Brands, Medical Use, Clinical Data
Drug Category
- Antihypertensive Agents
- Angiotensin-converting Enzyme Inhibitors
Dosage Forms
Brands / Synonyms
Acecor; Fosinopril; Fosinopril and Hydrochlorothiazide; Fosinopril Sodium; Monopril; Monopril-HCT; Secorvas; Staril
Indications
For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics. It is alos indicated in the management of heart failure.
Pharmacology
Fosinopril, an angiotensin-converting enzyme (ACE) inhibitor. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. By blocking ACE, Fosinopril decreases angiotensin II which is a vasoconstrictor. Fosinopril is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
Mechanism of Action
Fosinoprilat, the active metabolite of Fosinopril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Fosinoprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.
Absorption
~36% of an oral dose
Toxicity
Not Available
Biotrnasformation / Drug Metabolism
Not Available
Contraindications
Fosinopril sodium is 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).
Drug Interactions
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.
The possibility of hypotensive effects 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 (see DOSAGE AND ADMINISTRATION.)
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. Therefore, if concomitant use of such agents is
indicated, they should be given with caution, and the patient's serum potassium should be monitored frequently.
Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in
patients receiving ACE inhibitors during therapy with lithium. These drugs should be coadministered with caution, and
frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity
may be increased.
Antacids: In a clinical pharmacology study, coadministration of an antacid (aluminum hydroxide,
magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as
compared with fosinopril administered alone, suggesting that antacids may impair absorption of fosinopril. Therefore,
if concomitant administration of these agents is indicated, dosing should be separated by 2 hours.
Other: Neither fosinopril sodium nor its metabolites have been found to interact with food. In
separate single or multiple dose pharmacokinetic interaction studies with chlorthalidone, nifedipine, propanolol,
hydrochlorothiazide, cimetidine, metoclopramide, propantheline, digoxin, and warfarin, the bioavailability of
fosinoprilat was not altered by coadministration of fosinopril with any one of these drugs. In a study with
concomitant administration of aspirin and fosinopril sodium, the bioavailability of unbound fosinoprilat was not
altered.
In a pharmacokinetic interaction study with warfarin, bioavailability parameters, the degree of protein binding,
and the anticoagulant effect (measured by prothrombin time) of warfarin were not significantly changed.
Drug/Laboratory Test Interaction
Fosinopril may cause a false low measurement of serum digoxin levels with the Digi- Tab® RIA Kit for Digoxin.
Other kits, such as the Coat-A-Count® RIA Kit, may be used.
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