Monopril (Fosinopril Sodium)
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Monopril (Fosinopril Sodium)

MONOPRIL®
(fosinopril sodium) Tablets

USE IN PREGNANCY

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, MONOPRIL (fosinopril sodium) should be discontinued as soon as possible. See WARNINGS: Fetal/Neonatal Morbidity and Mortality.

DRUG DESCRIPTION

MONOPRIL® (fosinopril sodium tablets) is the sodium salt of fosinopril, the ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor, fosinoprilat. It contains a phosphinate group capable of specific binding to the active site of angiotensin-converting enzyme. Fosinopril sodium is designated chemically as: L-proline, 4-cyclohexyl-1-[[[2-methyl-1-(1-oxopropoxy)propoxy](4-phenylbutyl)phosphinyl]acetyl]-, sodium salt, trans-.

Fosinopril sodium is a white to off-white crystalline powder. It is soluble in water (100 mg/mL), methanol, and ethanol and slightly soluble in hexane.

Its structural formula is:

MONOPRIL®
  (fosinopril sodium) Structural Formula Illustration

Its empirical formula is C30H45NNaO7P, and its molecular weight is 585.65.

MONOPRIL (fosinopril sodium) is available for oral administration as 10 mg, 20 mg, and 40 mg tablets. Inactive ingredients include: lactose, microcrystalline cellulose, crospovidone, povidone, and sodium stearyl fumarate.

What are the possible side effects of fosinopril (Monopril)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • feeling light-headed, fainting;
  • urinating less than usual, or not at all;
  • fever, chills, body aches, flu symptoms;
  • severe blistering, peeling, and red skin rash;
  • pale skin, easy bruising or bleeding, unusual weakness;
  • pounding or uneven heartbeats;
  • slow heart rate, weak...

Read All Potential Side Effects and See Pictures of Monopril »

What are the precautions when taking fosinopril sodium (Monopril)?

Before taking fosinopril, tell your doctor or pharmacist if you are allergic to it; or to other ACE inhibitors (such as benazepril); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of an allergic reaction which included swelling of the face/lips/tongue/throat (angioedema), blood filtering procedures (such as LDL apheresis, dialysis), high level of potassium in the blood, collagen vascular disease (such as lupus, scleroderma).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are...

Read All Potential Precautions of Monopril »

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

MONOPRIL (fosinopril sodium) (fosinopril sodium tablets) is indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.

MONOPRIL (fosinopril sodium) is indicated in the management of heart failure as adjunctive therapy when added to conventional therapy including diuretics with or without digitalis (see DOSAGE AND ADMINISTRATION).

In using MONOPRIL (fosinopril sodium) , 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 MONOPRIL does not have a similar risk (see WARNINGS).

In considering use of MONOPRIL (fosinopril sodium) , 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 addition, ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients (see WARNINGS: Head and Neck Angioedema and Intestinal Angioedema).

DOSAGE AND ADMINISTRATION

Hypertension

Adults

The recommended initial dose of MONOPRIL (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 (2-6 hours) and trough (about 24 hours after dosing) blood levels. The usual dosage range needed to maintain a response at trough is 20-40 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 MONOPRIL (fosinopril sodium) alone, a diuretic may be added.

Concomitant administration of MONOPRIL (fosinopril sodium) with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics can lead to increases of serum potassium (see PRECAUTIONS).

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of MONOPRIL (fosinopril sodium) . To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with MONOPRIL (see WARNINGS). Then, if blood pressure is not controlled with MONOPRIL (fosinopril sodium) alone, diuretic therapy should be resumed. If diuretic therapy cannot be discontinued, an initial dose of 10 mg of MONOPRIL (fosinopril sodium) should be used with careful medical supervision for several hours and until blood pressure has stabilized. (See WARNINGS and PRECAUTIONS: Information for Patients and DRUG INTERACTIONS.)

Since concomitant administration of MONOPRIL (fosinopril sodium) with potassium supplements, or potassium-containing salt substitutes or potassium-sparing diuretics may lead to increases in serum potassium, they should be used with caution (see PRECAUTIONS).

Pediatrics

In children, doses of MONOPRIL (fosinopril sodium) between 0.1 and 0.6 mg/kg have been studied and shown to reduce blood pressure to a similar extent (see CLINICAL PHARMACOLOGY: Pharmacodynamics and Clinical Effects). Based on this, the recommended dose of

MONOPRIL (fosinopril sodium) in children weighing more than 50 kg is 5 to 10 mg once per day as monotherapy. An appropriate dosage strength is not available for children weighing less than 50 kg.

Heart Failure

Digitalis is not required for MONOPRIL (fosinopril sodium) to manifest improvements in exercise tolerance and symptoms. Most placebo-controlled clinical trial experience has been with both digitalis and diuretics present as background therapy.

The usual starting dose of MONOPRIL (fosinopril sodium) should be 10 mg once daily. Following the initial dose of MONOPRIL (fosinopril sodium) , the patient should be observed under medical supervision for at least 2 hours for the presence of hypotension or orthostasis, and if present, until blood pressure stabilizes. An initial dose of 5 mg is preferred in heart failure patients with moderate to severe renal failure or those who have been vigorously diuresed.

Dosage should be increased, over a several week period, to a dose that is maximal and tolerated but not exceeding 40 mg once daily. The usual effective dosage range is 20 to 40 mg once daily.

The appearance of hypotension, orthostasis, or azotemia early in dose titration should not preclude further careful dose titration. Consideration should be given to reducing the dose of concomitant diuretic.

