Inhibits class a carbapenemases and class c cephalosporinases. Dehydropeptidase is an enzyme found in the kidney and is responsible for degrading the antibiotic imipenem. The mean plasma halflives of imipenem and cilastatin are 91 7 minutes and 69 15 minutes, respectively. Multiple dosing has no effect on the pharmacokinetics of either imipenem or cilastatin, and no accumulation of imipenem cilastatin is observed. For the treatment of peritonitis in patients undergoing peritoneal dialysis. 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. Cilastatin is an inhibitor of dehydropeptidase i, an enzyme found in the brush border of the renal tubules.
Imipenem with cilastatin drug bnf content published by. Includes dosages for urinary tract infection, pyelonephritis and intraabdominal infection. Imipenem, cilastatin sodium, and relebactam monograph for. Removal of imipenem and cilastatin by hemodialysis in. Renal dosing adult if usual dose 500mg q6h crcl 6089. Feb 06, 2020 imipenem and cilastatin is given as an infusion into a vein. Each 125 mg, 250 mg, or 500 mg dose should be given by intravenous administration over 20 to 30 minutes. 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.
Developmental toxicity studies with imipenem and cilastatin sodium alone or in combination administered to mice, rats, rabbits, and monkeys at doses 0. Ibm micromedex along with its needed effects, a medicine may cause some unwanted effects. Evaluation of the appropriateness of imipenemcilastatin. Up to 500 mg dose should be given over 20 to 30 minutes. Multiple dosing has no effect on the pharmacokinetics of either imipenem or cilastatin, and no accumulation of imipenemcilastatin is observed. The dosage recommendations for primaxin represent the quantity of imipenem to be administered.
Imipenem and cilastatin drug monograph pediatric care online. Primaxin imipenemcilastatin dosing, indications, interactions. The binding of imipenem to human serum proteins is approximately 20% and that of cilastatin is approximately 40%. On day 4 the patient was agitated and developed violent visual and auditory hallucinations. Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary concen. Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary concentrations. On day 3 his imipenemcilastatin dose was increased as an adjustment to his improving renal function at the time serum creatinine 0. 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.
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. Pricing, sizing, legal catgories and other medicinal forms information for imipenem with cilastatin. Read and carefully follow any instructions for use provided with your medicine. When administered alone, imipenem is rapidly metabolized in the brush border of the proximal renal tubule by dehydropeptidase 1 dhp1.
Imipenem is a more common cause of seizures than other betalactam antibiotics, particularly when high doses are given 28 c, 29 ar. Drug removal during high efficiency and high flux hemodialysis. 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. 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. Imipenemcilastatin sodium dosage, interactions, side effects. Imipenem cilastatin was used for the treatment of 594 bacterial infections in 545 patients at a dosage of 1. The objective of this study is to evaluate the appropriateness of imipenemcilastatin prescription and dosing in a local tertiary care hospital. Out of the 49 patients who did not have renal impairment, only three 6. The dosing of imipenem cilastatin assessed in this study was shown to be appropriate in only 67% of the cases. Pediatric drugs analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in psychiatry. Imipenemcilastatin definition of imipenemcilastatin by. Imipenem, when administered alone, is metabolized in the kidneys by dehydropeptidase i. Fixed combination of imipenem, a betalactam antibiotic, and cilastatin. 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.
Cilastatin inhibits renal dihydropeptidase i, preventing imipenem metabolism. The dosage of primaxin in adult patients should be based on suspected or confirmed pathogen susceptibility as shownin table 1 below. Cilastatin can therefore be combined intravenously with imipenem in order to protect it from degradation, prolonging its antibacterial effect. The dosage of primaxin in adult patients should be based on suspected or confirmed pathogen susceptibility as shown in table 1 below. 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. 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. Cilastatin inhibits the human enzyme dehydropeptidase. Mark farrington, in clinical pharmacology eleventh edition, 2012. Recarbrio imipenem, cilastatin, and relebactam for injection, 1. 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.
Dailymed primaxin iv imipenem and cilastatin sodium. About 70% of imipenem and cilastin is recovered in the urine within 10 hr of administration. It is made from a combination of imipenem and cilastatin. After a 1 gram dose of imipenem and cilastatin for injection i. Imipenemcilastatin side effects, dosage, interactions. Renal clearance accounted for 54% of the plasma clearance of. The pharmacokinetics of imipenem thienamycinformamidine. 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.
It is given as the sodium salt with imipenem to prevent its renal metabolism and protect against nephrotoxic effects. Imipenemcilastatin, like other carbapenems, binds to bacterial penicillinbinding proteins and interferes with bacterial cell wall integrity and synthesis. Preliminary research on twostep dosing of imipenem. Imipenemcilastatin, sold under the brand name primaxin among others, is an antibiotic useful for the treatment of a number of bacterial infections. Compared with imipenemcilastatin 2 hours continuous dosing method and twostep dosing method 0.
Pharmacokinetics and pharmacodynamics of imipenem during. 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. Imipenem resists the actions of many enzymes that degrades most other penicillins and penicillinlike antiinfectives. Cilastatin prevents renal metabolism of imipenem by competitive inhibition of.
