This medicine will not work for colds, flu, or other virus infections. Imipenem and cilastatin drug monograph pediatric care online. Read and carefully follow any instructions for use provided with your medicine. In view of the important increase in halflife of cilastatin as a function of increasing renal failure, a dosage reduction is proposed in patients with severe renal failure. Imipenem and cilastatin must be mixed with a liquid diluent before using it. Mark farrington, in clinical pharmacology eleventh edition, 2012. Multiple dosing has no effect on the pharmacokinetics of either imipenem or cilastatin, and no accumulation of imipenem cilastatin is observed. Imipenem is rapidly hydrolysed by the enzyme dehydropeptidase i located on the brush border of renal tubular cells.
Neonates 32 wk gestation 4075 mgkgday iv divided q812h for at least 2wk. A reduction in dose must be made for patients with creatinine clearance less than 90 mlmin as shown in table 3 see dosage and administration 2. Cilastatin can therefore be combined intravenously with imipenem in order to protect it from degradation, prolonging its antibacterial effect. It is given as the sodium salt with imipenem to prevent its renal metabolism and protect against nephrotoxic effects. The dosage recommendations for primaxin represent the quantity of imipenem to be administered. It is made from a combination of imipenem and cilastatin. Usual dosing adults dosage and administration adults. Dosage regimen based on creatinine clearance mlminute1. Fixed combination of imipenem, a betalactam antibiotic, and cilastatin. The objective of this study is to evaluate the appropriateness of imipenemcilastatin prescription and dosing in a local tertiary care hospital.
Minimum inhibitory concentrations mcgml disk diffusion zone diameter in mm. Removal of imipenem and cilastatin by hemodialysis in. Because imipenem is rapidly inactivated by renal dehydropeptidase i, it is given in combination with cilastatin, a dhpi inhibitor which increases halflife and tissue penetration of imipenem. A healthcare provider will give your first dose and may teach you how to properly use the medication by yourself. For the treatment of peritonitis in patients undergoing peritoneal dialysis. Includes dosages for urinary tract infection, pyelonephritis and intraabdominal infection. Mar 24, 2015 the patients who received imipenemcilastatin at higher than recommended doses had an increased risk of seizures, especially the subgroup of patients with renal insufficiency. Cilastatin is a specific inhibitor of this enzyme and it prevents renal metabolism of imipenem. Dailymed imipenem and cilastatin imipenem and cilastatin.
Imipenem cilastatin was used for the treatment of 594 bacterial infections in 545 patients at a dosage of 1. Imipenem is a more common cause of seizures than other betalactam antibiotics, particularly when high doses are given 28 c, 29 ar. Dehydropeptidase is an enzyme found in the kidney and is responsible for degrading the antibiotic imipenem. Pharmacokinetics and pharmacodynamics of imipenem during. Renal dosing adult if usual dose 500mg q6h crcl 6089. Ibm micromedex along with its needed effects, a medicine may cause some unwanted effects. It is important to highlight the fact that the inappropriateness in the dosing regimen among the rest of the patients 33% was mainly evident in patients who already had a low crcl renal. Includes dosages for bacterial infection, urinary tract infection, bronchitis and more. Imipenem, when administered alone, is metabolized in the kidneys by dehydropeptidase i. Antiinfective pregnancy risk category c action acts against many grampositive and gramnegative organisms by binding to bacterial cell wall, causing cell death. The pharmacokinetics of imipenem thienamycinformamidine. Imipenemcilastatin, like other carbapenems, binds to bacterial penicillinbinding proteins and interferes with bacterial cell wall integrity and synthesis.
Imipenem and cilastatin injection comes as a powder to be mixed with liquid to be injected intravenously into a vein or intramuscularly into a muscle. Up to 500 mg dose should be given over 20 to 30 minutes. The binding of imipenem to human serum proteins is approximately 20% and that of cilastatin is approximately 40%. After a 1 gram dose of imipenem and cilastatin for injection i. Multiple dosing has no effect on the pharmacokinetics of either imipenem or cilastatin, and no accumulation of imipenemcilastatin is observed. Imipenem resists the actions of many enzymes that degrades most other penicillins and penicillinlike antiinfectives. It works by killing bacteria or preventing their growth.
Feb 06, 2020 imipenem and cilastatin is given as an infusion into a vein. Cilastatin is an inhibitor of dehydropeptidase i, an enzyme found in the brush border of the renal tubules. Preliminary research on twostep dosing of imipenem. Imipenem and cilastatin intravenous route, intramuscular. Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary concen. Imipenem and cilastatin professional patient advice. Cilastatin inhibits renal dihydropeptidase i, preventing imipenem metabolism. Tore midtvedt, in side effects of drugs annual, 2011. Detailed cilastatin imipenem relebactam dosage information for adults.
