Current trends of renal impairment in multiple myeloma fulltext. 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. Duong jk1, veal gj2, nath ce, shaw pj45, errington j2, ladenstein r6, boddy av1. Highdose melphalan and stem cell transplantation in patients. Data on the effectiveness and toxicity of high dose melphalan in patients with renal impairment ri are lacking. The clearance of melphalan is reduced in underweight patients, elderly people, and those with poor renal function. Chemotherapy regimens consisted of cycles of melphalan and. Part of the cancer treatment and research book series ctar, volume 112. We evaluated the impact of ri on outcomes of patients with multiple myeloma treated. If you are unable to swallow melphalan, talk to your care provider or pharmacist for possible options.
Highdose intravenous melphalan with autologous stem cell. Renal impairment in patients with multiple myeloma. These 4 to 5day courses are then repeated every 4 to 6 weeks if the granulocyte and platelet count have returned to normal levels. The drug is administered as a single infusion over 15 to 20 minutes. Melphalan hydrochloride for injectionfor intravenous. The renal drug handbook third edition edited by caroline ashley and aileen currie uk renal pharmacy group. Table refers to intravenous iv dosing except where specified. Iv melphalan arm 28% than in the oral melphalan arm 11%. Criteria for dosage adjustment in a randomized clinical trial wbcmm platelets percent of full dose. Acute renal insufficiency after highdose melphalan in. Pepaxto melphalan flufenamide disease interactions. When expressed as a bsabased mgm 2 dose, the total 2day dose would range from 3308 mgm 2 figure 1b. Fludarabine melphalan for reduced intensity conditioning allograft.
Dosing and drug administration in multiple myeloma. Renal impairment ri is a common complication of multiple. Melphalan mel is probably the most effective chemotherapeutic agent in multiple myeloma mm with a clear dose response effect. No bisphosphonates or calcitonin were used in this phase of the disease in our patients. Renal impairment ri is one of the most common complications of multiple myeloma mm. Alkeran for injection melphalan hydrochloride dose. Melphalan tablets fda prescribing information, side effects. High dose melphalan 140 mgm 2 and autologous stemcell. High dose intravenous melphalan and autologous stem cell transplantation induce remission of the plasma cell dyscrasia in a significant proportion of patients with al amyloidosis. Melphalan fda prescribing information, side effects and uses. The aims of the present study were to investigate factors that influence the pharmacokinetics of carboplatin in children with highrisk neuroblastoma, and whether target exposures for carboplatin were achieved using.
May 14, 2020 one regimen has been to administer courses of this drug at 0. Sep 06, 2017 dosage reduction of up to 50% should be considered in patients with renal insufficiency bun. A population pharmacokinetic model was built for carboplatin to evaluate various. The information on dosage adjustments in renal impairment given in this book is base. It can be escalated without excessive toxicity to 200 mgm2, a myeloablative dose requiring hematopoietic stem cell support. Safety of autotransplants with highdose melphalan in renal. Based on a clear dose response relation, intensified melphalan regimens 200 mgm 2 intravenously followed by autologous peripheral blood derived stemcell rescue prolong survival in patients with multiple myeloma 2. Mecamylamine, meclofenamic acid, mefenamic acid, mefloquine, melphalan, meperidine, meprobamate, meropenem, metaproterenol, metformin, methadone. Population pharmacokinetics of carboplatin, etoposide and melphalan in children.
Dr karthik ramasamy this is a controlled document and therefore must not be changed high dose melphalan for autograft. Preparative regimen dosing for hematopoietic stem cell. Aronoff recommends giving 75% of the dose for a crcl of. Carboplatin dosage is calculated by using the estimated glomerular filtration rate gfr to achieve a target plasma area under the plasma concentrationtime curve auc. Melphalan inhibits dna and rna synthesis via formation of interstrand cross links with dna, likely binding at the n.
The information on dosage adjustments in renal impairment given in this book is based on. Dose reduction is needed if there is renal impairment or if the patient is 70. Patients who had ari after high dose melphalan underwent dialysis more often p 0. Monitor patients with neutropenia for signs of infection. Renal impairment is a common complication of multiple myeloma mm. One regimen has been to administer courses of this drug at 0. Clinical pharmacology of melphalan and its implications for clinical. Mar 14, 2016 highdose therapy with autologous stem cell transplantation with melphalan 100 mgm 2 to 140 mgm 2 is feasible in patients with ri grade c. Kintzel recommends for crcl of 4660 mlmin, give 85% of dose. See full prescribing information for complete boxed warning. Two patients who received less than 100 mgm 2 recovered from marrow aplasia within 3 weeks without major complications. Treatment duration, the melphalan dosage, and thromboprophylaxis agentsrecommendations varied in these studies. High melphalan exposure is associated with improved overall. International myeloma working group recommendations for.
