What is the recommended dose of dexrazoxane for cardioprotection in patients receiving anthracycline (doxorubicin) therapy?

Recommended Dose of Dexrazoxane for Cardioprotection with Anthracycline Therapy

Patients receiving dexrazoxane for cardioprotection during anthracycline therapy should be administered dexrazoxane at a ratio of 10:1 with the doxorubicin dose (e.g., 500 mg/m² dexrazoxane for 50 mg/m² doxorubicin), given by slow IV push or short IV infusion 15-30 minutes before doxorubicin administration. 1, 2

Administration Protocol

The recommended dosing and administration procedure includes:

• Dosage ratio: 10:1 (dexrazoxane:doxorubicin)
• Timing: Administer dexrazoxane 15-30 minutes before doxorubicin
• Administration method: Slow IV push or rapid drip intravenous infusion
• Important note: Do not administer doxorubicin before dexrazoxane; doxorubicin should be given within 30 minutes after completing dexrazoxane infusion 2

Dose Adjustments

Renal Impairment

• For patients with moderate to severe renal impairment (creatinine clearance <40 mL/min):
  • Reduce dexrazoxane dose by 50% (dexrazoxane:doxorubicin ratio reduced to 5:1)
  • Example: 250 mg/m² dexrazoxane for 50 mg/m² doxorubicin 2

Hepatic Impairment

• Since doxorubicin dose reduction is recommended in patients with hyperbilirubinemia, reduce the dexrazoxane dosage proportionately (maintaining the 10:1 ratio) 2

Use with Epirubicin

For patients receiving epirubicin instead of doxorubicin:

• A ratio of 10:1 with the epirubicin dose may be reasonable
• However, the optimal dose ratio for epirubicin has not been definitively determined 1
• Clinical trials evaluating cardioprotection with epirubicin used dexrazoxane:epirubicin ratios ranging from 10:1 to 6.25:1 1, 3

Preparation and Handling

1. Reconstitute dexrazoxane with 0.167 Molar sodium lactate injection to achieve a concentration of 10 mg/mL
2. Reconstituted solution is stable for 6 hours at room temperature (20-25°C) or under refrigeration (2-8°C)
3. May be diluted with either 0.9% Sodium Chloride or 5% Dextrose to a concentration of 1.3-5 mg/mL
4. Use caution when handling; glove use is recommended 2

Monitoring Requirements

• Patients receiving dexrazoxane should continue to undergo cardiac monitoring
• After cumulative doxorubicin doses of 400 mg/m², cardiac monitoring should be frequent
• Recommended monitoring schedule:
  • Repeat monitoring after 500 mg/m²
  • Subsequently monitor after every additional 50 mg/m² of doxorubicin 1

When to Consider Termination of Therapy

Strongly consider terminating dexrazoxane/doxorubicin therapy if:

• Patient develops a decline in left ventricular ejection fraction (LVEF) below institutional normal limits
• Patient develops clinical congestive heart failure 1

Clinical Efficacy

Dexrazoxane has been shown to significantly reduce the incidence of anthracycline-induced cardiac events, including congestive heart failure, in multiple clinical trials 4, 5. The cardioprotective effect appears to be maintained regardless of whether dexrazoxane is started with the first dose of anthracycline or after a cumulative doxorubicin dose of ≥300 mg/m² 4, 6.

Common Pitfalls and Caveats

1. Timing of administration: Ensure dexrazoxane is given before doxorubicin, not after
2. Drug interactions: Do not mix dexrazoxane with other drugs 2
3. Monitoring: Do not discontinue cardiac monitoring just because dexrazoxane is being used 1
4. Myelosuppression: Be aware that dexrazoxane may increase the incidence of severe leukopenia compared to placebo (78% vs 68%) 4
5. Epirubicin dosing: When using with epirubicin, note that the optimal dose ratio is less well established than with doxorubicin 1