Moexipril warnings and precautions: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 7: Line 7:
====Anaphylactoid and Possibly Related Reactions====
====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 HCl and [[Hydrochlorothiazide]] Tablets, may be subject to a variety of adverse reactions, some of them serious.
Presumably because [[angiotensin-converting enzyme inhibitors]] affect the metabolism of [[eicosanoids]] and polypeptides, including endogenous [[bradykinin]], patients receiving ACE inhibitors, including moexipril hydrochloride, may be subject to a variety of adverse reactions, some of them serious.


====Head and Neck Angioedema====
====Head and Neck Angioedema====


[[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.
[[Angioedema]] involving the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients treated with ACE inhibitors, including moexipril hydrochloride. 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 HCl 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.
In cases of [[angioedema]], treatment 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.
[[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.


====Intestinal Angioedema====
====Intestinal Angioedema====


[[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.
[[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]].


====Anaphylactoid Reactions During Desensitization====
====Anaphylactoid Reactions During Desensitization====
Line 31: Line 31:
====Hypotension====
====Hypotension====


Moexipril HCl and [[Hydrochlorothiazide]] Tablets can cause symptomatic [[hypotension]], although, as with other ACE inhibitors, this is unusual in uncomplicated hypertensive patients treated with Moexipril HCl 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 HCl and Hydrochlorothiazide Tablets.
Moexipril hydrochloride can cause symptomatic [[hypotension]], although, as with other ACE inhibitors, this is unusual in uncomplicated hypertensive patients treated with moexipril hydrochloride 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.


The thiazide component of Moexipril HCl 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 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.


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 HCl 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 HCl 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 treatment usually can be continued following restoration of blood pressure and volume.
 
If [[hypotension]] occurs, the patient should be placed in a supine position and, if necessary, treated with an intravenous infusion of normal saline. Moexipril HCl and Hydrochlorothiazide Tablets treatment usually can be continued following restoration of blood pressure and volume.
 
====Impaired Renal Function====
 
Moexipril HCl 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 HCl 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 HCl and [[Hydrochlorothiazide]] Tablets. Evaluation of hypertensive patients should always include assessment of renal function.
 
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.


====Neutropenia/Agranulocytosis====
====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/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]].
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 hydrochloride, 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 are insufficient to show that moexipril hydrochloride does not cause [[agranulocytosis]] at rates similar to captopril.
 
====Fetal/Neonatal Morbidity and Mortality====


ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.
====Fetal Toxicity====


The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including [[hypotension]], neonatal [[skull hypoplasia]], [[anuria]], reversible or irreversible [[renal failure]], and death. [[Oligohydramnios]] has also been reported, presumably resulting from decreased fetal renal function; [[oligohydramnios]] in this setting has been associated with fetal limb contractures, [[craniofacial deformation]], and [[hypoplastic lung]] development. [[Prematurity]], [[intrauterine growth retardation]], and [[patent ductus arteriosus]] have also been reported, although it is not clear whether these were caused by the ACE inhibitor exposure.
====Pregnancy category D====


Fetal and neonatal morbidity do not appear to have resulted from intrauterine ACE inhibitor exposure limited to the first trimester. Mothers who have used ACE inhibitors only during the first trimester should be informed of this. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of Moexipril HCl and Hydrochlorothiazide Tablets as soon as possible.
Use of drugs that act on the [[renin-angiotensin system]] during the secondand 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.


Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment.
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, Moexipril HCl and Hydrochlorothiazide Tablets should be discontinued unless it is considered life-saving for the mother. [[Contraction stress testing]] (CST), a [[non-stress test]] (NST), or [[biophysical profiling]] (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not be detected until after the fetus has sustained irreversible injury.
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]]


Infants with histories of in utero exposure to ACE inhibitors should be closely observed for [[hypotension]], [[oliguria]], and [[hyperkalemia]]. If [[oliguria]] occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or [[peritoneal dialysis]] may be required as means of reversing hypotension and/or substituting for disordered renal function. Theoretically, the ACE inhibitor could be removed from the [[neonatal circulation]] by exchange transfusion, but no experience with this procedure has been reported.
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.
 
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.


====Hepatic Failure====
====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.
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.


====Impaired Hepatic Function====
==Precautions==  


Moexipril HCl 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 Cmax of moexipril was increased by about 50% and the AUC increased by about 120%, while the Cmax for moexiprilat was decreased by about 50% and the AUC increased by almost 300%. No formal pharmacokinetic studies have been carried out with Moexipril HCl and Hydrochlorothiazide Tablets in hypertensive patients with impaired liver function.
====General====


====Systemic Lupus Erythematosus====
====Impaired Renal Function====


Thiazide diuretics have been reported to cause exacerbation or activation of [[systemic lupus erythematosus]].
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 in the treatment of hypertension in patients with [[renal failure]].


