Betaxolol Hydrochloride eent

Class: beta-Adrenergic Blocking Agents
ATC Class: S01ED52
VA Class: OP101
Molecular Formula: C18H29NO3•ClH
CAS Number: 63659-19-8
Brands: Betoptic S

Introduction

β1-selective adrenergic blocking agent.1 2 3 4 5 6 7 8 9 10 121 122

Uses for Betaxolol Hydrochloride

Ocular Hypertension and Glaucoma

Reduction of elevated intraocular pressure (IOP) in patients with chronic open-angle glaucoma1 2 8 12 18 19 20 74 93 94 121 a b 122 and ocular hypertension.1 2 9 10 11 94 a b Used alone or in conjunction wth a topical miotic121 122 (e.g., pilocarpine),1 2 12 18 122 topical dipivefrin,1 2 99 122 topical epinephrine, 1 12 18 74 98 121 122 and/or a carbonic anhydrase inhibitor.1 2 10 12 121 122

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

May be used safely in selected patients with reactive airway disease (e.g., asthma, chronic bronchitis, COPD).1 2 20 21 30 97 (See Respiratory Effects under Cautions.)

Betaxolol Hydrochloride Dosage and Administration

General

  • Adjust dosage to individual requirements and response of patient as determined by tonometric readings before and during therapy.1 65

  • Because of diurnal variations in IOP, measure IOP at different times during the day to determine if an adequate hypotensive effect is maintained.107 Since IOP may not stabilize for a few weeks after initiating therapy, determine IOP after about 4 weeks of therapy; thereafter, determine IOP as necessary.1

Administration

Ophthalmic Administration

Apply topically to the eye as an ophthalmic solutionb or suspensiona .

Avoid contamination of the solution or suspension container.1 103 121 a b

Shake suspension well prior to use.121 122

Suspension should not be administered while wearing contact lenses.121

Dosage

Available as betaxolol hydrochloride; dosage expressed in terms of betaxolol.a

Suspension is therapeutically equivalent (in terms of magnitude and duration of hypotensive effect) to solution.121 122 126

Each 2.8 or 5.6 mg of betaxolol hydrochloride is equivalent to about 2.5 or 5 mg of betaxolol, respectively.1 2 121 a b

Adults

Ocular Hypertension and Glaucoma
Ophthalmic

Betaxolol solution: 1–2 drops of a 0.5% solution in affected eye(s) twice daily. b 8 2 121 122

Betaxolol suspension: 1–2 drops of a 0.25% suspension in affected eye(s) twice daily. 1 a 8 2 121 122

If further reduction of IOP is required, a topical miotic,1 2 18 74 121 topical dipivefrin,2 12 99 122 topical epinephrine,1 12 18 74 98 121 122 and/or a carbonic anhydrase inhibitor1 2 10 12 121 122 may be added.1 2 10 12 74 121 122

Cautions for Betaxolol Hydrochloride

Contraindications

Known hypersensitivity to betaxolol or any ingredient in the formulation.a b

Sinus bradycardia,1 18 121 a b AV block greater than first degree,1 18 121 cardiogenic shock,1 18 121 or overt cardiac failure 1 121 that is not adequately compensated (e.g., with cardiac glycosides and/or diuretics).104

Warnings/Precautions

Warnings

Systemic Effects

May be absorbed systemically following topical application to the eye; consider the usual precautions associated with systemic use of β-adrenergic blocking agents when using topical betaxolol.1 119 121 a

Cardiovascular Effects

Severe cardiac reactions, including death associated with cardiac failure, have been reported in patients receiving topical (ocular) betaxolol.a b

Minor effects on BP 1 2 8 9 22 23 93 110 121 122 and heart rate reported.1 2 8 9 22 23 93 110

Use with caution in patients with a history of cardiac failure or heart block.1 119 121 Discontinue therapy at the first sign or symptom of cardiac failure.1 119 121

Respiratory Effects

Severe respiratory reactions, including death resulting from bronchospasm, have been reported in patients with asthma receiving topical (ocular) betaxolol.1 2

