Names and pronunciation
(mel′fa-lan) Alkeran , Evomela
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Drug reference
(mel′fa-lan) Alkeran , Evomela
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Func. class.: Antineoplastic, alkylating agent
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Chem. class.: Nitrogen mustard
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Do not confuse: melphalan/Myleran/Leukeran
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ACTION: Responsible for cross-linking DNA strands, thereby leading to cell death; activity is not cell-cycle–phase specific
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USES: Multiple myeloma, advanced ovarian cancer
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CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity Precautions: Children, radiation ther- apy, infections, renal disease
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Black Box Warning: Bone marrow depression, secondary malignancy, ra- diation therapy, bleeding, infection, risk of serious hypersensitivity reaction; re- quires an experienced clinician Black Box Warning: Bone marrow depression: full nadir 2-3 wk; CBC, differential, platelet count weekly; notify prescriber, withhold product if WBC is <3000/mm3 or platelet count is <100,000/mm3; recovery usually oc- curs in 6 wk; IV product causes more myelosuppression • Renal studies: BUN, serum uric acid before, during therapy • I&O ratio; report fall in urine output to 30 mL/hr Black Box Warning: Infection: fever, cough, temperature, chills, sore throat; notify prescriber Black Box Warning: Secondary malig- nancy: acute leukemia, myeloprolifera- tive syndrome may occur due to chromo- some damage; risk is increased when using long-term treatment Black Box Warning: Requires an ex- perienced clinician: product should be used only by clinician knowledgeable in use of chemotherapy • Hepatotoxicity: hepatic studies be- fore, during therapy (bilirubin, AST, ALT, LDH) as needed; jaundiced skin and scle- ra, dark urine, clay-colored stools, itchy skin, abdominal pain, fever, diarrhea Black Box Warning: Bleeding: hematu- ria, guaiac, bruising or petechiae, mucosa or orifices often, no rectal temperature, IM injections if possible • Buccal cavity q8hr for dryness, sores, ulceration, white patches, oral pain, bleeding, dysphagia • Local irritation, pain, burning, discol- oration at inj site Black Box Warning: Severe allergic reaction: rash, pruritus, urticaria, purpu- ric skin lesions, itching, flushing; assess allergy to chlorambucil; cross-sensitivity may occur in 2% of patients; avoid • Hyperuricemia: Increased uric acid, joint pain, especially in extremities, provide fluids to 2L/day, may use with anti-gout medications such as al- lopurinol • Increase fluid intake to 2-3 L/day to prevent urate deposits, calculi formation • 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 Black Box Warning: Pregnancy/breast- feeding: Do not use during pregnancy or breastfeeding Black Box Warning: To report signs of infection: fever, sore throat, flulike symptoms • To report signs of anemia: fatigue, headache, faintness, SOB, irritability, nausea/vomiting, dehydration, decreased urine output • To avoid use of aspirin products, NSAIDs, alcohol • Hepatotoxicity: to report immediately yellowing of skin or eyes, dark urine, clay- colored stools, itchy skin, abdominal pain, fever, diarrhea • Pregnancy/breastfeeding: to report suspected pregnancy; to use contracep- tion during treatment
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SIDE EFFECTS GI: Nausea, vomiting, stomatitis, diar- rhea, hepatotoxicity, abdominal pain, anorexia, constipation GU: Amenorrhea, infertility HEMA: Thrombocytopenia, neutropenia, leukopenia, anemia INTEG: Pruritus, necrosis, extravasation, alopecia, rash RESP: Dyspnea, pneumonitis, broncho spasm SYST: Anaphylaxis, allergic reactions, secondary malignancies, edema CNS: Fatigue, fever, dizziness META: Hypokalemia, hypophosphatemia ENDO: Menstrual irregularities
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INTERACTIONS (IV MELPHALAN) Increase: toxicity—antineoplastics, radi- ation Increase: bleeding risk—NSAIDs, anti- coagulants, salicylates, thrombolytics, platelet inhibitors; avoid concurrent use Decrease: antibody response—live virus vaccines; bring up-to-date before use or postpone 3 mo after conclusion of treatment Increase: uric acid, HIAA Drug/Lab Test Decrease: HB, RBC, WBC, platelets False-positive: Direct Coombs’ test
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DOSAGE AND ROUTES Multiple myeloma (palliative) • Adult: PO 6 mg daily × 2-3 wk, adjust to blood counts weekly then stop for ≤4 wk or until WBC/platelets begin to rise, maintenance 2 mg/day; IV infusion 16 mg/m2 over 15-20 min q2wk × 4 doses, then q4wk, adjust to blood counts Multiple myeloma conditioning treatment before stem cell trans- plantation (Evomela only) • Adult: IV INFUSION 100 mg/m2/day over 30 min for 2 days before stem cell transplant (day 3, day 2; day 0 [trans- plant]) Epithelial ovarian carcinoma • Adult: PO 0.2 mg/kg/day × 5 days q4- 5wk; repeat q4-5wk depending on blood counts
