Moexipril hydrochloride and hydrochlorothiazide

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).

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 smaller in black patients, a predominantly low-renin population, than in nonblack hypertensive patients. Although moexipril monotherapy is less effective in blacks than in nonblacks, the efficacy of combination therapy appears to be independent of race.

Hydrochlorothiazide is a thiazide diuretic and antihypertensive. Thiazides affect the distal renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin, so coadministration of an ACE inhibitor tends to reverse the potassium loss associated with these diuretics. The mechanism of the antihypertensive effect of thiazides is unknown.

Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors, including moexipril hydrochloride and hydrochlorothiazide tablets, may be subject to a variety of adverse reactions, some of them serious.

Angioedema involving the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients treated with ACE inhibitors, including moexipril. Symptoms suggestive of angioedema or facial edema occurred in <0.5% of moexipril-treated patients in placebo-controlled trials. None of the cases were considered life-threatening and all resolved either without treatment or with medication (antihistamines or glucocorticoids). One patient treated with hydrochlorothiazide alone experienced laryngeal edema. No instances of angioedema were reported in placebo-treated patients.

In cases of angioedema, treatment with moexipril hydrochloride and hydrochlorothiazide tablets should be promptly discontinued and the patient carefully observed until the swelling disappears. In instances where swelling has been confined to the face and lips, the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms.

Angioedema associated with involvement of the tongue, glottis, or larynx may be fatal due to airway obstruction. Appropriate therapy, e.g., subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) and/or measures to ensure a patent airway, should be promptly provided (see ADVERSE REACTIONS ).

Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions did not occur when ACE inhibitors were temporarily withheld, but they reappeared when the ACE inhibitors were inadvertently readministered.

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Moexipril hydrochloride and hydrochlorothiazide tablets can cause symptomatic hypotension, although, as with other ACE inhibitors, this is unusual in uncomplicated hypertensive patients treated with moexipril hydrochloride and hydrochlorothiazide tablets alone. Symptomatic hypotension is most likely to occur in patients who have been salt- and/or volume-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume- and/or salt-depletion should be corrected before initiating therapy with moexipril hydrochloride and hydrochlorothiazide tablets (see ADVERSE REACTIONS ).

The thiazide component of moexipril hydrochloride and hydrochlorothiazide tablets may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. The antihypertensive effects of the thiazide component may also be enhanced in the postsympathectomy patient.

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 and hydrochlorothiazide 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 hydrochloride and hydrochlorothiazide tablets 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 and hydrochlorothiazide tablets treatment usually can be continued following restoration of blood pressure and volume.

Moexipril hydrochloride and hydrochlorothiazide tablets should be used with caution in patients with severe renal disease. Thiazide diuretics may precipitate azotemia in such patients and the effects of repeated dosing may be cumulative.

 As a consequence of inhibition of the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. There is no clinical experience of moexipril hydrochloride and hydrochlorothiazide tablets in the treatment of hypertension in patients with renal failure.

Some hypertensive patients with no apparent preexisting renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when moexipril has been given concomitantly with a thiazide diuretic. This is more likely to occur in patients with preexisting renal impairment. There may be a need for dose adjustment of Moexipril hydrochloride and hydrochlorothiazide tablets. Evaluation of hypertensive patients should always include assessment of renal function (see DOSAGE AND ADMINISTRATION ).

In hypertensive patients with severe congestive heart failure, whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including moexipril, may be associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death.

In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine have been observed in some patients following ACE inhibitor therapy. These increases were almost always reversible upon discontinuation of the ACE inhibitor and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy.

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/mm³) among patients given moexipril, 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 are insufficient to show that moexipril does not cause agranulocytosis at rates similar to captopril.

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 events include skull hypoplasia, anuria, hypotension, renal failure and death. When pregnancy is detected, discontinue moexipril hydrochloride and hydrochlorothiazide tabletsas 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 reninangiotensin 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 and hydrochlorothiazide 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 and hydrochlorothiazide tablets

for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use ).

Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Reproduction studies with the combination of moexipril hydrochloride and hydrochlorothiazide (ratio 7.5:12.5) indicated that the combination possessed no teratogenic properties up to the lethal dose of 800 mg/kg/day in rats and up to the maternotoxic dose of 160 mg/kg/day in rabbits.

