Dexrazoxane

(BAN, USAN, rINN)
Dexrazoxane Chemical formula
Synonyms: ADR-529; Dexrazoxano; Dexrazoxanum; ICRF-187; NSC169780. (+)-(S)-4,4′-Propylenebis(piperazine-2,6-dione).
Cyrillic synonym: Дексразоксан.

💊 Chemical information

Chemical formula: C11H16N4O4 = 268.3.
CAS — 24584-09-6.
ATC — V03AF02.
ATC Vet — QV03AF02.

💊 Adverse Effects and Precautions

Dexrazoxane may add to the bone-marrow depression caused by antineoplastics and frequent complete blood counts are recommended during therapy. Although dexrazoxane protects against the cardiotoxic effects of anthracyclines, cardiac function should continue to be monitored when dexrazoxane is used. Pain on injection has been reported. When used to reduce the cardiotoxicity of doxorubicin, licensed product information in the USA recommends that dexrazoxane should only be given to patients who have received a cumulative dose of doxorubicin of 300 mg/m 2 and who require continued use, since there is some evidence that dexrazoxane may reduce the efficacy of some antineoplastic regimens. Patients with known liver function disorders should have their liver function assessed before receiving dexrazoxane for anthracycline extravasation.

Effects on the skin.

Severe cutaneous and subcutaneous necrosis has been reported1 in a patient who received dexrazoxane by infusion into a peripheral forearm vein, followed by intravenous injection of doxorubicin at a different site in the same arm. Local pain occurred during the dexrazoxane infusion but there was no evidence of extravasation.
1. Lossos IS, Ben-Yehuda D. Cutaneous and subcutaneous necrosis following dexrazoxane-CHOP therapy. Ann Pharmacother 1999; 33: 253–4.

💊 Pharmacokinetics

Dexrazoxane is mainly excreted in the urine as unchanged drug and metabolites. The elimination halflife is reported to be about 2 hours.

💊 Uses and Administration

Dexrazoxane is the (+)-enantiomorph of the antineoplastic drug razoxane and is a cytoprotective agent that is used to reduce the cardiotoxicity of doxorubicin and other anthracyclines; it is also used in the management of anthracycline extravasation. It is hydrolysed to an active metabolite that is similar to edetic acid. This chelates iron within the cells and appears to prevent the formation of the anthracycline-iron complex that is thought to be responsible for cardiotoxicity. Dexrazoxane is used to reduce the incidence and severity of cardiomyopathy associated with doxorubicin or epirubicin in patients with advanced or metastatic cancer who have previously received anthracyclines; in the USA, it is only licensed for use in women with metastatic breast cancer who have received a cumulative dose of doxorubicin of 300 mg/m 2 and who require continued use. It is given as the hydrochloride, by slow intravenous injection or rapid intravenous infusion, starting within 30 minutes before the anthracycline. The dose is expressed as the base. In the USA, the dose is calculated on a 10:1 ratio with doxorubicin; typically, 500 mg/m 2 of dexrazoxane is given for every 50 mg/m 2 of doxorubicin. In the UK the dose is calculated on a 20:1 ratio with doxorubicin and a 10:1 ratio with epirubicin. A reduction in dose may be required in patients with renal impairment (see below). In patients with anthracycline extravasation, dexrazoxane is given intravenously into a large vein in an area other than that affected by the extravasation. It is given once daily for 3 days, by intravenous infusion over 1 to 2 hours, starting within 6 hours of extravasation; the dose should be given at about the same time each day. The usual dose is 1000 mg/m 2 on the first and second days, and 500 mg/m 2 on the third day; the maximum single dose for patients with a body-surface greater than 2 m 2 is 2000 mg. Dexrazoxane is also being investigated for use in various other malignancies.
1. Links M, Lewis C. Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy. Drugs 1999; 57: 293–308
2. Schuchter LM, et al. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2002; 20: 2895–903. Also available at: http:// www.jco.org/cgi/reprint/20/12/2895.pdf (accessed 04/10/05
3. Cvetković RS, Scott LJ. Dexrazoxane : a review of its use for cardioprotection during anthracycline chemotherapy. Drugs 2005; 65: 1005–24.

Administration in children.

Doxorubicin has been used in the treatment of acute lymphoblastic leukaemia in children but cardiotoxicity may be a problem. A randomised study1 in 206 children found that those given dexrazoxane with doxorubicin had fewer elevations of cardiac troponin T, a marker of myocardial damage, than those given doxorubicin alone, but longer follow-up was needed to assess effects on cardiac function and survival. Another study2 in children with Hodgkin’s disease suggested that use of dexrazoxane might increase the risk of secondary malignancies, but further analysis of the leukaemia study3 found no evidence of such an effect.
1. Lipshultz SE, et al. The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia. N Engl J Med 2004; 351: 145–53
2. Tebbi CK, et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin’s disease. J Clin Oncol 2007; 25: 493–500
3. Barry EV, et al. Absence of secondary malignant neoplasms in children with high-risk acute lymphoblastic leukemia treated with dexrazoxane. J Clin Oncol 2008; 26: 1106–11.

Administration in renal impairment.

Dexrazoxane is mainly excreted in the urine and the dose should be reduced in patients with renal impairment. A reduction of 50% is recommended for patients with a creatinine clearance below 40 mL/minute.

💊 Preparations

Proprietary Preparations

Austria: Cardioxane; Braz.: Cardioxane; Canad.: Zinecard; Cz.: Cardioxane; Savene; Denm.: Cardioxane; Fr.: Cardioxane; Gr.: Savene; Hung.: Cardioxane; Irl.: Cardioxane; Israel: Cardioxane; Ital.: Cardioxane; Mex.: Cardioxane; Pol.: Cardioxane; UK: Cardioxane; Savene; USA: Totect; Zinecard; Venez.: Cardioxane.
Published October 29, 2018.