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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
DOXOrubicin may be confused with DACTINomycin, DAUNOrubicin, DAUNOrubicin liposomal, doxacurium, doxapram, doxazosin, DOXOrubicin liposomal, epirubicin, IDArubicin, valrubicin
Adriamycin PFS® may be confused with achromycin, Aredia®, Idamycin®
Conventional formulation (Adriamycin PFS®, Adriamycin RDF®) may be confused with the liposomal formulation (Doxil®)
Use caution when selecting product for preparation and dispensing; indications, dosages and adverse event profiles differ between conventional DOXOrubicin hydrochloride solution and DOXOrubicin liposomal. Both formulations are the same concentration. As a result, serious errors have occurred.
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
ADR is an error-prone abbreviation
International issues:
Doxil® may be confused with Doxal® which is a brand name for doxepin in Finland, a brand name for doxycycline in Austria, and a brand name for pyridoxine/thiamine combination in Brazil
Rubex, a discontinued brand name for DOXOrubicin in the U.S, is a brand name for ascorbic acid in Ireland
Pronunciation
(doks oh ROO bi sin)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin's disease, malignant lymphoma, soft tissue and bone sarcomas, thyroid cancer, small cell lung cancer, breast cancer, gastric cancer, ovarian cancer, bladder cancer, neuroblastoma, and Wilms' tumor
Use: Unlabeled/Investigational
Treatment of multiple myeloma, endometrial carcinoma, uterine sarcoma, head and neck cancer, liver cancer, kidney cancer
Pregnancy Risk Factor
D
Pregnancy Considerations
Teratogenicity and embryotoxicity were observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Advise patients to avoid becoming pregnant (females) and to avoid causing pregnancy (males) during treatment. According to the National Comprehensive Cancer Network (NCCN) breast cancer guidelines, doxorubicin, if indicated, may be administered to pregnant women with breast cancer as part of a combination chemotherapy regimen, although chemotherapy should not be administered during the first trimester or after 35 weeks gestation.
Lactation
Enters breast milk/not recommended
Breast-Feeding Considerations
Doxorubicin and its metabolites are found in breast milk. Due to the potential for serious adverse reactions in the nursing infant, breast-feeding should be discontinued during treatment.
Contraindications
Hypersensitivity to doxorubicin, any component of the formulation, or to other anthracyclines or anthracenediones; recent MI, severe myocardial insufficiency, severe arrhythmia; previous therapy with high cumulative doses of doxorubicin, daunorubicin, idarubicin, or other anthracycline and anthracenediones; baseline neutrophil count <1500/mm3; severe hepatic impairment
Warnings/Precautions
Boxed warnings:
• Bone marrow suppression: See “Concerns related to adverse effects” below.
• Experienced physician: See “Other warnings/precautions” below.
• Hepatic impairment: See “Disease-related concerns” below.
• Myocardial toxicity: See “Concerns related to adverse effects” below.
• Secondary malignancy: See “Concerns related to adverse effects” below.
• Skin irritation/extravasation: See “Concerns related to adverse effects” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Bone marrow suppression: [U.S. Boxed Warning]: May cause severe myelosuppression; dose-limiting, primarily leukopenia and neutropenia.
• Myocardial toxicity: [U.S. Boxed Warning]: May cause cumulative, dose-related, myocardial toxicity (early or delayed). Cardiotoxicity is dose-limiting. Total cumulative dose should take into account previous or concomitant treatment with cardiotoxic agents or irradiation of chest. The incidence of irreversible myocardial toxicity increases as the total cumulative (lifetime) dosages approach 450-500 mg/m2. Although the risk increases with cumulative dose, irreversible cardiotoxicity may occur at any dose level. Patients with pre-existing heart disease, hypertension, concurrent administration of other antineoplastic agents, prior or concurrent chest irradiation, advanced age; and infants and children are at increased risk. Alternative administration schedules (weekly or continuous infusions) are associated with less cardiotoxicity. Baseline and periodic monitoring of ECG and LVEF (with either ECHO or MUGA scan) is recommended. Children are at increased for developing delayed cardiotoxicity.
