Rifampicin

Rifampicin

drugbox



width=280
IUPAC_name = 5,6,9,17,19,21-Hexahydroxy-23-methoxy-
2,4,12,16,18,20,22-heptamethyl-
8- ["N"-(4-methyl-1-piperazinyl)formimidoyl] -
2,7-(epoxypentadeca [1,11,13] trienimino)-
naphtho [2,1-"b"] furan-1,11(2"H")-dione 21-acetate
CAS_number = 13292-46-1
ATC_prefix=J04
ATC_suffix=AB02
PubChem=5360416
DrugBank=APRD00207
C = 43 | H = 58 | N = 4 | O = 12
molecular_weight = 822.94 g/mol
bioavailability = 90 to 95%
metabolism = Hepatic and intestinal wall
elimination_half-life = 6 to 7 hours
excretion = 15 to 30% renal
60% faecal
pregnancy_AU = C
legal_AU = S4
legal_UK = POM
routes_of_administration = Oral, IV

Rifampicin (INN) (pronEng|rɪˈfæmpəsɪn) or rifampin (USAN) is a bactericidal antibiotic drug of the rifamycin group.cite book |author=Masters, Susan B.; Trevor, Anthony J.; Katzung, Bertram G. |title=Katzung & Trevor's pharmacology |publisher=Lange Medical Books/McGraw Hill, Medical Pub. Division |location=New York |year=2005 |pages= |isbn=0-07-142290-0 |oclc= |doi= |accessdate=] It is a semisynthetic compound derived from "Amycolatopsis rifamycinica " (formerly known as "Amycolatopsis mediterranei" and "Streptomyces mediterranei"). Rifampicin may be abbreviated RIF, RMP, RD, RA or R. It is also known as rifaldazine, R/AMP, and Rofact (in Canada.) There are various types of rifamycins from which this is derived, but this particular form, with a 4-methyl-1-piperazinaminyl group, is by far the most clinically effective.

Indications

Rifampicin was introduced in 1967,cite book |author=Long, James W. |title=Essential Guide to Prescription Drugs 1992 |publisher=HarperCollins Publishers |location=New York |year=1991 |pages=pp. 925-929 |isbn=0-06-273090-8 |oclc= |doi= |accessdate=] as a major addition to the cocktail-drug treatment of tuberculosis and inactive meningitis, along with isoniazid, ethambutol, and streptomycin. There is no generic form. It requires a prescription in industrial North America, but is not a controlled substance. It must be administered regularly daily for several months without break otherwise the risk of drug-resistant tuberculosis is greatly increased. In fact, this is the primary reason that it is used in tandem with the three aforementioned drugs, particularly isoniazid.Erlich, Henry, W Ford Doolittle, Volker Neuhoff, and Et Al . Molecular Biology of Rifomycin. New York, NY: MSS Information Corporation, 1973. pp. 44-45, 66-75, 124-130.]

Rifampicin is typically used to treat "Mycobacterium" infections, including the aforementioned tuberculosis and leprosy; it also has a role in the treatment of methicillin-resistant "Staphylococcus aureus" (MRSA) in combination with fusidic acid. It is used in prophylactic therapy against "Neisseria meningitidis" (meningococcal) infection. Further, it has been used with Amphotericin B in largely unsuccessful attempts to treat primary amoebic meningoencephalitis caused by Naegleria fowleri.

It is also used to treat infection by "Listeria" species, "Neisseria gonorrhoeae", "Haemophilus influenzae" and "Legionella pneumophila". For these non-standard indications, sensitivity testing should be done (if possible) before starting rifampicin therapy. Rifampicin resistance develops quickly during treatment and rifampicin monotherapy should not be used to treat these infections — it should be used in combination with other antibiotics. With multidrug therapy (MDT) used as the standard treatment of leprosy, rifampicin is always used in combination with dapsone and clofazimine.

"Enterobacteriaceae", "Acinetobacter" and "Pseudomonas" species are intrinsically resistant to rifampicinFact|date=March 2008.

Pharmacodynamics (mechanism of action)

Rifampicin inhibits DNA-dependent RNA polymerase in bacterial cells by binding its beta-subunit, thus preventing transcription to RNA and subsequent translation to proteins. Its lipophilic nature makes it a good candidate to treat the meningitis form of tuberculosis, which requires distribution to the central nervous system and penetration through the blood-brain barrier.

