Fosinopril

Black Box Warnings

Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

Contraindications

Hypersensitivity

History of hereditary or angioedema associated with previous ACE inhibitor treatment

Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

Bilateral renal artery stenosis

Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)

Cautions

Renal impairment, hepatic impairment, volume depletion, electrolyte abnormalities

Risk of hyperkalemia, especially with renal impairment, DM, or those taking concomitant K+-elevating drugs

Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy

ACE inhibition also causes increased bradykinin levels which putatively mediates angioedema

Coadministration with mTOR inhibitors (eg, temsirolimus) may increased risk for angioedema

Discontinue STAT if pregnant (see Contraindications and Black Box Warnings)

Less effective in blacks

Renal impairment may occur

Neutropenia/agranulocytosis reported

Cough may occur within the first few months

Cholestatic jaundice may occur

Use caution in severe aortic stenosis

Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia

Fosinopril is a prescription medicine used to treat high blood pressure and heart failure.

The drug used to be sold under the brand name Monopril, but this brand is no longer available.

Lowering your blood pressure can reduce your risk of having a heart attack, a stroke, or another heart complication.

Fosinopril belongs to a class of drugs called angiotensin converting enzyme (ACE) inhibitors. It works by helping relax blood vessels.

The U.S. Food and Drug Administration (FDA) approved fosinopril in 1991. It's made and marketed by various pharmaceutical companies.

Fosinopril Warnings

Before taking fosinopril, tell your doctor if you have, or have ever had:

• Heart disease, heart failure, a heart attack, or other heart problems
• Liver disease
• Kidney disease or a kidney transplant
• Stroke
• Lupus (an autoimmune disease characterized by inflammation and a variety of symptoms)
• Bone marrow problems
• Diabetes
• Scleroderma (a skin condition)
• Rheumatoid arthritis
• An electrolyte imbalance
• Angioedema (swelling of the face, lips, tongue, throat, arms, or legs)
• Allergies to medication (especially ACE inhibitors)

Also, let your doctor know if you have diabetes and are taking the medicine Tekturna (aliskiren) or Amturnide (aliskiren, amlodipine, and hydrochlorothiazide).

Fosinopril may affect your blood sugar levels if you have diabetes. Be sure to monitor your condition carefully.

Tell your healthcare provider you're using fosinopril before having any type of medical test or surgery, including a dental procedure.

Excessive sweating, vomiting, diarrhea, or dehydration could increase your risk of low blood pressure. Tell your doctor if you experience any of these conditions.

Use caution when exercising or experiencing hot weather.

Fosinopril may cause you to sunburn more easily. Avoid unnecessary exposure to sunlight, and use sunscreen and wear protective clothing when outdoors.

Your doctor may recommend following a diet and exercise plan while taking fosinopril. You may also be told to drink more fluids. Follow these instructions carefully.

Don't take potassium or salt substitutes while using fosinopril unless your healthcare provider tells you to do so.

Keep all appointments with your doctor and laboratory while taking this medicine. You'll need to undergo frequent tests, including blood pressure checks.

This medicine may be less effective and increase the risk of angioedema in people of African descent. Talk to your doctor if this is a concern.

Pregnancy and Fosinopril

Fosinopril contains a black box warning because it may cause harm or death to an unborn baby if taken during pregnancy.

Tell your doctor right away if you become pregnant while taking fosinopril.

Use an effective form of birth control to prevent pregnancy while taking this medicine.

This drug passes into breast milk. Don't breastfeed a baby while using fosinopril.

Tell your doctor about all prescription, nonprescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially those listed in the Fosinopril Warnings section above, and any of the following:

• Diuretics (water pills)
• Lithobid (lithium)
• Nonprescription medicines that contain stimulants (may include diet pills and cold medicines)
• Nonsteroidal anti-inflammatory drugs (NSAIDs), such as Advil or Motrin (ibuprofen) and Indocin or Indo-Lemmon (indomethacin)
• Insulin and other diabetes medicines
• Gold injections for arthritis
• Antacids, such as Maalox or Mylanta
• Angiotensin receptor blocker drugs, such as Cozaar (losartan), Avapro (irbesartan), and Diovan HCT (valsartan)

Fosinopril and Other Interactions

Fosinopril may cause dizziness, lightheadedness, or fainting.

Use caution when driving, operating machinery, or performing other tasks that require alertness.