For Hypertensive or Heart Failure Patients With Renal Impairment: In patients with impaired renal function, the total body clearance of fosinoprilat is approximately 50% slower than in patients with normal renal function. Since hepatobiliary elimination partially compensates for diminished renal elimination, the total body clearance of fosinoprilat does not differ appreciably with any degree of renal insufficiency (creatinine clearances < 80 mL/min/1.73 m2), including end-stage renal failure (creatinine clearance < 10 mL/min/1.73 m2). This relative constancy of body clearance of active fosinoprilat, resulting from the dual route of elimination, permits use of the usual dose in patients with any degree of renal impairment. (See WARNINGS: Anaphylactoid reactions during membrane exposure and PRECAUTIONS: Hemodialysis.)

HOW SUPPLIED

MONOPRIL® (fosinopril sodium tablets)

10 mg tablets: White to off-white, biconvex flat-end diamond-shaped, compressed partially scored tablets with “BMS” on one side and “MONOPRIL (fosinopril sodium) 10” on the other. They are supplied in bottles of 90 (NDC 0087-0158-46) and 1000 (NDC 0087-0158-85). Bottles contain a desiccant canister.

20 mg tablets: White to off-white, oval-shaped, compressed tablets with “BMS” on one side and “MONOPRIL (fosinopril sodium) 20” on the other. They are supplied in bottles of 90 (NDC 0087-0609-42) and 1000 (NDC 0087-0609-85). Bottles contain a desiccant canister.

40 mg tablets: White to off-white, biconvex hexagonal-shaped, compressed tablets with “BMS” on one side and “MONOPRIL (fosinopril sodium) 40” on the other. They are supplied in bottles of 90 (NDC 0087-1202-13). Bottles contain a desiccant canister.

Storage

Store at 25°C (77°F); excursions permitted to 15°C - 30°C (59°F - 86°F) [see USP Controlled Room Temperature]. Protect from moisture by keeping bottle tightly closed.

Bristol-Myers Squibb Company Princeton, NJ 08543 USA. Rev July 2008.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

MONOPRIL (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 MONOPRIL (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 MONOPRIL (fosinopril sodium) -treated and placebo-treated patients, respectively. The most frequent reasons (0.4 to 0.9%) were headache, elevated transaminases, fatigue, cough (see PRECAUTIONS: General, Cough), diarrhea, and nausea and vomiting.

During clinical trials with any MONOPRIL (fosinopril sodium) regimen, the incidence of adverse events in the elderly ( ≥ 65 years old) was similar to that seen in younger patients.

Clinical adverse events probably or possibly related or of uncertain relationship to therapy, occurring in at least 1% of patients treated with MONOPRIL (fosinopril sodium) alone and at least as frequent on MONOPRIL (fosinopril sodium) as on placebo in placebo-controlled clinical trials are shown in the table below.

Clinical Adverse Events in Placebo-Controlled Trails (Hypertension)

  MONOPRIL (fosinopril sodium)
(N=688)
Incidence (Discontinuation)
Placebo
(N=184)
Incidence (Discontinuation)
Cough 2.2 (0.4) 0.0 (0.0)
Dizziness 1.6 (0.0) 0.0 (0.0)
Nausea/Vomiting 1.2 (0.4) 0.5 (0.0)

The following events were also seen at > 1% on MONOPRIL (fosinopril sodium) but occurred in the placebo group at a greater rate: headache, diarrhea, fatigue, and sexual dysfunction. Other clinical events probably or possibly related, or of uncertain relationship to therapy occurring in 0.2 to 1.0% of patients (except as noted) treated with MONOPRIL (fosinopril sodium) in controlled or uncontrolled clinical trials (N=1479) and less frequent, clinically significant events include (listed by body system):

General: Chest pain, edema, weakness, excessive sweating.

Cardiovascular: Angina/myocardial infarction, cerebrovascular accident, hypertensive crisis, rhythm disturbances, palpitations, hypotension, syncope, flushing, claudication.

Orthostatic hypotension occurred in 1.4% of patients treated with fosinopril monotherapy. Hypotension or orthostatic hypotension was a cause for discontinuation of therapy in 0.1% of patients.

Dermatologic: Urticaria, rash, photosensitivity, pruritus.

Endocrine/Metabolic: Gout, decreased libido.

Gastrointestinal: Pancreatitis, hepatitis, dysphagia, abdominal distention, abdominal pain, flatulence, constipation, heartburn, appetite/weight change, dry mouth.

Hematologic: Lymphadenopathy.

Immunologic: Angioedema. (See WARNINGS: Head and Neck Angioedema and Intestinal Angioedema.)

Musculoskeletal: Arthralgia, musculoskeletal pain, myalgia/muscle cramp.

Nervous/Psychiatric: Memory disturbance, tremor, confusion, mood change, paresthesia, sleep disturbance, drowsiness, vertigo.

Respiratory: Bronchospasm, pharyngitis, sinusitis/rhinitis, laryngitis/hoarseness, epistaxis. A symptom-complex of cough, bronchospasm, and eosinophilia has been observed in two patients treated with fosinopril.

Special Senses: Tinnitus, vision disturbance, taste disturbance, eye irritation.

Urogenital: Renal insufficiency, urinary frequency.

Heart Failure

In placebo-controlled clinical trials (361 MONOPRIL (fosinopril sodium) -treated patients), the usual duration of therapy was 3-6 months. Discontinuations due to any clinical or laboratory adverse event, except for heart failure, were 8.0% and 7.5% in MONOPRIL (fosinopril sodium) -treated and placebo-treated patients, respectively. The most frequent reason for discontinuation of MONOPRIL (fosinopril sodium) was angina pectoris (1.1%). Significant hypotension after the first dose of MONOPRIL (fosinopril sodium) occurred in 14/590 (2.4%) of patients; 5/590 (0.8%) patients discontinued due to first dose hypotension.