Rifampin acts directly on messenger RNA synthesis. It inhibits only prokaryotic DNA-primed RNA polymerase, especially those that are Gram-stain-positive, such as "Mycobacterium tuberculosis", which is slightly such. In fact, evidence shows that in vitro DNA treated with concentrations 5000 times higher than normal dosage remained unaffected; in vivo eukaryotic specimen's RNA and DNA polymerases suffered few problems as well. [Coulson, Christopher J. "Bacterial RNA-Polymerase - Rifampin as Antimycobacterial." Molecular Mechanisms of Drug Action. 2nd ed. Bristol, PA: Taylor Francis, 1994. pp. 40-41.] Much of these Gram-positive bacteria’s membrane is mycolic acid complexed with peptidoglycan which allows easy movement of the drug into the cell. Rifampicin interacts with the β subunit of RNA polymerase when it is in an α2β trimer. This halts mRNA transcription, therefore preventing translation of polypeptides. It should be made clear, however, that it cannot stop the elongation of mRNA once binding to the template-strand of DNA has been initiated.Hardman, Joel G., Lee E. Limbird, and Alfred G. Gilman, eds. "Rifampin." The Pharmacological Basis of Therapeutics. 10th ed. United States of America: The McGraw-Hill Companies, 2001. pp. 1277-1279.] The Rifampin-RNA polymerase complex is extremely stable and yet experiments have shown that this is not due to any form of covalent linkage. It is hypothesized that hydrogen bonds and π-π bond interactions between naphthoquinone and the aromatic amino acids are the major stabilizers, though this requires the oxidation of naphthohydroquinone which is found most commonly in Rifampin. It is this last hypothesis that explains the explosion of multi-drug-resistant bacteria: mutations in the rpoB gene that replace phenylalanine, tryptophan, and tyrosine with non-aromatic amino acids result in poor bonding between Rifampin and the RNA polymerase.

Rifampin-resistant bacteria produce RNA Polymerases with subtly different β subunit structures which are not readily inhibited by the drug.cite journal |author=O'Sullivan DM, McHugh TD, Gillespie SH |title=Analysis of rpoB and pncA mutations in the published literature: an insight into the role of oxidative stress in Mycobacterium tuberculosis evolution? |journal=J. Antimicrob. Chemother. |volume=55 |issue=5 |pages=674–9 |year=2005 |month=May |pmid=15814606 |doi=10.1093/jac/dki069 |url=] In molecular biology research, plasmids containing Rifampicin (abbrev. Rif) resistant gene are often used for colony screening. Many plasmids containing Rif resistant genes are commercially available to researchers.

Adverse effects

The most serious adverse effect is related to rifampicin's hepatotoxicity, and patients receiving rifampicin often undergo baseline and frequent liver function tests to detect liver damage. The dosage cannot exceed 600mg (average for a healthy adult) or the patient risks developing hepatitis.Collins, R Douglas. Atlas of Drug Reactions. New York, NY: ChurchillLivingstone, 1985. pp. 123.]

Rifampicin is an effective liver enzyme-inducer, promoting the upregulation of hepatic cytochrome P450 enzymes (such as CYP2D6 and CYP3A4) increasing the rate of metabolism of many other drugs that are cleared by the liver through these enzymes. As a consequence, rifampicin can cause a range of adverse reactions when taken concurrently with other drugs. For instance, patients undergoing long term anticoagulation therapy with warfarin have to be especially cautious and increase their dosage of warfarin accordingly. [Stockley, Ivan H. "Anticoagulant Drug Interactions." Drug Interactions. 3rd ed. Boston: Blackwell Scientific Publications, 1994. pp. 274-275.] Failure to do so could lead to under-treating with anticoagulation resulting in serious consequences of thromboembolism. Likewise, it can also reduce the efficacy of hormonal contraception.

The more common unwanted effects include fever, gastrointestinal disturbances, rashes and immunological reactions.

Taking rifampicin can cause certain bodily fluids, such as urine and tears, to become orange-red in color, a benign but sometimes frightening side-effect. This may permanently stain soft contact lenses. It also may be excreted in breast milk, therefore breast feeding should be avoided.

