Other Names/Brands

Fiocilas, Imiclast, Imipex, Pelascap, Pelastin, Tienam, Timipen, Xerxes IV

Mechanism of Action

Imipenem-cilastatin is a combination of two drugs that work together to treat severe bacterial infections. Imipenem is a carbapenem antibiotic that works by inhibiting bacterial cell wall synthesis, resulting in bacterial death.

However, imipenem can be broken down by the dehydropeptidase-I enzyme in the kidneys, which reduces its effectiveness. Therefore, this drug is combined with cilastatin, a dehydropeptidase-I inhibitor, to prevent imipenem's breakdown in the kidneys and prolong its duration of action in the body. This combination allows imipenem to achieve optimal therapeutic concentrations to kill a wide range of gram-positive and gram-negative bacteria.

Indications

Imipenem-cilastatin is indicated for the treatment of a variety of severe bacterial infections caused by susceptible microorganisms. This drug is used for lower respiratory tract infections, complicated urinary tract infections, intra-abdominal infections, skin and soft tissue infections, bone and joint infections, and gynecological infections such as endometritis.

This combination may also be given to patients with sepsis or other severe systemic infections, especially when a broad-spectrum antibiotic effective against gram-positive, gram-negative, and anaerobic bacteria is needed.

Contraindications

Imipenem-cilastatin is contraindicated in patients with hypersensitivity or allergy to imipenem, cilastatin, or other beta-lactam antibiotics such as penicillins and cephalosporins, as it can cause severe allergic reactions such as anaphylaxis.

This drug is also not recommended for use in patients with a history of severe, uncontrolled seizures, as imipenem can lower the seizure threshold. Furthermore, use should be avoided in patients with severe renal failure without appropriate dose adjustment, as it may increase the risk of drug toxicity.

Side Effects

Side effects of imipenem-cilastatin can include gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal pain. Allergic reactions, ranging from skin rashes to anaphylaxis, can also occur in patients sensitive to beta-lactam antibiotics.

This drug can cause central nervous system disturbances such as headache, dizziness, tremors, or seizures, especially in patients with impaired kidney function. Other possible side effects include elevated liver enzymes, thrombophlebitis at the injection site, and changes in laboratory values ​​such as increased creatinine or BUN.

Preparations

Imipenem-cilastatin is available as a powder for intravenous or intramuscular injection that must be dissolved before use. Each vial generally contains a combination of 250 mg or 500 mg of imipenem with an equivalent amount of cilastatin (250 mg or 500 mg), so the total dose per vial is usually 250/250 mg or 500/500 mg. This preparation is administered by intravenous infusion under medical supervision because it is used to treat severe infections that require parenteral antibiotic therapy.

Dosage

The dosage of imipenem-cilastatin varies depending on the type and severity of the infection, as well as the patient's renal function:

• The adult dose is 500 mg to 1 gram every 6–8 hours administered intravenously, with a total daily dose not exceeding 4 grams. In patients with impaired renal function, the dosage must be adjusted to prevent drug accumulation and the risk of side effects, such as seizures.
• The pediatric dose is usually calculated based on body weight, approximately 15–25 mg/kg every 6 hours, depending on the severity of the infection and the patient's clinical condition.

Safety of Drugs

Imipenem-cilastatin is classified as a pregnancy category C by the FDA, meaning that animal studies have shown adverse effects on the fetus, but there are no adequate, controlled studies in humans. Use in pregnant women is only permitted if the expected benefit outweighs the potential risk to the fetus. Furthermore, imipenem and cilastatin are excreted in breast milk, so caution should be exercised when using them in breastfeeding mothers.

Drug Interactions

Imipenem-cilastatin can interact with several other medications, affecting their effectiveness or increasing the risk of side effects. Combination with valproic acid can decrease valproate blood levels and increase the risk of seizures. Concurrent use with ganciclovir or cyclosporine can also increase the risk of seizures or central nervous system toxicity. Furthermore, coadministration with nephrotoxic medications (such as aminoglycosides or amphotericin B) can increase the risk of kidney dysfunction.

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