Comprehensive Guide to Imipenem/Cilastatin: Uses, Dosage, Side Effects, and More
What is Imipenem/Cilastatin?
Overview of Imipenem/Cilastatin
Generic Name: Imipenem/Cilastatin
Brand Name: Primaxin, generics
Drug Group: Carbapenem antibiotic (antibacterial)
Commonly Used For
- Treat complicated intra-abdominal infections.
- Manage hospital-acquired pneumonia.
- Address bacterial septicemia.
Key Characteristics
Form: Powder for intravenous infusion (250 mg/250 mg, 500 mg/500 mg) (detailed in Dosage section).
Mechanism: Imipenem inhibits peptidoglycan synthesis; Cilastatin inhibits dehydropeptidase-I, preventing degradation.
Approval: FDA-approved (1985 for Primaxin) and EMA-approved for severe infections.
Indications and Uses of Imipenem/Cilastatin
Imipenem/Cilastatin is indicated for a variety of severe bacterial infections, leveraging its broad-spectrum activity:
Complicated Intra-Abdominal Infections: Treats appendicitis, peritonitis, and abscesses caused by E. coli or Bacteroides fragilis, per infectious disease guidelines, supported by clinical trials showing 85–90% cure rates.
Hospital-Acquired Pneumonia: Manages ventilator-associated pneumonia caused by Pseudomonas aeruginosa, recommended in critical care protocols with evidence of reduced mortality.
Bacterial Septicemia: Controls bloodstream infections from multidrug-resistant (MDR) pathogens, with hematology-infectious disease data.
Complicated Urinary Tract Infections (cUTI): Treats pyelonephritis and catheter-related infections, reducing bacterial load, per urology studies.
Skin and Soft Tissue Infections: Investigated off-label for necrotizing fasciitis, with surgical-infectious disease evidence.
Meningitis: Managed off-label in MDR bacterial meningitis (e.g., Acinetobacter), with neurology-infectious disease research.
Febrile Neutropenia: Explored off-label in cancer patients with fever and low neutrophils, with oncology data.
Bone and Joint Infections: Used off-label for osteomyelitis caused by resistant strains, with orthopedic studies.
Endocarditis: Initiated off-label for prosthetic valve endocarditis, with cardiology-infectious disease evidence.
Cystic Fibrosis Exacerbations: Applied off-label to treat Pseudomonas lung infections, with pulmonology research.
Dosage of Imipenem/Cilastatin
Dosage for Adults
Complicated Intra-Abdominal Infections: 500 mg every 6 hours or 1 g every 8 hours via IV infusion over 20–30 minutes, for 5–14 days.
Hospital-Acquired Pneumonia: 1 g every 8 hours, adjusted for severity, for 7–14 days.
Bacterial Septicemia: 1 g every 6–8 hours, with a maximum of 4 g/day, for 7–21 days.
Dosage for Children (≥3 months)
Severe Infections: 15–25 mg/kg every 6 hours (max 1 g per dose or 4 g/day), under pediatric infectious disease supervision, for 7–14 days.
Dosage for Pregnant Women
Pregnancy Category C: Use only if benefits outweigh risks; consult an obstetrician and infectious disease specialist, with fetal monitoring.
Dosage Adjustments
Renal Impairment:
- CrCl 30–70 mL/min: 500 mg every 6–8 hours.
- CrCl 10–30 mL/min: 250–500 mg every 12 hours.
- CrCl <10 mL/min: 250 mg every 12 hours or avoid if on hemodialysis.
Hepatic Impairment:
Mild to moderate (Child-Pugh A or B): Use cautiously; severe (Child-Pugh C): Avoid due to limited data.
Concomitant Medications: Adjust if combined with valproic acid, reducing levels; monitor seizures.
Elderly: No specific adjustment; assess renal function and reduce dose if needed.
Hemodialysis: Administer 250–500 mg post-dialysis, with additional doses based on infection severity.
Additional Considerations
- Administer this active ingredient via IV infusion over 20–30 minutes to minimize venous irritation.
- Reconstitute with compatible fluids (e.g., 0.9% saline) and use within 4 hours if stored at room temperature.
- Monitor renal function and neurological status during therapy.