Increased airway resistance and pulmonary distress (i.e., dyspnea, bronchospasm, thickened bronchial secretions, asthma, respiratory failure) reported.1 21 95 121 122 Use caution in patients with evidence of reactive airway disease on pulmonary function testing or excessive restriction of pulmonary function.1 113 121 122

Sensitivity Reactions

History of Atopy or Anaphylactic Reactions

Possible increased reactivity to repeated accidental, diagnostic, or therapeutic challenges with a variety of allergens while taking β-adrenergic blocking agents.a b Such patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.a b

General Precautions

Diabetes Mellitus

β-Adrenergic blocking agents may mask sings and symptoms of acute hypoglycemia; administer with caution in patients subject to spontaneous hypoglycemia and in diabetic patients (especially those with labile diabetes) who are receiving hypoglycemic agents.1 88 121

Thyrotoxicosis

β-Adrenergic blocking agents may mask signs of hyperthyroidism (e.g., tachycardia).1 121

Possible thyroid storm if β-adrenergic blocking agent is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.1 121

Muscle Weakness

β-Adrenergic blocking agents reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, generalized weakness).1 121

Betaxolol reported rarely to increase muscle weakness in patients with myasthenia gravis or myasthenia symptoms.a b

Major Surgery

Possible increased risks associated with general anesthesia (e.g., severe hypotension, difficulty restarting or maintaining heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.1 121 Some clinicians recommend gradual withdrawal of β-adrenergic blocking agents prior to elective surgery.1 121

Angle-closure Glaucoma

Betaxolol has little to no effect on pupil size.1 2 8 9 11 12 18 93 99 121 122 Do not use alone in patients with angle-closure glaucoma; use only in combination with a miotic in these patients.1 121

Specific Populations

Pregnancy

Category C.a b

Lactation

Distributed into milk.83 Caution advised if used in nursing women.1 121

Pediatric Use

Safety and efficacy not established.1 11 121

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.a

Common Adverse Effects

Ocular stinging and discomfort on instillation.1 2 8 18 74 94 98 121 122 126

Interactions for Betaxolol Hydrochloride

Specific Drugs

Drug

Interaction

Comments

Adrenergic psychotropic agents

Possible antagonism of psychotropic agenta b

Use concomitantly with cautiona b

Catecholamine-depleting drugs (e.g., reserpine)

Possible additive effectsa b

Observe closely for evidence of marked hypotension or bradycardiaa b

Ocular hypotensive agents

Additive IOP-lowering effectsa b

Used to therapeutic advantagea b

Observe for additive effect of IOP reduction or systemic side effectsa b

Systemic β-adrenergic blocking agents

Additive systemic and ocular effectsa b

Betaxolol Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Extent of absorption following topical application not elucidated.104

Commercially available solution and suspension are bioequivalent.122 126

Onset

Following topical application to the eye with either the 0.25% suspension or the 0.5% solution, reduction in IOP usually evident within 0.5–1 hour and reaches a maximum within 2 hours.1 2 121

Duration

Reduction in IOP persists for ≥12 hours.1 2 121

Distribution

Extent

Distribution into human ocular tissues and fluids has not been characterized to date.104

Betaxolol crosses the placenta and is distributed into milk.83 108

Elimination

Metabolism

Systemically absorbed betaxolol is extensively metabolized to at least 5 metabolites.2 13 46

Stability

Storage

Ophthalmic

Solution

Tight containers at 15–30°C.b

Suspension

Upright at 15–30°C.a

Actions

  • Selective β1-adrenergic blocking agenta b 1 2 3 4 5 6 7 8 9 10 13 16 17 25 45 48 83 121 122 that does not exhibit intrinsic β1-agonist or membrane stabilizing (local anesthetic) activity.1 2 8 9 13 18 25 28 83 121 122

  • One of the most potent2 6 13 16 17 25 45 48 122 and selective2 13 16 17 25 48 122 β1-adrenergic blocking agents currently available.

