From the Guidelines
Rifampicin inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase, preventing transcription initiation, as stated in the American Journal of Respiratory and Critical Care Medicine 1. This mechanism of action allows rifampicin to be bactericidal against actively growing mycobacteria and many gram-positive and gram-negative bacteria. The drug specifically targets bacterial RNA polymerase while having minimal effect on human RNA polymerase, giving it selective toxicity. Some key points about rifampicin include:
- It penetrates well into tissues and cells, including macrophages, which makes it particularly effective against intracellular pathogens like Mycobacterium tuberculosis.
- Rifampicin is typically used at doses of 600mg daily for adults in tuberculosis treatment regimens, usually in combination with other antibiotics to prevent resistance development, as recommended in the Clinical Infectious Diseases journal 1.
- Rifampicin induces cytochrome P450 enzymes, which can significantly decrease the effectiveness of many medications including oral contraceptives, warfarin, and antiretrovirals, so drug interactions must be carefully monitored, as noted in 1.
- Patients should be informed that rifampicin will cause orange-red discoloration of body fluids including urine, tears, and sweat, as mentioned in 1. Some important considerations for rifampicin use include:
- Potential interactions with other medications, such as antiretrovirals, oral contraceptives, and warfarin, which may require dose adjustments or alternative treatments, as discussed in 1.
- The need for careful monitoring of patients with HIV infection or those taking other medications that may interact with rifampicin, as recommended in 1.
From the FDA Drug Label
Mechanism of Action Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible Mycobacterium tuberculosis organisms. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme.
The mechanism of action of rifampicin is the inhibition of DNA-dependent RNA polymerase activity in susceptible organisms, specifically interacting with bacterial RNA polymerase without affecting the mammalian enzyme 2.
From the Research
Mechanism of Action of Rifampicin
- Rifampicin is a bactericidal antibiotic that inhibits RNA polymerase (RNAP) in bacteria, thereby preventing RNA synthesis 3.
- The inhibitor binds in a pocket of the RNAP beta subunit deep within the DNA/RNA channel, but more than 12 A away from the active site 3.
- Rifampicin acts by directly blocking the path of the elongating RNA when the transcript becomes 2 to 3 nt in length 3.
- This mechanism of action explains the effects of rifampicin on RNAP function and its potent antibacterial activity 3.
Use of Rifampicin in Tuberculosis Treatment
- Rifampicin is a key component of anti-tuberculosis therapy and is often used in combination with other drugs such as isoniazid, ethambutol, and pyrazinamide 4, 5, 6.
- The combination of rifampicin and isoniazid is effective in treating tuberculosis, including cases with isoniazid-resistant strains 4.
- Rifampicin can be used in patients with various conditions, including pregnancy, diabetes mellitus, and renal failure, although dose adjustments may be necessary in some cases 5.