Names and pronunciation
(dox-oh-roo′bi-sin) Caelyx , Doxil, Myocet
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Drug reference
(dox-oh-roo′bi-sin) Caelyx , Doxil, Myocet
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Func. class.: Antineoplastic, antibiotic
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Chem. class.: Anthracycline glycoside
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Do not confuse: DOXOrubicin/DOXOrubicin liposomal/ DAUNOrubicin
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ACTION: Inhibits DNA synthesis primar- ily; replication is decreased by binding to DNA, which causes strand splitting; active throughout entire cell cycle; a vesicant
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USES: AIDS-related Kaposi’s sarcoma, multiple myeloma, metastatic ovarian carcinoma, multiple myeloma, refractory metastatic breast cancer
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CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity Precautions: Children, infection, leuko- penia, stomatitis, thrombocytopenia, sys- temic infections, cardiac disorders
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Black Box Warning: Cardiotoxicity, in- fusion reactions, myelosuppression, he- patic disease Black Box Warning: Care should be taken to avoid extravasation because the drug is irritating to extravascular tissue • Premedication with antiemetics is rec- ommended IV route • Reconstitution (Doxil): Dilute the ap- propriate dose, not to exceed 90 mg/250 mL D5W; do not mix with any other dilu- ent, drugs, or bacteriostatic agent; use aseptic technique; product contains no preservative or bacteriostatic agent; di- luted solution must be refrigerated and used within 24 hr • IV INFUSION (Doxil): Do not adminis- ter as a bolus injection or an undiluted solution; rapid injection can increase the risk of an infusion-related reaction • An acute infusion reaction can occur during the first infusion and is usually resolved by slowing the rate of infusion; most patients can tolerate subsequent infusions • Rate: Infuse at an initial rate of 1 mg/ min; if no infusion-related action, the rate can be increased to complete the infusion over 1 hr; do not filter • Give antiemetic 30-60 min prior to product to prevent vomiting • Use allopurinol or sodium bicarbon- ate to maintain uric acid levels, alkalini- zation of urine • Avoid mixing with other products • Increase fluid intake to 2-3 L/day to prevent urate, calculi formation • Store refrigerated for 24 hr after re- constituting Black Box Warning: Bone marrow depression: CBC, differential, platelet count weekly; withhold product if WBC is <4000/mm3 or platelet count is <75,000/ mm3; notify prescriber of these results • Renal studies: BUN; serum uric acid; urine CCr; electrolytes prior to, during therapy • I&O ratio: report fall in urine output to <30 mL/hr • Hepatotoxicity: Hepatic studies prior to, during therapy: bilirubin, AST, ALT, alka- line phosphatase as needed or monthly; check for jaundice of skin and sclera, dark urine, clay-colored stools, itchy skin, ab- dominal pain, fever, diarrhea Black Box Warning: Dysrhythmias: ECG: watch for ST-T wave changes, low QRS and T, possible dysrhythmias (sinus tachycardia, heart block, PVCs), ejection fraction prior to treatment, signs of irre- versible cardiomyopathy, can occur up to 6 mo after treatment begins • Bleeding: hematuria, guaiac, bruising, petechiae of mucosa or orifices every 8 hr • Effects of alopecia on body image; discuss feelings about body changes; al- most total alopecia is expected • Buccal cavity every 8 hr for dryness, sores, ulceration, white patches, oral pain, bleeding, dysphagia • Secondary malignancy: assess for acute myelogenous leukemia and oral cancer Black Box Warning: Extravasation: lo- cal irritation, pain, burning at injection site; a vesicant; if extravasation occurs, stop drug, restart at another site, apply ice, elevate extremity to reduce swelling; if resolution does not occur, surgical de- bridement may be required • GI symptoms: frequency of stools, cramping • Rinsing of mouth tid-qid with water, club soda; brushing of teeth bid-tid with soft brush or cotton-tipped appli- cators for stomatitis; use unwaxed den- tal floss
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SIDE EFFECTS CNS: Paresthesias, headache, depres- sion, insomnia, fatigue, fever CV: Chest pain, decreased B/P, cardiomy- opathy, heart failure, dysrhythmias, tachycardia EENT: Optic neuritis, rhinitis, pharyngi- tis, stomatitis GI: Nausea, vomiting, anorexia, mucositis, hepatotoxicity, abdominal pain HEMA: Thrombocytopenia, leukopenia, ane- mia, secondary malignancy INTEG: Rash, necrosis at injection site, dermatitis, reversible alopecia, exfoliative dermatitis, palmar-plantar erythrodysesthesia, thrombophlebitis at injection site RESP: Dyspnea, cough, respiratory infections
