Triamterene

Triamterene is a weak potassium sparing diuretic that blocks the epithelial sodium channel. It is used with a thiazide or loop diuretic to prevent hypokalaemia in oedema and hypertension. It causes hyperkalaemia, kidney stones, and rarely folate deficiency. It is seldom available alone in East Africa.

Classification. Potassium sparing diuretic; epithelial sodium channel blocker (not an aldosterone antagonist).

Mechanism. Blocks sodium entry through the epithelial sodium channel in the late distal tubule and collecting duct, reducing potassium and hydrogen ion secretion. It is also a weak folate antagonist.

Pharmacodynamics. Onset within 2 to 4 hours, peak at 6 hours, duration 12 to 16 hours. Weak diuretic used mainly with other agents.

Pharmacokinetics. Oral bioavailability about 50 to 60%. Half life 2 hours for the parent; the active hydroxylated sulphate metabolite has a half life of about 3 hours and accumulates in kidney impairment. Metabolised in the liver; excreted in urine.

Oedema, adult.

• Start 150 mg daily in 2 divided doses after breakfast and lunch.

• Reduce after 1 week to the lowest effective dose (usually 150 mg on alternate days, or 50 to 100 mg daily).

• Usual range 150 to 250 mg daily; maximum 300 mg daily.

Hypertension (as fixed combination with a thiazide), adult. Triamterene 37.5 mg with hydrochlorothiazide 25 mg once daily; may increase to 2 tablets daily in the label of some markets.

Children. Not established.

Contraindications. Hyperkalaemia; Addison disease; anuria; severe kidney impairment; severe hepatic impairment; concurrent potassium supplements, other potassium sparing diuretics, or aldosterone antagonists; hypersensitivity.

Warnings. Hyperkalaemia; kidney stones (triamterene stones); acute kidney injury when combined with indometacin or other non steroidal anti-inflammatory drugs; folate deficiency and megaloblastic anaemia (with long use, in cirrhosis, in pregnancy); photosensitivity; blue fluorescence of urine (harmless).

Adverse effects. Hyperkalaemia, nausea, vomiting, diarrhoea, dry mouth, headache, dizziness, muscle cramp, kidney stones, raised urea, rash, rarely megaloblastic anaemia or thrombocytopenia.

Interactions. Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, potassium supplements, trimethoprim, spironolactone, ciclosporin: hyperkalaemia. Indometacin and other non steroidal anti-inflammatory drugs: kidney injury. Lithium: raised levels. Amantadine: raised levels. Trimethoprim and other folate antagonists: more anaemia.

Special groups.

• Pregnancy: avoid; folate antagonism.

• Breastfeeding: excreted in milk; avoid.

• Patients of African ancestry: no change; monitor potassium.

• Older adults: use the lowest dose; high risk of hyperkalaemia.

• Kidney impairment: avoid with eGFR under 30 mL/min; metabolite accumulates.

• Liver impairment: avoid in severe disease; risk of folate deficiency.

Formulations. Tablets 50 mg; fixed combinations with hydrochlorothiazide (37.5/25 mg, 50/25 mg).

Administration. Oral after meals.

Baseline. Potassium, sodium, creatinine and eGFR, full blood count, urine for crystals if stones are suspected.

Monitoring. Potassium and creatinine at 1 week and 4 weeks after starting or any dose change, then every 3 to 6 months. Full blood count and folate in long term use. Halve the dose if potassium is above 5.5 mmol/L; stop if above 6.0 mmol/L.

Stopping. No taper. Hold on sick days.

Common prescribing errors. Using it with indometacin; adding a potassium supplement; missing hyperkalaemia in kidney impairment; continuing 300 mg daily without checking.