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Most adverse reactions have been mild and transient and are typical of beta-adrenergic blocking agents, eg, bradycardia, fatigue, dyspnea, and lethargy. Withdrawal of therapy in U.S. and European controlled clinical trials has been necessary in about 3.5% of patients, principally because of bradycardia, fatigue, dizziness, headache, and impotence.

Frequency estimates of adverse events were derived from controlled studies in which adverse reactions were volunteered and elicited in U.S studies and volunteered and/or elicited in European studies.

In the U.S., the placebo-controlled hypertension studies lasted for 4 weeks, while the active-controlled hypertension studies had a 22- to 24- week double-blind phase. The following doses were studied: betaxolol-5, 10, 20, and 40 mg once daily; atenolol-25, 50, and 100 mg once daily; and propranolol-40, 80, and 160 mg b.i.d.

Kerlone (betaxolol hydrochloride) , like other beta-blockers, has been associated with the development of antinuclear antibodies (ANA) (e.g., lupus erythematosus). In controlled clinical studies, conversion of ANA from negative to positive occurred in 5.3% of the patients treated with betaxolol, 6.3% of the patients treated with atenolol, 4.9% of the patients treated with propranolol, and 3.2% of the patients treated with placebo.

Betaxolol adverse events reported with a 2% or greater frequency, and selected events with lower frequency, in U.S. controlled studies are:

Dose Range Betaxolol
5-40 mg q.d.*
40-160 mg b.i.d.
25-100 mg q.d.
Body System/Adverse Reaction (%) (%) (%) (%)
  Bradycardia (heart rate < 50 BPM) 8.1 4.1 12.0 0
  Symptomatic bradycardia 0.8 1.4 0 0
  Edema 1.8 0 0 1.8
Central Nervous System
  Headache 6.5 4.1 5.3 15.6
  Dizziness 4.5 11.0 2.7 5.5
  Fatigue 2.9 9.6 4.0 0
  Lethargy 2.8 4.1 2.7 0.9
  Insomnia 1.2 8.2 2.7 0
  Nervousness 0.8 1.4 2.7 0
  Bizarre dreams 1.0 2.7 1.3 0
  Depression 0.8 2.7 4.0 0
  Impotence 1.2 0 0 0
  Dyspnea 2.4 2.7 1.3 0.9
  Pharyngitis 2.0 0 4.0 0.9
  Rhinitis 1.4 0 4.0 0.9
  Upper respiratory infection 2.6 0 0 5.5
  Dyspepsia 4.7 6.8 2.7 0.9
  Nausea 1.6 1.4 4.0 0
  Diarrhea 2.0 6.8 8.0 0.9
  Chest pain 2.4 1.4 2.7 0.9
  Arthralgia 3.1 0 4.0 1.8
  Rash 1.2 0 0 0
*Five patients received 80 mg q.d.
N=336 males; impotence is a known possible adverse effect of this pharmacological class.

Of the above adverse reactions associated with the use of betaxolol, only bradycardia was clearly dose related, but there was a suggestion of dose relatedness for fatigue, lethargy, and dyspepsia.

In Europe, the placebo-controlled study lasted for 4 weeks, while the comparative studies had a 4- to 52-week double-blind phase. The following doses were studied: betaxolol 20 and 40 mg once daily and atenolol 100 mg once daily.

From European controlled hypertension clinical trials, the following adverse events reported by 2% or more patients and selected events with lower frequency are presented:

Dose range Betaxolol
20-40 mg q.d.
100 mg q.d.
Body System/Adverse Reaction (%) (%) (%)
  Bradycardia (heartrate < 50 BPM) 5.8 5.0 0
  Symptomatic bradycardia 1.9 2.5 0
  Palpitation 1.9 3.7 1.7
  Edema 1.3 1.2 0
  Cold extremities 1.9 0 0
Central Nervous System
  Headache 14.8 9.9 23.3
  Dizziness 14.8 17.3 15.0
  Fatigue 9.7 18.5 0
  Asthenia 7.1 0 16.7
  Insomnia 5.0 3.7 3.3
  Paresthesia 1.9 2.5 0
  Nausea 5.8 1.2 0
  Dyspepsia 3.9 7.4 3.3
  Diarrhea 1.9 3.7 0
  Chest pain 7.1 6.2 5.0
  Joint pain 5.2 4.9 1.7
  Myalgia 3.2 3.7 3.3

