Ertapenem is an injectable carbapenem antibiotic, used to treat various serious infections (abdominal, lung, urinary, skin, pelvic) and to prevent infections after colon or rectal surgery.
Also known as: Ertapenem, Invanz
Ertapenem + valproate: ertapenem reduces valproic acid plasma levels, with inadequate seizure control (QUADRO 2).
Carbapenems, including ertapenem, rapidly and sometimes markedly reduce plasma concentrations of valproic acid/valproate, even after a few doses; the mechanism is not fully clarified (reduced intestinal reabsorption and reduced hydrolysis of the glucuronide with less recycling). The result is loss of seizure control in patients treated with valproate, and QUADRO 2 of Annex 7 explicitly lists ertapenem. The combination should be avoided; if the carbapenem is essential (severe resistant Gram-negative infection), alternative antiepileptic therapy should be considered and valproate levels monitored. The effect may persist for several days after antibiotic discontinuation, so seizure vigilance should continue in that period.
Ertapenem + valproate: ertapenem reduces valproic acid plasma levels — risk of seizures; avoid the combination and monitor levels.
Carbapenems (ertapenem) reduce valproic acid/valproate plasma levels — inadequate seizure control (QUADRO 2, Ertapenem: "May reduce plasma levels of valproic acid/valproate sodium with inadequate seizure control").
Monitor valproate levels and seizure control during the antibiotic.
Seizures (subtherapeutic valproate levels) during ertapenem.
Avoid the combination; if the carbapenem is required, consider alternative antiepileptic therapy and monitor valproate levels.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Ertapenem)
Ertapenem is given intravenously; food does not affect its pharmacokinetics.
Not applicable — intravenous administration.
DailyMed/FDA (NIH/NLM) — approved Invanz (ertapenem) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33f3b99b-fa82-42e0-26bf-f49891ae3d22
FDA label (CONTRAINDICATIONS): contraindicated in patients with known hypersensitivity to any component or to other drugs of the same class, or in patients with anaphylactic reactions to beta-lactams.
Contraindicated in patients with anaphylactic reactions to beta-lactams; enquire about allergy history before starting.
DailyMed/FDA (NIH/NLM) — Ertapenem (INVANZ), CONTRAINDICATIONS: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33f3b99b-fa82-42e0-26bf-f49891ae3d22
FDA label (8.1): available data from a small number of post-marketing cases are insufficient to inform the risk; in animal reproduction studies during organogenesis there was no evidence of developmental malformations.
Insufficient data in pregnant women; no evidence of malformations in animal studies.
No specific breastfeeding data in the label (section 8.2 not detailed in extraction).
Not applicable (no specific contraception requirements in the label).
DailyMed/FDA (NIH/NLM) — approved Ertapenem label (INVANZ), section 8.1: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33f3b99b-fa82-42e0-26bf-f49891ae3d22 ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 2, Drugs and Breastfeeding: Avoid; present in milk in animal studies.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal carbapenem: inhibition of bacterial cell wall synthesis; stable to many beta-lactamases, including ESBLs. Mean plasma concentrations after 1 g IV/IM presented in label section 12.3 (peak ~155 mcg/mL at 0.5 h after IV infusion).
Inhibition of bacterial cell wall synthesis (PBP binding) — bactericidal.
IV/IM administration; wide tissue distribution. Co-administration with probenecid inhibits active tubular secretion and increases concentrations (7.1).
Metabolism: hydrolysis of the beta-lactam ring to the inactive metabolite (ring opening), with no relevant CYP involvement.
Plasma half-life of approximately 4 hours in healthy young adults (section 12.3 data).
