"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)./"...
Kerledex is usually well tolerated in properly selected patients. Discontinuation of therapy due to adverse events in U.S. controlled clinical trials was necessary in about 4% of patients receiving betaxolol in combination with chlorthalidone. The most frequent reasons for discontinuation were fatigue (1.1%) and bradycardia (0.9%). The following reasons for discontinuation of therapy were reported in 0.4% (2 patients each) of the 465 patients receiving the combination in U.S. controlled studies: myalgia, depression, insomnia, lethargy, palpitation, and elevated serum transaminase levels.
In controlled clinical trials, Kerledex has been evaluated versus placebo and/or its component monotherapies in doses of 5/12.5 mg, 5/25 mg, 10/12.5 mg, 10/25 mg, and 20/25 mg for treatment periods lasting 3 to 24 weeks. In these controlled studies, the most common adverse reactions to Kerledex were bradycardia, headache, dizziness, arthralgia, dyspepsia, and fatigue.
Kerledex adverse events with a 2% or greater frequency, and selected events with lower frequency, in these controlled studies are:
|Kerledex (n=465) 5/12.5–20/25 mg q.d.||Placebo (n=199)||Betaxolol (n=306) 5–20 mg q.d.||Chlorthalidone (n=494) 12.5–25 mg q .d.|
|Bradycardia (heart rate < 50 BPM)||7.3||0||5.2||0.6|
|Central Nervous System|
|Hypokalemia (serum K+<3.0 mEq/L)||2.4||0||0||5.1|
|Upper respiratory infection||4.5||6.5||4.9||6.1|
|*Percentage based on number of males: Kerledex n=282; placebo n=131; betaxolol n=188; chlorthalidone n=311.|
The following selected (potentially important) adverse events have been reported in patients receiving Kerledex at an incidence of less than 2.0% in U.S. controlled and long-term clinical studies. It is not known whether a causal relationship exists between Kerledex and these events, they are listed to alert the physician to a possible relationship.
Autonomic: flushing, sweating.
Body as a whole: allergy, chest pain, fever, malaise, pain.
Cardiovascular: angina pectoris, hypotension, palpitations, syncope.
Central and peripheral nervous system: asthenia, ataxia, dysphonia, migraine, neuralgia, numbness, paresthesia, twitching, vertigo.
Gastrointestinal: anorexia, constipation, dry mouth, dysphagia, gastroenteritis, increased appetite, mouth ulceration, rectal disorder, stomatitis, vomiting.
Hearing and vestibular: earache, tinnitus.
Hematologic: anemia, hyperhemoglobinemia, leucocytosis, lymphadenopathy.
Liver and biliary: cholecystitis, increased AST, increased ALT.
Metabolic and nutritional: diabetes mellitus, hypercalcemia, hyperglycemia, hyperlipemia, hyperuricemia, increased alkaline phosphatase, weight gain, weight loss.
Musculoskeletal: arthropathy, myalgia, neck pain, tendinitis.
Platelet, bleeding and clotting: purpura.
Psychiatric: amnesia, emotional lability, euphoria, decreased libido, hallucinations, hysteria, nightmares.
Reproductive: amenorrhea, dysmenorrhea, dyspareunia, epididymitis, menstrual disorder, ovarian disorder, prostatitis.
Respiratory: apnea, bronchitis, bronchospasm, cough, epistaxis, sinusitis.
Skin: follicular rash, photosensitivity, pruritus, skin disorders.
Special senses: dysgeusia.
Urinary: cystitis, dysuria, micturition disorder, polyuria, renal calculus, urethral disorder.
Vascular: cerebrovascular disorder, cold extremities (peripheral ischemia), leg cramps, phlebitis.
Vision: abnormal lacrimation, abnormal vision, conjunctivitis.
