Ansamycins |
| Infectious Disease -ALL Agents (INDEX) |
| Background: "Ansamycins is a family of secondary metabolites that show antimicrobial activity against many gram-positive and some gram-negative bacteria and includes various compounds, among which: streptovaricins and rifamycins. In addition, these compounds demonstrate antiviral activity towards bacteriophages and poxviruses."
"Rifamycins are a subclass of ansamycins with high potency against mycobacteria. This resulted in their widespread use in the treatment of tuberculosis, leprosy, and AIDS-related mycobacterial infections. Since then various analogues have been isolated from other prokaryotes." [Source: https://en.wikipedia.org/wiki/Ansamycin] |
Ansamycins / Rifamycins
Rifaximin (XIFAXAN® )
Microbiology:
Mechanism of Action
Rifaximin is a non-aminoglycoside semi-synthetic antibacterial derived from rifamycin SV. Rifaximin acts by binding to the beta-subunit of bacterial DNA-dependent RNA polymerase resulting in inhibition of bacterial RNA synthesis.
Drug Resistance and Cross-Resistance
Escherichia coli has been shown to develop resistance to rifaximin in vitro. However, the clinical significance of such an effect has not been studied.
Rifaximin is a structural analog of rifampin. Organisms with high rifaximin minimum inhibitory concentration (MIC) values also have elevated MIC values against rifampin. Cross-resistance between rifaximin and other classes of antimicrobials has not been studied.
Activity In Vitro and in Critical Infections
Rifaximin has been shown to be active against the following pathogen in clinical studies of infectious diarrhea as described in the Indications and Usage (1) section: Escherichia coli (enterotoxigenic and enteroaggregative strains).
For HE, rifaximin is thought to have an effect on the gastrointestinal flora.
INDICATIONS AND USAGE:
To reduce the development of drug-resistant bacteria and maintain the effectiveness of XIFAXAN and other antibacterial drugs, XIFAXAN when used to treat infection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible 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.
Travelers’ Diarrhea
XIFAXAN 200 mg is indicated for the treatment of patients (≥12 years of age) with travelers’ diarrhea caused by noninvasive strains of Escherichia coli.
Limitations of Use
XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli.
Hepatic Encephalopathy
XIFAXAN 550 mg is indicated for reduction in risk of overt hepatic encephalopathy (HE) recurrence in
patients ≥ 18 years of age.
In the trials of XIFAXAN for HE, 91% of the patients were using lactulose concomitantly. Differences in the treatment effect of those patients not using lactulose concomitantly could not be assessed.
XIFAXAN has not been studied in patients with MELD (Model for End-Stage Liver Disease) scores > 25, and only 8.6% of patients in the controlled trial had MELD scores over 19. There is increased systemic exposure in patients with more severe hepatic dysfunction [see Warnings and Precautions].
WARNINGS AND PRECAUTIONS
--Travelers’ Diarrhea Not Caused by E. coli: XIFAXAN was not effective in diarrhea complicated by fever and/or blood in the stool or diarrhea due to pathogens other than E. coli. If diarrhea symptoms get worse or persist for more than 24-48 hours, discontinue XIFAXAN and consider alternative antibiotics.
--Clostridium difficile-Associated Diarrhea: Evaluate if diarrhea occurs after therapy or does not improve or worsens during therapy.
--Hepatic Impairment: Use with caution in patients with severe (Child-Pugh C) hepatic impairment.
--Concomitant P-glycoprotein inhibitor: Caution should be exercised when concomitant use of rifaximin and a P-glycoprotein inhibitor is needed.
USE IN SPECIFIC POPULATIONS
--Pregnancy: Based on animal data, may cause fetal harm.
--Nursing Mothers: Discontinue nursing or drug, taking into account the importance of the drug to the mother.
=======================================
DOSAGE AND ADMINISTRATION:
=======================================
----------------------------
Dosage for Travelers’ Diarrhea
----------------------------
The recommended dose of XIFAXAN is one 200 mg tablet taken orally three times a day for 3 days. XIFAXAN can be administered orally, with or without food.
----------------------------
Dosage for Hepatic Encephalopathy
----------------------------
The recommended dose of XIFAXAN is one 550 mg tablet taken orally two times a day, with or without food.
Renal Dosing:
The pharmacokinetics of rifaximin in patients with impaired renal function has not been studied.
SUPPLIED:
XIFAXAN is a pink-colored biconvex tablet and is available in the following strengths:
200 mg – a round tablet debossed with “Sx” on one side.
550 mg – an oval tablet debossed with “rfx” on one side.
SOURCE:
Package insert data:
Reference(s)
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates. A local search option of this data can be found here.
