FDA Label for Moexipril Hydrochloride

Warning Fetal Toxicity

                                                                                                                                              See full prescribing information for complete boxed warning.

• When pregnancy is detected, discontinue moexipril hydrochloride tablets as soon as possible.
• Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. SeeWARNINGS: Fetal Toxicity

Description

Moexipril Hydrochloride, USP, the hydrochloride salt of moexipril, has the empirical formula C ₂₇H ₃₄N ₂O ₇•HCl and a molecular weight of 535.04. It is chemically described as [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. It is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat and its structural formula is:

"Image Description" - moexipril hcl tabs structure

Moexipril Hydrochloride, USP is a fine white to off-white powder. It is soluble (about 10% weight-to-volume) in distilled water at room temperature.

Moexipril Hydrochloride Tablets, USP are supplied as scored, film-coated tablets containing 7.5 mg and 15 mg of moexipril hydrochloride for oral administration. In addition to the active ingredient, moexipril hydrochloride, the tablet core contains the following inactive ingredients: lactose monohydrate, crospovidone, magnesium oxide, povidone, colloidal silicon dioxide, and magnesium stearate. The film-coating contains hypromellose, polyethylene glycol, titanium dioxide, iron oxide red and iron oxide yellow.

Clinical Pharmacology

Mechanism Of Action

Moexipril hydrochloride is a prodrug for moexiprilat, which inhibits ACE in humans and animals. The mechanism through which moexiprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes the conversion of the inactive decapeptide angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates aldosterone secretion by the adrenal cortex and provides negative feedback on renin secretion. ACE is identical to kininase II, an enzyme that degrades bradykinin, an endothelium-dependent vasodilator. Moexiprilat is about 1000 times as potent as moexipril in inhibiting ACE and kininase II. Inhibition of ACE results in decreased angiotensin II formation, leading to decreased vasoconstriction, increased plasma renin activity, and decreased aldosterone secretion. The latter results in diuresis and natriuresis and a small increase in serum potassium concentration (mean increases of about 0.25 mEq/L were seen when moexipril was used alone, see PRECAUTIONS).

Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of moexipril remains to be elucidated. Although the principal mechanism of moexipril in blood pressure reduction is believed to be through the renin-angiotensin-aldosterone system, ACE inhibitors have some effect on blood pressure even in apparent low-renin hypertension. As is the case with other ACE inhibitors, however, the antihypertensive effect of moexipril is considerably smaller in black patients, a predominantly low-renin population, than in non-black hypertensive patients.

Pharmacodynamics And Clinical Effect

Single and multiple doses of 15 mg or more of moexipril hydrochloride tablets give sustained inhibition of plasma ACE activity of 80-90%, beginning within 2 hours and lasting 24 hours (80%).

In controlled trials, the peak effects of orally administered moexipril increased with the dose administered over a dose range of 7.5 to 60 mg, given once a day. Antihypertensive effects were first detectable about 1 hour after dosing, with a peak effect between 3 and 6 hours after dosing. Just before dosing (i.e., at trough), the antihypertensive effects were less prominently related to dose and the antihypertensive effect tended to diminish during the 24-hour dosing interval when the drug was administered once a day.

In multiple dose studies in the dose range of 7.5 to 30 mg once daily, moexipril hydrochloride tablets lowered sitting diastolic and systolic blood pressure effects at trough by 3 to 6 mmHg and 4 to 11 mmHg more than placebo, respectively. There was a tendency toward increased response with higher doses over this range. These effects are typical of ACE inhibitors but, to date, there are no trials of adequate size comparing moexipril with other antihypertensive agents.

The trough diastolic blood pressure effects of moexipril were approximately 3 to 6 mmHg in various studies. Generally, higher doses of moexipril leave a greater fraction of the peak blood pressure effect still present at trough. During dose titration, any decision as to the adequacy of a dosing regimen should be based on trough blood pressure measurements. If diastolic blood pressure control is not adequate at the end of the dosing interval, the dose can be increased or given as a divided (BID) regimen.

During chronic therapy, the antihypertensive effect of any dose of moexipril hydrochloride tablets is generally evident within 2 weeks of treatment, with maximal reduction after 4 weeks. The antihypertensive effects of moexipril hydrochloride tablets have been proven to continue during therapy for up to 24 months.