Other adverse events that have been reported with the individual components are listed by body system below:
Betaxolol: Autonomic: salivation;
Body as a whole: rigors;
Cardiovascular: arrhythmia, atrioventricular block, heart failure, hypertension, myocardial infarction, thrombosis;
Central and peripheral nervous system: neuropathy, speech disorder, stupor, tremor;
Hearing and vestibular: deafness, labyrinth disorders;
Metabolic and nutritional: acidosis, hypercholesterolemia, hyperkalemia, increased LDH, thirst;
Musculoskeletal: muscle cramps;
Psychiatric: abnormal thinking, impaired concentration, confusion;
Reproductive: breast pain, breast fibroadenosis, Peyronie's disease;
Respiratory: flu, pneumonia;
Special senses: taste loss;
Skin: alopecia, eczema, erythematous rash, hypertrichosis;
Urinary: oliguria, proteinuria, abnormal renal function, renal pain;
Vascular: intermittent claudication, thrombophlebitis;
Vision: blepharitis, cataract, dry eyes, iritis, ocular hemorrhage, 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 non-thrombocytopenic purpura; Gastrointestinal: Mesenteric arterial thrombosis, ischemic colitis; Vascular: Raynaud's phenomena.
The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with betaxolol during investigational use and extensive foreign experience. Dry eyes and skin rash, however, have been reported. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. Patients should be closely monitored following cessation of therapy.
Cardiovascular: orthostatic hypotension; Central and peripheral nervous system: xanthopsia; Gastrointestinal: cramping, gastric irritation, jaundice (intrahepatic cholestatic jaundice), pancreatitis; Hematologic: agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia; Dermatologic-Hypersensitivity: urticaria, necrotizing angiitis (vasculitis) (cutaneous vasculitis), Lyell's syndrome (toxic epidermal necrolysis); Miscellaneous: glycosuria, muscle spasm, restlessness, weakness.
Read the Kerledex (betaxolol hydrochloride and chlorthalidone) Side Effects Center for a complete guide to possible side effects
The following drugs have been coadministered with betaxolol and have not altered its pharmacokinetics: cimetidine, nifedipine, chlorthalidone, and hydrochlorothiazide. Concomitant administration of betaxolol with the oral anticoagulant warfarin has been shown not to potentiate the anticoagulant effect of warfarin.
Catecholamine-depleting drugs (eg, reserpine) may have an additive effect when given with beta-blocking agents. Patients treated with Kerledex plus a catecholamine depletor should, therefore, be closely observed for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Should it be decided to discontinue therapy in patients receiving Kerledex and clonidine concurrently, Kerledex should be discontinued slowly over several days before the gradual withdrawal of clonidine.
Literature reports suggest that oral calcium antagonists may be used in combination with beta-adrenergic blocking agents when heart function is normal, but should be avoided in patients with impaired cardiac function. Hypotension, AV conduction disturbances, and left ventricular failure have been reported in some patients receiving beta-adrenergic blocking agents when an oral calcium antagonist was added to the treatment regimen. Hypotension was more likely to occur if the calcium antagonist were a dihydropyridine derivative, eg, nifedipine, while left ventricular failure and AV conduction disturbances, including complete heart block, were more likely to occur with either verapamil or diltiazem.
Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.
Particular care should be taken when using anesthetic agents which depress the myocardium, such as ether, cyclopropane, and trichloroethylene (see WARNINGS, Major surgery).
Risk of anaphylactic reaction: Although it is known that patients on beta-blockers may be refractory to epinephrine in the treatment of anaphylactic shock, beta-blockers can, in addition, interfere with the modulation of allergic reaction and lead to an increased severity and/or frequency of attacks. Severe allergic reactions including anaphylaxis have been reported in patients exposed to a variety of allergens either by repeated challenge, or accidental contact, and with diagnostic or therapeutic agents while receiving beta-blockers. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.
Chlorthalidone: Medication such as digitalis may also influence serum electrolytes. Warning signs of electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, mental confusion, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting. Chlorthalidone and related drugs may increase the responsiveness to tubocurarine.
Chlorthalidone and related drugs may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.
Lithium generally should not be given with diuretics because they reduce its renal clearance and increase the risk of lithium toxicity. Read package inserts for lithium preparations before use of such preparations with Kerledex.
Drug/Laboratory test interactions
Chlorthalidone and related drugs may decrease serum PBI levels without signs of thyroid disturbance.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/11/2017
Additional Kerledex Information
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