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Fosinopril (Monograph)

Drug class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA class: CV800
Molecular formula: C30H46NO7P
CAS number: 88889-14-9

Medically reviewed by Drugs.com on Feb 23, 2024. Written by ASHP.

Warning

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 62 63 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue fosinopril as soon as possible.1 63

Introduction

Nonsulfhydryl ACE inhibitor.1 2 3

Uses for Fosinopril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 1200

ACE inhibitors are recommended as one of several preferred agents for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501 502 504 1200

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of < 130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 536 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.44 45 60 61 501 504 1200 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.1200

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.501 502 504 523 524 525 526 527 534 535 536 543 1200 1214 1215

Heart Failure

Management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).1 15 524 800

Some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.702 800

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria† [off-label] who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.53 54 55 56 57 535 536 1232

Fosinopril Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally once daily.1 Manufacturer makes no specific recommendations regarding administration with meals.1 43

Dosage

Available as fosinopril sodium; dosage expressed in terms of the salt.1

May minimize risk of hypotension in patients currently receiving diuretic therapy by discontinuing the diuretic, reducing diuretic dosage, or increasing salt intake prior to initiating fosinopril; if these changes are not possible, reduce initial fosinopril sodium dosage and observe patient closely for several hours until BP has stabilized.600 (See Hypotension under Cautions and see the individual dosage sections in Dosage and Administration.)

Pediatric Patients

Hypertension
Oral

Children ≥6 years of age and weighing <50 kg: Initial dosage of 0.1 mg/kg (up to 5 mg) daily recommended by some experts;1150 however, a dosage form suitable for providing an appropriate dosage for children weighing <50 kg is not commercially available in the US.1 Safety and efficacy of dosages >40 mg daily not established.1150

Children ≥6 years of age and weighing >50 kg: 5–10 mg once daily.1 1150 Some experts state that the drug should be initiated at the low end of the dosage range; dosage should be increased every 2–4 weeks until BP controlled, maximum dosage reached, or adverse effects occur.1150 Safety and efficacy of dosages >40 mg daily not established.1150

Adults

Hypertension
Fosinopril Therapy
Oral

Initially, 10 mg once daily in patients not receiving a diuretic.600 Adjust dosage based on BP response.600

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating fosinopril.3 600 May resume diuretic therapy if BP not controlled adequately with fosinopril alone.600 If usual initial dosage of 10 mg daily is used in patients receiving a diuretic, administer under close medical supervision for several hours until BP has stabilized.600

Usual maintenance dosage: Manufacturer states 20–40 mg daily.600 Some experts state 10–40 mg once daily.1200 Higher dosages (e.g., 80 mg daily) reportedly have resulted in increased response in some patients.600

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in divided doses.600

Fosinopril/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.43

If BP is not adequately controlled by monotherapy with fosinopril, can switch to the fixed-combination preparation containing fosinopril sodium 10 mg and hydrochlorothiazide 12.5 mg, or alternatively, fosinopril sodium 20 mg and hydrochlorothiazide 12.5 mg.43 43

On average, antihypertensive effect of fosinopril sodium 10 mg and hydrochlorothiazide 12.5 mg is similar to that of fosinopril sodium 40 mg or hydrochlorothiazide 37.5 mg as monotherapy.43

Heart Failure
Oral

Initially, 10 mg daily.1 524 If patient has been treated vigorously with diuretics, 5 mg initially.1 524 Monitor closely for ≥2 hours until BP has stabilized.1 To minimize risk of hypotension, reduce diuretic dosage, if possible.1

Adjust dosage gradually over several weeks to maximum tolerated dosage (up to 40 mg daily).1 524

Usual dosage: 20–40 mg once daily.1

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 40 mg daily.1 1150

Adults

Heart Failure
Oral

Maximum 40 mg daily.1

Special Populations

Hepatic Impairment

No specific dosage recommendations.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Hypertension

Dosage adjustment not required.1

Fosinopril/hydrochlorothiazide fixed combinations are not recommended in patients with Clcr <30 mL/minute or Scr ≥3 mg/dL.601

Heart Failure

Initially, 5 mg in patients with moderate to severe renal impairment.1

Geriatric Patients

Select dosage carefully; monitoring renal function may be useful.1

Detailed Fosinopril dosage information

Cautions for Fosinopril

Contraindications

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis, patients with diarrhea or vomiting).1

Risk of marked hypotension, sometimes associated with oliguria, azotemia, and, rarely, death, in patients with heart failure with or without associated renal insufficiency.1

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.1

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.1

May minimize potential for hypotension by correcting volume and/or salt depletion prior to initiating fosinopril therapy.1

Initiate therapy in patients with heart failure under close medical supervision; monitor closely for first 2 weeks following initiation of fosinopril or any increase in fosinopril or diuretic dosage.1 Consider reduced diuretic dosage in patients with low to normal BP who are hyponatremic or have received vigorous diuretic therapy.600

If excessive hypotension occurs, immediately place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride.1 Fosinopril therapy usually can be continued following restoration of volume and BP.1

