|
Hematology: In controlled trials, a mean hemoglobin decrease of 0.1 g/ dL was observed in fosinopril-treated patients. In individual patients decreases in hemoglo-bin 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: Text Continues Below
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. Drug Interactions With 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 can be minimized by either discontinuing the diuretic or increasing salt intake prior to initiation of treatment with MONOPRIL. 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). With potassium supplements and potassium-sparing diuretics: MONOPRIL 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. With 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. With antacids: In a clinical pharmacology study, coadministration of an antacid (alu-minum hydroxide, magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as compared with fosinopril adminis-trated 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. Other: Neither MONOPRIL 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, metoclo-pramide, 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, 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. 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 fre-quency of chromosomal aberrations when tested without metabolic activation at a concentration that was toxic to the cells. However, there was no increase in chro-mosomal 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 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 three days resulted in detectable levels of fosinoprilat in breast milk. MONOPRIL should not be administered to nursing mothers. Geriatric Use Clinical studies of MONOPRIL did not include a sufficient number 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 Safety and effectiveness in pediatric patients have not been established. Page: << Prev | 1 | 2 | 3 | 4 | 5
|
.gif)
