SN2 SHORT NOTE 5M ★ High-yield

Describe rifampicin with its mechanism, uses, adverse effects and interactions.

Pharmacology · 2nd Professional — Para-Clinical

Pharmacology

Rifampicin inhibits DNA-dependent RNA polymerase by binding its beta subunit, blocking transcription. It is bactericidal and acts on both dividing and semi-dormant organisms.

Its sterilising activity against persisters is why modern short-course chemotherapy is possible — rifampicin reduced treatment from 18 months to 6
Well absorbed orally (better on an empty stomach); excellent tissue and CSF penetration; excreted chiefly in bile with enterohepatic circulation
Resistance arises from a single-step mutation in the rpoB gene — which is why it must never be used alone, and why molecular detection of rifampicin resistance (CBNAAT) is such a useful proxy for MDR-TB

Uses

Tuberculosis — in every regimen for drug-sensitive disease
Leprosy — the most potent bactericidal antileprotic; a single monthly supervised dose is a component of multidrug therapy
Meningococcal carriage and contact prophylaxis
Staphylococcal infection of prosthetic material — rifampicin penetrates biofilm well and is added to another agent (never alone)
Brucellosis, Legionella, and MAC infection
Pruritus of cholestasis, an unrelated use exploiting enzyme induction

Adverse Effects

Effect	Details
Orange-red discolouration	Of urine, sweat, tears, sputum and saliva — entirely harmless, but alarming if not forewarned, and it permanently stains soft contact lenses. Failure to warn is a recognised cause of treatment default
Hepatotoxicity	Cholestatic pattern; potentiated by isoniazid and pyrazinamide; also causes a harmless unconjugated hyperbilirubinaemia early by competing for hepatic uptake
Intermittent-dose ("flu") syndrome	With intermittent or interrupted therapy — fever, chills, myalgia, headache; and less commonly thrombocytopenia, haemolytic anaemia, acute interstitial nephritis and shock, all immunologically mediated. These require permanent withdrawal
Gastrointestinal	Nausea, anorexia, abdominal pain
Cutaneous	Rash, pruritus, flushing

CLINICAL PEARL

Rifampicin is the most powerful enzyme inducer in common clinical use, and this causes more problems than its toxicity does. It induces CYP3A4 and P-glycoprotein within days, and the consequences include unplanned pregnancy from oral contraceptive failure, loss of anticoagulation, transplant rejection from reduced ciclosporin levels, and antiretroviral failure. In India, where rifampicin is prescribed to millions, this single interaction profile deserves as much attention as any adverse effect.

Interactions

Drugs whose levels fall substantially — oral contraceptives, warfarin, corticosteroids, ciclosporin and tacrolimus, oral hypoglycaemics, digoxin, phenytoin, theophylline, azole antifungals, and most antiretrovirals
Alternative contraception must be advised for the duration and for several weeks afterwards
Protease inhibitors cannot generally be given with rifampicin; rifabutin is substituted, being a much weaker inducer, and the dolutegravir dose is doubled
Induction persists for 1 to 2 weeks after stopping, so doses of the affected drugs must be readjusted downward at that point — a step often forgotten, with bleeding on warfarin as a result

Applied Aspects

Warn about orange secretions and contact lenses before the first dose
Review every other drug the patient takes when starting or stopping rifampicin, and again two weeks after stopping
Never give rifampicin alone for any mycobacterial infection; single-step resistance follows within weeks
CBNAAT detects rifampicin resistance in under 2 hours, and a positive result is treated as MDR-TB until proved otherwise — the single most useful diagnostic advance in Indian tuberculosis practice
Take it on an empty stomach, an hour before food, since absorption is reduced by a meal
Monitor liver function where risk factors exist, and counsel on the symptoms that require immediate attention

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