Hexalen^® (Capsules) Instructions for Use

Marketing Authorization Holder

MGI Pharma, Inc. (USA)

Manufactured By

AAI International (USA)

ATC Code

L01XX03 (Altretamine)

Active Substance

Altretamine (Rec.INN registered by WHO)

Dosage Form

Hexalen®

Capsules 50 mg: 20, 40, 60, 80, or 100 pcs.

Dosage Form, Packaging, and Composition

Capsules are hard gelatin, size No. 3, consisting of two transparent parts, with the inscription “USB 001” in blue ink on one part; the capsule contents are a white or almost white powder.

Excipients: gelatin, calcium stearate, anhydrous lactose.

10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.
10 pcs. – blister packs (8) – cardboard packs.
40 pcs. – polyethylene bottles (1) – cardboard packs.
100 pcs. – polyethylene bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent

Pharmacological Action

Antineoplastic agent, a derivative of s-triazine. It has a cytotoxic effect.

The antineoplastic action of altretamine is determined by the activity of its metabolites, which form covalent bonds with DNA (including the DNA of tumor cells).

Pharmacokinetics

When taken orally, Altretamine is well absorbed from the gastrointestinal tract. C_max in blood plasma is reached within 0.5-3 hours.

Altretamine undergoes rapid and intensive demethylation in the liver to form two main metabolites: pentamethylmelamine and tetramethylmelamine.

Altretamine and its metabolites bind to blood plasma proteins. The free fractions of altretamine, pentamethylmelamine, and tetramethylmelamine are 6%, 25%, and 50%, respectively.

The T_1/2 in the β-phase ranges from 4.7 to 10.2 hours.

Altretamine is excreted mainly by the kidneys within 24 hours.

Indications

As a second-line therapy for progressive ovarian cancer, including cases resistant to platinum-based drugs and/or combination chemotherapy using antineoplastic alkylating agents.

ICD codes

Dosage Regimen

Administer Hexalen orally as a single agent for second-line therapy of ovarian cancer.

Take the total daily dose as four divided doses after meals and at bedtime.

The recommended daily dose is 260 mg/m² of body surface area for 14 or 21 consecutive days in a 28-day cycle.

Calculate the exact number of 50 mg capsules based on the individual’s body surface area.

Continue treatment for a minimum of 3 months to adequately assess therapeutic response.

Adjust the dose based on hematologic tolerance and the severity of neurotoxicity.

For moderate hematologic toxicity, reduce the dose to 200 mg/m²/day.

For severe hematologic toxicity or progressive neurotoxicity, discontinue treatment immediately.

Do not administer to patients with a baseline platelet count below 50,000/mm³ or a neutrophil count below 1,000/mm³.

Perform complete blood counts and neurological examinations prior to each treatment cycle and regularly throughout therapy.

Adverse Reactions

From the digestive system: nausea and vomiting of mild to moderate severity; rarely – hepatotoxicity.

From the hematopoietic system: moderately pronounced leukopenia, thrombocytopenia, less often – anemia.

From the nervous system: peripheral neuropathy, mood disorders, consciousness disorders, ataxia, dizziness.

From the urinary system: rarely – nephrotoxicity.

Other: rarely – alopecia.

Contraindications

Severe impairment of the central or peripheral nervous system function, pronounced suppression of hematopoiesis, hypersensitivity to altretamine.

Use in Pregnancy and Lactation

Experimental studies have established that Altretamine has embryotoxic and teratogenic properties.

Although there are no data on the excretion of altretamine in breast milk, if it is necessary to use during lactation, it is recommended to discontinue breastfeeding.

Special Precautions

Treatment should be carried out only by an oncologist.

During treatment, regular monitoring of neurological status and blood count is necessary.

Drug Interactions

With simultaneous use with cimetidine and other inhibitors of liver microsomal enzymes, an increase in the T_1/2 of altretamine and an increase in its toxicity are possible.

With simultaneous use with antidepressants from the group of MAO inhibitors, the development of severe orthostatic hypotension is possible.

Due to the immunosuppressive action of altretamine, its simultaneous use with vaccines containing killed viruses may reduce the effectiveness of vaccination; when using vaccines containing live viruses, it is possible to potentiate virus replication and increase the side effects associated with the vaccine.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.