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Moexipril (Monograph)

Drug class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA class: CV800
Chemical name: (3S-(2(R*(R*)),3R*))-2-(2-((1 -(Ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid monohydrochloride
Molecular formula: C27H34N2O7•ClH
CAS number: 82586-52-5

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 83 110 111 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • If pregnancy is detected, discontinue as soon as possible.1 111

Introduction

Nonsulfhydryl ACE inhibitor.1

Uses for Moexipril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 5 25 83 1200

ACE inhibitors are recommended as one of several preferred drugs 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 1213

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 potentials 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.25 83 92 93 108 109 501 504 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† [off-label], usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).10 11 12 14 96 524 800

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.103 104 105 106 107 535 536 1232

Moexipril Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Oral Administration

Administer orally once or twice daily 1 hour before meals.1 3 83

Dosage

Available as moexipril hydrochloride; dosage expressed in terms of the salt.1 83

Adults

Hypertension
Moexipril Therapy
Oral

Initially, 7.5 mg once daily in patients not receiving a diuretic.1 5

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating moexipril or cautiously increase salt intake.1 8 9 10 11 12 13 14 37 46 May resume diuretic therapy if BP not controlled adequately with moexipril alone.1 28 29 30 39 If diuretic cannot be discontinued, give lower initial moexipril dose (3.75 mg) under close medical supervision until BP has stabilized.8 10 11 12 13 14 83 84

Usual dosage: 7.5–30 mg daily, given in 1 dose or 2 divided doses.1 83 1200

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.1

Moexipril/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.83

If BP is not adequately controlled by monotherapy with moexipril, can switch to the fixed-combination preparation containing moexipril hydrochloride 7.5 mg and hydrochlorothiazide 12.5 mg, moexipril hydrochloride 15 mg and hydrochlorothiazide 12.5 mg, or moexipril hydrochloride 15 mg and hydrochlorothiazide 25 mg.83 Adjust dosage of either or both drugs according to patient’s response.83

Prescribing Limits

Adults

Hypertension
Oral

Usually, maximum 30 mg daily.1 Dosages >60 mg daily have not been extensively evaluated in hypertensive patients.1 5

Special Populations

Renal Impairment

Hypertension
Oral

Initially, 3.75 mg once daily in patients with severe renal impairment (Clcr ≤40 mL/minute); titrate until BP is controlled or to maximum of 15 mg daily.1

Moexipril/hydrochlorothiazide fixed combination is not recommended in patients with severe renal impairment.83

Volume- and/or Salt-depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.1

Detailed Moexipril dosage information

Cautions for Moexipril

Contraindications

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.1 111 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.111

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.110 111

Discontinue ACE inhibitors (e.g., moexipril) as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.1 110 111 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.75

Hypotension

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

Risk of marked hypotension, sometimes associated with oliguria and azotemia, and rarely acute renal failure and death in patients with heart failure with or without associated renal insufficiency.1 Severe hypotension may result in MI or stroke in patients with ischemic heart disease, aortic stenosis, or cerebrovascular disease.1 12 34 35 36

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 withholding diuretic therapy and/or increasing sodium intake for 2–3 days prior to initiation of moexipril.1

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).1

Initiate therapy in patients with heart failure (with or without associated renal insufficiency) under close medical supervision; monitor closely for first 2 weeks following initiation of moexipril or any increase in moexipril or diuretic dosage.1

Neutropenia/Agranulocytosis

Neutropenia and agranulocytosis reported with ACE inhibitors.1 83 Risk of neutropenia appears to depend principally on degree of renal impairment and presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma); risk with moexipril is unknown.1 83

Consider monitoring leukocytes in patients with collagen vascular disease, especially if renal impairment exists.1 83

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

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible; if associated with laryngeal edema, may be fatal.1 83 Immediate medical intervention (e.g., epinephrine) required for involvement of tongue, glottis, or larynx.1 83 Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.1 83

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption1 51 52 83 or following initiation of hemodialysis that utilized high-flux membrane.1 47 48 49 83

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.1 83

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.1 83

General Precautions

Renal Effects

Inhibition of renin-angiotensin-aldosterone (RAA) system may cause renal impairment, and, rarely, acute renal failure and/or death in susceptible patients (e.g., hypertensive patients with severe heart failure).1 83

Deterioration in renal function possible in hypertensive patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitors and/or diuretic.1 83

Closely monitor renal function for first few weeks following initiation of therapy and periodically thereafter in such patients.1 83 Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.1 83

Effects on Potassium

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 (See Specific Drugs under Interactions.)

