Cerubidine (daunorubicin hydrochloride) is the hydrochloride salt of an anthracycline cytotoxic antibiotic produced by a strain of Streptomyces coeruleorubidus. It is provided as a sterile reddish lyophilized powder in vials for intravenous administration only. Each vial contains 21.4 mg daunorubicin hydrochloride (equivalent to 20 mg of daunorubicin), and 100 mg mannitol. It is soluble in water when adequately agitated and produces a reddish solution. It has the following structural formula which may be described with the chemical name of (1S,3S)-3-Acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside hydrochloride. Its molecular formula is C₂₇H₂₉NO₁₀•HCl with a molecular weight of 563.99. It is a hygroscopic crystalline powder. The pH of a 5 mg/mL aqueous solution is 4.5 to 6.5. The structural formula is as follows:

Last updated on RxList: 8/13/2008

Cerubidine in combination with other approved anticancer drugs is indicated for remission induction in acute nonlymphocytic leukemia (myelogenous, monocytic, erythroid) of adults and for remission induction in acute lymphocytic leukemia of children and adults.

Parenteral drug products should be inspected visually for particulate matter prior to administration, whenever solution and container permit.

Principles: In order to eradicate the leukemic cells and induce a complete remission, a profound suppression of the bone marrow is usually required. Evaluation of both the peripheral blood and bone marrow is mandatory in the formulation of appropriate treatment plans.

It is recommended that the dosage of Cerubidine be reduced in instances of hepatic or renal impairment. For example, using serum bilirubin and serum creatinine as indicators of liver and kidney function, the following dose modifications are recommended:

Serum Bilirubin	Serum Creatinine	Dose Reduction
1.2 to 3.0 mg%	-	25%
>3 mg%	-	50%
-	>3 mg%	50%

Representative Dose Schedules and Combination for the Approved Indication of Remission Induction in Adult Acute Nonlymphocytic Leukemia:

In Combination: For patients under age 60, Cerubidine 45 mg/m²/day IV on days 1, 2, and 3 of the first course and on days 1, 2 of subsequent courses AND cytosine arabinoside 100 mg/m²/day IV infusion daily for 7 days for the first course and for 5 days for subsequent courses.

For patients 60 years of age and above, Cerubidine 30 mg/m²/day IV on days 1, 2, and 3 of the first course and on days 1, 2 of subsequent courses AND cytosine arabinoside 100 mg/m²/day IV infusion daily for 7 days for the first course and for 5 days for subsequent courses. This Cerubidine dose-reduction is based on a single study and may not be appropriate if optimal supportive care is available.

The attainment of a normal-appearing bone marrow may require up to three courses of induction therapy. Evaluation of the bone marrow following recovery from the previous course of induction therapy determines whether a further course of induction treatment is required.

Representative Dose Schedule and Combination for the Approved Indication of Remission Induction in Pediatric Acute Lymphocytic Leukemia:

In Combination: Cerubidine 25 mg/m² IV on day 1 every week, vincristine 1.5 mg/m² IV on day 1 every week, prednisone 40 mg/m² PO daily. Generally, a complete remission will be obtained within four such courses of therapy; however, if after four courses the patient is in partial remission, an additional one or, if necessary, two courses may be given in an effort to obtain a complete remission.

In children less than 2 years of age or below 0.5 m² body surface area, it has been recommended that the Cerubidine dosage calculation should be based on weight (1 mg/kg) instead of body surface area.

Representative Dose Schedules and Combination for the Approved Indication of Remission Induction in Adult Acute Lymphocytic Leukemia:

In Combination: Cerubidine 45 mg/m²/day IV on days 1, 2, and 3 AND vincristine 2 mg IV on days 1, 8, and 15; prednisone 40 mg/m²/day PO on days 1 through 22, then tapered between days 22 to 29; L-asparaginase 500 IU/kg/day x 10 days IV on days 22 through 32.

The contents of a vial should be reconstituted with 4 mL of Sterile Water for Injection and agitated gently until the material has completely dissolved. The sterile vial contents provide 20 mg of daunorubicin, with 5 mg of daunorubicin per mL. The desired dose is withdrawn into a syringe containing 10 mL to 15 mL of 0.9% Sodium Chloride Injection, USP and then injected into the tubing or sidearm in a rapidly flowing IV infusion of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. Cerubidine should not be administered mixed with other drugs or heparin.

Storage and Handling: Store unreconstituted powder at controlled room temperature, 15° to 30°C (59° to 86°F). The reconstituted solution is stable for 24 hours at room temperature and 48 hours under refrigeration. It should be protected from exposure to sunlight. Protect from light. Retain in carton until time of use.