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.1 63 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.63

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.62 63

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.63 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.31 33

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.1

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.1

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril; risk of neutropenia appears to depend principally on presence of renal impairment and presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma); risk with fosinopril is unknown.1

Consider monitoring leukocytes in patients with collagen vascular disease, especially if renal impairment exists.1

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; angioedema involving tongue, glottis, or larynx may be fatal.1 If angioedema occurs, promptly discontinue perindopril and observe patient until swelling disappears.1 Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.1

Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.1 43

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.1

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.1

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.1

General Precautions

Renal Effects

Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.1 Possible increases in BUN and Scr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitor and/or diuretic.1

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe heart failure.1

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis.1 43 Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.1

Hyperkalemia

Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).1

Monitor serum potassium concentration carefully in these patients.1

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.1

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.43

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).1 (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Distributed into milk.1 Use not recommended.1

Pediatric Use

Safety and efficacy not established in children <6 years of age.1

Safety and efficacy of fosinopril in combination with hydrochlorothiazide not established in children.43

Geriatric Use

Insufficient experience in patients >65 years of age to determine whether geriatric patients respond differently than younger adults.1

Select dosage with caution because of greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in the elderly.1

Hepatic Impairment

Systemic exposure to fosinoprilat may be increased (see Special Populations under Pharmacokinetics), but no specific dosage recommendations.1

Renal Impairment

Deterioration of renal function may occur.1 (See Renal Effects under Cautions.)

Dosage adjustment generally not required in patients with hypertension.1 Decrease initial dose in patients with heart failure and moderate to severe renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Fosinopril/hydrochlorothiazide fixed combinations are not recommended in patients with Clcr <30 mL/minute or Scr ≥3 mg/dL.43

Black Patients

BP reduction may be smaller in black patients compared with patients of other races.44 45 (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.1 45 1200

Common Adverse Effects

Patients with hypertension: Cough, dizziness, nausea/vomiting.1

Patients with heart failure: Dizziness, cough, hypotension, musculoskeletal pain, nausea/vomiting, diarrhea, chest pain (noncardiac).1

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Antacids (aluminum-, magnesium-, and simethicone-containing)

Possible decreased fosinopril absorption1

Administer 2 hours apart1

Aspirin

Effect on fosinopril bioavailability unlikely1

Cimetidine

Effect on fosinopril bioavailability unlikely1

Digoxin

Effect on fosinopril bioavailability unlikely1

Diuretics

Increased hypotensive effect1

If possible, discontinue diuretic before initiating fosinopril1 (See Dosage under Dosage and Administration)

Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentration frequently1

Lithium

Increased lithium concentrations; possible toxicity1

Use with caution, monitor lithium concentrations frequently1

Potassium supplements or potassium-containing salt substitutes

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Propantheline

Effect on fosinopril bioavailability unlikely1

Propranolol

Effect on fosinopril bioavailability unlikely1

Warfarin

Pharmacokinetic or pharmacologic interaction unlikely1
Fosinopril drug interactions (more detail)

Fosinopril Pharmacokinetics

Absorption

Bioavailability

About 36% of oral dose is absorbed.1 Peak plasma concentration is achieved in approximately 3 hours.1

Onset

Following a single oral dose, antihypertensive effects are observed within 1 hour, with peak BP reductions at 2–6 hours.1

Duration

Antihypertensive effect of a single dose persists for about 24 hours.1

Food

Food may decrease rate but not extent of absorption.1 2

Distribution

Extent

Does not appear to cross blood-brain barrier.1

Crosses the placenta in animals.1 Distributed into human milk.1

Plasma Protein Binding

Fosinoprilat: About 99%.1

Elimination

Metabolism

Metabolized in the liver and gut wall, principally to an active metabolite (fosinoprilat).1

Elimination Route

Eliminated approximately equally by the liver and kidney.1

Not appreciably removed by hemodialysis or peritoneal dialysis.1

Half-life

Fosinoprilat: Approximately 12 hours.1

Special Populations

In patients with alcoholic or biliary cirrhosis, rate but not extent of metabolism of fosinopril may be decreased; clearance of fosinoprilat is approximately one-half that in patients with normal hepatic function.1

In patients with Clcr of 10–80 mL/minute, clearance of fosinoprilat is not appreciably altered.1 In patients with Clcr <10 mL/minute, clearance of fosinoprilat is approximately one-half that in patients with normal renal function.1

Stability

Storage

Oral

Tablets

15–30°C; protect from moisture.1 43

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Fosinopril Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg*

Fosinopril Sodium Tablets

20 mg*

Fosinopril Sodium Tablets

40 mg*

Fosinopril Sodium Tablets

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Fosinopril Sodium Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg with Hydrochlorothiazide 12.5 mg*

Fosinopril Sodium and Hydrochlorothiazide Tablets

20 mg with Hydrochlorothiazide 12.5 mg*

Fosinopril Sodium and Hydrochlorothiazide Tablets

AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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