Dexrazoxane 500 mg/50mL Injection, Powder, Lyophilized, For Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Cytoprotective Agent class.
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🩺 Clinical
- Dexrazoxane is given to help protect your heart from damage caused by doxorubicin, the chemotherapy you're receiving. Doxorubicin is very effective against breast cancer, but over...
- Why am I getting this medication along with my chemotherapy?
- This is actually by design. Clinical research showed that starting dexrazoxane at the same time as your very first doxorubicin treatment can actually reduce how well the chemothera...
- Why wasn't I given this from the very beginning of my chemo?
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $315.88 | $15,794.14 / 50 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J1190 | $41.441 / J1190 unit | — |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Dexrazoxane 500 mg 00143-9248-01 | Hikma | 1 vial | — | AP | FDA listed | — |
| Dexrazoxane 55150-0437-01 | Eugia | 1 kit | — | AP | FDA listed | — |
| Dexrazoxane 500 mg/50mL 68083-0195-01 | Gland | 1 vial | — | AP | FDA listed | — |
| Dexrazoxane 500 mg/50mL 72205-0248-01 | Novadoz | 1 vial | — | AP | FDA listed | — |
| Dexrazoxane 500 mg/50mL 72266-0101-01 | Fosun | 1 vial | — | AP | FDA listed | — |
| Dexrazoxane 500 mg/50mLthis 72611-0716-72 | Almaject, | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72611-0716-01 | 1 VIAL, SINGLE-DOSE in 1 CARTON (72611-716-01) / 50 mL in 1 VIAL, SINGLE-DOSE | 2020-09-01 | Active |
| 72611-0716-72 You're viewing this | 1 VIAL, SINGLE-DOSE in 1 CARTON (72611-716-72) / 50 mL in 1 VIAL, SINGLE-DOSE | 2022-06-01 | Active |
This pack accounts for about 24% of this product's recent Medicaid fills; most go to a different pack size. See all packs ↓
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What quantity is in NDC 72611-0716-72?
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Dexrazoxane for Injection is indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m 2 and who will continue to receive doxorubicin therapy to maintain tumor control. Do not use with the initiation of doxorubicin therapy [see Warnings and Precautions ( 5.2 )] . Dexrazoxane for Injection is a cytoprotective agent indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin therapy to maintain tumor control.
Do not use Dexrazoxane for Injection with doxorubicin initiation. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Reconstitute vial contents and dilute before use. ( 2.3 ) • Administer Dexrazoxane for Injection by intravenous infusion over 15 minutes. • DO NOT ADMINISTER VIA AN INTRAVENOUS PUSH. ( 2.1 , 2.3 ) • The recommended dosage ratio of Dexrazoxane for Injection to doxorubicin is 10:1 (e.g., 500 mg/m 2 Dexrazoxane for Injection to 50 mg/m 2 doxorubicin).
Do not administer doxorubicin before Dexrazoxane. ( 2.1 ) • Reduce dose by 50% for patients with creatinine clearance <40 mL/min. ( 2.2 , 8.7 )
2.1Recommended Dose Administer Dexrazoxane for Injection via intravenous infusion over 15 minutes. DO NOT ADMINISTER VIA AN INTRAVENOUS PUSH. The recommended dosage ratio of Dexrazoxane for Injection to doxorubicin is 10:1 (e.g., 500 mg/m 2 Dexrazoxane for Injection to 50 mg/m 2 doxorubicin). Do not administer doxorubicin before Dexrazoxane for Injection. Administer doxorubicin within 30 minutes after the completion of Dexrazoxane for Injection infusion.
2.2Dose Modifications Dosing in Patients with Renal Impairment Reduce Dexrazoxane for Injection dosage in patients with moderate to severe renal impairment (creatinine clearance values less than 40 mL/min) by 50% (Dexrazoxane for Injection to doxorubicin ratio reduced to 5:1; such as 250 mg/m 2 Dexrazoxane for Injection to 50 mg/m 2 doxorubicin) [ see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ]. Dosing in Patients with Hepatic Impairment Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, reduce the Dexrazoxane for Injection dosage proportionately (maintaining the 10:1 ratio) in patients with hepatic impairment.
2.3Preparation and Administration Preparation and Handling of Infusion Solution Reconstitute Dexrazoxane for Injection with Sterile Water for Injection, USP. Reconstitute with 50 mL for a Dexrazoxane for Injection 500 mg vial to give a concentration of 10 mg/mL. Dilute the reconstituted solution further with Lactated Ringer's Injection, USP to a concentration of 1.3 to 3.0 mg/mL in intravenous infusion bags for intravenous infusion.
