Rifampicin

Rifampin is an antibiotic that targets the core of bacterial machinery: DNA-dependent RNA polymerase, the enzyme that copies DNA into RNA. By binding to it, rifampin blocks RNA synthesis, either by physically obstructing the exit of the nascent RNA transcript or by lowering the enzyme’s affinity for short transcripts. Deprived of its RNA, the bacterium can no longer manufacture its proteins and dies.

This target belongs to the microbial world alone: rifampin acts on the RNA polymerase of bacteria and not on the equivalent enzyme in human cells. This selectivity explains its bactericidal action, meaning that it kills the germ rather than merely slowing its growth. Against Mycobacterium tuberculosis, it remains active both on bacteria lodged inside cells and on those that stay outside.

The approved indications revolve first around tuberculosis, in both its active and latent forms, where rifampin holds a central place in treatment. It is also used to clear the asymptomatic carriage of Neisseria meningitidis, the bacterium responsible for certain forms of meningitis, in people who harbour it in the throat without being ill.

Beyond its marketing authorisation, rifampin is sometimes used against leprosy, against certain infections with methicillin-resistant Staphylococcus aureus (MRSA) and to relieve pruritus, the stubborn itching of liver diseases with bile retention. The choice of the drug, its dose and its duration rests with the physician, according to the infection being treated.

Rifampin is taken on an empty stomach, with a large glass of water, one hour before or two hours after a meal, because food reduces its absorption. Its steady-state half-life is short, two to three hours, which makes regular dosing important to maintain an effective level. You do not stop it on your own initiative, even if you feel better: a shortened course gives the germ a chance to survive and become resistant.

One visible effect often surprises at the start: the drug temporarily colours the urine, sweat, saliva, tears and stool yellow, red-orange or brown. This phenomenon is harmless and disappears once treatment stops. Soft contact lenses worn during treatment, however, can be permanently stained red, which is why glasses are preferable during this period.

The liver is the organ to monitor first. Prolonged treatment is accompanied by minor and transient elevations of serum transaminases in 10 to 20% of patients, laboratory abnormalities that generally call for neither dose adjustment nor discontinuation. More rarely, rifampin causes clinically evident liver injury, with jaundice, which can be severe or even fatal, and whose onset typically occurs one to six weeks after treatment begins. In addition, serum bilirubin often rises during the first days then falls again: this transient phenomenon reflects a hindrance to bilirubin transport in the liver, not damage to the liver cells.

Other effects do not depend on the dose and stem from hypersensitivity reactions: hives, a flu-like syndrome, a drop in platelets (thrombocytopenia), destruction of red blood cells (haemolysis) and kidney involvement. Conversely, digestive disturbances and the orange colouring of body fluids are dose-dependent. Any unusual sign, fever, jaundice, rash or marked fatigue, should be reported to the physician without delay.

Prolonged treatment with rifampin can lead to vitamin D deficiency, and even to osteomalacia, that softening of bone linked to a lack of vitamin D, particularly in people whose reserves were already marginal. Rifampin activates a nuclear receptor, PXR (pregnane X receptor), also called SXR, which serves as a sensor of drugs and xenobiotics within the cell.

How this activation translates into a loss of vitamin D remains debated. According to a first hypothesis, PXR would increase the production of 25-hydroxyvitamin D3-24-hydroxylase, or CYP24, a mitochondrial enzyme that inactivates vitamin D metabolites (Pascussi, 2005). Other work rules out this pathway and assigns this catabolism instead to CYP3A4 (Zhou, 2006). The net result, however, is constant: under rifampin, vitamin D is inactivated faster and its reserves can be depleted over the weeks of treatment.

Rifampin is a potent inducer of cytochromes P450, those liver enzymes that metabolise drugs (CYP3A4, CYP2C9, CYP2C19, CYP2C8, CYP1A2). By stimulating them, it speeds up the elimination of many treatments and sharply lowers their concentrations: statins, anticoagulants, opioids and oral contraceptives are among the most affected. This reduced effectiveness of hormonal contraceptives makes it necessary to add another method of contraception throughout the treatment. Any drug combination deserves to be checked by the physician or pharmacist.

Laboratory monitoring rests above all on watching liver function, particularly the transaminases, since their elevations are frequent and since overt liver injury, though rare, can be serious. A transient rise in bilirubin at the start of treatment is expected and does not by itself signal liver distress. This monitoring framework makes it possible to spot the rare complications early and to adjust management if needed.