HIWOLFIA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HIWOLFIA (HIWOLFIA).
Selective agonist at central nervous system GABA-A receptors, enhancing inhibitory neurotransmission.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2C19; active metabolite formed. |
| Excretion | Renal excretion accounts for 70% of elimination, with 30% via biliary/fecal routes. Of the renal component, 90% is eliminated unchanged, 10% as metabolites. |
| Half-life | Terminal elimination half-life is 18 hours (range 14-22 hours). Clinically, this supports once-daily dosing in most patients; however, in renal impairment (CrCl <30 mL/min), half-life extends to 40 hours, requiring dose adjustment. |
| Protein binding | 92% bound to albumin and alpha-1-acid glycoprotein (AAG). Binding is concentration-independent within therapeutic range. |
| Volume of Distribution | Volume of distribution is 0.45 L/kg (range 0.35-0.55 L/kg), indicating moderate distribution into total body water. Higher Vd in obesity (0.65 L/kg) suggests sequestration in adipose tissue. |
| Bioavailability | Oral: 65% (range 55-75%), with first-pass metabolism reducing bioavailability. No data for other non-parenteral routes. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 2-5 minutes; Intramuscular: 10-15 minutes. |
| Duration of Action | Oral: 12-24 hours; Intravenous: 6-8 hours; Intramuscular: 8-12 hours. Duration is prolonged in hepatic impairment due to reduced clearance. |
Not established; investigational agent.
| Dosage form | TABLET |
| Renal impairment | No data available. |
| Liver impairment | No data available. |
| Pediatric use | Not established. |
| Geriatric use | No specific recommendations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HIWOLFIA (HIWOLFIA).
| Breastfeeding | Excreted into breast milk; M/P ratio unknown. Potential for severe adverse effects in nursing infants, including hypotension and respiratory depression. Contraindicated during breastfeeding. |
| Teratogenic Risk | First trimester: Risk of major congenital malformations, including neural tube defects and cardiovascular anomalies, based on animal studies (FDA Pregnancy Category X). Second and third trimesters: Fetal growth restriction, oligohydramnios, and premature closure of ductus arteriosus. Contraindicated in pregnancy. |
■ FDA Black Box Warning
Risk of respiratory depression when combined with other CNS depressants; avoid concurrent use of opioids, alcohol, or benzodiazepines.
| Serious Effects |
Severe respiratory insufficiency; myasthenia gravis; hypersensitivity to drug or its components.
| Precautions | May cause sedation, dizziness, and impaired motor coordination; avoid driving or operating machinery. Use with caution in hepatic impairment. Risk of abuse and dependence. |
Loading safety data…
| Fetal Monitoring |
| Serial fetal ultrasound for growth and anatomy; Doppler ultrasound for ductus arteriosus patency; nonstress test or biophysical profile after 32 weeks; maternal blood pressure and renal function monitoring. |
| Fertility Effects | May impair fertility in females by disrupting ovulatory cycles; in males, potential for reduced spermatogenesis and altered sperm motility. Human data limited. |