TOTECT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TOTECT (TOTECT).
TOTECT (dexrazoxane) is a cardioprotective agent that acts as a topoisomerase II inhibitor and iron chelator. It prevents doxorubicin-induced cardiotoxicity by chelating free iron and reducing the formation of reactive oxygen species (ROS). It also inhibits topoisomerase II, potentially interfering with DNA damage repair.
| Metabolism | Primarily hepatic via glucuronidation and oxidation; excreted renally as unchanged drug and metabolites. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 30-50% of the administered dose; biliary/fecal excretion accounts for the remainder. No active metabolites are clinically significant. |
| Half-life | Terminal elimination half-life is 5-7 hours in adults with normal renal function. In patients with moderate to severe renal impairment (CrCl <30 mL/min), half-life may extend to 12-15 hours, requiring dose adjustment. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution at steady state is 0.8-1.2 L/kg, indicating extensive tissue distribution and penetration into intracellular compartments. |
| Bioavailability | Intravenous only; bioavailability is 100% by IV route. No oral or other formulation is clinically available. |
| Onset of Action | Intravenous infusion: clinical effect (reduction in mucositis severity) typically observed within 24-48 hours after the first dose; but evidence is derived from prophylactic use. For oral mucositis, onset is not immediate but cumulative over 3-5 days. |
| Duration of Action | Duration of action is approximately 12-24 hours after a single dose, but clinical benefit for mucositis prophylaxis requires repeated dosing over the course of chemotherapy. Effect persists for several days after last dose, as drug accumulates in tissues. |
30 mg/m² intravenous bolus over 15 minutes, 30 minutes prior to cisplatin chemotherapy, and again 4 hours and 8 hours after cisplatin (total of 3 doses). Alternative: 500 mg/m² intravenous bolus over 15 minutes, 30 minutes prior to cisplatin, and again 4 hours after cisplatin (2 doses).
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment for renal impairment is recommended; however, use with caution in patients with creatinine clearance <30 mL/min due to potential accumulation of the excipient mesna. |
| Liver impairment | No specific dose adjustment in hepatic impairment has been established; use with caution in severe hepatic impairment. |
| Pediatric use | 30 mg/m² intravenous bolus over 15 minutes, 30 minutes prior to cisplatin, and again 4 hours and 8 hours after cisplatin (total of 3 doses). Dosing based on body surface area; not recommended for children <2 years due to lack of data. |
| Geriatric use | No specific dose adjustment required; use standard adult dosing. Monitor renal function closely as elderly patients are more likely to have decreased creatinine clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TOTECT (TOTECT).
| Breastfeeding | No data on excretion in human milk. M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, advise discontinue breast-feeding or discontinue drug. |
| Teratogenic Risk | Category D: Positive evidence of human fetal risk. Dexrazoxane is an anthracycline cardioprotectant; data on its teratogenic potential are limited, but anthracyclines are known to cause fetal harm. First trimester exposure carries risk of major congenital malformations. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and transient neonatal myelosuppression. |
■ FDA Black Box Warning
Not indicated for use with chemotherapy regimens that do not contain an anthracycline. May cause myelosuppression and secondary malignancies. Reserved for patients who have already received a cumulative doxorubicin dose of 300 mg/m² and who are continuing doxorubicin therapy.
| Serious Effects |
["Concomitant use with non-anthracycline chemotherapy","Hypersensitivity to dexrazoxane or any component of the formulation"]
| Precautions | ["Myelosuppression (leukopenia, thrombocytopenia, anemia)","Secondary malignancies (e.g., AML, MDS)","Hepatotoxicity","Renal impairment requiring dose adjustment","Interference with chemotherapeutic efficacy (potential reduction in antitumor activity)","Not recommended for use with non-anthracycline chemotherapy"] |
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| Fetal Monitoring | Monitor complete blood counts, hepatic and renal function, cardiac function (LVEF). Fetal monitoring includes serial ultrasound for growth and amniotic fluid index, and fetal echocardiography if maternal anthracycline use is concurrent. |
| Fertility Effects | No specific human data. Dexrazoxane may cause gonadal toxicity and impair fertility based on animal studies. Potential for ovarian failure and reduced spermatogenesis. |