Dexrazoxane

Mechanism :

The drug is an iron chelator and acts by binding to free iron or removes iron from doxorubicin-iron complex hence preventing oxygen free radical formation.

Indication :

• Prophylaxis against anthracyline-induced cardiomyopathy in children and adolescents.
• To decrease the incidence and severity of cardiomyopathy associated with doxorubicin use in females with metastatic breast carcinoma who have received a total doxorubicin dose of 300 mg/m2 and will continue to receive doxorubicin to maintain tumor control.
• For patients receiving epirubicin chemotherapy.to prevent cardiac toxicity.
• Management of extravasation due to intravenous anthracycline chemotherapy.

Contraindications :

Avoid use in case of known hypersensitivity to the drug during previous use or to a drug in the same class or to it’s components.

Leukopenia, neutropenia, thrombocytopenia

Hematologic toxicity: Low WBC count, low neutrophil count and low platelet count have been reported with dexrazoxane therapy; myelosuppression may be present when used in combination with cytotoxic chemotherapy. Prior to each course of chemotherapy, blood counts must be measured when dexrazoxane is used as a chemoprotective agent. Do not administer dexrazoxane until adequate hematologic parameters are met.

Renal impairment:

Exhibit caution when using dexrazoxane in patients with renal dysfunction. Dose should be initially adjusted in patients with creatinine clearance < 40 mL/min. Also monitor these patients for signs of hematological toxicity.

Hepatic dysfunction/Disease :

It is not recommended for use in the management of extravasation in patients with liver dysfunction as liver toxicity may occur, especially with doses higher than 1,000 mg/m2. So, AST, ALT, albumin must be monitored prior to administering each dose in patients who are known cases of hepatic disease. When using dexrazoxane as a chemoprotective drug, decrease its dose if the doxorubicin dose is decreased due to liver dysfunction, like in elevated bilirubin level and maintain the 10:1 dose ratio of dexrazoxane to doxorubicin.

Dosing :

Adverse Effect :

The side effects of dexrazoxane is generally due to use of concurrent antineoplastic and chemo-therapeutics. Some of its adverse events are pain and phlebitis at the injection site, bone marrow suppression.

Interaction :

Abacavir, abciximab, aceclofenac, acetaminophen, adalimumab, amikacin, alprazolam, amrinone, anthrax vaccine, BCG vaccine, benzatropine, bisoprolol are some drugs that can interact with this drug. 

Lactation :

Lactating women must be advised not to breastfeed during and until 2 weeks after the final dose of treatment owing to its serious adverse effects such as myelo-suppression.

Hepatic Dose :

Extravasation: not recommended

Cardiomyopathy: Decrease dose proportionately (10:1) as a doxorubicin dose decrease is necessary in the presence of hyperbilirubinemia

Pregnanacy :

Dexrazoxane, when administered intravenously, based on animal studies, was found to be a teratogen and can interfere during organogenesis in-utero. Various defects were noticed such as imperforate anus, microphthalmia, anophthalmia, thoracic malformations; hemorrhagic areas in the eye, heart and subcutaneous region, gallbladder and intermediate lobe of the lung agenesis.These findings were noticed at a dose nearly 0.1-0.2 times the normal human dose (1000 mg/m²), so caution must be advised. Prior to initiating chemotherapy, a pregnancy test must be performed. Risk of the potential hazard of the drug should be noted and well explained so can be avoided.

Advice about contraception:

• In females: Owing to its possible adverse effects, especially genotoxicity, women of reproductive age must be advised to use contraception during and until 6 months of the final dose of treatment.

• In males: Owing to its possible adverse effects, especially genotoxicity, male partners of women of reproductive age must be advised to use contraception during and until 3 months of the final dose of treatment.

Effect on fertility: Therapy may impair fertility in males which may not be reversible.