NDC 72266-101 Dexrazoxane
Dexrazoxane For Injection Injection, Powder, Lyophilized, For Solution Intravenous

Product Information

Product Code72266-101
Proprietary Name What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.
Dexrazoxane
Non-Proprietary Name What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.
Dexrazoxane For Injection
Product Type What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.
Human Prescription Drug
Dosage FormInjection, Powder, Lyophilized, For Solution - A dosage form intended for the solution prepared by lyophilization ("freeze drying"), a process which involves the removal of water from products in the frozen state at extremely low pressures; this is intended for subsequent addition of liquid to create a solution that conforms in all respects to the requirements for Injections.
Administration Route(s) What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.
  • Intravenous - Administration within or into a vein or veins.
Product Labeler Information What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.
Fosun Pharma Usa Inc.
Labeler Code72266
FDA Application Number What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.
ANDA207321
Marketing Category What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
ANDA - A product marketed under an approved Abbreviated New Drug Application.
Start Marketing Date What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.
03-18-2019
Listing Expiration Date What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.
12-31-2023
Exclude Flag What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".
N
NDC Code Structure

Usage Information


Product Packages

NDC 72266-101-01

Package Description: 1 VIAL in 1 CARTON > 50 mL in 1 VIAL

Product Details

Dexrazoxane is a human prescription drug product labeled by Fosun Pharma Usa Inc.. The generic name of Dexrazoxane is dexrazoxane for injection. The product's dosage form is injection, powder, lyophilized, for solution and is administered via intravenous form.


What are Dexrazoxane Active Ingredients?

The following is the list of active ingredients in this product. An active ingredient is the substance responsible for the medicinal effects of a product specified by the substance's molecular structure or if the molecular structure is not known, defined by an unambiguous definition that identifies the substance. Each active ingredient name is the preferred term of the UNII code submitted.


NDC to RxNorm Crosswalk

What is RxNorm? RxNorm is a normalized naming system for generic and branded drugs that assigns unique concept identifier(s) known as RxCUIs to NDC products.The NDC to RxNorm Crosswalk for this produdct indicates multiple concept unique identifiers (RXCUIs) are associated with this product:


Inactive Ingredient(s)

The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • HYDROCHLORIC ACID (UNII: QTT17582CB)


Pharmacologic Class(es)

A pharmacologic class is a group of drugs that share the same scientifically documented properties. The following is a list of the reported pharmacologic class(es) corresponding to the active ingredients of this product.


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Dexrazoxane Labeling and Warnings

FDA filings in the form of structured product labels are documents that include all published material associated whith this product. Product label information includes data like indications and usage generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Table of Contents



1 Indications & Usage



Dexrazoxane for Injection is indicated for reducing the incid ence and severity of cardiomyopathy associated with doxorubicin ad m inistration in wo men with metastatic breast cancer who have received a cu mulative doxorubicin dose of 300 mg / m 2and who will c ontinue to receive doxor ubicin therapy to maintain tu mor control. Do not use with the initiat ion of doxorubicin therapy [see Warnings and Precautions (5.2 ) ].




A d m inister Dexrazoxane for Injection via intravenous infusion over 15 m inutes. DO NOT ADMINIS TER VIA AN INTRAV ENOUS PU S H.

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 2doxorubicin). Do not ad m inister doxorubicin before Dexrazoxane for Injection. Ad m inister doxorubicin within 30 m inutes after the co mpletion of Dexrazoxane for Injection infu sion.


2.2 Dose 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/m2 Dexrazoxane for Injection to 50 mg/m2 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.


2.3 Preparation 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.


3 Dosage Forms & Strengths



Dexrazoxane for Injection is available in 500 mg single dose vials as sterile, pyrogen-free lyophilized.


4 Contraindications



Do not use Dexrazoxane for Injection with non-anthracycline chemotherapy regimens.


5.1 Myelosuppression



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.


5.2 Concomitant 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.


5.3 Cardiac 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.


5.4 Secondary 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)].


5.5 Embryo-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)].


6.1 Clinical 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 Brea st 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
Vo miting
59
42
72
49
Fatigue/Malaise
61
48
58
55
Anorexia
42
27
47
38
Sto matitis
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/Erythe ma
5
4
4
2
Phlebitis
6
3
3
5
Esophagitis
6
3
7
4
Dysphagia
8
0
10
5
H e morrhage
2
3
2
1
Extravasation
1
3
1
2
Urticaria
2
2
2
0
Recall Skin
Reaction
1
1
2
0

7 Drug Interactions



No drug interactions have been identified [see Clinical Pharmacology (12.3)].


8.1 Pregnancy



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.


8.3 Nursing 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.


8.4 Pediatric Use



The safety and effectiveness of dexrazoxane in pediatric patients have not been established [see Warnings and Precautions (5.4)].


8.5 Geriatric 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.


8.6 Females 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)].


8.7 Renal 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)].


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.


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 11H 16N 4O 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 0.1 N 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)].


