Fosinopril Sodium (Page 6 of 7)

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 Possible Related Reactions and PRECAUTIONS , Hemodialysis 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 fosinopril sodium on growth and development have not been studied.

OVERDOSAGE

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 sodium.

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

DOSAGE AND ADMINISTRATION

Hypertension Adults

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

Concomitant administration of fosinopril sodium tablets 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 fosinopril sodium tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with fosinopril sodium tablets (see WARNINGS). Then, if blood pressure is not controlled with fosinopril sodium tablets alone, diuretic therapy should be resumed. If diuretic therapy cannot be discontinued, an initial dose of 10 mg of fosinopril sodium tablets should be used with careful medical supervision for several hours and until blood pressure has stabilized (see WARNINGS, PRECAUTIONS, Information for Patients and Drug Interactions).

Since concomitant administration of fosinopril sodium tablets 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).

Pediatric Patients

In children, doses of MONOPRIL between 0.1 mg/kg 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 fosinopril sodium tablets in children weighing more than 50 kg is 5 mg 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 fosinopril sodium tablets 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 fosinopril sodium tablets should be 10 mg once daily. Following the initial dose of fosinopril sodium tablets, the patient should be observed under medical supervision for at least two 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 mg 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.