Clinical adverse events probably or possibly related or of uncertain relationship to therapy, occurring in at least 1% of patients treated with MONOPRIL (fosinopril sodium) and at least as common as the placebo group, in placebo-controlled trials are shown in the table below.

Clinical Adverse Events in Placebo-Controlled Trails (Heart Failure)

  MONOPRIL (fosinopril sodium)
(N=361)
Incidence (Discontinuation)
Placebo
(N=373)
Incidence (Discontinuation)
Dizziness 11.9 (0.6) 5.4 (0.3)
Cough 9.7 (0.8) 5.1 (0.0)
Hypotension 4.4 (0.8) 0.8 (0.0)
Musculoskeletal Pain 3.3 (0.0) 2.7 (0.0)
Nausea/Vomiting 2.2 (0.6) 1.6 (0.3)
Diarrhea 2.2 (0.0) 1.3 (0.0)
Chest Pain (non-cardiac) 2.2 (0.0) 1.6 (0.0)
Upper Respiratory Infection 2.2 (0.0) 1.3 (0.0)
Orthostatic Hypotension 1.9 (0.0) 0.8 (0.0)
Subjective Cardiac Rhythm Disturbance 1.4 (0.6) 0.8 (0.3)
Weakness 1.4 (0.3) 0.5 (0.0)

The following events also occurred at a rate of 1% or more on MONOPRIL (fosinopril sodium) (fosinopril sodium tablets) but occurred on placebo more often: fatigue, dyspnea, headache, rash, abdominal pain, muscle cramp, angina pectoris, edema, and insomnia.

The incidence of adverse events in the elderly ( ≥ 65 years old) was similar to that seen in younger patients.

Other clinical events probably or possibly related, or of uncertain relationship to therapy occurring in 0.4 to 1.0% of patients (except as noted) treated with MONOPRIL (fosinopril sodium) in controlled clinical trials (N=516) and less frequent, clinically significant events include (listed by body system):

General: Fever, influenza, weight gain, hyperhidrosis, sensation of cold, fall, pain.

Cardiovascular: Sudden death, cardiorespiratory arrest, shock (0.2%), atrial rhythm disturbance, cardiac rhythm disturbances, non-anginal chest pain, edema lower extremity, hypertension, syncope, conduction disorder, bradycardia, tachycardia.

Dermatologic: Pruritus.

Endocrine/Metabolic: Gout, sexual dysfunction.

Gastrointestinal: Hepatomegaly, abdominal distention, decreased appetite, dry mouth, constipation, flatulence.

Immunologic: Angioedema (0.2%).

Musculoskeletal: Muscle ache, swelling of an extremity, weakness of an extremity.

Nervous/Psychiatric: Cerebral infarction, TIA, depression, numbness, paresthesia, vertigo, behavior change, tremor.

Respiratory: Abnormal vocalization, rhinitis, sinus abnormality, tracheobronchitis, abnormal breathing, pleuritic chest pain.

Special Senses: Vision disturbance, taste disturbance.

Urogenital: Abnormal urination, kidney pain.

Fetal/Neonatal Morbidity and Mortality

See WARNINGS: Fetal/Neonatal Morbidity and Mortality.

Potential Adverse Effects Reported with ACE Inhibitors

Body as a whole: Anaphylactoid reactions (see WARNINGS: Anaphylactoid and Possibly Related Reactions and PRECAUTIONS: Hemodialysis).

Other medically important adverse effects reported with ACE inhibitors include: Cardiac arrest; eosinophilic pneumonitis; neutropenia/agranulocytosis, pancytopenia, anemia (including hemolytic and aplastic), thrombocytopenia; acute renal failure; hepatic failure, jaundice (hepatocellular or cholestatic); symptomatic hyponatremia; bullous pemphigus, exfoliative dermatitis; a syndrome which may include: arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermatologic manifestations, a positive ANA, leukocytosis, eosinophilia, or an elevated ESR.

Laboratory Test Abnormalities

Serum Electrolytes: Hyperkalemia, (see PRECAUTIONS); hyponatremia, (see PRECAUTIONS: DRUG INTERACTIONS, Diuretics).

BUN/Serum Creatinine: Elevations, usually transient and minor, of BUN or serum creatinine have been observed. In placebo-controlled clinical trials, there were no significant differences in the number of patients experiencing increases in serum creatinine (outside the normal range or 1.33 times the pre-treatment value) between the fosinopril and placebo treatment groups. Rapid reduction of longstanding or markedly elevated blood pressure by any antihypertensive therapy can result in decreases in the glomerular filtration rate, and in turn, lead to increases in BUN or serum creatinine. (See PRECAUTIONS: General.)

Hematology: In controlled trials, a mean hemoglobin decrease of 0.1 g/dL was observed in fosinopril-treated patients. In individual patients decreases in hemoglobin or hematocrit were usually transient, small, and not associated with symptoms. No patient was discontinued from therapy due to the development of anemia. Other: Neutropenia (see WARNINGS), leukopenia and eosinophilia.

Liver Function Tests: Elevations of transaminases, LDH, alkaline phosphatase, and serum bilirubin have been reported. Fosinopril therapy was discontinued because of serum transaminase elevations in 0.7% of patients. In the majority of cases, the abnormalities were either present at baseline or were associated with other etiologic factors. In those cases which were possibly related to fosinopril therapy, the elevations were generally mild and transient and resolved after discontinuation of therapy.

Pediatric Patients

The adverse experience profile for pediatric patients is similar to that seen in adult patients with hypertension. The long-term effects of MONOPRIL (fosinopril sodium) on growth and development have not been studied.

