"The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended the marketing of selexipag (Uptravi, Actelion Registration Ltd) for the treatment of adults with pulmonary arterial hypertension (PAH)./"...
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
|Body as a Whole||%||%||%|
|Upper respiratory infection||2.5||3.3||4.9|
|Skin and Appendages|
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
|Body as a Whole||%||%||%|
Potential Adverse Effects: In addition, certain adverse effects not listed above have been reported with other β-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.
Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.
Miscellaneous: Reversible alopecia and Peyronie's disease. The oculomucocutaneous syndrome associated with the β-blocker practolol has not been reported with levatol® during investigational use and extensive foreign clinical experience.
Read the Levatol (penbutolol sulfate) Side Effects Center for a complete guide to possible side effects
levatol® has been used in combination with hydrochlorothiazide in at least 100 patients without unexpected adverse reactions.
In one study, the combination of penbutolol and alcohol increased the number of errors in the eye-hand psychomotor function test.
Penbutolol increases the volume of distribution of lidocaine in normal subjects. This could result in a requirement for higher loading doses of lidocaine.
Cimetidine has no effect on the clearance of penbutolol. The major metabolite of penbutolol is a glucuronide, and it has been shown that cimetidine does not inhibit glucuronidation.
Synergistic hypotensive effects, bradycardia, and arrhythmias have been reported in some patients receiving β-adrenergic blocking agents when an oral calcium antagonist was added to the treatment regimen.
Generally, levatol® should not be used in patients receiving catecholamine-depleting drugs.
Digoxin: Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Anesthesia: Care should be taken when using anesthetic agents that depress the myocardium, such as ether, cyclopropane, and trichloroethylene, and it is prudent to use the lowest possible dose of levatol. levatol, like other β-blockers, is a competitive inhibitor of β-receptor agonists, and its effect on the heart can be reversed by cautious administration of such agents (eg, dobutamine or isoproterenol — see OVERDOSAGE). Manifestations of excessive vagal tone (eg, profound bradycardia, hypotension) may be corrected with atropine 1 to 3 mg IV in divided doses.
Risk of Anaphylactic Reaction: While taking β-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
Read the Levatol Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 6/10/2011
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