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Fosinopril


Pronunciation

 (foe SIN oh pril)


U.S. Brand Names

 Monopril®


Synonyms

 Fosinopril Sodium


Generic Available

 Yes


Canadian Brand Names

 Monopril®


Use

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


Pregnancy Risk Factor

 C/D (2nd and 3rd trimesters)


Pregnancy Implications

 Cranial defects, hypocalvaria/acalvaria, oligohydramnios, persistent anuria following delivery, hypotension, renal defects, renal dysgenesis/dysplasia, renal failure, pulmonary hypoplasia, limb contractures secondary to oligohydramnios, and stillbirth reported. ACE inhibitors should be avoided during pregnancy, particularly in the 2nd and 3rd trimesters.


Lactation

 Enters breast milk/not recommended


Contraindications

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


Warnings/Precautions

 Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Angioedema may involve head and neck (potentially affecting the airway) or the intestine (presenting with abdominal pain). Careful blood pressure monitoring (hypotension can occur especially in volume depleted patients). Dosage adjustment needed in severe renal impairment (Clcr<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. Rare toxicities associated with ACE inhibitors include cholestatic jaundice (which may progress to hepatic necrosis) and neutropenia/agranulocytosis with myeloid hyperplasia. Hypersensitivity reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, AN69). Hyperkalemia may 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.


Adverse Reactions

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

>10%: Central nervous system: Dizziness (2% to 12%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (1% to 2%), palpitation (1%)

Central nervous system: Dizziness (1% to 2%; up to 12% in CHF patients), headache (3%), fatigue (1% to 2%)

Endocrine & metabolic: Hyperkalemia (2.6%)

Gastrointestinal: Diarrhea (2%), nausea/vomiting (1.2% to 2.2%)

Hepatic: Transaminases increased

Neuromuscular & skeletal: Musculoskeletal pain (<1% to 3%), noncardiac chest pain (<1% to 2%), weakness (1%),

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

Respiratory: Cough (2% to 10%)

Miscellaneous: Upper respiratory infection (2%)

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

<1% (Limited to important or life-threatening): Angina, MI, cerebrovascular accident, syncope, hypotension, hypertensive crisis, claudication, flushing, edema, insomnia, memory disturbance, drowsiness, angioedema, urticaria, rash, photosensitivity, pruritus, gout, decreased libido, pancreatitis, hepatitis, dysphagia, abdominal distension, flatulence, constipation, heartburn, xerostomia, lymphadenopathy, arthralgia, myalgia, tremor, mood change, confusion, paresthesia, sleep disturbance, vertigo, drowsiness, bronchospasm, pharyngitis, laryngitis, epistaxis, tinnitus, vision disturbance, 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.

Other events reported with ACE inhibitors: Acute renal failure, agranulocytosis, anemia, aplastic anemia, bullous pemphigus, cardiac arrest, eosinophilic pneumonitis, exfoliative dermatitis, gynecomastia, hemolytic anemia, hepatic failure, jaundice, neutropenia, pancytopenia, Stevens-Johnson syndrome, symptomatic hyponatremia, thrombocytopenia. 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.


Overdosage/Toxicology

 Mild hypotension has been the primary 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. Treatment is symptom-directed and supportive.


Drug Interactions

Alpha1 blockers: Hypotensive effect increased.

Antacids (aluminum hydroxide, magnesium hydroxide and simethicone): Absorption of fosinopril impaired; separate dose by 2 hours.

Aspirin: The effects of ACE inhibitors may be blunted by aspirin administration, particularly at higher dosages (see Cardiovascular Considerations) and/or increase adverse 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.

NSAIDs: May attenuate hypertensive efficacy; effect has been seen with captopril and may occur with other ACE inhibitors; monitor blood pressure. May increase risk of adverse renal effects.

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.


Ethanol/Nutrition/Herb Interactions

 Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, garlic, yohimbe, ginseng (may worsen hypertension).


Stability

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


Mechanism of Action

 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


Pharmacodynamics/Kinetics

Onset of action: 1 hour

Duration: 24 hours

Absorption: 36%

Protein binding: 95%

Metabolism: Prodrug, hydrolyzed to its active metabolite fosinoprilat by intestinal wall and hepatic esterases

Bioavailability: 36%

Half-life elimination, serum (fosinoprilat): 12 hours

Time to peak, serum: ~3 hours

Excretion: Urine and feces (as fosinoprilat and other metabolites in roughly equal proportions, 45% to 50%)


Dosage

 Oral:

Children >50 kg: Hypertension: Initial: 5-10 mg once daily

Adults:

Hypertension: Initial: 10 mg/day; most patients are maintained on 20-40 mg/day. May need to divide the dose into two if trough effect is inadequate; discontinue the diuretic, if possible 2-3 days before initiation of therapy; resume diuretic therapy carefully, if needed.

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%)


Monitoring Parameters

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


Test Interactions

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


Dietary Considerations

 Should not take a potassium salt supplement without the advice of healthcare provider.