Read the Monopril (fosinopril sodium) Side Effects Center for a complete guide to possible side effects »

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 MONOPRIL (fosinopril sodium tablets). The possibility of hypotensive effects with MONOPRIL (fosinopril sodium) can be minimized by either discontinuing the diuretic or increasing salt intake prior to initiation of treatment with MONOPRIL (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: MONOPRIL (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 administrated 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.

Gold: Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including MONOPRIL (fosinopril sodium) .

Other: Neither MONOPRIL (fosinopril sodium) nor its metabolites have been found to interact with food. In separate single or multiple dose pharmacokinetic interaction studies with chlorthalidone, nifedipine, propranolol, 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 MONOPRIL (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.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

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 MONOPRIL (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. If laryngeal stridor or angioedema of the face, lips, mucous membranes, tongue, glottis, or extremities occurs, treatment with MONOPRIL (fosinopril sodium) should be discontinued and appropriate therapy instituted immediately. Where there is involvement of the tongue, glottis, or larynx, likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) should be promptly administered (see PRECAUTIONS: Information for Patients and ADVERSE REACTIONS).

Intestinal Angioedema: Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Anaphylactoid reactions during desensitization: Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

Anaphylactoid reactions during membrane exposure: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Hypotension

MONOPRIL (fosinopril sodium) can cause symptomatic hypotension. Like other ACE inhibitors, fosinopril has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension is most likely to occur in patients who have been volume- and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with MONOPRIL (fosinopril sodium) .

In patients with heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia, and (rarely) with acute renal failure and death. In such patients, MONOPRIL (fosinopril sodium) therapy should be started under close medical supervision; they should be followed closely for the first 2 weeks of treatment and whenever the dose of fosinopril or diuretic is increased. Consideration should be given to reducing the diuretic dose in patients with normal or low blood pressure who have been treated vigorously with diuretics or who are hyponatremic.

If hypotension occurs, the patient should be placed in a supine position, and, if necessary, treated with intravenous infusion of physiological saline. MONOPRIL (fosinopril sodium) treatment usually can be continued following restoration of blood pressure and volume.

Neutropenia/Agranulocytosis

Another angiotensin-converting enzyme inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in uncomplicated patients, but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Available data from clinical trials of fosinopril are insufficient to show that fosinopril does not cause agranulocytosis at similar rates. Monitoring of white blood cell counts should be considered in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.

Fetal/Neonatal Morbidity and Mortality

ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.

The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE-inhibitor exposure.

These adverse effects do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of fosinopril as soon as possible.

Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment.

If oligohydramnios is observed, fosinopril should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Fosinopril is poorly dialyzed from the circulation of adults by hemodialysis and peritoneal dialysis. There is no experience with any procedure for removing fosinopril from the neonatal circulation.

When fosinopril was given to pregnant rats at doses about 80 to 250 times (on a mg/kg basis) the maximum recommended human dose, three similar orofacial malformations and one fetus with situs inversus were observed among the offspring. No teratogenic effects of fosinopril were seen in studies in pregnant rabbits at doses up to 25 times (on a mg/kg basis) the maximum recommended human dose.

Hepatic Failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

PRECAUTIONS

General

Impaired Renal Function: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors, including MONOPRIL (fosinopril sodium tablets), may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death.

In hypertensive patients with renal artery stenosis in a solitary kidney or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur. Experience with another angiotensin-converting enzyme inhibitor suggests that these increases are usually reversible upon discontinuation of ACE inhibitor and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy. Some hypertensive patients with no apparent preexisting renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when MONOPRIL (fosinopril sodium) has been given concomitantly with a diuretic. This is more likely to occur in patients with preexisting renal impairment. Dosage reduction of MONOPRIL (fosinopril sodium) and/or discontinuation of the diuretic may be required.

Evaluation of patients with hypertension or heart failure should always include assessment of renal function (see DOSAGE AND ADMINISTRATION).

Impaired renal function decreases total clearance of fosinoprilat and approximately doubles AUC. In general, no adjustment of dosing is needed. However, patients with heart failure and severely reduced renal function may be more sensitive to the hemodynamic effects (e.g., hypotension) of ACE inhibition (see CLINICAL PHARMACOLOGY).

Hyperkalemia: In clinical trials, hyperkalemia (serum potassium greater than 10% above the upper limit of normal) has occurred in approximately 2.6% of hypertensive patients receiving MONOPRIL (fosinopril sodium) . In most cases, these were isolated values which resolved despite continued therapy. In clinical trials, 0.1% of patients (2 patients) were discontinued from therapy due to an elevated serum potassium. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes, which should be used cautiously, if at all, with MONOPRIL (fosinopril sodium tablets) (see PRECAUTIONS: DRUG INTERACTIONS).

Cough: Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Impaired Liver Function: Since fosinopril is primarily metabolized by hepatic and gut wall esterases to its active moiety, fosinoprilat, patients with impaired liver function could develop elevated plasma levels of unchanged fosinopril. In a study in patients with alcoholic or biliary cirrhosis, the extent of hydrolysis was unaffected, although the rate was slowed. In these patients, the apparent total body clearance of fosinoprilat was decreased and the plasma AUC approximately doubled.

Surgery/Anesthesia: In patients undergoing surgery or during anesthesia with agents that produce hypotension, fosinopril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

Hemodialysis

Recent clinical observations have shown an association of hypersensitivity-like (anaphylactoid) reactions during hemodialysis with high-flux dialysis membranes (e.g., AN69) in patients receiving ACE inhibitors as medication. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of medication. (See WARNINGS: Anaphylactoid reactions during membrane exposure.)