Following reconstitution with Sterile Water for Injection, USP, Dexrazoxane for Injection is stable for 30 minutes at room temperature or if storage is necessary, up to 3 hours from the time of reconstitution when stored under refrigeration, 2° to 8°C (36° to 46°F). The pH of the resultant solution is 1.0 to 3.0. DISCARD UNUSED SOLUTIONS.
The diluted infusion solutions are stable for one hour at room temperature or if storage is necessary, up to 4 hours when stored under refrigeration, 2° to 8°C (36° to 46°F). The infusion solutions have a pH of 3.5 to 5.5. DISCARD UNUSED SOLUTIONS.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Solutions containing a precipitate should be discarded. Use caution when handling and preparing the reconstituted solution.
The use of gloves is recommended. If Dexrazoxane for Injection powder or solutions contact the skin or mucosae, wash exposed area immediately and thoroughly with soap and water. Follow special handling and disposal procedures 1 .
Administration Do not mix Dexrazoxane for Injection with other drugs. Administer the final diluted solution of Dexrazoxane for Injection by intravenous infusion over 15 minutes before the administration of doxorubicin. DO NOT ADMINISTER VIA AN INTRAVENOUS PUSH.
Administer doxorubicin within 30 minutes after the completion of Dexrazoxane for Injection infusion.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Dexrazoxane for Injection is available in 500 mg single dose vials as sterile, pyrogen-free lyophilized. 500 mg single dose vials as sterile, pyrogen-free lyophilized. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Do not use Dexrazoxane for Injection with non-anthracycline chemotherapy regimens. Dexrazoxane for Injection should not be used with non-anthracycline chemotherapy regimens. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Myelosuppression: Dexrazoxane for Injection may increase the myelosuppresive effects of chemotherapeutic agents. Perform hematological monitoring. ( 5.1 ) • Embryo-Fetal Toxicity: Can cause fetal harm. Advise female patients of reproductive potential of the potential hazard to the fetus. ( 5.5 , 8.1 )
5.1Myelosuppression Dexrazoxane for Injection may add to the myelosuppression caused by chemotherapeutic agents. Obtain a complete blood count prior to and during each course of therapy, and administer Dexrazoxane for Injection and chemotherapy only when adequate hematologic parameters are met.
5.2Concomitant Chemotherapy Only use Dexrazoxane for Injection in those patients who have received a cumulative doxorubicin dose of 300 mg/m 2 and are continuing with doxorubicin therapy. Do not use with chemotherapy initiation as Dexrazoxane for Injection may interfere with the antitumor activity of the chemotherapy regimen. In a trial conducted in patients with metastatic breast cancer who were treated with fluorouracil, doxorubicin, and cyclophosphamide (FAC) with or without Dexrazoxane for Injection starting with their first cycle of FAC therapy, patients who were randomized to receive Dexrazoxane for Injection had a lower response rate (48% vs.
63%) and shorter time to progression than patients who were randomized to receive placebo.
5.3Cardiac Toxicity Treatment with Dexrazoxane for Injection does not completely eliminate the risk of anthracycline-induced cardiac toxicity. Monitor cardiac function before and periodically during therapy to assess left ventricular ejection fraction (LVEF). In general, if test results indicate deterioration in cardiac function associated with doxorubicin, the benefit of continued therapy should be carefully evaluated against the risk of producing irreversible cardiac damage.
5.4Secondary Malignancies Secondary malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been reported in studies of pediatric patients who have received Dexrazoxane for Injection in combination with chemotherapy. Dexrazoxane for Injection is not indicated for use in pediatric patients. Some adult patients who received Dexrazoxane for Injection in combination with anti-cancer agents known to be carcinogenic have also developed secondary malignancies, including AML and MDS.
Razoxane is the racemic mixture, of which dexrazoxane is the S(+)-enantiomer. Secondary malignancies (primarily acute myeloid leukemia) have been reported in patients treated chronically with oral razoxane. In these patients, the total cumulative dose of razoxane ranged from 26 to 480 grams and the duration of treatment was from 42 to 319 weeks.
One case of T-cell lymphoma, one case of B-cell lymphoma, and six to eight cases of cutaneous basal cell or squamous cell carcinoma have also been reported in patients treated with razoxane. Long-term administration of razoxane to rodents was associated with the development of malignancies [see Nonclinical Toxicology ( 13.1 )].
