Doxorubicin hydrochloride: Difference between revisions

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Revision as of 03:17, 22 December 2014

Doxorubicin hydrochloride
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]

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Black Box Warning

CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, AND SEVERE MYELOSUPPRESSION
See full prescribing information for complete Boxed Warning.
  • Cardiomyopathy: Myocardial damage, including acute left ventricular failure can occur with doxorubicin HCl. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% - 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin HCl is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess LVEF before and regularly during and after treatment with doxorubicin HCl.
  • Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin HCl.
  • Extravasation and Tissue Necrosis: Extravasation of doxorubicin HCl can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area.
  • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur.: (k)

Overview

Doxorubicin hydrochloride is an Antineoplastic and antibiotic that is FDA approved for the treatment of women with axillary lymph node involvement following resection of primary breast cancer, leukemias, lymphomas and metastasis neoplasms. There is a Black Box Warning for this drug as shown here. Common adverse reactions include alopecia, nauseas and vomiting.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Adjuvant in breast cancer

  • Dosage: 60 mg/m2 administered as an intravenous bolus on day 1 of each 21-day treatment cycle, in combination with cyclophosphamide, for a total of four cycles

Metastasic Neoplasm, Lymphomas or Leukemias

  • The recommended dose of doxorubicin HCl when used as a single agent is 60 to 75 mg/m2 intravenously every 21 days.
  • The recommended dose of doxorubicin HCl, when administered in combination with other chemotherapy drugs, is 40 to 75 mg/m2 intravenously every 21 to 28 days.
  • Consider use of the lower doxorubicin dose in the recommended dose range or longer intervals between cycles for heavily pretreated patients, elderly patients, or obese patients.
  • Cumulative doses above 550 mg/m2 are associated with an increased risk of cardiomyopathy
Doxorubicin Hydrochloride is indicated for the following metastasic neoplasms
- Metastatic Breast cancer 
- Metastatic Wilm's tumor
- Metastatic Neuroblastoma
- Metastatic Soft tissue sarcoma
- Metastatic Bone sarcomas
- Metastatic Ovarian carcinoma
- Metastatic Transitional cell bladder carcinoma 
- Metastatic Thyroid carcinoma 
- Metastatic Gastric carcinoma
- Metastatic Bronchogenic carcinoma

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Doxorubicin Hydrochloride in adult patients.

Non–Guideline-Supported Use

Adrenal Carcinoma
  • Multidrug dosage:
    • Doxorubicin 20 mg/m2 IV on days 1 and 8[1]
    • Etoposide: 100 mg/m2 IV on days 5 through 7
    • Cisplatin: 40 mg/m2 IV on days 2 and 9
Bladder Carcinoma
                                         This treatment must be applied for 3 cycles.
Endometrial Carcinoma

Used in women with stage III and IV or recurrent endometrial carcinoma.

  • Multidrug dosage:
Primary Liver Carcinoma
Malignant Tumor of Thymus
  • Multidrug Dosage:
    • Scheme 1: Neoadjuvant chemotherapy
    • Scheme 2: Treatment for recurrent or metastasic thymoma
      • Doxorubicin[5]: 50 mg/m2 - Each 21 days (8 cycles)
      • Cyclophosphamide: 500 mg/m2 - Each 21 days (8 cycles)
      • Cisplatin: 50 mg/m2 - Each 21 days (8 cycles)
    • Scheme 3: treatment for Invasive thymoma
      • Doxorubicin[6]: 40 mg/m2 - Day 1 (repeat each 3 weeks)
      • Vincristine: 0.6 mg/m2 - Day 3 (repeat each 3 weeks)
      • Cisplatin: 50 mg/m2 - Day 1 (repeat each 3 weeks)
      • Cyclophosphamide: 700 mg/m2 - Day 4 (repeat each 3 weeks)
Multiple Myeloma
Transitional Cell Carcinoma of the Urinary Tract

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Doxorubicin hydrochloride FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Doxorubicin Hydrochloride in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Doxorubicin Hydrochloride in pediatric patients.

