DOXOrubicin hydrochloride (redirected from Myocet)

DOXOrubicin hydrochloride

[dok′səro̅o̅′bisin]

an anthracycline antibiotic.

indications It is prescribed in the treatment of a wide variety of malignant neoplastic diseases, including leukemias, lymphomas, sarcomas, germ cell tumors, and carcinomas (e.g., lung, breast, prostate, ovary).

contraindications Myelosuppression, heart disease, concurrent administration of DAUNOrubicin, or known hypersensitivity to this drug prohibits its use.

adverse effects Among the more serious adverse reactions are myelosuppression and cardiomyopathy. Stomatitis, GI disturbances, and alopecia commonly occur.

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doxorubicin hydrochloride Warning - Hazardous drug!

Adriamycin PFS, Adriamycin RDF, Rubex

Pharmacologic class: Anthracycline

Therapeutic class: Antibiotic antineoplastic

Pregnancy risk category D

FDA Boxed 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, 100 mg, 150 mg

⊘Indications and dosages

➣ Solid tumors, including bladder, breast, lung, stomach, and thyroid cancers; malignant lymphomas, including Hodgkin's disease; acute leukemia; 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
• Chronic lymphocytic leukemia
• Multiple myeloma

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.
☞ 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.
☞ Avoid rapid infusion, because this may increase risk of acute infusion-related reactions (back pain, chest tightness, flushing).
☞ If extravasation occurs, stop infusion immediately, apply ice, and notify prescriber.

Route	Onset	Peak	Duration
I.V.	Rapid	2 hr	24-36 days

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

☞ Watch for acute life-threatening arrhythmias, which may occur during or within a few hours after administration.
☞ 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.
☞ Check for superinfection or hemorrhage caused by persistent bone marrow depression (but expect WBC counts as low as 1,000/mm³ during therapy).
☞ Watch closely for infusion-related reactions and anaphylaxis.
• Monitor CBC, hepatic profile, coagulation tests, ejection fraction, and glucose, uric acid, and calcium blood levels.

Patient teaching

☞ 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.

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doxorubicin hydrochloride, liposomal Warning - Hazardous drug!

Caelyx (CA) (UK), Doxil, Myocet (UK)

Pharmacologic class: Anthracycline

Therapeutic class: Antibiotic antineoplastic

Pregnancy risk category D

FDA Boxed Warning

• Drug may cause cardiotoxicity. Myocardial damage may lead to heart failure and may occur as total cumulative dose (which includes previous use of other anthracyclines or anthracenediones) approaches 550 mg/m2. Toxicity may occur at lower cumulative doses in patients who have had previous mediastinal irradiation or are receiving concurrent cyclophosphamides.
• Acute infusion-related reactions occur in up to 10% of patients. They usually resolve over several hours to 1 day after infusion ends; in some patients, they resolve with slower infusion rate. Serious and sometimes life-threatening allergic or anaphylactoid-like infusion reactions may occur. Keep emergency equipment and drugs to treat reaction available for immediate use.
• Drug may cause severe myelosuppression.
• Reduce dosage in hepatic impairment.
• Accidental substitution of liposomal form for doxorubicin hydrochloride may cause severe adverse effects. Don't substitute on mg-per-mg basis.

Action

Unclear. Thought to inhibit DNA and RNA synthesis by forming complex with DNA. Also exerts immunosuppressive activity. Liposomal encapsulation increases uptake by tumors, prolongs drug action, and may decrease toxicity. Cell-cycle-S-phase specific.

Availability

Liposomal dispersion for injection: 20 mg/10 ml in 10-ml vials

⊘Indications and dosages

➣ AIDS-related Kaposi's sarcoma

Adults: 20 mg/m² I.V. over 30 minutes once q 3 weeks

➣ Metastatic ovarian carcinoma

Adults: Initially, 50 mg/m² I.V. at a rate of 1 mg/minute q 4 weeks for at least four courses. If no adverse reactions occur, increase infusion rate to complete the infusion over 1 hour.

Dosage adjustment

• Hepatic impairment

Contraindications

• Hypersensitivity to drug
• Malignant melanoma
• CNS metastases
• Bone marrow depression
• Cardiac disease
• Breastfeeding

Precautions

Use cautiously in:
• hepatic impairment, brain tumor, renal carcinoma
• elderly patients
• females of childbearing age
• pregnant patients
• children.

Administration

• Follow facility policy for handling and preparing antineoplastics.
• Dilute dose (up to 90 mg) in 250 ml of dextrose 5% in water. Don't use any other diluent.
☞ Don't dilute solution with bacteriostatic diluent. Don't mix with other drugs.
• Don't use in-line filter.
• Administer slowly by I.V. infusion. Don't give as I.V. bolus.
☞ Avoid rapid infusion, which may increase the risk of infusion-related reactions (back pain, chest tightness, flushing).
☞ If extravasation occurs, stop infusion immediately, apply ice, and notify prescriber.
• Don't give I.M. or subcutaneously.
• Know that drug is a translucent red dispersion, not a clear solution.

Route	Onset	Peak	Duration
I.V.	10 days	14 days	21-24 days

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, abdominal pain, enlarged abdomen, dyspepsia, moniliasis, stomatitis, glossitis, oral candidiasis, esophagitis, dysphagia

GU: albuminuria, red urine

Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia, bone marrow depression

Hepatic: jaundice

Metabolic: hypocalcemia, hyperglycemia

Musculoskeletal: myalgia, back pain

Respiratory: dyspnea, increased cough, pneumonia

Skin: rash, dry skin, pruritus, skin discoloration, alopecia, diaphoresis, exfoliative dermatitis, palmar-plantar erythrodysesthesia

Other: altered taste, fever, chills, infection, herpes zoster, injection site reactions, allergic reactions including anaphylaxis, acute infusion reaction

Interactions

Drug-drug. Antineoplastics: additive bone marrow depression

Cyclophosphamide: increased risk of hemorrhagic cystitis

Cyclosporine: profound and prolonged hematologic toxicity, increased risk of coma and seizures, increased cardiotoxicity

Dactinomycin (in children): increased risk of pneumonitis

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Mercaptopurine: hepatitis

Paclitaxel (if administered 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 risk and severity of neutropenia and thrombocytopenia

Streptozocin: prolonged 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: decreased levels

Patient monitoring

☞ Observe patient closely for anaphylaxis and bleeding problems.
☞ Stay alert for acute life-threatening arrhythmias, which may occur during or within a few hours after administration.
☞ Assess for cardiomyopathy and subsequent heart failure with chronic overdose (more common in children).
☞ Monitor closely for acute infusion reaction.
• Assess for and report liver engorgement and yellowing of skin or eyes.
• Check CBC, coagulation tests, hepatic profile, and bilirubin, glucose, calcium and uric acid levels.
• Watch for nausea and vomiting. Give antiemetics, as needed and prescribed.
• Assess for constipation and give fluids and stool softeners, as needed and prescribed.

Patient teaching

☞ Instruct patient to immediately report shortness of breath, rash, chest pain, or palpitations.
• Advise patient to avoid people with colds, flu, or other contagious illnesses.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.