Fosinopril Sodium 20 MG Oral Tablet


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 ).

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 our 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 impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma.

Available data from clinical trials of fosinopril are insufficient to show that fosinopril does not cause agranulocytosis at similar rates.

Monitoring of white blood cell counts should be considered in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.

Fetal toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death.

Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.

Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death.

When pregnancy is detected, discontinue fosinopril as soon as possible.

These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy.

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents.

Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.

Perform serial ultrasound examinations to assess the intra-amniotic environment.

If oligohydramnios is observed, discontinue fosinopril, unless it is considered lifesaving for the mother.

Fetal testing may be appropriate, based on the week of pregnancy.

Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Closely observe infants with histories of in utero exposure to fosinopril for hypotension, oliguria, and hyperkalemia (see Precautions , Pediatric Use ).

No teratogenic effects of fosinopril were seen in studies of pregnant rats and rabbits.

On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose.


Drug Interactions 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 acute renal failure) compared to monotherapy.

Closely monitor blood pressure, renal function and electrolytes in patients on fosinopril and other agents that affect the RAS.

Do not co-administer aliskiren with fosinopril in patients with diabetes.

Avoid use of aliskiren with fosinopril in patients with renal impairment (GFR <60 mL/min).

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 fosinopril sodium.

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.


With potassium supplements and potassium-sparing diuretics: Fosinopril sodium 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 co administered 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 (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 and administration of these agents is indicated, dosing should be separated by 2 hours.

Other: Neither fosinopril sodium 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, metoclopramide, propantheline, digoxin, and warfarin, the bioavailability of fosinoprilat was not altered by coadministration of fosinopril with any one of these drugs.

In study with concomitant administration of aspirin and fosinopril sodium.

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.


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 over dosage is likely to hypotension.

Laboratory determination 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.

There is published report of a 20 month-old female, weighing 12 kg, who ingested approximately 200 mg MONOPRIL.

After receiving gastric lavage and activated charcoal within one hour of the ingestion, she made an eventful recovery.

Information from clinical studies of fosinopril sodium administered as a single dose greater than the approved dose in the treatment of hypertension in the pediatric patients is available in the approved labeling for Bristol-Myers Squibb Company’s fosinopril sodium drug products.

However, due to Bristol-Myer Squibb’s marketing exclusively rights, this drug product is not labeled for pediatric use.


Fosinopril sodium tablet, USP is the sodium salt of fosinopril USP, 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, USP is designated chemically as:L-proline,4-cyclohexyl-1-[[[2-methyl-1-(1-oxopropoxy)propoxy](4- phenylbutyl)phosphinyl]acetyl]-, sodium salt, trans-.

Fosinopril sodium,USP 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: Its empirical formula is C 30 H 45 NNaO 7 P, and its molecular weight is 585.65.

Fosinopril Sodium, USP is available for oral administrations as 10 mg, 20 mg, and 40 mg tablets.

Inactive ingredients include: crospovidone, lactose, microcrystalline cellulose, magnesium stearate, and povidone.

Chemical Structure


Repackaged by Aphena Pharma Solutions – TN.

See Repackaging Information for available configurations.

Fosinopril Sodium Tablets, USP 10 mg tablets: White, round, biconvex partially scored tablets debossed with “IG”on one side and “200” on other side.

They are supplied in bottles of 90 (NDC 76282-200-90) and 1000 (NDC 76282-200-10).

Bottles contain a desiccant canister.

20 mg tablets: White, round, biconvex tablets debossed with “IG” on one side and “201” on other side.

They are supplied in bottles of 90 (NDC 76282-201-90) and 1000 (NDC 76282-201-10).

Bottles contain a desiccant canister.

40 mg tablets: White, round, biconvex tablets debossed with “IG” on one side and “202” on other side.

They are supplied in bottles of 90 (NDC 76282-202-90) and 1000 (NDC 76282-202-10).

Bottles contain a desiccant canister.

STORAGE Store at 20° C to 25° C (68° to 77°F) [see USP Controlled Room Temperature] Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Manufactured by: InvaGen Pharmaceuticals, Inc.

Hauppauge, NY 11788.

Manufactured for: Exelan Pharmaceuticals, Inc.

Lawrenceville, GA 30046.

Rev: 12/13


Geriatric Use Clinical studies of fosinopril sodium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Other reported clinical experience has not identified differences in response between the elderly and younger patients.

In general, dose selection for and 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.


Fosinopril sodium tablets, USP are indicated for the treatment of hypertension.

It may be used alone or in combination with thiazide diuretics.

Fosinopril sodium tablets, USP 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 ).


Pediatric Use Neonates with a history of in utero exposure to fosinopril sodium tablets: 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 ).


Nursing Mothers Ingestion of 20 mg daily for three days resulted in detectable levels of fosinoprilat in breast milk.

Fosinopril sodium should not be administered to nursing mothers.


WARNING: FETAL TOXICITY When pregnancy is detected, discontinue fosinopril sodium tablets as soon as possible.

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

See Warnings: Fetal Toxicity


Information for Patients Angioedema: Angioedema, including laryngeal edema, can occur with treatment with ACE inhibitors, especially following the first dose.

Patients should be advised to immediately report to their physician any signs or symptoms suggesting angioedema (e.g., swelling of face, eyes, lips, tongue, larynx, mucous membranes, and extremities; difficulty in swallowing or breathing; hoarseness) and to discontinue therapy.

(See WARNINGS: Head and Neck Angioedema and ADVERSE REACTIONS .) Symptomatic Hypotension: Patients should be cautioned that lightheadedness can occur, especially during the first days of therapy, and it should be reported to a physician.

Patients should be told that if syncope occurs, fosinopril sodium should be discontinued until the physician has been consulted.

All patients should be cautioned that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope.

Hyperkalemia: Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting the physician.

Neutropenia: Patients should be told to promptly report any indication of infection (e.g., sore throat, fever), which could be a sign of neutropenia.

Pregnancy: Female patients of childbearing age should be told about the consequences of second-and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester.

These patients should be asked to report pregnancies to their physician as soon as possible.


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 (2-6 hours) and trough (about 24 hours after dosing) blood levels.

The usual dosage range needed to maintain a response at trough is 20-40 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 fosinopril sodium alone, a diuretic may be added.

Concomitant administration of fosinopril sodium 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 ).

Pediatrics Information related to the dosing of fosinopril sodium in the treatment of hypertension in pediatric patients weighing more than 50 kg is available in the approved labeling for Bristol-Myers Squibb Company’s fosinopril sodium drug product.

However, due to Bristol-Myers Squibb’s marketing exclusivity rights, this drug product is not labeled for pediatric use.

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 presents 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 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 totally body clearance for fosinoprilat does not differ appreciably with any degree of renal insufficiency (creatinine clearances <80 mL/min/1.73m 2 ), including end stage renal failure (creatinine clearance <10 mL/min/1.73m 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 .)