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of a carcinogenic effect was found when fosinopril was given in the diet to mice and rats for up to 24 months at doses up to 400 mg/kg/day. On a body weight basis, the highest dose in mice and rats is about 250 times the maximum human dose of 80 mg, assuming a 50 kg subject. On a body surface area basis, in mice, this dose is 20 times the maximum human dose; in rats, this dose is 40 times the maximum human dose. Male rats given the highest dose level had a slightly higher incidence of mesentery/omentum lipomas.

Neither fosinopril nor the active fosinoprilat was mutagenic in the Ames microbial mutagen test, the mouse lymphoma forward mutation assay, or a mitotic gene conversion assay. Fosinopril was also not genotoxic in a mouse micronucleus test in vivo and a mouse bone marrow cytogenetic assay in vivo.

In the Chinese hamster ovary cell cytogenetic assay, fosinopril increased the frequency of chromosomal aberrations when tested without metabolic activation at a concentration that was toxic to the cells. However, there was no increase in chromosomal aberrations at lower drug concentrations without metabolic activation or at any concentration with metabolic activation.

There were no adverse reproductive effects in male and female rats treated with 15 or 60 mg/kg daily. On a body weight basis, the high dose of 60 mg/kg is about 38 times the maximum recommended human dose. On a body surface area basis, this dose is 6 times the maximum recommended human dose. There was no effect on pairing time prior to mating in rats until a daily dose of 240 mg/kg, a toxic dose, was given; at this dose, a slight increase in pairing time was observed. On a body weight basis, this dose is 150 times the maximum recommended human dose. On a body surface area basis, this dose is 24 times the maximum recommended human dose.

Pregnancy

Pregnancy Categories C (first trimester) and D (second and third trimesters)

See WARNINGS: Fetal/Neonatal Morbidity and Mortality.

Nursing Mothers

Ingestion of 20 mg daily for 3 days resulted in detectable levels of fosinoprilat in breast milk. MONOPRIL (fosinopril sodium) should not be administered to nursing mothers.

Geriatric Use

Clinical studies of MONOPRIL (fosinopril sodium) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pediatric Use

The antihypertensive effects of fosinopril have been evaluated in a double-blind study in pediatric patients 6 to 16 years of age (see CLINICAL PHARMACOLOGY: Pharmacodynamics and Clinical Effects: Hypertension). The pharmacokinetics of fosinopril have been evaluated in pediatric patients 6 to 16 years of age (see CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism). Fosinopril was generally well tolerated and adverse effects were similar to those described in adults (see ADVERSE REACTIONS: Pediatric Patients).

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Oral doses of fosinopril at 2600 mg/kg in rats were associated with significant lethality. Human overdoses of fosinopril have not been reported, but the most common manifestation of human fosinopril overdosage is likely to be hypotension.

Laboratory determinations of serum levels of fosinoprilat and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of fosinopril overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of fosinopril and its metabolites. Fosinoprilat is poorly removed from the body by both hemodialysis and peritoneal dialysis.

Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of fosinopril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of fosinopril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat fosinopril overdose by infusion of normal saline solution.

No adverse clinical events were reported in 23 pediatric patients, age 6 months to 6 years, given a single 0.3 mg/kg oral dose of fosinopril.

There is a published report of a 20-month-old female, weighing 12 kg, who ingested approximately 200 mg MONOPRIL (fosinopril sodium) . After receiving gastric lavage and activated charcoal within 1 hour of the ingestion, she made an uneventful recovery.

CONTRAINDICATIONS

MONOPRIL (fosinopril sodium) (fosinopril sodium tablets) 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).

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

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. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of MONOPRIL (fosinopril sodium) remains to be elucidated.

While the mechanism through which MONOPRIL (fosinopril sodium) lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, MONOPRIL (fosinopril sodium) has an antihypertensive effect even in patients with low-renin hypertension. Although MONOPRIL (fosinopril sodium) was antihypertensive in all races studied, black hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to ACE inhibitor monotherapy than non-black patients.

In patients with heart failure, the beneficial effects of MONOPRIL (fosinopril sodium) are thought to result primarily from suppression of the renin-angiotensin-aldosterone system; inhibition of the angiotensin-converting enzyme produces decreases in both preload and afterload.

Pharmacokinetics and Metabolism

Following oral administration, fosinopril (the prodrug) is absorbed slowly. The absolute absorption of fosinopril averaged 36% of an oral dose. The primary site of absorption is the proximal small intestine (duodenum/jejunum). While the rate of absorption may be slowed by the presence of food in the gastrointestinal tract, the extent of absorption of fosinopril is essentially unaffected.

Fosinoprilat is highly protein-bound (approximately 99.4%), has a relatively small volume of distribution, and has negligible binding to cellular components in blood. After single and multiple oral doses, plasma levels, areas under plasma concentration-time curves (AUCs), and peak concentrations (Cmaxs) are directly proportional to the dose of fosinopril. Times to peak concentrations are independent of dose and are achieved in approximately 3 hours.

After an oral dose of radiolabeled fosinopril, 75% of radioactivity in plasma was present as active fosinoprilat, 20-30% as a glucuronide conjugate of fosinoprilat, and 1-5% 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.

After intravenous administration, fosinoprilat was eliminated approximately equally by the liver and kidney. 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 two studies involving healthy subjects, the mean body clearance of intravenous fosinoprilat was between 26 and 39 mL/min.

In healthy subjects, the terminal elimination half-life (t½) of an intravenous dose of radiolabeled fosinoprilat is approximately 12 hours. In hypertensive patients with normal renal and hepatic function, who received repeated doses of fosinopril, the effective t½ for accumulation of fosinoprilat averaged 11.5 hours. In patients with heart failure, the effective t½ was 14 hours.