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.

Moexipril hydrochloride and hydrochlorothiazide tablets should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. In patients with mild to moderate cirrhosis given single 15 mg doses of moexipril, the C_max of moexipril was increased by about 50% and the AUC increased by about 120%, while the C_max for moexiprilat was decreased by about 50% and the AUC increased by almost 300%. No formal pharmacokinetic studies have been carried out with moexipril hydrochloride and hydrochlorothiazide tablets in hypertensive patients with impaired liver function.

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Serum Electrolyte Imbalances: In clinical trials with moexipril monotherapy, persistent hyperkalemia (serum potassium above 5.4 mEq/L) occurred in approximately 1.3% of hypertensive patients receiving moexipril. Risk factors for the development of hyperkalemia with ACE inhibitors include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

Treatment with thiazide diuretics has been associated with hypokalemia, hyponatremia, and hypochloremic alkalosis. These disturbances sometimes manifest as one or more of the following: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, and vomiting. Hypokalemia has also been reported to sensitize or exaggerate the response of the heart to the toxic effects of digitalis. The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients experiencing a brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes, and in patients receiving concomitant therapy with corticosteroids or ACTH.

The opposite effects of moexipril and hydrochlorothiazide on serum potassium will approximately counterbalance each other in many patients, so that little net effect upon serum potassium will be seen. Initial and periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Chloride deficits generally are mild and require specific treatment only under extraordinary circumstances ( e.g., in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients; appropriate therapy is water restriction rather than administration of salt, except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Calcium excretion is reduced by thiazides. In a few patients on prolonged thiazide therapy, pathological changes in the parathyroid gland have been seen, with hypercalcemia and hypophosphatemia. More serious complications of hyperparathyroidism (renal lithiasis, bone resorption, and peptic ulceration) have not been seen.Thiazides enhance urinary excretion of magnesium and hypomagnesemia may result.

Other Metabolic Disturbances: Thiazide diuretics may reduce glucose tolerance and may raise serum levels of cholesterol, triglycerides, and uric acid. These effects are usually minor, but frank gout or overt diabetes may be precipitated in susceptible patients.

Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, moexipril may block the effects of compensatory renin release. If hypotension occurs in this setting and is considered to be due to this mechanism, it can be corrected by volume expansion.

Cough: Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. In placebo-controlled trials with moexipril hydrochloride and hydrochlorothiazide tablets, cough was present in 3% of moexipril hydrochloride and hydrochlorothiazide tablets patients and 1% of patients given placebo.

Food: Patients should be advised to take moexipril hydrochloride and hydrochlorothiazide tablets one hour before a meal (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ).

Angioedema: Angioedema, including laryngeal edema, may occur with treatment with ACE inhibitors, usually occurring early in therapy (within the first month). Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of the face, extremities, eyes, lips, tongue, difficulty in breathing) and to take no more drug until they have consulted with the prescribing physician.

Symptomatic Hypotension: Patients should be cautioned that lightheadedness can occur with moexipril hydrochloride and hydrochlorothiazide tablets, especially during the first few days of therapy. If fainting occurs, the patient should stop taking moexipril hydrochloride and hydrochlorothiazide tablets and consult the prescribing physician.

All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult their physician if they develop these conditions.

Hyperkalemia: Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting their physician.

Neutropenia: Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) that could be a sign of neutropenia.

Pregnancy: Female patients of childbearing age should be told about the consequences of exposure to moexipril hydrochloride and hydrochlorothiazide tablets 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.

Potassium Supplements and Potassium-Sparing Diuretics: As noted above ( Serum Electrolyte Imbalances ), the net effect of moexipril hydrochloride and hydrochlorothiazide tablets may be to elevate a patient's serum potassium, to reduce it, or to leave it unchanged. Potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium supplements can increase the risk of hyperkalemia. 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 of moexipril monotherapy 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. Because renal clearance of lithium is reduced by thiazides, the risk of lithium toxicity is presumably raised further when, as in therapy with moexipril hydrochloride and hydrochlorothiazide tablets, a thiazide diuretic is coadministered with the ACE inhibitor. These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

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 and hydrochlorothiazide tablets.

