Jan 24, 2020 melphalan is practically insoluble in water and has a pka 1 of 2. Renal impairment crcl mlmin melphalan dose 50 100% 3050 2reduce dose to 140mgm dosing in obesity defined as body mass index 30kgm2 consider dosing patients using actual body weight. The bsa dosing resulted in a wide range of melphalan. Oct 22, 2009 as renal excretion is an important elimination pathway for melphalan 7, 8, an effect of creatinine clearance on melphalan total and unbound clearance can be expected. Autologous stem cell transplant using low dose melphalan 140mgm2 as. Cisplatin may affect melphalan kinetics by inducing renal dysfunction and subsequently altering melphalan clearance. Trivalent forms of arsenic are methylated in humans and mostly excreted in urine. Although the contribution of renal elimination to melphalan clearance appears to be low, one study noted an increase in the occurrence of severe leukopenia in patients with elevated bun after 10 weeks of therapy. Adult drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in. Toxicity in standard melphalanprednisone therapy among myeloma. Allopurinol 300 mg a day po can be considered for those with a high disease burden. The racemic dl form is known as merphalan or sarcolysin. Patients with renal impairment are at risk for uremic marrow. The rate of severe leukopenia in the iv arm in the patients with bun over 30 mgdl decreased from 50% 816 before protocol amendment to 11%328 p.
A novel classification of ckd, based on crcl, has been recently produced table 2. Patients with renal impairment are treated on protocol b. Melphalan will be given as a single dose not split over 2 or more days and given on day1. Part of the cancer treatment and research book series ctar, volume 112. Melphalan alkylates dna at the n7 position of guanine and induces dna interstrand crosslinkages, resulting in the inhibition of dna and rna synthesis and cytotoxicity against both dividing and nondividing tumor cells.
Alkeran for injection melphalan hydrochloride dose. Melphalan is used to treat multiple myeloma a type of blood cancer and cancer of the ovary. Melphalan pharmacokinetics in children with malignant disease. Melphalan is used to treat multiple myeloma a type of.
Melphalan intravenous route side effects mayo clinic. One child with impaired renal function was given a reduced melphalan dose of 100 mg m. Fludarabine 20%25% dose reduction in the setting of mildtomoderate renal impairment. High dose melphalan 140 mgm2 and autologous stemcell. A randomized study comparing cyclic oral mp and continuous oral melphalan in newly diagnosed multiple myeloma concluded that response rates were better with mp than with continuous oral melphalan 45% vs 31%, p dosing in detail and conclude with a brief overview of current. Melphalan hydrochloride for injection is supplied as a sterile, nonpyrogenic, freezedried powder. A randomized trial compared prednisone plus iv melphalan to prednisone plus oral 62 melphalan in the treatment of myeloma. Stem cell infusion will occur on day 0 and will be at least 20 hours after the infusion of melphalan. Dr karthik ramasamy this is a controlled document and therefore must not be changed high dose melphalan for autograft.
Continuous oral lowdose melphalan as a single drug regimen has been used previously in multiple myeloma. Dosage adjustment for cytotoxics in renal impairment. Melphalan is also used to treat a certain type of ovarian cancer cancer that begins in the female reproductive organs where eggs are formed. Melphalan ch18cl2n2o2 cid 460612 structure, chemical names, physical and. Melphalan most often is used with prednisone to treat multiple myeloma. Renal impairment crcl mlmin melphalan dose 50 100% 3050 2reduce dose to 140mgm dose may be split over 2 days hepatic impairment there are no dose recommendations for melphalan in hepatic impairment. May 21, 2019 plasma melphalan levels are highly variable after oral dosing, both with respect to the time of the first appearance of melphalan in plasma range approximately 0 to 6 hours and to the peak plasma concentration cmax range 70 to 4,000 ngml, depending upon the dose achieved.
Although not all of these side effects may occur, if they do occur they may need medical attention. Auto transplant high dose melphalan vs high dose melphalan. Other dosing regimens in combination therapy unlabeled. Possibility of delayed myelosuppression that can last 46 wk. Avoid contact with people who have infections that may spread to others such as chickenpox, measles, flu. Read the patient information leaflet if available from your pharmacist before you start using melphalan and each time you receive. The level of renal function below which the dose of a drug must be reduced depends largely on the extent of renal metabolism and elimination, and on the drugs toxicity. Renal impairment is a common complication of multiple myeloma mm.
Melphalan is a cancer medication that interferes with the growth and spread of cancer cells in the body. Potential covariates included demographics, pretransplant serum albumin and renal and liver function tests, and mgkg melphalan dose received. Melphalan injection, at high intravenous dosage, is indicated, with or without haematopoietic stem cell transplantation, for the treatment of multiple myeloma and childhood neuroblastoma. Melphalan 50 mg powder and solvent for solution for injection. Acute renal insufficiency after highdose melphalan in. Renal impairment in patients with multiple myeloma. Melphalan inhibits dna and rna synthesis via formation of interstrand cross links with dna, likely binding at the n. Osserman and takatsuki have used an initial course of 10 mgday for 7 to 10 days. Lowdose continuous oral melphalan for the treatment of. How melphalan works, side effects, interactions and. The information on dosage adjustments in renal impairment given in this book is based on. Table refers to intravenous iv dosing except where specified. Dosing will be based on body surface area calculated using actual body weight stem cell infusion.
Pediatric drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in psychiatry. Dosing will be based on body surface area calculated using actual body weight. Efficacy and safety of melphalan 140mgm2 conditioned autologous stem cell transplantation in elderly predialysis and dialysis patients with multiple myeloma. Document in medical notes all the information that has been given. Melphalan is both secreted and reabsorbed in the renal tubules. Melphalan side effects, dosage, interactions drugs. Dose reduction is needed if there is renal impairment or if the patient is. Melphalan injection, at conventional intravenous dosage, is indicated in the treatment of multiple myeloma and ovarian cancer.