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Available forms: Tabs 2 mg, powder for inj 50 mg
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Administer: • Antiemetic 30-60 min before product to prevent vomiting PO route • Give on empty stomach • Protect from light; store refrigerated Intermittent IV INF route • Use gloves during administration; if skin exposure occurs, wash immediately with soap and water, use cytotoxic han- dling procedures M Evomela Reconstitution: • Add 8.6 mL of 0.9% NaCl injection to the vial for a final vial concentration of 5 mg/mL • Negative pressure should be present in the vial; discard any vial that does not have a vacuum present during recon stitution • Storage after reconstitution: Store at room temperature for up to 1 hr or re- frigerated up to 24 hr IV infusion: • Dilute the appropriate dose with 0.9% NaCl to a final concentration not to ex- ceed 0.45 mg/mL • The diluted solution may be stored at room temperature for up to 4 hr (in addition to 1 hr after reconstitution) • Give over 30 min when used as con- ditioning treatment before stem cell transplant or IV over 15-20 min when used as palliative treatment in multiple myeloma • Infuse into an injection port or by in- jecting slowly into a fast-running IV infu- sion via a central venous line to avoid extravasation Alkeran/generic melphalan Reconstitution: • Using a 20-gauge or larger needle, rapidly inject 10 mL of the supplied dilu- ent into a 50-mg vial for a final concen- tration of 5 mg/mL • Immediately shake the vial until clear and all material is dissolved • Dilute the reconstituted vial immedi- ately; the solution is unstable • Do not refrigerate the reconstituted vial; a precipitate will form IV infusion: • Dilute the dose in 0.9% NaCl to a final concentration max 0.45 mg/mL • Give over 15-20 min; and complete the infusion within 60 min from vial recon- stitution • The diluted solution is unstable; about 1% of the labeled dose hydrolyzes every 10 min after dilution with sodium chloride • Infuse through a central line to avoid extravasation Y-site compatibilities: Acyclovir, amikacin, aminophylline, ampicillin, aztreonam, bleo- mycin, bumetanide, buprenorphine, butor- phanol, calcium gluconate, CARBOplatin, carmustine, ceFAZolin, cefepime, cefopera- zone, cefotaxime, cefoTEtan, cefTAZidime, ceftizoxime, cefTRIAXone, cefuroxime, cimetidine, CISplatin, clindamycin, cyclo- phosphamide, cytarabine, dacarbazine, DACTINomycin, DAUNOrubicin, dexametha- sone, diphenhydrAMINE, DOXOrubicin, doxycycline, droperidol, enalaprilat, etopo- side, famotidine, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gal- lium, ganciclovir, gentamicin, granisetron, haloperidol, heparin, hydrocortisone, hydrocortisone sodium phosphate, HYDRO- morphone, hydrOXYzine, IDArubicin, ifos- famide, imipenem-cilastatin, LORazepam, mannitol, mechlorethamine, meperidine, mesna, methotrexate, methylPREDNISolone, metoclopramide, metroNIDAZOLE, micon- azole, minocycline, mitoMYcin, mitoXAN- TRONE, morphine, nalbuphine, netilmicin, ondansetron, pentostatin, piperacillin, plica- mycin, potassium chloride, prochlorpera- zine, promethazine, raNITIdine, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, tobramycin, trimethoprim-sulfamethoxa- zole, vancomycin, vinBLAStine, vinCRIStine, vinorelbine, zidovudine
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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: • That usually sterility, amenorrhea oc- cur; reversible after discontinuing treat- ment • To avoid foods with citric acid, hot temperature, or rough texture • To report any bleeding, white spots, or ulcerations in mouth to prescriber; to examine mouth daily M
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PHARMACOKINETICS Metabolized in liver, excreted in urine, half-life 2 hr, protein binding ≤30%
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• Adult: PO 6 mg daily × 2-3 wk, adjust to blood counts weekly then stop for ≤4 wk or until WBC/platelets begin to rise, maintenance 2 mg/day; IV infusion 16 mg/m2 over 15-20 min q2wk × 4 doses, then q4wk, adjust to blood counts Multiple myeloma conditioning treatment before stem cell trans- plantation (Evomela only)
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• Adult: IV INFUSION 100 mg/m2/day over 30 min for 2 days before stem cell transplant (day 3, day 2; day 0 [trans- plant]) Epithelial ovarian carcinoma
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• Adult: PO 0.2 mg/kg/day × 5 days q4- 5wk; repeat q4-5wk depending on blood counts
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