Levatol (Penbutolol Sulfate) - Side Effects and Adverse Reactions

Adverse Reactions

levatol® is usually well tolerated in properly selected patients. Most adverse effects observed during clinical trials have been mild and reversible.

Table 1 lists the adverse reactions reported from 4 controlled studies conducted in the United States involving once-a-day administration of levatol® (at doses ranging from 10 to 120 mg) as monotherapy or in combination with hydrochlorothiazide. levatol® doses above 40 mg/day are not, however, recommended. The table includes only those events where the prevalence rate in the levatol® group was at least 1.5%, or where the reaction is of particular interest.

Over a dose range from 10 to 40 mg, once a day, fatigue, nausea, and sexual impotence occurred at a greater frequency as the dose was increased.

Table 1: ADVERSE REACTIONS DURING CONTROLLED US STUDIES

Body System Experience	Penbutolol (N=628)	Placebo (N=212)	Propranolol (N=266)
Body as a Whole	%	%	%
Asthenia	1.6	0.9	4.9
Pain, chest	2.4	2.8	2.3
Pain, limb	2.4	1.4	1.5
Digestive System
Diarrhea	3.3	1.9	2.6
Nausea	4.3	0.9	2.3
Dyspepsia	2.7	1.4	5.3
Nervous System
Dizziness	4.9	2.4	4.2
Fatigue	4.4	1.9	2.6
Headache	7.8	6.1	7.5
Insomnia	1.9	0.9	2.6
Respiratory System
Cough	2.1	0.5	1.1
Dyspnea	2.1	1.4	3.4
Upper respiratory infection	2.5	3.3	4.9
Skin and Appendages
Sweating, excessive	1.6	0.5	2.3
Urogenital System
Impotence, sexual	0.5	0.0	0.8

In a double-blind clinical trial comparing levatol® (40 mg and greater once a day) and propranolol (40 mg or more twice a day), heart rates of less than 60 beats/min. were recorded at least once in 25% of the patients in the group receiving levatol® and in 37% of the patients in the propranolol group. Corresponding figures for heart rates of less than 50 beats/min. were 1.2% and 6% respectively. No symptoms associated with bradycardia were reported.

Discontinuations of levatol® because of adverse reactions have ranged between 2.4% and 6.9% of patients in double-blind, parallel, controlled clinical trials, as compared to 1.8% to 4.1% in the corresponding control groups that were given placebo. The frequency and severity of adverse reactions have not increased during long-term administration of levatol®. The prevalence of adverse reactions reported from 4 controlled clinical trials (referred to in Table 1) as reasons for discontinuation of therapy by > 0.5% of the levatol® group is listed in Table 2.

Table 2: DISCONTINUATIONS DURING CONTROLLED US STUDIES

Body System Experience	Penbutolol (N=628)	Placebo (N=212)	Propranolol (N=266)
Body as a Whole	%	%	%
Asthenia	0.6	0.0	0.4
Pain, chest	0.6	1.4	0.4
Digestive System
Nausea	0.8	0.0	0.8
Nervous System
Depression	0.6	0.5	0.8
Dizziness	0.6	0.0	0.4
Fatigue	0.5	0.5	0.0
Headache	0.6	0.5	0.4

Potential Adverse Effects: In addition, certain adverse effects not listed above have been reported with other ß-blocking agents and should also be considered as potential adverse effects of levatol®.

Central Nervous System: Reversible mental depression progressing to catatonia (an acute syndrome characterized by disorientation for time and place), short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance (neuropsychometrics).

Cardiovascular: Intensification of AV block (see CONTRAINDICATIONS).

Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Hematologic: Agranulocytosis, nonthrombocytopenic and thrombocytopenic purpura.

Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.

Miscellaneous: Reversible alopecia and Peyronie’s disease. The oculomucocutaneous syndrome associated with the ß-blocker practolol has not been reported with levatol® during investigational use and extensive foreign clinical experience.