• Secondary malignancy: [U.S. Boxed Warnings]: Secondary acute myelogenous leukemia and myelodysplastic syndrome have been reported following treatment.
• Skin irritation/extravasation: [U.S. Boxed Warning]: I.V. administration only. Potent vesicant; if extravasation occurs, severe local tissue damage leading to ulceration and necrosis, and pain may occur.
• Tumor lysis syndrome: May cause tumor lysis syndrome and hyperuricemia (in patients with rapidly growing tumors).
Disease-related concerns:
• Hepatic impairment: [U.S. Boxed Warning]: Use with caution in patients with hepatic impairment; toxicities may be increased in patients with hepatic impairment; dosage adjustment recommended. Use with caution in patients with hepatobiliary dysfunction.
Special populations:
• Pediatrics: Children are at increased risk for developing delayed cardiotoxicity; follow-up cardiac function monitoring is recommended. Doxorubicin may contribute to prepubertal growth failure in children; may also contribute to gonadal impairment (usually temporary). Radiation recall pneumonitis has been reported in children receiving concomitant dactinomycin and doxorubicin.
• Radiation recipients: Use with caution in patients who have received radiation therapy; reduce dosage in patients who are receiving radiation therapy simultaneously.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• Vaccines: Administration of live vaccines to immunosuppressed patients may be hazardous.
Adverse Reactions
Frequency not defined.
Cardiovascular:
Acute cardiotoxicity: Atrioventricular block, bradycardia, bundle branch block, ECG abnormalities, extrasystoles (atrial or ventricular), sinus tachycardia, ST-T wave changes, supraventricular tachycardia, tachyarrhythmia, ventricular tachycardia
Delayed cardiotoxicity: LVEF decreased, CHF (manifestations include ascites, cardiomegaly, dyspnea, edema, gallop rhythm, hepatomegaly, oliguria, pleural effusion, pulmonary edema, tachycardia); myocarditis, pericarditis
Central nervous system: Malaise
Dermatologic: Alopecia, itching, photosensitivity, radiation recall, rash; discoloration of saliva, sweat, or tears
Endocrine & metabolic: Amenorrhea, dehydration, infertility (may be temporary), hyperuricemia
Gastrointestinal: Abdominal pain, anorexia, colon necrosis, diarrhea, GI ulceration, mucositis, nausea, vomiting
Genitourinary: Discoloration of urine
Hematologic: Leukopenia/neutropenia (75%; nadir: 10-14 days; recovery: by day 21); thrombocytopenia and anemia
Local: Skin “flare” at injection site, urticaria
Neuromuscular & skeletal: Weakness
Postmarketing and/or case reports: Anaphylaxis, azoospermia, bilirubin increased, chills, coma (when in combination with cisplatin or vincristine), conjunctivitis, fever, gonadal impairment (children), growth failure (prepubertal), hepatitis, hyperpigmentation (nail, skin & oral mucosa), infection, keratitis, lacrimation, myelodysplastic syndrome, neutropenic fever, oligospermia, onycholysis, peripheral neurotoxicity (with intra-arterial doxorubicin), phlebosclerosis, radiation recall pneumonitis (children), secondary acute myelogenous leukemia, seizure (when in combination with cisplatin or vincristine), sepsis, shock, systemic hypersensitivity (including urticaria, pruritus, angioedema, dysphagia, and dyspnea), transaminases increased, urticaria
Metabolism/Transport Effects
Substrate (major) of CYP2D6, 3A4; Inhibits CYP2B6 (moderate), 2D6 (weak), 3A4 (weak)
Drug Interactions
Bevacizumab: May enhance the cardiotoxic effect of Antineoplastic Agents (Anthracycline). Risk C: Monitor therapy
Cardiac Glycosides: Antineoplastic Agents may decrease the absorption of Cardiac Glycosides. This may only affect digoxin tablets. Exceptions: Digitoxin. Risk C: Monitor therapy
Cardiac Glycosides: May diminish the cardiotoxic effect of Antineoplastic Agents (Anthracycline). Antineoplastic Agents (Anthracycline) may decrease the serum concentration of Cardiac Glycosides. The effects of liposomal formulations may be unique from those of the free drug, as liposomal formulation have unique drug disposition and toxicity profiles, and liposomes themselves may alter digoxin absorption/distribution. Risk C: Monitor therapy
CycloSPORINE: May decrease the metabolism of DOXOrubicin. Risk D: Consider therapy modification
