Para Aminosalicylic Acid

Para aminosalicylic acid is an oral bacteriostatic antituberculosis drug now used mainly as a companion in longer regimens for rifampicin-resistant tuberculosis when better options cannot be assembled. Poor gastrointestinal tolerance, a large pill burden and hypothyroidism limit its use.

Class. Folate synthesis antagonist; second-line antituberculosis drug.

Mechanism. Acts as a substrate for dihydropteroate synthase, producing a false folate analogue that blocks folate-dependent synthesis. Resistance arises through thyA and folC mutations.

Pharmacokinetics. Absorbed in the small intestine; granule forms give higher levels with acidic food. Half life about 1 hour. Acetylated in the liver and excreted in urine, so acetylated metabolites and the sodium load accumulate in kidney failure.

Rifampicin-resistant and multidrug-resistant tuberculosis (adults). - 8 to 12 g daily in 2 to 3 divided doses; usual 4 g two or three times daily; maximum 12 g daily. - Titration: start 2 g and increase to full dose over 1 to 2 weeks. - Loading dose: none. Maintenance dose: 8 to 12 g daily. - Duration: set by the regimen, often 18 to 20 months.

Children. 200 to 300 mg/kg daily in 2 to 4 divided doses, maximum 10 g daily.

Main alternative. Ethionamide or prothionamide, linezolid and clofazimine, depending on regimen.

Contraindications. Hypersensitivity to salicylates, severe kidney impairment, and heart failure or hypertension where sodium load matters (sodium salt).

Serious adverse effects. Hepatitis, hypersensitivity syndrome (fever, rash, eosinophilia, lymphadenopathy), hypothyroidism, haemolytic anaemia in G6PD deficiency, hypokalaemia, malabsorption syndrome and crystalluria.

Common adverse effects. Nausea, vomiting, diarrhoea and abdominal pain.

Interactions. Reduces absorption of vitamin B12, digoxin and rifampicin (separate by 4 hours); additive hypothyroidism with ethionamide and prothionamide; additive hepatotoxicity with other antituberculosis drugs.

Common prescribing errors. Starting at full dose, failing to discard degraded granules (brown or purple discolouration), omitting thyroid and potassium checks, and giving it with an alkaline drink.

Special groups. - Pregnancy: limited data; used only when needed. - Breastfeeding: small amounts in milk; use with monitoring. - Children: weight-based; tolerability is poor in young children. - Older adults: usual dose; monitor electrolytes. - Kidney impairment: with CrCl under 30 mL/min, give 4 g twice daily at most; avoid in severe disease. - Liver impairment: avoid in severe disease.

Formulations. Granules 4 g sachets (enteric-coated) and tablets.

Administration. Give granules sprinkled on acidic soft food or drink such as yoghurt, apple sauce or orange juice; do not crush. Take with food.

Baseline. Liver tests, TSH, potassium, creatinine and G6PD status.

Monitoring. Liver tests monthly; TSH every 3 months; potassium and creatinine monthly.

Stopping thresholds. Stop for hypersensitivity syndrome, hepatitis (ALT over three times the upper limit of normal with symptoms, or over five times without) or intractable vomiting.

Referral and escalation. Manage within a drug-resistant tuberculosis programme; endocrine review for overt hypothyroidism.