ADVERSE REACTIONS
Safety data are available in more than 30,000 patients or volunteers. Frequency estimates and rates of withdrawal of therapy for adverse events were derived from two U.S. placebo-controlled studies.
In Study A, doses of 5 mg, 10 mg, and 20 mg bisoprolol fumarate were administered for 4 weeks. In Study B, doses of 2.5 mg, 10 mg, and 40 mg of bisoprolol fumarate were administered for 12 weeks. A total of 273 patients were treated with 5 mg to 20 mg of bisoprolol fumarate; 132 received placebo.
Withdrawal of therapy for adverse events was 3.3% for patients receiving bisoprolol fumarate and 6.8% for patients on placebo. Withdrawals were less than 1% for either bradycardia or fatigue/lack of energy.
The following table presents adverse experiences, whether or not considered drug related, reported in at least 1% of patients in these studies, for all patients studied in placebo-controlled clinical trials (2.5 mg to 40 mg), as well as for a subgroup that was treated with doses within the recommended dosage range (5 mg to 20 mg). Of the adverse events listed in the table, bradycardia, diarrhea, asthenia, fatigue, and sinusitis appear to be dose related.
Body System/Adverse Experience
|
All Adverse Experiences (%
)
Bisoprolol
Fumarate
|
|
Placebo
(n=132)
%
|
5 mg to 20 mg
(n=273)
%
|
2.5 mg to 40 mg
(n=404)
%
|
Skin
|
Increased Sweating
|
1.5
|
0.7
|
1.0
|
Musculoskeletal
|
Arthralgia
|
2.3
|
2.2
|
2.7
|
Central Nervous System
|
Dizziness
|
3.8
|
2.9
|
3.5
|
Headache
|
11.4
|
8.8
|
10.9
|
Hypoaesthesia
|
0.8
|
1.1
|
1.5
|
Autonomic Nervous System
|
Dry Mouth
|
1.5
|
0.7
|
1.3
|
Heart Rate/Rhythm
|
Bradycardia
|
0
|
0.4
|
0.5
|
Psychiatric
|
Vivid Dreams
|
0
|
0
|
0
|
Insomnia
|
2.3
|
1.5
|
2.5
|
Depression
|
0.8
|
0
|
0.2
|
Gastrointestinal
|
Diarrhea
|
1.5
|
2.6
|
3.5
|
Nausea
|
1.5
|
1.5
|
2.2
|
Vomiting
|
0
|
1.1
|
1.5
|
Respiratory
|
Bronchospasm
|
0
|
0
|
0
|
Cough
|
4.5
|
2.6
|
2.5
|
Dyspnea
|
0.8
|
1.1
|
1.5
|
Pharyngitis
|
2.3
|
2.2
|
2.2
|
Rhinitis
|
3.0
|
2.9
|
4.0
|
Sinusitis
|
1.5
|
2.2
|
2.2
|
URI
|
3.8
|
4.8
|
5.0
|
Body as a Whole
|
Asthenia
|
0
|
0.4
|
1.5
|
Chest Pain
|
0.8
|
1.1
|
1.5
|
Fatigue
|
1.5
|
6.6
|
8.2
|
Edema (Peripheral)
|
3.8
|
3.7
|
3.0
|
The following is a comprehensive list of adverse experiences reported with bisoprolol fumarate in worldwide studies, or in postmarketing experience (in italics):
Central Nervous System:
Dizziness, unsteadiness, vertigo, syncope, headache, paresthesia, hypoesthesia, hyperesthesia, somnolence, sleep disturbances, anxiety/restlessness, decreased concentration/memory.
Autonomic Nervous System:
Dry mouth.
Cardiovascular:
Bradycardia, palpitations and other rhythm disturbances, cold extremities, claudication, hypotension, orthostatic hypotension, chest pain, congestive heart failure, dyspnea on exertion.
Psychiatric:
Vivid dreams, insomnia, depression.
Gastrointestinal:
Gastric/epigastric/abdominal pain, gastritis, dyspepsia, nausea, vomiting, diarrhea, constipation, peptic ulcer.
Musculoskeletal:
Muscle/joint pain, arthralgia, back/neck pain, muscle cramps, twitching/tremor.
Skin:
Rash, acne, eczema, psoriasis, skin irritation, pruritus, flushing, sweating, alopecia, dermatitis
,angioedema
,
exfoliative
dermatitis, cutaneous vasculitis.
Special Senses:
Visual disturbances, ocular pain/pressure, abnormal lacrimation, tinnitus, decreased hearing, earache, taste abnormalities.
Metabolic:
Gout.
Respiratory:
Asthma/bronchospasm, bronchitis, coughing, dyspnea, pharyngitis, rhinitis, sinusitis, URI.
Genitourinary:
Decreased libido/impotence, Peyronie’s
disease, cystitis, renal colic, polyuria.
Hematologic:
Purpura.
General:
Fatigue, asthenia, chest pain, malaise, edema, weight gain, angioedema.
In addition, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and should be considered potential adverse effects of bisoprolol fumarate:
Central Nervous System:
Reversible mental depression progressing to catatonia, hallucinations, an acute reversible syndrome characterized by disorientation to time and place, emotional lability, slightly clouded sensorium.
Allergic:
Fever, combined with aching and sore throat, laryngospasm, respiratory distress.
Hematologic:
Agranulocytosis, thrombocytopenia, thrombocytopenic purpura.