In patients with mild to severe renal insufficiency (creatinine clearance 10-80 mL/min/1.73 m2), the clearance of fosinoprilat does not differ appreciably from normal, because of the large contribution of hepatobiliary elimination. In patients with end-stage renal disease (creatinine clearance < 10 mL/min/1.73 m2), the total body clearance of fosinoprilat is approximately one-half of that in patients with normal renal function. (See DOSAGE AND ADMINISTRATION.)

Fosinopril is not well dialyzed. Clearance of fosinoprilat by hemodialysis and peritoneal dialysis averages 2% and 7%, respectively, of urea clearances.

In patients with hepatic insufficiency (alcoholic or biliary cirrhosis), the extent of hydrolysis of fosinopril is not appreciably reduced, although the rate of hydrolysis may be slowed; the apparent total body clearance of fosinoprilat is approximately one-half of that in patients with normal hepatic function.

In elderly (male) subjects (65-74 years old) with clinically normal renal and hepatic function, there appear to be no significant differences in pharmacokinetic parameters for fosinoprilat compared to those of younger subjects (20-35 years old).

In pediatric patients, (N=20) age 6 to 16 years, with glomerular filtration rate ≥ 25 mL/min, given a single dose of fosinopril (0.3 mg/kg given as solution), the mean AUC and Cmax values of fosinoprilat (the active form of fosinopril) were similar to those seen in healthy adults receiving 20 mg (about 0.3 mg/kg for a 70 kg adult) of fosinopril as a solution. The terminal elimination half-life of fosinoprilat in pediatric patients was 11-13 hours, also similar to that observed in adults.

Fosinoprilat was found to cross the placenta of pregnant animals.

Studies in animals indicate that fosinopril and fosinoprilat do not cross the blood-brain barrier.

Pharmacodynamics and Clinical Effects

Serum ACE activity was inhibited by ≥ 90% at 2 to 12 hours after single doses of 10 to 40 mg of fosinopril. At 24 hours, serum ACE activity remained suppressed by 85%, 93%, and 93% in the 10, 20, and 40 mg dose groups, respectively.

Hypertension

Adult

Administration of MONOPRIL (fosinopril sodium tablets) to patients with mild to moderate hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt- and/or volume-depleted (see WARNINGS). Use of MONOPRIL (fosinopril sodium) in combination with thiazide diuretics gives a blood pressure-lowering effect greater than that seen with either agent alone.

Following oral administration of single doses of 10-40 mg, MONOPRIL (fosinopril sodium) lowered blood pressure within 1 hour, with peak reductions achieved 2-6 hours after dosing. The antihypertensive effect of a single dose persisted for 24 hours. Following 4 weeks of monotherapy in placebo-controlled trials in patients with mild to moderate hypertension, once daily doses of 20-80 mg lowered supine or seated systolic and diastolic blood pressures 24 hours after dosing by an average of 8-9/6-7 mmHg more than placebo. The trough effect was about 50-60% of the peak diastolic response and about 80% of the peak systolic response.

In most trials, the antihypertensive effect of MONOPRIL (fosinopril sodium) increased during the first several weeks of repeated measurements. The antihypertensive effect of MONOPRIL (fosinopril sodium) has been shown to continue during long-term therapy for at least 2 years. Abrupt withdrawal of MONOPRIL (fosinopril sodium) has not resulted in a rapid increase in blood pressure.

Limited experience in controlled and uncontrolled trials combining fosinopril with a calcium channel blocker or a loop diuretic has indicated no unusual drug-drug interactions. Other ACE inhibitors have had less than additive effects with beta-adrenergic blockers, presumably because both drugs lower blood pressure by inhibiting parts of the renin-angiotensin system.

ACE inhibitors are generally less effective in blacks than in non-blacks. The effectiveness of MONOPRIL (fosinopril sodium) was not influenced by age, sex, or weight.

In hemodynamic studies in hypertensive patients, after 3 months of therapy, responses (changes in BP, heart rate, cardiac index, and PVR) to various stimuli (e.g., isometric exercise, 45° head-up tilt, and mental challenge) were unchanged compared to baseline, suggesting that MONOPRIL (fosinopril sodium) does not affect the activity of the sympathetic nervous system. Reduction in systemic blood pressure appears to have been mediated by a decrease in peripheral vascular resistance without reflex cardiac effects. Similarly, renal, splanchnic, cerebral, and skeletal muscle blood flow were unchanged compared to baseline, as was glomerular filtration rate.

Pediatric

Reduction of blood pressure with low (0.1 mg/kg), medium (0.3 mg/kg) and high (0.6 mg/kg) target doses of once-daily 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. Fosinopril doses in the medium and high dose groups were titrated to target doses after 1 week and the total duration of treatment was 4 weeks. The maximum dose studied was 40 mg once daily. At the end of 4 weeks of treatment, the mean reductions from baseline in trough systolic blood pressure were similar in all three dose groups. Withdrawal of fosinopril treatment resulted in an increase in blood pressure towards baseline over a 2-week period. Fosinopril was generally well tolerated.

Heart Failure

In a randomized, double-blind, placebo-controlled trial, 179 patients with heart failure, all receiving diuretics and some receiving digoxin, were administered single doses of 1, 20, or 40 mg of MONOPRIL (fosinopril sodium) or placebo. Doses of 20 and 40 mg of MONOPRIL (fosinopril sodium) resulted in acute decreases in pulmonary capillary wedge pressure (preload) and mean arterial blood pressure and systemic vascular resistance (afterload). One hundred fifty-five of these patients were re-randomized to once daily therapy with MONOPRIL (fosinopril sodium) (1, 20, or 40 mg) for an additional 10 weeks. Hemodynamic measurements made 24 hours after dosing showed (relative to baseline) 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 and 40 mg dose groups. No tachyphylaxis was seen.