The only adverse event whose frequency clearly rose with increasing dose was bradycardia. Elderly patients were especially susceptible to bradycardia, which in some cases responded to dose-reduction (see PRECAUTIONS).

The following selected (potentially important) adverse events have been reported at an incidence of less than 2% in U.S. controlled and open, long-term clinical studies, European controlled clinical trials, or in marketing experience. It is not known whether a causal relationship exists between betaxolol and these events; they are listed to alert the physician to a possible relationship:

Autonomic: flushing, salivation, sweating.

Body as a whole: allergy, fever, malaise, pain, rigors.

Cardiovascular: angina pectoris, arrhythmia, atrioventricular block, heart failure, hypertension, hypotension, myocardial infarction, thrombosis, syncope.

Central and peripheral nervous system: ataxia, neuralgia, neuropathy, numbness, speech disorder, stupor, tremor, twitching.

Gastrointestinal: anorexia, constipation, dry mouth, increased appetite, mouth ulceration, rectal disorders, vomiting, dysphagia.

Hearing and Vestibular: earache, labyrinth disorders, tinnitus, deafness.

Hematologic: anemia, leucocytosis, lymphadenopathy, purpura, thrombocytopenia.

Liver and biliary: increased AST, increased ALT.

Metabolic and nutritional: acidosis, diabetes, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipemia, hyperuricemia, hypokalemia, weight gain, weight loss, thirst, increased LDH.

Musculoskeletal: arthropathy, neck pain, muscle cramps, tendonitis.

Psychiatric:abnormal thinking, amnesia, impaired concentration, confusion, emotional lability, hallucinations, decreased libido.

Reproductive disorders: Female: breast pain, breast fibroadenosis, menstrual disorder; Male: Peyronie's disease, prostatitis.

Respiratory: bronchitis, bronchospasm, cough, epistaxis, flu, pneumonia, sinusitis.

Skin: alopecia, eczema, erythematous rash, hypertrichosis, pruritus, skin disorders.

Special senses: abnormal taste, taste loss.

Urinary system: cystitis, dysuria, micturition disorder, oliguria, proteinuria, abnormal renal function, renal pain.

Vascular:cerebrovascular disorder, intermittent claudication, leg cramps, peripheral ischemia, thrombophlebitis.

Vision: abnormal lacrimation, abnormal vision, blepharitis, ocular hemorrhage, conjunctivitis, dry eyes, iritis, cataract, scotoma.

Potential adverse effects: Although not reported in clinical studies with betaxolol, a variety of adverse effects have been reported with other beta-adrenergic blocking agents and may be considered potential adverse effects of betaxolol:

Central 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 with slightly clouded sensorium, and decreased performance on neuropsychometric tests.

Allergic: Fever combined with aching and sore throat, laryngospasm, respiratory distress.

Hematologic: Agranulocytosis, thrombocytopenic purpura, and nonthrombocytopenic purpura.

Gastrointestinal: Mesenteric arterial thrombosis, ischemic colitis.

Metabolic: Hypoglycemia.

Miscellaneous: Raynaud's phenomena. There have been reports of skin rashes and/or dry eyes associated with the use of beta-adrenergic blocking drugs. The reported incidence is small, and in most cases, the symptoms have cleared when treatment was withdrawn. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. Patients should be closely monitored following cessation of therapy.

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with Kerlone (betaxolol hydrochloride) during investigational use and extensive foreign experience. However, dry eyes have been reported.