ADVERSE REACTIONS
Hypertension and Angina
Most adverse effects have been mild and transient. The following adverse reactions have been reported for immediate release metoprolol tartrate.
Central Nervous System: Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, somnolence, nightmares, and insomnia have also been reported.
Cardiovascular: Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; syncope; chest pain; and hypotension have been reported in about 1 of 100 patients (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).
Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients (see WARNINGS).
Gastrointestinal: Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, digestive tract disorders, and heartburn have been reported in about 1 of 100 patients.
Hypersensitive Reactions: Pruritus or rash have occurred in about 5 of 100 patients. Worsening of psoriasis has also been reported.
Miscellaneous: Peyronie’s disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, decreased libido, and tinnitus have also been reported.
There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with metoprolol.
Potential Adverse Reactions
In addition, there are a variety of adverse reactions not listed above, which have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to TOPROL-XL.
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 (see CONTRAINDICATIONS).
Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.
Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm, and respiratory distress.
Heart Failure
In the MERIT-HF study, serious adverse events and adverse events leading to discontinuation of study medication were systematically collected. In the MERIT-HF study comparing TOPROL-XL in daily doses up to 200 mg (mean dose 159 mg once-daily) (n=1990) to placebo (n=2001), 10.3% of TOPROL-XL patients discontinued for adverse events vs. 12.2% of placebo patients.
The table below lists adverse events in the MERIT-HF study that occurred at an incidence of equal to or greater than 1% in the TOPROL-XL group and greater than placebo by more than 0.5%, regardless of the assessment of causality.
Adverse Events Occurring in the MERIT-HF Study at an Incidence ≥ 1% in the TOPROL-XL Group and Greather Than Placebo by More Than 0.5% |
TOPROL-XL
|
Placebo
|
|
N=1990
|
N=2001
|
|
% of patients
|
% of patients
|
|
Dizziness/vertigo
|
1.8
|
1.0
|
|
Bradycardia
|
1.5
|
0.4
|
|
Accident and/or injury
|
1.4
|
0.8
|
Other adverse events with an incidence of > 1% on TOPROL-XL and as common on placebo (within 0.5%) included myocardial infarction, pneumonia, cerebrovascular disorder, chest pain, dyspnea/dyspnea aggravated, syncope, coronary artery disorder, ventricular tachycardia/arrhythmia aggravated, hypotension, diabetes mellitus/diabetes mellitus aggravated, abdominal pain, and fatigue.
Post-Marketing Experience
The following adverse reactions have been reported with TOPROL-XL in worldwide post-marketing use, regardless of causality:
Cardiovascular: 2nd and 3rd degree heart block, cardiogenic shock in patients with acute myocardial infarction.
Gastrointestinal: hepatitis, vomiting.
Hematologic: thrombocytopenia.
Musculoskeletal: arthralgia.
Nervous System/Psychiatric: anxiety/nervousness, hallucinations, paresthesia.
Reproductive, male: impotence.
Skin: increased sweating, photosensitivity, urticaria.
Special Sense Organs: taste disturbances.
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