5.5Embryo-Fetal Toxicity Dexrazoxane for Injection can cause fetal harm when administered to pregnant women. Dexrazoxane administration during the period of organogenesis resulted in maternal toxicity, embryotoxicity and teratogenicity in rats and rabbits at doses significantly lower than the clinically recommended dose [see Use in Specific Populations ( 8.1 )]. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Advise female patients of reproductive potential to avoid becoming pregnant and to use highly effective contraception during treatment [see Use in Specific Populations ( 8.6 )].
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS In clinical studies, Dexrazoxane for Injection was administered to patients also receiving chemotherapeutic agents for cancer. Pain on injection was observed more frequently in patients receiving Dexrazoxane for Injection versus placebo. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Almaject, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice. The adverse reaction profile described in this section was identified from randomized, placebo controlled, double-blind studies in patients with metastatic breast cancer who received the combination of the FAC chemotherapy regimen with or without Dexrazoxane for Injection.
The dose of doxorubicin was 50 mg/m 2 in each of these trials. Treatment was administered every three weeks until disease progression or cardiac toxicity. Patients in clinical trials who received FAC with Dexrazoxane for Injection experienced more severe leukopenia, granulocytopenia, and thrombocytopenia than patients receiving FAC without Dexrazoxane for Injection [see Warnings and Precautions ( 5.1 )].
Table 1 below lists the incidence of adverse reactions for patients receiving FAC with either Dexrazoxane for Injection or placebo in the breast cancer studies. Adverse experiences occurring during courses 1 through 6 are displayed for patients receiving Dexrazoxane for Injection or placebo with FAC beginning with their first course of therapy (columns 1 and 3, respectively). Adverse experiences occurring at course 7 and beyond for patients who received placebo with FAC during the first six courses and who then received either Dexrazoxane for Injection or placebo with FAC are also displayed (columns 2 and 4, respectively).
The adverse reactions listed below in Table 1 demonstrate that the frequency of adverse reaction “Pain on Injection” has been greater for Dexrazoxane for Injection arm, as compared to placebo. Table 1 Adverse Reaction Percentage (%) of Breast Cancer Patients With Adverse Reaction FAC + Dexrazoxane for Injection FAC + Placebo Courses 1- 6 N = 413 Courses ≥ 7 N = 102 Courses 1- 6 N = 458 Courses ≥ 7 N = 99 Alopecia 94 100 97 98 Nausea 77 51 84 60 Vomiting 59 42 72 49 Fatigue/Malaise 61 48 58 55 Anorexia 42 27 47 38 Stomatitis 34 26 41 28 Fever 34 22 29 18 Infection 23 19 18 21 Diarrhea 21 14 24 7 Pain on Injection 12 13 3 0 Sepsis 17 12 14 9 Neurotoxicity 17 10 13 5 Streaking/Erythema 5 4 4 2 Phlebitis 6 3 3 5 Esophagitis 6 3 7 4 Dysphagia 8 0 10 5 Hemorrhage 2 3 2 1 Extravasation 1 3 1 2 Urticaria 2 2 2 0 Recall Skin Reaction 1 1 2 0
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No drug interactions have been identified [see Clinical Pharmacology ( 12.3 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Nursing Mothers: Discontinue drug or nursing. ( 8.3 )
8.1Pregnancy Pregnancy Category D Risk Summary Dexrazoxane for Injection can cause fetal harm when administered to pregnant women. Dexrazoxane administration resulted in maternal toxicity, embryotoxicity and teratogenicity in rats and rabbits at doses significantly lower than the clinically recommended dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Warnings and Precautions ( 5.5 )].
Animal Data Dexrazoxane resulted in maternal toxicity in rats at doses of ≥2 mg/kg (1/40 the human dose on a mg/m 2 basis) and embryotoxicity and teratogenicity at 8 mg/kg (approximately 1/10 the human dose on a mg/m 2 basis) when given daily to pregnant rats during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg.
In rabbits, doses of ≥5 mg/kg (approximately 1/10 the human dose on a mg/m 2 basis) daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg (1/2 the human dose on a mg/m 2 basis) were embryotoxic and teratogenic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung.
8.3Nursing Mothers It is not known whether dexrazoxane or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from dexrazoxane, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
8.4Pediatric Use The safety and effectiveness of dexrazoxane in pediatric patients have not been established [see Warnings and Precautions ( 5.4 )].
