Rifampicin

INTRODUCTION:
  • First line anti-tubercular drugs are same in children and adults INH, rifampicin, Ethambutol, pyrazinamide, and streptomycin.
  • Refamycins are a group of macrocyclic antibiotics which are Produced by Streptomyces mediterranei.
  • Refamycins inhibit the enzyme RNA polymerase and prevent RNA synthesis.Than in turn prevent protein synthesis.
  • So they are useful in treating tuberculosis, leprosy,Mycobacterium avium complex (MAC) infection, andStaphylococcus infections.
  • Eventually 7, rifamycins were developed they are Rifamycin A,B,C,D,E,S,SV.
  • Refampicin is a semi-synthetic rifamycin made from Rifamycin-B isolated from streptomyces mediterranei in 1957
MECHANISM OF ACTION:
  • Refampin is bactericidal at 0.005-0.2micrograms/ml vsMicobacterium tuberculosis.
  • Rifampicin inhibits Grampositive bacteria and works byBinding non-covalently to DNA-dependent RNA polymeraseand inhibiting the start of RNA synthesis
  • The DNA-dependent RNA polymerases in eukaryotic cellsare unaffected, since the drug binds to a peptide chain not Present in the mamalian RNA polymerase. Therefore it is highly selective.
  • It acts by inhibiting DNA-dependent RNA polymerase(DDRP)of mycobacteria and other microorganisms by binding strongly to their β-subunits viz ( α, α1, β, β1And sigma) and there by supression of inhibiting the m-RNA synthesis
RESISTANCE:
  • Mutation in rpoB, the gene for ß-subunit of RNA polymerase.
  • Mutations-Result in reduced binding of rifampin to RNA polymerase.
  • MDR tuberculosis is defined by Resistance to isoniazid and rifampicin
Pharmacokinetics:
  • Absorbed after oral administration
  • Rifampicin reaches inside of caseous material
  • Excerted –through liver into bile.
  • Distributed widely in body tissue & fluids.
  • Highly protein bound, adequate CSF conc. –meningeal inflammation
  • Dose of rifampicin in RNTCP is 450mg given three times in a week
  • Maximum sterilising action is shown by Rifampicin
  • Rifampicin do not require reduction in dose in patient with renal failure
CLINICAL USES:
  • Rifampicin is most active against both dormant & non-dormant bacilli 
  • Most effective antitubercular drug against slow multiplying intracellular mycobacteria
  • Mycobacterial infections- 600mg orally
  • . Atypical Mycobacterial infect.& in leprosy.
  • Fastest acting drug in leprosy is rifampicin
  • Prophylaxis ( only in pts with INH-resistance)
  • OTHERS:
  1. Meningococcal carriers.
  2. Prophylaxis--H.influenzae type B
  3. Staphylococcal carriage.
  4. Staph. Infect. As osteomyelitis, prostatic valve endocarditis.
  5. For treatment of paucibacillary leprosy drugs used are Rifampicin & dapsone
  6. Treatment of choice for HIV and TB along with Rifampicin is Ritonavir
DRUG INTERACTION:
  • Therapeutic efficacy may be decreased of some drugs because of liver enzyme-inducing properties of rifampin Interaction
  1. Azole , 
  2. BZDs 
  3. Beta-blockers, 
  4. Chloramphenicol, 
  5. Clarithromycin, 
  6. Clozapine, 
  7. Oral contraceptives, 
  8. Corticosteroids, 
  9. Cyclosporine, 
  10. Delavirdine, 
  11. Digitoxin, 
  12. Doxycycline, 
  13. Erythromycin,
  14. Estrogens, 
  15. Haloperidol,
  16. Ritonavir, indinavir and saquinavir 
  17. Hydantoins,
  18. Losartan, 
  19. Methadone, 
  20. Mexiletine, 
  21. Morphine,
  22. Ondansetron, 
  23. Oral anticoagulants,
  24. Sulfonylureas, 
  25. Tacrolimus, 
  26. Theophyllines,
  27. TCA,
  28. 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 the metabolism of warfarin, as rifampicin is a microsomal enzyme inducer.
SIDE EFFECTS:
  • Hepatotoxicity is the major side effect of rifampicin
  • Harmless orange color to urine, sweat, tears, contact lenses.
  • Rashes(cutaneous syndrome), thrombocytopenia & nephritis.
  • Cholestatic jaundice(abdominal syndrome), light chain proteinuria.
  • Flu-like syndrome, fever, chills, myalgia, anemia, thrombocytopenia, acute tubular necrosis.
  • Strongly induces most cytochrome P450 isoforms.(inc. elimination of methadone, anticoagulants, cyclosporine, anticonvulsants, PI, NNRTI, contraceptives).
  • Lower serum level of the above drugs.
  • During the treatment with rifampicin some patients will have mild elevation in the bilirubin with normal transaminases due to Hepatic adaptation
CONTRAINDICATION:
  • Rifampicin is contraindicated in known cases of hypersensitivity to the drug. 
  • It may be contraindicated in pregnancy (because of teratogenicity noted in animal studies and since the effects of drugs on fetus has not been established) except in the presence of a disease such as severe tuberculosis.
  • It is contraindicated in alcoholics with severely impaired liver function and with jaundice.
Exam Question
  • Treatment of choice for HIV and TB along with Rifampicin is Ritonavir
  • Rifampicin acts by DNA dependent RNA polymerase
  • Rifampicin is Microsomal enzyme inducer
  • Rifampicin May cause OCP failure
  • Rifampicin is Bactericidal in nature
  • Rifampicin enhance the metabolism of warfarin
  • A tuberculosis patient with only rifampicin resistance will be treated under Cat IV
  • During the treatment with rifampicin some patients will have mild elevation in the bilirubin with normal transaminases due to Hepatic adaptation
  • Rifampicin do not require reduction in dose 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 color 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