If Cerubidine contacts the skin or mucosae, the area should be washed thoroughly with soap and water. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.^1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Cerubine (daunorubicin HCl) for Injection, is available in butyl-rubber-stoppered vials, each containing 21.4 mg daunorubicin hydrochloride (equivalent to 20 mg of daunorubicin) and 100 mg of mannitol, as a sterile reddish lyophilized powder. When reconstituted with 4 mL of Sterile Water for Injection, USP, each mL contains 5 mg daunorubicin activity.

NDC 55390-281-10 20 mg, single dose vials; carton of 10.

REFERENCES

1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. NIH Publication No. 83-2621. For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.

2. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA, March 15,1985.

3. National Study Commission on Cytotoxic Exposure Recommendations for Handling Cytotoxic Agents. Available from Louis R Jeffrey, Sc.D., Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115.

4. Clinical Oncological Society of Australia: Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia 1:426-428, 1983.

5. Jones RB, et al: Safe handling of chemotherapeutic agents: A report from the Mount Sinai Medical Center, Ca A Cancer Joumal for Clinicians Sept/Oct, 258-263, 1983.

6. American Society of Hospital Pharmacists technical assistance bulletin on handling cytotox-ic and hazardous drugs. Am J Hosp Pharm 47:1033-1049, 1990.

7. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines), Am JHealth-Syst Pharm, 15:1669-1685, 1996.

Manufactured by: Ben Venue Laboratories, Bedford, OH 44146. Manufactured for: Bedford Laboratories Inc, Bedford, OH 44146. June 2004. FDA Rev date: 12/13/00

Last updated on RxList: 8/13/2008

Dose-limiting toxicity includes myelosuppression and cardiotoxicity (See WARNINGS). Other reactions include:

Cutaneous: Reversible alopecia occurs in most patients. Rash, contact dermatitis and urticaria have occurred rarely.

Gastrointestinal:Acute nausea and vomiting occur but are usually mild. Antiemetic therapy may be of some help. Mucositis may occur 3 to 7 days after administration. Diarrhea and abdominal pain have occasionally been reported.

Local: If extravasation occurs during administration, severe local tissue necrosis, severe celluli-tis, thrombophlebitis, or painful induration can result.

Acute Reactions: Rarely, anaphylactoid reaction, fever, and chills can occur. Hyperuricemia may occur, especially in patients with leukemia, and serum uric acid levels should be monitored.

Use of Cerubidine in a patient who has previously received doxorubicin increases the risk of cardiotoxicity. Cerubidine should not be used in patients who have previously received the recommended maximum cumulative doses of doxorubicin or Cerubidine. Cyclophosphamide used concurrently with Cerubidine may also result in increased cardiotoxicity. Dosage reduction of Cerubidine may be required when used concurrently with other myelosup-pressive agents.

Hepatotoxic medications, such as high-dose methotrexate, may impair liver function and increase the risk of toxicity.

Last updated on RxList: 8/13/2008

Bone Marrow: Cerubidine is a potent bone marrow suppressant. Suppression will occur in all patients given a therapeutic dose of this drug. Therapy with Cerubidine should not be started in patients with pre-existing drug-induced bone marrow suppression unless the benefit from such treatment warrants the risk. Persistent, severe myelosuppression may result in superinfection or hemorrhage.

Cardiac Effects: Special attention must be given to the potential cardiac toxicity of Cerubidine, particularly in infants and children. Pre-existing heart disease and previous therapy with doxorubicin are co-factors of increased risk of Cerubidine-induced cardiac toxicity and the benefit-to-risk ratio of Cerubidine therapy in such patients should be weighed before starting Cerubidine. In adults, at total cumulative doses less than 550 mg/m², acute congestive heart failure is seldom encountered. However, rare instances of pericarditis-myocarditis, not dose-related, have been reported.

In adults, at cumulative doses exceeding 550 mg/m², there is an increased incidence of drug-induced congestive heart failure. Based on prior clinical experience with doxorubicin, this limit appears lower, namely 400 mg/m², in patients who received radiation therapy that encompassed the heart.

In infants and children, there appears to be a greater susceptibility to anthracycline-induced car-diotoxicity compared to that in adults, which is more clearly dose-related. Anthracycline therapy (including daunorubicin) in pediatric patients has been reported to produce impaired left ventricular systolic performance, reduced contractility, congestive heart failure or death. These conditions may occur months to years following cessation of chemotherapy. This appears to be dose-dependent and aggravated by thoracic irradiation. Long-term periodic evaluation of cardiac function in such patients should, thus, be performed. In both children and adults, the total dose of Cerubidine administered should also take into account any previous or concomitant therapy with other potentially cardiotoxic agents or related compounds such as doxorubicin.