Moexipril hydrochloride tablets, like other ACE inhibitors, are less effective in decreasing trough blood pressures in blacks than in non-blacks. Placebo-corrected trough group mean diastolic blood pressure effects in blacks in the proposed dose range varied between +1 to -3 mmHg compared with responses in non-blacks of -4 to -6 mmHg.

The effectiveness of moexipril hydrochloride tablets was not significantly influenced by patient age, gender, or weight. Moexipril hydrochloride tablets have been shown to have antihypertensive activity in both pre- and post-menopausal women who have participated in placebo-controlled clinical trials.

Formal interaction studies with moexipril have not been carried out with antihypertensive agents other than thiazide diuretics. In these studies, the added effect of moexipril was similar to its effect as monotherapy. In general, ACE inhibitors have less than additive effects with beta-adrenergic blockers, presumably because both work by inhibiting the renin-angiotensin system.

Indications And Usage

Moexipril hydrochloride tablets are indicated for treatment of patients with hypertension. It may be used alone or in combination with thiazide diuretics.

In using moexipril hydrochloride tablets, consideration should be given to the fact that another ACE inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that moexipril hydrochloride tablets do not have a similar risk (see WARNINGS).

In considering use of moexipril hydrochloride tablets, it should be noted that in controlled trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. In addition, ACE inhibitors (for which adequate data are available) cause a higher rate of angioedema in black than in non-black patients (see WARNINGS, Angioedema).

Contraindications

Moexipril hydrochloride tablets are contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an ACE inhibitor.

Do not co-administer aliskiren with moexipril hydrochloride tablets in patients with diabetes (see PRECAUTIONS, Drug Interactions).

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 moexipril hydrochloride tablets, may be subject to a variety of adverse reactions, some of them serious.

Hypotension

Moexipril hydrochloride tablets can cause symptomatic hypotension, although, as with other ACE inhibitors, this is unusual in uncomplicated hypertensive patients treated with moexipril hydrochloride tablets alone. Symptomatic hypotension was seen in 0.5% of patients given moexipril and led to discontinuation of therapy in about 0.25%. Symptomatic hypotension is most likely to occur in patients who have been salt- and volume-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume- and salt-depletion should be corrected and, in general, diuretics stopped, before initiating therapy with moexipril hydrochloride tablets (see PRECAUTIONS, Drug Interactions, and ADVERSE REACTIONS).

In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or progressive azotemia, and rarely, with acute renal failure and death. In these patients, moexipril hydrochloride tablets therapy should be started under close medical supervision, and patients should be followed closely for the first two weeks of treatment and whenever the dose of moexipril or an accompanying diuretic is increased. Care in avoiding hypotension should also be taken in patients with ischemic heart disease, aortic stenosis, or cerebrovascular disease, in whom an excessive decrease in blood pressure could result in a myocardial infarction or a cerebrovascular accident.

If hypotension occurs, the patient should be placed in a supine position and, if necessary, treated with an intravenous infusion of normal saline. Moexipril hydrochloride tablets treatment usually can be continued following restoration of blood pressure and volume.

Neutropenia/Agranulocytosis

Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in patients with uncomplicated hypertension, but more frequently in hypertensive patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Although there were no instances of severe neutropenia (absolute neutrophil count <500/mm ³) among patients given moexipril hydrochloride tablets, as with other ACE inhibitors, monitoring of white blood cell counts should be considered for patients who have collagen-vascular disease, especially if the disease is associated with impaired renal function. Available data from clinical trials of moexipril hydrochloride tablets are insufficient to show that moexipril hydrochloride tablets do not cause agranulocytosis at rates similar to captopril.

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 moexipril hydrochloride tablets 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 moexipril hydrochloride tablets, 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 moexipril hydrochloride tablets for hypotension, oliguria, and hyperkalemia. (see Precautions, Pediatric Use).

No embryotoxic, fetotoxic, or teratogenic effects were seen in rats or in rabbits treated with up to 90.9 and 0.7 times, respectively, the Maximum Recommended Human Dose (MRHD) on a mg/m ²basis.

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.

Information For Patients

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No evidence of carcinogenicity was detected in long-term studies in mice and rats at doses up to 14 or 27.3 times the Maximum Recommended Human Dose (MRHD) on a mg/m ²basis.

