FDA approves Recarbrio for complicated UTI and intra-abdominal infections

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The FDA has announced the approval of Merck’s combination drug Recarbrio (imipenem, cilastatin, and relebactam), indicated for the treatment of complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) in patients 18 years or older who have limited or no alternative treatment options. 

Per prescribing information, Recarbrio should only be used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. 

“The FDA remains focused on facilitating the development of safe and effective new antibacterial drugs to give patients more options to fight serious infections,” said Ed Cox, MD, Director for the Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research, in a statement. “It is important that the use of Recarbrio be reserved for situations when there are limited or no alternative antibacterial drugs for treating a patient’s infection.”

The recent approval is based upon two studies examining the efficacy and safety of imipenem-cilastatin for the treatment of cUTI and cIAI. In the cUTI study, 298 adult patients received treatment, with 99 patients receiving the proposed dose of Recarbrio. In the cIAI study, 347 patients were included, with 117 receiving proposed doses of Recarbrio.

Recarbrio is suggested to be administered at 1.25 g (imipenem 500 mg, cilastatin 500 mg, relebactam 250 mg) by intravenous infusion over 30 minutes every 6 hours in patients 18 years of age and older with creatine clearance (CrCl) of 90 mL/min or greater. Patients with CrCl under 15 mL/min should not receive Recarbrio unless hemodialysis is instituted within 48 hours. 

The most common adverse events reported throughout the clinical trials included nausea, diarrhea, headache, fever, and increased liver enzymes.

Recarbrio is contraindicated in patients with a known severe hypersensitivity to any component of the combination drug. 

Known adverse drug interactions listed in the prescribing information for Recarbrio include gancivlovir and valproic acid or divalproex sodium. 

Prescribing information for Recarbrio comes with warnings of hypersensitivity reactions, seizure, and central nervous system adverse reactions, increased seizure potential due to interaction with valproic acid, and Clostridium difficile-associated diarrhea.

Use in pregnant and lactating patients

There are insufficient data to establish the safety of Recarbrio for use in the pregnant patient. Developmental toxicity studies, embryofetal development studies, and reproductive studies using the components of Recarbrio were conducted in mice, rats, rabbits, and monkeys, and embryonic loss and fetal abnormalities were observed in some groups. Details are contained in the prescribing information. Pregnant women should be advised of the potential of major birth defects, miscarriage or adverse maternal or fetal outcomes with the use of Recarbrio.

Because Recarbrio is excreted by the kidneys the risk of adverse effects may be greater in patients with impaired renal function.

Insufficient data exist on the presence of Recarbrio and its components in human breast milk and the effect of these drugs on the breastfeeding child. No studies were conducted regarding the effect of Recarbrio on human milk production. When considering the use of Recarbrio, the manufacturers recommend that the benefits of breastfeeding be considered against the patient’s clinical need for the medication as well as the potential adverse effects from the underlying maternal condition on both mother and child.