There is no absolutely reliable method of predicting the patients in whom acute congestive heart failure will develop as a result of the cardiac toxic effect of Cerubidine. However, certain changes in the electrocardiogram and a decrease in the systolic ejection fraction from pre-treatment baseline may help to recognize those patients at greatest risk to develop congestive heart failure. On the basis of the electrocardiogram, a decrease equal to or greater than 30% in limb lead QRS voltage has been associated with a significant risk of drug-induced cardiomyopathy. Therefore, an electrocardiogram and/or determination of systolic ejection fraction should be performed before each course of Cerubidine. In the event that one or the other of these predictive parameters should occur, the benefit of continued therapy must be weighed against the risk of producing cardiac damage. Early clinical diagnosis of drug-induced congestive heart failure appears to be essential for successful treatment.

Evaluation of Hepatic and Renal Function: Significant hepatic or renal impairment can enhance the toxicity of the recommended doses of Cerubidine; therefore, prior to administration, evaluation of hepatic function and renal function using conventional clinical laboratory tests is recommended (See DOSAGE AND ADMINISTRATION).

Pregnancy: Cerubidine may cause fetal harm when administered to a pregnant woman. An increased incidence of fetal abnormalities (parieto-occipital cranioschisis, umbilical hernias, or rachischisis) and abortions was reported in rabbits at doses of 0.05 mg/kg/day or approximately 1/100th of the highest recommended human dose on a body surface area basis. Rats showed an increased incidence of esophageal, cardiovascular and urogenital abnormalities as well as rib fusions at doses of 4 mg/kg/day or approximately 1/2 the human dose on a body surface area basis. Decreases in fetal birth weight and post-delivery growth rate were observed in mice. There are no adequate and well-controlled studies in pregnant women. 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 the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

Secondary Leukemias: There have been reports of secondary leukemias in patients exposed to topoi-somerase II inhibitors when used in combination with other antineoplastic agents or radiation therapy.

Extravasation at Injection Site: Extravasation of Cerubidine at the site of intravenous administration can cause severe local tissue necrosis. (See ADVERSE REACTIONS)

General: Therapy with Cerubidine requires close patient observation and frequent complete blood-count determinations. Cardiac, renal, and hepatic function should be evaluated prior to each course of treatment.

Appropriate measures must be taken to control any systemic infection before beginning therapy with Cerubidine.

Cerubidine may transiently impart a red coloration to the urine after administration, and patients should be advised to expect this.

Laboratory Tests: Cerubidine may induce hyperuricemia secondary to rapid lysis of leukemic cells. As a precaution, allopurinol administration is usually begun prior to initiating antileukemic therapy. Blood uric acid levels should be monitored and appropriate therapy initiated in the event that hyperuricemia develops.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Cerubidine, when injected subcutaneously into mice, causes fibrosarcomas to develop at the injection site. When administered to mice thrice weekly intraperitoneally, no carcinogenic effect was noted after 18 months of observation. In male rats administered Cerubidine thrice weekly for 6 months, at 1/70th the recommended human dose on a body surface area basis, peritoneal sarcomas were found at 18 months. A single IV dose of Cerubidine administered to rats at 1.6 fold the recommended human dose on a body surface area basis caused mammary adenocarcinomas to appear at 1 year. Cerubidine was mutagenic in vitro (Ames assay, V79 hamster cell assay), and clastogenic in vitro (CCRFCEM human lymphoblasts) and in vivo (SCE assay in mouse bone marrow) tests. In male dogs at a daily dose of 0.25 mg/kg administered intravenously, testicular atrophy was noted at autopsy. Histologic examination revealed total aplasia of the spermatocyte series in the seminiferous tubules with complete aspermatogenesis.

Pregnancy Category D (See WARNINGS)

Nursing Mothers: It is not known whether this drug is 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 Cerubidine, mothers should be advised to discontinue nursing during Cerubidine therapy.

Elderly: See CLINICAL PHARMACOLOGY, Special Populations, Geriatric Patients.

Pediatric Use: See CLINICAL PHARMACOLOGY, Special Populations, Pediatric Patients and WARNINGS, Cardiac Effects.

Last updated on RxList: 8/13/2008

No information provided.

Cerubidine is contraindicated in patients who have shown a hypersensitivity to it.

