Fosinopril Sodium 10 mg Tablet, 90-count — NDC 62135-041-90 (Billing 62135-0041-90)

WARNINGS Anaphylactoid and Possible Related Reactions Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including 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 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 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 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, 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.

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 imp… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS Fosinopril sodium has been evaluated for safety in more than 2,100 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 fosinopril sodium-treated patients), the usual duration of therapy was two to three months.

Discontinuations due to any clinical or laboratory adverse event were 4.1% and 1.1% in 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 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 fosinopril sodium alone and at least as frequent on fosinopril sodium as on placebo in placebo-controlled clinical trials are shown in the table below. Clinical Adverse events In Placebo-Controlled Trials (Hypertension) 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 fosinopril sodium tablets 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 fosinopril sodium in controlled or uncontrolled clinical trials (N; 1 ,479) 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, Anaphylactoid and Possible Related Reactions, 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. Urogenita l: Renal insufficiency, urinary frequency. Heart Failure In placebo-controlled clinical trials (361 fosinopril sodium-treated patients), the usual duration of therapy was 3 to 6 months.

Discontinuations due to any clinical or laboratory adverse event, except for heart failure, were 8.0% and 7.5% in fosinopril sodium-treated and placebo-treated patients, respectively. The most frequent reason for discontinuation of fosinopril sodium was angina pectoris (1.1 %). Significant hypotension after the first dose of fosinopril sodium occurred in 14/590 (2.4%) of patients; 5/590 (0.8%) pa… [Excerpted — this section continues on DailyMed.]

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 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 pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when fosinopril sodium has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of 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 fosinopril sodium. In most cases, these were isolated values which resolved despite continued therapy.

In clinical trials, 0.1% of patients (two 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 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 p… [Excerpted — this section continues on DailyMed.]