Losartan

Losartan is an angiotensin II type 1 receptor blocker given as a prodrug-like parent with an active carboxylic acid metabolite. It treats hypertension, heart failure with reduced ejection fraction when an angiotensin converting enzyme inhibitor is not tolerated, and diabetic kidney disease. It is widely available and low cost in East Africa.

Classification. Angiotensin receptor blocker (AT1); biphenyl tetrazole.

Mechanism. Blocks the AT1 receptor, preventing vasoconstriction and aldosterone release from angiotensin II. It does not raise bradykinin, so cough is uncommon. It has a mild uricosuric effect.

Pharmacodynamics. Onset within 1 hour; peak effect on blood pressure at 3 to 6 weeks; duration 24 hours (some patients need twice daily dosing). Reduces proteinuria and slows diabetic nephropathy.

Pharmacokinetics. Oral bioavailability about 33%; food has little effect. Half life 2 hours for the parent and 6 to 9 hours for the active metabolite. Metabolised by CYP2C9 and CYP3A4; excreted in urine and bile.

Hypertension, adult.

• Start 50 mg once daily (25 mg if volume depleted, older than 75 years, or hepatic impairment).

• Increase after 3 to 6 weeks to 100 mg once daily or 50 mg twice daily.

• Maximum 100 mg daily.

Heart failure with reduced ejection fraction, adult (angiotensin converting enzyme inhibitor intolerant). Start 12.5 mg once daily; double the dose weekly to a target of 50 to 150 mg once daily; maximum 150 mg daily.

Diabetic kidney disease with albuminuria, adult. 50 mg once daily, increased to 100 mg once daily.

Hypertension with left ventricular hypertrophy, adult. 50 mg once daily; add a thiazide like diuretic or increase to 100 mg.

Children aged 6 to 16 years over 20 kg, hypertension. 0.7 mg/kg once daily (maximum 50 mg), increased as needed to a maximum 1.4 mg/kg or 100 mg daily. Not for creatinine clearance under 30 mL/min.

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

Warnings. Hypotension, hyperkalaemia and decline in kidney function. Angioedema is rare but can occur, including in patients who had it with an angiotensin converting enzyme inhibitor (use with caution). Sick day rule: hold during vomiting, diarrhoea or dehydration. Do not combine routinely with an angiotensin converting enzyme inhibitor.

Adverse effects. Dizziness, hypotension, hyperkalaemia, creatinine rise, fatigue, diarrhoea, rarely cough or angioedema.

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury and reduced effect. Lithium: toxicity. Fluconazole and other CYP2C9 inhibitors: reduce active metabolite. Rifampicin lowers levels.

Special groups.

• Pregnancy: contraindicated; foetal kidney injury and oligohydramnios; stop when pregnancy is confirmed.

• Breastfeeding: avoid; limited data.

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

• Older adults: start at 25 mg if over 75 years.

• Kidney impairment: no starting dose change; monitor creatinine and potassium.

• Liver impairment: start 25 mg; severe: avoid.

Formulations. Tablets 25, 50, 100 mg; combinations with hydrochlorothiazide.

Administration. Oral once daily at the same time, with or without food.

Baseline. Blood pressure, creatinine and eGFR, potassium, 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. Blood pressure at 2 to 4 weeks.

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

Common prescribing errors. Prescribing in pregnancy or women planning pregnancy without contraception advice; combining with an angiotensin converting enzyme inhibitor; omitting potassium and creatinine checks; continuing during dehydrating illness.