ALTRETAMINE, HEXAMETHYLMELAMINE

ALTRETAMINE, HEXAMETHYLMELAMINe
(al-tre'ta-meen)
Hexalen
Classifications: antineoplastic; alkylating agent;
Therapeutic:antineoplastic

Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

50 mg capsules

Action

Altretamine is a synthetic cytotoxic antineoplastic drug. It is metabolized to metabolites with cytotoxic properties.

Therapeutic Effect

Altretamine has demonstrated neoplastic activity in patients resistant to alkylating agents.

Uses

Ovarian cancer.

Unlabeled Uses

Breast, cervical, colon, endometrial, head, and neck cancer; small-cell lung cancers and lymphomas.

Contraindications

Hypersensitivity to altretamine, severe bone marrow depression, neurologic toxicity, neurologic disease; intramuscular injections, pregnancy (category D), lactation.

Cautious Use

History of viral infections, i.e., herpes simplex; radiation therapy. Safety and efficacy in children are not established.

Route & Dosage

Ovarian Cancer
Adult: PO 260 mg/m2/d for 14 or 21 consecutive d in a 28-d cycle

Administration

Oral
  • Give only under supervision of a qualified physician experienced in the use of antineoplastics.
  • Give in 4 divided doses after meals and at bedtime.
  • Discontinue altretamine for 14 d or longer and restart at 200 mg/m2/d if any of the following occur: severe GI intolerance; WBC count <2000/mm3, granulocyte count <1000/mm3; or progressive neurotoxicity.
  • Store at room temperature, 15°–30° C (59°–86° F).

Adverse Effects (≥1%)

CNS: Paresthesias, hyporeflexia, muscle weakness, peripheral numbness, ataxia, Parkinson-like tremors. GI: Nausea, vomiting. Hematologic: Leukopenia, thrombocytopenia. Urogenital: Slight increase in serum creatinine. Skin: Alopecia and eczema.

Interactions

Drug: Concomitant administration of altretamine and tricyclic antidepressants (imipramine, amitriptyline), monoamine oxidase inhibitors, or selegiline have been reported to result in incapacitating dizziness and syncopal episodes during the first week of altretamine treatment. Patients became asymptomatic 24–96 h after discontinuing antidepressants.

Pharmacokinetics

Absorption: Rapidly from GI tract. Approximately 25% reaches systemic circulation due to extensive hepatic first-pass metabolism. Metabolism: Rapidly demethylated in the liver. Elimination: 62% of the dose is excreted in the urine in 24 h. A small amount is excreted through the lungs. Half-Life: 13 h.

Nursing Implications

Assessment & Drug Effects

  • Lab tests: Monitor blood counts at least monthly and prior to each course of therapy.
  • Perform a neurologic examination regularly; question patient about the presence of: paresthesias, hypoesthesias, muscle weakness, peripheral numbness, ataxia, decreased sensations, and alterations in mood or consciousness.
  • Withhold medication if neurologic symptoms fail to resolve with dose reduction. Notify physician.
  • Monitor for nausea and vomiting, which are related to the cumulative dose of altretamine. After several weeks some patients develop tolerance to the GI effects. Antiemetics may be required to control GI distress.

Patient & Family Education

  • Taking altretamine after meals or with food or milk may decrease nausea.
  • Report symptoms indicative of neurotoxicity to physician (paresthesias, hypoesthesias, muscle weakness, peripheral numbness, ataxia, decreased sensations, and alterations in mood or consciousness).
  • Note: GI, hematologic, and neurologic adverse effects may be severe.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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