Rifampicin
Encyclopedia
Rifampicin (icon) or rifampin (USAN
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

) is a bactericidal antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

 drug of the rifamycin
Rifamycin
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis mediterranei or artificially. They are a subclass of the larger family Ansamycin...

 group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica (formerly known as Amycolatopsis mediterranei and Streptomyces mediterranei). Rifampicin may be abbreviated R, RMP, RA, RF, or RIF (US).

In 1957, a soil sample from a pine forest on the French Riviera was brought for analysis to the Lepetit Pharmaceuticals research lab in Milan
Milan
Milan is the second-largest city in Italy and the capital city of the region of Lombardy and of the province of Milan. The city proper has a population of about 1.3 million, while its urban area, roughly coinciding with its administrative province and the bordering Province of Monza and Brianza ,...

, Italy. There, a research group headed by Prof. Piero Sensi (1920-) and Dr. Maria Teresa Timbal (1925 - 1969) discovered a new bacterium. This new species appeared immediately of great scientific interest since it was producing a new class of molecules with antibiotic activity. Because Sensi, Timbal and the researchers were particularly fond of the French crime story Rififi
Rififi
Rififi is a 1955 French crime film adaptation of Auguste le Breton's novel of the same name. Directed by American filmmaker Jules Dassin, the film stars Jean Servais as the aging gangster Tony le Stéphanois, Carl Möhner as Jo le Suédois, Robert Manuel as Mario Farrati, and Jules Dassin as César le...

(about a jewel heist and rival gangs), they decided to call these compounds "rifamycins". After two years of attempts to obtain more stable semi-synthetic products, a new molecule with high efficacy and good tolerability was produced in 1959 and was named "rifampicin".

Rifampicin is also known as rifaldazine, R/AMP, rofact (in Canada), and rifampin in the United States. There are various types of rifamycins from which this is derived, but the rifampicin form, with a 4-methyl-1-piperazinaminyl
Piperazine
Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste....

 group, is by far the most clinically effective.

Rifampicin is an intensely red solid, and the small fraction which reaches body fluids is known for imparting a harmless red-orange color to the urine (and to a lesser extent, also sweat and tears) of users, for a few hours after a dose. Maximal concentrations in the blood are decreased by about a third when the antibiotic is taken with food.

Rifampicin is used in the treatment of a number of bacteria, but best known for activity against Mycobacterium
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...

strains, such as cause tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 and Hansen's Disease. Rifampicin can be used as monotherapy for a few days as prophylaxis against meningitis, but resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 develops quickly during long treatment of active infections, so the drug is always used against active infections in combination with other antibiotics.

Indications

Rifampicin was introduced in 1967, as a major addition to the cocktail-drug treatment of tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 and inactive meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

, along with isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...

, ethambutol
Ethambutol
Ethambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is usually given in combination with other tuberculosis drugs, such as isoniazid, rifampicin and pyrazinamide....

, pyrazinamide
Pyrazinamide
Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.-Abbreviations:...

 and streptomycin
Streptomycin
Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...

. It requires a prescription in North America. 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. This is also the primary motivation behind directly observed therapy for tuberculosis.

Rifampicin resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 develops quickly during treatment and rifampicin monotherapy should not be used to treat these infections — it should be used in combination with other antibiotics.

Rifampicin is also used in the treatment of cholestatic pruritus

Mycobacteria

Rifampicin is typically used to treat Mycobacterium
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...

infections, including tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 and Hansen's Disease. It can be used to treat BCG-oma
BCG-oma
A BCG-oma is an abscess caused by the BCG strain of Mycobacterium bovis. It follows incorrect administration of BCG . It is treated as for any Mycobacterium bovis infection ....

, which follows as an uncommon complication of BCG
BCG
BCG can stand for:Medicine*Bacillus Calmette-Guérin, a vaccine for tuberculosis*Ballistocardiography, a vital sign caused by the mechanical movement of the heart which can be recorded from the surface of the bodyBusiness...

 vaccination for tuberculosis.

With multidrug therapy used as the standard treatment of Hansen's Disease, rifampicin is always used in combination with dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...

 and clofazimine
Clofazimine
Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients and...

 to avoid eliciting drug resistance.

Other bacteria

Rifampicin also has a role in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in combination with fusidic acid
Fusidic acid
Fusidic acid is a bacteriostatic antibiotic that is often used topically in creams and eyedrops, but may also be given systemically as tablets or injections...

