Trade Names:Hexalen- Gelatin capsules 50 mg
The precise mechanism by which altretamine exerts its cytotoxic effect is unknown. Synthetic monohydroxymethylmelamines and products of altretamine metabolism in vitro and in vivo can form covalent adducts with tissue macromolecules including DNA, but the relevance of these reactions to antitumor activity is unknown.
Well absorbed; T max of 0.5 to 3 h; C max is 0.2 to 20.8 mg/L.
Does bind to plasma proteins.
Metabolism occurs in the liver with rapid and extensive demethylation to 2 metabolites.
T ½ of the beta-phase is 4.7 to 10.2 h. 90% is excreted in the urine at 72 h. Less than 1% of unmetabolized altretamine is excreted at 24 h.
Palliative therapy of refractory ovarian cancer.
Hypersensitivity to altretamine; pre-existing severe bone marrow depression or severe neurologic toxicity. Careful monitoring of neurologic function in these patients is essential.
PO 260 mg/m 2 /day for 14 or 21 days in a 28-day cycle, given in 4 divided doses (round dose to the nearest 50 mg) after meals and at bedtime (usual dose, 400 mg/day). Discontinue therapy for at least 14 days and resume at 200 mg/m 2 /day in any of the following situations: treatment-resistant GI adverse effects; WBC less than 2,000/mm 3 ; granulocyte count less than 1,000/mm 3 ; platelet count less than 75,000/mm 3 ; progressive neurotoxicity. Discontinue permanently if neurologic symptoms persist after dose reduction.
Store capsules at controlled room temperature in a tightly closed container.
May increase altretamine's half-life and toxicity.CYP-450 enzymes
Altretamine elimination may be altered by agents that inhibit or induce CYP-450 enzymes.Tricyclic antidepressants or MAOIs
Coadministration of altretamine with these drugs may cause orthostatic hypotension.
None well documented.
Reversible peripheral neuropathy; ataxia; depression; vertigo; agitation; confusion; hallucinations.
Moderate potential for nausea and vomiting.
Bone marrow suppression; nadir at 3 to 4 wk with intermittent therapy (for 14 to 21 days in a cycle) and at 6 to 8 wk with continuous administration.
Altretamine causes mild to moderate neurotoxicity. Peripheral neuropathy and CNS symptoms (eg, mood disorders, disorders of consciousness, ataxia, dizziness, vertigo) have occurred. These are more likely to occur in patients receiving continuous high-dose daily altretamine. Neurologic toxicity appears to be reversible when therapy is discontinued.
Perform neurologic exams regularly during therapy.Hematologic
Altretamine causes mild to moderate dose-related myelosuppression.
Perform peripheral blood counts at baseline; prior to each course, at least monthly and when clinically indicated.
Ensure that CBC and differential are determined at baseline, prior to each course, and as indicated during therapy.Neurologic examination
Ensure that a neurologic examination is performed at baseline, prior to each course, and as indicated during therapy.
Category D .
Safety and efficacy not established.
Drugs with similar mechanisms of actions are carcinogenic.
With continuous high-dose daily altretamine, nausea and vomiting of gradual onset occur frequently.
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