12.1 Mechanism 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.


12.3 Pharmacokinetics



The pharmacokinetics of dexrazoxane have been studied in advanced cancer patients with normal renal and hepatic function. The pharmacokinetics of dexrazoxane can be adequatelydescribed 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 Clearence (L/h/m 2)
Renal Clearence (L/h/m 2)
bVolume 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 22.4 L/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 3.35 L/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 hepatic impairment. The Dexrazoxane for Injection dose is dependent upon the dose of doxorubicin [see Dosage and Administration (2.2)].

Drug Interactions
There was no significant change in the pharmacokinetics of doxorubicin (50 mg/m 2) and its predominant metabolite, doxorubicinol, in the presence of dexrazoxane (500 mg/m 2) in a crossover study in cancer patients.


13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility



No long-term carcinogenicity studies have been carried out with dexrazoxane in animals. Nevertheless, a study by the National Cancer Institute has reported that long-term dosing with razoxane (the racemic mixture of dexrazoxane, ICRF-187, and its enantiomer ICRF-186) is associated with the development of malignancies in rats and possibly in mice [see Warnings and Precautions (5.4)].

Dexrazoxane was not mutagenic in the bacterial reverse mutation (Ames) test, but was found to be clastogenic to human lymphocytes in vitro and to mouse bone marrow erythrocytes in vivo (micronucleus test).

Dexrazoxane for Injection has the potential to impair fertility in male patients based on effects in repeat-dose toxicology studies. Testicular atrophy was seen with dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (1/3 the human dose on a mg/m 2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (approximately equal to the human dose on a mg/m 2 basis).


14 Clinical Studies



The ability of Dexrazoxane for Injection to prevent/reduce the incidence and severity of doxorubicin-induced cardiomyopathy was evaluated in three prospectively randomized placebo-controlled studies. In these studies, patients were treated with a doxorubicin-containing regimen and either Dexrazoxane for Injection or placebo starting with the first course of chemotherapy. There was no restriction on the cumulative dose of doxorubicin. Cardiac function was assessed by measurement of the LVEF, utilizing resting multigated nuclear medicine (MUGA) scans, and by clinical evaluations. Patients receiving Dexrazoxane for Injection had significantly smaller mean decreases from baseline in LVEF and lower incidences of congestive heart failure than the control group; however, in the largest study, patients with advanced breast cancer receiving FAC with Dexrazoxane for Injection had a lower response rate (48% vs. 63%) and a shorter time to progression than patients who received FAC versus placebo.

In the clinical trials, patients who were initially randomized to receive placebo were allowed to receive Dexrazoxane for Injection after a cumulative dose of doxorubicin above 300 mg/m 2. Retrospective historical analyses showed that the risk of experiencing a cardiac event (see Table 3 for definition) at a cumulative dose of doxorubicin above 300 mg/m 2 was greater in the patients who did not receive Dexrazoxane for Injection beginning with their seventh course of FAC than in the patients who did receive Dexrazoxane for Injection (HR=13.08; 95% CI: 3.72, 46.03; p<0.001). Overall, 3% of patients treated with Dexrazoxane for Injection developed CHF compared with 22% of patients not receiving Dexrazoxane for Injection.

Table 3: Definition of Cardiac Events:
        1. Development of congestive heart failure, defined as having two or more of the following:
            a. Cardiomegaly by X-ray
            b. Basilar Rales
            c. S3 Gallop
            d. Paroxysmal nocturnal dyspnea and/or orthopnea and/or significant dyspnea on exertion.
        2. Decline from baseline in LVEF by ≥10% and to below the lower limit of normal for the institution.
        3. Decline in LVEF by ≥20% from baseline value.
        4. Decline in LVEF to ≥5% below lower limit of normal for the institution.

Figure 1 shows the number of patients still on treatment at increasing cumulative doses.

Figure 1
Cumulative Number of Patients on Treatment FAC vs. FAC/Dexrazoxane for Injection Patients Patients Receiving at Least Seven Courses of Treatment


15 References



1. "OSHA Hazardous Drugs."  OSHA, http://www.osha.gov/SLTC/hazardousdrugs/index.html


16 How Supplied/Storage And Handling



Dexrazoxane for injection is available in the following strength as sterile, pyrogen-free lyophilized.

NDC 72266-101-01
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.


17.1 Myelosuppression



Treatment with Dexrazoxane for Injection is associated with leukopenia, neutropenia, and thrombocytopenia. Perform hematological monitoring [see Warnings and Precautions (5.1), (5.6)].


17.2 Embryo-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)].

Distributed by:

Fosun Pharma USA Inc.

Princeton, NJ 08540

Made in India

January 2019


Package Label.Principal Display Panel



NDC 72266-101-01

Dexrazoxane for Injection 500 mg/50 mL vial
FOR INTRAVENOUS USE ONLY
Single Dose Vial
Vial Label

NDC 72266-101-01

Dexrazoxane for Injection 500 mg/50 mL vial
FOR INTRAVENOUS USE ONLY

Single Dose Vial
Carton Label


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