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Rifamycin Sodium

Class: Rifamycins
Chemical Name: [(7~{S},9~{E},11~{S},12~{R},13~{S},14~{R},15~{R},16~{R},17~{S},18~{S},19~{E},21~{Z})-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^{4,7}.0^{5,28}]triaconta-1(29),2,4,9,19,21,25,27-octaen-13-yl] acetate
Molecular Formula: C37H47NO12
CAS Number: 15105-92-7
Brands: Aemcolo

Medically reviewed by Drugs.com. Last updated on Feb 11, 2019.

Introduction

Rifamycin sodium is a rifamycin antibiotic.

Uses for Rifamycin Sodium

Rifamycin sodium has the following uses:

Rifamycin sodium is a rifamycin antibacterial indicated for the treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in adults.1

Rifamycin sodium has the following limitations of use:

Rifamycin sodium 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.1

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

Rifamycin Sodium Dosage and Administration

General

Rifamycin sodium is available in the following dosage form(s) and strength(s):

Delayed-release tablets: 194 mg of rifamycin (equivalent to 200 mg of rifamycin sodium).1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration
  • The recommended dosage of rifamycin is 388 mg (two tablets) orally twice daily for three days.1

  • Take each dose with a glass of liquid. Do NOT take rifamycin sodium concomitantly with alcohol.1

  • Rifamycin sodium can be taken with or without food.1

  • Swallow rifamycin sodium tablets whole. Do NOT crush, break or chew the tablets.1

Cautions for Rifamycin Sodium

Contraindications

Rifamycin sodium is contraindicated in patients with a known hypersensitivity to rifamycin, any of the other rifamycin class antimicrobial agents (e.g. rifaximin), or any of the components in the rifamycin sodium formulation.1

Warnings/Precautions

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

Rifamycin sodium was not shown to be effective in patients with diarrhea complicated by fever and/or bloody stool. Patients with these conditions treated with rifamycin sodium had prolonged time to last unformed stool (TLUS). The effectiveness of rifamycin sodium in travelers' diarrhea caused by pathogens other than E. coli has not been demonstrated. Rifamycin sodium is not recommended for use in patients with diarrhea accompanied by fever or bloody stools or due to pathogens other than noninvasive strains of E. coli.1

Discontinue rifamycin sodium if diarrhea gets worse or persists more than 48 hours and consider alternative antibacterial therapy.1

Clostridium difficile-associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, which may lead to overgrowth of C. difficile.1

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile may cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.1

If CDAD is suspected or confirmed, antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, specific antibiotic treatment of C. difficile, and/or surgical evaluation should be instituted as clinically indicated.1

Development of Drug-resistant Bacteria

Prescribing rifamycin sodium in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.1

Specific Populations

Pregnancy

Risk Summary: There are no available data on rifamycin sodium use in pregnant women to inform any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Systemic absorption of rifamycin sodium in humans is negligible following oral administration of the recommended dose of rifamycin sodium. Due to the negligible systemic exposure, it is not expected that maternal use of oral rifamycin sodium will result in fetal exposure to the drug.1

In animal reproduction studies, no malformations were observed in pregnant rats or rabbits at exposures 25,000 and 500 times (based on AUC), respectively, the human exposure achieved with the recommended clinical dose of oral rifamycin sodium. Treatment of pregnant rats with oral rifamycin sodium at more than 1,000 times the maximum plasma concentration (Cmax) and 25,000 times the systemic exposure (based on AUC) during the period of organogenesis resulted in maternal toxicity, decreased fetal weight, and variations in diaphragm formation. Similarly, treatment of pregnant rabbits with oral rifamycin sodium at more than 10 times the maximum human plasma concentration (Cmax), resulted in maternal toxicity, decreased fetal weight, and slightly delayed fetal ossifications.1

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Advise pregnant women of the potential risk to a fetus.1

Animal Data: Embryofetal toxicity studies in rats and rabbits did not show malformations up to the maximum tested doses of 855 and 85.5 mg/kg, (25,000 and 500 times greater plasma exposure based on AUC), respectively, of rifamycin given orally during the period of organogenesis (gestational days 6-17/18). In rats, the high dose of 855 mg/kg/day caused reduction in maternal food consumption, reduced fetal weight and a higher number of fetuses with thin tendinous diaphragm. In rabbits, the high dose of 85.5 mg/kg/day caused a reduction in food consumption and bodyweight gain in pregnant dams, as well as reduced fetal weights and slight delay in ossification, including slightly higher incidences of fetuses with skull suture bone variations, enlarged skull fontanelle and incompletely ossified digit 5 medial phalanx of both forelimbs. No adverse fetal effects were observed in rats and rabbits administered lower doses of oral rifamycin.1

