Metoprololside effects

The following adverse reactions are described elsewhere in labeling: Worsening angina or myocardial infarction Worsening heart failure. Worsening AV block.

Most common adverse reactions: tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension, diarrhea, pruritus, rash. To report SUSPECTED ADVERSE REACTIONS, contact Advagen Pharma Ltd. at 866-488-0312 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience 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 the clinical trials of another drug and may not reflect the rates observed in practice. Hypertension and Angina Most adverse effects have been mild and transient.

Central Nervous System: Tiredness and dizziness have occurred in about 10% of patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported.

Cardiovascular: Shortness of breath and bradycardia have occurred in approximately 3% of patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; heart failure exacerbations; peripheral edema; and hypotension have been reported in about 1% of patients. Gangrene in patients with preexisting severe peripheral circulatory disorders has also been reported..

Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1% of patients. Rhinitis has also been reported.

Gastrointestinal: Diarrhea has occurred in about 5% of patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1% of patients. Vomiting was a common occurrence.

Hypersensitive Reactions: Pruritus or rash have occurred in about 5% of patients. Photosensitivity and worsening of psoriasis has been reported.

Miscellaneous: Peyronie’s disease, musculoskeletal pain, blurred vision, and tinnitus has been reported. Myocardial Infarction In general, the adverse reactions observed in trials with metoprolol in MI are consistent with the hypertension and angina experience. In the randomized comparison of Metoprolol tartrate and placebo in the setting of acute MI the following adverse reactions were reported: Metoprolol Tartrate Placebo Hypotension (systolic BP < 90 mm Hg) 27.4% 23.2% Bradycardia (heart rate < 40 beats/min) 15.9% 6.7% Second- or third-degree heart block 4.7% 4.7% First-degree heart block (P-R ≥ 0.26 sec) 5.3% 1.9% Heart failure 27.5% 29.6%

6.2 Post-Marketing

Experience The following adverse reactions have been identified during post-approval use of drug METOPROLOL TARTRATE. 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.

Central Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics.

Cardiovascular: Intensification of AV block.

Hematologic: Agranulocytosis, nonthrombocytopenic purpura and thrombocytopenic purpura.

Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm and respiratory distress.

Laboratory Findings: Increase in blood triglycerides, elevated transaminase and decrease in High Density Lipoprotein (HDL)