CYP2B6 Substrates: CYP2B6 Inhibitors (Moderate) may decrease the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Dabigatran Etexilate: P-Glycoprotein Inducers may decrease the serum concentration of Dabigatran Etexilate. Risk C: Monitor therapy
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
P-Glycoprotein Inducers: May decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Inhibitors: May increase the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
P-Glycoprotein Substrates: P-Glycoprotein Inducers may decrease the serum concentration of P-Glycoprotein Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy
Sorafenib: May increase the serum concentration of DOXOrubicin. Risk C: Monitor therapy
Stavudine: DOXOrubicin may diminish the therapeutic effect of Stavudine. Risk D: Consider therapy modification
Taxane Derivatives: May decrease the metabolism of DOXOrubicin. Exceptions: Docetaxel. Risk D: Consider therapy modification
Taxane Derivatives: May enhance the adverse/toxic effect of Antineoplastic Agents (Anthracycline). Taxane Derivatives may increase the serum concentration of Antineoplastic Agents (Anthracycline). Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Risk D: Consider therapy modification
Trastuzumab: May enhance the cardiotoxic effect of Antineoplastic Agents (Anthracycline). Risk D: Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live virus vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Antineoplastic Agents may enhance the anticoagulant effect of Vitamin K Antagonists. Antineoplastic Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zidovudine: DOXOrubicin may enhance the adverse/toxic effect of Zidovudine. DOXOrubicin may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid St John's wort (may decrease doxorubicin levels). Avoid black cohosh, dong quai in estrogen-dependent tumors.
Storage
Store intact vials of solution under refrigeration at 2°C to 8°C. Protected from light. Store intact vials of lyophilized powder at room temperature (15°C to 30°C). Reconstituted vials are stable for 7 days at room temperature (25°C) and 15 days under refrigeration (5°C) when protected from light. Infusions are stable for 48 hours at room temperature (25°C) when protected from light. Solutions diluted in 50-1000 mL D5W or NS are stable for 48 hours at room temperature (25°C) when protected from light.
Reconstitution
Reconstitute lyophilized powder with NS to a final concentration of 2 mg/mL (may further dilute in 50-1000 mL D5W or NS for infusion). Unstable in solutions with a pH <3 or >7.
Compatibility
Stable in D5W, LR, NS.
Y-site administration: Compatible: Amifostine, aztreonam, bleomycin, chlorpromazine, cimetidine, cisplatin, cladribine, cyclophosphamide, dexamethasone sodium phosphate, diphenhydramine, droperidol, etoposide phosphate, famotidine, filgrastim, fludarabine, fluorouracil, gatifloxacin, gemcitabine, granisetron, hydromorphone, leucovorin, linezolid, lorazepam, melphalan, methotrexate, methylprednisolone sodium succinate, metoclopramide, mitomycin, morphine, ondansetron, paclitaxel, prochlorperazine edisylate, promethazine, ranitidine, sargramostim, sodium bicarbonate, teniposide, thiotepa, topotecan, vinblastine, vincristine, vinorelbine. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, ganciclovir, piperacillin/tazobactam, propofol. Variable (consult detailed reference): Furosemide, heparin.
Compatibility in syringe: Compatible: Bleomycin, cisplatin, cyclophosphamide, droperidol, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine. Incompatible: Furosemide, heparin. Variable (consult detailed reference): Fluorouracil.
Compatibility when admixed: Compatible: Dacarbazine, ondansetron, ondansetron with vincristine, paclitaxel, vinblastine. Incompatible: Aminophylline, diazepam, fluorouracil. Variable (consult detailed reference): Dacarbazine with ondansetron, etoposide with vincristine.
Mechanism of Action
Inhibition of DNA and RNA synthesis by intercalation between DNA base pairs by inhibition of topoisomerase II and by steric obstruction. Doxorubicin intercalates at points of local uncoiling of the double helix. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA. Doxorubicin is also a powerful iron chelator; the iron-doxorubicin complex can bind DNA and cell membranes and produce free radicals that immediately cleave the DNA and cell membranes.