When imipenem and cilastatin is injected intravenously, it is usually infused injected slowly over a period of 20 minutes to 1 hour every 6 or 8 hours. On day 4 the patient was agitated and developed violent visual and auditory hallucinations. Primaxin imipenemcilastatin dosing, indications, interactions. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Imipenemcilastatin sodium dosage, interactions, side effects. Drug removal during high efficiency and high flux hemodialysis. Each 125 mg, 250 mg, or 500 mg dose should be given by intravenous administration over 20 to 30 minutes. Frequency of convulsions during treatment with imipenem cilastatin is dose dependent. The most common side effects of imipenem are diarrhea, nausea, vomiting, skin rash, pruritus and injection site reactions.
Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary concentrations. These doses should be used for patients with creatinine clearance of greater than or equal to 90 mlmin. Cilastatin sodium, an inhibitor of this enzyme, effectively prevents renal metabolism of imipenem so that when imipenem and cilastatin sodium are given concomitantly, increased levels of imipenem are achieved in the urine. Cilastatin prevents renal metabolism of imipenem by competitive inhibition of. The combination of imipenem and cilastatin is available generically and under the brand name primaxin as 250 mg or 500 mg infusion bottles for iv use or 500 mg or 750 mg vials of lyophilized powder for im injection. The dosage of primaxin in adult patients should be based on suspected or confirmed pathogen susceptibility as shownin table 1 below. Imipenemcilastatin an overview sciencedirect topics. Imipenemcilastatin daviss drug guide for rehabilitation. This medication is given by injection into a muscle or vein, usually every 6 to 8 hours or as directed by your doctor. Imipenem and cilastatin combination is used in the treatment of infections caused by bacteria.
Imipenemcilastatin side effects, dosage, interactions. Thus, it is used as combination with cilastatin, a reversible inhibitor of dehydropeptidase i, which has matched pharmacokinetics with imipenem t12 of both is. Pricing, sizing, legal catgories and other medicinal forms information for imipenem with cilastatin. Specifically it is used for pneumonia, sepsis, endocarditis, joint infections, intraabdominal infections, and urinary tract infections. It is recommended that the maximum dose of imipenem cilastatin would be limited to either mg twice daily or 500500 mg four times daily in patients with a. Jul 16, 2019 imipenem and cilastatin for injection, usp for intravenous use is a combination of imipenem, a penem antibacterial, and cilastatin, a renal dehydropeptidase inhibitor, indicated for the treatment of the following serious infections caused by designated susceptible bacteria. When administered alone, imipenem is rapidly metabolized in the brush border of the proximal renal tubule by dehydropeptidase 1 dhp1. Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary.
Risk factors for this complication are renal failure and an underlying neurological disease. Sep 06, 2019 in healthy elderly volunteers 65 to 75 years of age with normal renal function for their age, the pharmacokinetics of a single dose of imipenem 500 mg and cilastatin 500 mg administered intravenously over 20 minutes are consistent with those expected in subjects with slight renal impairment for which no dosage alteration is considered necessary. The most common indications for therapy were nosocomial pneumonias followed by intraabdominal postoperative infections, and skin and soft tissue infections. Imipenem binds to the bacterial cell wall, resulting in cell death. Compared with imipenemcilastatin 2 hours continuous dosing method and twostep dosing method 0. Cilastatin inhibits the human enzyme dehydropeptidase. When imipenem and cilastatin are given concomitantly, approximately 70% of the administered imipenem and cilastatin are recovered unchanged in the urine within 10 hours of administration, after which no further urinary excretion is detectable. Evaluation of the appropriateness of imipenemcilastatin prescription. Imipenem and cilastatin dosage in renal impairment reduced i. There may be an increased risk of seizures when doses of 500 mg every 12 hours are administered to these patients. Pdf multipledose pharmacokinetics of imipenemcilastatin. Inhibits class a carbapenemases and class c cephalosporinases. Dosing regimens were determined by the physicians caring for the patients and selected based on clinical indication, institutional dosing guidelines, and published dosing guides available to the medical house staff.
Renal clearance accounted for 54% of the plasma clearance of. However, imipenem exerts its bactericidal activity by inhibiting bacterial cell wall synthesis in grampositive and gramnegative bacteria through binding to penicillinbinding proteins and cilastatin is a competitive, reversible and specific inhibitor of dehydropeptidasei, the renal enzyme which metabolizes and inactivates imipenem. Imipenem, cilastatin sodium, and relebactam monograph for. In vitro studies have demonstrated that imipenem has an extremely wide spectrum of antibacterial activity against gramnegative and grampositive aerobic and anaerobic bacteria, even against. Cilastatin helps imipenem work more effectively by preventing the breakdown of the antibiotic in the kidneys. When administered alone, imipenem is metabolized in the kidneys by dehydropeptidase, resulting in low imipenem urine levels. Dailymed primaxin iv imipenem and cilastatin sodium. The recommended dosage is 250 mg to 1 gram given intravenously.
