Moexipril Hydrochloride

Drug Interactions Diuretics Excessive reductions in blood pressure may occur in patients on diuretic therapy when ACE inhibitors are started. The possibility of hypotensive effects with moexipril hydrochloride can be minimized by discontinuing diuretic therapy for several days or cautiously increasing salt intake before initiation of treatment with moexipril hydrochloride. If this is not possible, the starting dose of moexipril should be reduced (see WARNINGS and DOSAGE AND ADMINISTRATION ). Potassium Supplements and Potassium-Sparing Diuretics Moexipril hydrochloride can increase serum potassium because it decreases aldosterone secretion. Use of potassium-sparing diuretics (spironolactone, triamterene, amiloride) or potassium supplements concomitantly with ACE inhibitors can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, they should be given with caution and the patient’s serum potassium should be monitored. Oral Anticoagulants Interaction studies with warfarin failed to identify any clinically important effect on the serum concentrations of the anticoagulant or on its anticoagulant effect. Lithium Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including moexipril hydrochloride. Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDS, including selective COX-2 inhibitors, with ACE inhibitors, including moexipril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving moexipril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including moexipril, may be attenuated by NSAIDS. Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on moexipril hydrochloride and other agents that affect the RAS. Do not coadminister aliskiren with moexipril hydrochloride in patients with diabetes. Avoid use of aliskiren with moexipril hydrochloride in patients with renal impairment (GFR < 60 mL/min). Other Agents No clinically important pharmacokinetic interactions occurred when moexipril hydrochloride was administered concomitantly with hydrochlorothiazide, digoxin, or cimetidine. Moexipril hydrochloride has been used in clinical trials concomitantly with calcium-channel-blocking agents, diuretics, H 2 blockers, digoxin, oral hypoglycemic agents, and cholesterol-lowering agents. There was no evidence of clinically important adverse interactions.

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 ).

DOSAGE AND ADMINISTRATION

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 ADVERSE EVENT MOEXIPRIL HYDROCHLORIDE TABLETS (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/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 PRECAUTIONS and 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 PRECAUTIONS and 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.