Strength: 2mg / 5mg
Pack Size: 1 x 25
Drug Class: antineoplastic,alkylating agents
Dosage and Administration:
The usual oral dose is 6 mg (3 tablets) daily. The entire daily dose may be given at one time. The dose is adjusted, as required, on the basis of blood counts done at approximately weekly intervals. After 2 to 3 weeks of treatment, the drug should be discontinued for up to 4 weeks, during which time the blood count should be followed carefully. When the white blood cell and platelet counts are rising, a maintenance dose of 2 mg daily rimy be instituted. Because of the patient-to-patient variation in melphalan plasma levels following oral administration of the drug. several investigators have recommended that the dosage of Melphalan be cautiously escalated until some rnyelosuppression is observed in order to assure that potentially therapeutic levels of the drug have been reached.
Other dosage regimens have been used by various investigators. 0sserm an and Takatsuki have used an initial coursed 10 mg/day for 7 to 10 days. They report Mat maximal suppression of the leukocyte and platelet counts occurs within 3 to 5 weeks arid recovery within 4 to a week5. Continuous maintenance therapy with 2 mg/day is instituted when the white blood cell count is greater than 4,000 cells/mcL and the platelet count is greater than 100,000 cells/mcL. Dosage is adjusted to between land 3 mglday depending upon the hematological response. II is desirable to tni to maintain a significant degree of bone marrow depression sass to keep the leukocyte count in the range of 3,000 to 3,500 cells/mcL.
Hoogstraten et el have started treatment with 0,15 mg/kg/day for 7 days. This is followed by rest period of at least 14 days, but it may be as Icing as 5 to 6 weeks. Maintenance therapy is started when the white blood cell and platelet counts are rising. The maintenance dose is 0.05 mg/kg/day or less and readjusted according tote blood count.
Available evidence suggests that about one third to one half of the patients with multiple rnyeloma show a favorable response to oral administration of the drug.
One study by Alexanian el al has shown that the use of Melphalan in combination with prednisone significantly improves the percentage of patients with multiple myeloma who achieve palliation. One regimen has been to administer courses of Melphalan at 0.25 mg/kg/day ay for 4 consecutive days (or, 0.20 mg/kg/day for 5 consecutive days) for a total time of I mg/kg/course. These 4- to 5-day courses are then repeated every 4 to 6 weeks if the granulocyte count and the platelet count have returned to normal levels.
It is to be emphasized that response may be very gradual over many months: it is important that repeated courses or continuous therapy be given since improvement may continue slowly over many months, and the maximum benefit maybe missed if treatment is abandoned too soon.
In patients with moderate to severe renal impairment, currently available pharmacokinetic data do not justify an absolute recommendation on dosage reduction to those patients, but it may be prudent to use a reduced dose initially.
Epithelial Ovarian Cancer: One commonly employed regimen for the treatment of ovarian carcinoma has been to administer Melphalan at a dose of 0.2 mg/kg daily for 5 days as a single course. Courses are repeated every 4 to 5 weeks depending upon hematologic tolerance.
Cold Storage: yes
Melphalan is a white to cream-colored powder. It is practically insoluble in water, chloroform and ether, slightly soluble in methanol, and dissolves in dilute mineral acids.
Melphalan, also known as L-phenylalanine mustard, phenylalanine mustard. L-PAM, or L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a bifunctional alkylating agent that is active against selective human neoplastic diseases. It is known chemically as 4-[bis(2-chloroethyl) amino)-L- phenylalanine. The molecular formula C13H18Cl2N2O2 and the molecular weight is 305.20. The Chemical structure is:
Melphalan is indicated for the palliative treatment of multiple rnyeloma and advanced ovarian adenocarcinorna. Melphalan has a significant therapeutic effect in a proportion of patients suffering from advanced breast carcinoma and may be used in the treatment of policythaemia vera.
Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. When cellular proliferation in malignant tissues is greater than in most normal tissues, methotrexate may impair malignant growth without irreversible damage to normal tissues. The mechanism of action in rheumatoid arthritis is unknown; it may affect immune function. Two reports describe in vitro methotrexate inhibition of DNA precursor uptake by stimulated mononuclear cells, and another describes in animal polyarthritis partial correction by methotrexate of spleen cell hyporesponsiveness and suppressed IL 2 production. Other laboratories, however, have been unable to demonstrate similar effects. Clarification of methotrexate’s effect on immune activity and its relation to rheumatoid immunopathogenesis await further studies. In patients with rheumatoid arthritis, effects of methotrexate on articular swelling and tenderness can be seen as early as 3 to 6 weeks. Although methotrexate clearly ameliorates symptoms of inflammation (pain, swelling, stiffness), there is no evidence that it induces remission of rheumatoid arthritis nor has a beneficial effect been demonstrated on bone erosions and other radiologic changes which result in impaired joint use, functional disability, and deformity.
- Keep out of reach of children.
- Do not exceed daily recommended dose.
Melphalan Is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.
Provided the outer coating of the tablet Is intact, there is no risk in handling Melphalan tablets.
Melphalan tablets should not be divided. Do not break, crust or chew the tablets. Since Melphalan is a potent myelosuppressive agent, it is essential that careful attention should be paid to the monitoring of blood counts to avoid the possibility of excessive rnyelosuppression and the risk of irreversible bone marrow aplasia. Therefore, the following tests should be performed at the start of therapy and prior to each subsequent course of Melphalan: platelet count, haemoglobin, white blood cell count, and differential.
Thrombocytopenia and/or leucopoenia 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 or blood counts at the nadir and day of treatment should be considered. See DOSAGEANDADMINISTRATION.
Although controlled trials comparing intravenous (IV) to oral melphalan have shown more myelosuppression with the IV formulation, severe bone marrow suppression with resulting infection or bleeding fray occur Melphalan should be used with extreme caution in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy or whose marrow function is recovering horn previous cytotoxic therapy.
Renal impairment: Melphalan clearance may be reduced in patients with renal impairment, who may also haye uraemic bone marrow suppression. Dosage reduction may therefore be necessary (see Dosage and Administration), and these patients should be closely observed.
Administration Precautions: Procedures For proper handling and disposal of anticancer drugs should be considered.