Select therapeutic use:

CHF and arrhythmias:

Indications for: Fosinopril

Adjunct to diuretics in heart failure, with or without digitalis.

Clinical Trials:

Randomized, double-blind, placebo-controlled trial

  • The trial included 179 patients with heart failure. Patients (all receiving diuretics and some receiving digoxin) were administered single doses of 10 mg, 20 mg, or 40 mg of fosinopril sodium or placebo.

  • Treatment with fosinopril 20 mg and 40 mg resulted in acute decreases in pulmonary capillary wedge pressure (preload) and mean arterial blood pressure and systemic vascular resistance (afterload). 

  • 155 of these patients were re-randomized to receive once daily doses of fosinopril 10 mg, 20 mg, or 40 mg for an additional 10 weeks. Hemodynamic measurements showed continued reduction in pulmonary capillary wedge pressure, mean arterial blood pressure, right atrial pressure and an increase in cardiac index and stroke volume for the 20 mg and 40 mg dose groups.

3 double-blind, placebo-controlled trials

  • The trials evaluated fosinopril sodium 10–40 mg daily in 734 patients with heart failure. In 2 of the 3 trials, patients received concomitant diuretics and digitalis. In the third trial, patients were receiving only diuretics.

  • Results from all trials showed statistically significant benefits of fosinopril sodium therapy compared with placebo, in 1 or more of the following: exercise tolerance (one study), symptoms of dyspnea, orthopnea and paroxysmal nocturnal dyspnea (2 studies), NYHA classification (2 studies), hospitalization for heart failure (2 studies), study withdrawals for worsening heart failure (2 studies), and/or need for supplemental diuretics (2 studies). 

  • Favorable effects were maintained for up to 2 years.

Adult Dosage:

Initially 10mg once daily. Moderate to severe renal failure or volume depleted: initially 5mg once daily. Maintenance: 20–40mg once daily.

Children Dosage:

Contact manufacturer.

Fosinopril Contraindications:

Hypersensitivity to fosinopril or any other ACE inhibitor (eg, angioedema). Concomitant use with aliskiren in patients with diabetes.

Fosinopril Warnings/Precautions:

Salt/volume depletion. Renal or hepatic impairment. Monitor WBCs in renal or collagen vascular disease. CHF. Dialysis (esp. high-flux membrane). Renal artery stenosis. Monitor for hyperkalemia in diabetics. Discontinue if angioedema, laryngeal edema, jaundice, or markedly elevated liver enzymes occurs. Surgery. Pregnancy (Cat.C in 1st trimester). Nursing mothers: not recommended.

Fosinopril Classification:

ACE inhibitor.

Fosinopril Interactions:

Potentiated by diuretics. Potassium or K+-sparing diuretics may cause hyperkalemia. May increase lithium levels. Separate antacid dosing by 2hrs. May cause false low serum digoxin measurements.

Adverse Reactions:

Angina, orthostatic hypotension, dizziness, cough, GI upset, pain, hyperkalemia, upper respiratory infection, arrhythmias, asthenia; angioneurotic edema (discontinue if occurs).

Note:

Formerly known under the brand name Monopril.

Metabolism:

After an oral dose of radiolabeled fosinopril, 75% of radioactivity in plasma was present as active fosinoprilat, 20% to 30% as a glucuronide conjugate of fosinoprilat, and 1% to 5% as a p-hydroxy metabolite of fosinoprilat. Since fosinoprilat is not biotransformed after intravenous administration, fosinopril, not fosinoprilat, appears to be the precursor for the glucuronide and p-hydroxy metabolites. In rats, the p-hydroxy metabolite of fosinoprilat is as potent an inhibitor of ACE as fosinoprilat; the glucuronide conjugate is devoid of ACE inhibitory activity.

Drug Elimination:

After oral administration of radiolabeled fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces. In hypertensive patients with normal renal and hepatic function, who received repeated doses of fosinopril, the effective half-life for accumulation of fosinoprilat averaged 11.5 hours. In patients with heart failure, the effective half-life was 14 hours.