  • Reduces both elevated1 2 8 9 11 12 14 19 93 94 121 122 and normal1 2 7 IOP8 9 10 11 14 19 93 94 121 without affecting pupillary size1 2 8 9 11 12 18 93 94 99 122 or accommodation2 8 9 11 122 and without producing miosis and/or ciliary spasm associated with miotic agents.1 2 8 9 11 12 18

  • Reduces IOP by about 20–35% from baseline in patients with elevated IOP.a b 1 8 9 11 122

  • Exact mechanism of action not fully elucidated; tonography and fluorophotometric studies suggest that reduced aqueous humor formation is the principal effect. a b 1 2 8 9 11 12 18 93 122

  • May block endogenous catecholamine-stimulated increases in cyclic adenosine monophosphate (AMP) concentrations within the ciliary processes and subsequent formation of aqueous humor.64 65 115 116 117 118

  • Does not appear to affect aqueous outflow resistance.7 19

  • Tolerance may develop with prolonged use;1 however, IOP-lowering effect maintained for ≥4 years of continuous use in some patients.2 104

Advice to Patients

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the product.a

  • Importance of not using suspension while having contact lenses in eyes.a

  • Advise patients to consult a clinician immediately regarding continued use of ophthalmic preparations if an intercurrent ocular condition (e.g., trauma, infection) occurs.

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.a

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing patients of other important precautionary information. a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Betaxolol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.5% (of betaxolol)*

Betaxolol Hydrochloride Ophthalmic Solution

Akorn, Apotex, Bausch & Lomb, Falcon

Suspension

0.25% (of betaxolol)

Betoptic S (with benzalkonium chloride)

Alcon

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Betaxolol HCl 0.5% Solution (SANDOZ): 15/$147.36 or 30/$289.80

Betoptic-S 0.25% Suspension (ALCON VISION): 10/$158.02 or 30/$449.00

Betoptic-S 0.25% Suspension (ALCON VISION): 15/$227.98 or 45/$668.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Alcon Laboratories. Betoptic (betaxolol hydrochloride) solution prescribing information. Ft. Worth, TX; 1991 Feb.

2. Alcon Laboratories. Betoptic product monograph. Ft. Worth, TX; 1985 Sep.

3. Weiner N. Drugs that inhibit adrenergic nerves and block adrenergic receptors. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York: Macmillan Publishing Company; 1985:181-214.

4. Windholz M, ed. The Merck index. 10th ed. Rahway, NJ: Merck & Co, Inc; 1983:169.

5. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:1684.

6. Manoury P. Betaxolol: chemistry and biological profile in relation to its physicochemical properties. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:13-9.

7. Reiss GR, Brubaker RF. The mechanism of betaxolol, a new ocular hypotensive agent. Ophthalmology. 1983; 90:1369-72. [PubMed 6664677]

8. Berrospi R, Leibowitz HM. Betaxolol: a new β-adrenergic blocking agent for treatment of glaucoma. Arch Ophthalmol. 1982; 100:943-6. [IDIS 151861] [PubMed 6124227]

9. Caldwell DR, Salisbury CR, Guzek JP. Effects of topical betaxolol in ocular hypertensive patients. Arch Ophthalmol. 1984; 102:539-40. [IDIS 183932] [PubMed 6704008]

10. Smith JP, Weeks RH, Newland EF et al. Betaxolol and acetazolamide: combined ocular hypotensive effect. Arch Ophthalmol. 1984; 102:1794-5. [IDIS 192616] [PubMed 6391442]

11. Radius RL. Use of betaxolol in the reduction of elevated intraocular pressure. Arch Ophthalmol. 1983; 101:898-900. [IDIS 171713] [PubMed 6860201]

12. Levy NS, Boone L, Ellis E. A controlled comparison of betaxolol and timolol with long-term evaluation of safety and efficacy. Glaucoma. 1985; 7:54-62.

13. Cavero I, Lefèevre-Borg F, Manoury P et al. In vitro and in vivo pharmacological evaluation of betaxolol, a new, potent, and selective β1-adrenoceptor antagonist. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:31-42.

14. Levy NS, Boone L. Effect of 0.25% betaxolol v placebo. Glaucoma. 1983; 5:230-2.

15. Vareilles P, Silverstone D, Plazonnet B et al. Comparison of the effects of timolol and other adrenergic agents on intraocular pressure in the rabbit. Invest Ophthalmol Vis Sci. 1977; 16:987-96. [PubMed 21145]

16. Shanks RG. Comparison of betaxolol with other β-blocking drugs in healthy volunteers. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:133-41.

