Altretamine

U.S. BRAND NAMES — Hexalen®
PHARMACOLOGIC CATEGORY Antineoplastic Agent, Miscellaneous
DOSING: ADULTS — Refer to individual protocols.
Ovarian cancer: Oral: 260 mg/m2/day in 4 divided doses for 14 or 21 days of a 28-day cycle Alternatively (unlabeled use): 4-12 mg/kg/day in 3-4 divided doses for 21-90 days Alternatively (unlabeled use): 240-320 mg/m2/day in 3-4 divided doses for 21 days, repeated every 6 weeks Alternatively (unlabeled use): 150 mg/m2/day in 3-4 divided doses for 14 days of a 28-day cycle
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gelcap: Hexalen®: 50 mg
DOSAGE FORMS: CONCISE Gelcap: Hexalen®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer total daily dose as 3-4 divided doses after meals and at bedtime.
USE — Palliative treatment of persistent or recurrent ovarian cancer
ADVERSE REACTIONS SIGNIFICANT >10%: Central nervous system: Peripheral sensory neuropathy (31%; moderate-to-severe 9%), neurotoxicity (21%; may be progressive and dose-limiting) Gastrointestinal: Nausea/vomiting (33% to 70%; severe 1%), diarrhea (48%) Hematologic: Anemia (33%), leukopenia (5% to 15%; grade 4: 1%), neutropenia
1% to 10%: Central nervous system: Fatigue (1%), seizure (1%) Gastrointestinal: Stomach cramps, anorexia (1%) Hematologic: Thrombocytopenia (9%) Hepatic: Alkaline phosphatase increased (9%)
<1% (Limited to important or life-threatening): Alopecia, ataxia, depression, dizziness, hepatotoxicity, mood disorders, pruritus, rash, tremor, vertigo
CONTRAINDICATIONS — Hypersensitivity to altretamine or any component of the formulation; pre-existing severe bone marrow suppression or severe neurologic toxicity; pregnancy
WARNINGS / PRECAUTIONS Box warnings: Bone marrow suppression: See "Concerns related to adverse effects" below. Experienced physician: See "Other warnings/precautions" below. Neurotoxicity: See "Concerns related to adverse effects" below.
Special handling: Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects: Bone marrow suppression: [U.S. Boxed Warning]: Peripheral blood counts should be done routinely before and after drug therapy; bone marrow suppression is common. Use with caution in patients previously treated with other myelosuppressive drugs. Neurotoxicity: [U.S. Boxed Warning]: Neurologic examinations should be done routinely before and after drug therapy; neurotoxicity is common. USe with caution in patients with pre-existing neurotoxicity.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment. Renal impairment: Use with caution in patients with renal impairment.
Special populations: Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
DRUG INTERACTIONS MAO inhibitors: Altretamine may enhance the orthostatic effect of MAO inhibitors.
Pyridoxine: May diminish the therapeutic effect of altretamine; concurrent use not recommended.
Tricyclic antidepressants: Altretamine may enhance the orthostatic effect of tricyclic antidepressants.
PREGNANCY RISK FACTOR — D (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were noted in animal studies. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should avoid becoming pregnant while on therapy.
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential toxicity in the nursing infant, breast-feeding is not recommended.
DIETARY CONSIDERATIONS — Should be taken after meals at bedtime.
MONITORING PARAMETERS — CBC with differential, liver function tests; neurologic examination
TOXICOLOGY / OVERDOSE COMPREHENSIVE — Symptoms include nausea, vomiting, peripheral neuropathy, and severe bone marrow suppression. Treatment is symptom-directed and supportive.
CANADIAN BRAND NAMES — Hexalen®
INTERNATIONAL BRAND NAMES — Hexalen (AU, BG, CA, CN, GB, IE, IL, JP, NZ, SE, TH); Hexastat (DK, FR, NO, PT); Hexinawas (ES)
MECHANISM OF ACTION — Although altretamine's clinical antitumor spectrum resembles that of alkylating agents, the drug has demonstrated activity in alkylator-resistant patients. The drug selectively inhibits the incorporation of radioactive thymidine and uridine into DNA and RNA, inhibiting DNA and RNA synthesis; reactive intermediates covalently bind to microsomal proteins and DNA; can spontaneously degrade to demethylated melamines and formaldehyde which are also cytotoxic.
PHARMACODYNAMICS / KINETICS Absorption: Well absorbed (75% to 89%)
Distribution: Highly concentrated hepatically and renally; low in other organs
Protein binding: 50% to 94%
Metabolism: Hepatic; rapid and extensive demethylation to active metabolites (pentamethylmelamine and tetramethylmelamine)
Half-life elimination: 13 hours
Time to peak, plasma: 0.5-3 hours
Excretion: Urine (90%, <1% as unchanged drug)
PATIENT INFORMATION — Report any numbness or tingling in extremities. Nausea and vomiting may occur