About this Calculator

The Imipenem-Cilastatin-Relebactam Dose Calculator is a clinical support tool designed to assist healthcare professionals in determining the appropriate dosing regimen for RECARBRIO™ based on patient-specific factors. It focuses on dosage adjustments required for patients with renal impairment, a critical consideration for ensuring both efficacy and safety of this antibiotic combination.

Outputs

After processing the inputs, the calculator provides a clear, actionable dosing recommendation. The output includes:

• Recommended Dose: The total combined dose (e.g., 1.25 g) to be administered.
• Component Breakdown: The specific amount of imipenem, cilastatin, and relebactam in the recommended dose.
• Administration Details: The required frequency (every 6 hours) and infusion time (30 minutes).
• Patient Parameters: The calculated creatinine clearance (CrCl) and the corresponding renal function category.
• Clinical Context: The indication selected for treatment.
• Important Notes: Special considerations, such as dosing instructions for patients on hemodialysis or warnings for severe renal impairment without dialysis.

How to Use

To use the calculator, enter the following patient data into the corresponding fields:

1. Indication for Use: Select the relevant indication (Complicated Urinary Tract Infection or Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia).
2. Patient Age: Enter the patient's age in years.
3. Patient Weight: Provide the patient's actual body weight in either kilograms (kg) or pounds (lbs).
4. Patient Sex: Select male or female, as this is a factor in the Cockcroft-Gault equation.
5. Serum Creatinine (SCr): Input the most recent serum creatinine value, selecting the correct units (mg/dL or µmol/L).
6. Hemodialysis Status: Check the box if the patient is on maintenance hemodialysis.

Dosing Overview

The dosage of imipenem-cilastatin-relebactam must be adjusted according to the patient's estimated creatinine clearance (eCrCl) to prevent drug accumulation and potential toxicity, particularly CNS adverse reactions. The standard administration is a 30-minute intravenous infusion every 6 hours.

For patients with eCrCl <15 mL/min who are not on hemodialysis, there is insufficient clinical data to recommend a dose. This medication should be used with caution in this population.

Switching Therapy

When switching a patient to imipenem-cilastatin-relebactam from another antimicrobial agent, clinicians should consider the patient's clinical status, the spectrum of activity of the previous agent, and local susceptibility patterns. A new renal function assessment should be performed before initiating therapy to ensure the correct starting dose.

Missed Dose

If a dose is missed, it should be administered as soon as possible. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Patients should be instructed not to take a double dose to make up for a missed one. The regular dosing schedule should be resumed thereafter.

Safety Alerts

Imipenem-cilastatin-relebactam is associated with several important safety considerations:

• Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported with carbapenems. Inquire about previous hypersensitivity to carbapenems, penicillins, or other beta-lactam agents before initiation.
• Seizures and CNS Adverse Reactions: Carbapenems may cause CNS adverse reactions, including seizures, confusional states, and myoclonic activity. The risk is increased in patients with renal impairment and pre-existing CNS disorders. Ensure dose is adjusted for renal function.
• Clostridioides difficile-Associated Diarrhea (CDAD): CDAD has been reported with nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis.

Frequently Asked Questions

What formula does the calculator use to estimate renal function?
The calculator uses the Cockcroft-Gault equation to estimate creatinine clearance (CrCl), as specified in the drug's prescribing information for dose adjustments.

Does the calculation use actual, ideal, or adjusted body weight?
The Cockcroft-Gault calculation within this tool uses the patient's Actual Body Weight (ABW).

What is the dose for patients with CrCl < 15 mL/min who are not on hemodialysis?
There is insufficient information to provide a dosing recommendation for this population. Use of the drug should be carefully considered and based on a risk-benefit assessment by the clinical team.

How should the dose be timed for a hemodialysis patient?
For patients on maintenance hemodialysis, the dose of imipenem-cilastatin-relebactam should be administered after the hemodialysis session is complete.

Can this calculator be used for pediatric patients?
This calculator is intended for use in adult patients only. The safety and effectiveness of imipenem-cilastatin-relebactam have not been established in pediatric patients.

Why is the dose reduced for patients with normal renal function (CrCl 60-89 mL/min) compared to those with high function (CrCl ≥ 90 mL/min)?
The dosing reflects findings from pharmacokinetic modeling. The 1 g dose in patients with CrCl 60-89 mL/min and the 1.25 g dose in those with CrCl ≥ 90 mL/min achieve comparable systemic exposures.

How does the calculator handle different units for weight and serum creatinine?
The tool automatically converts pounds (lbs) to kilograms (kg) and micromoles per liter (µmol/L) to milligrams per deciliter (mg/dL) to perform the calculation correctly.

References

1. RECARBRIO™ (imipenem, cilastatin, and relebactam) Prescribing Information. Merck Sharp & Dohme LLC. U.S. Food and Drug Administration. Revised: 06/2023.
2. RECARBRIO™ Professional Site. Merck & Co., Inc.
3. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111.
4. Drugs@FDA: FDA-Approved Drugs. U.S. Food and Drug Administration.