Cardioxane (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Clinigen Healthcare Ltd. (United Kingdom)

Manufactured By

Cenexi-Laboratoires Thissen, S.A. (Belgium)

ATC Code

V03AF02 (Dexrazoxane)

Active Substance

Dexrazoxane (Rec.INN registered by WHO)

Dosage Form

Cardioxane

Lyophilizate for preparation of solution for infusion 500 mg: fl. 1 pc.

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for infusion white or almost white with a yellowish tint.

Excipients : 0.1N hydrochloric acid.

500 mg – dark glass vials (1) – cardboard packs.

Clinical-Pharmacological Group

Chelating agent. Cardioprotectant in anthracycline therapy

Pharmacotherapeutic Group

Chelating agent

Pharmacological Action

Complexing compound. It is an analog of ethylenediaminetetraacetic acid. It has a cardioprotective effect during chemotherapy with anthracycline antibiotics.

The mechanism of cardioprotective action has not been definitively established; it is assumed that Dexrazoxane undergoes hydrolysis in the myocardium to form a compound whose molecules bind metal ions (iron, copper) and, according to the generally accepted hypothesis, prevent the formation of the anthracycline-iron complex, thereby preventing the formation of cardiotoxic oxygen free radicals.

Dexrazoxane does not affect the antitumor activity of anthracycline antibiotics. It is believed that the selectivity of dexrazoxane’s action is associated with differences in its metabolism in tumor cells and myocardial cells.

Pharmacokinetics

After IV administration, plasma protein binding is 2%. Dexrazoxane passes through the histohematic barrier and accumulates in the liver and kidneys.

It is eliminated by the kidneys, partially as metabolites and partially unchanged (42%). T_1/2 is 2.5 hours.

Indications

Prevention of cardiomyopathy, cumulative chronic cardiotoxicity of anthracyclines (during cytotoxic therapy with anthracyclines in patients with a favorable long-term prognosis; who have previously received or are simultaneously receiving radiation therapy; with tumor recurrence after adjuvant chemotherapy with anthracyclines; with arterial hypertension; diabetes mellitus; in patients over 65 years of age and children with cancer); Kaposi’s sarcoma against the background of AIDS (mono- or combination therapy).

ICD codes

Dosage Regimen

Dexrazoxane should be used under the supervision of qualified specialists experienced in antitumor therapy.

Dexrazoxane is administered intravenously before each anthracycline administration. For adults, the recommended dose of dexrazoxane is 20 times the dose of the anthracycline. The maximum cumulative dose of dexrazoxane is 1000 mg/m².

For children, the dose of dexrazoxane should exceed the dose of the anthracycline by 10-15 times.

Adverse Reactions

From the hematopoietic system: mild (progressing to moderate) leukopenia, mild (progressing to moderate) thrombocytopenia, anemia, decreased blood hemoglobin, vitamin B₁₂, serum iron.

From the blood coagulation system: impaired blood coagulation.

From the digestive system: nausea, vomiting (immediately after administration), transient increase in liver enzyme levels, transient increase in triglyceride and amylase content.

From the urinary system: increased iron and zinc content in urine.

Other: general malaise, slight increase in body temperature, allergic reactions, alopecia, decreased serum calcium levels. Less frequently – phlebitis at the injection site, black discoloration of nails.

Contraindications

Hypersensitivity to dexrazoxane; pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in cases of impaired liver function.

Use in Renal Impairment

In patients with signs of renal failure, the clearance of dexrazoxane may decrease and the hematotoxic effect may increase.

Pediatric Use

Can be used in children according to indications in recommended regimens and doses.

Geriatric Use

Can be used in elderly patients according to indications in recommended regimens and doses.

Special Precautions

Use with caution in cases of impaired liver function.

During the first 2 courses of treatment, regular monitoring of the peripheral blood picture is necessary, as Dexrazoxane may enhance the toxic effects of chemo- and radiation therapy.

In patients with signs of renal failure, the clearance of dexrazoxane may decrease and the hematotoxic effect may increase.

During treatment, patients should use reliable methods of contraception.

During treatment, monitoring of cardiac activity is necessary.

Drug Interactions

Dexrazoxane enhances the myelotoxic effect of myelodepressants (antineoplastic drugs and radiation therapy).

Dexrazoxane must not be mixed with other medicinal products in the same vial.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°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.