17. Cadigan PJ, London D, Pentecost BL. Effects of betaxolol, given in single doses by mouth, on pulse rate and blood pressure in normal subjects. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:101-7.

18. Berry DP Jr, Van Buskirk EM, Shields MB. Betaxolol and timolol: a comparison of efficacy and side effects. Arch Ophthalmol. 1984; 102:42-5. [IDIS 180348] [PubMed 6367723]

19. Allen RC, Epstein DL. A double-masked clinical trial of betaxolol and timolol in glaucoma patients. Invest Ophthalmol Vis Sci. 1982; 22(Suppl):40.

20. Allen RC, Boys-Smith J. Betaxolol in patients with coexistant glaucoma and pulmonary disease. Invest Ophthalmol Vis Sci. 1984; 25(Suppl 3):305.

21. Schoene RB, Abuan T, Ward RL et al. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol. 1984; 97:86-92. [IDIS 180609] [PubMed 6141730]

22. Atkins JM, Pugh BR Jr, Timewell RM. Cardiovascular effects of topical beta-blockers during exercise. Am J Ophthalmol. 1985; 99:173-5. [IDIS 205613] [PubMed 3970121]

23. Hernandez y Hernandez H, Cervantes R, Frati A et al. Cardiovascular effects of topical glaucoma therapies in normal subjects. J Toxicol Cutaneous Ocul Toxicol. 1983; 2:99-106.

24. Bloom E, Richmond C, Alvarado J et al. Betaxolol vs. timolol: plasma radio-receptor assays to evaluate systemic complications of beta blocker therapy for glaucoma. Invest Ophthalmol. 1985; 26(Suppl):125.

25. Boudot JP, Cavero I, Féenard S et al. Preliminary studies on SL 75212, a new potent cardioselective β-adrenoceptor antagonist. Br J Pharmacol. 1979; 66:445P. [PubMed 43176]

26. Kilborn JR, Morselli PL, Saunders J et al. The effects of the new β-adrenoceptor blocker SL 75212 on the cardiovascular responses to insulin induced hypoglycaemia in man. Br J Clin Pharmacol. 1979; 8:409P. [IDIS 105845] [PubMed 41561]

27. Davis BJ, Turner P. The spectrofluorimetric estimation and buccal absorption of SL 75212, a novel β-adrenoceptor antagonist. Br J Clin Pharmacol. 1979; 8:405P. [IDIS 105840] [PubMed 41558]

28. Cadigan PJ, London DR, Pentecost BL et al. Cardiovascular effects of single oral doses of the new β-adrenoceptor blocking agent betaxolol (SL 75212) in healthy volunteers. Br J Clin Pharmacol. 1980; 9:569-75. [IDIS 115944] [PubMed 6104498]

29. Salonen JT, Palminteri R. Comparison of two doses of betaxolol and placebo in hypertension: a randomized, double-blind cross-over trial. Eur J Clin Pharmacol. 1982; 23:491-4. [IDIS 175848] [PubMed 6761136]

30. Vukich JA, Leef DL, Allen RC. Betaxolol in patients with coexistant chronic open angle glaucoma and pulmonary disease. Invest Ophthalmol. 1985; 26(Suppl):227.

31. DeSantis L, Chandler M. Cardiac beta blockade after ocular instillation of beta adrenergic blockers in alert cynomolgus monkeys: safety profile for betaxolol. Invest Ophthalmol. 1985; 26(Suppl):227.

32. Balnave K, Neill JD, Russell CJ et al. The duration of effect of SL 75212 on an exercise tachycardia. Br J Clin Pharmacol. 1980; 9:297P. [IDIS 115177] [PubMed 6102471]

33. Fillastre JP, Godin M, Cazor JL et al. Renal effects of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:183-93.

34. Friedmann JC. Safety evaluation of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:43-50.

35. Palminteri R, Kaik G. Time course of the bronchial response to salbutamol after placebo, betaxolol and propranolol. Eur J Clin Pharmacol. 1983; 24:741-5. [IDIS 173392] [PubMed 6136412]

36. Stroobandt R, Kesteloot H. Dose-related efficacy of betaxolol in patients with angina pectoris. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:257-60.