Last updated on RxList: 8/13/2008

Mechanism of Action: Cerubidine has antimitotic and cytotoxic activity through a number of proposed mechanisms of action. Cerubidine forms complexes with DNA by intercalation between base pairs. It inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. Single strand and double strand DNA breaks result.

Cerubidine may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA.

Cerubidine possesses an antitumor effect against a wide spectrum of animal tumors, either grafted or spontaneous.

Pharmacokinetics

General: Following intravenous injection of Cerubidine, plasma levels of daunorubicin decline rapidly, indicating rapid tissue uptake and concentration. Thereafter, plasma levels decline slowly with a half-life of 45 minutes in the initial phase and 18.5 hours in the terminal phase. By 1 hour after drug administration, the predominant plasma species is daunorubicinol, an active metabolite, which disappears with a half-life of 26.7 hours.

Distribution: Cerubidine is rapidly and widely distributed in tissues, with highest levels in the spleen, kidneys, liver, lungs, and heart. The drug binds to many cellular components, particularly nucleic acids. There is no evidence that Cerubidine crosses the blood-brain barrier, but the drug apparently crosses the placenta.

Metabolism and Elimination: Cerubidine is extensively metabolized in the liver and other tissues, mainly by cytoplasmic aldo-keto reductases, producing daunorubicinol, the major metabolite which has antineoplastic activity. Approximately 40% of the drug in the plasma is present as daunorubicinol within 30 minutes and 60% in 4 hours after a dose of daunorubicin. Further metabolism via reduction cleavage of the glycosidic bond, 4-O demethylation, and conjugation with both sulfate and glucuronide have been demonstrated. Simple glycosidic cleavage of daunorubicin or daunorubicinol is not a significant metabolic pathway in man. Twenty-five percent of an administered dose of Cerubidine is eliminated in an active form by urinary excretion and an estimated 40% by biliary excretion.

Special Populations

Pediatric Patients: Although appropriate studies with Cerubidine have not been performed in the pediatric population, cardiotoxicity may be more frequent and occur at lower cumulative doses in children.

Geriatric Patients: Although appropriate studies with Cerubidine have not been performed in the geriatric population, cardiotoxicity may be more frequent in the elderly. Caution should also be used in patients who have inadequate bone marrow reserves due to old age. In addition, elderly patients are more likely to have age-related renal function impairment, which may require reduction of dosage in patients receiving Cerubidine.

Renal and Hepatic Impairment: Doses of Cerubidine should be reduced in patients with hepatic and renal impairment. Patients with serum bilirubin concentrations of 1.2 to 3 mg/dL should receive 75% of the usual daily dose and patients with serum bilirubin concentrations greater than 3 mg/dL should receive 50% of the usual daily dose. Patients with serum creatinine concentrations of greater than 3 mg/dL should receive 50% of the usual daily dose. (See WARNINGS, Evaluation of Hepatic and Renal Function).

Clinical Studies: In the treatment of adult acute nonlymphocytic leukemia, Cerubidine, used as a single agent, has produced complete remission rates of 40 to 50%, and in combination with cytarabine, has produced complete remission rates of 53 to 65%.

The addition of Cerubidine to the two-drug induction regimen of vincristine-prednisone in the treatment of childhood acute lymphocytic leukemia does not increase the rate of complete remission. In children receiving identical CNS prophylaxis and maintenance therapy (without consolidation), there is prolongation of complete remission duration (statistically significant, p < 0.02) in those children induced with the three drug (Cerubidine-vincristine-prednisone) regimen as compared to two drugs. There is no evidence of any impact of Cerubidine on the duration of complete remission when a consolidation (intensification) phase is employed as part of a total treatment program. In adult acute lymphocytic leukemia, in contrast to childhood acute lymphocytic leukemia, Cerubidine during induction significantly increases the rate of complete remission, but not remission duration, compared to that obtained with vincristine, prednisone, and L-asparaginase alone. The use of Cerubidine in combination with vincristine, prednisone, and L-asparaginase has produced complete remission rates of 83% in contrast to a 47% remission in patients not receiving Cerubidine.

Last updated on RxList: 8/13/2008

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 8/13/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DAUNORUBICIN - INJECTION

(dawn-oh-REWB-eh-sin)

COMMON BRAND NAME(S): Cerubidine

WARNING: Daunorubicin must be given only by injection into a vein. Do not give by injection into a muscle or under the skin. If this medication accidentally leaks into the skin/muscle around the injection site, it may cause severe damage. Tell your doctor immediately if you notice redness, pain, or swelling at or near the injection site.

