Alkeran

Name: Alkeran

About melphalan tablets

Type of medicineAn alkylating chemotherapy medicine
Used forMultiple myeloma; polycythaemia vera
Available asTablets

Melphalan is used to treat some cancers and conditions where cells in the body rapidly divide and multiply. It is most commonly prescribed for conditions such as multiple myeloma and polycythaemia vera. Multiple myeloma is a cancer of the bone marrow. Polycythaemia vera is a bone marrow disease that leads to an abnormal increase in the number of red blood cells in the body. It makes your blood 'thicker' and can make you feel dizzy and short of breath.

In these conditions, certain cells in the body grow and multiply too fast. Melphalan works by preventing cells from multiplying. This reduces the number of cancer cells or unwanted blood cells.

Indications

ALKERAN (melphalan) Tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.

Overdose

Overdoses, including doses up to 50 mg/day for 16 days, have been reported. Immediate effects are likely to be vomiting, ulceration of the mouth, diarrhea, and hemorrhage of the gastrointestinal tract. The principal toxic effect is bone marrow suppression. Hematologic parameters should be closely followed for 3 to 6 weeks. An uncontrolled study suggests that administration of autologous bone marrow or hematopoietic growth factors (i.e., sargramostim, filgrastim) may shorten the period of pancytopenia. General supportive measures, together with appropriate blood transfusions and antibiotics, should be instituted as deemed necessary by the physician. This drug is not removed from plasma to any significant degree by hemodialysis.

Patient information

Patients should be informed that the major toxicities of ALKERAN (melphalan) are related to bone marrow suppression, hypersensitivity reactions, gastrointestinal toxicity, and pulmonary toxicity. The major long-term toxicities are related to infertility and secondary malignancies. Patients should never be allowed to take the drug without close medical supervision and should be advised to consult their physician if they experience skin rash, vasculitis, bleeding, fever, persistent cough, nausea, vomiting, amenorrhea, weight loss, or unusual lumps/masses. Women of childbearing potential should be advised to avoid becoming pregnant.

Side Effects of Alkeran

Common side effects of Alkeran include the following:

  • nausea
  • vomiting
  • diarrhea
  • mouth ulcers

This is not a complete list of Alkeran side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Interactions for Alkeran

Specific Drugs

Drug

Interaction

Comments

Carmustine

Possible reduced threshold for carmustine-induced pulmonary toxicity with IV melphalan106 119 c

Cimetidine

Possible reduced serum melphalan concentrations secondary to cimetidine-induced inhibition of GI absorption of melphalan 109

Monitor for decreased melphalan activity109

Cisplatin

Possible decreased clearance of melphalan secondary to cisplatin-induced renal impairment106 119 c

Cyclosporine

Possible increased risk of cyclosporine-induced nephrotoxicity107 112 c

Monitor renal function107 112 c

Consider reducing cyclosporine dosage in patients receiving high-dose melphalan112

Interferon alfa

Interferon alfa-induced fever may increase plasma elimination of melphalan110 111

Nalidixic acid

Possible increased incidence of severe hemorrhagic necrotic enterocolitis in pediatric patients106 119 c

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Melphalan

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

2 mg

Alkeran (scored)

Celgene

Melphalan Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

50 mg (of melphalan)

Alkeran

Celgene

Contraindications

Melphalan should not be used in patients whose disease has demonstrated prior resistance to this agent. Patients who have demonstrated hypersensitivity to melphalan should not be given the drug.

Warnings

Alkeran for Injection may cause local tissue damage should extravasation occur, and consequently it should not be administered by direct injection into a peripheral vein. It is recommended that Alkeran for Injection be administered by injecting slowly into a fast-running IV infusion via an injection port, or via a central venous line (see DOSAGE AND ADMINISTRATION: Administration Precautions).

Melphalan should be administered in carefully adjusted dosage by or under the supervision of experienced physicians who are familiar with the drug's actions and the possible complications of its use.

As with other nitrogen mustard drugs, excessive dosage will produce marked bone marrow suppression. Bone marrow suppression is the most significant toxicity associated with Alkeran for Injection in most patients. Therefore, the following tests should be performed at the start of therapy and prior to each subsequent dose of Alkeran: platelet count, hemoglobin, white blood cell count, and differential. Thrombocytopenia and/or leukopenia are indications to withhold further therapy until the blood counts have sufficiently recovered. Frequent blood counts are essential to determine optimal dosage and to avoid toxicity. Dose adjustment on the basis of blood counts at the nadir and day of treatment should be considered.

Hypersensitivity reactions including anaphylaxis have occurred in approximately 2% of patients who received the IV formulation (see ADVERSE REACTIONS). These reactions usually occur after multiple courses of treatment. Treatment is symptomatic. The infusion should be terminated immediately, followed by the administration of volume expanders, pressor agents, corticosteroids, or antihistamines at the discretion of the physician. If a hypersensitivity reaction occurs, IV or oral melphalan should not be readministered since hypersensitivity reactions have also been reported with oral melphalan.

Carcinogenesis

Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating agents (including melphalan). Some patients also received other chemotherapeutic agents or radiation therapy. Precise quantitation of the risk of acute leukemia, myeloproliferative syndrome, or carcinoma is not possible. Published reports of leukemia in patients who have received melphalan (and other alkylating agents) suggest that the risk of leukemogenesis increases with chronicity of treatment and with cumulative dose. In one study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral melphalan therapy was 19.5% for cumulative doses ranging from 730 to 9,652 mg. In this same study, as well as in an additional study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral melphalan therapy was less than 2% for cumulative doses under 600 mg. This does not mean that there is a cumulative dose below which there is no risk of the induction of secondary malignancy. The potential benefits from melphalan therapy must be weighed on an individual basis against the possible risk of the induction of a second malignancy.

Adequate and well-controlled carcinogenicity studies have not been conducted in animals. However, intraperitoneal (IP) administration of melphalan in rats (5.4 to 10.8 mg/m2) and in mice (2.25 to 4.5 mg/m2) 3 times per week for 6 months followed by 12 months post-dose observation produced peritoneal sarcoma and lung tumors, respectively.

Mutagenesis

Melphalan has been shown to cause chromatid or chromosome damage in humans. Intramuscular administration of melphalan at 6 and 60 mg/m2 produced structural aberrations of the chromatid and chromosomes in bone marrow cells of Wistar rats.

Impairment of Fertility

Melphalan causes suppression of ovarian function in premenopausal women, resulting in amenorrhea in a significant number of patients. Reversible and irreversible testicular suppression have also been reported.

Pregnancy

Pregnancy Category D. Melphalan may cause fetal harm when administered to a pregnant woman. While adequate animal studies have not been conducted with IV melphalan, oral (6 to 18 mg/m2/day for 10 days) and IP (18 mg/m2) administration in rats was embryolethal and teratogenic. Malformations resulting from melphalan included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, as well as hepatocele (exomphaly). There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

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