Fosinopril and Alcohol

Alcohol may increase the risk of certain side effects of fosinopril.

Don't drink alcoholic beverages while taking fosinopril without first talking to your doctor.

Fosinopril is part of the drug class:

• ACE INHIBITORS, PLAIN

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of fosinopril, salt substitutes containing potassium should be avoided.

Take fosinopril exactly as prescribed. Follow the directions on your prescription label carefully.

The recommended starting dose is usually 10 mg once daily. Your healthcare provider may increase your dose if necessary to achieve the desired blood pressure response. The usual recommended dosing range is between 20 mg and 40 mg a day.

Based on how your body responds to the medication and side effects you experience your healthcare provider may decide to increase or decrease your dose. The dose you receive is also based on the following factors:

• your age
• the medical condition you are being treated for
• other medical conditions you may have 
• other medications you are taking including diuretics

Fosinopril is an ACE inhibitor. ACE stands for angiotensin converting enzyme.

Fosinopril is used to treat high blood pressure (hypertension) or heart failure.

Fosinopril may also be used for purposes not listed in this medication guide.

You should not use this medicine if you are allergic to fosinopril or similar medications, such as benazepril, captopril, enalapril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.

If you have diabetes, do not use fosinopril together with any medication that contains aliskiren (such as Amturnide, Tekturna, Tekamlo).

You may also need to avoid taking fosinopril with aliskiren if you have kidney disease.

To make sure fosinopril is safe for you, tell your doctor if you have:

• kidney disease (or if you are on dialysis);

• cirrhosis or other liver disease;

• a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis;

• if you are on a low-salt diet; or

• if you have ever had a severe allergic reaction.

Do not use if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away. Fosinopril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

Fosinopril can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Do not give this medication to a child younger than 6 years old.

Fosinopril is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled .

Fosinopril works by blocking an enzyme in the body that is necessary to produce a substance that causes blood vessels to tighten. As a result, the blood vessels relax. This lowers blood pressure and increases the supply of blood and oxygen to the heart .

In addition, fosinopril is used to treat congestive heart failure or may be used for other conditions as determined by your doctor .

fosinopril is available only with your doctor's prescription .

• It is used to treat high blood pressure.
• It is used to treat heart failure (weak heart).
• It may be given to you for other reasons. Talk with the doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Take fosinopril at the same time of day.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• Do not take antacids within 2 hours of fosinopril.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Mechanism of Action

In animals and humans, Fosinopril sodium is hydrolyzed by esterases to the pharmacologically active form, Fosinoprilat, a specific competitive inhibitor of angiotensin-converting enzyme (ACE).

ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium.

In 647 hypertensive patients treated with Fosinopril alone for an average of 29 weeks, mean increases in serum potassium of 0.1 mEq/L were observed. Similar increases were observed among all patients treated with Fosinopril, including those receiving concomitant diuretic therapy. Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Fosinopril sodium remains to be elucidated.

While the mechanism through which Fosinopril sodium lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, Fosinopril sodium has an antihypertensive effect even in patients with low-renin hypertension. Although Fosinopril sodium was antihypertensive in all races studied, black hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to ACE inhibitor monotherapy than non-black patients.

In patients with heart failure, the beneficial effects of Fosinopril sodium are thought to result primarily from suppression of the renin-angiotensin-aldosterone system; inhibition of the angiotensin-converting enzyme produces decreases in both preload and afterload.

Pharmacokinetics and Metabolism

Following oral administration, Fosinopril (the prodrug) is absorbed slowly. The absolute absorption of Fosinopril averaged 36% of an oral dose. The primary site of absorption is the proximal small intestine (duodenum/jejunum). While the rate of absorption may be slowed by the presence of food in the gastrointestinal tract, the extent of absorption of Fosinopril is essentially unaffected.

Fosinoprilat is highly protein-bound (approximately 99.4%), has a relatively small volume of distribution, and has negligible binding to cellular components in blood. After single and multiple oral doses, plasma levels, are as under plasma concentration-time curves (AUCs) and peak concentrations (Cmaxs) are directly proportional to the dose of Fosinopril. Times to peak concentrations are independent of dose and are achieved in approximately 3 hours.