37. Kesteloot H, Missotten A, Coupez-Lopinot R et al. Effect of betaxolol on heart rate at rest and during exercise. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:155-9.

38. Saunders J, Gomeni R, Kilborn JR et al. A comparison between propranolol, practolol and betaxolol (SL 75212) on the circulatory and metabolic responses to insulin-induced hypoglycaemia. Eur J Clin Pharmacol. 1981; 21:177-84. [IDIS 142918] [PubMed 6119203]

39. Bianchetti G, Chauvin M, Giudicelli JF et al. Comparison of the β-adrenoceptor blocking properties and pharmacokinetics of SL 75212 and propranolol in man. Br J Clin Pharmacol. 1979; 8:407-8P.

40. Bianchetti G, Blatrix C, Gomeni R et al. Pharmacokinetics of the new β-adrenoceptor blocker SL 75212 in man after repeated oral administration. Br J Clin Pharmacol. 1979; 8:408P. [IDIS 105844] [PubMed 41560]

41. Bianchetti G, Gomeni R, Kilborn JR et al. Blood concentrations and pharmacodynamic effects of SL 75212, a new β-adrenoceptor antagonist, after oral and intravenous administration. Br J Clin Pharmacol. 1979; 8:403-4P.

42. Giudicelli JF, Richer C, Ganansia J et al. Betaxolol: β-adrenoceptor blocking effects and pharmacokinetics in man. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:89-99.

43. Balnave K, Neill JD, Russell CJ et al. Observations on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective β-adrenoceptor blocking drug. Br J Clin Pharmacol. 1981; 11:171-80. [IDIS 137812] [PubMed 6111331]

44. Palminteri R, Assael BM, Bianchetti G et al. Betaxolol kinetics in hypertensive children with normal and abnormal renal function. Clin Pharmacol Ther. 1984; 35:141-7. [IDIS 181904] [PubMed 6692644]

45. Morselli PL, Thiercelin JF, Padovani P et al. Comparative pharmacokinetics of several β-blockers in renal and hepatic insufficiency. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:233-41.

46. Ferrandes B, Durand A, Andrée-Fraisse J et al. Pharmacokinetics and metabolism of betaxolol in various animal species and man. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:51-64.

47. Thiercelin JF, Bianchetti G, Larribaud J et al. Effects of a meal and its composition on the bioavailability of betaxolol administered orally to healthy subjects. World Rev Nutr Diet. 1984; 43:183-6. [PubMed 6147938]

48. Warrington SJ, Taylor EA, Kilborn JR. Comparison of pharmacodynamic effects of betaxolol with atenolol, practolol, and propranolol given intravenously. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:109-22.

49. Warrington SJ, Turner P, Kilborn JR et al. Blood concentrations and pharmacodynamic effects of betaxolol (SL 75212) a new β-adrenoceptor antagonist after oral and intravenous administration. Br J Clin Pharmacol. 1980; 10:449-52. [IDIS 128199] [PubMed 6108127]

50. Weiss Y, Boutonnet G, Chenard A et al. Antihypertensive action and kinetics of a single daily dose of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:267-75.

51. Wax MB, Molinoff PB. Distribution and properties of beta-adrenergic receptors in human iris/ciliary body. Invest Ophthalmol Vis Sci. 1984; 25(Suppl):305.

52. Boger WP. Timolol: short term “escape” and long term “drift.” Ann Ophthalmol. 1979; 11:1239-42. Editorial.

53. Van Buskirk EM. Adverse reactions from timolol administration. Ophthalmology. 1980; 87:447-50. [PubMed 7402590]

54. Williams T, Ginther WH. Hazard of ophthalmic timolol. N Engl J Med. 1982; 306:1485-6. [IDIS 150902] [PubMed 7078595]

55. McMahon CD, Shaffer RN, Hoskins HD Jr et al. Adverse effects experienced by patients taking timolol. Am J Ophthalmol. 1979; 88:736-8. [IDIS 104858] [PubMed 507146]