, although recent inquiries have raised questions over the lack of studies into the efficacy of this treatment. It is used in prophylactic therapy against Neisseria meningitidis (meningococcal) infection.

It is also used to treat infection by Listeria species, Neisseria gonorrhoeae
Neisseria gonorrhoeae
Neisseria gonorrhoeae, also known as gonococci , or gonococcus , is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.N...

, Haemophilus influenzae
Haemophilus influenzae
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...

and Legionella pneumophila
Legionella pneumophila
Legionella pneumophila is a thin, ærobic, pleomorphic, flagellated, non-spore forming, Gram-negative bacterium of the genus Legionella. L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of legionellosis or Legionnaires' disease.-Characterization:L...

. For these non-standard indications, sensitivity testing should be done (if possible) before starting rifampicin therapy.

The Enterobacteriaceae
Enterobacteriaceae
The Enterobacteriaceae is a large family of bacteria that includes many of the more familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella. This family is the only representative in the order Enterobacteriales of the class Gammaproteobacteria in the...

, Acinetobacter
Acinetobacter
Acinetobacter [asz−in−ée−toe–back−ter] is a genus of Gram-negative bacteria belonging to the Gammaproteobacteria. Acinetobacter species are non-motile and oxidase-negative, and occur in pairs under magnification....

, and Pseudomonas
Pseudomonas
Pseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...

species are intrinsically resistant to rifampicin.

Further, it has been used with amphotericin B
Amphotericin B
Amphotericin B is a polyene antifungal drug, often used intravenously for systemic fungal infections...

 in largely unsuccessful attempts to treat primary amoebic meningoencephalitis
Primary amoebic meningoencephalitis
Primary amoebic meningoencephalitis is a disease of the central nervous system caused by infection from Naegleria fowleri.-Presentation:...

 caused by Naegleria fowleri
Naegleria fowleri
Naegleria fowleri is a free-living excavate form of protist typically found in warm bodies of fresh water, such as ponds, lakes, rivers, and hot springs. It is also found in soil, near warm-water discharges of industrial plants, and unchlorinated swimming pools in an amoeboid or temporary...

.

Mechanism of action

Rifampicin inhibits DNA-dependent RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

 in bacterial cells by binding its beta-subunit, thus preventing transcription to RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 and subsequent translation to proteins. Its lipophilic nature makes it a good candidate to treat the meningitis form of tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

, which requires distribution to the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 and penetration through the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

.

Rifampicin acts directly on messenger RNA synthesis. It inhibits only prokaryotic
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...

 DNA-primed RNA polymerase, especially those that are Gram-stain-positive and Mycobacterium tuberculosis. Much of this acid-fast positive bacteria's membrane is mycolic acid
Mycolic acid
Mycolic acids are long fatty acids found in the cell walls of the mycolata taxon, a group of bacteria that includes Mycobacterium tuberculosis, the causative agent of the disease tuberculosis. They form the major component of the cell wall of mycolata species...

 complexed with peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...

, which allows easy movement of the drug into the cell. Evidence shows that in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

 DNA treated with concentrations 5000 times higher than normal dosage remained unaffected; in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

 eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 specimens' RNA and DNA polymerases suffered few problems as well. Rifampicin interacts with the β subunit of RNA polymerase when it is in an α2β trimer. This halts mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

, 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. The Rifampin-RNA polymerase complex is extremely stable and yet experiments have shown that this is not due to any form of covalent
Covalent bond
A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

 linkage. It is hypothesized that hydrogen bonds and π-π bond interactions between naphthoquinone
Naphthoquinone
Naphthoquinone is a class of natural phenols based on the C6-C4 skeleton.1,4-Naphthoquinone can be viewed as derivatives of naphthalene through the replacement of two hydrogen atoms by two ketone groups....

 and the aromatic amino acids are the major stabilizers, though this requires the oxidation of naphthohydroquinone which is found most commonly in rifampicin. It is this last hypothesis that explains the explosion of multi-drug-resistant bacteria: mutations in the rpoB
RpoB
rpoB is a bacterial gene that codes for part of an enzyme which synthesises RNA. Specifically, rpoB is the β subunit of the bacterial RNA polymerase. It is the subunit which possesses the polymerase activity, that is, it catalyzes the synthesis of RNA...

 gene that replace phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...

, tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...

, and tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...

 with non-aromatic amino acids result in poor bonding between rifampicin and the RNA polymerase.

Rifampicin-resistant bacteria produce RNA Polymerases with subtly different β subunit structures which are not readily inhibited by the drug. In molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

 research, plasmids containing rifampicin-resistant genes are often used for colony screening. Many plasmids containing these resistant genes are commercially available to researchers.

Adverse effects

The most serious adverse effect
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

 is related to rifampicin's hepatotoxicity
Hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...

, and patients receiving rifampicin often undergo baseline and frequent liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...

 to detect liver damage.

Rifampicin is an effective liver enzyme-inducer, promoting the upregulation of hepatic cytochrome P450 enzymes (such as CYP2C9
CYP2C9
Cytochrome P450 2C9 is a protein that in humans is encoded by the CYP2C9 gene.- Function :CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes...

 and CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...

), 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
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...

 have to be especially cautious and increase their dosage of warfarin accordingly. Failure to do so could lead to under-treating with anticoagulation resulting in serious consequences of thromboembolism.

Upregulation of hepatic metabolism of hormones decreases their levels, and rifampicin can also in similar fashion reduce the efficacy of hormonal contraception
Hormonal contraception
Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...

, to the extent the unintended pregnancies have been reported among users of oral contraceptives taking rifampicin in even short courses (for example, as prophylaxis against exposure to bacterial meningitis).

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 side effect which can be frightening if it is not expected and prepared for. This effect may also be used to monitor effective absorption of the drug (if drug color is not seen in the urine, the patient may wish to move the drug dose farther in time from food or milk intake). The discolorizion of sweat and tears is not directly noticeable, but sweat may stain light clothing orange, and tears may permanently stain soft contact lenses.

Since rifampicin may be excreted in breast milk, breast feeding should be avoided while it is being taken.

Adverse effects include:
  • Hepatotoxic - Hepatitis
    Hepatitis
    Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

    , jaundice
    Jaundice
    Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

    , liver failure in severe cases
  • Respiratory - breathlessness
  • Cutaneous - flushing, pruritus, rash, redness and watering of eyes
  • Abdominal - nausea
    Nausea
    Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

    , vomiting, abdominal cramps with or without diarrhea
    Diarrhea
    Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

  • Flu-like symptoms - with chills, fever, headache, arthralgia
    Arthralgia
    Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....

    , and malaise
    Malaise
    Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...

    . Rifampin has good penetration into the brain, and this may directly explain some malaise and dysphoria
    Dysphoria
    Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...

     in a minority of users.

Pharmacokinetics

Orally-administered rifampicin results in peak plasma concentrations in about 2 to 4 hours. 4-Aminosalicylic acid (another antituburculosis drug) significantly reduces absorption of rifampicin, and peak concentrations may not be reached. If these two drugs must be used concurrently (which happens often in treatment of TB), they must be given separately with an interval of 8 to 12 hours between administrations.

Rifampicin is easily absorbed from the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

; its ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

 functional group is quickly hydrolyzed in the bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

; and it is 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
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...

 of rifampicin 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. When rifampicin is taken with a meal peak blood concentration fall by 36%. Antacids do not affect absorption, however. The decrease in rifampin absorption with food is sometimes enough to noticeably affect urine color, which can be used as a marker for whether or not a dose of the drug has been effectively absorbed.

Distribution of the drug is high throughout the body, and reaches effective concentrations in many organs and body fluids, including the CSF
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

. Since the substance itself is red, 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.

rifampicin is considered as liver microsomal enzyme inducer lead to "high metabolic rate"

Interactions

Rifampicin is an inducer
Enzyme inducer
An enzyme inducer is a type of drug which binds to an enzyme and increases its metabolic activity.Classic examples: barbiturates , antiepileptics and rifampin....

 of many enzymes of the cytochrome P450 superfamily, including CYP2B6
CYP2B6
Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene. CYP2B6 is a member of the Cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances.- Function :...

, CYP2C8
CYP2C8
Cytochrome P4502C8 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body.- CYP2C8 Ligands :...

, CYP2C9
CYP2C9
Cytochrome P450 2C9 is a protein that in humans is encoded by the CYP2C9 gene.- Function :CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes...

, CYP2C19
CYP2C19
Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...

, CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

, CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...

