Usage
Imipenem, administered in combination with Cilastatin, is a broad-spectrum carbapenem antibiotic indicated for the treatment of various bacterial infections, including:
- Lower respiratory tract infections
- Urinary tract infections
- Intra-abdominal infections
- Gynecological infections
- Skin and skin structure infections
- Bacterial septicemia
- Bone and joint infections
- Endocarditis
Pharmacological Classification: Carbapenem Antibiotic
Mechanism of Action: Imipenem exerts its bactericidal effect by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs). Cilastatin, a renal dehydropeptidase inhibitor, prevents the renal metabolism of Imipenem, thereby increasing its serum half-life and efficacy.
Alternate Names
Imipenem is primarily known by its generic name. It is most commonly administered in a fixed-dose combination with Cilastatin.
Brand Names: Primaxin IM, Primaxin IV, Recarbrio (in combination with Cilastatin and Relebactam).
How It Works
Pharmacodynamics: Imipenem’s bactericidal action stems from its ability to irreversibly bind to PBPs, crucial enzymes involved in the final stages of peptidoglycan synthesis, a key component of the bacterial cell wall. This binding disrupts cell wall integrity, leading to bacterial cell death.
Pharmacokinetics:
- Absorption: Imipenem is administered intravenously (IV) or intramuscularly (IM). It exhibits rapid and complete absorption after IV administration.
- Distribution: Widely distributed throughout the body, including tissues and fluids.
- Metabolism: Imipenem is metabolized in the kidneys by dehydropeptidase I. Cilastatin effectively inhibits this metabolism, enhancing Imipenem’s efficacy.
- Elimination: Primarily eliminated renally, with approximately 70% excreted unchanged in the urine within 10 hours.
Mode of Action: Imipenem targets PBPs located on the inner bacterial cell membrane. Its binding to PBPs disrupts the transpeptidation and transglycosylation reactions essential for peptidoglycan cross-linking and elongation, ultimately leading to bacterial cell lysis and death.
Elimination Pathways: Predominantly renal excretion.
Dosage
Standard Dosage
Adults:
- IV: 250 mg to 1 g every 6 to 8 hours, infused over 20-30 minutes for doses ≤500 mg and 40-60 minutes for doses >500 mg. Maximum daily dose: 4 g or 50 mg/kg, whichever is lower.
- IM: 500 mg to 750 mg every 12 hours.
Children (≥ 3 months):
- 15-25 mg/kg every 6 hours IV. Maximum daily dose: 2 g for fully susceptible organisms or 4 g for moderately susceptible organisms.
Special Cases:
- Elderly Patients: No dose adjustment is needed for patients with normal renal function. Monitor renal function.
- Patients with Renal Impairment: Dose adjustment is required. Consult specific guidelines based on creatinine clearance.
- Patients with Hepatic Dysfunction: No dose adjustment is typically needed.
Clinical Use Cases
Dosage adjustments may be necessary based on infection severity and pathogen susceptibility. Consult local guidelines and expert recommendations.
Dosage Adjustments
Dosage adjustments are necessary based on renal function. Consult specific guidelines based on creatinine clearance for appropriate dose reduction.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Pain, swelling, or redness at the injection site
- Rash
Rare but Serious Side Effects:
- Seizures
- Allergic reactions (anaphylaxis, hives, difficulty breathing)
- Clostridium difficile-associated diarrhea
- Bone marrow suppression (neutropenia, thrombocytopenia)
- Pseudomembranous colitis
- Toxic epidermal necrolysis
- Stevens-Johnson Syndrome
Adverse Drug Reactions (ADR):
- Anaphylaxis requiring immediate intervention with epinephrine.
- Seizures requiring anticonvulsant therapy and discontinuation of Imipenem.
Contraindications
- Hypersensitivity to Imipenem, Cilastatin, or other carbapenems.
- Hypersensitivity to beta-lactam antibiotics (penicillins, cephalosporins).
Drug Interactions
- Valproic Acid/Divalproex Sodium: Decreased valproic acid levels and risk of seizures.
- Ganciclovir: Increased risk of seizures.
- Probenecid: Increased Imipenem serum concentrations.
- Anticoagulants (Warfarin): May enhance anticoagulant effects. Careful monitoring is advised
Pregnancy and Breastfeeding
- Pregnancy: Use only if clearly needed. Risk Summary: Potential risks based on embryonic loss observed in animal studies. Insufficient data available on use in pregnant women.
- Breastfeeding: LactMed considers use acceptable. However, weigh the benefits of breastfeeding against potential risks to the infant. Some sources do not recommend breastfeeding, or advise careful consideration of risks/benefits.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.
- Side Effects: Nausea, vomiting, diarrhea, injection site reactions, rash; seizures, allergic reactions (rare but serious).
- Contraindications: Hypersensitivity to Imipenem, Cilastatin, or beta-lactams.
- Drug Interactions: Valproic acid, ganciclovir, probenecid, anticoagulants.
- Pregnancy & Breastfeeding: Use with caution; potential risks to the fetus and neonate.
- Dosage: See dosage section for details.
- Monitoring Parameters: Renal function, signs of hypersensitivity, complete blood count, liver function tests.
Popular Combinations
Imipenem/Cilastatin is often used alone. The addition of other antibiotics is generally not recommended due to the broad spectrum of Imipenem.
Precautions
- General Precautions: Assess renal function before and during therapy. Monitor for signs of hypersensitivity.
- Specific Populations: See Special Cases under Dosage.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Imipenem/Cilastatin?
A: See the Dosage section for detailed information, including adjustments for specific populations.
Q2: What are the most serious side effects of Imipenem/Cilastatin?
A: Seizures, allergic reactions (including anaphylaxis), Clostridium difficile infection, and bone marrow suppression.
Q3: What drug interactions should be considered with Imipenem/Cilastatin?
A: Avoid concurrent use with valproic acid/divalproex sodium and ganciclovir due to the increased risk of seizures. Use with caution in patients on anticoagulants.
Q4: Can Imipenem/Cilastatin be used during pregnancy and breastfeeding?
A: Use during pregnancy only if the benefits outweigh the potential risks to the fetus. Consult with a specialist. While LactMed considers its use during breastfeeding acceptable, some sources suggest caution, recommending that a decision be made based on weighing the benefits of breastfeeding against potential risks to the infant.
Q5: How is Imipenem/Cilastatin administered?
A: Administered intravenously (IV) or intramuscularly (IM).
Q6: What are the indications for Imipenem/Cilastatin?
A: Indicated for a wide range of bacterial infections, including lower respiratory tract infections, urinary tract infections, intra-abdominal infections, gynecological infections, skin infections, and septicemia.
Q7: What is the mechanism of action of Imipenem/Cilastatin?
A: Imipenem inhibits bacterial cell wall synthesis, while Cilastatin prevents renal metabolism of Imipenem.
Q8: How should Imipenem/Cilastatin dosage be adjusted in patients with renal impairment?
A: Dosage adjustments are based on creatinine clearance. Consult specific guidelines for appropriate dosage reduction.
Q9: What should I do if a patient experiences a seizure while taking Imipenem/Cilastatin?
A: Discontinue Imipenem/Cilastatin immediately and administer appropriate anticonvulsant therapy.
