Fosinopril

DOSAGE AND ADMINISTRATION Hypertension Adults The recommended initial dose of fosinopril sodium tablets USP 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 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 USP alone, a diuretic may be added. Concomitant administration of fosinopril sodium tablets USP 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 USP. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with fosinopril sodium tablets USP (see WARNINGS ). Then, if blood pressure is not controlled with fosinopril sodium tablets USP alone, diuretic therapy should be resumed. If diuretic therapy cannot be discontinued, an initial dose of 10 mg of fosinopril sodium tablets USP 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 fosinopril sodium tablets USP 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 fosinopril sodium tablets 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 fosinopril sodium tablets USP 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 fosinopril sodium tablets USP 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 USP should be 10 mg once daily. Following the initial dose of fosinopril sodium tablets USP, 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 m 2 ), including end-stage renal failure (creatinine clearance < 10 mL/min/1.73 m 2 ). 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 ).

Pediatric Use Neonates with a history of in utero exposure to fosinopril: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of fosinopril, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means. 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 ).