How to Use Imipenem/Cilastatin
Administration:
IV Infusion: Reconstitute with 10 mL sterile water, dilute in 100 mL compatible fluid, and infuse over 20–30 minutes.
Use a dedicated line to avoid incompatibility with other drugs.
Timing: Administer every 6–8 hours as prescribed, maintaining consistent intervals.
Monitoring: Watch for seizures, rash, or signs of superinfection (e.g., diarrhea, fever); report changes immediately.
Additional Tips:
- Store powder at 15–30°C (59–86°F), protecting from moisture; reconstituted solution stable for 4 hours at room temperature or 24 hours if refrigerated.
- Keep out of reach of children; dispose of unused vials per hospital protocols.
- Educate patients on signs of allergic reactions or neurological symptoms; ensure IV site care to prevent phlebitis.
- Schedule regular blood tests (e.g., CBC, renal function) every 2–3 days to monitor for toxicity or resistance.
- Avoid rapid infusion to reduce seizure risk, especially in patients with renal impairment.
Contraindications for Imipenem/Cilastatin
Hypersensitivity: Patients with a known allergy to Imipenem, Cilastatin, other carbapenems, or penicillins.
Severe Renal Impairment: Contraindicated in CrCl <10 mL/min without dialysis due to accumulation risk.
History of Seizures: Avoid in patients with uncontrolled epilepsy due to CNS toxicity.
Hypersensitivity to Beta-Lactams: Contraindicated in those with severe reactions to cephalosporins or penicillins.
Clostridioides difficile Infection: Avoid in active cases to prevent exacerbation.
Infants <3 Months: Contraindicated due to immature renal function and safety data gaps.
Warnings & Precautions for Imipenem/Cilastatin
General Warnings
Seizures: Risk of CNS toxicity, especially in renal impairment; monitor EEG if symptoms arise.
Clostridioides difficile Infection: Risk of pseudomembranous colitis; assess diarrhea promptly.
Renal Toxicity: Risk of nephrotoxicity with prolonged use; check CrCl regularly.
Allergic Reactions: Risk of anaphylaxis or Stevens-Johnson syndrome; discontinue if severe.
Superinfection: Risk of fungal or resistant bacterial growth; monitor for new symptoms.
Additional Warnings
Hepatic Injury: Rare elevation of liver enzymes; monitor hepatic function.
Hypotension: Risk with rapid IV administration; infuse slowly.
Blood Disorders: Rare neutropenia or thrombocytopenia; check CBC.
Neurological Effects: Risk of confusion or myoclonus; assess mental status.
Hypersensitivity Reactions: Rare severe reactions; stop if rash or swelling occurs.
Use in Specific Populations
Pregnancy: Category C; use with caution, monitoring fetal outcomes.
Breastfeeding: Use caution; monitor infant for diarrhea or rash.
Elderly: Higher risk of renal decline; adjust dose and monitor closely.
Children: Safe for ≥3 months with supervision.
Renal/Hepatic Impairment: Adjust or avoid based on severity.
Additional Precautions
- Inform your doctor about kidney disease, seizure history, or allergies before starting this medication.
- Avoid concurrent use with valproic acid unless monitored for seizure control.
- Use aseptic technique during IV administration to prevent contamination.
Overdose and Management of Imipenem/Cilastatin
Overdose Symptoms
- Nausea, vomiting, or diarrhea.
- Severe cases: Seizures, encephalopathy, or renal failure.
- Dizziness, confusion, or tremor as early signs.
- Coma or profound hypotension with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help if overdose occurs.
Supportive Care: Monitor vital signs, provide IV fluids, and manage seizures with benzodiazepines if needed.
Specific Treatment: No specific antidote; use hemodialysis to remove drug in severe cases.
Monitor: Check renal function, EEG, and neurological status for 24–48 hours.
Patient Education: Advise against self-administering extra doses and to report accidental over-infusion.
Additional Notes
- Overdose risk is linked to renal impairment or dosing errors; store securely and verify doses.
- Report persistent symptoms (e.g., severe headache, persistent vomiting) promptly.
Side Effects of Imipenem/Cilastatin
Common Side Effects
- Nausea (10–20%, managed with antiemetics)
- Diarrhea (5–15%, controlled with hydration)
- Rash (3–10%, relieved with antihistamines)
- Injection Site Reaction (2–8%, decreases with site rotation)
- Headache (2–6%, managed with rest)
These effects may subside with adaptation.
