Moexipril Hydrochloride

Nonsulfhydryl ACE inhibitor.1

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 500

ACE inhibitors are recommended as one of several preferred drugs for the initial management of hypertension; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501 502 503 504 While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.500 501 502 504 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).500 501 502 503 504 515

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease, or cerebrovascular disease or post-MI.500 501 502 504 520 523 524 525 526 527 534 535 536 543

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors.25 83 92 93 108 109 500 501 504 However, diminished response to an ACE inhibitor is largely eliminated when administered concomitantly with a calcium-channel blocker or thiazide diuretic.25 83 500 504

The optimum BP threshold for initiating antihypertensive drug therapy is controversial.501 504 505 506 507 508 515 523 530 Further study needed to determine optimum BP thresholds/goals; individualize treatment decisions.501 503 507 515 526 530

JNC 7 recommends initiation of drug therapy in all patients with uncomplicated hypertension and BP ≥140/90 mm Hg;500 JNC 8 panel recommends SBP threshold of 150 mm Hg for patients ≥60 years of age.501 Although many experts agree that SBP goal of <150 mm Hg may be appropriate for patients ≥80 years of age,502 504 505 530 application of this goal to those ≥60 years of age is controversial, especially for those at higher cardiovascular risk.501 502 505 506 508 511 515

In the past, initial antihypertensive drug therapy was recommended for patients with diabetes mellitus or chronic kidney disease who had BP ≥130/80 mm Hg;500 503 current hypertension management guidelines generally recommend a BP threshold of 140/90 mm Hg for these individuals (same as for the general population of patients without these conditions), although a goal of <130/80 mm Hg may still be considered.501 502 503 504 520 530 535 536 541

Heart Failure

Management of heart failure†, 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† 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.103 104 105 106 107 520 535 536

Contraindications

• Known hypersensitivity (e.g., history of angioedema) to moexipril or another ACE inhibitor.1 83

Warnings/Precautions

Warnings

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 and agranulocytosis reported with captopril; 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

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 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

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) 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

Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.1 83 Possible increases in BUN and Scr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitors and/or diuretic.1 83

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe heart failure.1 83

Closely monitor renal function following initiation of therapy in such patients.1 83 Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic and/or adequate sodium repletion.1 83

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

Persistent and nonproductive cough; resolves after drug discontinuance.1

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

Specific Populations

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

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

Safety and efficacy not established.1

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

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

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.1 500

Common Adverse Effects

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

• Prodrug; not pharmacologically active until hydrolyzed in the liver to moexiprilat.1

• Suppresses the renin-angiotensin-aldosterone system.1

• Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.1 Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.1

• Importance of reporting signs of infection (e.g., sore throat, fever).1

• Risk of hypotension.1 Importance of informing clinicians promptly if lightheadedness or fainting occurs.1

• Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.1

• Risks of use during pregnancy.1 110 111 (See Boxed Warning.)

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).1

• Importance of taking moexipril 1 hour before meals.1

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of advising patients of other important precautionary information.1 (See Cautions.)