MONOPRIL (fosinopril sodium) was studied in 3 double-blind, placebo-controlled, 12-24 week trials including a total of 734 patients with heart failure, with MONOPRIL (fosinopril sodium) doses from 10 to 40 mg daily. Concomitant therapy in 2 of these 3 trials included diuretics and digitalis; in the third trial patients were receiving only diuretics. All 3 trials showed statistically significant benefits of MONOPRIL (fosinopril sodium) therapy, compared to placebo, in one or more of the following: exercise tolerance (1 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. Effects of MONOPRIL (fosinopril sodium) on long-term mortality in heart failure have not been evaluated. The once daily dosage for the treatment of congestive heart failure was the only dosage regimen used during clinical trial development and was determined by the measurement of hemodynamic responses.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Angioedema: Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose. Patients should be advised to immediately report to their physician any signs or symptoms suggesting angioedema (e.g., swelling of face, eyes, lips, tongue, larynx, mucous membranes, and extremities; difficulty in swallowing or breathing; hoarseness) and to discontinue therapy. (See WARNINGS: Head and Neck Angioedema and Intestinal Angioedema and ADVERSE REACTIONS.)

Symptomatic Hypotension Patients should be cautioned that lightheadedness can occur, especially during the first days of therapy, and it should be reported to a physician. Patients should be told that if syncope occurs, MONOPRIL (fosinopril sodium) should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Hyperkalemia: Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting the physician.

Neutropenia: Patients should be told to promptly report any indication of infection (e.g., sore throat, fever), which could be a sign of neutropenia.

Pregnancy: Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Angioedema: Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose. Patients should be advised to immediately report to their physician any signs or symptoms suggesting angioedema (e.g., swelling of face, eyes, lips, tongue, larynx, mucous membranes, and extremities; difficulty in swallowing or breathing; hoarseness) and to discontinue therapy. (See WARNINGS: Head and Neck Angioedema and Intestinal Angioedema and ADVERSE REACTIONS.)

Symptomatic Hypotension Patients should be cautioned that lightheadedness can occur, especially during the first days of therapy, and it should be reported to a physician. Patients should be told that if syncope occurs, MONOPRIL (fosinopril sodium) should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Hyperkalemia: Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting the physician.

Neutropenia: Patients should be told to promptly report any indication of infection (e.g., sore throat, fever), which could be a sign of neutropenia.

Pregnancy: Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Monopril Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

FOSINOPRIL - ORAL

(fos-IN-oh-pril)

COMMON BRAND NAME(S): Monopril

WARNING: This drug can cause serious (possibly fatal) harm to an unborn baby if used during pregnancy. Therefore, it is important to prevent pregnancy while taking this medication. Consult your doctor for more details and to discuss the use of reliable forms of birth control while taking this medication. If you are planning pregnancy, become pregnant, or think you may be pregnant, contact your doctor immediately.

USES: Fosinopril is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to treat heart failure.

Fosinopril is an ACE inhibitor and works by relaxing blood vessels so that blood can flow more easily.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to help protect the kidneys from harm due to diabetes.

HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually once or twice daily.

The dosage is based on your medical condition and response to treatment.

Antacids containing aluminum or magnesium can decrease the absorption of fosinopril. If you are taking an antacid that contains aluminum or magnesium, take it at least 2 hours before or 2 hours after taking this product.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time(s) each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

For the treatment of high blood pressure, it may take several weeks before you get the full benefit of this medication. For the treatment of heart failure, it may take weeks to months before you get the full benefit of this medication. Tell your doctor if your condition does not improve or if it worsens (such as your blood pressure readings remain high or increase).

Disclaimer

Monopril Consumer (continued)

SIDE EFFECTS: Dizziness or lightheadedness may occur as your body adjusts to the medication. Dry cough may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these unlikely but serious side effects occur: fainting, muscle weakness, signs of infection (such as fever, chills, persistent sore throat), change in the amount of urine.

This drug may rarely cause serious (possibly fatal) liver problems. Tell your doctor right away if you notice any of the following rare but serious side effects: yellowing eyes/skin, dark urine, severe stomach/abdominal pain, persistent nausea/vomiting.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Monopril (fosinopril sodium) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking fosinopril, tell your doctor or pharmacist if you are allergic to it; or to other ACE inhibitors (such as benazepril); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of an allergic reaction which included swelling of the face/lips/tongue/throat (angioedema), blood filtering procedures (such as LDL apheresis, dialysis), high level of potassium in the blood, collagen vascular disease (such as lupus, scleroderma).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Too much sweating, diarrhea, or vomiting may cause loss of too much body water (dehydration) and increase your risk of lightheadedness. Report prolonged diarrhea or vomiting to your doctor. Be sure to drink enough fluids to prevent dehydration unless your doctor directs you otherwise.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This product may increase your potassium levels. Before using potassium supplements or salt substitutes that contain potassium, consult your doctor or pharmacist.

Older adults may be more sensitive to the effects of this product, especially dizziness.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details. (See also Warning section.)

This medication passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Monopril Consumer (continued)

DRUG INTERACTIONS: See also How to Use and Precautions section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: aliskiren, lithium, drugs that may increase your potassium level (including birth control products that contain drospirenone).

Check the labels on all your medicines (such as cough-and-cold products, diet aids, or NSAIDs such as ibuprofen, naproxen) because they may contain ingredients that could increase your blood pressure or worsen your heart failure. Ask your pharmacist for more details.

Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day) should be continued. Consult your doctor or pharmacist for more details.

A very serious reaction may occur if you are getting injections for bee/wasp sting allergy (desensitization) and are also taking fosinopril. Make sure all your doctors know which medicines you are using.

This medication may interfere with certain laboratory tests (including digoxin levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Laboratory and/or medical tests (such as kidney function, potassium levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Check your blood pressure regularly while taking this medication. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised March 2012. Copyright(c) 2012 First Databank, Inc.

Monopril Patient Information Including Side Effects

Brand Names: Monopril

Generic Name: fosinopril (Pronunciation: foe SIN oh pril)

What is fosinopril (Monopril)?

Fosinopril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme.

Fosinopril is used to treat high blood pressure (hypertension) or heart failure.

Fosinopril may also be used for other purposes not listed in this medication guide.

Fosinopril 10 mg-APO

peanut, white, imprinted with APO, FOS-10

Fosinopril 10 mg-GG

diamond, white, imprinted with 10, 2737

Fosinopril 10 mg-TEV

rectangular, white, imprinted with 9 3, 72 22

Fosinopril 20 mg-APO

oval, white, imprinted with APO, FOS-20

Fosinopril 20 mg-TEV

oblong, white, imprinted with 93, 7223

Fosinopril 40 mg-APO

round, white, imprinted with APO, FOS 40

Fosinopril 40 mg-EON

round, white, imprinted with E 47

Fosinopril 40 mg-TEV

round, white, imprinted with 93, 7224

Monopril 10 mg

diamond, white, imprinted with BMS, MONOPRIL 10

Monopril 20 mg

oval, white, imprinted with BMS, MONOPRIL 20

Monopril 40 mg

hexagonal, white, imprinted with BMS, MONOPRIL 40

What are the possible side effects of fosinopril (Monopril)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • feeling light-headed, fainting;
  • urinating less than usual, or not at all;
  • fever, chills, body aches, flu symptoms;
  • severe blistering, peeling, and red skin rash;
  • pale skin, easy bruising or bleeding, unusual weakness;
  • pounding or uneven heartbeats;
  • slow heart rate, weak pulse, muscle weakness, tingly feeling;
  • jaundice (yellowing of the skin or eyes);
  • chest pain; or
  • swelling, rapid weight gain.

Less serious side effects may include:

  • cough;
  • muscle or joint pain;
  • dizziness, headache, tired feeling;
  • runny or stuffy nose;
  • nausea, vomiting, diarrhea; or
  • mild skin itching or rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Monopril (fosinopril sodium) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about fosinopril (Monopril)?

Avoid taking an antacid within 2 hours before or after you take fosinopril.

Avoid drinking alcohol. It can further lower your blood pressure and may increase some of the side effects of fosinopril.

Do not use salt substitutes or potassium supplements while taking fosinopril, unless your doctor has told you to.

Vomiting, diarrhea, or heavy sweating can cause you to become dehydrated. This can lead to very low blood pressure, electrolyte disorders, or kidney failure while you are taking fosinopril. Drink plenty of water daily while you are taking this medication.

Side Effects Centers

Monopril Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking fosinopril (Monopril)?

You should not use this medication if you are allergic to fosinopril or to any other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).

If you have any of these other conditions, you may need a dose adjustment or special tests to safely use fosinopril:

  • kidney disease (or if you are on dialysis);
  • liver disease;
  • heart disease or congestive heart failure;
  • diabetes;
  • a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis; or
  • if you have ever had a severe allergic reaction.

FDA pregnancy category D. Do not use this medication without telling your doctor if you are pregnant or planning a pregnancy. Fosinopril could cause birth defects in the baby if you take the medication during pregnancy. Use an effective form of birth control. Stop using this medication and tell your doctor right away if you become pregnant during treatment.

Fosinopril can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give this medication to a child younger than 6 years old.

How should I take fosinopril (Monopril)?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Take each dose with a full glass of water.

Fosinopril can be taken with or without food.

Vomiting, diarrhea, or heavy sweating can cause you to become dehydrated. This can lead to very low blood pressure, electrolyte disorders, or kidney failure while you are taking fosinopril. Drink plenty of water each day while you are taking this medication.

To be sure this medication is helping your condition, your blood pressure will need to be checked on a regular basis. Your kidney or liver function may also need to be tested. Do not miss any scheduled visits to your doctor.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking fosinopril. You may need to stop using the medicine for a short time.

This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using fosinopril.

If you are being treated for high blood pressure, keep using this medication even if you feel fine. High blood pressure often has no symptoms.

Store fosinopril at room temperature away from moisture and heat.

Side Effects Centers

Monopril Patient Information including If I Miss a Dose

What happens if I miss a dose (Monopril)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Monopril)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include feeling extremely dizzy or light-headed, or fainting.

What should I avoid while taking fosinopril (Monopril)?

Avoid taking an antacid within 2 hours before or after you take fosinopril.

Avoid drinking alcohol. It can further lower your blood pressure and may increase some of the side effects of fosinopril.

Do not use salt substitutes or potassium supplements while taking fosinopril, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

What other drugs will affect fosinopril (Monopril)?

Before taking fosinopril, tell your doctor if you are taking any of the following drugs:

  • gold injections to treat arthritis;
  • lithium (Lithobid, Eskalith);
  • a potassium supplement such as K-Dur, Klor-Con;
  • salt substitutes that contain potassium; or
  • a diuretic (water pill).

This list is not complete and there may be other drugs that can interact with fosinopril. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about fosinopril.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 7.02. Revision date: 12/15/2010.

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