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The '''rifamycins''' are a group of [[antibiotic]]s which are synthesized either naturally by the bacterium ''Amycolatopsis mediterranei'', or artificially.  They are a subclass of the larger family, [[Ansamycin]].  Rifamycins are particularly effective against [[mycobacteria]], and are therefore used to treat [[tuberculosis]], [[leprosy]], and [[mycobacterium avium complex]] (MAC) infections.
<!--FDA-Labeled Indications and Dosage (Adult)-->
|fdaLIADAdult======Condition1=====


The rifamycin group includes the "classic" rifamycin drugs as well as the rifamycin derivatives [[Rifampicin]], [[Rifabutin]] and [[Rifapentine]].
* Dosing Information


==Bacterium==
:* Dosage
''Streptomyces mediterranei'' was first isolated in 1957 from a soil sample collected near the beachside town of [[Saint-Raphaël, Var|St Raphael]] in southern France. The name was originally given by two microbiologists working with the Italian drug company Group Lepetit SpA in [[Milan]], the Italian Grazia Beretta and Pinhas Margalith of Israel.


In 1969 the bacterium was renamed ''Nocardia mediterranei'' when another scientist named Thiemann found that it had a cell wall typical of the Nocardia species. Then in 1986 the bacterium was renamed again as ''Amycolatopsis mediterranei'', as the first species of a new genus, because a scientist named Lechevalier discovered that the cell wall lacked mycolic acid and was not able to be infected by the Nocardia and Rhodococcus phages.
=====Condition2=====


==First drugs==
* Dosing Information
Rifamycins were first isolated in 1957 from a fermentation culture of ''Streptomyces mediterranei'' at the laboratory of Gruppo Lepetit SpA in Milan by a scientist named Piero Sensi, working with the Israeli scientist Pinhas Margalith. Eventually around seven rifamycins were discovered, named Rifamycin A, B, C, D, E, S and SV.


                              [[Image:Rifamycin_B_%26_SV.gif]]
:* Dosage


Of the various rifamycins Rifamycin B was first introduced commercially. Lepetit filed for patent protection of Rifamycin B in the UK in August 1958 and in the US in March 1959. The British patent GB921045 was granted in March 1963 and U.S. Patent 3,150,046 was granted in September 1964. The drug is widely regarded as having helped conquer the issue of drug-resistant tuberculosis in the 1960s.
=====Condition3=====


==Clinical Trials==
* Dosing Information
Rifamycins have been used for the treatment of many diseases, most importantly HIV-related Tuberculosis.  Due to the large number of available analogues and derivatives, rifamycins have been widely utilized in the elimination of pathogenic bacteria that have become resistant to commonly used antibiotics.  For instance, Rifampicin is known for its potent effect and ability to prevent drug resistance.  It rapidly kills fast-dividing bacilli strains as well as “persisters” cells, which remain biologically inactive for long periods of time that allow them to evade antibiotic activity <ref>{{cite journal |author=Pozniak, A. L.; Miller, R. |journal=AIDS |title=The treatment of tuberculosis in HIV-infected persons |volume=13 |pages=435 |year=1999}}</ref>.  In addition, rifabutin and rifapentine have both been used against tuberculosis acquired in HIV-positive patients.


==Mechanism of Action==
:* Dosage
The biological activity of rifamycins relies on the inhibition of DNA-dependent RNA synthesis <ref>{{cite journal |author=Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. |journal=Nature |title=Effect of rifamycin on protein synthesis |volume=207 |pages=417 |year=1965}}</ref>.  This is due to the high affinity of rifamycins to prokaryotic RNA polymerase.  Crystal structure data of the antibiotic bound to RNA polymerase indicates that rifamycin blocks synthesis by causing strong steric clashes with the growing oligonucleotide.  If rifamycin binds the polymerase after the chain elongation process has started, no effect is observed on the biosynthesis, which is consistent with a model that suggests rifamycin physically blocks the chain elongation <ref>{{cite journal |author=Floss, H.G.; Yu, T. |journal=Chem. Rev. |title=Rifamycin-Mode of Action, Resistance, and Biosynthesis |volume=105 |pages=621 |year=2005}}</ref>.  In addition, rifamycins showed potency towards tumors.  This is due to their inhibition of the enzyme reverse transcriptase, which is essential for tumor persistence.  However, rifamycins potency proved to be mild and this never lead to their introduction to clinical trials.


==Biosynthesis==
=====Condition4=====
Despite the fact that Rifamycin B is a mild antibacterial compound, it is known to be the precursor of various other clinically-utilized potent derivatives.  The general scheme of biosynthesis starts with the uncommon starting unit, 3-amino-5-dihydroxybenzoic acid ('''AHBA'''), via type I polyketide pathway ('''PKS I''') in which chain extension is performed using 2 acetate and 8 propionate units <ref>{{cite book |author=Lancini, G.; Cavalleri, B. |title=In Biotechnology of Antibiotics |year=1997 |pages=521|publisher: Marcel Dekker, New York, USA}}</ref>.  AHBA is believed to have originated from the Shikimate pathway, however this was not incorporated into the biosynthetic mechanism.  This is due to the observation that 3 amino-acid analogues converted into AHBA in cell-free extracts of  ''A. mediterranei''. <ref>{{cite journal |author=Floss, H.G.; Yu, T. |journal=Chem. Rev. |title=Rifamycin-Mode of Action, Resistance, and Biosynthesis |volume=105 |pages=621 |year=2005}}</ref>.