Monitor serum potassium concentration carefully in these patients.1

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.1

Surgery/Anesthesia

Hypotension may occur during surgery or anesthesia with agents that produce hypotension; moexipril may block the effects on compensatory renin release in such patients.1 83 May correct such hypotension by volume expansion.1 83

Use of Fixed Combinations

When moexipril is used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.83

Specific Populations

Pregnancy

Category D.1 83

Can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.1 83 (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Not known whether moexipril is distributed into milk.1 Caution advised if used in nursing women.1

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to moexipril, support BP and renal function; exchange transfusions or dialysis may be required.1 83 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Safety and efficacy not established.1

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 age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1

Renal Impairment

Systemic exposure to moexipril and moexiprilat may be increased.1 Initial dosage adjustment recommended in patients with severe renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Moexipril/hydrochlorothiazide fixed combination is not recommended in patients with severe renal impairment.83

Black Patients

BP reduction may be smaller in black patients compared with patients of other races.25 83 92 93 108 109 (See Hypertension under Uses.)

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

Common Adverse Effects

Cough, dizziness, diarrhea, flu syndrome, fatigue, pharyngitis, flushing, rash, myalgia.1

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Aliskiren

Increased risk of renal impairment, hyperkalemia, and hypotension1 83

Generally, avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1 83

Angiotensin II receptor antagonists

Increased risk of renal impairment, hyperkalemia, and hypotension1 83

Generally, avoid concomitant use; monitor BP, renal function, and electrolytes if used concomitantly1 83

Anticoagulants, oral

Clinically important interaction not observed1

Cimetidine

Clinically important interaction not observed1

Digoxin

Clinically important interaction not observed1

Diuretics

Increased hypotensive effect1

If possible, discontinue diuretic before initiating moexipril1 (see Dosage under Dosage and Administration)

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

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Gold

Nitroid reactions reported rarely in patients receiving concomitant therapy with sodium aurothiomalate and an ACE inhibitor1 83

Lithium

Increased serum lithium concentrations; possible toxicity1

Use with caution; monitor serum lithium concentration frequently1

NSAIAs (including COX-2 inhibitors)

May result in deterioration of renal function, including possible renal failure, in geriatric patients, volume-depleted patients, or patients with compromised renal function;1 83 effects usually reversible1 83

Monitor renal function periodically 1 83

Potassium supplements or potassium-containing salt substitutes.

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1
Moexipril drug interactions (more detail)

Moexipril Pharmacokinetics

Absorption

Bioavailability

About 13% of oral dose is absorbed.1 Peak plasma concentration of moexiprilat is achieved within about 1.5 hours.1

Onset

Following a single oral dose, antihypertensive effects are observed within about 1 hour with peak BP reduction at 3–6 hours.1

During chronic therapy, maximum antihypertensive effect with any dose is achieved after 4 weeks.1

Duration

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

Food

Food reduces peak plasma concentration of moexipril; administer 1 hour before meals.1

Special Populations

In patients with cirrhosis, peak plasma concentration and AUC of moexipril following a single oral dose were increased, while peak plasma concentration of moexiprilat was decreased and AUC of moexiprilat was increased.1

In patients with renal impairment, increased moexipril and moexiprilat concentrations.1

Distribution

Extent

Not known whether distributed into milk.1

Plasma Protein Binding

Moexiprilat: 50%.1

Elimination

Metabolism

Metabolized in the liver, principally to an active metabolite, moexiprilat.1

Elimination Route

Following oral administration, eliminated in feces (53%), principally as moexiprilat, and to a lesser extent in urine (13%).1

Following IV administration, eliminated principally in urine, as moexiprilat (40%) and moexipril (26%), and to lesser extent in feces (about 20%, mainly as moexiprilat).1

Half-life

Moexiprilat: 12 hours.1

Special Populations

In patients with renal impairment (Clcr 10–40 mL/minute), threefold to fourfold increase in moexiprilat half-life.1

Stability

Storage

Oral

Tablets

Tight containers at 15–30°C.1

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

Moexipril Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

7.5 mg*

Moexipril Hydrochloride Tablets

15 mg*

Moexipril Hydrochloride Tablets

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

Moexipril Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

7.5 mg with Hydrochlorothiazide 12.5 mg*

Moexipril Hydrochloride and Hydrochlorothiazide Tablets

15 mg with Hydrochlorothiazide 12.5 mg*

Moexipril Hydrochloride and Hydrochlorothiazide Tablets

15 mg with Hydrochlorothiazide 25 mg*

Moexipril Hydrochloride 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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