Fosinopril Sodium

Fosinopril is in a class of drugs called angiotensin converting enzyme (ACE) inhibitors. ACE inhibitors are used for treating high blood pressure, heart failure and for preventing kidney failure due to high blood pressure and diabetes. Other ACE inhibitors include enalapril (Vasotec), quinapril (Accupril), captopril (Capoten), ramipril (Altace), benazepril (Lotensin), lisinopril (Zestril, Prinivil), moexipril (Univasc) and trandolapril (Mavik). ACE is an enzyme in blood which controls the formation of angiotensin II, a chemical that circulates in blood and causes constriction of arteries and veins. Constriction of arteries and veins elevates blood pressure. ACE inhibitors inhibit ACE and block the formation of angiotensin II. By blocking the formation of angiotensin II, fosinopril relaxes the arteries and veins and lowers blood pressure. By reducing blood pressure, fosinopril also reduces the work that the heart must do to pump blood through the arteries and veins. This improves the output of blood from the heart especially when the heart is failing. The FDA approved fosinopril in May 1991.

GENERIC AVAILABLE: Yes

ACE inhibitors, including fosinopril, can be harmful to the fetus and should not be taken by pregnant women.

Fosinopril is secreted in breast milk and is not recommended for nursing mothers.

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)

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)

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.

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.

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.

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.

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• ACE Inhibitors
• Congestive Heart Failure (CHF) Symptoms, Stages, and Prognosis
• Diabetes (Type 1 and Type 2)
• Heart Attack
• High Blood Pressure (Hypertension) Medications
• Kidney Failure

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