Irbesartan

Irbesartan is an angiotensin receptor blocker with high oral bioavailability that is unaffected by food. It treats hypertension and slows progression of diabetic nephropathy in type 2 diabetes with hypertension and proteinuria.

Classification. Angiotensin receptor blocker (AT1); non prodrug.

Mechanism. Blocks the AT1 receptor, reducing vasoconstriction, aldosterone secretion and efferent arteriolar tone.

Pharmacodynamics. Onset within 2 hours; full effect over 4 to 6 weeks; duration 24 hours. Reduces proteinuria and slows progression to end stage kidney disease in diabetic nephropathy.

Pharmacokinetics. Bioavailability 60 to 80%. Half life 11 to 15 hours. Metabolised by CYP2C9 and glucuronidation; excreted in bile and urine.

Hypertension, adult.

• Start 150 mg once daily (75 mg if volume depleted, on haemodialysis, or older than 75 years).

• Increase after 4 to 6 weeks to 300 mg once daily.

• Maximum 300 mg daily.

Hypertension with type 2 diabetes and nephropathy, adult. Start 150 mg once daily; increase to 300 mg once daily as the maintenance and target dose.

Children aged 6 to 16 years (licensed in some markets). Under 35 kg: 75 mg once daily; 35 kg and over: 150 mg once daily; increase as needed to a maximum 150 mg and 300 mg daily respectively. Specialist.

Contraindications. Pregnancy; bilateral renal artery stenosis; hyperkalaemia; hypersensitivity; aliskiren in diabetes or kidney impairment.

Warnings. Hypotension, hyperkalaemia and kidney function decline. Angioedema is rare. Sick day rule: hold during dehydrating illness. Raised creatine kinase and muscle symptoms, rarely.

Adverse effects. Dizziness, hypotension, hyperkalaemia, creatinine rise, fatigue, musculoskeletal pain, rarely angioedema.

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury. Lithium: toxicity. Rifampicin lowers levels; CYP2C9 inhibitors raise levels.

Special groups.

• Pregnancy: contraindicated; stop when pregnancy is confirmed.

• Breastfeeding: avoid; no data.

• Patients of African ancestry: smaller response as monotherapy; combine with a calcium channel blocker or thiazide like diuretic.

• Older adults: start at 75 mg if over 75 years.

• Kidney impairment: no adjustment; start 75 mg on haemodialysis.

• Liver impairment: no adjustment in mild to moderate; severe: not studied.

Formulations. Tablets 75, 150, 300 mg; combinations with hydrochlorothiazide.

Administration. Oral once daily, with or without food.

Baseline. Blood pressure, creatinine and eGFR, potassium, urine albumin, pregnancy status.

Monitoring. Creatinine and potassium 1 to 2 weeks after starting or each dose increase, then every 6 to 12 months. Accept a creatinine rise up to 30%; reduce or stop if over 30% or potassium is over 6.0 mmol/L; review contributors if potassium is over 5.5 mmol/L. Urine albumin to creatinine ratio every 6 to 12 months in diabetes.

Stopping. Stop for pregnancy, angioedema, or creatinine rise over 30% or potassium over 6.0 mmol/L.

Common prescribing errors. Using it in pregnancy; omitting albuminuria monitoring in diabetes; not starting at 75 mg in dialysis; combining with an angiotensin converting enzyme inhibitor.