Fosinopril

Fosinopril is an angiotensin-converting enzyme (ACE) inhibitor, a medicine that relaxes blood vessels and lowers blood pressure. It is authorised as a medicine and is being studied in a Phase 3 clinical trial involving 368 participants with heart failure, where it appears as one of several guideline-directed medical therapies being optimised.^[1]

Table of contents

• What is fosinopril?
• How does fosinopril work?
• Which conditions is it used or studied for?
• How is fosinopril given?
• What do the clinical trials show?
• What side effects are known?

What is fosinopril?

Fosinopril is an angiotensin-converting enzyme (ACE) inhibitor. It is a chemically synthesised substance, available as the sodium salt of fosinopril, which is an ester prodrug of the active form fosinoprilat.^[2] The medicine is authorised for use and is classified under the ATC code C09AA09.^[3] In the EU Clinical Trials Information System, fosinopril appears as a test substance in two trial records, including the heart failure trial described below.^[1]

How does fosinopril work?

Fosinopril works by inhibiting the angiotensin-converting enzyme (ACE). This enzyme normally converts angiotensin I to angiotensin II, a substance that narrows blood vessels and stimulates the release of aldosterone, which raises blood pressure. By blocking ACE, fosinopril reduces the production of angiotensin II, leading to relaxation of blood vessels and lower blood pressure.^[2] ACE is also identical to kininase, an enzyme that breaks down bradykinin, a substance that widens blood vessels; whether increased bradykinin levels contribute to the therapeutic effect is not fully established.^[2]

Which conditions is it used or studied for?

• High blood pressure (hypertension) — fosinopril is authorised as a medicine and has been studied in hypertensive patients; 647 patients treated with fosinopril alone for an average of 29 weeks showed a mean increase in serum potassium of 0.1 mEq/L.^[2]
• Heart failure — fosinopril is included in a Phase 3 clinical trial as one of several guideline-directed medical therapies being optimised in women with heart failure.^[1]
• Cardiovascular diseases — the therapeutic area in the registry records is cardiovascular diseases.^[1]

How is fosinopril given?

Fosinopril is available as tablets for oral administration in strengths of 10 mg, 20 mg, and 40 mg.^[2] An oral solution formulation of 20 mg/5 ml is also listed in the NHS dictionary of medicines.^[3] In the heart failure trial, fosinopril is listed at doses of 20 mg and 40 mg for buccal use.^[1]

What do the clinical trials show?

The clinical trial registry contains one Phase 3 trial in heart failure that includes fosinopril among many other heart medicines. The trial is currently authorised and plans to enrol 368 participants.^[1] It has two parts: a retrospective study describing the current state of guideline-directed medical therapy prescribing nationally and sex-related inequalities, and a prospective study evaluating whether up-titration of guideline-directed medical therapy following the STRONG-HF titration programme, compared with usual care, affects morbidity and mortality, quality of life, adherence to medication, and side effects in women with heart failure at 12 months of follow-up.^[1] The primary outcome for the prospective part is all-cause mortality within one year, or heart failure readmission, or worsening heart failure.^[1] Fosinopril is one of 53 drug entries listed in the trial interventions, at doses of 20 mg and 40 mg, alongside other ACE inhibitors, angiotensin receptor blockers, beta blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors.^[1]

What side effects are known?

The product information for fosinopril sodium tablets carries a boxed warning about fetal toxicity: when pregnancy is detected, fosinopril should be discontinued as soon as possible, because drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.^[2] A small increase in serum potassium of 0.1 mEq/L was observed in 647 hypertensive patients treated with fosinopril alone for an average of 29 weeks, and similar increases were seen in patients receiving concomitant diuretic therapy.^[2]