No mutagenicity was detected in the Ames test and microbial reverse mutation assay, with and without metabolic activation, or in an in vivonucleus anomaly test. However, increased chromosomal aberration frequency in Chinese hamster ovary cells was detected under metabolic activation conditions at a 20-hour harvest time.

Reproduction studies have been performed in rabbits at oral doses up to 0.7 times the MRHD on a mg/m ²basis, and in rats up to 90.9 times the MRHD on a mg/m ²basis. No indication of impaired fertility, reproductive toxicity, or teratogenicity was observed.

Nursing Mothers

It is not known whether moexipril hydrochloride tablets are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when moexipril hydrochloride tablets are given to a nursing mother.

Pediatric Use

Neonates with a history of in uteroexposure to moexipril hydrochloride tablets

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

Safety and effectiveness of moexipril hydrochloride tablets in pediatric patients have not been established.

Geriatric Use

Clinical studies of moexipril hydrochloride tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Adverse Reactions

Moexipril hydrochloride tablets have been evaluated for safety in more than 2500 patients with hypertension; more than 250 of these patients were treated for approximately one year. The overall incidence of reported adverse events was only slightly greater in patients treated with moexipril hydrochloride tablets than patients treated with placebo.

Reported adverse experiences were usually mild and transient, and there were no differences in adverse reaction rates related to gender, race, age, duration of therapy, or total daily dosage within the range of 3.75 mg to 60 mg. Discontinuation of therapy because of adverse experiences was required in 3.4% of patients treated with moexipril hydrochloride tablets and in 1.8% of patients treated with placebo. The most common reasons for discontinuation in patients treated with moexipril hydrochloride tablets were cough (0.7%) and dizziness (0.4%).

All adverse experiences considered at least possibly related to treatment that occurred at any dose in placebo-controlled trials of once-daily dosing in more than 1% of patients treated with moexipril hydrochloride tablets alone and that were at least as frequent in the moexipril hydrochloride tablets group as in the placebo group are shown in the following table:

ADVERSE EVENTS IN PLACEBO-CONTROLLED STUDIES

Other adverse events occurring in more than 1% of patients on moexipril that were at least as frequent on placebo include: headache, upper respiratory infection, pain, rhinitis, dyspepsia, nausea, peripheral edema, sinusitis, chest pain, and urinary frequency. SeeWARNINGSandPRECAUTIONSfor discussion of anaphylactoid reactions, angioedema, hypotension, neutropenia/agranulocytosis, second and third trimester fetal/neonatal morbidity and mortality, hyperkalemia, and cough.

Other potentially important adverse experiences reported in controlled or uncontrolled clinical trials in less than 1% of moexipril patients or that have been attributed to other ACE inhibitors include the following:

Cardiovascular:Symptomatic hypotension, postural hypotension, or syncope were seen in 9/1750 (0.51%) patients; these reactions led to discontinuation of therapy in controlled trials in 3/1254 (0.24%) patients who had received moexipril hydrochloride tablets monotherapy and in 1/344 (0.3%) patients who had received moexipril hydrochloride tablets with hydrochlorothiazide (see PRECAUTIONSand WARNINGS). Other adverse events included angina/myocardial infarction, palpitations, rhythm disturbances, and cerebrovascular accident.

Renal:Of hypertensive patients with no apparent preexisting renal disease, 1% of patients receiving moexipril hydrochloride tablets alone and 2% of patients receiving moexipril hydrochloride tablets with hydrochlorothiazide experienced increases in serum creatinine to at least 140% of their baseline values (see PRECAUTIONSand DOSAGE AND ADMINISTRATION).

Gastrointestinal:Abdominal pain, constipation, vomiting, appetite/weight change, dry mouth, pancreatitis, hepatitis.

Respiratory:Bronchospasm, dyspnea, eosinophilic pneumonitis.

Urogenital:Renal insufficiency, oliguria.

Dermatologic:Apparent hypersensitivity reactions manifested by urticaria, rash, pemphigus, pruritus, photosensitivity, alopecia.

Neurological and Psychiatric:Drowsiness, sleep disturbances, nervousness, mood changes, anxiety.

Other:Angioedema (see WARNINGS), taste disturbances, tinnitus, sweating, malaise, arthralgia, hemolytic anemia.

Clinical Laboratory Test Findings

Serum Electrolytes:Hyperkalemia (see PRECAUTIONS), hyponatremia.

