The challenge is to treat patients with renal insufficiency rr with a safe dose, based on crcl, providing equivalent biological exposure to patients with preserved renal. Dosing is based on body surface are bsa, while renal function is the only. Safety of dose reduced pemetrexed in patients with renal insufficiency article in journal of oncology pharmacy practice 255. Renal impairment during pemetrexed maintenance in patients with. Pemetrexed pem is an anticancer agent used for the treatment of nonsmall cell lung cancer, malignant pleural mesothelioma and thymoma. Dosing is based on body surface are bsa, while renal function is the only determinant for exposure and thus. Bsabased dosing introduces large variability in exposure and may lead to hematotoxicity in patients with impaired renal function. Pemetrexed side effects, dosage, interactions drugs everyday health search.
Phase i and pharmacokinetic study of pemetrexed administered. Patients must also receive one 1 intramuscular injection of vitamin b. Pemetrexed auc and cmax increase proportionally with dose. The renal drug handbook the st georges hospital, adult critical. Binding is not affected by degree of renal impairment. Advanced nonsmall cell lung cancer patients are at significant risk of renal impairment during pemetrexed maintenance, which may. Reportedly, pem has higher efficacy and safety when used in combination with platinumbased agents. The information on dosage adjustments in renal impairment given in this book is based on. The primary objective of this study is to describe the safety of dose reduced pemetrexed in patients with a crcl dosing. It is almost exclusively excreted by the kidney and an egfr lower 45 mlmin is a contraindication for its use. Purpose pemetrexed has been shown to be effective in the treatment of advanced and metastatic nonsquamous nonsmall cell lung cancer.
If your institution subscribes to this resource, and you dont have a myaccess profile, please contact your librarys reference desk for information on how to. Determine creatinine clearance before each dose and periodically monitor renal function during treatment with alimta. Patients with creatinine clearances of 45, 50, and 80 mlmin had 65%, 54%, and % increases, respectively in systemic exposure auc compared to patients with creatinine clearance of 100 mlmin. Guidelines for chemotherapy dosage adjustment hematology. Renal impairment during pemetrexed maintenance in patients with advanced nonsmallcell lung cancer. Pediatric drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in psychiatry. Pharmacokineticallyguided dosing of pemetrexed in a patient with. For nsaids with longer elimination halflives, patient taking these nsaids should interrupt dosing for at least 5 days before, the day of, and 2 days after pemetrexed administration alimta pemetrexed, eli lilly and company, indianapolis, in. The incidences of renal failure in clinical studies in which patients received alimta with cisplatin were 2. A 60 yearold man with unresectable pleural mesothelioma was treated. Safety of dosereduced pemetrexed in patients with renal.
Mrk, known as msd outside the united states and canada, today announced the resubmission of its supplemental biologics license. There is no recommended dose for patients whose creatinine clearance is less than 45 mlmin see use in specific populations 8. Purpose this phase i study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function. Dose escalations in new patients were conducted independently within each treatment.
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. Optimal survival benefit from different lines of anticancer treatment in advanced nonsmall cell lung cancer nsclc requires conservation of renal function. The mechanism responsible for renal damage remains unknown. Includes dosages for nonsmall cell lung cancer and malignant pleural mesothelioma. Effect of renal function on pemetrexedinduced haematotoxicity. Pharmacokinetic, summary of product characteristics spc, relevant pharmaceutical company data and various references have been. Kidney tubular toxicity of maintenance pemetrexed therapy featuring kenar jhaveri, md, eajkd blog editor and authors. The halflive of drug elimination was 65 hours, which is markedly prolonged. Hill j12, vargo c1, smith m1, streeter j1, carbone dp3. Dosing is based on body surface are bsa, while renal function is the only determinant for exposure and thus toxicity. For renally excreted drugs with a narrow therapeutic index, the total daily maintenance dose may be reduced either by decreasing the dose or by increasing the dosing interval, or sometimes by a combination of both.
The most common nonhematologic side effect is elevation of hepatic enzyme levels. In a prospective multicentre cohort study, we evaluated the incidence of acutechronic kidney disease akdckd, its related treatment discontinuation. Find patient medical information for alimta intravenous on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Safety of dosereduced pemetrexed in patients with renal insufficiency. Starting doses were based on renalfunction stratification. There is a significant risk of renal impairment during pemetrexed maintenance, which may jeopardise further treatment footnotes this manuscript has recently been accepted for publication in the european respiratory journal. Pemetrexed is a parenterally administered folate antagonist and antineoplastic. Pemetrexed in maintenance in patients with impaired renal. Other toxicities include rash, mucositis, nausea, and vomiting 2,3,4,5.