Gastrointestinal:
Mesenteric arterial thrombosis, ischemic colitis.
Miscellaneous:
The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with bisoprolol fumarate during investigational use or extensive foreign marketing experience.
Laboratory Abnormalities
In clinical trials, the most frequently reported laboratory change was an increase in serum triglycerides, but this was not a consistent finding.
Sporadic liver test abnormalities have been reported. In the U.S. controlled trials experience with bisoprolol fumarate treatment for 4 to 12 weeks, the incidence of concomitant elevations in SGOT and SGPT from 1 to 2 times normal was 3.9%, compared to 2.5% for placebo. No patient had concomitant elevations greater than twice normal.
In the long-term, uncontrolled experience with bisoprolol fumarate treatment for 6 to 18 months, the incidence of one or more concomitant elevations in SGOT and SGPT from 1 to 2 times normal was 6.2%. The incidence of multiple occurrences was 1.9%. For concomitant elevations in SGOT and SGPT of greater than twice normal, the incidence was 1.5%. The incidence of multiple occurrences was 0.3%. In many cases these elevations were attributed to underlying disorders, or resolved during continued treatment with bisoprolol fumarate.
Other laboratory changes included small increases in uric acid, creatinine, BUN, serum potassium, glucose, and phosphorus and decreases in WBC and platelets. These were generally not of clinical importance and rarely resulted in discontinuation of bisoprolol fumarate.
As with other beta-blockers, ANA conversions have also been reported on bisoprolol fumarate. About 15% of patients in long-term studies converted to a positive titer, although about one-third of these patients subsequently reconverted to a negative titer while on continued therapy.
|
REPORTS OF SUSPECTED BISOPROLOL SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Bisoprolol. The information is not vetted and should not be considered as verified clinical evidence.
Possible Bisoprolol side effects / adverse reactions in 44 year old male
Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2011-10-05
Patient: 44 year old male
Reactions: Weight Decreased, Hepatic Function Abnormal, Intentional Overdose, Hypoglycaemia, Coma, Coma Scale Abnormal, Fall, Transaminases Increased, Hypokalaemia, Liver Function Test Abnormal, Multiple Drug Overdose Intentional, Pneumonia, Hypothermia, Aspergilloma, Hypotension, Malnutrition, Toxicity TO Various Agents, Cachexia, Hypophosphataemia, Sepsis, Feeding Disorder, Bradycardia, Depressed Mood, Asthenia, Pulmonary Cavitation
Adverse event resulted in: hospitalization
Suspect drug(s):
Bisoprolol
Dosage: unk
Indication: Product Used FOR Unknown Indication
Olanzapine
Dosage: unk
Indication: Product Used FOR Unknown Indication
Acetaminophen
Dosage: unk
Indication: Product Used FOR Unknown Indication
Possible Bisoprolol side effects / adverse reactions in 89 year old female
Reported by a physician from Italy on 2011-10-10
Patient: 89 year old female
Reactions: Drug Hypersensitivity, Prurigo
Adverse event resulted in: hospitalization
Suspect drug(s):
Enoxaparin Sodium
Indication: Thrombosis Prophylaxis
Start date: 2011-07-28
End date: 2011-08-06
Luvion
Administration route: Oral
Indication: Hyperaldosteronism
Start date: 2011-07-06
End date: 2011-08-06
Lasix
Administration route: Oral
Start date: 2011-07-06
End date: 2011-08-06
Ramipril
Administration route: Oral
Indication: Hypertension
Start date: 2011-05-20
End date: 2011-08-06
Levofloxacin
Administration route: Oral
Indication: Respiratory Tract Infection
Start date: 2011-07-06
End date: 2011-08-06
Lasix
Administration route: Oral
Indication: Cardiac Failure
Start date: 2011-07-06
End date: 2011-08-06
Allopurinol
Administration route: Oral
Indication: Gout
Start date: 2011-07-06
End date: 2011-08-06
Bisoprolol
Administration route: Oral
Indication: Cardiac Failure Chronic
Start date: 2011-07-06
End date: 2011-08-06
Possible Bisoprolol side effects / adverse reactions in 71 year old male
Reported by a health professional (non-physician/pharmacist) from France on 2011-10-13
Patient: 71 year old male
Reactions: Pulmonary Hypertension, Ventricular Extrasystoles, Bundle Branch Block Right, Cholestasis, Tricuspid Valve Incompetence, Hepatitis, Cholelithiasis, Hepatotoxicity, Mitral Valve Incompetence, Aortic Valve Incompetence, Atrioventricular Block First Degree
Adverse event resulted in: hospitalization
Suspect drug(s):
Prednisone
Dosage: 50 mg/day
Imuran
Dosage: 150 mg, 1x/day at lunch time
Administration route: Oral
Start date: 2011-05-01
End date: 2011-07-01
Furadantin
Dosage: 50 mg, unk
Start date: 2011-07-01
End date: 2011-07-01
Ramipril
Dosage: 1.5 mg, 1x/day in the morning
End date: 2011-07-01
Atorvastatin Calcium
Dosage: 40 mg, 1x/day at night
Administration route: Oral
End date: 2011-07-01
Bisoprolol
Dosage: 2.5 mg, 1x/day in the morning
End date: 2011-07-01
Other drugs received by patient: Lantus; Princi-B; Aspirin; Calcium Carbonate; Nexium; Acetaminophen
|