IMKELDI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for IMKELDI (IMKELDI).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for IMKELDI (IMKELDI).

Breastfeeding	Excreted in breast milk; M/P ratio unknown. Potential for infant hypoglycemia; use with caution and monitor infant blood glucose.
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

Warnings & precautions

■ FDA Black Box Warning

None. There is no FDA boxed warning for Imkelde.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Known hypersensitivity to any component of Imkelde (imipenem, cilastatin, relebactam) or other beta-lactam antibiotics.","Contraindicated in patients with severe hypersensitivity (e.g., anaphylaxis) to any beta-lactam."]

Clinical Precautions

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."]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

IMKELDI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for IMKELDI (IMKELDI).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for IMKELDI (IMKELDI).

Breastfeeding	Excreted in breast milk; M/P ratio unknown. Potential for infant hypoglycemia; use with caution and monitor infant blood glucose.
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

Warnings & precautions

■ FDA Black Box Warning

None. There is no FDA boxed warning for Imkelde.

Side Effect Profile

Serious Effects

Absolute Contraindications

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…