This medication may infrequently result in serious (rarely fatal) heart problems (including heart failure). This may occur both during treatment or months to years after treatment is completed. The risk of heart problems is affected by your dose, medical history (including previous heart disease, radiation treatment to the chest area), and previous use of this and other drugs (including doxorubicin). Tell your doctor immediately if you notice symptoms such as irregular heartbeat, shortness of breath, or swelling ankles/feet.

Daunorubicin may cause certain severe blood and bone marrow disorders (low red blood cells/white blood cells/platelets). This can affect your body's ability to stop bleeding or fight infection. Tell your doctor immediately if you develop easy bleeding/bruising or signs of infection (e.g., fever, chills, persistent sore throat).

Very rarely, people with cancer who are treated with this type of medication have developed other cancers (e.g., secondary leukemia). The risk may be increased when this medication is given with certain anti-cancer drugs or radiation treatment. Consult your doctor for more details.

Before starting treatment with this medication, tell your doctor if you have liver or kidney problems. Your dose may need to be adjusted.

USES: Daunorubicin is used to treat leukemia and other cancers. It belongs to a class of drugs known as anthracyclines and works by slowing or stopping the growth of cancer cells.

HOW TO USE: This medication is given by injection into a vein as directed by your doctor. Dosage is based on your medical condition, body size, and response to treatment.

Read and learn all preparation and usage instructions supplied by the manufacturer. Follow all instructions for proper mixing with the correct IV fluids. Before using, check the product visually for particles or discoloration. If either is present, do not use the liquid.

If this medication touches your skin, immediately wash the area well with soap and water. If this medication gets in your eye, open the eyelids and flush with water for 15 minutes, then seek immediate medical attention. Caregivers should take precautions (e.g., wear gloves) to prevent contact with the patient's urine and other body fluids.

Learn how to store and discard needles, medical supplies, and medical waste safely. Consult your pharmacist for details.

Drink plenty of fluids while using this medication unless otherwise directed by your doctor. Doing so helps decrease the risk of certain side effects (e.g., increased uric acid).

SIDE EFFECTS: See also Warning section.

Nausea, vomiting, constipation, diarrhea, and loss of appetite may occur. In some cases, your doctor may prescribe medication to prevent or relieve nausea and vomiting. Eating several small meals, not eating before treatment, or limiting activity may help lessen some of these effects. If these effects persist or worsen, tell your doctor or pharmacist promptly.

This medication may cause your urine to turn a reddish color. This is a normal, harmless effect of the drug and should not be mistaken for blood in your urine.

Temporary hair loss is a common side effect. Normal hair growth should return after treatment has ended.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: unusual bleeding/bruising (e.g., small red spots on the skin, black/bloody stools, bloody urine, vomit that looks like coffee grounds).

Pain or sores in the mouth and throat may occur. Brush your teeth gently/carefully, avoid using mouthwash that contains alcohol, and rinse your mouth frequently with cool water mixed with baking soda or salt. It may also be best to eat soft, moist foods.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling (especially of throat/face), trouble breathing, severe dizziness.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using daunorubicin, tell your doctor or pharmacist if you are allergic to it; or to other anthracyclines (e.g., doxorubicin); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: blood/bleeding disorders (e.g., anemia, low blood cell counts), gout, heart disease (e.g., congestive heart failure, irregular heartbeat), kidney disease, liver disease, radiation treatment (especially to chest area).

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine or flu vaccine inhaled through the nose. Wash your hands well to prevent the spread of infections.

To lower your risk of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.

Before having surgery, tell your doctor or dentist that you are using this medication.

Caution is advised when using this drug in children because they may be more sensitive to the effects of the drug, especially effects on the heart.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. If you become pregnant or think you may be pregnant, tell your doctor immediately. To avoid pregnancy, both males and females using this drug should use reliable form(s) of birth control (e.g., birth control pills, condoms) during treatment. Consult your doctor for details and to discuss effective forms of birth control.

It is not known whether this drug passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other anti-cancer drugs (especially anthracyclines such as doxorubicin), cyclophosphamide.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., kidney/liver function tests, complete blood count, EKG) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor to establish a new dosing schedule. Do not double the dose to catch up.

STORAGE: Before mixing, store the dry powder in the original carton at room temperature between 59-86 degrees F (15-30 degrees C). After mixing, store at room temperature or in the refrigerator. If stored at room temperature, use/discard the mixed solution within 24 hours. If stored in the refrigerator, use/discard the mixed solution within 48 hours.

Protect all forms of this medication from light and freezing. Consult the package instructions or your pharmacist for other storage details. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.