Melphalan 50 mg intravenous solution alkylating agents webmd. Melphalan 50 mg powder and solvent for solution for. Highdose melphalan and stem cell transplantation in. The 5year overall survival was 54% and associated with achievement of complete hematologic response after hdmsct. As discussed below, overall response rates at week 22 were. Clinical pharmacology of melphalan and its implications for clinical. Melphalan, a bifunctional nitrogen mustardderivative alkylating agent, is the lisomer of mechlorethamine. A randomized trial compared prednisone plus iv melphalan to prednisone plus oral melphalan in the treatment of myeloma. Acute renal insufficiency after high dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation nelson leung, jeff m.
Melphalan 100140 mgm2 for patients with renal impairment and those who. Acute renal insufficiency after highdose melphalan in patients with primary systemic amyloidosis during stem cell transplantation nelson leung, jeff m. Renal drug handbook gfr 2050mlsmin dose as in normal renal function. Melphalan, a bifunctional nitrogen mustardderivative alkylating agent, is the l isomer of mechlorethamine.
Melphalan is practically insoluble in water and has a pka 1 of 2. Indications, dose, contraindications, sideeffects, interactions, cautions, warnings and other safety information for melphalan. Safety of autotransplants with highdose melphalan in renal failure. Efficacy and safety of melphalan 140mgm2 conditioned. Population pharmacokinetics of melphalan in patients with. Melphalan, sold under the trade name alkeran among others, is a chemotherapy medication used to treat multiple myeloma, ovarian cancer, melanoma, and amyloidosis. Melphalan can make you more likely to get infections or may worsen any current infections.
Preassessment ensure pretransplant workup investigation form b. Initially 610 mg daily for 57 days, then reduced to 24 mg daily until satisfactory response, then reduced to 26 mg once weekly. Iv melphalan may also reduce the threshold for bcnu lung toxicity. Melphalan is the active lisomer of the compound and was first synthesized in 1953 by bergel and stock. Renal impairment, leukopenia, thrombocytopenia, anemia, cll.
Melphalan 2 mg tablets summary of product characteristics. How to use melphalan 50 mg intravenous solution alkylating agents. Nov 09, 2018 melphalan is a cancer medication that interferes with the growth and spread of cancer cells in the body. Mar 18, 2014 in 18 patients administered melphalan 0. Toxicity in standard melphalanprednisone therapy among myeloma patients with renal failurea retrospective analysis and recommendations for dose. Oct 17, 2011 melphalan will be given as a single dose not split over 2 or more days and given on day1. As renal excretion is an important elimination pathway for melphalan 7, 8, an effect of creatinine clearance on melphalan total and unbound clearance can be expected. Dosing in obesity defined as body mass index 30kgm2 consider dosing patients using actual body weight. High dose melphalan has been used as a single agent or in combination with other anticancer agents e. Melphalan injection should not be given without haematopoietic stem cell rescue at doses of above 140 mgm 2 for intravenous administration, it is recommended that melphalan injection solution is injected slowly into a fastrunning infusion solution via a swabbed injection port. Pharmacokinetic, summary of product characteristics spc, relevant pharmaceutical company data and various references have been. Melphalan pharmacokinetics in children with malignant. Melphalan is an alkylating agent that has demonstrated activity against a number of malignant diseases in children.
Half the patients received six 28day cycles of melphalan 0. Melphalan clearance may be decreased in renal impairment see dosage and administration renal impairment and warnings and precautions renal impairment. Preparative regimen dosing for hematopoietic stem cell. Uclh dosage adjustment for cytotoxics in renal impairment version 3 updated january2009 page 3 of 24 drug pharmacokinetics available information recommendation arsenic trioxide arsenic is stored mainly in liver, kidney, heart, lung, hair and nails. This is a controlled document and therefore must not be changed. Melphalan injection is for intravenous use and regional arterial perfusion only. Ibm micromedex along with its needed effects, a medicine may cause some unwanted effects. Melphalan dose reduction in one child with impaired renal function.
The development of severe renal failure has been reported in patients treated with a single dose of iv melphalan followed by standard oral doses of cyclosporine. Melphalan is a phenylalanine derivative of nitrogen mustard with antineoplastic activity. Alkeran tablets melphalan chemotherapy, side effects. Feb 17, 2016 the development of severe renal failure has been reported in patients treated with a single dose of iv melphalan followed by standard oral doses of cyclosporine. Melphalan fda prescribing information, side effects and uses. Highdose melphalan and stem cell transplantation in patients. Highdose melphalan and stem cell transplantation hdmsct is valuable in selected patients with immunoglobulin lightchain amyloidosis and monoclonal immunoglobulin deposition diseaseassociated endstage renal disease. Uclh dosage adjustment for cytotoxics in renal impairment version 3 updated january2009 page 2 of 24 dosage adjustment for cytotoxics in renal impairment this table is a guide only. High dose melphalan is not recommended in patients with a more severe renal. Feb 01, 2020 melphalan is the active lisomer of the compound and was first synthesized in 1953 by bergel and stock. Each singledose vial contains melphalan hydrochloride equivalent to 50 mg melphalan and 20 mg povidone k12. An association was noted between poor renal function and myelosuppression. In our study, low creatinine clearance was associated with low clearance of total and unbound melphalan shown in figures 1,2, 2, which would consequently lead to. The renal drug handbook the st georges hospital, adult critical.
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