Altretamine
Pronunciation
(al TRET a meen)
U.S. Brand Names
Hexalen®
Synonyms
Hexamethylmelamine; HEXM; HMM; HXM; NSC-13875
Generic Available
No
Canadian Brand Names
Hexalen®
Use
Palliative treatment of persistent or recurrent ovarian cancer
Pregnancy Risk Factor
D
Lactation
Excretion in breast milk unknown
Contraindications
Hypersensitivity to altretamine or any component of the formulation; pre-existing severe bone marrow suppression or severe neurologic toxicity; pregnancy
Warnings/Precautions
The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Peripheral blood counts and neurologic examinations should be done routinely before and after drug therapy. Use with caution in patients previously treated with other myelosuppressive drugs or with pre-existing neurotoxicity; use with caution in patients with renal or hepatic dysfunction; altretamine may be slightly mutagenic.
Adverse Reactions
>10%:
Central nervous system: Peripheral sensory neuropathy, neurotoxicity (21%; may be progressive and dose-limiting)
Gastrointestinal: Nausea/vomiting (50% to 70%), anorexia (48%), diarrhea (48%)
Hematologic: Anemia, thrombocytopenia (31%), leukopenia (62%), neutropenia
1% to 10%:
Central nervous system: Seizures
Gastrointestinal: Stomach cramps
Hepatic: Alkaline phosphatase increased
<1%: Alopecia, depression, dizziness, hepatotoxicity, rash, tremor
Overdosage/Toxicology
Symptoms of overdose include nausea, vomiting, peripheral neuropathy, severe bone marrow suppression. Treatment is supportive.
Drug Interactions
Decreased effect: Phenobarbital may increase metabolism of altretamine
Increased toxicity: May cause severe orthostatic hypotension when administered with MAO inhibitors; cimetidine may decrease metabolism of altretamine
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (due to GI irritation).
Mechanism of Action
Although altretamine 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
Metabolism: Hepatic; rapid and extensive demethylation; active metabolites
Half-life elimination: 13 hours
Time to peak, plasma: 0.5-3 hours
Excretion: Urine (<1% as unchanged drug)
Dosage
Refer to individual protocols. Oral:
Adults: 4-12 mg/kg/day in 3-4 divided doses for 21-90 days
Alternatively: 240-320 mg/m
2
/day in 3-4 divided doses for 21 days, repeated every 6 weeks
Alternatively: 260 mg/m
2
/day for 14-21 days of a 28-day cycle in 4 divided doses
Alternatively: 150 mg/m
2
/day in 3-4 divided doses for 14 days of a 28-day cycle
Administration
Administer total daily dose as 3-4 divided doses after meals and at bedtime.
Dietary Considerations
Should be taken after meals at bedtime.
Patient Education
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take anything new (including aspirin or any aspirin-containing products) during treatment unless approved by prescriber. Take exactly as directed, preferably after meals. Avoid alcohol. May cause nausea or vomiting (small, frequent meals, good mouth care, chewing gum, or sucking lozenges may help). You will be more susceptible to infection (avoid crowds and exposure to infection). Report any numbness, tingling, or pain in extremities; unrelieved nausea or vomiting; tremors; yellowing of skin or eyes; fever; chills; easy bruising or unusual bleeding; extreme weakness; or increased fatigue.
Pregnancy/breast-feeding precautions:
Do not get pregnant while taking this medication. Consult prescriber for appropriate barrier contraceptive measures. Consult prescriber if breast-feeding.
Nursing Implications
Advise patient to report any numbness or tingling in extremities to physician; nausea and vomiting may occur
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Neurotoxicity is common; rarely may produce depression
Mental Health: Effects on Psychiatric Treatment
Bone marrow suppression may be seen; use caution with carbamazepine and clozapine; may produce seizures caution with bupropion and clozapine; may cause severe orthostatic hypotension when administered with MAO inhibitors
Oncology: Emetic Potential
Moderate (30% to 60%)
Oncology: Vesicant
No
Dosage Forms
Gelcap: 50 mg [contains lactose]
References
Ames MM, "Hexamethylmelamine: Pharmacology and Mechanism of Action,"
Cancer Treat Rev
, 1991, 18(Suppl A):3-14.
Bruckner HW and Schleifer SJ, "Orthostatic Hypotension as a Complication of Hexamethylmelamine Antidepressant Interaction,"
Cancer Treat Rep
, 1983, 67:516.
Damia G and D'Incalci M, "Clinical Pharmacokinetics of Altretamine,"
Clin Pharmacokinet
, 1995, 28(6):439-48.
Hahn DA and Black C, "Hexamethylamine: A Review,"
Drug Intell Clin Pharm
, 1980, 14:541-7.
Hansen LA and Hughes TE, "Altretamine,"
DICP
, 1991, 25(2):146-52.
Lee CR and Faulds D, "Altretamine. A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Cancer Chemotherapy,"
Drugs
, 1995, 49(6):932-53.
Manetta A, Mac Neill C, Lyter JA, et al, "Hexamethylmelamine as a Single Second-Line Agent in Ovarian Cancer,"
Gynecol Oncol
, 1990, 36(1):93-6.
Sutton GP, "Secondary Therapy for Epithelial Ovarian Cancer - 1994,"
Semin Oncol
, 1994, 21(4 Suppl 7):32-6.
Thigpen JT, Vance RB, and Khansur T, "Second-Line Chemotherapy for Recurrent Carcinoma of the Ovary,"
Cancer
, 1993, 71(4 Suppl):1559-64.
International Brand Names
Hexalen® (AU, CA, GB, NO, NZ, SE); Hexastat® (AR, HK)
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