Iropen(500 mg+500 mg)/vial

Imipenem and cilastatin is a broad-spectrum injectable carbapenem antibiotic used for the treatment of serious infections caused by susceptible bacteria, including:

• Lower respiratory tract infections
• Urinary tract infections (complicated and uncomplicated)
• Intra-abdominal infections
• Gynaecological infections
• Bacterial septicaemia
• Bone and joint infections
• Skin and soft tissue infections
• Endocarditis
• Polymicrobial infections, given its very broad spectrum of activity

Contains imipenem (a carbapenem antibiotic) and cilastatin sodium (a dehydropeptidase inhibitor) as active ingredients, supplied as a powder for reconstitution for intravenous infusion, in combined vial strengths, dosed and expressed in terms of the imipenem component.

Imipenem is a very broad-spectrum carbapenem antibiotic, one of the most powerful classes of antibiotics available, used for serious bacterial infections, often when other antibiotics have failed or resistant organisms are suspected. It is always combined with cilastatin, which blocks an enzyme in the kidney that would otherwise break down imipenem before it could work, protecting the antibiotic and preventing formation of a potentially toxic breakdown product. Imipenem/cilastatin is considered the most epileptogenic (seizure-triggering) carbapenem antibiotic, and its dose must be carefully adjusted for kidney function to minimize this risk, particularly in patients with a history of seizures or central nervous system disorders.

Therapeutic Class: Antibiotic (Carbapenem)

Imipenem is extensively hydrolyzed by an enzyme (dehydropeptidase I) in the kidney's proximal tubule, producing a potentially nephrotoxic inactive metabolite; cilastatin specifically inhibits this enzyme, preventing this breakdown and protecting the kidney, which is why imipenem is always given together with cilastatin rather than alone. Both components are eliminated by the kidneys, requiring dose adjustment in renal impairment, with a specific increased seizure risk when dosing is not appropriately reduced for reduced kidney function.

• Given only by intravenous infusion, by trained healthcare professionals, over the specific infusion time recommended for the dose being given (commonly 20-60 minutes, per institutional protocol)
• Nausea and vomiting during infusion are more likely with more rapid administration; slowing the infusion rate can help if this occurs
• Continue anticonvulsant therapy in patients with a known seizure disorder
• If focal tremors, myoclonus, or seizures occur during treatment, the patient should be evaluated neurologically, placed on anticonvulsant therapy if not already started, and the dose reassessed

The following interactions are particularly important:

• Valproic acid / divalproex sodium: imipenem/cilastatin can significantly decrease valproic acid blood levels, potentially below the therapeutic range, increasing the risk of breakthrough seizures; this combination is generally not recommended, and if unavoidable, additional or alternative anticonvulsant therapy should be considered, with close monitoring.
• Ganciclovir: combined use has been associated with generalized seizures; avoid combining unless the potential benefit outweighs the risk.
• Other medicines that lower the seizure threshold (such as certain antidepressants, quinolone antibiotics, or theophylline): may increase seizure risk when combined with imipenem/cilastatin.

Common side effects

• Phlebitis (vein inflammation) and pain at the injection site
• Nausea, diarrhoea, vomiting
• Rash
• Fever

Serious side effects (seek urgent medical attention)

• Seizures: imipenem/cilastatin carries a higher seizure risk than other carbapenems, particularly with inadequate dose reduction for renal function, high doses, pre-existing CNS disorders, or a history of seizures; report any tremors, muscle twitching, or seizure activity immediately.
• Clostridioides difficile-associated diarrhoea (CDAD): can range from mild diarrhoea to severe, fatal colitis; evaluate promptly if diarrhoea occurs, particularly if severe or persistent.
• Serious, occasionally fatal hypersensitivity reactions, including anaphylaxis; a careful allergy history to beta-lactam antibiotics (penicillins, cephalosporins, other carbapenems) should be taken before starting.
• Hepatotoxicity, including rare reports of fulminant hepatitis and hepatic failure; jaundice and tooth/tongue staining have also been reported.
• Blood disorders: pancytopenia, bone marrow suppression, thrombocytopenia, neutropenia, leukopenia, haemolytic anaemia, and agranulocytosis have been reported.