Development of a real time pharmacokinetic testing method. Impact of renal impairment on outcomes after autologous. The authors have noted the development of acute renal insufficiency. Velcade dose should be reduced by 1 dose level from 1. We indicated that the dose of melphalan escalation may result in higher response rates. The usual melphalan dose is 200mgm 2 although a riskadapted approach, with dose reduction to 140 mgm 2 used in higherrisk patients in order to reduce transplantrelated toxicity. Melphalan is administered at 2week intervals for 4 doses, then, after adequate recovery from toxicity, at 4week intervals. Renal impairment ri is a negative prognostic factor in multiple myeloma. The rate of severe leukopenia in the iv arm in the patients with bun. The 24hour urinary excretion of parent drug in these patients was 10% 4. Melphalan 100140 mgm2 for patients with renal impairment and those who. Each vial of sterile diluent contains sodium citrate 0.
Safety of autotransplants with high dose melphalan in renal failure. Patients with primary systemic amyloidosis al have a poor prognosis. A catalogue record for this book is available from the british library. High dose melphalan and stem cell transplantation hdmsct is effective for selected patients with al the kidney is the most common organ affected by immunoglobulin lightchain al amyloidosis and monoclonal immunoglobulin deposition disease midd, often leading to endstage renal disease esrd. It is recommended to perform the following tests at the start of therapy and prior to each subsequent dose of melphalan flufenamide. Impact of renal impairment on outcomes with lenalidomide and. Melphalan 200 mgm 2 in patients with renal impairment is. Fludarabine 20%25% dose reduction in the setting of mildtomoderate renal impairment.
Dose delay or dose reduction may be required to allow recovery of platelets. Multiple myeloma animal medical center of southern california. Melphalan causes impairment of spermatogenesis such as azoospermia in men. Three patients with severe renal impairment first received a low test dose of mel 16 mgm2 for pharmacokinetic studies. High dose melphalan with haematopoietic stem cell rescue has been used successfully even in dialysis dependent patients with endstage renal failure. Population pharmacokinetics of carboplatin, etoposide and. 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.
Median survival time from standard treatments is only 17 months. The role of thalidomide, bortezomib and lenalidomide in multiple myeloma patients presenting with renal impairment was evaluated in 3. A novel classification of ckd, based on crcl, has been recently produced table 2. No dose adjustment of melphalan flufenamide is recommended in patients with creatinine clearance crcl 45 to 89 mlmin. Iv melphalan 16 mgm q 2 weeks x 4 over 6 weeks followed by the same dose every 4 weeks. Patients with renal impairment are treated on protocol b. Monitor neutrophil counts at baseline, during treatment and as clinically indicated. The level of renal function below which the dose of a drug must be reduced. Evaluation of pharmacokineticbased dose predictions of. Dosing in obesity defined as body mass index 30kgm2 consider dosing patients using actual body weight. Melphalan hydrochloride for injection is reconstituted using the sterile diluent provided. Conventional dosages of 16 mgm 2 intravenously every 2 weeks or 0.
The development of endstage renal disease esrd is common among patients with amyloid lightchain al amyloidosisassociated renal disease and survival of these patients is poor. Optimal dosing of melphalan as highdose therapy before. Melphalan has been used for more than 50 years for a variety of malignant tumors. Highlights of prescribing information hypotension can occur. Preassessment ensure pretransplant workup investigation form b.
The recommended dose of evomela for palliative treatment is 16 mgm 2 administered as a single intravenous infusion over 1520 minutes at 2week intervals for 4 doses, then, after adequate recovery from toxicity, at 4week intervals. Fludarabinemelphalan for reduced intensity conditioning. Safety of autotransplants with highdose melphalan in. Prednisone or prednisolone is given concurrently at a dose of 0. Melphalan 458 mepacrine hydrochloride unlicensed product 460 meptazinol 461. Each singledose vial contains melphalan hydrochloride equivalent to 50 mg melphalan and 20 mg povidone. As melphalan dose and renal function are both determinants of. Consider reduction of the melphalan dose by 25% in the next cycle. Melphalan is a cell cycle phasenonspecific alkylating agent, often given in combination with prednisone to treat dogs with mm. Published studies of novel agentbased regimen in myeloma patients with ri. Melphalan 50 mg powder and solvent for solution for injection. The dose is adjusted, as required, on the basis of blood counts done at approximately weekly intervals.
