Monopril (fosinopril) is an angiotensin-converting-enzyme (ACE) inhibitor, marketed by Bristol-Myers-Squibb, that is used to treat high blood pressure and heart failure.

ACE inhibitors slow the progression of kidney disease and may improve life expectancy in Alport syndrome patients. They also work to lower levels of proteinuria (protein in the urine), which are associated with kidney damage.

How Monopril works

ACE inhibitors such as Monopril block an enzyme called angiotensin-converting-enzyme (ACE). ACE is involved in the regulation of blood pressure by converting a hormone called angiotensin 1 into a hormone called angiotensin 2.

Angiotensin 2 increases blood pressure through multiple mechanisms. It causes blood vessels to narrow, leading to a rise in blood pressure as the blood has to push harder against vessel walls. It also stimulates the release of a hormone called aldosterone, which promotes the retention of sodium and chloride in the blood, also causing blood pressure to rise.

By decreasing angiotensin 2 levels, ACE inhibitors work to lower blood pressure.

Of importance to Alport patients, ACE inhibitors are also known to lower the glomerular filtration pressure and to decrease the permeability of the glomeruli, the small blood vessels in the kidney that filter waste products from the blood. Both mechanisms are thought to contribute to a reduction in proteinuria.

Monopril in clinical trials

Monopril has not been tested in randomized clinical trials specifically in Alport syndrome patients.  One trial, however, assessed Monopril’s effect on blood pressure and proteinuria.

The randomized placebo-controlled Phase 3 trial (NCT03073018) assessed whether being treated with Monopril or pravastatin worked to prevent cardiovascular and kidney disease in people with microalbuminuria (defined as urinary albumin concentrations of more than 10 mg per liter in the early morning). Elevated levels of albumin in the urine (called albuminuria) are associated with an increased risk of cardiovascular and kidney disease, including end-stage renal failure. The trial also investigated treatments’ effect on blood pressure.

About 430 participants randomly received either 20 mg of Monopril or a placebo daily (half of the 864 enrolled were given pravastatin, 40 mg daily, or placebo). Results showed that blood pressure and urinary albumin excretion decreased significantly among those on Monopril compared to placebo within three months of treatment and remained low during four years of follow-up. People given Monopril also had a lower incidence of cardiovascular mortality and hospitalization for cardiovascular disease. Pravastatin did not significantly reduce either urinary albumin excretion or cardiovascular events.

Additional information

ACE inhibitors promote the retention of potassium. Potassium-rich foods, such as dairy products, salt substitutes, nuts, and certain fruits and vegetable should be avoided while taking medications such as Monopril.

Common side effects of Monopril include dizziness, headaches, nausea, diarrhea, and skin itching.

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