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Univasc

Generic Name: Moexipril Hydrochloride
Class: Angiotensin-Converting Enzyme 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

Warning(s)

  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.1 110 111 (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 Univasc

Hypertension

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

One of several preferred initial therapies in hypertensive patients with heart failure, post-MI, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.95

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Can be used as monotherapy for initial management of uncomplicated hypertension;1 however, thiazide diuretics are preferred by JNC 7.95

CHF

Management of symptomatic CHF, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.10 11 12 14 94 96

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy in hypertensive patients with diabetes mellitus.100 101 102

Univasc Dosage and Administration

General

  • Moexipril/hydrochlorothiazide fixed combination should not be used for initial treatment of hypertension.83

Administration

Oral Administration

Administer orally once or twice daily 1 hour before meals.1 3 18 83

Dosage

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

Adults

Hypertension
Oral

Initially, 7.5 mg once daily as monotherapy.1 3 5 18 95

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating moexipril.1 8 9 10 11 12 13 14 37 46 May cautiously resume diuretic therapy if BP not controlled adequately with moexipril alone.1 28 29 30 39 If diuretic cannot be discontinued, increase sodium intake and give lower initial moexipril dose (3.75 mg) under close medical supervision.1 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 95

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 Combination Therapy
Oral

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

Cautions for Univasc

Contraindications

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

Warnings/Precautions

Warnings

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, or with CHF).1 Risk of marked hypotension, sometimes associated with oliguria and azotemia, and rarely acute renal failure and death in patients with CHF 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 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 CHF (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

Hematologic Effects

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

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 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

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) 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

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 CHF.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

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 (See Specific Drugs under Interactions.)

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.83

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

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

Pediatric Use

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

Blacks

BP reduction may be smaller in black patients compared with nonblack patients; however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.25 83 92 93 95 108 109 Use in combination with a diuretic.25 83 86 95

Higher incidence of angioedema reported with ACE inhibitors in blacks compared with other races.1

Common Adverse Effects

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

Interactions for Univasc

Specific Drugs

Drug

Interaction

Comments

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

Lithium

Increased serum lithium concentrations; possible toxicity1

Use with caution; monitor serum lithium concentration frequently1

Potassium supplements or potassium-containing salt substitutes.

Enhanced hyperkalemic effect1

Use with caution; monitor serum potassium concentrations frequently1

Univasc 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

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

  • Suppresses the renin-angiotensin-aldosterone system.1

Advice to Patients

  • 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.)

Preparations

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

* 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

Teva

Univasc (scored)

Schwarz

15 mg*

Moexipril Hydrochloride Tablets

Teva

Univasc (scored)

Schwarz

Moexipril Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

7.5 mg with Hydrochlorothiazide 12.5 mg

Uniretic (scored)

Schwarz

15 mg with Hydrochlorothiazide 12.5 mg

Uniretic (scored)

Schwarz

15 mg with Hydrochlorothiazide 25 mg

Uniretic (scored)

Schwarz

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Moexipril HCl 15MG Tablets (PADDOCK): 30/$41.99 or 90/$109.98

Moexipril HCl 7.5MG Tablets (KREMERS URBAN): 30/$40.99 or 90/$100.97

Moexipril-Hydrochlorothiazide 15-12.5MG Tablets (WATSON LABS): 100/$109.98 or 300/$315.96

Moexipril-Hydrochlorothiazide 15-25MG Tablets (WATSON LABS): 30/$36.99 or 90/$89.97

Moexipril-Hydrochlorothiazide 7.5-12.5MG Tablets (WATSON LABS): 30/$37.99 or 90/$95.97

Uniretic 15-12.5MG Tablets (SCHWARZ PHARMA): 30/$84.99 or 90/$228.98

Uniretic 15-25MG Tablets (SCHWARZ PHARMA): 30/$84.99 or 90/$228.98

Uniretic 7.5-12.5MG Tablets (SCHWARZ PHARMA): 30/$84.99 or 90/$231.97

Univasc 15MG Tablets (SCHWARZ PHARMA): 30/$85.99 or 90/$229.96

Univasc 7.5MG Tablets (SCHWARZ PHARMA): 30/$61.99 or 90/$164.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

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