8.5Geriatric Use Clinical studies of Dexrazoxane for Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
8.6Females of Reproductive Potential Contraception Dexrazoxane for Injection can cause fetal harm when administered during pregnancy. Advise female patients of reproductive potential to use highly effective contraception during treatment [see Use in Specific Populations ( 8.1 )].
8.7Renal Impairment Greater exposure to dexrazoxane may occur in patients with compromised renal function. Reduce the Dexrazoxane for Injection dose by 50% in patients with creatinine clearance values <40 mL/min [see Dosage and Administration ( 2.2 ) and Clinical Pharmacology ( 12.3 )].
🤰 Pregnancy ▾
8.1Pregnancy Pregnancy Category D Risk Summary Dexrazoxane for Injection can cause fetal harm when administered to pregnant women. Dexrazoxane administration resulted in maternal toxicity, embryotoxicity and teratogenicity in rats and rabbits at doses significantly lower than the clinically recommended dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Warnings and Precautions ( 5.5 )].
Animal Data Dexrazoxane resulted in maternal toxicity in rats at doses of ≥2 mg/kg (1/40 the human dose on a mg/m 2 basis) and embryotoxicity and teratogenicity at 8 mg/kg (approximately 1/10 the human dose on a mg/m 2 basis) when given daily to pregnant rats during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg.
In rabbits, doses of ≥5 mg/kg (approximately 1/10 the human dose on a mg/m 2 basis) daily during the period of organogenesis caused maternal toxicity and doses of 20 mg/kg (1/2 the human dose on a mg/m 2 basis) were embryotoxic and teratogenic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of dexrazoxane in pediatric patients have not been established [see Warnings and Precautions ( 5.4 )].
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of Dexrazoxane for Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
🆘 Overdosage ▾
10 OVERDOSAGE There are no data on overdosage in the cardioprotective trials; the maximum dose administered during the cardioprotective trials was 1000 mg/m 2 every three weeks. Disposition studies with Dexrazoxane for Injection have not been conducted in cancer patients undergoing dialysis, but retention of a significant dose fraction (>0.4) of the unchanged drug in the plasma pool, minimal tissue partitioning or binding, and availability of greater than 90% of the systemic drug levels in the unbound form suggest that it could be removed using conventional peritoneal or hemodialysis.
There is no known antidote for dexrazoxane. Instances of suspected overdose should be managed with good supportive care until resolution of myelosuppression and related conditions is complete. Management of overdose should include treatment of infections, fluid regulation, and maintenance of nutritional requirements.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism by which Dexrazoxane for Injection exerts its cytoprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane is converted intracellularly to a ring-opened chelating agent that interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy.
12.3Pharmacokinetics The pharmacokinetics of dexrazoxane have been studied in advanced cancer patients with normal renal and hepatic function. The pharmacokinetics of dexrazoxane can be adequately described by a two-compartment open model with first-order elimination. Dexrazoxane has been administered as a 15 minute infusion over a dose range of 60 to 900 mg/m 2 with 60 mg/m 2 of doxorubicin, and at a fixed dose of 500 mg/m 2 with 50 mg/m 2 doxorubicin.
The disposition kinetics of dexrazoxane are dose-independent, as shown by linear relationship between the area under plasma concentration-time curves and administered doses ranging from 60 to 900 mg/m 2 . The mean peak plasma concentration of dexrazoxane was 36.5 μg/mL at 15- minute after intravenous administration of 500 mg/m 2 dose of Dexrazoxane for Injection over 15 to 30 minutes prior to the 50 mg/m 2 doxorubicin dose. The important pharmacokinetic parameters of dexrazoxane are summarized in Table 2: Table 2: SUMMARY OF MEAN (%CV a ) DEXRAZOXANE PHARMACOKINETIC PARAMETERS AT A DOSAGE RATIO OF 10:1 OF DEXRAZOXANE FOR INJECTION: DOXORUBICIN Dose Doxirubicin (mg/m 2 ) Dose Dexrazoxane for Injection (mg/m 2 ) Number of Subjects Elimination Half-Life (h) Plasma Clearance (L/h/m 2 ) Renal Clearance (L/h/m 2 ) b Volume of Distribution (L/m 2 ) 50 60 500 600 10 5 2.5(16) 2.1 (29) 7.88 (18) 6.25 (31) 3.35 (36) ------- 22.4 (22) 22.0 (55) a Coefficient of variation b Steady-state volume of distribution Distribution Following a rapid distributive phase (0.2 to 0.3 hours), dexrazoxane reaches post-distributive equilibrium within two to four hours.
