VASCOR SIDE EFFECTS

SIDE EFFECTS

Adverse reactions were assessed in placebo and active-drug controlled trials of 4-12 weeks duration and longer-term uncontrolled studies. The most common side effects occurring more frequently than in control groups were upper gastrointestinal complaints (nausea, dyspepsia or GI distress) in about 22%, diarrhea in about 8%, dizziness in about 15%, asthenia in about 10% and nervousness in about 7%. The adverse reactions seen in at least 2% of bepridil patients in controlled trials are shown in the following table.

 

SRC: NLM .

 

 

Adverse Experiences by Body System and Treatment in Greater Than 2% of Bepridil Patients in Controlled Trials
Adverse Reaction	Bepridil HCl (N = 529)	Nifedipine (N = 50)	Propranolol (N = 88)	Diltiazem (N = 41)	Placebo (N = 190)
Body as a Whole
Asthenia	9.83	22.00	22.73	12.20	7.37
Headache	11.34	22.00	13.64	7.32	14.21
Flu Syndrome	2.08	8.00	2.27	a	1.05
Cardiovascular/Respiratory
Palpitations	2.27	6.00	2.27	0.00	1.58
Dyspnea	3.59	4.00	5.68	4.88	2.11
Respiratory Infection	2.84	4.00	3.41	4.88	3.68
Gastrointestinal
Dyspepsia	6.81	4.00	5.68	4.88	1.58
G.I. Distress	4.35	10.00	6.82	a	2.11
Nausea	12.29	14.00	11.36	2.44	3.68
Dry Mouth	3.40	0.00	0.00	2.44	2.63
Anorexia	3.02	0.00	2.27	0.00	1.58
Diarrhea	7.75	2.00	9.09	2.44	2.63
Abdominal Pain	3.02	4.00	1.14	a	3.16
Constipation	2.84	6.00	1.14	4.88	2.11
Central Nervous System
Drowsy	3.78	4.00	4.55	a	3.68
Insomnia	2.65	6.00	3.41	a	1.05
Dizziness	14.74	30.00	10.23	4.88	9.47
Tremor	4.91	4.00	0.00	a	1.05
Tremor of Hand	3.02	4.00	0.00	a	0.53
Paresthesia	2.46	2.00	1.14	4.88	3.16
Psychiatric
Nervous	7.37	16.00	1.14	2.44	3.68
a No data available.

In one twelve week controlled study, daily doses of 200, 300, and 400 mg were compared to placebo. The following table shows the rates of more common reactions (at least 5% in at least one bepridil group).

 

 

Adverse Experiences by Body System and Treatment In Greater Than 5% of Bepridil Patients in Controlled Trials
Adverse Reaction	Bepridil HCl 200 mg	Bepridil HCl 300 mg	Bepridil HCl 400 mg	Placebo
	(N = 43)	(N = 46)	(N = 44)	(N = 44)
Body as a Whole
Asthenia	13.95	6.52	11.36	2.27
Headache	6.98	8.70	13.64	15.91
Cardiovascular/Respiratory
Palpitations	0.00	6.52	4.55	0.00
Dyspnea	2.33	8.70	0.00	2.27
Gastrointestinal
G.I. Distress	6.98	0.00	4.55	4.55
Nausea	6.98	26.09	18.18	2.27
Anorexia	0.00	2.17	6.82	2.27
Diarrhea	0.00	10.87	6.82	0.00
Central Nervous System
Drowsy	6.98	6.52	0.00	4.55
Dizziness	11.63	15.22	27.27	6.82
Tremor	6.98	0.00	4.55	0.00
Tremor of Hand	9.30	0.00	4.55	0.00
Psychiatric
Nervous	11.63	8.70	11.36	0.00
Special Senses
Tinnitus	0.00	6.52	2.27	2.27

Adverse experiences in long-term open studies were generally similar to those seen in controlled trials.

Although adverse experiences were frequent (at least one being reported in 71% of patients participating in controlled clinical trials), most were well-tolerated. About 15% of patients however, discontinued bepridil treatment because of adverse experiences. In controlled clinical trials, these were principally gastrointestinal (1.0%), dizziness (1.0%) ventricular arrhythmias (1.0%) and syncope (0.6%). The major reasons for discontinuation, with comparison to control agents, are shown below.

 

 

Most Common Events Resulting in Discontinuation
Adverse Reaction	Bepridil (N = 515) n (%)	Placebo (N = 288) n (%)	Positive Control (N = 119) n (%)
Dizziness	5 (0.97)	0 (0.0)	2 (1.68)
Gastrointestinal Symptoms	5 (0.97)	0 (0.0)	5 (4.20)
Ventricular Arrhythmia	5 (0.97)	0 (0.0)	0 (0.0)
Syncope	3 (0.58)	0 (0.0)	0 (0.0)

Across all controlled and uncontrolled trials, VASCOR (bepridil) was evaluated in over 800 patients with chronic angina. In addition to the adverse reactions noted above, the following were observed in 0.5 to 2.0% of the VASCOR (bepridil) patients or are rarer, but potentially important events seen in clinical studies or reported in post marketing experience. In most cases it is not possible to determine whether there is a causal relationship to bepridil treatment.

Body as a Whole:   Fever, pain, myalgic asthenia, superinfection, flu syndrome.

Cardiovascular/Respiratory:   Sinus tachycardia, sinus bradycardia, hypertension, vasodilation, edema, ventricular premature contractions, ventricular tachycardia, prolonged QT interval, rhinitis, cough, pharyngitis.

Gastrointestinal:   Flatulence, gastritis, appetite increase, dry mouth, constipation.

Musculoskeletal:   Arthritis.

Central Nervous System:   Fainting, vertigo, akathisia, drowsiness, insomnia, tremor.

Psychiatric:   Depression, anxiousness, adverse behavior effect.

Skin:   Rash, sweating, skin irritation.

Special Senses:   Blurred vision, tinnitus, taste change.

Urogenital:   Loss of libido, impotence.

Abnormal Lab Values:   Abnormal liver function test, SGPT increase.

In postmarketing experience with other calcium blockers, gynecomastia has been rarely observed.

Certain cardiovascular events, such as acute myocardial infarction (about 3% of patients) worsened heart failure (1.9%), worsened angina (4.5%), severe arrhythmia (about 2.4% VT/VF) and sudden death (1.6%) have occurred in patients receiving bepridil, but have not been included as adverse events because they appear to be, and cannot be distinguished from, manifestations of the patient’s underlying cardiac disease. Such events as torsades de pointes arrhythmias, prolonged QT/QTc, bradycardia, first degree heart block, which are probably related to bepridil, are included in the tables.