doxorubicin hydrochloride
doxorubicin hydrochloride
Pharmacologic class: Anthracycline
Therapeutic class: Antibiotic antineoplastic
Pregnancy risk category D
FDA Box Warning
• Administer I.V. only-never I.M. or subcutaneously. Extravasation causes severe local tissue necrosis.
• Myocardial toxicity may occur during therapy or months to years afterward. Risk factors (cardiovascular disease, previous or concurrent radiotherapy to mediastinal or pericardial area, previous therapy with doxorubicin or other anthracyclines or anthracenediones, and concomitant use of other cardiotoxic drugs) may increase myocardial toxicity risk. Toxicity may occur at higher or lower cumulative doses even in patients without cardiac risk factors. Pediatric patients have increased risk of delayed cardiotoxicity.
• Secondary acute myelogenous leukemia (AML) may occur. Refractory secondary leukemia is more common when drug is given in combination with DNA-damaging antineoplastics, when patients have been heavily pretreated with cytotoxic drugs, and with dosage escalation. Pediatric patients also are at risk for secondary AML.
• Reduce dosage in hepatic impairment.
• Drug may cause severe myelosuppression.
• Give under supervision of physician experienced in cancer chemotherapy.
Action
Unclear. Thought to inhibit DNA and RNA synthesis by forming complex with DNA. Also exerts immunosuppressive activity. Cell-cycle-S-phase specific.
Availability
Injection (preservative-free): 2 mg/ml
Powder for injection: 10 mg, 20 mg, 50 mg
Indications and dosages
➣ Solid tumors, including bladder, breast, lung, stomach, and thyroid cancers; malignant lymphomas, including Hodgkin's disease; acute leukemia; chronic lymphocytic leukemia; multiple myeloma; Wilms' tumor; neuroblastoma
Adults: 60 to 75 mg/m2 I.V. as a single dose at 21-day cycles, or 30 mg/m2 I.V. as a single daily dose on first to third days of 4-week cycle, or 20 mg/m2 I.V. once weekly. Maximum cumulative dosage is 550 mg/m2.
Dosage adjustment
• Bone marrow depression
• Impaired cardiac or hepatic function
Off-label uses
• Endometrial carcinoma, islet cell carcinoma
Contraindications
• Hypersensitivity to drug
• Severe bone marrow depression
• Previous treatment with maximum cumulative doses of doxorubicin, other anthracyclines, or anthracenes
Precautions
Use cautiously in:
• cardiac disease, hepatic impairment, depressed bone marrow reserve, CNS metastases, brain tumor, malignant melanoma, renal carcinoma
• elderly patients
• females of childbearing age
• pregnant or breastfeeding patients
• children.
Administration
• Follow facility policy for handling and preparing antineoplastics.
See Don't dilute solution with bacteriostatic diluent. Don't mix with other drugs.
• Dilute as directed with normal saline solution to a final concentration of 2 mg/ml.
• Administer slowly over 3 to 5 minutes into tubing of free-flowing I.V. infusion of normal saline solution or dextrose 5% in water.
• Deliver into large vein using butterfly needle. Avoid veins over joints or extremities with compromised venous or lymphatic drainage.
See Avoid rapid infusion, because this may increase risk of acute infusion-related reactions (back pain, chest tightness, flushing).
See If extravasation occurs, stop infusion immediately, apply ice, and notify prescriber.
Adverse reactions
CNS: drowsiness, dizziness, asthenia, fatigue, malaise, paresthesia, headache, depression, insomnia, anxiety, emotional lability
CV: chest pain, hypotension, tachycardia, peripheral edema, cardiomyopathy, heart failure, arrhythmias, pericardial effusion
GI: nausea, vomiting, diarrhea, constipation, enlarged abdomen, abdominal pain, dyspepsia, oral candidiasis, moniliasis, stomatitis, glossitis, esophagitis, dysphagia
GU: albuminuria, hyperuricosuria, red urine
Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia, bone marrow depression
Metabolic: hyperglycemia, hypocalcemia
Musculoskeletal: myalgia, back pain
Respiratory: dyspnea, increased cough, pneumonia
Skin: rash, dry skin, pruritus, skin discoloration, alopecia, diaphoresis, exfoliative dermatitis, palmar-plantar erythrodysesthesia
Other: abnormal taste, infection, chills, fever, herpes zoster, injection site reactions, allergic reactions including anaphylaxis, acute infusion-associated reactions
Interactions
Drug-drug. Antineoplastics: additive bone marrow depression
Cyclophosphamide: increased risk of hemorrhagic cystitis, increased cardiotoxicity
Cyclosporine: profound and prolonged hematologic toxicity, increased risk of coma and seizures
Dactinomycin (in children): increased risk of pneumonitis
Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions
Mercaptopurine: hepatitis
Paclitaxel (if given first): reduced doxorubicin clearance, increased incidence and severity of neutropenia and stomatitis
Phenobarbital: increased clearance and decreased effects of doxorubicin
Phenytoin: decreased phenytoin blood level
Progesterone: increased incidence and severity of neutropenia and thrombocytopenia
Streptozocin: increased doxorubicin half-life
Verapamil: increased doxorubicin blood level
Drug-diagnostic tests. Alkaline phosphatase, bilirubin, glucose, prothrombin time, serum and urine uric acid: increased levels
Calcium, hemoglobin, neutrophils, platelets, white blood cells (WBCs): decreased levels
Patient monitoring
See Watch for acute life-threatening arrhythmias, which may occur during or within a few hours after administration.
See Monitor for cardiomyopathy and subsequent heart failure with chronic overdose (more common in children).
• Stay alert for erythematous streaking along vein next to injection site, which may indicate too-rapid infusion.
• Watch for nausea and vomiting. Administer antiemetics as needed.
See Check for superinfection or hemorrhage caused by persistent bone marrow depression (but expect WBC counts as low as 1,000/mm3 during therapy).
See Watch closely for infusion-related reactions and anaphylaxis.
• Monitor CBC, hepatic profile, coagulation tests, ejection fraction, and glucose, uric acid, bilirubin, and calcium blood levels.
Patient teaching
See Advise patient to promptly report irregular heartbeats, easy bruising or bleeding, or signs of hypersensitivity reaction, such as a rash.
• Caution patient to avoid people with colds, flu, or other contagious illnesses.
• Explain that drug may cause complete but reversible hair loss.
• Inform patient that drug may turn urine red for 1 or 2 days.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.