Fosinopril

Fosinopril is a phosphinate containing angiotensin converting enzyme inhibitor prodrug converted to fosinoprilat. Unlike most others it is cleared by both liver and kidney, which makes it less dependent on renal function. It is used for hypertension and heart failure and is stocked in few East African markets.

Classification. Angiotensin converting enzyme inhibitor; phosphinate prodrug.

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

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

Pharmacokinetics. Oral bioavailability about 36%; hydrolysed in the gut wall and liver to fosinoprilat. Half life of the active drug about 12 hours. Balanced elimination in urine and bile.

Hypertension, adult.

• Start 10 mg once daily (5 mg in older adults or on a diuretic).

• Increase after 4 weeks if needed.

• Usual maintenance 20 to 40 mg once daily.

• Maximum 80 mg daily in some markets; most label ceilings are 40 mg.

Heart failure with reduced ejection fraction, adult.

• Start 5 to 10 mg once daily under supervision.

• Increase over weeks to a target of 20 to 40 mg once daily.

• Maximum 40 mg daily.

Children aged 6 to 16 years over 50 kg, hypertension. 5 to 10 mg once daily; maximum 40 mg daily. Under 50 kg: 0.1 mg/kg (specialist).

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). Dry cough. First dose hypotension. Hyperkalaemia and decline in kidney function. Sick day rule: hold during dehydrating illness. Neutropenia (rare).

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

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury. Lithium: toxicity. Diuretics: hypotension. Antacids reduce absorption; separate by 2 hours. Aliskiren: avoid in diabetes and kidney impairment. Sacubitril: angioedema.

Special groups.

• Pregnancy: contraindicated; stop when pregnancy is confirmed.

• Breastfeeding: avoid; limited data.

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

• Older adults: start at 5 mg.

• Kidney impairment: no routine adjustment; start low (5 to 10 mg) and monitor in advanced disease.

• Liver impairment: clearance is reduced; start low and titrate.

Formulations. Tablets 10 and 20 mg.

Administration. Oral once daily with or without food. Separate from antacids.

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. Assuming no monitoring is needed because of dual elimination; use in pregnancy; giving with antacids; omitting the potassium and creatinine checks.