n site erythema, and infusion site pain.eCentral nervous system adverse reactions include agitation, apathy, confusional states, delirium, disorientation, slow speech,and somnolence.
fHypertension includes hypertension and blood pressure increased.
Other Adverse Reactions Associated with Imipenem/Cilastatin
Adverse reactions reported with imipenem/cilastatin in clinical studies or during post-marketingexperience, that are not listed above for patients treated with imipenem 500 mg/cilastatin 500 mg plusrelebactam 250 mg in Trials 1 and 2 are listed below:
Blood and Lymphatic System Disorders: agranulocytosis, increased eosinophils, hemolytic anemiaNervous System Disorders: seizureHepatobiliary Disorders: hepatic failure, jaundiceSkin and Subcutaneous Tissue Disorders: rashLaboratory Investigations: blood lactate dehydrogenase increased, coombs test positive, eosinophil count
increased
7 DRUG INTERACTIONS
7.1 Ganciclovir
Generalized seizures have been reported in patients who received ganciclovir concomitantly withimipenem/cilastatin, a component of RECARBRIO. Ganciclovir should not be used concomitantly withRECARBRIO unless the potential benefits outweigh the risks.
7.2 Valproic Acid
Based on case reports in the literature concomitant use of carbapenems, including imipenem/cilastatin(components of RECARBRIO) with valproic acid or divalproex sodium may decrease valproic acidconcentrations which may increase the risk of breakthrough seizures [see Warnings and Precautions(5.3)]. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g)back to valproic acid, thus decreasing the serum concentrations of valproic acid. Avoid concomitant useof RECARBRIO with valproic acid or divalproex sodium. Consider alternative antibacterials other thancarbapenems to treat infections in patients whose seizures are well controlled on valproic acid ordivalproex sodium.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Embryonic loss was observed in monkeys treated with imipenem/cilastatin, and fetal abnormalities wereobserved in relebactam-treated mice; therefore, advise pregnant women of the potential risks topregnancy and the fetus. There are insufficient human data to establish whether there is a drugassociatedrisk for major birth defects, miscarriage, or adverse maternal or fetal outcomes with RECARBRIO, imipenem, cilastatin, or relebactam in pregnant women.
Developmental toxicity studies with imipenem and cilastatin (alone or in combination) administeredparenterally during organogenesis to mice, rats, rabbits, and monkeys at doses 1 to 5 times the maximumrecommended human dose (MRHD of imipenem 500 mg/ cilastatin 500 mg every 6 hours for total dailydoses of imipenem 2000 mg/cilastatin 2000 mg) based on body surface area comparison, showed nodrug-induced fetal malformations. Embryofetal development studies with imipenem/cilastatin administered
to cynomolgus monkeys at doses similar to the MRHD (based on body surface area comparison) showedan increase in embryonic loss. In an embryofetal study, parental administration of relebactam to pregnantmice during the period of organogenesis was associated with a non-dose responsive increase in the litterincidence of cleft palate at a plasma relebactam exposure approximately equ |
