No

Angiotensin-Converting Enzyme (ACE) Inhibitors

Treatment of hypertension, either alone or in combination with other antihypertensive agents; treatment of congestive heart failure, left ventricular dysfunction after myocardial infarction

C/D (2nd and 3rd trimesters)

Hypersensitivity to fosinopril or any component; angioedema related to previous treatment with an ACE inhibitor; patients with idiopathic or hereditary angioedema; bilateral renal artery stenosis; primary hyperaldosteronism; pregnancy (2nd and 3rd trimesters)

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Careful blood pressure monitoring (hypotension can occur especially in volume depleted patients). Dosage adjustment needed in severe renal impairment (Cl_cr <10 mL/minute). Use with caution in hypovolemia; collagen vascular diseases; valvular stenosis (particularly aortic stenosis); hyperkalemia; or before, during, or immediately after anesthesia. Avoid rapid dosage escalation which may lead to renal insufficiency. Hypersensitivity reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, AN69). Hyperkalemia may rarely occur. Neutropenia/agranulocytosis with myeloid hyperplasia can rarely occur. If patient has renal impairment, then a baseline WBC with differential and serum creatinine should be evaluated and monitored closely during initial therapy. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency. Safety and efficacy in pediatric patients have not been established.

Note: Frequency ranges include data from hypertension and heart failure trials. Higher rates of adverse reactions have generally been noted in patients with congestive heart failure. However, the frequency of adverse effects associated with placebo is also increased in this population.

1% to 10%: Cardiovascular: Orthostatic hypotension (1.4% to 1.9%), palpitation (1.4%)

Central nervous system: Dizziness (1% to 2%; up to 12% in CHF patients), headache (3.2%), weakness (1.4%), fatigue (1% to 2%)

Endocrine and metabolic: Hyperkalemia (2.6%)

Gastrointestinal: Diarrhea (2.2%), nausea/vomiting (1.2% to 2.2%)

Hepatic: Increased transaminases

Neuromuscular & skeletal: Musculoskeletal pain (<1% to 3.3%), noncardiac chest pain (<1% to 2.2%)

Renal: Increased serum creatinine, worsening of renal function (in patients with bilateral renal artery stenosis or hypovolemia)

Respiratory: Cough (2.2% to 9.7%)

Miscellaneous: Upper respiratory infection (2.2%)

>1% but less than or equal to frequency in patients receiving placebo: Sexual dysfunction, fever, flu-like syndrome, dyspnea, rash, headache, insomnia

<1% (Limited to important or life-threatening symptoms): Angina, myocardial infarction, cerebrovascular accident, syncope, hypotension, hypertensive crisis, claudication, flushing, edema, vertigo, insomnia, memory disturbance, drowsiness, angioedema, urticaria, rash, photosensitivity, pruritus, gout, decreased libido, pancreatitis, hepatitis, dysphagia, abdominal distension, flatulence, constipation, heartburn, xerostomia, lymphadenopathy, arthralgia, myalgia, memory disturbance, tremor, mood change, confusion, paresthesia, sleep disturbance, vertigo, drowsiness, bronchospasm, pharyngitis, laryngitis, epistaxis. tinnitus, vision, taste disturbance, eye irritation, renal insufficiency, urinary frequency, weight gain, hyperhydrosis, lower extremity edema, shock, sudden death, hypertension, bradycardia, tachycardia, hepatomegaly, TIA, cerebral infarction, numbness, behavioral change, sinus abnormality, tracheobronchitis, pleuritic chest pain, anaphylactoid reaction. In a small number of patients, a symptom complex of cough, bronchospasm, and eosinophilia has been observed with fosinopril.

Case reports: Gynecomastia, scleroderma, eosinophilic vasculitis

Other events reported with ACE inhibitors: Neutropenia, agranulocytosis, eosinophilic pneumonitis, cardiac arrest, pancytopenia, hemolytic anemia, anemia, aplastic anemia, thrombocytopenia, acute renal failure, hepatic failure, jaundice, symptomatic hyponatremia, bullous pemphigus, exfoliative dermatitis, Stevens-Johnson syndrome. In addition, a syndrome which may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia and positive ANA, and elevated ESR has been reported for other ACE inhibitors.

Mild hypotension has been the only toxic effect seen with acute overdose. Bradycardia may also occur; hyperkalemia occurs even with therapeutic doses, especially in patients with renal insufficiency and those taking NSAIDs

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning.

Alpha₁ blockers: Hypotensive effect increased.

Aspirin and NSAIDs may decrease ACE inhibitor efficacy and/or increase risk of renal effects.