After an oral dose of radiolabeled Fosinopril, 75% of radioactivity in plasma was present as active Fosinoprilat, 20% to 30% as a glucuronide conjugate of Fosinoprilat, and 1% to 5% as a p-hydroxy metabolite of Fosinoprilat. Since Fosinoprilat is not biotransformed after intravenous administration, Fosinopril, not Fosinoprilat, appears to be the precursor for the glucuronide and p-hydroxy metabolites. In rats, the p-hydroxy metabolite of Fosinoprilat is as potent an inhibitor of ACE as Fosinoprilat; the glucuronide conjugate is devoid of ACE inhibitory activity.

After intravenous administration, Fosinoprilat was eliminated approximately equally by the liver and kidney. After oral administration of radiolabeled Fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces. In two studies involving healthy subjects, the mean body clearance of intravenous Fosinoprilat was between 26 and 39 mL/min.

In healthy subjects, the terminal elimination half-life (t1/2) of an intravenous dose of radiolabeled Fosinoprilat is approximately 12 hours. In hypertensive patients with normal renal and hepatic function, who received repeated doses of Fosinopril, the effective t1/2 for accumulation of Fosinoprilat averaged 11.5 hours. In patients with heart failure, the effective t1/2 was 14 hours.

In patients with mild-to-severe renal insufficiency (creatinine clearance 10 to 80 mL/min/1.73m2), the clearance of Fosinoprilat does not differ appreciably from normal, because of the large contribution of hepatobiliary elimination. In patients with end-stage renal disease (creatinine clearance <10 mL/min/1.73m2), the total body clearance of Fosinoprilat is approximately one-half of that in patients with normal renal function. (See DOSAGE AND ADMINISTRATION.)

Fosinopril is not well dialyzed. Clearance of Fosinoprilat by hemodialysis and peritoneal dialysis averages 2% and 7%, respectively, of urea clearances.

In patients with hepatic insufficiency (alcoholic or biliary cirrhosis), the extent of hydrolysis of Fosinopril is not appreciably reduced, although the rate of hydrolysis may be slowed; the apparent total body clearance of Fosinoprilat is approximately one half of that in patients with normal hepatic function.

In elderly (male) subjects (65 to 74 years old) with clinically normal renal and hepatic function, there appear to be no significant differences in pharmacokinetic parameters for Fosinoprilat compared to those of younger subjects (20 to 35 years old).

In pediatric patients, (N=20) age 6 to 16 years, with glomerular filtration rate ≥25 mL/min, given a single dose of Fosinopril (0.3 mg/kg given as solution), the mean AUC and Cmax values of Fosinoprilat (the active form of Fosinopril) were similar to those seen in healthy adults receiving 20 mg (about 0.3 mg/kg for a 70 kg adult) of Fosinopril as a solution. The terminal elimination half-life of Fosinoprilat in pediatric patients was 11 to 13 hours, also similar to that observed in adults.

Fosinoprilat was found to cross the placenta of pregnant animals.

Studies in animals indicate that Fosinopril and Fosinoprilat do not cross the blood-brain barrier.

Pharmacodynamics and Clinical Effects

Serum ACE activity was inhibited by ≥90% at 2 to 12 hours after single doses of 10 to 40 mg of Fosinopril. At 24 hours, serum ACE activity remained suppressed by 85%, 93%, and 93% in the 10, 20, and 40 mg dose groups, respectively.

Hypertension

Adult

Administration of Fosinopril sodium tablets to patients with mild to moderate hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt-and/or volume-depleted (see WARNINGS). Use of Fosinopril sodium in combination with thiazide diuretics gives a blood pressure-lowering effect greater than that seen with either agent alone.

Following oral administration of single doses of 10 mg to 40 mg, Fosinopril sodium lowered blood pressure within one hour, with peak reduction achieved 2 to 6 hours after dosing. The antihypertensive effect of a single dose persisted for 24 hours. Following four weeks of monotherapy in placebo-controlled trials in patients with mild to moderate hypertension, once daily doses of 20 to 80 mg lowered supine or seated systolic and diastolic blood pressures 24 hours after dosing by an average of 8 to 9/6 to 7 mmHg more than placebo. The trough effect was about 50% to 60% of the peak diastolic response and about 80% of the peak systolic response.

In most trials, the antihypertensive effect of Fosinopril sodium increased during the first several weeks of repeated measurements. The antihypertensive effect of Fosinopril sodium has been shown to continue during long-term therapy for at least 2 years. Abrupt withdrawal of Fosinopril sodium has not resulted in a rapid increase in blood pressure.

