Moexipril Hydrochloride (4 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- MOEXIPRIL HYDROCHLORIDE
- MOEXIPRIL HYDROCHLORIDE AND HYDROCHLOROTHIAZIDE
- UNIRETIC
- UNIVASC
Boxed Warning
• When pregnancy is detected, discontinue moexipril hydrochloride as soon as possible. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity.
Indications and Usage
Moexipril hydrochloride tablets are indicated for treatment of patients with hypertension. They 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 is 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 in patients with diabetes (see PRECAUTIONS, Drug Interactions).
Adverse Reactions
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 ADVERSE EVENT MOEXIPRIL HYDROCHLORIDE (N=674) PLACEBO (N=226) N (%) N (%) Cough Increased 41 (6.1) 5 (2.2) Dizziness 29 (4.3) 5 (2.2) Diarrhea 21 (3.1) 5 (2.2) Flu Syndrome 21 (3.1) 0 (0) Fatigue 16 (2.4) 4 (1.8) Pharyngitis 12 (1.8) 2 (0.9) Flushing 11 (1.6) 0 (0) Rash 11 (1.6) 2 (0.9) Myalgia 9 (1.3) 0 (0) 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. See WARNINGS and PRECAUTIONS for discussion of anaphylactoid reactions, angioedema, hypotension, neutropenia/agranulocytosis, second and third trimester fetal/neona
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.
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.