Fosinopril

Fosinopril sodium tablets are indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics. Fosinopril sodium tablets are indicated in the management of heart failure as adjunctive therapy when added to conventional therapy including diuretics with or without digitalis. In using fosinopril sodium tablets, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that fosinopril sodium tablets do not have a similar risk. In considering use of fosinopril sodium tablets, it should be noted that in controlled trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks.

In animals and humans, fosinopril sodium is hydrolyzed by esterases to the pharmacologically active form, fosinoprilat, a specific competitive inhibitor angiotensin-converting enzyme (ACE). ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. In 647 hypertensive patients treated with fosinopril alone for an average of 29 weeks, mean increases in serum potassium of 0.1 mEq/L were observed. Similar increases were observed among all patients treated with fosinopril, including those receiving concomitant diuretic therapy.

Hypertension Adults The recommended initial dose of fosinopril sodium tablets is 10 mg once a day, both as monotherapy and when the drug is added to a diuretic. Dosage should then be adjusted according to blood pressure response at peak (2 to 6 hours) and trough (about 24 hours after dosing) blood levels. The usual dosage range needed to maintain a response at trough is 20 to 40 mg but some patients appear to have a further response to 80 mg. In some patients treated with once daily dosing, the antihypertensive effect may diminish toward the end of the dosing interval. If trough response is inadequate, dividing the daily dose should be considered. If blood pressure is not adequately controlled with fosinopril sodium tablets alone, a diuretic may be added.

Fosinopril sodium tablets are contraindicated in patients who are hypersensitive to this product or to any other angiotensin-converting enzyme inhibitor (e.g., a patient who has experienced angioedema with any other ACE inhibitor therapy).

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue fosinopril sodium tablets as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity Anaphylactoid and Possibly Related Reactions Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including fosinopril sodium) may be subject to a variety of adverse reactions, some of them serious. Head and Neck Angioedema Angioedema involving the extremities, face, lips, mucous membranes, tongue, glottis, or larynx has been reported in patients treated with ACE inhibitors. If angioedema involves the tongue, glottis, or larynx, airway obstruction may occur and be fatal.

Fosinopril sodium has been evaluated for safety in more than 2100 individuals in hypertension and heart failure trials, including approximately 530 patients treated for a year or more. Generally adverse events were mild and transient, and their frequency was not prominently related to dose within the recommended daily dosage range. Hypertension In placebo-controlled clinical trials (688 fosinopril sodium-treated patients), the usual duration of therapy was 2 to 3 months. Discontinuations due to any clinical or laboratory adverse event were 4.1% and 1.1% in fosinopril sodium-treated and placebo-treated patients, respectively. The most frequent reasons (0.4 to 0.9%) were headache, elevated transaminases, fatigue, cough, diarrhea, and nausea and vomiting.

Diuretics Patients on diuretics, especially those with intravascular volume depletion, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with fosinopril sodium tablets. The possibility of hypotensive effects with fosinopril sodium can be minimized by either discontinuing the diuretic or increasing salt intake prior to initiation of treatment with fosinopril sodium. If this is not possible, the starting dose should be reduced and the patient should be observed closely for several hours following an initial dose and until blood pressure has stabilized. Potassium supplements and potassium-sparing diuretics Fosinopril sodium can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia.

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F). Protect from moisture by keeping bottle tightly closed.