Published on 11/28/2018 12:33:00 PM
FDA Approves AEMCOLO (Rifamycin) for the Treatment of Travelers' Diarrhea Caused by Noninvasive Strains of Escherichia Coli in Adults
On November 16, 2018, the US Food and Drug Administration (FDA) approved AEMCOLO (rifamycin) for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli
in adults. AEMCOLO is not recommended for use in patients with diarrhea complicated by fever and/or bloody stool or due to pathogens other than noninvasive strains of E. coli
. To reduce the development of drug-resistant bacteria and maintain the effectiveness of AEMCOLO and other antibacterial drugs, AEMCOLO should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
The approved recommended dosage of AEMCOLO is 388 mg (two delayed-release tablets) orally twice daily (in the morning and evening) for three days. AEMCOLO should not be taken concomitantly with alcohol. AEMCOLO can be taken with or without food. AEMCOLO should be taken whole and do not crush, break or chew the delayed-release tablets.
Additional information regarding warnings and precautions related to the risk of persistent or worsening diarrhea complicated by fever and/or bloody stool, Clostridium difficile
-associated diarrhea, and development of drug-resistant bacteria can be found in the full prescribing information linked below.
Mechanism of Action (MOA) and Pharmacokinetics (PK)
- MOA: Rifamycin is an ansamycin class antibacterial drug.
- General PK: At the approved recommended dosage, the maximum observed rifamycin concentration in plasma was 8.72 ng/mL (6 hours after the last dose). A majority (67%) of rifamycin concentrations in plasma were below the limit of quantification (< 2 ng/mL) at this time point.
- Absorption: Rifamycin (taken as AEMCOLO) has limited systemic exposure after oral administration of the recommended dosage. Based on total urinary excretion data, bioavailability was < 0.1% under fasting conditions.
- Distribution: Plasma protein binding was approximately 80% in vitro. Binding was primarily to albumin and was inversely proportional to concentration.
- Elimination: The apparent half-life of orally administered rifamycin (taken as AEMCOLO) in plasma is unknown.
- Metabolism: Cytochrome P450 (CYP) based metabolism of rifamycin was not observed in vitro.
- Excretion: After a single oral dose of 400 mg AEMCOLO (388 mg rifamycin base) in fasting healthy adults, fecal excretion of rifamycin was on average 86% of the nominal dose.
Clinical drug-drug interaction studies of rifamycin (taken as AEMCOLO) have not been conducted. Additional information regarding in vitro
studies can be found in the full prescribing information linked below.
Use in Specific Populations
The pharmacokinetics of rifamycin (taken as AEMCOLO) in patients with impaired renal or hepatic function have not been studied.
Efficacy and Safety
Primary evidence of efficacy of AEMCOLO was demonstrated at the recommended dosage in one multi-center, randomized, double-blind, placebo-controlled trial in adults with travelers' diarrhea. A second active-controlled trial provided supportive evidence for the efficacy of AEMCOLO. The clinical efficacy of AEMCOLO was assessed by the time to last unformed (watery or soft) stool (TLUS) before achieving clinical cure. Clinical cure was defined as two or fewer soft stools and minimal enteric symptoms at the beginning of a 24-hour period or no unformed stools at the beginning of a 48-hour period. Additional information regarding efficacy trial(s) can be found in the full prescribing information linked below.
Most common adverse reactions (incidence > 2%) are headache and constipation.
Full prescribing information is available at https://go.usa.gov/xPAyn
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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.