ONLINE PHARMACY find all drugs you want

Trade Names:
Alkeran
- Tablets 2 mg
- Powder for injection 50 mg

Mechanism of Action

Pharmacology

Melphalan is a bifunctional, alkylating agent of the bischloroethylamine type. Its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA. Like other bifunctional alkylating agents, it is active against resting and rapidly dividing tumor cells.

Pharmacokinetics

Absorption

C _max is 0.166 to 3,741 mcg/mL; may vary depending on absorption or metabolism.

Distribution

Vdss is 0.54 kg; protein binding is 60% to 90% (approximately 30% irreversibly bound). CSF penetration is low.

Metabolism

Melphalan undergoes hydrolysis to form monohydroxy and dihydroxy melphalan.

Elimination

The t _½ is approximately 75 min for IV and approximately 90 min for oral.

Indications and Usage

Palliative therapy of multiple myeloma (oral and IV) and non-resectable epithelial carcinoma of the ovary (oral).

Unlabeled Uses

Breast carcinoma, testicular carcinoma, bone marrow transplantation.

Contraindications

Standard considerations.

Dosage and Administration

PO 6 mg/day for 2 to 3 wk as a single daily dose. Resume therapy with 2 mg/day after a rest period at no more than 4 wk and increase dose as necessary.

PO 0.25 mg/kg/day for 4 to 7 days or 0.15 mg/kg/day for 7 days. Either regimen can be repeated at 4- to 6-wk intervals after toxicity has resolved. Continuous daily dosing may increase the risk of severe bone marrow depression and secondary malignancy.

IV 16 mg/m ² every 2 wk for 4 doses, then as tolerated every 4 wk. The dose should be decreased 50% in patients with BUN at least 30 mg/dL (or serum creatinine at least 1.5 mg/dL).

PO 0.2 mg/kg/day for 5 days every 4 to 5 wk.

PO/IV All doses should be adjusted based on hematological parameters at nadir. If WBC is at least 4,000 cells/mm ³ and platelet count is at least 100,000 cells/mm ³ , administer 100% of prior dose. If WBC is at least 3,000 cells/mm ³ and platelet count is at least 75,000 cells/mm ³ , administer 75% of prior dose. If WBC is at least 2,000 cells/mm ³ and platelet count is at least 50,000 cells/mm ³ , administer 50% of prior dose. If WBC is less than 2,000 cells/mm ³ and platelet count is at least 50,000 cells/mm ³ , no prior dose is to be given. The manufacturer recommends discontinuing drug for leukocyte count is less than 3,000/mm ³ or platelet count is less than 100,000/mm ³ .

Storage/Stability

Store tablets in refrigerator (36° to 46°F) in glass bottles. Protect from light. Store powder for oral injection at controlled room temperature (59° to 86°F). Protect from light. Do not refrigerate reconstituted solution.

Drug Interactions

Melphalan may increase the likelihood of carmustine pulmonary toxicity.

May decrease serum concentrations of melphalan.

May alter melphalan Cl, resulting in renal function impairment.

Bone marrow transplant patients receiving melphalan followed by cyclosporine had a high frequency of severe renal function impairment in 1 study.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Dermatologic

Alopecia.

Endocrine

Syndrome of inappropriate antidiuretic hormone secretion with high IV doses.

GI

Very low potential for nausea and vomiting with oral use; moderate potential for nausea and vomiting when used IV in bone marrow transplantation; diarrhea, mucositis; hepatic veno-occlusive disease after bone marrow transplantation.

Genitourinary

Ovarian and testicular suppression.

Hematologic

Bone marrow suppression, nadir at 2 to 3 wk.

Hypersensitivity

Anaphylactoid reaction (2.4% frequency) after IV administration may require stopping the infusion and giving fluids, corticosteroids, antihistamines, or pressors.

Respiratory

Pulmonary fibrosis, interstitial pneumonitis.

Miscellaneous

Increased risk of acute leukemia or myeloproliferative syndrome with high cumulative doses and long duration of therapy.

Precautions

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy in children have not been established.

Renal Function

Consider dose reduction in patients with renal function impairment receiving IV melphalan.

Fertility

Suppression of ovarian function may occur in premenopausal women, resulting in amenorrhea.

Extravasation

IV melphalan is a vesicant; extravasation can cause severe local necrosis.

Prior radiation and chemotherapy

Use with extreme caution in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy or whose marrow function is recovering from previous cytotoxic therapy.

Overdosage

Symptoms

Severe nausea; vomiting; decreased consciousness; convulsions; muscular paralysis; cholinomimetic effects; severe mucositis; stomatitis; colitis; diarrhea; hemorrhage of the GI tract.

Patient Information

• Inform patients that the major toxicities are related to myelosuppression, hypersensitivity, GI toxicity, pulmonary toxicity, infertility, and non-lymphocytic leukemia. Do not take without close medical supervision.
• Notify health care provider of unusual bleeding or bruising, fever, chills, sore throat, shortness of breath, yellow discoloration of skin or eyes, persistent cough, flank or stomach pain, joint pain, mouth sores, black tarry stools, skin rash, vasculitis, amenorrhea, nausea, vomiting, weight loss, or unusual lumps or masses.
• Contraceptive measures are recommended during therapy.