Alcohol, Barbiturates, or Narcotics: Potentiation of orthostatic hypotension may occur in patients on thiazide diuretic therapy with concomitant use of alcohol, barbiturates, or narcotics.

Antidiabetic Agents: Use of thiazide diuretics concomitantly with antidiabetic agents (oral agents and insulin) may require dosage adjustment of the antidiabetic agent. Moexipril has been used in clinical trials concomitantly with oral hypoglycemic agents and there was no evidence of any clinically important adverse interactions.

Cholestyramine and Colestipol Resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.

Corticosteroids, ACTH: Use of thiazide diuretics concomitantly with corticosteroids or ACTH may intensify electrolyte depletion, particularly hypokalemia.

Pressor Amines: Thiazide diuretics may decrease arterial responsiveness to pressor amines (e.g. norepinephrine), but not enough to preclude effectiveness of the pressor agent for therapeutic use.

Skeletal Muscle Relaxants, Nondepolarizing: Thiazide diuretics may increase the responsiveness to tubocurarine. 

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, co-administration 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 and hydrochlorothiazide, as well as the diuretic and natriuretic effects of hydrochlorothiazide, 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 hydrochlorothiazide tablets and other agents that affect the RAS.

Do not co-administer aliskiren with moexipril hydrochloride and hydrochlorothiazide tablets in patients with diabetes. Avoid use of aliskiren with moexipril hydrochloride and hydrochlorothiazide tablets in patients with renal impairment (GFR <60 mL/min).

Other Agents: No clinically important pharmacokinetic interactions occurred when moexipril was administered concomitantly with digoxin or cimetidine.

Moexipril has been used in clinical trials concomitantly with calcium-channel-blocking agents, diuretics, H₂ blockers, digoxin, and cholesterol-lowering agents. There was no evidence of clinically important adverse interactions. In general, ACE inhibitors have less than additive effects with beta-adrenergic blockers, presumably because both work by inhibiting the renin-angiotensin system.

Coadministration of propantheline or guanabenz increased the absorption of hydrochlorothiazide.

It is not known whether moexipril or moexiprilat is excreted in human milk. Thiazides are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from hydrochlorothiazide and the unknown effects of moexipril or moexiprilat in infants, a decision should be made whether to discontinue nursing or to discontinue moexipril hydrochloride and hydrochlorothiazide tablets, taking into account the importance of the drug to the mother.

Neonates with a history of in utero exposure to moexipril hydrochloride and hydrochlorothiazide 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 and hydrochlorothiazide tablets in pediatric patients have not been established.

Of the patients who received moexipril hydrochloride and hydrochlorothiazide tablets in controlled clinical studies, 24% were 65 years of age or older. No overall differences in effectiveness or safety were observed between these patients and younger patients. In elderly patients receiving moexipril, plasma levels of drug are slightly higher and renal clearance is reduced when compared to younger patients, but these effects did not have detectable consequences. Hydrochlorothiazide is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Other adverse experiences occurring in more than 1% of patients treated with moexipril hydrochloride and hydrochlorothiazide tablets are in controlled or uncontrolled trials, some of which were of uncertain drug relationship, listed in decreasing frequency include: upper respiratory infection, headache, pain, flu syndrome, pharyngitis, hyperuricemia, diarrhea, back pain, rhinitis, sinusitis, abnormal ECG, infection, abdominal pain, chest pain, dyspepsia, hyperglycemia, hypokalemia, rash, vertigo, nausea, hypertonia, increased SGPT, urinary tract infection, impotence, peripheral edema, pyuria, bronchitis, and fever. See WARNINGS and PRECAUTIONS for discussion of anaphylactoid reactions, angioedema, hypotension, neutropenia/agranulocytosis, fetal/neonatal morbidity and mortality, serum electrolyte imbalances, and cough.

The following adverse experiences, some of which are of uncertain drug relationship, were reported in moexipril hydrochloride and hydrochlorothiazide tablets controlled or uncontrolled clinical trials in less than 1% of patients or have been attributed to other ACE inhibitors. Within each organ system, adverse experiences are listed in decreasing frequency.