The estimated mean steady-state volume of distribution of dexrazoxane is
22.4L/m 2 after 500 mg/m 2 of Dexrazoxane for Injection dose followed by 50 mg/m 2 of doxorubicin, suggesting distribution throughout total body water (25 L/m 2 ). In vitro studies have shown that dexrazoxane is not bound to plasma proteins. Metabolism Qualitative metabolism studies with dexrazoxane have confirmed the presence of unchanged drug, a diacid-diamide cleavage product, and two monoacid-monoamide ring products in the urine of animals and man.
The metabolite levels were not measured in the pharmacokinetic studies. Excretion Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of a 500 mg/m 2 dose of Dexrazoxane for Injection was excreted in the urine.
Renal clearance averages
3.35L/h/m 2 after the 500 mg/m 2 Dexrazoxane for Injection dose followed by 50 mg/m 2 of doxorubicin. Specific Populations Pediatric Pharmacokinetics following Dexrazoxane for Injection administration have not been evaluated in pediatric patients. Effect of Renal Impairment The pharmacokinetics of dexrazoxane were assessed following a single 15-minute IV infusion of 150 mg/m 2 of Dexrazoxane for Injection.
Dexrazoxane clearance was reduced in subjects with renal dysfunction. Compared with controls, the mean AUC 0-inf value was two-fold greater in subjects with moderate (CL CR 30-50 mL/min) to severe (CL CR <30 mL/min) renal dysfunction. Modeling demonstrated that equivalent exposure (AUC 0-inf ) could be achieved if dosing were reduced by 50% in subjects with creatinine clearance values <40 mL/min compared with control subjects (CL CR >80 mL/min) [see Use in Specific Populations ( 8.7 ) and Dosage and Administration ( 2.2 )].
Effect of Hepatic Impairment Pharmacokinetics following Dexrazoxane for Injection administration have not been evaluated in patients with hepat…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism by which Dexrazoxane for Injection exerts its cytoprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane is converted intracellularly to a ring-opened chelating agent that interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Dexrazoxane for injection is available in the following strength as sterile, pyrogen-free lyophilized. NDC 72611-716-01 500 mg single dose vial with a blue flip-top seal, packaged in single vial packs. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Follow special handling and disposal procedures. 1
📋 Description ▾
11 DESCRIPTION Dexrazoxane for injection, a cardioprotective agent for use in conjunction with doxorubicin, is a sterile, pyrogen-free lyophilizate intended for intravenous administration. Chemically, dexrazoxane is (S)-4,4'-(1-methyl-1,2-ethanediyl)bis-2,6-piperazinedione. The structural formula is as follows: C 11 H 16 N 4 O 4 M.W.
268.28 Dexrazoxane, an intracellular chelating agent, is a derivative of EDTA. Dexrazoxane is a whitish crystalline powder that melts at 191° to 197°C. It is sparingly soluble in water and
0.1N HCl, slightly soluble in ethanol and methanol, and practically insoluble in nonpolar organic solvents. The pKa is 2.1. Dexrazoxane has an octanol/water partition coefficient of 0.025 and degrades rapidly above a pH of 7.0.
Each 500 mg vial contains dexrazoxane hydrochloride equivalent to 500 mg dexrazoxane. Hydrochloric Acid, NF is added for pH adjustment. When reconstituted as directed with 50 mL of Sterile Water for Injection, USP, each mL contains: 10 mg dexrazoxane.
The pH of the resultant solution is 1.0 to 3.0. The reconstituted Dexrazoxane for Injection solutions prepared from Sterile Water for Injection, USP, are intended for further dilution with Lactated Ringer’s Injection, USP, for rapid intravenous drip infusion. DO NOT ADMINISTER VIA AN INTRAVENOUS PUSH [see Dosage and Administration (2.1 , 2.3)] . structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION
17.1Myelosuppression Treatment with Dexrazoxane for Injection is associated with leukopenia, neutropenia, and thrombocytopenia. Perform hematological monitoring [see Warnings and Precautions ( 5.1 ) , (5.6)].
17.2Embryo-Fetal Toxicity Counsel patients on pregnancy planning and prevention. Advise female patients of reproductive potential that Dexrazoxane for Injection can cause fetal harm and to use highly effective contraception during treatment [see Warnings and Precautions ( 5.5 ) and Use in Specific Populations ( 8. 1 , 8.6 )].