Lactation

There is no information regarding the presence of orally administered rifamycin sodium in human milk, the effects on the breastfed infant, or the effects on milk production. Systemic absorption of rifamycin sodium in humans is negligible following oral administration of the recommended dose of rifamycin sodium; therefore, exposure to a breastfed infant through breastmilk is expected to be negligible. There are no animal lactation data following oral rifamycin administration. Following single intravenous injection of rifamycin to lactating ewes, rifamycin has been shown to pass into milk.1

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for rifamycin sodium and any potential adverse effects on the breast-fed infant from rifamycin sodium or from the underlying maternal condition.1

Pediatric Use

The safety and effectiveness of rifamycin sodium has not been established in pediatric patients less than 18 years of age with travelers' diarrhea.1

Geriatric Use

Clinical studies with rifamycin sodium for travelers' diarrhea did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.1

Renal Impairment

The pharmacokinetics of rifamycin sodium in patients with impaired renal function has not been studied. Given the minimal systemic exposure of rifamycin (taken orally as rifamycin sodium) and minor role of renal excretion in elimination of rifamycin, renal impairment is not expected to have a clinically meaningful effect on rifamycin systemic exposure necessitating a dose adjustment.1

Hepatic Impairment

The pharmacokinetics of rifamycin sodium in patients with impaired hepatic function has not been studied. Given the minimal systemic exposure of rifamycin (taken orally as rifamycin sodium), hepatic impairment is not expected to have a clinically meaningful effect on rifamycin systemic exposure necessitating a dose adjustment.1

Common Adverse Effects

Most common adverse reactions (incidence >2%) are headache and constipation.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

No clinical drug-drug Interactions (DDIs) have been studied. Based on the minimal systemic rifamycin concentrations observed after the recommended oral dose of rifamycin sodium, clinically relevant DDIs are not expected.1

Actions and Spectrum

Mechanism Of Action

Rifamycin is an antibacterial drug.1

Rifamycin belongs to the ansamycin class of antibacterial drugs and acts by inhibiting the beta-subunit of the bacterial DNA-dependent RNA polymerase, blocking one of the steps in DNA transcription. This results in inhibition of bacterial synthesis and consequently growth of bacteria.1

Spectrum

Rifamycin has been shown to be active against most isolates of the following pathogen both in vitro and in clinical studies of travelers' diarrhea: 1

  • Escherichia coli (enterotoxigenic and enteroaggregative isolates)1

Resistance

Resistance to rifamycin is associated with mutations in the RNA polymerase beta subunit. Among E. coli strains, the spontaneous mutation frequency rate of rifamycin ranged from 10−6 to 10−10 at 4–16 times the rifamycin minimum inhibitory concentration (MIC); the mutation frequency was independent of rifamycin concentration. Increases in the minimum inhibitory concentrations were observed both in vitro and while on treatment following exposure to rifamycin. Cross-resistance between rifamycin and other ansamycins has been observed.1

Advice to Patients

Persistent Diarrhea

Inform the patient being treated for travelers' diarrhea to discontinue rifamycin sodium if diarrhea persists more than 48 hours or worsens. Advise the patient to seek medical care for fever and/or blood in the stool.1

Fever and/or Bloody Stool

Inform the patient that rifamycin sodium is not recommended for use if they have fever and/or bloody stool.1

Clostridium difficile-Associated Diarrhea

Advise patients that diarrhea is a common problem caused by antibacterial drugs, which usually ends when the antibacterial drugs is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery or bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of rifamycin sodium. Inform the patient that if diarrhea occurs after therapy or does not improve or worsens during therapy, patients should contact their physician as soon as possible.1

Important Administration Instructions

Instruct the patients that: 1

  • Rifamycin sodium tablets should be swallowed whole with a full glass of liquid (6–8 ounces).1

  • Rifamycin sodium must not be taken concomitantly with alcohol.1

  • Rifamycin sodium tablets must not be chewed, crushed or broken.1

  • Rifamycin sodium may be taken with or without food.1

Antibacterial Resistance

Patients should be counseled that antibacterial drugs including rifamycin sodium should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When rifamycin sodium is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by rifamycin sodium or other antibacterial drugs in the future.1

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.

Rifamycin Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, delayed-release

194 mg (of rifamycin)

Aemcolo

Aries Pharmaceuticals Inc

AHFS Drug Information. © Copyright 2020, Selected Revisions February 11, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Aries Pharmaceuticals Inc. Aemcolo (Rifamycin) ORAL prescribing information. 2018 Nov. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=509338f4-a1b3-4c10-a3cb-7fb03fd01f12