==Precautions==
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 hydrochloride 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/or the discontinuation of the [[thiazide]] diuretic.


====General====
Evaluation of hypertensive patients should always include assessment of renal function.


====Serum Electrolyte Imbalances====
====Hypertensive Patients With Congestive Heart Failure====


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.
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 hydrochloride, may be associated with [[oliguria]] and/or progressive [[azotemia]] and, rarely, [[acute renal failure]] and/or death.


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]].
====Hypertensive Patients With Renal Artery Stenosis====


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.
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.
 
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====
====Hyperkalemia====


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.
In clinical trials, persistent [[hyperkalemia]] (serum potassium above 5.4 mEq/L) occurred in approximately 1.3% of hypertensive patients receiving moexipril hydrochloride. 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, which should be used cautiously, if at all, with moexipril hydrochloride.


====Surgery/Anesthesia====
====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.
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====
====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 HCl and Hydrochlorothiazide Tablets, cough was present in 3% of Moexipril HCl and Hydrochlorothiazide Tablets patients and 1% of patients given placebo.<ref name="dailymed.nlm.nih.gov">{{Cite web  | last =  | first =  | title = MOEXIPRIL HYDROCHLORIDE TABLET [APOTEX CORP.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d18108f5-98ca-1220-d145-bcf4e71ceaee | publisher =  | date =  | accessdate = }}</ref>
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 controlled trials with moexipril, cough was present in 6.1% of moexipril patients and 2.2% of patients given placebo.<ref name="dailymed.nlm.nih.gov">{{Cite web  | last =  | first =  | title = MOEXIPRIL HYDROCHLORIDE TABLET [APOTEX CORP.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d18108f5-98ca-1220-d145-bcf4e71ceaee | publisher =  | date =  | accessdate = }}</ref>




Revision as of 21:23, 14 February 2014


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2], Amr Marawan, M.D. [3]

Moexipril

Moexipril and Hydrochlorothiazide tablet

Overview

Moexipril tablet is an angiontensin converting enzyme inhibitor drug that is FDA approved for the treatment of hypertension, heart failure, left ventricular dysfunction after myocardial infarction, diabetic nephropathy. Adverse reactions include hypotension, rash, hyperkalemia, disorder of taste, cough. hypotension, rash, hyperkalemia, disorder of taste, cough.

Category

Antihypertensive Agents, Angiotensin Converting Enzyme Inhibitors. Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4]; Associate Editor(s)-in-Chief: Amr Marawan, M.D. [5]

Warnings

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

Head and Neck Angioedema

Angioedema involving the face, extremities, lips, tongue, glottis, and/or larynx has been reported in patients treated with ACE inhibitors, including moexipril hydrochloride. 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 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.

Intestinal Angioedema

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.

Anaphylactoid Reactions During Desensitization

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 During Membrane Exposure

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.

Hypotension

Moexipril hydrochloride can cause symptomatic hypotension, although, as with other ACE inhibitors, this is unusual in uncomplicated hypertensive patients treated with moexipril hydrochloride 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.

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 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 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/mm3) among patients given moexipril hydrochloride, 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 are insufficient to show that moexipril hydrochloride does 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 secondand 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.

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.

Precautions

General

Impaired Renal Function

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 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 hydrochloride 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/or the discontinuation of the thiazide diuretic.

Evaluation of hypertensive patients should always include assessment of renal function.

Hypertensive Patients With Congestive Heart Failure

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 hydrochloride, may be associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death.

Hypertensive Patients With Renal Artery Stenosis

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.

Hyperkalemia

In clinical trials, persistent hyperkalemia (serum potassium above 5.4 mEq/L) occurred in approximately 1.3% of hypertensive patients receiving moexipril hydrochloride. 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, which should be used cautiously, if at all, with moexipril hydrochloride.

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 controlled trials with moexipril, cough was present in 6.1% of moexipril patients and 2.2% of patients given placebo.[1]


References

  1. ↑ "MOEXIPRIL HYDROCHLORIDE TABLET [APOTEX CORP.]".

Adapted from the FDA Package Insert.

Retrieved from "https://www.wikidoc.org/index.php?title=Moexipril_warnings_and_precautions&oldid=943787"