Active ingredient: Altretamine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antineoplastic Agents

Dosage Forms

• Capsule

Brands / Synonyms

Altretaminum [Inn-Latin]; Hemel; Hexalen; HEXAMETHYLMELAMINE; Hexastat; HMM; HTM; HXM; Melamine, Hexamethyl-

Indications

For use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agent-based combination.

Pharmacology

Altretamine is a novel antineoplastic agent. The precise mechanism by which altretamine exerts its cytotoxic effect is unknown, although a number of theoretical possibilities have been studied. Structurally, altretamine resembles the alkylating agent triethylenemelamine, yet in vitro tests for alkylating activity of altretamine and its metabolitics have been negative. Altretamine has been demonstrated to be efficacious for certain ovarian tumors resistant to classical alkylating agents. Metabolism of altretamine is a requirement of cytotoxicity. 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.

Mechanism of Action

The precise mechanism by which altretamine exerts its cytotoxic effect is unknown.

Absorption

Not Available

Toxicity

Not Available

Biotrnasformation / Drug Metabolism

Not Available

Contraindications

HEXALEN is contraindicated in patients who have shown hypersensitivity to it. HEXALEN should not be employed in patients with preexisting severe bone marrow depression or severe neurologic toxicity. HEXALEN has been administered safely, however, to patients heavily pretreated with cisplatin and/or alkylating agents, including patients with preexisting cisplatin neuropathies. Careful monitoring of neurologic function in these patients is essential.

Drug Interactions

Concurrent administration of HEXALEN and antidepressants of the MAO inhibitor class may cause severe orthostatic hypotension.Cimetidine, an inhibitor of microsomal drug metabolism, increased altretamine's half-life and toxicity in a rat model.

Data from a randomized trial of HEXALEN and cisplatin plus or minus pyridoxine in ovarian cancer indicated that pyridoxine significantly reduced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with HEXALEN and/or cisplatin.¹