The dosing of imipenem cilastatin assessed in this study was shown to be appropriate in only 67% of the cases. The dosage of primaxin in adult patients should be based on suspected or confirmed pathogen susceptibility as shown in table 1 below. Evaluation of the appropriateness of imipenemcilastatin. Imipenemcilastatin definition of imipenemcilastatin by. Indications and usage primaxin for intravenous use is a combination of imipenem, a penem antibacterial, and cilastatin, a renal. Combination of imipenem and cilastatin that is used in the treatment of bacterial infections. Recarbrio imipenem, cilastatin, and relebactam for injection, 1. Imipenem with cilastatin medicinal forms bnfc content. Primaxin imipenem and cilastatin for injection, for intravenous use initial u.
Evaluation of the appropriateness of imipenem cilastatin prescription and dosing in a tertiary care hospital wissam k kabbara, george t nawas, wijdan h ramadandepartment of pharmacy practice, school of pharmacy, lebanese american university, byblos, lebanon background. Analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in psychiatry. About 70% of imipenem and cilastin is recovered in the urine within 10 hr of administration. Patients enrolled into the study received imipenem cilastatin as part of their medical care. Oct 18, 2012 imipenem is the first available semisynthetic thienamycin and is administered intravenously in combination with cilastatin,1 a renal dipeptidase inhibitor that increases urinary excretion of active drug. The total daily dosage of imipenem should be based on the type or severity of infection and given in equally divided doses based on consideration of degree of susceptibility of the pathogens, renal function and bodyweight. Imipenemcilastatin, sold under the brand name primaxin among others, is an antibiotic useful for the treatment of a number of bacterial infections. Cilastatin, a renal dipeptidase inhibitor, inhibits the enzymatic breakdown of imipenem and increases urinary excretion of the active drug.
Imipenem and cilastatin for injection is a sterile formulation of imipenem a thienamycin antibiotic and cilastatin sodium the inhibitor of the renal dipeptidase, dehydropeptidase l, with sodium bicarbonate added as a buffer. In one newborn who received a 15mgkg intravenous dose, concentrations of 1. Following intravenous infusion of imipenem and cilastatin at a combined concentration of 10 mgkg of body weight, drug levels in plasma were determined serially during off and onhemodialysis periods, which were 2 and 4 h, respectively. Developmental toxicity studies with imipenem and cilastatin sodium alone or in combination administered to mice, rats, rabbits, and monkeys at doses 0. Pediatric drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in psychiatry. In adults, renal clearance of imipenem resembles creatinine clearance. Addition of cilastatin prevents renal inactivation of imipenem, resulting in increased urinary concentration. An equivalent amount of cilastatin is also present in the solution. In dogs and cats, the usual dose of imipenem with cilastatin is 2. Cilastatin prevents renal metabolism of imipenem by competitive.
Imipenem with cilastatin drug bnf content published by. Compared with iv administration, imipenem is approximately 75% bioavailable after im use with cilastatin being 95% bioavailable. For intravenous infusion dilute to a concentration of 5 mg as imipenemml in sodium chloride 0. Imipenem with cilastatin drug bnf content published by nice. Dosing interval 60 to 89 1 gram imipenem 400 mg, cilastatin 400 mg, and relebactam 200 mg every 6 hours 30 to 59 0.
Imipenemcilastatin is a topic covered in the johns hopkins abx guide to view the entire topic, please sign in or purchase a subscription official website of the johns hopkins antibiotic abx, hiv, diabetes, and psychiatry guides, powered by unbound medicine. Because imipenem is rapidly inactivated by renal dehydropeptidase i. Medscape indicationspecific dosing for primaxin imipenemcilastatin. Nov 09, 2018 imipenem is an antibiotic that fights bacteria. For intravenous infusion dilute to a concentration of 5 mg as imipenem ml in sodium chloride 0. Out of the 49 patients who did not have renal impairment, only three 6. Detailed cilastatin imipenem dosage information for adults and children. Doses as high as 5 mg per pound 10 mgkg every 8 hours have been. The mean plasma halflives of imipenem and cilastatin are 91 7 minutes and 69 15 minutes, respectively. On day 3 his imipenemcilastatin dose was increased as an adjustment to his improving renal function at the time serum creatinine 0. Although not all of these side effects may occur, if they do occur they may need medical attention. The removal of imipenem and cilastatin by hemodialysis was studied in 14 for imipenem and 6 for cilastatin subjects.
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