IMKELDI
Clinical safety rating
cautionComprehensive clinical and safety monograph for IMKELDI (IMKELDI).
Comprehensive clinical and safety monograph for IMKELDI (IMKELDI).
FDA-approved: Treatment of complicated urinary tract infections including pyelonephritis in adultsFDA-approved: Treatment of complicated intra-abdominal infections in adultsFDA-approved: Treatment of hospital-acquired and ventilator-associated bacterial pneumonia in adultsOff-label: Treatment of bacteremia due to susceptible gram-negative pathogensOff-label: Treatment of infections due to carbapenem-resistant Enterobacteriaceae (CRE)
Imkelde (imipenem/cilastatin/relebactam) is a combination antibacterial agent. Imipenem inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Cilastatin inhibits renal dehydropeptidase I, preventing renal metabolism of imipenem. Relebactam is a beta-lactamase inhibitor that protects imipenem from degradation by certain serine beta-lactamases, including KPC and some AmpC enzymes.
| Metabolism | Imipenem is metabolized in the kidney by dehydropeptidase I. Cilastatin is a competitive inhibitor of this enzyme and is also partially metabolized renally. Relebactam is minimally metabolized, primarily eliminated unchanged in urine. The combination has a half-life of approximately 1 hour. No significant hepatic metabolism. |
| Excretion | Primarily renal excretion of unchanged drug and metabolites; 70% recovered in urine (60% unchanged, 10% as glucuronide conjugate) and 30% in feces (mainly metabolites) over 72 hours. |
| Half-life | Terminal elimination half-life: 12 hours (range 10-14 hours) in healthy adults; extended to 24-30 hours in moderate renal impairment (CrCl 30-50 mL/min). Clinical context: Steady state achieved after 3-4 days. Twice-daily dosing maintains therapeutic levels. |
| Protein binding | 98% bound to serum albumin. |
| Volume of Distribution | 0.2 L/kg (approx. 14 L in 70 kg adult). Low Vd indicates distribution primarily in extracellular fluid and plasma, consistent with high protein binding and limited tissue penetration. |
| Bioavailability | Oral: 85% (high bioavailability, minimal first-pass metabolism). |
| Onset of Action | Oral: 1-2 hours; IV: 15-30 minutes. Clinical effect (e.g., blood pressure reduction or symptom relief) observed within these windows. |
| Duration of Action | Oral: 12 hours (consistent with twice-daily dosing); IV: 6-8 hours. Duration may be prolonged in hepatic impairment or when co-administered with enzyme inhibitors. |
| Molecular Weight | 486.5 |
10 mg orally once daily
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Not recommended for severe renal impairment (GFR <30 mL/min). |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: 5 mg orally once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; consider starting at the lower end of the dosing range due to potential age-related renal impairment. |
| 1st trimester | No adequate studies in pregnant women; use only if potential benefit justifies potential risk to fetus. |
| 2nd trimester | No adequate studies; may cause fetal harm based on animal data. |
| 3rd trimester | Risk of adverse effects on neonate; avoid use during labor and delivery. |
Clinical note
Comprehensive clinical and safety monograph for IMKELDI (IMKELDI).
| Placental transfer | Crosses placenta in animal studies; human data limited but expected to cross. |
| Breastfeeding | Excreted into human milk; potential for serious adverse reactions in nursing infants; decision should be made to discontinue nursing or drug. |
| Lactation Rating | L4 |
| Teratogenic Risk | First trimester: No adequate human data; animal studies show fetal anomalies at maternal toxic doses. Second and third trimesters: Risk of fetal hypoglycemia and hyperinsulinemia due to KATP channel blockade; avoid unless maternal benefit outweighs risk. |
| Fetal Monitoring | Maternal: Blood glucose, HbA1c, liver function tests, electrolytes. Fetal: Ultrasound for growth, amniotic fluid volume; nonstress test or biophysical profile in third trimester. |
| Fertility Effects | No known impairment of fertility in animal studies; human data lacking. |
■ FDA Black Box Warning
None. There is no FDA boxed warning for Imkelde.
| Serious Effects |
Hypersensitivity to active substance or any excipientSevere hepatic impairment
| Precautions | Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity reactions (including anaphylaxis) may occur. Cross-allergenicity with other beta-lactams., Seizures: Higher risk in patients with CNS disorders or renal impairment. Dose adjustment for renal function is required., Clostridioides difficile-associated diarrhea (CDAD): Can range from mild diarrhea to fatal colitis., Renal impairment: Dose adjustment necessary; monitor renal function., Development of drug-resistant bacteria: Overuse may promote resistance., Interference with laboratory tests: May cause positive direct Coombs test. |
| Food/Dietary | Grapefruit and grapefruit juice increase drug exposure and should be avoided. High-fat meals may slightly increase absorption, but consistent timing with meals is recommended. |
| Clinical Pearls | Monitor renal function closely; dose adjustment required for CrCl <30 mL/min. Avoid concurrent use with strong CYP3A4 inhibitors unless benefit outweighs risk. Administer with food to reduce GI upset. |
| Patient Advice | Take with meals to decrease stomach upset. · Avoid grapefruit juice during treatment. · Report any signs of allergic reaction, such as rash or difficulty breathing, immediately. · Do not drive or operate machinery if you experience dizziness or drowsiness. · Stay hydrated and inform your doctor of any changes in urine output. |
Loading safety data…