Pharmacodynamics/Kinetics
Absorption: Oral: Poor (<50%)
Distribution: Vd: 809-1214 L/m2; to many body tissues, particularly liver, spleen, kidney, lung, heart; does not distribute into the CNS; crosses placenta
Protein binding, plasma: 70% to 76%
Metabolism: Primarily hepatic to doxorubicinol (active), then to inactive aglycones, conjugated sulfates, and glucuronides
Half-life elimination:
Distribution: 5-10 minutes
Elimination: Doxorubicin: 1-3 hours; Metabolites: 3-3.5 hours
Terminal: 17-48 hours
Male: 54 hours; Female: 35 hours
Excretion: Feces (~40% to 50% as unchanged drug); urine (~5% to 12% as unchanged drug and metabolites)
Clearance: Male: 113 L/hour; Female: 44 L/hour
Dosage
I.V.: Refer to individual protocols. Note: Lower dosage should be considered for patients with inadequate marrow reserve (due to old age, prior treatment or neoplastic marrow infiltration)
Children:
35-75 mg/m2/dose every 21 days or
20-30 mg/m2/dose once weekly or
60-90 mg/m2/dose given as a continuous infusion over 96 hours every 3-4 weeks
Adults: Usual or typical dose: 60-75 mg/m2/dose every 21 days or
60 mg/m2/dose every 2 weeks (dose dense) or
40-60 mg/m2/dose every 3-4 weeks or
20-30 mg/m2/day for 2-3 days every 4 weeks or
20 mg/m2/dose once weekly
Dosing adjustment in toxicity: The following delays and/or dose reductions have been used:
Neutropenic fever/infection: Consider reducing to 75% of dose in subsequent cycles
ANC <1000/mm3: Delay treatment until ANC recovers to ?1000/mm3
Platelets <100,000/mm3: Delay treatment until platelets recover to ?100,000/mm3
Dosing adjustment in renal impairment:
Adjustments are not required.
Hemodialysis: Supplemental dose is not necessary.
Dosing adjustment in hepatic impairment:
The FDA-approved labeling recommends the following adjustments:
Serum bilirubin 1.2-3 mg/dL: Administer 50% of dose
Serum bilirubin 3.1-5 mg/dL: Administer 25% of dose
Severe hepatic impairment: Use is contraindicated
The following guidelines have been used by some clinicians: Floyd, 2006:
Transaminases 2-3 times ULN: Administer 75% of dose
Transaminases >3 times ULN or serum bilirubin 1.2-3 mg/dL: Administer 50% of dose
Serum bilirubin 3.1-5 mg/dL: Administer 25% of dose
Serum bilirubin >5 mg/dL: Do not administer
Dosage: Combination Regimens
Bladder cancer:
CAP
CISCA
M-VAC (Bladder Cancer)
Breast cancer:
AT
AC
AC/Paclitaxel (Sequential)
AC-Paclitaxel-Trastuzumab
CAF
Dox-CMF (Sequential)
FAC
MVAC (Breast Cancer)
TAC
VATH
VD
Cervical cancer: MVAC (Cervical Cancer)
Endometrial cancer:
AP
MVAC (Endometrial Cancer)
Gastric cancer:
EAP
FAM
FAMe
FAP
FAMTX
Gestational trophoblastic tumor:
CHAMOCA (Modified Bagshawe Regimen)
CHAMOMA (Bagshawe Regimen)
Head and Neck cancer: MVAC (Head and Neck Cancer)
Hepatoblastoma:
IPA
PA-CI
Leukemia, acute lymphocytic:
Hyper-CVAD + Imatinib
Hyper-CVAD (Leukemia, Acute Lymphocytic)
VAD/CVAD
Lung cancer (small cell): CAVE
Lymphoma, Hodgkin's:
ABVD
BEACOPP
CAD/MOPP/ABV
Etoposide-Vinblastine-Doxorubicin (Hodgkin's)
MOPP/ABV Hybrid
MOPP/ABVD
OPA
OPPA
Stanford V Regimen
Lymphoma, non-Hodgkin's:
CHOP
CODOX-M/IVAC
COP-BLAM
EPOCH Dose-Adjusted (AIDS-Related Lymphoma)
EPOCH Dose-Adjusted (NHL)
EPOCH (Dose-Adjusted)-Rituximab (NHL)
EPOCH (NHL)
EPOCH-Rituximab (NHL)
Hyper-CVAD (Lymphoma, non-Hodgkin's)
MACOP-B
m-BACOD
Pro-MACE-CytaBOM
Rituximab-CHOP
Lymphoma, non-Hodgkin's (Burkitt's): CODOX-M/IVAC
Lymphoma, non-Hodgkin's (Mantle cell): Hyper-CVAD + Rituximab
Multiple Myeloma:
Bortezomib-Doxorubicin-Dexamethasone
DTPACE
Hyper-CVAD (Multiple Myeloma)