Impact of renal impairment on outcomes after autologous stem cell. Renal failure rf is one of the most common complications of multiple. If several velcade doses in consecutive cycles are withheld due to toxicity. All patients received 200 mgm2 mel divided into two equal doses of 100 mgm2 i. Administer prophylactic antiemetics see warnings and precautions 5. The usual melphalan dose is 200 mgm 2 although a riskadapted approach, with dose reduction to 140 mgm 2 used in higherrisk patients in order to reduce transplantrelated toxicity. Sixty percent of the active metabolite 2fluoroaraa faraa is cleared renally. Using doptimality approaches we determined that reducing blood sampling from 8 to 4 time points did not affect. Pharmacokinetics of oral melphalan in relation to renal. The timing of renal injury strongly suggests melphalan as the causative agent. High dose melphalan 200 mgm 2 is associated with excessive. Melphalan is both secreted and reabsorbed in the renal tubules.
The role of novel agents on the reversibility of renal impairment in. Melphalan 458 mepacrine hydrochloride unlicensed product 460 meptazinol 461 mercaptopurine 462 meropenem 463 mesalazine 464 mesna 465 metformin hydrochloride 466 methadone hydrochloride 467 methenamine hippurate 468 methotrexate 469 methyldopa 471 methylprednisolone 472 metoclopramide hydrochloride 473 metolazone 474 metoprolol tartrate 475. Feb 19, 2021 melphalan tablets dosage and administration multiple myeloma. Care should be exercised when using this agent in patients with crcl 15 to 44 mlmin as the safety. The book provides essential information on drug dosing in patients with different levels of kidney. If leukopenia develops, melphalan therapy should be discontinued until white blood cell counts return to normal. We have previously examined the population pharmacokinetics of high dose melphalan in 100 patients with multiple myeloma who received a 200 mg m 2 dose with adjustments for renal impairment or obesity and we observed a 5. The definition of ri, according to the novel imwg criteria for.
International myeloma working group recommendations for the. Welcome to the fifth edition of the renal drug handbook. An association was noted between poor renal function and myelosuppression. Jul 01, 2014 20%25% dose reduction in the setting of mildtomoderate renal impairment. Comparison of two melphalan protocols and evaluation of. Mar 10, 2020 melphalan should be taken on an empty stomach at least 1 hour before or 2 hours after a meal or snack, but at the same time each day. Renal impairment is associated with poor prognosis in myeloma. Data on children receiving high dose carboplatin, etoposide and melphalan for neuroblastoma were obtained from two study sites european international society for paediatric oncology siop neuroblastoma study, childrens hospital at westmead. Doses of melphalan were adjusted according to the following criteria. Autologous stem cell transplantation in multiple myeloma with.
High dose intravenous melphalan followed by peripheral blood stem cell transplant pbsct appears to be the most promising therapy, but treatment mortality can be high. An overview of the use of highdose melphalan with autologous. Ongoing tubular injury may be a prerequisite for renal injury by melphalan as evidenced by the active urinary sediment. High melphalan exposure is associated with improved. Highdose melphalan and stem cell transplantation in. Data on the effectiveness and toxicity of highdose melphalan in patients with renal impairment ri are lacking. From the studies we included, most of them were according to the novel. May 16, 2016 data on the effectiveness and toxicity of highdose melphalan in patients with renal impairment ri are lacking. Oral melphalan in combination with lenalidomide 10 mg po daily on days 1 to 21 and dexamethasone 40 mg po on days 1, 8, 15, and 22 repeated every 28 days has been evaluated in nonrandomized studies. Dosage reduction of up to 50% should be considered in patients with renal insufficiency bun. Bone marrow suppression is the most significant toxicity associated with melphalan flufenamide in most patients. The rate of severe leukopenia in the intravenous arm in the patients with bun over 30 mgdl. Intravenous melphalan has been used to treat rhabdomyosarcoma, lymphomas, multiple myeloma, and neuroblastoma 1. Development of a real time pharmacokinetic testing method to.
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