Rifamycin is an oral ansamycin class antibacterial drug indicated for treatment of traveler's diarrhea caused by noninvasive strains of Escherichia coli (E. coli), not complicated by fever or blood in the stool. Rifamycin is minimally absorbed; therefore, systemic concentrations are generally below the level of detection. Clinically relevant drug interactions are not expected. The multi-matrix structure (MMX) technology creates a modified-release formulation that allows rifamycin to be delivered to the distal small bowel and colon without interfering with the normal flora in the upper GI tract.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer with a glass of liquid (6 to 8 ounces).
-Do not take with alcohol.
-Tablets may be taken with or without food.
-Swallow the tablets whole. Do not crush, break, or chew the delayed-release tablets.
One of the most frequent adverse reactions leading to the discontinuation of rifamycin was abdominal pain (0.5%). Other gastrointestinal adverse events included constipation (3.5%) and dyspepsia (less than 2%).
One of the most frequent adverse reactions leading to the discontinuation of rifamycin was pyrexia or fever (0.3%).
Headache was reported in 3.3% of rifamycin-treated patients during clinical trials.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with rifamycin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.
Rifamycin is contraindicated in patients with known rifamycin hypersensitivity or hypersensitivity to any other rifamycin class antimicrobial agents (e.g., rifaximin).
Rifamycin 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. Rifamycin was not found to be effective in patients with diarrhea complicated by fever and/or bloody stool (GI bleeding). Patients with these conditions treated with rifamycin had prolonged time to last unformed stool. The effectiveness of rifamycin in diarrhea due to pathogens other than E.coli has not been demonstrated. Discontinue rifamycin if diarrhea gets worse or persists more than 48 hours and consider alternative therapy. Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including rifamycin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.
There are no available data regarding the use of rifamycin during human pregnancy to inform any drug associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, systemic absorption of rifamycin in humans is negligible after oral administration of the recommended dose. Therefore, it is not expected that maternal use of rifamycin will result in fetal exposure to the drug. 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 rifamycin clinical dose.
There is no information regarding the presence of rifamycin in human breastmilk, the effects on the breast-fed infant, or the effects on milk production. Systemic absorption of rifamycin in humans is negligible after oral administration of the recommended dose; therefore, exposure to a breast-fed infant through breastmilk is expected to be negligible. There are no animal lactation data with oral rifamycin. After a single intravenous dose in lactating ewes, rifamycin was shown to pass into milk. Consider the benefits of breast-feeding along with the mother's clinical need for rifamycin and any potential adverse effects on the breast-fed infant from rifamycin or the underlying maternal condition.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Escherichia coli
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of traveler's diarrhea due to noninvasive strains of E. coli:
Oral dosage:
Adults: 388 mg PO twice daily for 3 days. Rifamycin is not indicated for patients with diarrhea complicated by fever or bloody stool. May reserve use for patients unable to take a quinolone or azithromycin. Antibiotic treatment is not recommended for mild cases, may be considered for moderate cases, and should be used for severe cases.
Maximum Dosage Limits:
-Adults
776 mg/day PO.
-Geriatric
776 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Rifamycin products.
Rifamycin belongs to the ansamycin class of antibacterial drugs and inhibits the beta-subunit of bacterial DNA-dependent RNA polymerase, thereby blocking a step of DNA transcription. This results in inhibition of bacterial synthesis and consequently growth of bacteria.
Resistance to rifamycin is associated with mutation in the RNA polymerase beta-subunit. Increases in the MICs were observed in vitro and while on treatment after exposure to rifamycin. Cross-resistance between rifamycin and other agents in the ansamycin class has been observed.
Rifamycin is administered orally. Plasma protein binding is approximately 80% in vitro. Binding is primarily to albumin and is inversely proportional to the concentration. After a single oral dose in fasting healthy adults, fecal excretion of rifamycin was on average 86% of the normal dose. Cytochrome P450 based metabolism was not observed in vitro.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4/5, CYP2B6, P-gp, BCRP, OAT3, MATE1, MATE2-K
Clinical drug-drug interactions of rifamycin have not been conducted. Systemic concentrations of rifamycin are minimal after administration of the recommended dose; therefore, clinically relevant drug interactions are unlikely. Based on in vitro transporter studies, rifamycin is a substrate of P-glycoprotein (P-gp) and anticipated to be an inhibitor of P-gp and breast cancer resistant protein (BCRP) in the gut. Additionally, rifamycin is an inhibitor of renal transporters organic anion transporter (OAT) 3, multidrug and toxin extrusion (MATE) 1, and MATE2-K transporters. Rifamycin is an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5 in vitro. Rifamycin is an inducer of CYP3A4 and CYP2B6, but not CYP1A2 in vitro. Rifamycin is not a substrate of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5.
-Route-Specific Pharmacokinetics
Oral Route
Rifamycin has limited systemic exposure after oral administration at the recommended dose. Based on total urinary excretion data, bioavailability was less than 0.1% under fasting conditions. In healthy adults receiving rifamycin 388 mg PO twice daily for 3 days, the maximum observed rifamycin plasma concentration was 8.72 ng/mL at 6 hours after the last dose. Plasma rifamycin concentrations were below the quantification limit (less than 2 ng/mL) 67% of the time at this time point. In a food-effect study with healthy volunteers, food decreased the systemic exposure of rifamycin, but the decrease in systemic rifampin exposure is not expected to be clinically relevant.
The multi-matrix structure (MMX) technology creates a modified-release formulation that allows the active ingredient of rifamycin to be delivered to the distal small bowel and colon without interfering with the normal flora in the upper GI tract.
-Special Populations
Hepatic Impairment
The pharmacokinetics of rifamycin have not been studied in patients with impaired hepatic function.
Renal Impairment
The pharmacokinetics of rifamycin have not been studied in patients with impaired renal function.