Azilsartan

Azilsartan medoxomil is a prodrug converted to azilsartan, an angiotensin receptor blocker with strong, slowly dissociating binding and greater blood pressure lowering than some older drugs in its class at maximum doses. It treats hypertension. It is not available in many East African markets.

Classification. Angiotensin receptor blocker (AT1); prodrug.

Mechanism. Binds the AT1 receptor with slow dissociation, blocking vasoconstriction and aldosterone release.

Pharmacodynamics. Onset within 2 hours; full effect over 2 to 4 weeks; duration 24 hours. Stronger systolic reductions than valsartan or olmesartan at maximum doses in comparison studies.

Pharmacokinetics. Bioavailability about 60%; food has no effect. Half life about 11 hours. Metabolised by CYP2C9; excreted in urine and faeces.

Hypertension, adult.

• Start 80 mg once daily; 40 mg in patients on high dose diuretics, or volume depleted.

• Maintenance 40 to 80 mg once daily; maximum 80 mg daily.

• Combination tablets with chlorthalidone are available.

Children. Not established.

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. Excess lowering of blood pressure in volume depleted patients.

Adverse effects. Dizziness, hypotension, diarrhoea, hyperkalaemia, creatinine rise, fatigue, muscle spasm.

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury. Lithium: toxicity. Fluconazole and other 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: no adjustment; monitor.

• Kidney impairment: no starting dose change; monitor; limited data in severe impairment.

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

Formulations. Tablets 40 and 80 mg; combination with chlorthalidone.

Administration. Oral once daily, 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. Using it in pregnancy; combining with an angiotensin converting enzyme inhibitor; omitting potassium and creatinine checks; starting at 80 mg with high dose diuretics.