Limited experience in controlled and uncontrolled trials combining Fosinopril with a calcium channel blocker or a loop diuretic has indicated no usual drug-drug interactions. Other ACE inhibitors have had less than additive effects with beta-adrenergic blockers, presumably because both drugs lower blood pressure by inhibiting parts of the renin-angiotensin system.
ACE inhibitors are generally less effective in blacks than in non-blacks. The effectiveness of Fosinopril sodium was not influenced by age, sex, or weight.

In hemodynamic studies in hypertensive patients, after three months of therapy, responses (changes in BP, heart rate, cardiac index, and PVR) to various stimuli (e.g., isometric exercise, 45° head-up tilt, and mental challenge) were unchanged compared to baseline, suggesting that Fosinopril sodium does not affect the activity of the sympathetic nervous system. Reduction in systemic blood pressure appears to have been mediated by a decrease in peripheral vascular resistance without reflex cardiac effects. Similarly, renal, splanchnic, cerebral, and skeletal muscle blood flows were unchanged compared to baseline, as was glomerular filtration rate.

Pediatric
Reduction of blood pressure with low (0.1 mg/kg), medium (0.3 mg/kg) and high (0.6 mg/kg) target doses of once-daily Fosinopril was evaluated in a randomized, double-blind study of 252 pediatric patients 6 to 16 years of age with hypertension or high-normal blood pressure. Fosinopril doses in the medium and high dose groups were titrated to target doses after one week and the total duration of treatment was four weeks. The maximum dose studied was 40 mg once daily. At the end of four weeks of treatment, the mean reductions from baseline in trough systolic blood pressure were similar in all three dose groups. Withdrawal of Fosinopril treatment resulted in an increase in blood pressure towards baseline over a two week period. Fosinopril was generally well tolerated.

Heart Failure

In a randomized, double-blind, placebo-controlled trial, 179 patients with heart failure, all receiving diuretics and some receiving digoxin, were administered single doses of 10,20,or 40 mg of Fosinopril sodium or placebo. Doses of 20 and 40 mg of Fosinopril sodium resulted in acute decreases in pulmonary capillary wedge pressure (preload) and mean arterial blood pressure and systemic vascular resistance (afterload). One hundred fifty-five of these patients were re-randomized to once daily therapy with Fosinopril sodium (10, 20, or 40 mg) for an additional 10 weeks. Hemodynamic measurements made 24 hours after dosing showed (relative to baseline) continued reduction in pulmonary capillary wedge pressure, mean arterial blood pressure, right atrial pressure and an increase in cardiac index and stroke volume for the 20 mg and 40 mg dose groups. No tachyphylaxis was seen.

Fosinopril sodium was studied in 3 double-blind, placebo controlled, 12 to 24 week trials including a total of 734 patients with heart failure, with Fosinopril sodium doses from 10 mg to 40 mg daily. Concomitant therapy in 2 of these 3 trials included diuretics and digitalis; in the third trial patients were receiving only diuretics. All 3 trials showed statistically significant benefits of Fosinopril sodium therapy, compared to placebo, in one or more of the following: exercise tolerance (one study), symptoms of dyspnea, orthopnea and paroxysmal nocturnal dyspnea (2 studies), NYHA classification (2 studies), hospitalization for heart failure (2 studies), study withdrawals for worsening heart failure (2 studies), and/or need for supplemental diuretics (2 studies). Favorable effects were maintained for up to two years. Effects of Fosinopril sodium on long-term mortality in heart failure have not been evaluated. The once daily dosage for the treatment of congestive heart failure was the only dosage regimen used during clinical trial development and was determined by the measurement of hemodynamic responses.

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.

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 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 angiotensinconverting 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.

When Fosinopril was given to pregnant rats at doses about 80 to 250 times (on a mg/kg basis) the maximum recommended human dose, three similar orofacial malformations and one fetus with situs inversus were observed among the offspring.

Hepatic Failure

Rarely, ACE Inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

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 be 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.

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 one hour of the ingestion, she made an uneventful recovery.

24 hours

Half-Life Elimination

Serum (fosinoprilat):

Children and Adolescents 6-16 years: 11-13 hours

Adults: 12 hours

Adults with CHF: 14 hours

Protein Binding

>99%

There are no dosage adjustments provided in the manufacturer’s labeling.

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

More frequently reported side effects include: cough and headache. See below for a comprehensive list of adverse effects.