Contraindications

Warnings

CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, AND SEVERE MYELOSUPPRESSION
See full prescribing information for complete Boxed Warning.
  • Cardiomyopathy: Myocardial damage, including acute left ventricular failure can occur with doxorubicin HCl. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% - 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin HCl is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess LVEF before and regularly during and after treatment with doxorubicin HCl.
  • Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin HCl.
  • Extravasation and Tissue Necrosis: Extravasation of doxorubicin HCl can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area.
  • Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions, hospitalization, and death may occur.: (k)
Cardiomyopathy

Doxorubicin HCl can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy is generally proportional to the cumulative exposure. Include prior doses of other anthracyclines or anthracenediones in calculations of total cumulative dosage for doxorubicin HCl. Cardiomyopathy may develop during treatment or up to several years after completion of treatment and can include decrease in LVEF and signs and symptoms of congestive heart failure (CHF). The probability of developing cardiomyopathy is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m2 of doxorubicin HCl, 3 to 5% at a dose of 400 mg/m2, 5 to 8% at a dose of 450 mg/m2, and 6 to 20% at a dose of 500 mg/m2, when doxorubicin HCl is administered every 3 weeks. There is an additive or potentially synergistic increase in the risk of cardiomyopathy in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents such as cyclophosphamide and trastuzumab. Pericarditis and myocarditis have also been reported during or following doxorubicin HCl treatment.

Assess left ventricular cardiac function (e.g., MUGA or echocardiogram) prior to initiation of doxorubicin HCl, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Increase the frequency of assessments as the cumulative dose exceeds 300 mg/m2. Use the same method of assessment of LVEF at all time points. Consider the use of dexrazoxane to reduce the incidence and severity of cardiomyopathy due to doxorubicin HCl administration in patients who have received a cumulative doxorubicin HCl dose of 300 mg/m2 and who will continue to receive doxorubicin HCl.

Arrhythmias

Doxorubicin HCl can result in arrhythmias, including life-threatening arrhythmias, during or within a few hours after doxorubicin HCl administration and at any time point during treatment. Tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia may occur. Electrocardiographic changes including non-specific ST-T wave changes, atrioventricular and bundle-branch block can also occur. These electrocardiographic changes may be transient and self-limited and may not require dose-modifications of doxorubicin HCl.

Secondary Malignancies

The risk of developing secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) is increased following treatment with doxorubicin HCl. Cumulative incidences ranged from 0.2% at five years to 1.5% at 10 years in two separate trials involving the adjuvant treatment of women with breast cancer. These leukemias generally occur within 1 to 3 years of treatment.

Extravasation and Tissue Necrosis

Extravasation of doxorubicin HCl can result in severe local tissue injury manifesting as blistering, ulceration, and necrosis requiring wide excision of the affected area and skin grafting. When given via a peripheral venous line, infuse doxorubicin over 10 minutes or less to minimize the risk of thrombosis or perivenous extravasation. If signs or symptoms of extravasation occur, immediately terminate the injection or infusion [see DOSAGE AND ADMINISTRATION (2.3)]. Extravasation may be present in patients who do not experience a stinging or burning sensation or when blood return is present on aspiration of the infusion needle. If extravasation is suspected, apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days. If appropriate, administer dexrazoxane at the site of extravasation as soon as possible and within the first 6 hours after extravasation.

Severe Myelosuppression

Doxorubicin HCl can cause myelosuppression. In Study 1, the incidence of severe myelosuppression was: grade 4 leukopenia (0.3%), grade 3 leukopenia (3%), and grade 4 thrombocytopenia (0.1%). A dose-dependent, reversible neutropenia is the predominant manifestation of hematologic toxicity from doxorubicin HCl. When doxorubicin HCl is administered every 21 days, the neutrophil count reaches its nadir 10 to 14 days after administration with recovery usually occurring by the 21st day. Obtain baseline assessment of blood counts and carefully monitor patients during treatment for possible clinical complications due to myelosuppression.

Use in Patients with Hepatic Impairment

The clearance of doxorubicin is decreased in patients with elevated serum bilirubin with an increased risk of toxicity [see USE IN SPECIFIC POPULATIONS (8.7) and CLINICAL PHARMACOLOGY (12.3)]. Reduce the dose of doxorubicin HCl in patients with serum bilirubin levels of 1.2–5.0 mg/dL [see DOSAGE AND ADMINISTRATION (2.2)]. Doxorubicin is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see CONTRAINDICATIONS (4)]. Obtain liver tests including SGOT, SGPT, alkaline phosphatase, and bilirubin prior to and during doxorubicin HCl therapy.

