Moexipril drug interactions: Difference between revisions

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==Drug Interactions==
==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.


====Potassium Supplements and Potassium-Sparing Diuretics====
====Potassium Supplements and Potassium-Sparing Diuretics====


As noted above (Serum Electrolyte Imbalances), the net effect of Moexipril HCl 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.
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====
====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.
Interaction studies with [[warfarin]] failed to identify any clinically important effect on the serum concentrations of the anticoagulant or on its anticoagulant effect.


====Lithium====
====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 HCl 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.
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====
====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 HCl and Hydrochlorothiazide Tablets.
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.
 
====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.
====Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)====


====Skeletal Muscle Relaxants, Nondepolarizing====
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, including moexipril hydrochloride, may be attenuated by NSAIDS.


Thiazide diuretics may increase the responsiveness to [[tubocurarine]].
====Dual Blockade of the Renin-Angiotensin System (RAS)====


====Non-steroidal Anti-inflammatory Drugs====
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]].


In some patients, the administration of a [[non-steroidal anti-inflammatory]] agent can reduce the diuretic, [[natriuretic]], and anti-hypertensive effects of loop, potassium-sparing and thiazide diuretics. Thus, when Moexipril HCl and Hydrochlorothiazide Tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
Do not co-administer [[aliskiren]] with moexipril in patients with diabetes. Avoid use of aliskiren with moexipril hydrochloride in patients with renal impairment (GFR <60 mL/min).


====Other Agents====
====Other Agents====


No clinically important pharmacokinetic interactions occurred when moexipril was administered concomitantly with [[digoxin]] or [[cimetidine]].
No clinically important pharmacokinetic interactions occurred when moexipril hydrochloride was administered concomitantly with [[hydrochlorothiazide]], [[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.
Moexipril hydrochloride has been used in clinical trials concomitantly with calcium-channel-blocking agents, diuretics, H2 blockers, digoxin, oral hypoglycemic agents, and cholesterol-lowering agents. There was no evidence of clinically important adverse interactions.


====Carcinogenesis, Mutagenesis, Impairment of Fertility====
====Carcinogenesis, Mutagenesis, Impairment of Fertility====


Moexipril Hydrochloride
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 evidence of carcinogenicity was detected in long-term studies when moexipril was administered to 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 (CHO) 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.
 
====Hydrochlorothiazide====
 
Under the auspices of the National Toxicology Program, rats and mice received [[hydrochlorothiazide]] in their feed for two years, at doses up to 600 mg/kg/day in mice and up to 100 mg/kg/day in rats. These studies uncovered no evidence of a carcinogenic potential of [[hydrochlorothiazide]] in rats or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (the Ames test); in the CHO test for chromosomal aberrations; or in in vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes; and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide of 43–1300 mcg/mL. Positive test results were also obtained in the [[Aspergillus nidulans]] nondisjunction assay, using an unspecified concentration of hydrochlorothiazide.
 
[[Hydrochlorothiazide]] had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diets, to doses up to 100 and 4 mg/kg/day, respectively, prior to mating and throughout gestation.


====Pregnancy====
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.


Pregnancy Categories C (first trimester) and D (second and third trimesters).<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>
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.<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 21:31, 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]

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.

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, 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, including moexipril hydrochloride, 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 co-administer aliskiren with moexipril 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, H2 blockers, digoxin, oral hypoglycemic agents, and cholesterol-lowering agents. There was no evidence of clinically important adverse interactions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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.[1]


References

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

Adapted from the FDA Package Insert.

Major Interactions

Moderate Interactions

Minor Interactions


Adapted from the FDA Package Insert.

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