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, 10, and 20 mg bisoprolol fumarate were administered for 4 weeks. In Study B, doses of 2.5, 10, and 40 mg of bisoprolol fumarate were administered for 12 weeks. A total of 273 patients were treated with 5-20 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 (2.5-40 mg), as well as for a subgroup that was treated with doses within the recommended dosage range (5-20 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)
|
5-20 mg (n=273)
|
2.5-40 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 ZEBETA:
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 ZEBETA (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 4-12 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 6-18 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 ZEBETA SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Zebeta. The information is not vetted and should not be considered as verified clinical evidence.
Possible Zebeta side effects / adverse reactions in 71 year old female
Reported by a health professional (non-physician/pharmacist) from Germany on 2012-07-03
Patient: 71 year old female
Reactions: Hypotension, Dizziness
Adverse event resulted in: hospitalization
Suspect drug(s):
Lyrica
Dosage: 50 mg, unk
Administration route: Oral
Start date: 2012-02-09
Lyrica
Dosage: 100 mg, unk
Administration route: Oral
Start date: 2012-02-08
End date: 2012-02-08
Lyrica
Dosage: 50 mg, daily
Administration route: Oral
Indication: Hypertension
Start date: 2012-01-27
End date: 2012-02-07
Mirtazapine
Dosage: 15 mg, daily
Administration route: Oral
Start date: 2012-01-26
Pipamperone
Dosage: 160 mg, daily
Administration route: Oral
Start date: 2012-02-07
End date: 2012-02-08
Prothipendyl
Dosage: 80 mg, daily
Administration route: Oral
Start date: 2012-01-31
Prothipendyl
Dosage: 40 mg, single
Administration route: Oral
Indication: Product Used FOR Unknown Indication
Start date: 2012-01-30
End date: 2012-01-30
Ramipril
Dosage: 2.5 mg, daily
Administration route: Oral
Indication: Product Used FOR Unknown Indication
Seroquel
Dosage: 100 mg, daily
Administration route: Oral
Torasemide
Dosage: 50 mg, daily
Administration route: Oral
Zebeta
Dosage: 2.5 mg, daily
Administration route: Oral
Other drugs received by patient: Voltaren; Moviprep; Pantoprazole; Simvastatin; Gliquidone; Acetylsalicylic Acid; Clonazepam
|