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| __NOTOC__
| | #REDIRECT [[Eplerenone#Adverse Reactions]] |
| {{Eplerenone}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Adverse Reactions==
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| The following adverse reactions are discussed in greater detail in other sections of the labeling:
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| *[[hyperkalemia]] [See WARNINGS AND PRECAUTIONS (5.1)]
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| Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
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| ===6.1 Clinical Trials Experience===
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| ====Congestive Heart Failure Post-Myocardial Infarction====
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| In EPHESUS, safety was evaluated in 3307 patients treated with INSPRA and 3301 placebo-treated patients. The overall incidence of adverse events reported with INSPRA (78.9%) was similar to placebo (79.5%). Adverse events occurred at a similar rate regardless of age, gender, or race. Patients discontinued treatment due to an adverse event at similar rates in either treatment group (4.4% INSPRA vs. 4.3% placebo), with the most common reasons for discontinuation being [[hyperkalemia]], [[myocardial infarction]], and abnormal renal function.
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| Adverse reactions that occurred more frequently in patients treated with INSPRA than placebo were [[hyperkalemia]] (3.4% vs. 2.0%) and increased creatinine (2.4% vs. 1.5%). Discontinuations due to [[hyperkalemia]] or abnormal renal function were less than 1.0% in both groups. [[Hypokalemia]] occurred less frequently in patients treated with INSPRA (0.6% vs. 1.6%).
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| The rates of sex hormone-related adverse events are shown in Table 2.
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| {|
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| |[[File:Eplerenone02.jpg|thumb|800px]]
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| ====Hypertension====
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| INSPRA has been evaluated for safety in 3091 patients treated for [[hypertension]]. A total of 690 patients were treated for over 6 months and 106 patients were treated for over 1 year.
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| In placebo-controlled studies, the overall rates of adverse events were 47% with INSPRA and 45% with placebo. Adverse events occurred at a similar rate regardless of age, gender, or race. Therapy was discontinued due to an adverse event in 3% of patients treated with INSPRA and 3% of patients given placebo. The most common reasons for discontinuation of INSPRA were [[headache]], [[dizziness]], [[angina pectoris]]/[[myocardial infarction]], and increased GGT. The adverse events that were reported at a rate of at least 1% of patients and at a higher rate in patients treated with INSPRA in daily doses of 25 to 400 mg versus placebo are shown in Table 3.
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| {|
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| |[[File:Eplerenone03.jpg|thumb|800px]]
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| Gynecomastia and abnormal vaginal bleeding were reported with INSPRA but not with placebo. The rates of these sex hormone-related adverse events are shown in Table 4. The rates increased slightly with increasing duration of therapy. In females, abnormal vaginal bleeding was also reported in 0.8% of patients on antihypertensive medications (other than spironolactone) in active control arms of the studies with INSPRA.
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| {|
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| |[[File:Eplerenone04.jpg|thumb|800px]]
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| ===6.2 Clinical Laboratory Test Findings===
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| Congestive Heart Failure Post-Myocardial Infarction
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| Creatinine: Increases of more than 0.5 mg/dL were reported for 6.5% of patients administered INSPRA and for 4.9% of placebo-treated patients.
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| Potassium: In EPHESUS [see CLINICAL STUDIES (14.1)], the frequencies of patients with changes in potassium (<3.5 mEq/L or >5.5 mEq/L or ≥6.0 mEq/L) receiving INSPRA compared with placebo are displayed in Table 5.
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| {|
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| |[[File:Eplerenone05.jpg|thumb|800px]]
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| {|
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| |[[File:Eplerenone06.jpg|thumb|800px]]
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| {|
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| |[[File:Eplerenone07.jpg|thumb|800px]]
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| ====Hypertension====
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| Potassium: In placebo-controlled fixed-dose studies, the mean increases in serum potassium were dose-related and are shown in Table 8 along with the frequencies of values >5.5 mEq/L.
