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 95% bound to serum albumin and alpha-1-acid glycoprotein (AAG). |
| Volume of Distribution | 2–4 L/kg, indicating extensive tissue distribution (e.g., liver, kidney, lung) with potential for accumulation in erythrocytes. |
| Bioavailability | Oral: 60–75% (first-pass metabolism); Intravenous: 100%. |
| Onset of Action | Oral: ~2–4 hours; Intravenous: within 15 minutes; peak effect at 1–2 hours. |
| Duration of Action | 12–24 hours after a single oral dose; up to 24–36 hours after intravenous administration due to prolonged half-life; clinical effect may persist beyond serum concentration decline due to tissue binding. |
Oral: 500 mg twice daily. Intravenous: 500 mg over 1 hour every 6 hours.
| Dosage form | TAMPON |
| Renal impairment | GFR 30-59 mL/min: 250 mg twice daily. GFR 15-29 mL/min: 250 mg once daily. GFR <15 mL/min: 250 mg every 48 hours. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | 10-15 mg/kg/dose every 12 hours orally or intravenously, max 500 mg/dose. |
| Geriatric use | Start at 250 mg twice daily; adjust based on renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GENAPAX (GENAPAX).
| Breastfeeding | Excreted into human breast milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants (e.g., immunosuppression, growth suppression). Contraindicated during breastfeeding; if unavoidable, pump and discard milk for 5 elimination half-lives after last dose. |
| Teratogenic Risk | First trimester: Known human teratogen; high risk of major congenital malformations (neural tube defects, cardiovascular anomalies, cleft palate). Second and third trimesters: Increased risk of fetal growth restriction, premature birth, and neurodevelopmental impairment. Avoid use in pregnancy unless no safer alternative. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with MAOIs.","History of QT prolongation or congenital long QT syndrome.","Severe hepatic impairment (Child-Pugh Class C)."]
| Precautions | ["QTc prolongation risk, particularly in patients with hypokalemia, hypomagnesemia, or concurrent use of QTc-prolonging drugs.","Serotonin syndrome risk with coadministration of other serotonergic drugs.","Avoid use with MAOIs or within 14 days of MAOI discontinuation.","Dose adjustment required in hepatic impairment."] |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood counts, liver function, and renal function monthly. Fetal ultrasound every 4 weeks for growth and anatomy. For third trimester use, neonatal monitoring for hypoglycemia, hypocalcemia, and jaundice. |
| Fertility Effects | May reduce fertility in both sexes due to gonadotropin suppression. Reversible upon discontinuation. Advise pregnancy prevention for at least 3 months after cessation. |