Captopril

Captopril is the original angiotensin converting enzyme inhibitor, a sulphydryl containing active drug with a short duration of action. It needs two or three daily doses. It remains widely used in East Africa because it is cheap, and it is the preferred angiotensin converting enzyme inhibitor in breastfeeding.

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

Mechanism. Blocks angiotensin converting enzyme, lowering angiotensin II and aldosterone and increasing bradykinin. The sulphydryl group may scavenge free radicals.

Pharmacodynamics. Onset 15 to 30 minutes, peak 1 to 1.5 hours, duration 6 to 12 hours. Short duration allows controlled first dose titration.

Pharmacokinetics. Oral bioavailability 60 to 75%, reduced by 30 to 40% with food. Half life about 2 hours (longer in kidney failure). Excreted mostly in urine; some metabolites are active.

Hypertension, adult.

• Start 12.5 mg twice daily (6.25 mg in diuretic treated, volume depleted or older patients).

• Increase after 2 weeks to 25 mg twice daily, then to 50 mg twice daily.

• Usual maintenance 25 to 50 mg twice daily; maximum 150 mg daily.

Heart failure with reduced ejection fraction, adult.

• Start 6.25 mg three times daily (first dose supervised).

• Increase every 1 to 2 weeks to 25 mg, then 50 mg three times daily.

• Target 50 mg three times daily; maximum 150 mg daily.

After myocardial infarction, haemodynamically stable, adult. 6.25 mg on day 1 (from 3 days after the event), then 12.5 mg three times daily, then 25 mg three times daily, to a target of 50 mg three times daily.

Diabetic kidney disease with albuminuria, adult. 75 to 100 mg daily in divided doses.

Children, hypertension. 0.3 mg/kg three times daily initially; titrate to a maximum 6 mg/kg daily in 2 to 3 divided doses. Neonates and infants: lower doses, specialist.

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

Warnings. Taste disturbance, rash, proteinuria and neutropenia, more often with kidney impairment, collagen vascular disease and high doses. Angioedema (higher frequency in patients of African ancestry). Dry cough. First dose hypotension. Hyperkalaemia and decline in kidney function. Sick day rule: hold during dehydrating illness.

Adverse effects. Cough, dysgeusia, rash, hypotension, hyperkalaemia, creatinine rise, proteinuria, neutropenia, angioedema.

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury and reduced effect. Lithium: toxicity. Allopurinol: hypersensitivity and neutropenia. Immunosuppressants and cytotoxics: neutropenia. Antacids reduce absorption. Sacubitril: angioedema.

Special groups.

• Pregnancy: contraindicated; stop when pregnancy is confirmed.

• Breastfeeding: preferred angiotensin converting enzyme inhibitor with enalapril; very small amounts in milk.

• Patients of African ancestry: reduced response as monotherapy; higher angioedema risk.

• Older adults: start at 6.25 mg.

• Kidney impairment: creatinine clearance 10 to 50 mL/min: use 75% of the usual dose; under 10 mL/min: 50% of the usual dose, at longer intervals; monitor white cells.

• Liver impairment: no adjustment.

Formulations. Tablets 12.5, 25, 50, 100 mg; oral solution in some markets.

Administration. Take 1 hour before food, since food reduces absorption.

Baseline. Blood pressure, creatinine and eGFR, potassium, full blood count, urine protein, 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. White cell count every 3 months for the first year in kidney impairment or collagen vascular disease, then periodically. Urine protein.

Stopping. Stop for angioedema, pregnancy, neutropenia (neutrophils under 1.0 x 10^9/L), or creatinine rise over 30% or potassium over 6.0 mmol/L.

Common prescribing errors. Giving with food; not reducing the dose in kidney impairment; omitting white cell monitoring; use in pregnancy.