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INTERACTIONS Increase: life-threatening dysrhyth- mias—posaconazole, fluconazole; do not use together Increase: QT prolongation—other drugs that increase QT prolongation Increase: neutropenia, thrombocytopenia— progesterone Increase: cardiomyopathy—calcium chan nel blockers Increase: toxicity—other antineoplastics, cycloSPORINE, radiation, mercaptopurine Increase: hemorrhagic cystitis risk, car- diac toxicity—cyclophosphamide Increase: effect of—phenytoin, fosphe- nytoin Increase: DOXOrubicin effect—strepto- zocin Decrease: DOXOrubicin effect—PHENo- barbital Decrease: antibody response—live virus vaccine Decrease: antineoplastic effect—hema- topoietic progenitor cells; do not use 24 hr prior to or after treatment Decrease: clearance of DOXOrubicin— PACLitaxel Drug/Lab Test Increase: uric acid
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DOSAGE AND ROUTES Max lifetime cumulative dose 550 mg/m2; 400 mg/m2 for those who have received other cardiotoxics or mediastinal radiation Kaposi’s sarcoma • Adult: IV 20 mg/m2 every 3 wk Multiple myeloma • Adult: IV 30 mg/m2 IV infusion on day 4 every 3 wk plus bortezomib 1.3 mg/m2/ dose IV bolus on days 1, 4, 8, 11 of each cycle; give DOXOrubicin liposomal after bortezomib receipt on day 4; administer up to 8 treatment cycles or until disease pro- gression or unacceptable toxicity occurs Ovarian cancer • Adult: IV 50 mg/m2 q4wk Refractory metastatic breast cancer • Adult: IV 50 mg/m2 q4wk Hematologic toxicity in patients with ovarian cancer or HIV-related Kapo- D si’s sarcoma Grade 1 (ANC of 1500-1900/mm3, platelets ≥75,000/mm3): No dose re- duction; grade 2 (ANC of 1000-1499/ mm3, platelets ≥50,000/mm3 and <75,000/mm3: Wait until ANC ≥1500 cells/mm3 and platelets ≥75,000 cells/ mm3; redose with no dose reduction; grade 3 (ANC of 500-999/mm3, plate- lets ≥25,000/mm3 and <50,000/mm3): Wait until ANC ≥1500 cells/mm3 and platelets ≥75,000 cells/mm3; redose with no dose reduction; grade 4 (ANC <500/ mm3, platelets <25,000/mm3): Wait until ANC ≥1500 cells/mm3 and platelets ≥75,000 cells/mm3; reduce dose by 25% or continue with full dose with colony- stimulating factor
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Available forms: Liposomal dispersion for injection: 2 mg/mL
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Administer: • Use cytotoxic protocol according to agency policy • Prepared liposomal DOXOrubicin is translucent, red liposomal dispersion; visually inspect for particulate matter and discoloration prior to use • Pegylated liposomal DOXOrubicin (Doxil) is for IV INFUSION use only and should not be given IM/SUBCUT; give under the supervision of a physician who is expe- rienced in cancer chemotherapy
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Assess:
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Evaluate: • Therapeutic response: decreased tu- mor size, spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To add 2-3 L of fluids unless contra- indicated prior to and for 24-48 hr after to decrease possible hemorrhagic cystitis • To report any complaints, side effects to nurse or prescriber • That hair may be lost during treat- ment; that wig or hairpiece might make patient feel better; that new hair may be different in color, texture • To avoid foods with citric acid, hot temperature, or rough texture • To report any bleeding, white spots, ulcerations in mouth to prescriber; to examine mouth daily D • That urine, other body fluids may be red-orange for 48 hr • To avoid crowds and persons with infections when granulocyte count is low • To avoid vaccinations because reac- tions can occur; to avoid alcohol • Pregnancy/breastfeeding: that bar- rier contraceptive measures are recom- mended during therapy and for 4 mo after therapy ends; to avoid breastfeeding
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PHARMACOKINETICS Half-life 55 hr; metabolized by liver; crosses placenta; excreted in urine, bile, breast milk
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• Adult: IV 20 mg/m2 every 3 wk Multiple myeloma
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• Adult: IV 30 mg/m2 IV infusion on day 4 every 3 wk plus bortezomib 1.3 mg/m2/ dose IV bolus on days 1, 4, 8, 11 of each cycle; give DOXOrubicin liposomal after bortezomib receipt on day 4; administer up to 8 treatment cycles or until disease pro- gression or unacceptable toxicity occurs Ovarian cancer
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• Adult: IV 50 mg/m2 q4wk Refractory metastatic breast cancer
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• Adult: IV 50 mg/m2 q4wk Hematologic toxicity in patients with ovarian cancer or HIV-related Kapo- D si’s sarcoma Grade 1 (ANC of 1500-1900/mm3, platelets ≥75,000/mm3): No dose re- duction; grade 2 (ANC of 1000-1499/ mm3, platelets ≥50,000/mm3 and <75,000/mm3: Wait until ANC ≥1500 cells/mm3 and platelets ≥75,000 cells/ mm3; redose with no dose reduction; grade 3 (ANC of 500-999/mm3, plate- lets ≥25,000/mm3 and <50,000/mm3): Wait until ANC ≥1500 cells/mm3 and platelets ≥75,000 cells/mm3; redose with no dose reduction; grade 4 (ANC <500/ mm3, platelets <25,000/mm3): Wait until ANC ≥1500 cells/mm3 and platelets ≥75,000 cells/mm3; reduce dose by 25% or continue with full dose with colony- stimulating factor
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