Lisinopril

Lisinopril is a lysine analogue of enalaprilat that is active without liver conversion. It is excreted unchanged by the kidneys and has a long half life that allows once daily dosing. Uses are hypertension, heart failure, acute myocardial infarction and diabetic kidney disease.

Classification. Angiotensin converting enzyme inhibitor; active drug; hydrophilic.

Mechanism. Blocks angiotensin converting enzyme, lowering angiotensin II and aldosterone and increasing bradykinin.

Pharmacodynamics. Onset 1 hour, peak 6 hours, duration 24 hours. Full blood pressure effect over 2 to 4 weeks. Lowers proteinuria.

Pharmacokinetics. Oral bioavailability about 25% (variable); not affected by food. Effective half life 12 hours; terminal half life longer. Not metabolised; excreted unchanged in urine; removed by haemodialysis.

Hypertension, adult.

• Start 10 mg once daily; 2.5 to 5 mg if on a diuretic, older, or with kidney impairment.

• Usual maintenance 20 to 40 mg once daily.

• Maximum 80 mg daily; doses over 40 mg add little.

Heart failure with reduced ejection fraction, adult.

• Start 2.5 mg once daily.

• Increase by 2.5 to 5 mg every 2 weeks as tolerated.

• Target 20 to 35 mg once daily; maximum 40 mg daily.

Acute myocardial infarction, haemodynamically stable, adult. 5 mg orally within 24 hours of symptoms, 5 mg after 24 hours, 10 mg after 48 hours, then 10 mg once daily for at least 6 weeks. Do not start if systolic pressure is under 100 mmHg.

Diabetic kidney disease with albuminuria, adult. 10 mg daily, titrated to 20 mg daily, to reduce proteinuria.

Children aged 6 to 16 years, hypertension. 0.07 mg/kg once daily (maximum 5 mg) initially; titrate to a maximum 0.61 mg/kg or 40 mg daily. Not for creatinine clearance under 30 mL/min.

Contraindications. Pregnancy; history of angioedema; bilateral renal artery stenosis; hyperkalaemia; concurrent sacubitril with valsartan (36 hour gap); hypotension.

Warnings. Angioedema (higher frequency in patients of African ancestry; stop permanently if it occurs). Dry cough. First dose hypotension. Hyperkalaemia and decline in kidney function. Sick day rule: hold during dehydrating illness. Neutropenia and cholestatic jaundice (rare).

Adverse effects. Cough, dizziness, headache, hypotension, hyperkalaemia, creatinine rise, diarrhoea, angioedema.

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim, heparin: hyperkalaemia. Non steroidal anti-inflammatory drugs: reduced effect and kidney injury. Lithium: toxicity. Diuretics: hypotension. Aliskiren: avoid in diabetes and kidney impairment. Sacubitril: angioedema.

Special groups.

• Pregnancy: contraindicated; foetal harm in the second and third trimesters; stop when pregnancy is confirmed.

• Breastfeeding: avoid in early weeks and preterm infants; enalapril or captopril are preferred.

• Patients of African ancestry: reduced response as monotherapy; add a calcium channel blocker or diuretic.

• Older adults: start at 2.5 to 5 mg.

• Kidney impairment: creatinine clearance 10 to 30 mL/min: start 2.5 to 5 mg (hypertension 5 mg), maximum 40 mg; under 10 mL/min or on dialysis: start 2.5 mg.

• Liver impairment: no adjustment.

Formulations. Tablets 2.5, 5, 10, 20, 40 mg; oral solution in some markets.

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

Baseline. Blood pressure, creatinine and eGFR, potassium, pregnancy status, history of angioedema.

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.

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

Common prescribing errors. Not reducing the starting dose with a diuretic or kidney impairment; use in pregnancy; omitting potassium and creatinine checks; combining with potassium sparing diuretics and trimethoprim.