Analgesics antihypertensive and cardiovascular agents antimicrobial agents miscellaneous agents sedatives, hypnotics, and other drugs used in psychiatry. Dosing interval 60 to 89 1 gram imipenem 400 mg, cilastatin 400 mg, and relebactam 200 mg every 6 hours 30 to 59 0. 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. Specifically it is used for pneumonia, sepsis, endocarditis, joint infections, intraabdominal infections, and urinary tract infections. Imipenem and cilastatin must be mixed with a liquid diluent before using it. Cilastatin helps imipenem work more effectively by preventing the breakdown of the antibiotic in the kidneys. Imipenem with cilastatin drug bnf content published by nice. Imipenemcilastatin an overview sciencedirect topics.
Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Usual dosing adults dosage and administration adults. Imipenem and cilastatin professional patient advice. There may be an increased risk of seizures when doses of 500 mg every 12 hours are administered to these patients.
Imipenem and cilastatin combination is used in the treatment of infections caused by bacteria. It works by killing bacteria or preventing their growth. In adults, renal clearance of imipenem resembles creatinine clearance. Pdf multipledose pharmacokinetics of imipenemcilastatin.
An equivalent amount of cilastatin is also present in the solution. 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. The most common indications for therapy were nosocomial pneumonias followed by intraabdominal postoperative infections, and skin and soft tissue infections. Patients enrolled into the study received imipenem cilastatin as part of their medical care. Minimum inhibitory concentrations mcgml disk diffusion zone diameter in mm. 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. Metabolized by kidneys, moderately dialyzable 2050% plasma protein binding % imi.
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. These doses should be used for patients with creatinine clearance of greater than or equal to 90 mlmin. When administered alone, imipenem is metabolized in the kidneys by dehydropeptidase, resulting in low imipenem urine levels. Doses as high as 5 mg per pound 10 mgkg every 8 hours have been. Indications and usage primaxin for intravenous use is a combination of imipenem, a penem antibacterial, and cilastatin, a renal. This medicine will not work for colds, flu, or other virus infections. Although not all of these side effects may occur, if they do occur they may need medical attention. Imipenem and cilastatin intravenous route, intramuscular. 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. Imipenem binds to the bacterial cell wall, resulting in cell death. This medication is given by injection into a muscle or vein, usually every 6 to 8 hours or as directed by your doctor. Includes dosages for bacterial infection, urinary tract infection, bronchitis and more.
The removal of imipenem and cilastatin by hemodialysis was studied in 14 for imipenem and 6 for cilastatin subjects. 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. 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. A healthcare provider will give your first dose and may teach you how to properly use the medication by yourself.
Detailed cilastatin imipenem dosage information for adults and children. Imipenemcilastatin daviss drug guide for rehabilitation. Imipenem with cilastatin medicinal forms bnfc content. Combination of imipenem and cilastatin that is used in the treatment of bacterial infections. 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 is rapidly hydrolysed by the enzyme dehydropeptidase i located on the brush border of renal tubular cells. The recommended dosage is 250 mg to 1 gram given intravenously.
For intravenous infusion dilute to a concentration of 5 mg as imipenemml in sodium chloride 0. Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary. Imipenem and cilastatin dosage in renal impairment reduced i. 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. Thus, it is used as combination with cilastatin, a reversible inhibitor of dehydropeptidase i, which has matched pharmacokinetics with imipenem t12 of both is. Dosage regimen based on creatinine clearance mlminute1.
Addition of cilastatin prevents renal inactivation of imipenem, resulting in increased urinary concentration. Evaluation of the appropriateness of imipenemcilastatin prescription. If infection suspectedproven due to susceptible bacterial species. In dogs and cats, the usual dose of imipenem with cilastatin is 2. Compared with iv administration, imipenem is approximately 75% bioavailable after im use with cilastatin being 95% bioavailable. Tore midtvedt, in side effects of drugs annual, 2011. Cilastatin, a renal dipeptidase inhibitor, inhibits the enzymatic breakdown of imipenem and increases urinary excretion of the active drug. Primaxin imipenem and cilastatin for injection, for intravenous use initial u.
Injection vial 500mg imipenem and 500mg cilastatin powder add 10ml of. Dailymed imipenem and cilastatin imipenem and cilastatin. 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. In one newborn who received a 15mgkg intravenous dose, concentrations of 1.
Imipenem is metabolized in the kidney by dehydropeptidase 1. Detailed cilastatin imipenem relebactam dosage information for adults. Developmental toxicity studies with imipenem and cilastatin alone or in combination administered parenterally during organogenesis to mice, rats, rabbits, and monkeys at doses 1 to 5 times the maximum recommended human dose mrhd of imipenem 500 mg cilastatin 500 mg every 6 hours for total daily doses of imipenem 2 g cilastatin 2 g based on. 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. Cilastatin prevents renal metabolism of imipenem by competitive. Cilastatin is a specific inhibitor of this enzyme and it prevents renal metabolism of imipenem. Nov 09, 2018 imipenem is an antibiotic that fights bacteria. Medscape indicationspecific dosing for primaxin imipenemcilastatin. Neonates 32 wk gestation 4075 mgkgday iv divided q812h for at least 2wk. For intravenous infusion dilute to a concentration of 5 mg as imipenem ml in sodium chloride 0.
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