, CYP3A5
CYP3A5
Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.-Further reading:...

, and CYP3A7
CYP3A7
CYP3A7 is a member of the cytochrome P450 family. It serves in fetuses a role similar to the role CYP3A4 serves in adults....

. Thus it will speed up the metabolism of any drug that is metabolized by any of these enzymes in the body. A complete list of drugs metabolized by each of these enzymes can be found here http://medicine.iupui.edu/clinpharm/DDIs/table.aspx.

Other possible interactions which may not be listed include antiretroviral agents, everolimus
Everolimus
Everolimus is the 40-O- derivative of sirolimus and works similarly to sirolimus as an mTOR inhibitor....

, atorvastatin
Atorvastatin
Atorvastatin , sold by Pfizer under the trade name Lipitor, is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms...

, rosiglitazone
Rosiglitazone
Rosiglitazone is an antidiabetic drug in the thiazolidinedione class of drugs. It works as an insulin sensitizer, by binding to the PPAR receptors in fat cells and making the cells more responsive to insulin...

/pioglitazone
Pioglitazone
Pioglitazone is a prescription drug of the class thiazolidinedione with hypoglycemic action.Pioglitazone is marketed as trademarks Actos in the USA, Canada, the UK and Germany, Glustin in Europe,"Glizone" and "Pioz" in India by Zydus CND and USV respectively and Zactos in Mexico by Takeda...

, celecoxib
Celecoxib
Celecoxib INN is a sulfa non-steroidal anti-inflammatory drug and selective COX-2 inhibitor used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial...

, clarithromycin
Clarithromycin
Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia , skin and skin structure infections...

, caspofungin
Caspofungin
Caspofungin is an antifungal drug, the first of a new class termed the echinocandins from Merck & Co., Inc. It shows activity against infections with Aspergillus and Candida, and works by inhibiting the enzyme β-D-Glucan synthase and thereby disturbing the integrity of the fungal cell wall...

, and lorazepam
Lorazepam
Lorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...

.

Preparations

Rifampicin is available in:
  • Bulgaria as Tubocin (by Actavis
    Actavis
    Actavis is an international generic pharmaceutical company based in Iceland that was founded in 1956 as Pharmaco. Listed on the Icelandic Stock Exchange until 2007, it was taken private by Novator Partners, an investment vehicle of the chairman Björgólfur Thor Björgólfsson.In the late 1990s,...

    /Balkanpharma)
  • Romania as Sinerdol (Sicomed)
  • UK as Rifadin (Aventis
    Aventis
    Aventis was a pharmaceutical and lab assay testing company. It was formed in 1999 when Rhône-Poulenc S.A. merged with Hoechst AG. The merged company was based in Strasbourg, France. With its headquarters in Strasbourg, Aventis was the product of the first transnational merger to combine large...

    ), Rimactan (Sandoz
    Sandoz
    Founded in 2003, Sandoz presently is the generic drug subsidiary of Novartis, a multinational pharmaceutical company. The company develops, manufactures and markets generic drugs as well as pharmaceutical and biotechnological active ingredients....

    ), Rifater a combination with isoniazid
    Isoniazid
    Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...

     and pyrazinamide
    Pyrazinamide
    Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.-Abbreviations:...

     (Aventis), Rifinah a combination with isoniazid (Aventis), and Rimactazid a combination with isoniazid (Sandoz)
  • U.S. as Rifadin (Aventis), Rifater combination with isoniazid and pyrazinamide (Aventis), Rimactane (Novartis
    Novartis
    Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...

    )
  • France as Rifadine (Aventis)
  • India R-Cinex 600 (Lupin Ltd)/Micox, a combination of rifampicin and isoniazid
  • Australia as Rimycin (Alphapharm
    Alphapharm
    Alphapharm is a generic drug manufacturing company based in Australia. Alphapharm manufactures many different generic pharmaceutical medicines. It is an owned by Mylan Pharmaceuticals . Alphapharm's logo is a green circle with a white lowercase alpha enclosed. Alphapharm is the greatest sole...

    )
  • Egypt as Rimactan (Sandoz
    Sandoz
    Founded in 2003, Sandoz presently is the generic drug subsidiary of Novartis, a multinational pharmaceutical company. The company develops, manufactures and markets generic drugs as well as pharmaceutical and biotechnological active ingredients....

    )
  • Germany as Eremfat (Riemser)

External links

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