Cardiovascular: palpitation, flushing, syncope, tachycardia, myocardial infarct, hypotension, postural hypotension, arrhythmia, first degree AV block, ventricular extrasystoles, atrial fibrillation, migraine, hemorrhage, sinus bradycardia, bigeminy, bradycardia, bundle branch block, heart arrest, myocardial ischemia, peripheral vascular disorder, prolonged QT interval, inverted T wave, ventricular fibrillation.

Dermatologic: eczema, pruritus, sweating, acne, dry skin, herpes simplex, contact dermatitis, herpes zoster, psoriasis, alopecia, angioedema, erythema nodosum, fungal dermatitis, furunculosis, maculopapular rash, purpuric rash, skin carcinoma, subcutaneous nodule, urticaria, pemphigus.

Gastrointestinal: vomiting, constipation, gastroenteritis, periodontal abscess, cholelithiasis, gastritis, gingivitis, esophagitis, flatulence, anorexia, colitis, dysphagia, tooth caries, cheilitis, enteritis, eructation, gastrointestinal carcinoma, gastrointestinal hemorrhage, glossitis, increased appetite, jaundice, melena, rectal hemorrhage, stomatitis, tongue discoloration, tongue edema.

Hematologic: anemia, hypochromic anemia, leukopenia, abnormal erythrocytes, ecchymosis, lymphocytosis, hemolysis, lymphadenopathy, eosinophilia, petechia, abnormal WBC, hemolytic anemia.

Metabolic: hyperlipemia, increased SGOT, gout, bilirubinemia, increased creatinine, hypercholesterolemia, increased BUN, increased CPK, diabetes mellitus, hyponatremia, thirst, edema, increased alkaline phosphatase, increased amylase, dehydration, decreased glucose tolerance, goiter, hypercalcemia, hyperkalemia, hypocalcemia, hypochloremia, hypoproteinemia, weight gain

Neurologic/Psychiatric: insomnia, postural dizziness, somnolence, dry mouth, anxiety, nervousness, paresthesia, depression, neuritis, hypesthesia, decreased libido, neuralgia, amnesia, ataxia, cerebral infarct, emotional lability, facial paralysis, hypokinesia, neurosis, vocal cord paralysis

Renal: albuminuria, urinary frequency, hematuria, glycosuria, cystitis, dysuria, nocturia, polyuria, kidney calculus, pyelonephritis, urate crystalluria, urinary casts, and urinary retention.

Respiratory: epistaxis, pneumonia, dyspnea, asthma, lung carcinoma, hemoptysis, laryngitis, voice alteration, eosinophilic pneumonitis.

Urogenital: vaginal hemorrhage, breast carcinoma, scrotal edema, vaginitis, breast enlargement, breast pain, dysmenorrhea, leukorrhea.

Other: asthenia, conjunctivitis, myalgia, arthralgia, arthrosis, hernia, neck pain, cyst, tenosynovitis, abnormal vision, allergic reaction, arthritis, cataract, cellulitis, moniliasis, otitis media, eye hemorrhage, chills, abscess, bursitis, deafness, ear pain, glaucoma, iritis, neck rigidity, photosensitivity, retinal degeneration, tinnitus.

Monotherapy with moexipril has been evaluated for safety in over 3000 patients. In clinical trials, the observed adverse experiences with moexipril were similar to those seen in the moexipril hydrochloride and hydrochlorothiazide tablets trials.

The following adverse reactions have been reported with hydrochlorothiazide and, within each organ system, are listed by decreasing severity.

Cardiovascular: orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics)

Gastrointestinal: pancreatitis, jaundice (intrahepatic cholestatic, see WARNINGS ), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, anorexia.

Neurologic/Psychiatric: vertigo, dizziness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, restlessness.

Musculoskeletal: muscle spasm.

Hematologic: aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Metabolic: hyperglycemia, glycosuria, hyperuricemia.

Hypersensitivity: necrotizing angiitis, Stevens-Johnson syndrome, respiratory distress including pneumonitis and pulmonary edema, purpura, urticaria, rash, photosensitivity

Serum Electrolytes: See PRECAUTIONS, General .

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 less than 1% of patients with essential hypertension who were treated with moexipril hydrochloride and hydrochlorothiazide tablets. Increases are more likely to occur 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 and hydrochlorothiazide tablets administration.