HEXALEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HEXALEN (HEXALEN).
Alkylating agent that crosslinks DNA, inhibiting DNA replication and transcription, and inducing apoptosis in rapidly dividing cells.
| Metabolism | Hepatic via demethylation and oxidation; metabolites include monodemethylated and didemethylated products. |
| Excretion | Primarily renal and hepatic metabolism; 60-70% excreted in urine as unchanged drug and metabolites; 15-20% eliminated in feces via biliary secretion. |
| Half-life | Terminal elimination half-life is 12-13 hours; prolonged to 24 hours in renal impairment. |
| Protein binding | 90-95% bound to albumin. |
| Volume of Distribution | Vd approximately 5.5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 100%. |
| Onset of Action | Oral: 1-2 hours after administration. |
| Duration of Action | Duration of action is 6-8 hours; clinical cytoreductive effects persist for several days. |
260 mg/m2/day orally in 4 divided doses for 14 or 21 days of a 28-day cycle.
| Dosage form | CAPSULE |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) as drug is primarily renally eliminated. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment, reduce dose by 50%. |
| Pediatric use | Safety and efficacy not established; limited data suggest dosing based on body surface area similar to adults with close monitoring. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and adjust accordingly due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HEXALEN (HEXALEN).
| Breastfeeding | It is unknown if altretamine is excreted in human breast milk. Due to potential for serious adverse reactions in nursing infants (e.g., myelosuppression, carcinogenesis), breastfeeding is not recommended during HEXALEN therapy. M/P ratio is not available. |
| Teratogenic Risk | HEXALEN (altretamine) is embryotoxic and teratogenic in animal studies. In humans, it is classified as FDA Pregnancy Category D. There is positive evidence of human fetal risk, but potential benefits may warrant use in pregnant women despite risks. First trimester exposure carries highest risk of major congenital malformations (neural tube defects, cardiovascular anomalies). Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and preterm birth. Use only if clearly needed and no safer alternative. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to altretamine, severe bone marrow suppression, and pre-existing severe neurological impairment.
| Precautions | Bone marrow suppression (leukopenia, thrombocytopenia), neurotoxicity (ataxia, paresthesias), gastrointestinal toxicity (nausea, vomiting), and carcinogenicity. |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential and platelets weekly due to myelosuppression. Assess liver function (AST, ALT, bilirubin) and renal function (serum creatinine, BUN) at baseline and periodically. Monitor for neurotoxicity (peripheral neuropathy) and gastrointestinal toxicity (nausea, vomiting). In pregnancy, perform serial ultrasound for fetal growth and amniotic fluid volume assessment. Consider fetal echocardiography if first trimester exposure. |
| Fertility Effects | HEXALEN may impair fertility in both males and females. In males, it can cause oligospermia, azoospermia, and testicular atrophy. In females, amenorrhea, premature ovarian failure, and reduced fertility have been reported. Effects may be irreversible at higher cumulative doses. |