Tumor Lysis Syndrome

Doxorubicin HCl may induce tumor lysis syndrome in patients with rapidly growing tumors. Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome.

Radiation Sensitization and Radiation Recall

Doxorubicin HCl can increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver. Radiation recall, including but not limited to cutaneous and pulmonary toxicity, can occur in patients who receive doxorubicin HCl after prior radiation therapy.

Embryofetal Toxicity

Doxorubicin HCl can cause fetal harm when administered to a pregnant woman. Doxorubicin HCl was teratogenic and embryotoxic in rats and rabbits at doses lower than the recommended human dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus. Advise female patients of reproductive potential to use highly effective contraception during treatment with doxorubicin HCl and for 6 months after treatment. Advise patients to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking doxorubicin HCl.

Adverse Reactions

Clinical Trials Experience

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of doxorubicin HCl. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac
  • Cardiogenic shock
Cutaneous
Gastrointestinal
Hypersensitivity
Laboratory Abnormalities
Neurological
Ocular
Vascular
Other

Drug Interactions

There is limited information regarding Doxorubicin hydrochloride Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Doxorubicin hydrochloride in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Doxorubicin hydrochloride in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Doxorubicin hydrochloride during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Doxorubicin hydrochloride in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Doxorubicin hydrochloride in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Doxorubicin hydrochloride in geriatric settings.

Gender

There is no FDA guidance on the use of Doxorubicin hydrochloride with respect to specific gender populations.

Race

There is no FDA guidance on the use of Doxorubicin hydrochloride with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Doxorubicin hydrochloride in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Doxorubicin hydrochloride in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Doxorubicin hydrochloride in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Doxorubicin hydrochloride in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Doxorubicin hydrochloride Administration in the drug label.

Monitoring

There is limited information regarding Doxorubicin hydrochloride Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Doxorubicin hydrochloride and IV administrations.

Overdosage

There is limited information regarding Doxorubicin hydrochloride overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Doxorubicin hydrochloride Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Doxorubicin hydrochloride Mechanism of Action in the drug label.

Structure

There is limited information regarding Doxorubicin hydrochloride Structure in the drug label.

Pharmacodynamics

There is limited information regarding Doxorubicin hydrochloride Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Doxorubicin hydrochloride Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Doxorubicin hydrochloride Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Doxorubicin hydrochloride Clinical Studies in the drug label.

How Supplied

There is limited information regarding Doxorubicin hydrochloride How Supplied in the drug label.

Storage

There is limited information regarding Doxorubicin hydrochloride Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Doxorubicin hydrochloride Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Doxorubicin Hydrochloride interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Doxorubicin hydrochloride Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Doxorubicin hydrochloride Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Berruti A, Terzolo M, Sperone P, Pia A, Della Casa S, Gross DJ; et al. (2005). "Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial". Endocr Relat Cancer. 12 (3): 657–66. doi:10.1677/erc.1.01025. PMID 16172198.
  2. ↑ "Adjuvant Treatment in Bladder Carcinoma".
  3. ↑ Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR; et al. (2004). "Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study". J Clin Oncol. 22 (11): 2159–66. doi:10.1200/JCO.2004.07.184. PMID 15169803.
  4. ↑ Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ; et al. (2004). "Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report". Lung Cancer. 44 (3): 369–79. doi:10.1016/j.lungcan.2003.12.010. PMID 15140551.
  5. ↑ Loehrer PJ, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D; et al. (1994). "Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group". J Clin Oncol. 12 (6): 1164–8. PMID 8201378.
  6. ↑ Fornasiero A, Daniele O, Ghiotto C, Piazza M, Fiore-Donati L, Calabró F; et al. (1991). "Chemotherapy for invasive thymoma. A 13-year experience". Cancer. 68 (1): 30–3. PMID 2049749.
  7. ↑ Lee CK, Barlogie B, Munshi N, Zangari M, Fassas A, Jacobson J; et al. (2003). "DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma". J Clin Oncol. 21 (14): 2732–9. doi:10.1200/JCO.2003.01.055. PMID 12860952.
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