Rifampicin
RIFAMPICIN
INTRODUCTION:
- Semisynthetic derivative of rifamycin B obtained from Streptomyces mediterranei.
- Included in macrolide antibiotic group.
- Eventually, 7 types were developed they are Rifamycin A, B, C, D, E, S, SV.
MECHANISM OF ACTION:
- Bactericidal at 0.005-0.2micrograms/ml.
- Inhibits gram-positive bacteria.
- Works by binding non-covalently to β-subunits of DNA-dependent RNA polymerase (DDRP) —> Inhibiting RNA synthesis initiation.
- DNA-dependent RNA polymerases in eukaryotic cells are unaffected.
- Because of drug binding subunit is unavailable in mammalian RNA polymerase.
- Hence, highly selective in action.
RESISTANCE:
- Mutation in rpoB, ß-subunit gene of RNA polymerase.
- Mutations-result in reduced rifampin binding to RNA polymerase.
- MDR tuberculosis is defined by resistance to isoniazid & rifampicin.
PHARMACOKINETICS:
- Absorbed after oral administration.
- Distributed widely in body tissue & fluids.
- Highly protein bound.
- Adequate CSF conc.–Meningeal inflammation.
DOSAGE:
Dose of rifampicin in RNTCP:
- 450mg given three times in a week.
- Does not require dose reduction in renal failure patients.
CLINICAL USES:
- Most active against both dormant & non-dormant bacilli.
- Useful in treating tuberculosis, leprosy, Mycobacterium avium complex (MAC) infection & staphylococcus infections.
- Reaches inside of caseous material of infections.
First line anti-tubercular drugs in children & adults:
- Most effective antitubercular drug against slow multiplying intracellular mycobacteria.
- INH, rifampicin, ethambutol, pyrazinamide & streptomycin.
- Mycobacterial infections- 600mg orally.
- Atypical Mycobacterial infect.& in leprosy.
- Fastest acting drug in leprosy.
- Prophylaxis (only in patients with INH-resistance).
- Maximum sterilising action.
OTHER USES:
- Meningococcal carriers.
- Prophylaxis–H.influenzae type B
- Staphylococcal carriage.
- Staph. Infect.
- As osteomyelitis, prostatic valve endocarditis
- For treatment of paucibacillary leprosy drugs
- Rifampicin & dapsone
- Treatment of choice for HIV & TB.
- Along with Rifampicin is Ritonavir.
CONTRAINDICATION:
- Known cases of drug hypersensitivity.
- In pregnancy.
- Due to teratogenicity noted in animal studies.
- Not recommended except in presence of severe tuberculosis.
- In alcoholics with severely impaired liver function & with jaundice.
SIDE EFFECTS:
- Hepatotoxicity – Major.
- Harmless orange colour to urine, sweat, tears, contact lenses.
Cutaneous syndrome:
- Rashes, thrombocytopenia & nephritis.
Abdominal syndrome:
- Cholestatic jaundice & light chain proteinuria.
Flu-like syndrome:
- Fever, chills, myalgia, anaemia, thrombocytopenia, acute tubular necrosis.
Strongly induces most cytochrome P450 isoforms:
- Increases elimination of methadone, anticoagulants, cyclosporine, anticonvulsants, PI, NNRTI, contraceptives.
- Lowers their serum level.
During rifampicin treatment,
- Mild bilirubin elevation with normal transaminases due to hepatic adaptation.
DRUG INTERACTION:
- Therapeutic efficacy may be decreased of some drugs.
- Due to liver enzyme-inducing properties of rifampin interaction.
Eg:
- Azole.
- BZDs.
- Beta-blockers.
- Chloramphenicol.
- Clarithromycin.
- Clozapine.
- Oral contraceptives.
- Corticosteroids.
- Cyclosporine.
- Delavirdine.
- Digitoxin,
- Doxycycline,
- Erythromycin,
- Estrogens,
- Haloperidol,
- Ritonavir, indinavir and saquinavir.
- Hydantoins,
- Losartan,
- Methadone,
- Mexiletine,
- Morphine,
- Ondansetron,
- Oral anticoagulants,
- Sulfonylureas,
- Tacrolimus,
- Theophyllines,
- TCA,
- Verapamil
- Digoxin: May decrease digoxin serum concentrations.
- Enalapril: May significantly increase BP.
- Halothane: Hepatotoxicity and hepatic encephalopathy have been reported with coadministration.
- Ketoconazole: May cause treatment failure of either ketoconazole or rifampin.
- Probenecid: Elevates rifampin levels.
- Warfarin: Enhance metabolism.
- Because rifampicin is a microsomal enzyme inducer.
Exam Question
- Treatment of choice for HIV and TB:
- Rifampicin + Ritonavir.
- Rifampicin acts by DNA dependent RNA polymerase.
- Rifampicin is microsomal enzyme inducer.
- Rifampicin may cause OCP failure.
- Rifampicin is bactericidal in nature.
- Rifampicin enhances warfarin metabolism.
- A tuberculosis patient with only rifampicin resistance will be treated under Cat IV.
- During rifampicin treatment, some patients will have mild elevation in the bilirubin with normal transaminases due to hepatic adaptation.
- Rifampicin does not require dose reduction in patient with renal failure.
- Rifampicin reaches inside of caseous material.
- Rifampicin is most active against both dormant & non-dormant bacilli.
- Rifampicin is most effective antitubercular drug against slow multiplying intracellular mycobacteria.
- Rifampicin shows harmless orange colour to urine, sweat, tears, contact lenses.
- Contact lens staining occurs in rifampicin.
- Hepatotoxicity is the major side effect of rifampicin.
- MDR tuberculosis is defined by resistance to isoniazid and rifampicin.
- Rifampicin is not used with ritonavir, indinavir and saquinavir.
- The treatment of contacts of meningococcal meningitis is by rifampicin.
- Dose of rifampicin in RNTCP is 450mg given three times in a week.
- First line anti-tubercular drugs are same in children and adults INH, rifampicin, ethambutol, pyrazinamide, and streptomycin.
- For treatment of paucibacillary leprosy drugs used are rifampicin & dapsone.
- Toxic amblyopia is produced by rifampicin.
- Rifampicin is associated with side effects as respiratory syndrome, cutaneous syndrome, Flu syndrome and abdominal syndrome.
- Maximum sterilising action is shown by rifampicin.
- Rifampicin is obtained from Bacteria Streptomyces mediterranei.
- Gene responsible for resistance to rifampicin – Rpo B gene.
Don’t Forget to Solve all the previous Year Question asked on Rifampicin
