Valsartan

Valsartan is an angiotensin receptor blocker used in hypertension, heart failure with reduced ejection fraction and after myocardial infarction with left ventricular dysfunction. It is active without metabolic conversion and has a short half life, with 24 hour effect at usual doses.

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

Mechanism. Blocks the AT1 receptor, preventing vasoconstriction, sodium retention and aldosterone release.

Pharmacodynamics. Onset within 2 hours; peak blood pressure effect at 4 to 6 weeks; duration 24 hours. Reduces hospital admission in heart failure.

Pharmacokinetics. Oral bioavailability about 25%; food reduces exposure by about 40% without loss of effect. Half life about 6 hours. Mostly excreted unchanged in faeces (bile); about 13% in urine. A substrate of hepatic uptake transporters (OATP1B1) and efflux transporters.

Hypertension, adult.

• Start 80 mg once daily (40 mg if volume depleted); 160 mg if more reduction is needed.

• Increase after 3 to 4 weeks to 160 mg, then 320 mg once daily.

• Maximum 320 mg daily.

Heart failure with reduced ejection fraction, adult.

• Start 40 mg twice daily.

• Increase every 2 weeks to 80 mg, then 160 mg twice daily as tolerated.

• Target and maximum 160 mg twice daily (320 mg daily).

After myocardial infarction with left ventricular dysfunction, adult. Start 20 mg twice daily from 12 hours after the event; increase over weeks to a target of 160 mg twice daily.

Children aged 6 to 17 years, hypertension. 1.3 mg/kg once daily (maximum 40 mg) initially; titrate to a maximum 2.7 mg/kg or 160 mg daily. Not for creatinine clearance under 30 mL/min.

Contraindications. Pregnancy; bilateral renal artery stenosis; hyperkalaemia; severe hepatic impairment, biliary cirrhosis and cholestasis; hypersensitivity; aliskiren in diabetes or kidney impairment.

Warnings. Hypotension, hyperkalaemia and kidney function decline. Angioedema is rare. Sick day rule: hold during dehydrating illness. Do not combine routinely with an angiotensin converting enzyme inhibitor and a mineralocorticoid antagonist (hyperkalaemia).

Adverse effects. Dizziness, hypotension, hyperkalaemia, creatinine rise, fatigue, cough (uncommon), diarrhoea.

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury. Lithium: toxicity. Ciclosporin, ritonavir and rifampicin: raise valsartan exposure through transporter inhibition.

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 40 mg in frail patients.

• Kidney impairment: creatinine clearance under 30 mL/min: use with caution and monitor.

• Liver impairment: mild to moderate non biliary: maximum 80 mg daily in some labels; severe: avoid.

Formulations. Tablets 40, 80, 160, 320 mg; capsules; oral solution in some markets.

Administration. Oral once or twice daily, with or without food.

Baseline. Blood pressure, creatinine and eGFR, potassium, liver function, 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 and symptoms.

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

Common prescribing errors. Using it in pregnancy; stepping to 320 mg without checking potassium and creatinine; combining with an angiotensin converting enzyme inhibitor, aliskiren and a mineralocorticoid antagonist; confusing it with the sacubitril combination.