Creatinine and Blood Urea Nitrogen:As with other ACE inhibitors, minor increases in blood urea nitrogen or serum creatinine, reversible upon discontinuation of therapy, were observed in approximately 1% of patients with essential hypertension who were treated with moexipril hydrochloride tablets. Increases are more likely to occur in patients receiving concomitant diuretics and in patients with compromised renal function (see PRECAUTIONS, General).

Other (causal relationship unknown):Clinically important changes in standard laboratory tests were rarely associated with moexipril hydrochloride tablets administration.

Elevations of liver enzymes and uric acid have been reported. In trials, less than 1% of moexipril-treated patients discontinued moexipril hydrochloride tablets treatment because of laboratory abnormalities. The incidence of abnormal laboratory values with moexipril was similar to that in the placebo-treated group.

Overdosage

Human overdoses of moexipril have not been reported. In case reports of overdoses with other ACE inhibitors, hypotension has been the principal adverse effect noted. Single oral doses of 2 g/kg moexipril were associated with significant lethality in mice. Rats, however, tolerated single oral doses of up to 3 g/kg.

No data are available to suggest that physiological maneuvers (e.g., maneuvers to change the pH of the urine) would accelerate elimination of moexipril and its metabolites. The dialyzability of moexipril is not known.

Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of moexipril overdose, but angiotensin II is essentially unavailable outside of research facilities. Because the hypotensive effect of moexipril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat moexipril overdose by infusion of normal saline solution. In addition, renal function and serum potassium should be monitored.

Hypertension

The recommended initial dose of moexipril hydrochloride tablets in patients not receiving diuretics is 7.5 mg, one hour prior to meals, once daily. Dosage should be adjusted according to blood pressure response. The antihypertensive effect of moexipril hydrochloride tablets may diminish towards the end of the dosing interval. Blood pressure should, therefore, be measured just prior to dosing to determine whether satisfactory blood pressure control is obtained. If control is not adequate, increased dose or divided dosing can be tried. The recommended dose range is 7.5 to 30 mg daily, administered in one or two divided doses one hour before meals. Total daily doses above 60 mg a day have not been studied in hypertensive patients.

In patients who are currently being treated with a diuretic, symptomatic hypotension may occasionally occur following the initial dose of moexipril hydrochloride tablets. The diuretic should, if possible, be discontinued for 2 to 3 days before therapy with moexipril hydrochloride tablets is begun, to reduce the likelihood of hypotension (see WARNINGS). If the patient’s blood pressure is not controlled with moexipril hydrochloride tablets alone, diuretic therapy may then be reinstituted. If diuretic therapy cannot be discontinued, an initial dose of 3.75 mg of moexipril hydrochloride tablets should be used with medical supervision until blood pressure has stabilized (see WARNINGSand PRECAUTIONS, Drug Interactions).

Dosage Adjustment In Renal Impairment

For patients with a creatinine clearance ≤40 mL/min/1.73 m ², an initial dose of 3.75 mg once daily should be given cautiously. Doses may be titrated upward to a maximum daily dose of 15 mg.

How Supplied

Moexipril Hydrochloride, USP 7.5 mgtablets are light beige, round, film-coated scored tablets, debossed with “ C” above and “ E” below the score on one side and “ 266” on other side.
They are supplied as follows:

Bottles of 90 NDC 62135-967-90

Moexipril Hydrochloride, USP 15 mgtablets are dark beige, round, film-coated scored tablets, debossed with “ C” above and “ E” below the score on one side and “ 267” on other side.
They are supplied as follows:

Bottles of 90 NDC 62135-969-90

Store, tightly closed, at 20° to 25°C (68° to 77°F). Excursions permitted between 15° and 30°C (59° and 86°F) [See USP Controlled Room Temperature]. Protect from excessive moisture.

If product package is subdivided, dispense in tight containers as described in USP-NF.

Manufactured for:
Chartwell RX, LLC.
Congers, NY 10920

L72585

Rev. 03/2025

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Moexipril Hydrochloride Tablets, USP 7.5 mg - NDC 62135-967-90 - 90s Tabs Bottle Label

"Image Description" - moexipril hcl tabs 7pt5mg 90s bottle label

Moexipril Hydrochloride Tablets, USP 15 mg - NDC 62135-969-90 - 90s Tabs Bottle Label