Bystolic (Nebivolol) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

The data described below reflect worldwide clinical trial exposure to BYSTOLIC in 6545 patients, including 5038 patients treated for hypertension and the remaining 1507 subjects treated for other cardiovascular diseases. Doses ranged from 0.5 mg to 40 mg. Patients received BYSTOLIC for up to 24 months, with over 1900 patients treated for at least 6 months, and approximately 1300 patients for more than one year. In placebo-controlled clinical trials comparing BYSTOLIC with placebo, discontinuation of therapy due to adverse events was reported in 2.8% of patients treated with nebivolol and 2.2% of patients given placebo. The most common adverse events that led to discontinuation of BYSTOLIC were headache (0.4%), nausea (0.2%) and bradycardia (0.2%).

Adverse Reactions in Controlled Trials

Table 2 lists treatment-emergent signs and symptoms that were reported in three 12-week, placebo-controlled monotherapy trials involving 1597 hypertensive patients treated with either 5 mg, 10 mg or 20-40 mg of BYSTOLIC and 205 patients given placebo and for which the rate of occurrence was at least 1% of patients treated with nebivolol and greater than the rate for those treated with placebo in at least one dose group.

Table 2. Treatment-Emergent Adverse Events with an Incidence (over 6 weeks) ≥ 1% in BYSTOLIC-Treated Patients and at a Higher Frequency than Placebo-Treated Patients

	Placebo (n = 205) (%)	Nebivolol 5 mg (n = 459) (%)	Nebivolol 10 mg (n = 461) (%)	Nebivolol 20-40 mg (n = 677) (%)
Headache	6	9	6	7
Fatigue	1	2	2	5
Dizziness	2	2	3	4
Diarrhea	2	2	2	3
Nausea	0	1	3	2
Insomnia	0	1	1	1
Chest pain	0	0	1	1
Bradycardia	0	0	0	1
Dyspnea	0	0	1	1
Rash	0	0	1	1
Peripheral edema	0	1	1	1

Other Adverse Events Observed During Worldwide Clinical Trials

Listed below are other reported adverse events with an incidence of at least 1% in the more than 5300 patients treated with BYSTOLIC in controlled or open-label trials, whether or not attributed to treatment, except for those already appearing in Table 2, terms too general to be informative, minor symptoms, or events unlikely to be attributable to drug because they are common in the population. These adverse events were in most cases observed at a similar frequency in placebo-treated patients in the controlled studies.

Body as a whole: asthenia.

Gastrointestinal System Disorders: abdominal pain

Metabolic and Nutritional Disorders: hypercholesterolemia and hyperuricemia

Nervous System Disorders: paraesthesia

Laboratory

In controlled monotherapy trials, BYSTOLIC was associated with an increase in BUN, uric acid, triglycerides and a decrease in HDL cholesterol and platelet count.

Events Identified from Spontaneous Reports of BYSTOLIC Received Worldwide

The following adverse events have been identified from spontaneous reports of BYSTOLIC received worldwide and have not been listed elsewhere. These adverse events have been chosen for inclusion due to a combination of seriousness, frequency of reporting or potential causal connection to BYSTOLIC. Events common in the population have generally been omitted. Because these events were reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency or establish a causal relationship to BYSTOLIC exposure: abnormal hepatic function (including increased AST, ALT and bilirubin), acute pulmonary edema, acute renal failure, atrioventricular block (both second and third degree), bronchospasm, erectile dysfunction, hypersensitivity (including urticaria, allergic vasculitis and rare reports of angioedema), myocardial infarction, pruritus, psoriasis, Raynaud's phenomenon, peripheral ischemia/claudication, somnolence, syncope, thrombocytopenia, various rashes and skin disorders, vertigo, and vomiting.

REPORTS OF SUSPECTED BYSTOLIC SIDE EFFECTS / ADVERSE REACTIONS

Possible Bystolic side effects / adverse reactions in 64 year old female

Reported by a consumer/non-health professional from United States on 2011-10-13

Patient: 64 year old female weighing 79.4 kg (174.6 pounds)

Reactions: Alopecia

Suspect drug(s):
Bystolic

Possible Bystolic side effects / adverse reactions in 77 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-19

Patient: 77 year old female weighing 72.3 kg (159.1 pounds)

Reactions: Bladder Dilatation, Blood Uric Acid Increased, Bacterial Test Positive, Blood Glucose Increased, Renal Failure Acute, Respiratory Rate Increased, Urine Analysis Abnormal, Alanine Aminotransferase Increased, Blood Lactate Dehydrogenase Increased, Atrial Fibrillation, Urinary Casts Present, Body Temperature Decreased, White Blood Cells Urine Positive, Heart Rate Decreased, Aspartate Aminotransferase Increased, RED Blood Cells Urine Positive

Adverse event resulted in: hospitalization

Suspect drug(s):
Crizotinib (Crizotinib)
    Dosage: 250 mg (250 mg, 2 in 1 d), oral
    Administration route: Oral
    Indication: Lung Neoplasm Malignant
    Start date: 2011-06-02
    End date: 2011-06-22

Valsartan
    Dosage: 320 mg (160 mg, 2 in 1 d), oral
    Administration route: Oral
    Indication: Hypertension
    Start date: 2009-01-01
    End date: 2011-06-21

Torsemide
    Dosage: 10 mg (10 mg, 1 in 1 d), oral
    Administration route: Oral
    Indication: Hypertension
    Start date: 2009-01-01
    End date: 2011-06-21

Bystolic
    Dosage: 5 mg (5 mg, 1 in 1 d), oral
    Administration route: Oral
    Indication: Hypertension
    Start date: 2011-06-02
    End date: 2011-06-21

Possible Bystolic side effects / adverse reactions in 39 year old male

Reported by a consumer/non-health professional from United States on 2011-10-28

Patient: 39 year old male

Reactions: Dyspnoea, Chest Pain, Drug Interaction, Dizziness

Suspect drug(s):
Bystolic
    Administration route: Oral
    Start date: 2008-01-01

Zocor
    Start date: 2008-01-01

Advair Diskus 100/50
    Indication: Asthma
    Start date: 2008-01-01

Other drugs received by patient: Bystolic; Zocor