Rifamycin (Monograph)

Brand name: Aemcolo
Drug class: Rifamycins

Medically reviewed by Drugs.com on Nov 20, 2023. Written by ASHP.

Introduction

Rifamycin antibiotic.¹

Uses for Rifamycin

Travelers' Diarrhea

Treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in adults.^{1 2 3} 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.¹

To reduce the development of drug-resistant bacteria and maintain effectiveness of rifamycin and other antibacterial drugs, use only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.¹

Guidelines generally consider rifaximin an alternative to fluoroquinolones or azithromycin for noninvasive moderate-to-severe travelers’ diarrhea.^{1000 1001 1002 1003} Although rifamycin was not approved at the time of publication of most guidelines, the drug is generally considered an alternative to rifaximin.¹⁰⁰¹

Rifamycin Dosage and Administration

General

Patient Monitoring

• Monitor for worsening or persistence of travelers’ diarrhea for more than 48 hours.¹ Discontinue rifamycin if either occurs, and consider treatment with an alternative anti-infective.¹

Administration

Oral Administration

Administer orally without regard to food.¹ Do not administer with alcohol.¹ Take each dose with 6–8 ounces of liquid.¹

Swallow tablets whole; do not crush, break, or chew.¹

Dosage

Dosage of rifamycin sodium is expressed in terms of rifamycin.¹

Adults

Travelers' Diarrhea Caused by Noninvasive Strains of E. coli

Oral

388 mg (2 tablets) twice daily (in the morning and evening) for 3 days.¹

If diarrhea worsens or persists for >48 hours after rifamycin initiation, discontinue and consider an alternative anti-infective.¹

Special Populations

Hepatic Impairment

Given minimal systemic absorption, hepatic impairment may not necessitate dosage adjustment.¹

Renal Impairment

Given minimal systemic absorption, renal impairment may not necessitate dosage adjustment.¹

Geriatric Use

No specific dosage recommendations at this time.¹

Cautions for Rifamycin

Contraindications

• Known hypersensitivity to rifamycin, any of the other rifamycin class antimicrobial agents (e.g., rifaximin), or any of the components.¹

Warnings/Precautions

Risk of Persistent or Worsening Diarrhea Complicated by Fever and/or Bloody Stool

Do not use to treat travelers’ diarrhea complicated by fever or bloody stools or for treatment of diarrhea known or suspected to be caused by pathogens other than noninvasive strains of E. coli.¹ Not shown to be effective in patients with diarrhea complicated by fever and/or bloody stool.¹ Effectiveness in travelers' diarrhea caused by pathogens other than E. coli not demonstrated.¹

If diarrhea worsens or persists for >48 hours, discontinue rifamycin and consider another anti-infective.¹

Clostridium difficile-associated Diarrhea

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.¹ C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including rifamycin, and may range from mild diarrhea to fatal colitis.¹

C. difficile produces toxins A and B, which contribute to CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.¹ Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.¹

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.¹ Initiate appropriate supportive therapy, anti-infective therapy directed against C. difficile, and surgical evaluation as clinically indicated.¹

Development of Drug-resistant Bacteria

In absence of a diagnosed or strongly suspected bacterial infection or a prophylactic indication for use, rifamycin is unlikely beneficial and increases risk of development of drug-resistant bacteria.¹

Specific Populations

Pregnancy

Data not available regarding use in pregnant women.¹ Due to minimal systemic absorption, fetal exposure not expected with maternal use.¹

Maternal toxicity, decreased fetal weight, and teratogenicity observed in animal reproductive studies.¹

Lactation

Not known whether the drug is distributed into human milk, affects milk production, or affects breast-fed infant.¹

Undergoes minimal systemic absorption; level of exposure in breastmilk expected to be negligible.¹

Pediatric Use

Safety and efficacy not established in children and adolescents <18 years of age.¹

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger subjects.¹ Other reported clinical experience has not identified differences.¹

Hepatic Impairment

Pharmacokinetics not studied in hepatic impairment.¹ Given minimal systemic absorption, hepatic impairment not expected to have a clinically meaningful effect on exposure.¹

Renal Impairment

Pharmacokinetics not studied in renal impairment.¹ Given minimal systemic absorption and renal excretion to a minor extent, renal impairment not expected to have a clinically meaningful effect on exposure.¹

Common Adverse Effects

Most common adverse reactions (>2%): headache, constipation.¹

Drug Interactions

No clinical drug interaction studies conducted.¹ Based on minimal systemic absorption at recommended doses, clinically relevant interactions not expected.¹

Not a substrate of CYP isoenzymes 1A2, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4/5.¹ In vitro studies indicate rifamycin induces CYP3A4 and 2B6, but not 1A2; however, clinically relevant induction of these enzymes unlikely.¹ In vitro studies indicate rifamycin inhibits CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5; clinically relevant inhibition of these enzymes not likely.¹

Substrate of P-glycoprotein (P-gp); inhibits both P-gp and breast cancer resistance protein (BCRP) in the GI tract.¹ In vitro, studies indicate rifamycin inhibits renal organic anion transport (OAT) 3, multidrug and toxin extrusion (MATE) 1, and MATE2-K; clinically relevant inhibition of these transporters not likely.¹

Rifamycin Pharmacokinetics

Absorption

In healthy subjects, maximum plasma concentrations observed 6 hours after final dose of recommended 3-day dosing regimen.¹

Bioavailability

Under fasting conditions, <0.1% based on total urinary excretion data.¹

Food

No clinically relevant impact.¹

Distribution

Extent

Not known if present in human milk; unlikely, given minimal systemic absorption.¹

Plasma Protein Binding

80% bound, primarily to albumin¹

Elimination

Metabolism

In vitro, metabolism via CYP isoenzymes not observed.¹

Elimination Route

After a single 388 mg-dose, approximately 86% of the dose excreted in feces.¹

Half-life

Plasma elimination half-life unknown.¹

Stability

Storage

Oral

Tablets, delayed-release

Store at 20–25ºC (excursions permitted to 15–30ºC).¹

Actions

• Inhibits bacterial synthesis and growth via inhibition of the ß-subunit of the bacterial DNA-dependent RNA polymerase, blocking DNA transcription.¹

• Escherichia coli: Active in vitro and in clinical infections (i.e., travelers’ diarrhea) against most isolates of enterotoxigenic E. coli and enteroaggregative E. coli.¹

• Resistance generally associated with mutations in the RNA polymerase ß-subunit.¹ Among E. coli isolates, the spontaneous mutation frequency rate of rifamycin ranged from 10−6 to 10−10 at 4–16 times the MIC.¹

• In vitro, and following exposure to rifamycin, increases in MICs observed.¹

• Cross-resistance observed between rifamycin and other ansamycins.¹

Advice to Patients

• Advise the patient to seek medical care for fever and/or blood in the stool, or if diarrhea persists more than 48 hours or worsens.¹

• Inform patients that rifamycin is not recommended for use if they have fever and/or bloody stool.¹

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹

• Importance of instructing patients on recommended administration of rifamycin, including to swallow tablets whole with a full glass of liquid (6–8 ounces) with or without food, to not take rifamycin concomitantly with alcohol, and to not chew, crush, or break tablets.¹

• Advise patients that antibacterials (including rifamycin) should only be used to treat bacterial infections and not used to treat viral infections.¹

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with rifamycin or other antibacterials in the future.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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