How Supplied:

Contact supplier.

Hypertension:

Indications for: Fosinopril

Hypertension.

Clinical Trials:

Adults

  • Following four weeks of monotherapy in placebo-controlled trials in patients with mild to moderate hypertension, once daily doses of fosinopril 20 mg to 80 mg lowered supine or seated systolic and diastolic blood pressures 24 hours after dosing by an average of 8 to 9/6 to 7 mmHg more than placebo. The trough effect was about 50% to 60% of the peak diastolic response and about 80% of the peak systolic response.

  • In most trials, fosinopril sodium showed an increased antihypertensive effect during the first several weeks of repeated measurements. The antihypertensive effect was found to continue during long-term therapy for at least 2 years.

Pediatric

  • The efficacy of fosinopril was evaluated in a randomized, double-blind study of 252 pediatric patients 6 to 16 years of age with hypertension or high-normal blood pressure. Patients were titrated to target doses of low (0.1 mg/kg), medium (0.3 mg/kg), and high (0.6 mg/kg) after one week and a total duration of 4 weeks.

  • The mean reductions from baseline to week 4 in trough systolic blood pressure were similar in all 3 dose groups.

  • Withdrawal of fosinopril resulted in an increase in blood pressure towards baseline over a 2 week period.

Adult Dosage:

Initially 10mg once daily. Usual maintenance: 20–40mg daily in single or 2 divided doses; max 80mg/day. If on diuretic: suspend diuretic for 2–3 days before starting if possible; resume diuretic if pressure not controlled with fosinopril alone. If diuretic cannot be discontinued: give 10mg and monitor carefully.

Children Dosage:

<6yrs (≤50kg): not recommended. ≥6yrs (>50kg): 5–10mg once daily.

Fosinopril Contraindications:

Hypersensitivity to fosinopril or any other ACE inhibitor (eg, angioedema). Concomitant use with aliskiren in patients with diabetes.

Fosinopril Warnings/Precautions:

Salt/volume depletion. Renal or hepatic impairment. Monitor WBCs in renal or collagen vascular disease. CHF. Dialysis (esp. high-flux membrane). Renal artery stenosis. Monitor for hyperkalemia in diabetics. Discontinue if angioedema, laryngeal edema, jaundice, or markedly elevated liver enzymes occurs. Surgery. Pregnancy (Cat.C in 1st trimester). Nursing mothers: not recommended.

Fosinopril Classification:

ACE inhibitor.

Fosinopril Interactions:

Potentiated by diuretics. Potassium or K+-sparing diuretics may cause hyperkalemia. May increase lithium levels. Separate antacid dosing by 2hrs. May cause false low serum digoxin measurements.

Adverse Reactions:

Headache, cough, dizziness, GI upset, hyperkalemia, orthostatic hypotension, angioneurotic edema (discontinue if occurs).

Note:

Formerly known under the brand name Monopril.

Metabolism:

After an oral dose of radiolabeled fosinopril, 75% of radioactivity in plasma was present as active fosinoprilat, 20% to 30% as a glucuronide conjugate of fosinoprilat, and 1% to 5% as a p-hydroxy metabolite of fosinoprilat. Since fosinoprilat is not biotransformed after intravenous administration, fosinopril, not fosinoprilat, appears to be the precursor for the glucuronide and p-hydroxy metabolites. In rats, the p-hydroxy metabolite of fosinoprilat is as potent an inhibitor of ACE as fosinoprilat; the glucuronide conjugate is devoid of ACE inhibitory activity.

Drug Elimination:

After oral administration of radiolabeled fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces. In hypertensive patients with normal renal and hepatic function, who received repeated doses of fosinopril, the effective half-life for accumulation of fosinoprilat averaged 11.5 hours. In patients with heart failure, the effective half-life was 14 hours.

How Supplied:

Contact supplier.