Pregnancy

There are no adequate, well-controlled studies of imipenem/cilastatin in pregnant women; animal developmental toxicity studies have not shown evidence of teratogenicity. Use during pregnancy should only occur if the potential benefit justifies the potential risk to mother and fetus, as determined by the treating physician.

Breastfeeding

Imipenem passes into breast milk in small amounts; use during breastfeeding should be discussed with a healthcare professional, with the nursing infant monitored for diarrhoea or thrush.

• Seizure risk: the dose must be carefully adjusted for renal function to minimize this risk; use with particular caution in patients with a history of seizures, CNS lesions, or other risk factors for seizure activity - a well-controlled seizure disorder is not necessarily a reason to avoid a carbapenem, but requires careful, informed dosing.
• Renal dose adjustment is essential - inadequate reduction of dose in renal impairment significantly increases seizure risk.
• Beta-lactam allergy: take a careful allergy history, given the risk of cross-reactivity and serious hypersensitivity reactions with this antibiotic class.
• Prolonged use may lead to overgrowth of non-susceptible organisms, including fungi.
• Avoid combining with valproic acid/divalproex sodium where possible, given the significant risk of reduced valproic acid levels and breakthrough seizures.

Overdose may cause exaggerated gastrointestinal effects and, particularly relevant to this antibiotic, an increased risk of seizures, especially in patients with renal impairment where drug clearance is reduced. Suspected significant overdose should be evaluated by a healthcare professional; treatment is generally supportive, including seizure management as clinically indicated, and haemodialysis can help remove imipenem/cilastatin from the blood in patients with significant renal impairment and overdose.

Store unreconstituted powder at controlled room temperature, protected from light, as directed on the product label. Reconstituted and diluted infusion solutions should be used within the manufacturer's specified time frame; discard any unused portion after this period.

• Renal impairment: Requires significant dose reduction based on creatinine clearance, given both accumulation risk and the specific increased seizure risk associated with this antibiotic; not recommended when creatinine clearance is below 15 mL/min unless haemodialysis is instituted within 48 hours.
• Patients with a seizure history or CNS disorders: Use with caution, given imipenem's higher epileptogenic potential compared to other carbapenems; ensure anticonvulsant therapy is optimized and appropriately continued.
• Children 3 months and older: Established for use, with weight-based dosing per the treating physician's protocol.
• Elderly: Often have reduced renal function even with normal-appearing serum creatinine; careful renal-function-based dosing is particularly important in this group.

Treatment duration depends on the specific infection and clinical response, commonly ranging from several days to two weeks or longer for more serious infections (such as endocarditis or bone/joint infections), as determined by the treating physician.

The lyophilized powder must be reconstituted per the specific product's instructions (commonly with an appropriate IV diluent) immediately before use, then infused over the recommended duration for the dose being given. Reconstituted and diluted solutions should be used within the manufacturer's specified stability window.

Drug Class: Carbapenem antibacterial (imipenem) combined with a dehydropeptidase-I inhibitor (cilastatin)

Imipenem works by binding to penicillin-binding proteins involved in bacterial cell wall synthesis, disrupting the ability of a very broad range of gram-positive, gram-negative, and anaerobic bacteria to build and maintain their cell walls, which kills the bacteria. Cilastatin itself has no antibacterial activity; its sole role is to block the kidney enzyme that would otherwise rapidly break down imipenem, ensuring adequate imipenem levels are maintained in the urinary tract and bloodstream.

Imipenem and cilastatin is used in children 3 months of age and older for serious bacterial infections, with weight-based dosing determined by the treating physician; it was the first carbapenem evaluated for severe infections in children, though its epileptogenic potential is a particular concern in paediatric patients with bacterial meningitis, where alternative carbapenems with a lower seizure risk are often preferred for that specific indication.