Rifampicin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis, Mycobacterium avium complex, leprosy, and Legionnaires' disease. It is almost always used together with other antibiotics with two notable exceptions: when given as a "preferred treatment that is strongly recommended" for latent TB infection; and when used as post-exposure prophylaxis to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria. Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended. Rifampicin may be given either by mouth or intravenously.
Common side effects include nausea, vomiting, diarrhea, and loss of appetite. It often turns urine, sweat, and tears a red or orange color. Liver problems or allergic reactions may occur. It is part of the recommended treatment of active tuberculosis during pregnancy, though its safety in pregnancy is not known. Rifampicin is of the rifamycin group of antibiotics. It works by decreasing the production of RNA by bacteria.
Rifampicin was discovered in 1965, marketed in Italy in 1968, and approved in the United States in 1971. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies rifampicin as critically important for human medicine. It is available as a generic medication. Rifampicin is made by the soil bacterium Amycolatopsis rifamycinica.
Medical uses
Mycobacteria
Rifampicin is used for the treatment of tuberculosis in combination with other antibiotics, such as pyrazinamide, isoniazid, and ethambutol. For the treatment of tuberculosis, it is administered daily for at least six months. Combination therapy is used to prevent the development of resistance and to shorten the length of treatment. Resistance of Mycobacterium tuberculosis to rifampicin develops quickly when it is used without another antibiotic, with laboratory estimates of resistance rates from 10−7 to 10−10 per tuberculosis bacterium per generation.Rifampicin can be used alone in patients with latent tuberculosis infections to prevent or delay the development of active disease because only small numbers of bacteria are present. A Cochrane review found no difference in efficacy between a 3- to 4-month regimen of rifampicin and a 6-month regimen of isoniazid for preventing active tuberculosis in patients not infected with HIV, and patients who received rifampicin had a lower rate of hepatotoxicity. However, the quality of the evidence was judged to be low. A shorter 2-month course of rifampicin and pyrazinamide had previously been recommended but is no longer recommended due to high rates of hepatotoxicity.
Rifampicin should be taken on an empty stomach with a glass of water. It is generally taken either at least one hour before meals or two hours after meals.
Rifampicin is also used to treat nontuberculous mycobacterial infections including leprosy and Mycobacterium kansasii.
With multidrug therapy used as the standard treatment of Hansen's disease, rifampicin is always used in combination with dapsone and clofazimine to avoid causing drug resistance.
It is also used in the treatment of Mycobacterium ulcerans infections as associated with Buruli ulcer, usually in combination with clarithromycin or other antibiotics.
Other bacteria and protozoans
In 2008, tentative evidence showed rifampicin may be useful in the treatment of methicillin-resistant Staphylococcus aureus in combination with other antibiotics, including in difficult-to-treat infections such as osteomyelitis and prosthetic joint infections. As of 2012, if rifampicin combination therapy was useful for pyogenic vertebral osteomyelitis was unclear. A meta-analysis concluded that adding adjunctive rifampicin to a β-lactam or vancomycin may improve outcomes in staphylococcus aureus bacteremia. However, a more recent trial found no benefit from adjunctive rifampicin.It is also used as preventive treatment against Neisseria meningitidis infections. Rifampicin is also recommended as an alternative treatment for infections by the tick-borne pathogens Borrelia burgdorferi and Anaplasma phagocytophilum when treatment with doxycycline is contraindicated, such as in pregnant women or in patients with a history of allergy to tetracycline antibiotics.
It is also sometimes used to treat infections by Listeria species, Neisseria gonorrhoeae, Haemophilus influenzae, and Legionella pneumophila. For these nonstandard indications, antimicrobial susceptibility testing should be done before starting rifampicin therapy.
The Enterobacteriaceae, Acinetobacter species, and Pseudomonas species are intrinsically resistant to rifampicin.
It has been used with amphotericin B in largely unsuccessful attempts to treat primary amoebic meningoencephalitis caused by Naegleria fowleri.
Rifampicin can be used as monotherapy for a few days as prophylaxis against meningitis, but resistance develops quickly during long-term treatment of active infections, so the drug is always used against active infections in combination with other antibiotics.
Rifampicin is relatively ineffective against spirochetes, which has led to its use as a selective agent capable of isolating them in materials being cultured in laboratories.
Viruses
Rifampicin has some effectiveness against vaccinia virus.Pathogen susceptibility
The minimum inhibitory concentrations of rifampicin for several medically significant pathogens are:- Mycobacterium tuberculosis — 0.002 – 64 μg/mL
- Mycobacterium bovis — 0.125 μg/mL
- Staphylococcus aureus — ≤ 0.006–256 μg/mL
- Chlamydia pneumoniae — 0.005 μg/mL
Primary biliary cholangitis
Hidradenitis suppurativa
Rifampicin with clindamycin has been used to treat the skin disease hidradenitis suppurativa.Adverse effects
The most serious adverse effect is hepatotoxicity, and people receiving it often undergo baseline and frequent liver function tests to detect early liver damage.The more common side effects include fever, gastrointestinal disturbances, rashes, and immunological reactions. Taking rifampicin usually causes certain bodily fluids, such as urine, sweat, and tears, to become orange-red in color, a benign side effect that nonetheless can be frightening if it is not expected. This may also be used to monitor effective absorption of the drug. The discolorization 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, breastfeeding should be avoided while it is being taken.
Other adverse effects include:
- Liver toxicity—hepatitis, liver failure in severe cases
- Respiratory—breathlessness
- Cutaneous—flushing, pruritus, rash, hyperpigmentation, redness and watering of eyes
- Abdominal — nausea, vomiting, abdominal cramps, diarrhea
- Flu-like symptoms—chills, fever, headache, arthralgia, and malaise. Rifampicin has good penetration into the brain, and this may directly explain some malaise and dysphoria in a minority of users.
- Allergic reaction—rashes, itching, swelling of the tongue or throat, severe dizziness, and trouble breathing
Chemical structure
The critical functional groups of rifampicin in its inhibitory binding of bacterial RNA polymerase are the four critical hydroxyl groups of the ansa bridge and the naphthol ring, which form hydrogen bonds with amino acid residues on the protein.
Rifampicin is the derivative of rifamycin SV.
Interactions
Rifampicin is the most powerful known inducer of the hepatic cytochrome P450 enzyme system, including isoenzymes CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP3A5, and CYP3A7. It increases metabolism of many drugs and as a consequence, can make them less effective, or even ineffective, by decreasing their levels. For instance, patients undergoing long-term anticoagulation therapy with warfarin have to increase their dosage of warfarin and have their clotting time checked frequently because failure to do so could lead to inadequate anticoagulation, resulting in serious consequences of thromboembolism.Rifampicin can reduce the efficacy of birth control pills or other hormonal contraception by its induction of the cytochrome P450 system, to the extent that unintended pregnancies have occurred in women who use oral contraceptives and took rifampicin even for very short courses.
Other interactions include decreased levels and less effectiveness of antiretroviral agents, everolimus, atorvastatin, rosiglitazone, pioglitazone, celecoxib, clarithromycin, caspofungin, voriconazole, and lorazepam.
Rifampicin is antagonistic to the microbiologic effects of the antibiotics gentamicin and amikacin. The activity of rifampicin against some species of mycobacteria can be potentiated by isoniazid and ambroxol.