Dosage adjustment for cytotoxics in renal impairment. Important safety information alimta pemetrexed for. Patients at risk for renal impairment during pemetrexed maintenance. The pharmacokinetics of pemetrexed do not change over multiple treatment cycles. For those drugs in which renal excretion is an important determinant of elimination of the intact drug or an active metabolite, dose adjustment is often required if renal function is impaired. Patients must also receive an intramuscular injection of vitamin b 12 micrograms in the week preceding the first dose of pemetrexed and once every three cycles thereafter. Alimta pemetrexed disodium dose, indications, adverse. Pemetrexed is a cancer medication that interferes with the growth and spread of cancer cells in the body.
Alimta for mesothelioma in patients with renal impairment. Patients and methods patients received a 10minute infusion of 150 to 600 mgm2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration. Pemetrexed side effects, dosage, interactions drugs. Although the prevalence of an elevated serum creatinine is low in cancer patients dosing based on the package insert recommendations for renal insufficiency. Plasma clearance of pemetrexed decreases as renal function decreases, with a resultant increase in systemic exposure. Pemetrexed has been shown to be effective in the treatment of advanced and metastatic nonsquamous nonsmall cell lung cancer. Pemetrexed induced acute kidney injury in patients with.
The information on dosage adjustments in renal impairment given in this book is based on cockcroftgault creatinine clearance and not egfr, since the majority. Alimta, pemetrexed for injection, is available in sterile singleuse vials containing 100 mg pemetrexed. Alimta can cause severe, and sometimes fatal, renal toxicity. Management of pemetrexed toxicity in acute renal failure. The study concludes that pharmacokineticallyguided dosing makes alimta for mesothelioma feasible, even in patients with renal impairment. Pemetrexed has a steadystate volume of distribution of 16. Youll have access to the site in a moment, or click continue to close this message and advance directly to the site. Dosing carboplatin in patients assigned to hemodialysis. Pemetrexed is indicated for nonsmall cell lung cancer and mesothelioma. We evaluated the development of renal impairment during pemetrexed maintenance. Pemetrexed has a prominent role in the firstline and maintenance treatment of pulmonary adenocarcinoma but its first indication was as secondline therapy. Now you can find the tools you need to help manage your patients, all in one place.
Pharmacokineticallyguided dosing of pemetrexed in a. The calvert equation is the simplest equation and was approved by the fda in 1995 for dosing of carboplatin. Relevant articles are summarized below, particularly as they relate to our case report. In patients with normal renal function, the greatest excretion of carboplatin occurs within the first eight hours after administration, with 60% to 90% of the dose excreted unchanged in the urine. Renal function was calculated using both ideal and actual body weights of patients. Ilya glezerman, md renal service, attending nephrologist memorial sloan kettering cancer center surya seshan, md chief of renal pathology, professor of pathology weill cornell medical center pemetrexed is an antifolate agent. Adjusted dosing and schedule of pemetrexed in impaired renal. Dosing guidelines for varying degrees of renal impairment are stated accordingly.
Renal impairment during pemetrexed maintenance in patients. Adjusted dosing and schedule of pemetrexed in impaired. This agent is excreted unchanged by the kidneys 70%90% in 24 hours, with a halflife of 3. In the presented case, pemetrexed plasma levels six days after a dose of 500 mgm2 were 100. In pts with normal renal function, pemetrexed plasma concentrations peak early and become undetectable after about 48 hours. Increased risk of toxicity with concomitant ibuprofen in renal impairment crcl 4579mlmin. The dose adjustment of pemetrexed is performed as a function of body surface area sc without any pharmacokinetic rational. Alimta dosing recommendations are provided for patients with a creatinine clearance calculated by cockcroftgault equation of 45 mlmin or greater see dosage and administration 2. There is no recommended dose for patients whose creatinine clearance is less than 45mlmin see use in specific populations 8. In vitro studies indicate that pemetrexed is approximately 81% bound to plasma proteins. Adult drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in. Therefore, pemetrexed is contraindicated in renal impairment. It is published here in its accepted form prior to copyediting and typesetting by our production team.
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