ADVERSE REACTIONS
BLOCADREN is usually well tolerated in properly selected patients. Most adverse effects have been mild and transient.
In a multicenter (12-week) clinical trial comparing timolol maleate and placebo in hypertensive patients, the following adverse reactions were reported spontaneously and considered to be causally related to timolol maleate:
| |
Timolol Maleate
(n = 176)
%
|
Placebo
(n = 168)
%
|
BODY AS A WHOLE
fatigue/tiredness
headache
chest pain
asthenia |
3.4
1.7
0.6
0.6 |
0.6
1.8
0
0 |
CARDIOVASCULAR
bradycardia
arrhythmia
syncope
edema |
9.1
1.1
0.6
0.6 |
0
0.6
0
1.2 |
DIGESTIVE
dyspepsia
nausea |
0.6
0.6 |
0.6
0 |
SKIN
pruritus |
1.1 |
0 |
NERVOUS SYSTEM
dizziness
vertigo
paresthesia |
2.3
0.6
0.6 |
1.2
0
0 |
PSYCHIATRIC
decreased libido |
0.6 |
0 |
RESPIRATORY
dyspnea
bronchial spasm
rales |
1.7
0.6
0.6 |
0.6
0
0 |
SPECIAL SENSES
eye irritation
tinnitus |
1.1
0.6 |
0.6
0 |
These data are representative of the incidence of adverse effects that may be observed in properly selected patients treated with BLOCADREN, i.e., excluding patients with bronchospastic disease, congestive heart failure or other contraindications to beta blocker therapy.
In patients with migraine the incidence of bradycardia was 5 percent.
In a coronary artery disease population studied in the Norwegian multi-center trial (see CLINICAL PHARMACOLOGY), the frequency of the principal adverse reactions and the frequency with which these resulted in discontinuation of therapy in the timolol and placebo groups were:
| | Adverse Reaction
| Withdrawal
|
| | Timolol
(n=945)
%
| Placebo
(n=939)
%
| Timolol
(n=945)
%
| Placebo
(n=939)
%
|
| Asthenia or Fatigue | 5 | 1 | <1 | <1 |
| Heart Rate <40 beats/minute | 5 | <1 | 4 | <1 |
| Cardiac Failure-Nonfatal | 8 | 7 | 3 | 2 |
| Hypotension | 3 | 2 | 3 | 1 |
| Pulmonary Edema-Nonfatal | 2 | <1 | <1 | <1 |
| Claudication | 3 | 3 | 1 | <1 |
| AV Block - 2nd or 3rd degree | <1 | <1 | <1 | <1 |
| Sinoatrial Block | <1 | <1 | <1 | <1 |
| Cold Hands and Feet | 8 | <1 | <1 | 0 |
| Nausea or Digestive Disorders | 8 | 6 | 1 | <1 |
| Dizziness | 6 | 4 | 1 | 0 |
| Bronchial Obstruction | 2 | <1 | 1 | <1 |
The following additional adverse effects have been reported in clinical experience with the drug: Body as a Whole: anaphylaxis, extremity pain, decreased exercise tolerance, weight loss, fever; Cardiovascular: cardiac arrest, cardiac failure, cerebral vascular accident, worsening of angina pectoris, worsening of arterial insufficiency, Raynaud's phenomenon, palpitations, vasodilatation; Digestive: gastrointestinal pain, hepatomegaly, vomiting, diarrhea, dyspepsia; Hematologic: nonthrombocytopenic purpura; Endocrine: hyperglycemia, hypoglycemia; Skin: rash, skin irritation, increased pigmentation, sweating, alopecia; Musculoskeletal: arthralgia; Nervous System: local weakness, increase in signs and symptoms of myasthenia gravis; Psychiatric: depression, nightmares, somnolence, insomnia, nervousness, diminished concentration, hallucinations; Respiratory: cough; Special Senses: visual disturbances, diplopia, ptosis, dry eyes; Urogenital: impotence, urination difficulties.
There have been reports of retroperitoneal fibrosis in patients receiving timolol maleate and in patients receiving other beta-adrenergic blocking agents. A causal relationship between this condition and therapy with beta-adrenergic blocking agents has not been established.
Potential Adverse Effects: In addition, a variety of adverse effects not observed in clinical trials with BLOCADREN, but reported with other beta-adrenergic blocking agents, should be considered potential adverse effects of BLOCADREN: 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); Digestive: Mesenteric arterial thrombosis, ischemic colitis; Hematologic: Agranulocytosis, thrombocytopenic purpura; Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Miscellaneous: Peyronie's disease.
There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis, and sclerosing serositis attributed to the beta-adrenergic receptor blocking agent, practolol. This syndrome has not been reported with BLOCADREN.
Clinical Laboratory Test Findings: Clinically important changes in standard laboratory parameters were rarely associated with the administration of BLOCADREN. Slight increases in blood urea nitrogen, serum potassium, uric acid, and triglycerides, and slight decreases in hemoglobin, hematocrit and HDL cholesterol occurred, but were not progressive or associated with clinical manifestations. Increases in liver function tests have been reported.
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