                    [[Image:AHBA_biosyn1.gif]]
* Dosing Information
                    [[Image:Rifamycin_biosynthesis.gif]]
                    [[Image:Rifamycin_biosynthesis2.gif]]


The ''rif'' cluster is responsible for the biosynthesis of rifamycins.  It contains genes ''rifG'' through ''rifN'', which were shown to biosynthesize AHBA.[10]  ''RifK'', ''rifL'', ''rifM'',and ''rifN'' are believed to act as transaminases in order to form the AHBA precursor kanosamine <ref>{{cite journal |author=Arakawa, K.; Müller, R.; Mahmud, T.; Yu, T.-W.; Floss, H. G. |journal=J. Am. Chem. Soc. |title= Characterization of the Early Stage Aminoshikimate Pathway in the Formation of 3-Amino-5-hydroxybenzoic Acid: The RifN Protein Specifically Converts Kanosamine into Kanosamine 6-Phosphate |volume=124 |pages=10644 |year=2002}}</ref>.  ''RifA'' through ''rifE'' encode a type I polyketide synthase module, with the loading module being a non-ribosomal peptide synthase.  In all, ''rifA-E'' assemble a linear undecaketide and are followed by ''rifF'', which encodes an amide synthase and causes the undecaketide to release and form a macrolactam structure.  Moreover, the ''rif'' cluster contains various regulatory proteins and glycosilating genes that appear to be silent.  Other types of genes seem to perform post-synthase modifications of the original polyketide.
:* Dosage


                    [[Image:Biosyn_genes1.gif]]
<!--Off-Label Use and Dosage (Adult)-->


==Derivatives==
<!--Guideline-Supported Use (Adult)-->
Lepetit introduced Rifampicin, an orally active rifamycin, around 1966. Rifabutin, a derivative of rifamycin S, was invented around 1975 and came on to the US market in 1993. Hoechst Marion Roussel (now part of [[Aventis]]) introduced rifapentine in 1999.
|offLabelAdultGuideSupport======Condition1=====


[[Rifaximin]] is an oral rifamycin marketed in the US by [[Salix Pharmaceuticals]] that is not absorbed from the intestine.  It is intended to treat intestinal infections due to ''[[Escherichia coli]]''.
* Developed by:


==Currently available rifamycins==
* Class of Recommendation:
*[[Rifampicin]]
*[[Rifabutin]]
*[[Rifapentine]]
*[[Rifaximin]]


==References==
* Strength of Evidence:
* Sensi. ''et al.'', Farmaco Ed. Sci. (1959) 14, 146-147 - the paper announcing the discovery of the rifamycins.
* Thieman ''et al.'' Arch. Microbiol. (1969), 67 147-151 - the paper which renamed ''Streptomyces mediterranei'' as ''Nocardia mediterranei''.
* Lechevalier ''et al.'', Int. J. Syst. Bacteriol. (1986), 36, 29) - the paper which renamed ''Nocardia mediterranei'' as ''Amycolatopsis mediterranei''.
<references/>


==External links==
* Dosing Information
*[http://v3.espacenet.com/origdoc?DB=EPODOC&IDX=US3150046&F=0&QPN=US3150046 U.S. Patent 3,150,046 for Rifamycin B].
{{Antimycobacterials}}
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[[Category:Rifamycin antibiotics]]
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[[de:Rifamycine]]
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[[Category:Drug]]

Revision as of 14:07, 26 January 2015

Rifamycin
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

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Black Box Warning

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See full prescribing information for complete Boxed Warning.
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  • Content

Overview

Rifamycin is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

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Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Rifamycin in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Rifamycin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Rifamycin in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Rifamycin in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Rifamycin in pediatric patients.

Contraindications

  • Condition1

Warnings

ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content
  • Description

Precautions

  • Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Rifamycin in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Rifamycin in the drug label.

Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous

Drug Interactions

  • Drug
  • Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Rifamycin in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Rifamycin during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Rifamycin with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Rifamycin with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Rifamycin with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Rifamycin with respect to specific gender populations.

Race

There is no FDA guidance on the use of Rifamycin with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Rifamycin in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Rifamycin in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Rifamycin in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Rifamycin in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral
  • Intravenous

Monitoring

There is limited information regarding Monitoring of Rifamycin in the drug label.

  • Description

IV Compatibility

There is limited information regarding IV Compatibility of Rifamycin in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Description

Management

  • Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Rifamycin in the drug label.

Pharmacology

There is limited information regarding Rifamycin Pharmacology in the drug label.

Mechanism of Action

Structure

File:Rifamycin01.png
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Rifamycin in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Rifamycin in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Rifamycin in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Rifamycin in the drug label.

How Supplied

Storage

There is limited information regarding Rifamycin Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

{{#ask: Label Page::Rifamycin |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Rifamycin in the drug label.

Precautions with Alcohol

  • Alcohol-Rifamycin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)

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