Dosing and uses of Totect, Zinecard (dexrazoxane)
Adult dosage forms and strengths
powder for injection
- 250mg
- 500mg
Doxorubicin-Induced Cardiomyopathy, Prophylaxis (Zinecard/Generic)
10:1 ratio of dexrazoxane to doxorubicin dose (500 mg/m² dexrazoxane : 50 mg/m² doxorubicin) slow IVP or rapid drip IV infusion
Give doxorubicin within 30 minutes of beginning of dexrazoxane infusion
Monitor cardiac function and discontinue combination therapy in patients who develop a decline in left ventricular ejection fraction or develop clinical congestive failure
Renal impairment
- Moderate-to-severe: 5x doxorubicin dose
Anthracycline Extravasation (Totect)
Give first infusion within 6 hr after extravastion
Day 1: 1000 mg/m² IV; not to exceed 2000 mg
Day 2: 1000 mg/m² IV; not to exceed 2000 mg
Day 3: 500 mg/m² IV; not to exceed 1000 mg
Infuse IV over 1-2 hr; begin treatment within 6 hr of extravasation
Renal Impairment
CrCl <40 mL/min: Reduce dose by 50%
Pediatric dosage forms and strengths
Safety and efficacy not established
Cardiomyopathy Prophylaxis (Orphan)
Orphan designation for prevention of anthracyline-induced cardiomyopathy in children and adolescents
Sponsor
- Satiscor, LLC; 45 Marine Road; Boston, MA 02127
Totect, Zinecard (dexrazoxane) adverse (side) effects
Frequency not defined
Most ADRs due to concurrent antineoplastic treatment
Injection site pain, phlebitis, and increased myelosuppression are only major specific ADr
Warnings
Contraindications
Hypersensitivity
Use (Zinecard) in chemotherapy when an anthracycline is not being administered
Cautions
May interfere with activity of antineoplastic drugs; do NOT initiate until cumulative doxorubicin dose reaches 300 mg/m²
Do NOT give doxorubicin prior to dexrazoxane
Does not eliminate potential for anthracycline-induced cardiac toxicity; monitor cardiac function carefully
Secondary malignancies (eg, AML, MDS) reported with combination chemotherapy
Pregnancy and lactation
Pregnancy category: D; animal studies have shown embryotoxic and teratogenic effects during the period of organogenesis at doses significantly lower than the clinically recommended dose
Lactation: Unknown if excreted in human breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Totect, Zinecard (dexrazoxane)
Mechanism of action
EDTA derivative; intracellular chelating agent; exact mechanism not understood
Pharmacokinetics
Half-Life: 2-2.5 hr
Peak Plasma: 36.5 mcg/mL
Protein Bound: No
Vd: 22.4 L/m²
Renal Clearance: 3.35 L/hr/sq.meter
Excretion: Urine (42%)
Dialyzable: Yes
Administration
Zinecard/generic
IV Preparation
- Reconstitute w/ supplied Na-lactate 1/6M diluent (25 mL for 250 mg vial, 50 mL for 500 mg vial) to obtain 10 mg/mL soln
- Reconstituted soln may be further diluted with either NS or D5W to a concentration of 1.3-5 mg/mL in intravenous infusion bags
- Reconstituted & diluted solns stable for 6 hr at room temp or in fridge
IV Administration
- Doxorubicin should not be given prior to dexrazoxane
- Give dexrazoxane by slow IVP or rapid drip IV infusion over 5-15 min
- Give doxorubicin within 30 min after beginning of dexrazoxane infusion
Storage
- Store intact vials at controlled room temp
Totect
IV Preparation
- Do not mix or administer with any other drug during infusion
- 3 days of Tx for 1 pt contains 10 vials Totect & 10 vials diluent
- Before infusion, mix each vial (500 mg) w/ 50 mL diluent
- THEN, inject all required mixed solutions into the same 1000 mL NS bag
- Inspect visually for particulate matter prior to administration; should be slight yellow, discard if ppt visible
- Use within 2 hr of preparation
- Discard unused soln after 2 hr
IV Administration
- Infuse over 1-2 hr
- Use large caliber vein in area other than one affected by extravasation
- Remove cooling packs from area at least 15 min before Totect administration
- Start Tx on day 2 & 3 at same hour (±3 hr) as on first day
Storage
- Stable for 4 hr from time of mixing/diluting when stored below 25°C (77°F)