In short, adverse effects include
* Hepatotoxic - Hepatitis, jaundice, liver failure in severe cases.
* Respiratory - breathlessness
* Cutaneous - flushing, pruritus, rash, redness and watering of eyes.
* Abdominal - nausea, vomiting, abdominal cramps with or without diarrhoea
* Flu-like symptoms - with chills, fever, headache, arthralgia and malaise

Pharmacokinetics

Orally administered Rifampin results in peak plasma concentrations in about 2 to 4 hours. Aminosalicyclic acid may significantly reduce absorption of Rifampin, and peak concentrations may not be reached. If these two drugs must be used concurrently, they must be given separately with an interval of 8 to 12 hours between administrations.

Rifampin is easily absorbed from the gastrointestinal tract and its ester functional group is quickly hydrolyzed in the bile and catalyzed by a high pH and substrate-specific enzymes called esterases. After about 6 hours, almost all of the drug is deacetylated. Even in this deacetylated form, Rifampin is still a potent antibiotic; however, it can no longer be reabsorbed by the intestines and it is subsequently eliminated from the body. Only about 7% of the administered drug will be excreted unchanged through the urine, though urinary elimination accounts for only about 30% of the dose of the drug that is excreted. About 60% to 65% is excreted through the feces.

The half-life of Rifampin ranges from 1.5 to 5 hours, though hepatic impairment will significantly increase it. Food consumption, on the other hand, inhibits absorption from the GI tract, and the drug is more quickly eliminated.

Distribution of the drug is high throughout the body, and reaches effective concentrations in many organs and body fluids, including the CSF. This high distribution is the reason for the orange-red color of the saliva, tears, sweat, urine, and feces. About 60% to 90% of the drug is bound to plasma proteins.

Preparations

In Bulgaria it is marketed as Tubocin (by Actavis/Balkanpharma), in Israel as Rimactan (Sandoz) and in Romania as Sinerdol (Sicomed). In the UK marketed as Rifadin (Aventis), Rimactan (Sandoz), Rifater a combination with isoniazid and pyrazinamide (Aventis), Rifinah a combination with isoniazid (Aventis) and Rimactazid a combination with isoniazid (Sandoz). In the U.S. as Rifadin (Aventis), Rifater combination with isoniazid and pyrazinamide (Aventis), Rimactane (Novartis).In India Rifampicin is available as R-Cinex 600 (Lupin Ltd). Its a combination of Rifampicin and Isoniazid.

References

External links

* [http://products.sanofi-aventis.us/rifadin/Rifadin.pdf Prescribing Information for RIFADIN by Sanofi-Aventis]


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Look at other dictionaries:

  • Rifampicin — Strukturformel Allgemeines Freiname Rifampicin Andere Namen …   Deutsch Wikipedia

  • Rifampicin — Ri|fam|pi|cin [Kunstw. aus [(Methylpiperazinyl)iminomethyl]rifamycin (Rifamycin angeblich aus Rififi (frz. Film) u. ↑ mycin)}}], das; s: ein halbsynthetisches ↑ Ansamycin, das gegen Tuberkulose eingesetzt wird. * * * Rifampicin   das, s,… …   Universal-Lexikon

  • rifampicin — noun see rifampin …   New Collegiate Dictionary

  • rifampicin — Semi synthetic member of the rifamycin group of antibiotics …   Dictionary of molecular biology

  • rifampicin — noun rifampin …   Wiktionary

  • rifampicin — SYN: rifampin. * * * n. an antibiotic used to treat various infections, particularly tuberculosis. It is administered by mouth; digestive upsets and sensitivity reactions sometimes occur. Trade names: Rifadin, Rimactane. * * * rif·am·pi·cin… …   Medical dictionary

  • rifampicin — [rɪ fampɪsɪn] (also rifampin) noun Medicine a bacterial antibiotic used chiefly to treat tuberculosis and leprosy. Origin 1960s: from rifamycin (a related antibiotic) + the insertion of pi from piperazine …   English new terms dictionary

  • rifampicin — rif·am·pi·cin …   English syllables

  • rifampicin — n. an antibiotic used to treat various infections, particularly tuberculosis and leprosy. It is administered by mouth; digestive upsets and sensitivity reactions sometimes occur. Trade names: Rifadin, Rimactane …   The new mediacal dictionary

  • rifampicin — noun see rifampin …   Useful english dictionary

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