Serious Side Effects
Seek immediate medical attention for:
- Neurological: Seizures or encephalopathy.
- Gastrointestinal: Pseudomembranous colitis or severe diarrhea.
- Renal: Acute kidney injury or oliguria.
- Allergic: Anaphylaxis or Stevens-Johnson syndrome.
- Hematologic: Neutropenia or thrombocytopenia.
Additional Notes
Regular monitoring with renal function tests (e.g., CrCl) and CBC every 3–5 days is essential to detect toxicity.
Patients with a history of C. difficile should be monitored for recurrence, with probiotics considered.
EEG monitoring is recommended if neurological symptoms persist beyond 48 hours.
Report any unusual symptoms (e.g., confusion, blood in stool) immediately to an infectious disease specialist.
Prolonged use (>14 days) requires stool cultures to rule out resistant pathogens.
Drug Interactions with Imipenem/Cilastatin
This active ingredient may interact with:
- Valproic Acid: Reduces levels, increasing seizure risk; monitor and adjust.
- Ganciclovir: Increases seizure risk; use cautiously.
- Probenecid: Inhibits renal excretion, raising levels; avoid combination.
- Other Antibiotics: Potential antagonism with aminoglycosides; separate administration.
- Neurological Agents: Enhances CNS effects (e.g., phenytoin); monitor.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Use this carbapenem as prescribed for severe infections, following the IV schedule.
Monitoring: Report seizures, diarrhea, or signs of allergy immediately.
Lifestyle: Avoid alcohol to reduce gastrointestinal irritation; maintain hydration.
Diet: No specific restrictions; take with food if nausea occurs.
Emergency Awareness: Know signs of overdose or superinfection; seek care if present.
Follow-Up: Schedule regular check-ups every 2–3 days to monitor renal and neurological status.
Pharmacokinetics of Imipenem/Cilastatin
Absorption: IV only, immediate; no oral bioavailability.
Distribution: Volume of distribution ~0.2–0.3 L/kg; 20% protein-bound.
Metabolism: Imipenem metabolized by dehydropeptidase-I (inhibited by Cilastatin); Cilastatin unchanged.
Excretion: Primarily renal (70–75% unchanged); half-life 1 hour (Imipenem), 1 hour (Cilastatin).
Half-Life: 1 hour each, prolonged in renal impairment.
Pharmacodynamics of Imipenem/Cilastatin
This drug exerts its effects by:
Imipenem binding to penicillin-binding proteins, inhibiting cell wall synthesis in Gram-positive and Gram-negative bacteria.
Cilastatin preventing renal degradation, extending Imipenem’s half-life.
Exhibiting broad-spectrum activity against MDR pathogens, with dose-dependent risks of seizures and colitis.
Storage of Imipenem/Cilastatin
Temperature: Store powder at 15–30°C (59–86°F); protect from moisture.
Protection: Keep in original container, away from heat and light.
Safety: Store in a secure location out of reach of children and pets due to toxicity risk.
Disposal: Dispose of unused vials per hospital or local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Imipenem/Cilastatin treat?
A: This medication treats severe bacterial infections.
Q: Can this active ingredient cause nausea?
A: Yes, nausea is common; report if severe.
Q: Is Imipenem/Cilastatin safe for children?
A: Yes, for ≥3 months with supervision.
Q: How is this drug taken?
A: Via IV infusion, as directed.
Q: How long is Imipenem/Cilastatin treatment?
A: Typically 7–14 days, depending on infection.
Q: Can I use Imipenem/Cilastatin if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 1985 (Primaxin) for severe infections.
European Medicines Agency (EMA): Approved for hospital-acquired infections and septicemia.
Other Agencies: Approved globally for antibacterial therapy; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Primaxin (Imipenem/Cilastatin) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Imipenem/Cilastatin Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Imipenem/Cilastatin: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Imipenem/Cilastatin.
- WHO’s inclusion of Imipenem/Cilastatin for severe infections.
- Clinical Infectious Diseases. (2022). Imipenem/Cilastatin in MDR Infections.
- Peer-reviewed article on Imipenem/Cilastatin efficacy (note: access may require a subscription).
