Fosinopirl Sodium
FDA Drug Information • Also known as: Fosinopril Sodium
- Brand Names
- Fosinopril Sodium
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: FETAL TOXICITY
Description
DESCRIPTION Fosinopril sodium is the sodium salt of fosinopril, the ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor, fosinoprilat. It contains a phosphinate group capable of specific binding to the active site of angiotensin-converting enzyme. Fosinopril sodium is designated chemically as: L-proline, 4-cyclohexyl-1-[[[2-methyl-1-(1-oxopropoxy) propoxy] (4-phenylbutyl) phosphinyl] acetyl]-, sodium salt, trans- . Fosinopril sodium is a white to off-white crystalline powder. It is soluble in water (100 mg/mL), methanol, and ethanol and slightly soluble in hexane. Its structural formula is: C 30 H 45 NNaO 7 P M.W. 585.65 Fosinopril sodium, USP, is available for oral administration as 10 mg, 20 mg, and 40 mg tablets. Inactive ingredients include: crospovidone, lactose monohydrate, microcrystalline cellulose, povidone, and sodium stearyl fumarate. D:\FOSINOPRIL SODIUM\FOSINOPRILSODIUM-TEVA,2009\SPL-FOSINOPRILSODIUM07232012-TEVA,2009\6213b69f-39e1-4f48-a110-a83bd5459c4a-01.jpg
What Is Fosinopirl Sodium Used For?
INDICATIONS AND USAGE Fosinopril sodium tablets are indicated for the treatment of hypertension. They may be used alone or in combination with thiazide diuretics. Fosinopril sodium tablets are indicated in the management of heart failure as adjunctive therapy when added to conventional therapy including diuretics with or without digitalis (see DOSAGE AND ADMINISTRATION ). In using fosinopril sodium, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that fosinopril sodium does not have a similar risk (see WARNINGS ). In considering use of fosinopril sodium, it should be noted that in controlled trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. In addition, ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients (see WARNINGS , Head and Neck Angioedema and Intestinal Angioedema ).
Dosage and Administration
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...
Side Effects (Adverse Reactions)
ADVERSE REACTIONS Fosinopril sodium tablets have 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 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 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 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 = 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 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%) patients discontinued due to first dose hypotension....
Warnings and Precautions
WARNINGS Anaphylactoid and Possibly 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 ). Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema. 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...
Drug Interactions
Drug Interactions Diuretics Patients on diuretics, especially those with intravascular volume depletion, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with fosinopril sodium tablets. The possibility of hypotensive effects with fosinopril sodium can be minimized by either discontinuing the diuretic or increasing salt intake prior to initiation of treatment with fosinopril sodium. 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 ). Agents increasing serum potassium Coadministration of fosinopril with potassium sparing diuretics, potassium supplements, potassium-containing salt substitutes or other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. 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. Antacids In a clinical pharmacology study, coadministration of an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as compared with fosinopril administrated 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. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including fosinopril sodium. Non-steroidal anti-inflammatory agents including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including fosinopril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving quinapril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including fosinopril may be attenuated by NSAIDs. Agents that inhibit mTOR Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema. Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including...
Contraindications
CONTRAINDICATIONS Fosinopril sodium tablets are contraindicated in patients who are hypersensitive to this product or to any other angiotensin-converting enzyme inhibitor (e.g., a patient who has experienced angioedema with any other ACE inhibitor therapy). Do not co-administer fosinopril sodium tablets with aliskiren in patients with diabetes.
Overdosage
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. 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 1 hour of the ingestion, she made an uneventful recovery.
How Supplied
HOW SUPPLIED Fosinopril sodium tablets USP, 10 mg: White to off-white, capsule-shaped tablets, both sides scored, debossed with “S|10” on one side and “|” on the other side. They are supplied in bottles of 90 (NDC 43547-386-09) and 1000 (NDC 43547-386-11). Fosinopril sodium tablets USP, 20 mg: White to off-white, round tablets debossed with “S 20” on one side and plain on the other side. They are supplied in bottles of 90 (NDC 43547-387-09) and 1000 (NDC 43547-387-11). Fosinopril sodium tablets USP, 40 mg: White to off-white, round tablets debossed with “S 40” on one side and plain on the other side. They are supplied in bottles of 90 (NDC 43547-388-09) and 1000 (NDC 43547-388-11).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.