Patient Education

 Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Do not use potassium supplement or salt substitutes without consulting prescriber. Take exactly as directed; do not discontinue without consulting prescriber. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, or 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); or nausea, vomiting, abdominal pain, dry mouth, or loss of appetite (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help) - report if these persist. Report chest pain or palpitations; mouth sores; fever or chills; swelling of extremities, face, mouth, or tongue; skin rash; numbness, tingling, or pain in muscles; respiratory difficulty; unusual cough; or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 2nd or 3rd trimester of pregnancy. Consult prescriber for appropriate contraceptive measures if necessary. Breast-feeding is not recommended.


Anesthesia and Critical Care Concerns/Other Considerations

 ACE inhibitor therapy may elicit rapid increases in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. When ACE inhibition is introduced in patients with pre-existing diuretic therapy who are hypovolemic, the ACE inhibitor may induce acute hypotension. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. Because of the potent teratogenic effects of ACE inhibitors, these drugs should be avoided, if possible, when treating women of childbearing potential not on effective birth control measures.

ACE inhibitors decrease morbidity and mortality in patients with asymptomatic and symptomatic left ventricular dysfunction. ACE inhibitors are also indicated in patients postmyocardial infarction in whom left ventricular ejection fraction is <40%. ACE inhibitors have renal protective effects in patients with proteinuria and possibly cardioprotective effects in high-risk patients.


Cardiovascular Considerations

 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. According to 2004 ACC/AHA STEMI guidelines, an ACE inhibitor should be administered orally within the first 24 hours of STEMI to patients with anterior infarction, pulmonary congestion or LVEF <0.4, in the absence of hypotension or known contraindications to that class of medicines. In the emergency management of complicated STEMI, a short-acting ACEI (eg, captopril 1-6.25 mg) may be added once the patient's systolic blood pressure is >100 mm Hg and not <30 mm Hg below baseline. 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.

ACE inhibitor therapy may elicit rapid increases in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. When ACE inhibition is introduced in patients with pre-existing diuretic therapy who are hypovolemic, the ACE inhibitor may induce acute hypotension. In those patients experiencing cough on an ACE inhibitor, the ACE inhibitor may be discontinued and, if necessary, angiotensin receptor blocker therapy instituted. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema. Because of the potent teratogenic effects of ACE inhibitors, these drugs should be avoided, if possible, when treating women of childbearing potential not on effective birth control measures.

In the treatment of unstable angina/non-ST-segment elevation MI, ACE inhibitors are recommended when hypertension persists despite treatment with nitroglycerin and a beta-blocker in patients with LV systolic dysfunction or CHF and in ischemic patients with diabetes (Class I). ACE inhibitors are also recommended for all post-ACS individuals (Class IIa).


Dental Health: Effects on Dental Treatment

 Key adverse event(s) related to dental treatment: Orthostatic hypotension.


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 May cause drowsiness or dizziness; may rarely cause insomnia


Mental Health: Effects on Psychiatric Treatment

 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


Dosage Forms

 Tablet, as sodium: 10 mg, 20 mg, 40 mg


References

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)," Circulation, 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina)," J Am Coll Cardiol , 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Chase MP, Fiarman GS, Scholz FJ, et al, "Angioedema of the Small Bowel Due to an Angiotensin-Converting Enzyme Inhibitor," J Clin Gastroenterol , 2000, 31(3):254-7.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Conlin P, Moore T, Swartz S, et al, "Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients," Hypertension , 2000, 36(3):461-5.

"Consensus Recommendations for the Management of Chronic Heart Failure. On Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure," Am J Cardiol , 1999, 83(2A):1A-38A.

"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)," Circulation , 1995, 92(9):2764-84.

Hunt SA, Baker DW, Chin MH, et al, "ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure)," J Am Coll Cardiol , 2001, 38(7):2101-13.

"K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Kidney Disease Outcome Quality Initiative," Am J Kidney Dis , 2002, 39(2 Suppl 2):1-246. Available at: http://www.kidney.org/professionals/doqi/kdoqi/toc.htm. Accessed August 1, 2003.

Konstam MA, "Heart Failure Evaluation and Care of Patients With Left Ventricular Systolic Dysfunction," Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy Research, 1994. Clinical Practice Guideline: Number 94-0612.

Packer M, Poole-Wilson PA, Armstrong PW, et al, "Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure," Circulation , 1999, 100(23):2312-8.

Pfeffer MA, Greaves SC, Arnold JM, et al, "Early Versus Delayed Angiotensin-Converting Enzyme Inhibition Therapy in Acute Myocardial Infarction. The Healing and Early Afterload Reducing Therapy Trial," Circulation , 1997, 95(12):2643-51.

Smoger SH and Sayed MA, "Simultaneous Mucosal and Small Bowel Angioedema Due to Captopril," South Med J , 1998, 91(11):1060-3.


International Brand Names

 Acenor-M® (ID); Dynacil® (DE); Eliten® (IT); Fosinil® (BE, ES, LU); Fosinopril® (AT, GB); Fosinorm® (DE); Fosipres® (IT); Fositen® (CH); Fositens® (AT, ES); Fovas® (IN); Fozitec® (FR); Hiperlex® (ES); Monopril® (AU, BR, CA, CL, CO, CR, CZ, DK, EC, GT, HN, HR, HU, NO, PA, PL, RO, SE, SG, SI, SV, TH, TR, YU, ZA); Newace® (NL); Staril® (GB); Tensocardil® (ES); Tensogard® (IT); Tenso Stop® (ES); Vasopril® (IL)


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