Treosulfan (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Emcure Pharmaceuticals, Ltd. (India)

Manufactured By

Naprod Life Sciences, Pvt. Ltd. (India)

ATC Code

L01AB02 (Treosulfan)

Active Substance

Treosulfan (Rec.INN registered by WHO)

Dosage Form

Treosulfan

Lyophilizate for preparation of solution for infusion 5 g: vial 1 pc.

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for infusion as a white mass or powder.

* Each ml of the reconstituted solution contains 50 mg of treosulfan.

Colorless glass vials (type I) with a capacity of 100 ml (1) – cardboard packs.

Clinical-Pharmacological Group

Antitumor drug. Alkylating compound

Pharmacotherapeutic Group

Antineoplastic agents; alkylating agents; alkyl sulfonates

Pharmacological Action

Antitumor agent, a precursor of the bifunctional alkylating cytotoxic substance diepoxybutane.

Under physiological conditions, the pharmacologically inactive Treosulfan with a T_1/2 of 2.2 hours is converted into 2 active metabolites – mono- and diepoxybutane, which alkylate the nucleophilic centers of DNA.

The metabolites specifically suppress hematopoietic stem cells, T- and B-lymphocytes, and exert a cytotoxic effect on a number of solid and hematopoietic tumors.

Pharmacokinetics

After intravenous administration, it is rapidly distributed in the body.

It is eliminated according to first-order kinetics.

T_1/2 is 88 minutes.

It is excreted by the kidneys unchanged (22% within 24 hours, 90% of this amount – within the first 6 hours after administration).

Indications

Epithelial tumors of the ovary stages II-IV (as monotherapy or in combination with cisplatin or other antitumor agents).

ICD codes

Dosage Regimen

Administer intravenously as an infusion. Determine the dose individually based on the treatment regimen and patient risk profile.

For monotherapy in ovarian carcinoma, administer 7 g/m² body surface area daily for 3 consecutive days. Repeat this cycle at 4-week intervals.

For combination therapy with cisplatin, administer treosulfan 5 g/m² daily for 3 consecutive days. Administer cisplatin at a dose of 50 mg/m² on day 1 of each cycle.

Calculate the exact dose based on body surface area immediately prior to each administration cycle. Adjust the dose for patients with impaired renal function.

Reconstitute the 5 g lyophilisate with 100 mL of Water for Injections. The resulting solution contains 50 mg of treosulfan per mL. Use the reconstituted solution immediately; do not store.

Infuse the total daily dose over a period of 60-120 minutes. Ensure adequate hydration before and after administration to prevent hemorrhagic cystitis.

Monitor peripheral blood counts weekly. Increase monitoring frequency from the third course onward due to the cumulative myelosuppressive effect.

Adverse Reactions

From the hematopoietic system: leukopenia, neutropenia, thrombocytopenia, anemia, myelosuppression.

Dermatological reactions: alopecia, skin pigmentation (bronze-colored spots), urticaria, erythema, scleroderma, psoriasis.

From the respiratory system: allergic alveolitis, pneumonia, pulmonary fibrosis.

From the digestive system: nausea, vomiting.

Local reactions: pain, inflammation of the subcutaneous tissue.

Other: flu-like syndrome, paresthesia, hemorrhagic cystitis, adrenal cortex hypofunction, hypoglycemia, cardiomyopathy (single case).

Contraindications

Bone marrow hematopoiesis suppression, pregnancy, lactation (breastfeeding), hypersensitivity to treosulfan.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation. Patients of childbearing potential should use reliable methods of contraception during and for 3 months after treatment.

Special Precautions

Treatment should be carried out under the supervision of a physician experienced in the use of cytotoxic agents.

Peripheral blood counts should be monitored once a week, and from the 3rd course of therapy – more frequently (taking into account the cumulative nature of myelosuppression), which is especially important when combined with other types of myelosuppressive therapy (radiation therapy). Bone marrow function suppression is usually reversible.

Within 24 hours after treosulfan administration, ample fluid intake is recommended to prevent hemorrhagic cystitis.

During long-term therapy with oral forms of treosulfan, 1.4% of patients developed acute non-lymphoblastic leukemia.

Effect on ability to drive vehicles and operate machinery

During treatment, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

When co-administered with ibuprofen and/or chloroquine, a decrease in the antitumor effect is possible.

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.