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Indications and Dosage
Oral
Palliative treatment of ovarian carcinoma Adult: 260 mg/m2 daily in 4 divided doses, for 14 or 21 consecutive days out of a 28-day cycle, up to 12 cycles. If WBC count is <2,000/mm3, granulocyte count is <1,000/mm3, platelet count is <75,000/mm3, or if neurotoxicity or intolerable GI symptoms occur, therapy should be temporarily discontinued for ≥14 days prior to restarting at 200 mg/m2 daily.
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Administration
Should be taken with food.
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Contraindications
Pre-existing severe bone marrow depression, severe neurologic toxicity. Lactation. Concomitant use w/ antidepressants of the MAOI class.
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Special Precautions
Patient previously treated w/ other myelosuppressive agents. Pregnancy.
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Adverse Reactions
Bone marrow depression, manifested by leucopenia, thrombocytopenia, anaemia; nausea, vomiting, peripheral (e.g. neuropathy) and central (e.g. ataxia, depression, confusion, drowsiness, hallucination, mood disorder, dizziness, vertigo) neurotoxicity. Rarely, rashes, pruritus, alopecia, hepatotoxicity.
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Patient Counseling Information
This drug is an irritant, avoid contact w/ skin or mucous membranes.
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Monitoring Parameters
Perform peripheral blood counts at least mthly, prior to initiation of each course of therapy and as clinically indicated. Monitor neurologic function regularly. Monitor for GI upset and anaemia.
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Drug Interactions
Reduced activity w/ pyridoxine. Increased half-life and toxicity w/ inhibitors of microsomal metabolism (e.g. cimetidine).
Potentially Fatal: May cause severe orthostatic hypotension w/ antidepressants of the MAOI class (e.g. phenelzine). |
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Action
Description:
Mechanism of Action: Altretamine, a synthetic triazine derivative, is a cytotoxic antineoplastic agent structurally similar to triethylenemelamine, although its mode of action may be different. While its cytotoxic effect is not fully characterised, it is theorised that its activated oxidative N-demethylation metabolites bind to and damage DNA. Pharmacokinetics: Absorption: Well absorbed from the GI tract. Time to peak plasma concentration: 0.5-3 hr. Distribution: Distributed into tissues high in lipid content and tumour tissues. Metabolism: Rapidly and extensively metabolised in the liver via oxidative N-demethylation into pentamethylmelamine and tetramethylmelamine. Excretion: Via urine (90%, mainly as metabolites and <1% as unchanged drug). Elimination half-life: 4-10 hr. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Database. Altretamine, CID=2123, https://pubchem.ncbi.nlm.nih.gov/compound/Altretamine (accessed on Jan. 20, 2020) |
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Storage
Store at or below 25°C.
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MIMS Class
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ATC Classification
L01XX03 - altretamine ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
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References
Anon. Altretamine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 22/07/2016. Buckingham R (ed). Altretamine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 22/07/2016. Hexalen Capsule (Eisai Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/07/2016. Hexalen Capsule (MGI Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/07/2016. McEvoy GK, Snow EK, Miller J et al (eds). Altretamine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 22/07/2016.
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