Antimicrobials/Antituberculous

Anti-TB drugs (RIPE)

also: rifampicin · isoniazid · pyrazinamide · ethambutol · RIPE · tuberculosis

Overview

The four-drug TB regimen — 2 months RIPE then 4 months RI. Each drug has a signature toxicity, and rifampicin is a potent enzyme inducer.

Mechanism

Combination therapy prevents resistance. Rifampicin inhibits RNA polymerase; isoniazid inhibits mycolic-acid synthesis; pyrazinamide active in acidic environments; ethambutol inhibits arabinosyl transferase.

Indications

Active TB (2 mo RIPE → 4 mo rifampicin+isoniazid)
Latent TB (rifampicin+isoniazid, or isoniazid alone)

The agents

RifampicinR

POTENT CYP450 INDUCER (↓OCP — barrier method; ↓warfarin/anticonvulsants); orange secretions; hepatotoxic.

IsoniazidI

Peripheral neuropathy → give PYRIDOXINE (B6); hepatotoxic; drug-induced lupus.

PyrazinamideP

first 2 months

Hepatotoxic; hyperuricaemia/gout.

EthambutolE

OPTIC NEURITIS (colour vision) — baseline + monitor visual acuity.

Adverse effects

Hepatotoxicity (R, I, P)serious

Monitor LFTs.

Isoniazid peripheral neuropathyclassic

Prevent with pyridoxine.

Ethambutol optic neuritisserious

Rifampicin: orange urine/tears + enzyme inductionclassic

Cautions & contraindications

Rifampicin + combined oral contraceptiveall

Enzyme induction → contraceptive failure (use barrier).

Pre-existing optic neuropathy (ethambutol)all

Interactions

Rifampicin induces CYP (OCP, warfarin, anticonvulsants, HIV drugs, steroids)

Monitoring & kinetics

LFTs; ethambutol — visual acuity/colour; isoniazid — give B6

Oral, directly-observed therapy if adherence concern. Notifiable disease.

Choosing it

true

Source: NICE NG33 — Tuberculosis · BNF — Antituberculous drugs