Moexipril

Female patients of childbearing age should be told about the consequences of exposure to moexipril hydrochloride during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

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 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, 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 for hypotension, oliguria, and hyperkalemia.

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/m² basis.

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

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/m² basis.

No mutagenicity was detected in the Ames test and microbial reverse mutation assay, with and without metabolic activation, or in an in vivo nucleus 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/m² basis, and in rats up to 90.9 times the MRHD on a mg/m² basis. No indication of impaired fertility, reproductive toxicity, or teratogenicity was observed.

Moexipril hydrochloride has 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 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 and in 1.8% of patients treated with placebo. The most common reasons for discontinuation in patients treated with moexipril hydrochloride 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 alone and that were at least as frequent in the moexipril hydrochloride 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.

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 monotherapy and in 1/344 (0.3%) patients who had received moexipril hydrochloride with hydrochlorothiazide. 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 alone and 2% of patients receiving moexipril hydrochloride with hydrochlorothiazide experienced increases in serum creatinine to at least 140% of their baseline values.

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, taste disturbances, tinnitus, sweating, malaise, arthralgia, hemolytic anemia.

Clinical Laboratory Test Findings

Serum Electrolytes

Hyperkalemia, 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. Increases are more likely to occur in patients receiving concomitant diuretics and in patients with compromised renal function.

Other (causal relationship unknown)

Clinically important changes in standard laboratory tests were rarely associated with moexipril hydrochloride administration.

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