Diuretics: Hypovolemia due to diuretics may precipitate acute hypotensive events or acute renal failure.

Insulin: Risk of hypoglycemia may be increased.

Lithium: Risk of lithium toxicity may be increased; monitor lithium levels, especially the first 4 weeks of therapy.

Mercaptopurine: Risk of neutropenia may be increased.

Potassium-sparing diuretics (amiloride, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion; a CNS mechanism may also be involved in hypotensive effect as angiotensin II increases adrenergic outflow from CNS; vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure

Onset of effect: 1 hour

Duration: 24 hours

Absorption: 36%

Metabolism: Fosinopril is a prodrug and is hydrolyzed to its active metabolite fosinoprilat by intestinal wall and hepatic esterases

Half-life, serum (fosinoprilat): 12 hours

Time to peak serum concentration: ~3 hours

Elimination: In the urine and bile as fosinoprilat and it conjugates in roughly equal proportions (45% to 50%)

Adults: Oral:

Heart failure: Initial: 10 mg/day (5 mg if renal dysfunction present) and increase, as needed, to a maximum of 40 mg once daily over several weeks; usual dose: 20-40 mg/day. If hypotension, orthostasis, or azotemia occur during titration, consider decreasing concomitant diuretic dose, if any.

Dosing adjustment/comments in renal impairment: None needed since hepatobiliary elimination compensates adequately diminished renal elimination.

Hemodialysis: Moderately dialyzable (20% to 50%)

Blood pressure (supervise for at least 2 hours after the initial dose or any increase for significant orthostasis); serum potassium, calcium, creatinine, BUN, WBC

Positive Coombs' [direct]; may cause false-positive results in urine acetone determinations using sodium nitroprusside reagent

ACE inhibitors decrease morbidity and mortality in patients with asymptomatic and symptomatic left ventricular dysfunction. In this situation, they decrease hospitalizations for, and retard progression to, congestive heart failure. ACE inhibitors are also indicated in patients postmyocardial infarction in whom left ventricular ejection fraction is <40%. When used in patients with heart failure, the target dose of 20-40 mg daily should be achieved, if possible. Lower daily doses of ACE inhibitors have not demonstrated the same cardioprotective effects. ACE inhibitors have renal protective effects in patients with proteinuria and possibly cardioprotective effects in high-risk patients.

May cause drowsiness or dizziness; may rarely cause insomnia

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. This drug does not eliminate need for diet or exercise as recommended by prescriber. Do not use potassium supplements or salt substitutes containing potassium without consulting prescriber. May cause dizziness, fainting, lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or climbing stairs); nausea, dry cough, diarrhea, or transient loss of appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help) - report if these persist; sexual dysfunction (will usually resolve). Report chest pain or palpitations; difficulty breathing or unusual cough; acute headache; or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Consult prescriber if breast-feeding.

May cause depression in some patients; discontinue if angioedema of the face, extremities, lips, tongue, or glottis occurs; watch for hypotensive effects within 1-3 hours of first dose or new higher dose

Tablet: 10 mg, 20 mg

Anderson RJ, Duchin KL, Gore RD, et al, "Once-Daily Fosinopril in the Treatment of Hypertension," Hypertension, 1991, 17(5):636-42.

Binder SB, "ACE Inhibitors: Review of Four New Agents," Am Fam Physician, 1993, 48(5):851-7.

Guthrie R, "Fosinopril: An Overview," Am J Cardiol, 1993, 72(20):22H-4H.

Herings RM, deBoer A, Stricker BH, et al, "Hypoglycaemia Associated With Use of Inhibitors of Angiotensin Converting Enzyme," Lancet, 1995, 345(8959):1195-8.

Konstam MA, Drakup K, Baker DW, et al, "Heart Failure: Evaluation and Care of Patients With Left Ventricular Systolic Dysfunction," Clinical Practice Guideline No 11, Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, 1994.

McAreavey D and Robertson JIS, "Angiotensin Converting Enzyme Inhibitors and Moderate Hypertension," Drugs, 1990, 40(3):326-45.

Murdoch D and McTavish D, "Fosinopril: A Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Essential Hypertension," Drugs, 1992, 43(1):123-40.

Williams JF, Bristow MR, Fowler MB, et al, "Guidelines for the Evaluation and Management of Heart Failure: Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure)," J Am Coll Cardiol, 1995, 26:1376-8.

Woo OF, "Captopril and Related Drugs," Poisoning and Drug Overdose, 2nd ed, Olson KR, ed, East Norwalk, CT: Appleton and Lange, 1994, 117-8.