VAD
VBAP
VCAP
Neuroblastoma:
CAV-P/VP
CCDDT (Neuroblastoma)
CE-CAdO
HIPE-IVAD
N4SE Protocol
N6 Protocol
OPEC-D
PE-CAdO
Regimen A1
Regimen A2
Osteosarcoma:
MTX-CDDPAdr
POG-8651
Ovarian cancer: PAC (CAP)
Pancreatic cancer: FAM
Prostate cancer:
Doxorubicin + Ketoconazole
Doxorubicin + Ketoconazole/Estramustine + Vinblastine
Retinoblastoma: CCCDE (Retinoblastoma)
Sarcoma:
CYVADIC
VAC Alternating With IE (Ewing's Sarcoma)
Sarcoma, soft tissue:
AD
AI
MAID
Wilms' tumor:
AAV (DD)
AVD
VDA-C (Wilms' Tumor)
Administration: I.V.
Vesicant. I.V. push over at least 3-5 minutes or IVPB over 15-60 minutes. Infusion via central venous line recommended.
Administration: I.V. Detail
May be further diluted in either NS of D5W for I.V. administration. Avoid extravasation associated with severe ulceration and soft tissue necrosis. Flush with 5-10 mL of I.V. solution before and after drug administration. Incompatible with heparin. Monitor for local erythematous streaking along vein and/or facial flushing (may indicate rapid infusion rate).
pH: 3.8-6.5 (lyophilized doxorubicin HCl reconstituted with sodium chloride 0.9%); 2.5-4.5 (adjusted solution)
Monitoring Parameters
CBC with differential and platelet count; liver function tests (bilirubin, ALT/AST, alkaline phosphatase); serum uric acid, calcium, potassium, phosphate and creatinine; cardiac function (baseline, periodic, and followup): ECG, left ventricular ejection fraction (echocardiography [ECHO] or multigated radionuclide angiography [MUGA])
Patient Education
Do not take any new medication during therapy unless approved by prescriber. This medication can only be administered intravenously. Report immediately any swelling, pain, burning, or redness at infusion site. Maintain adequate nutrition (small, frequent meals may help). You will be more susceptible to infection (avoid crowds and exposure to infection and do not have any vaccinations without consulting prescriber). May cause nausea or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); diarrhea; loss of hair (reversible); or darker yellow urine (normal). Report immediately chest pain, swelling of extremities, respiratory difficulty, palpitations, or rapid heartbeat. Report unresolved nausea, vomiting, or diarrhea; alterations in urinary pattern (increased or decreased); opportunistic infection (fever, chills, unusual bruising or bleeding fatigue, purulent vaginal discharge, unhealed mouth sores); abdominal pain or blood in stools; excessive fatigue; or yellowing of eyes or skin. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant while taking this medication or for 1 month following therapy. Consult prescriber for appropriate barrier contraceptives. Do not breast-feed.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Stomatitis and mucositis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Myelosuppression is common; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (eg, potential to reduce or increase levels/effects of doxorubicin). See Administration infusion specifics. Premedication with antiemetic is recommended (especially with larger doses). Infusion site must be closely monitored; extravasation can cause sloughing or tissue necrosis (do not apply heat or sodium bicarbonate). Assess results of laboratory tests and patient response prior to each treatment and on a regular basis throughout therapy. Teach patient possible side effects/appropriate interventions (eg, importance of adequate hydration) and adverse symptoms to report.