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| {|
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| |[[File:Eplerenone08.jpg|thumb|800px]]
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| Patients with both type 2 diabetes and microalbuminuria are at increased risk of developing persistent [[hyperkalemia]]. In a study of such patients taking INSPRA 200 mg, the frequencies of maximum serum potassium levels >5.5 mEq/L were 33% with INSPRA given alone and 38% when INSPRA was given with enalapril.
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| Rates of [[hyperkalemia]] increased with decreasing renal function. In all studies, serum potassium elevations >5.5 mEq/L were observed in 10.4% of patients treated with INSPRA with baseline calculated creatinine clearance <70 mL/min, 5.6% of patients with baseline creatinine clearance of 70 to 100 mL/min, and 2.6% of patients with baseline creatinine clearance of >100 mL/min. [See WARNINGS AND PRECAUTIONS (5.1).]
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| '''Sodium''': Serum sodium decreased in a dose-related manner. Mean decreases ranged from 0.7 mEq/L at 50 mg daily to 1.7 mEq/L at 400 mg daily. Decreases in sodium (<135 mEq/L) were reported for 2.3% of patients administered INSPRA and 0.6% of placebo-treated patients.
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| '''Triglycerides''': Serum [[triglycerides ]]increased in a dose-related manner. Mean increases ranged from 7.1 mg/dL at 50 mg daily to 26.6 mg/dL at 400 mg daily. Increases in [[triglycerides ]](above 252 mg/dL) were reported for 15% of patients administered INSPRA and 12% of placebo-treated patients.
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| '''Cholesterol''': Serum [[cholesterol ]]increased in a dose-related manner. Mean changes ranged from a decrease of 0.4 mg/dL at 50 mg daily to an increase of 11.6 mg/dL at 400 mg daily. Increases in serum [[cholesterol ]]values greater than 200 mg/dL were reported for 0.3% of patients administered INSPRA and 0% of placebo-treated patients.
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| '''Liver Function Tests''': Serum alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (GGT) increased in a dose-related manner. Mean increases ranged from 0.8 U/L at 50 mg daily to 4.8 U/L at 400 mg daily for ALT and 3.1 U/L at 50 mg daily to 11.3 U/L at 400 mg daily for GGT. Increases in ALT levels greater than 120 U/L (3 times upper limit of normal) were reported for 15/2259 patients administered INSPRA and 1/351 placebo-treated patients. Increases in ALT levels greater than 200 U/L (5 times upper limit of normal) were reported for 5/2259 of patients administered INSPRA and 1/351 placebo-treated patients. Increases of ALT greater than 120 U/L and bilirubin greater than 1.2 mg/dL were reported 1/2259 patients administered INSPRA and 0/351 placebo-treated patients. Hepatic failure was not reported in patients receiving INSPRA.
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| '''BUN/Creatinine''': Serum creatinine increased in a dose-related manner. Mean increases ranged from 0.01 mg/dL at 50 mg daily to 0.03 mg/dL at 400 mg daily. Increases in blood urea nitrogen to greater than 30 mg/dL and serum creatinine to greater than 2 mg/dL were reported for 0.5% and 0.2%, respectively, of patients administered INSPRA and 0% of placebo-treated patients.
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| '''Uric Acid''': Increases in uric acid to greater than 9 mg/dL were reported in 0.3% of patients administered INSPRA and 0% of placebo-treated patients.
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| ===6.3 Postmarketing Experience===
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| The following adverse reactions have been identified during postapproval use of INSPRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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| Skin: angioneurotic edema, rash<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = INSPRA (EPLERENONE) TABLET, FILM COATED [G.D. SEARLE LLC DIVISION OF PFIZER INC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a55a39ff-1bd5-428b-a64f-c44262e2f3ed | publisher = | date = | accessdate = 28 February 2014 }}</ref>
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| ==References==
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| {{Reflist}}
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| [[Category:Aldosterone antagonists]]
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| [[Category:Pfizer]]
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| [[Category:Lactones]]
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| [[Category:Epoxides]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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