Normal Dose of Imipenem-Cilastatin for Adults with Normal Renal Function
For adults with normal renal function (creatinine clearance ≥90 mL/min), the standard dosing is 500 mg every 6 hours OR 1,000 mg every 8 hours, with 1,000 mg every 6 hours reserved for severe infections. 1
Standard Dosing Regimens
The FDA-approved dosing options for adults with normal renal function include three regimens 1:
- 500 mg every 6 hours (2 g/day total)
- 1,000 mg every 8 hours (3 g/day total)
- 1,000 mg every 6 hours (4 g/day total) - for severe infections
Indication-Specific Dosing
For critically ill patients with healthcare-associated intra-abdominal infections, the recommended dose is 1 g every 8 hours 2, 3. This aligns with the higher end of standard dosing for serious infections.
For drug-resistant tuberculosis (when used as a second-line agent), the dosing is 1,000 mg 3-4 times daily 4. This represents the upper limit of dosing and should be combined with clavulanate (250 mg three times daily) to enhance activity 4.
Weight-Based Dosing Considerations
For adults weighing considerations 2:
- Over 50 kg: 1 g twice daily (intravenously)
- Under 50 kg: 15 mg/kg twice daily (intravenously)
Administration Details
Each dose must be administered by intravenous infusion after proper reconstitution and dilution 1. The infusion should be given slowly to minimize gastrointestinal side effects, particularly nausea and vomiting, which occur commonly during IV administration 5.
Pharmacokinetic Rationale
The dosing intervals are based on imipenem's pharmacokinetics 6, 7:
- Half-life: Approximately 1 hour in patients with normal renal function
- Plasma clearance: Averages 220 mL/min
- Renal clearance: Accounts for 60-70% of total clearance when co-administered with cilastatin
- Therapeutic levels: Maintained for 8-10 hours after a 500 mg dose
The 1:1 ratio of imipenem to cilastatin is essential because cilastatin inhibits renal dehydropeptidase-I, preventing imipenem degradation and increasing urinary recovery from 5.5-42.5% (imipenem alone) to approximately 70% (with cilastatin) 8.
Critical Monitoring Requirements
Routine drug level monitoring is not required 2, 9. However, for prolonged treatment, periodic assessment should include 2, 9:
- Complete blood count
- Renal function tests
- Liver function tests
Important Safety Considerations
Seizure risk increases with higher doses and in specific patient populations 1, 5:
- Seizures occur in 1-3% of treated patients
- Risk factors include renal insufficiency and underlying CNS disease
- If seizures occur, evaluate neurologically, initiate anticonvulsants, and consider dose reduction or discontinuation
Avoid co-administration with valproic acid/divalproex sodium, as imipenem reduces valproic acid concentrations below therapeutic range, increasing breakthrough seizure risk 9, 1.
Concomitant use with ganciclovir increases seizure risk 2, 9.
Common Pitfalls to Avoid
- Do not use in patients with meningitis - safety and efficacy not established 1
- Do not exceed maximum doses without clear indication - higher doses increase seizure risk 5
- Do not use eGFR for dosing calculations - use Cockcroft-Gault formula for creatinine clearance instead 9
- Do not administer as rapid IV push - infuse slowly to minimize nausea and vomiting 5