Oncology: Emetic Potential
Moderate (30% to 90%)
Oncology: Vesicant
Yes; see Management of Drug Extravasations.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as hydrochloride: 10 mg, 50 mg
Adriamycin®: 10 mg, 20 mg, 50 mg, [contains lactose]
Injection, solution, as hydrochloride: 2 mg/mL (5 mL, 10 mL, 25 mL, 100 mL)
Adriamycin®: 2 mg/mL (5 mL, 10 mL, 25 mL, 100 mL)
References
Berg SL, Grisell DL, DeLaney TF, et al, “Principles of Treatment of Pediatric Solid Tumors,” Pediatr Clin North Am, 1991, 38(2):249-67.
Brown JR and Iman SH, “Recent Studies on Doxorubicin and Its Analogues,” Prog Med Chem, 1984, 21:169-236.
Cummings J and Smyth JF, “Pharmacology of Adriamycin: The Message to the Clinician,” Eur J Cancer Clin Oncol, 1988, 24(4):579-82.
Curran CF, “Acute Doxorubicin Overdoses,” Ann Intern Med, 1991, 115(11):913-4.
Curran CF and Luce JK, “Accidental Acute Exposure to Doxorubicin,” Cancer Nurs, 1989, 12(6):329-31.
Davis HL and Davis TE, “Daunorubicin and Adriamycin in Cancer Treatment: An Analysis of Their Roles and Limitations,” Cancer Treat Rep, 1979, 63(5):809-15.
Floyd J, Mirza I, Sachs B, et al, “Hepatotoxicity of Chemotherapy,” Semin Oncol, 2006, 33(1):50-67.
Floyd JD, Nguyen DT, Lobins RL, et al, “Cardiotoxicity of Cancer Therapy,” J Clin Oncol, 2005, 23(30):7685-96.
Gordon KB, Tajuddin A, Guitart J, et al, “Hand-Foot Syndrome Associated With Liposome-Encapsulated Doxorubicin Therapy,” Cancer, 1995, 75(8):2169-73.
Ishii E, Hara T, Ohkubo K, et al, “Treatment of Childhood Acute Lymphoblastic Leukemia With Intermediate Dose Cytosine Arabinoside and Adriamycin,” Med Pediatr Oncol, 1986, 14(2):73-7.
King PD and Perry MC, “Hepatotoxicity of Chemotherapy,” Oncologist, 2001, 6(2):162-76.
Lauvin R, Miglianico L, and Hellegouarc'h R, “Skin Cancer Occurring 10 Years After the Extravasation of Doxorubicin,” N Engl J Med, 1995, 332(11):754.
Legha SS, Benjamin RS, Mackay B, et al, “Reduction of Doxorubicin Cardiotoxicity by Prolonged Continuous Intravenous Infusion,” Ann Intern Med, 1982, 96(2):133-9.
Namer M, “Anthracyclines in the Adjuvant Treatment of Breast Cancer,” Drugs, 1993, 45(Suppl 2):4-9.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Breast Cancer,” Version 1.2008. Available at http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf.
Seifert CF, Nesser ME, and Thompson DF, “Dexrazoxane in the Prevention of Doxorubicin-Induced Cardiotoxicity,” Ann Pharmacother, 1994, 28(9):1063-72.
Speth PA, van Hoesel QG, and Haanen C, “Clinical Pharmacokinetics of Doxorubicin,” Clin Pharmacokinet, 1988, 15(1):15-31.
Speyer JL, Green MD, Kramer E, et al, “Protective Effect of the Bispiperazinedione ICRF-187 Against Doxorubicin-Induced Cardiac Toxicity in Women With Advanced Breast Cancer,” N Engl J Med, 1988, 319(12):745-52.
Zimmerman S, Adkins D, Graham M, et al, “Irreversible, Severe, Congestive Cardiomyopathy Occurring in Association With Interferon Alpha Therapy,” Cancer Biother, 1994, 9(4):291-9.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2009
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