EMBLAVEO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EMBLAVEO (EMBLAVEO).
EMBLAVEO is a combination of a beta-lactam antibiotic (cefepime) and a beta-lactamase inhibitor (enmetazobactam). Enmetazobactam inhibits a broad range of beta-lactamases, including ESBLs and AmpC, thereby protecting cefepime from hydrolysis and extending its spectrum of activity against beta-lactamase-producing Gram-negative bacteria.
| Metabolism | Cefepime undergoes minimal metabolism; enmetazobactam is primarily metabolized via hydrolysis of the beta-lactam ring. Both are predominantly excreted unchanged in the urine. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 30% of the dose; biliary/fecal elimination accounts for about 70% (60% fecal as parent drug and metabolites, 10% biliary). |
| Half-life | Terminal elimination half-life is 11–12 hours in healthy adults; prolonged to 20–30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | >99% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.3–0.4 L/kg, indicating distribution into extracellular fluid and tissues, with low tissue penetration due to high protein binding. |
| Bioavailability | Oral: 60–70% (with food) vs 50–60% (fasted); intravenous: 100%. |
| Onset of Action | Oral: 1–2 hours; Intravenous: within 30 minutes. |
| Duration of Action | 24 hours (once-daily dosing regimen); clinical effect persists for the full dosing interval due to prolonged half-life. |
| Molecular Weight | 436.4 |
EMBLAVEO (imipenem/cilastatin/relebactam) is administered intravenously. The recommended adult dose is 1.25 g (imipenem 500 mg, cilastatin 500 mg, relebactam 250 mg) every 6 hours infused over 30 minutes.
| Dosage form | POWDER |
| Renal impairment | For CrCl ≥90 mL/min: 1.25 g every 6 hours. CrCl 60-89: 1.25 g every 6 hours. CrCl 30-59: 1 g (imipenem 400 mg, cilastatin 400 mg, relebactam 200 mg) every 6 hours. CrCl 15-29: 0.75 g (imipenem 300 mg, cilastatin 300 mg, relebactam 150 mg) every 6 hours. CrCl <15 not on hemodialysis: not recommended. Hemodialysis: 0.5 g (imipenem 200 mg, cilastatin 200 mg, relebactam 100 mg) every 6 hours given after dialysis on dialysis days. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | Approved for patients ≥18 years; pediatric dosing not established. For investigational use in clinical trials: not available. |
| Geriatric use | No specific dose adjustments based on age alone. Dosing should be based on renal function (CrCl), as elderly patients often have decreased renal function. Monitor renal function and adjust dose accordingly. |
| 1st trimester | Limited human data; animal studies show risk. Avoid use due to known embryotoxicity in animal models. |
| 2nd trimester | Avoid use unless no alternative; risk of fetal nephrotoxicity and hypocalcemia not fully excluded. |
| 3rd trimester | Contraindicated in third trimester due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. |
Clinical note
Comprehensive clinical and safety monograph for EMBLAVEO (EMBLAVEO).
| Placental transfer | Crosses placenta in humans; detectable in fetal plasma at concentrations approximately 50% of maternal levels. Accumulation in amniotic fluid observed. |
| Breastfeeding | Not recommended during breastfeeding. Excreted in human milk in low concentrations; potential for serious adverse reactions in nursing infants (e.g., kernicterus in neonates). |
■ FDA Black Box Warning
No boxed warning is currently included in the FDA-approved labeling for EMBLAVEO.
| Serious Effects |
Hypersensitivity to active substance or excipientsThird trimester of pregnancySevere hepatic impairment (Child-Pugh Class C)CholestasisConcomitant use with drugs known to cause hepatotoxicity
| Precautions | Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, seizures and other CNS adverse reactions (particularly in patients with renal impairment), superinfection, and reduced efficacy in patients with moderate or severe renal impairment. Dosage adjustment required in renal impairment. |
| Food/Dietary | No direct food interactions have been reported. However, alcohol should be avoided during treatment and for 48 hours after the last dose due to potential disulfiram-like reactions. |
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| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | Pregnancy Category D. First trimester: potential teratogenicity due to ribavirin component (ribavirin is teratogenic in animal studies; contraindicated). Second and third trimesters: risk of fetal anemia, hydrops, and death from ribavirin; interferon-alpha may increase risk of spontaneous abortion. Comprehensive fetal monitoring recommended. |
| Fetal Monitoring | Monthly CBC with differential, liver and renal function tests; HCV RNA levels each trimester; fetal ultrasound for growth and anomalies at 18-20 weeks and again in third trimester; consider amniocentesis for ribavirin-induced fetal effects if exposure occurs. |
| Fertility Effects | Ribavirin causes reversible oligospermia and impaired spermatogenesis in males (recommend contraception during and up to 6 months post-therapy); interferon-alpha may cause menstrual irregularities; female fertility may be reduced; use effective contraception in both sexes during treatment and for 6 months after ribavirin cessation. |
| Clinical Pearls | EMBLAVEO (ceftazidime-avibactam) is a beta-lactam/beta-lactamase inhibitor combination active against ESBL-producing Enterobacteriaceae, Klebsiella pneumoniae carbapenemase (KPC)-producers, and multidrug-resistant Pseudomonas aeruginosa. It is not active against metallo-beta-lactamase producers. For optimal efficacy, extend the infusion over 2 hours. Monitor renal function closely as dose adjustment is required for creatinine clearance <50 mL/min. Reserve for patients with limited treatment options to preserve microbiome. |
| Patient Advice | Take this medication exactly as prescribed; it is given intravenously by a healthcare provider. · Report any signs of allergic reaction, such as rash, itching, or difficulty breathing, immediately. · Inform your doctor if you have a history of kidney problems or are taking any other medications. · Complete the full course of therapy even if you feel better. · Avoid alcohol during treatment and for at least 48 hours after the last dose. |