56. Harrison R. Betaxolol and timolol. Arch Ophthalmol. 1984; 102:1424. [PubMed 6148923]

57. Berry DP Jr, Shields MB, Van Buskirk M. Betaxolol and timolol. Arch Ophthalmol. 1984; 102:1424-5.

58. Jones FL Jr, Ekberg NL. Exacerbation of obstructive airway disease by timolol. JAMA. 1980; 244:2730. [IDIS 124860] [PubMed 7441859]

59. Ahmad S. Cardiopulmonary effects of timolol eyedrops. Lancet. 1979; 2:1028. [IDIS 105027] [PubMed 91770]

60. Zimmerman TJ, Leader BJ, Golob DS. Potential side effects of timolol therapy in the treatment of glaucoma. Ann Ophthalmol. 1981; 13:683-9. [PubMed 7020551]

61. Schoene RB, Martin TR, Charan NB et al. Timolol-induced bronchospasm in asthmatic bronchitis. JAMA. 1981; 245:1460-1. [IDIS 129427] [PubMed 7206150]

62. Anon. Additions to Timoptic contraindications. FDA Drug Bull. 1981; 11:1. [PubMed 7215728]

63. Taylor P. Anticholinesterase agents. In: Gilman AG, Goodman LS, Rall TW et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York: Macmillan Publishing Company; 1985:110-27.

64. Remis LL, Epstein DL. Treatment of glaucoma. Ann Rev Med. 1984; 35:195-205. [PubMed 6426371]

65. Havener WH. Ocular pharmacology. 5th ed. St. Louis: The CV Mosby Company; 1983:18-43,261-417,635-72.

66. Henry JA, Mitchell SN. Effect of pH on human plasma protein binding of a series of β-adrenoceptor antagonists. Br J Clin Pharmacol. 1981; 11:119-20P.

67. Fraunfelder FT, Barker AF. Respiratory effects of timolol. N Engl J Med. 1984; 311:1441. [IDIS 192601] [PubMed 6493304]

68. Machin PJ, Hurst DN, Bradshaw RN et al. β1-Selective adrenoceptor antagonists. 2: 4-ether-linked phenoxypropanolamines. J Med Chem. 1983; 26:1570-6. [IDIS 177952] [PubMed 6138435]

69. Shell JW. Pharmacokinetics of topically applied ophthalmic drugs. Surv Ophthalmol. 1982; 26:207-18. [PubMed 7041308]

70. Smith LH. β-Adrenergic blocking agents. 15: 1-substituted ureidophenoxy-3-amino-2-propanols. J Med Chem. 1977; 20:705-8. [PubMed 16137]

71. Smith LH. β-Adrenergic blocking agents. 16: 1-(acylaminomethyl-, ureidomethyl-, and ureidoethylphenoxy)-3-amino-2-propanols. J Med Chem. 1977; 20:1254-8. [PubMed 20502]

72. Smith LH, Tucker H. β-Adrenergic blocking agents. 17: 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols. J Med Chem. 1977; 20:1653-6. [PubMed 22750]

73. Engel G. Subclasses of beta-adrenoceptors—a quantitative estimation of beta1- and beta2-adrenoceptors in guinea pigs and human lung. Postgrad Med J. 1981; 57(Suppl 1):77-83. [PubMed 6272254]

74. Allen RC. Betaxolol in the treatment of glaucoma: multi-clinic trials. Ophthalmology. 1984; 91(Suppl):142.

75. Langer SZ, Galzin AM. β-Adrenoceptors and noradrenergic neurotransmission: effects of betaxolol on the stimulation-evoked release of3H-norepinephrine in isolated rat atria and rabbit hypothalamic slices. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:21-30.

76. Söonksen PH, Brown PM, Saunders J et al. Metabolic and cardiovascular effects of betaxolol during hypoglycemia and exercise in normal volunteers. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:143-54.

77. Libersa C, Carrée A, Bertrand M et al. Study of the acute hemodynamic effects of betaxolol in noncomplicated essential hypertension. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:171-8.

78. Harrison DC, Buchbinder M, Schroeder JS. Acute hemodynamic effects of betaxolol. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:179-81.

79. Pathée M, Steimer C, Cazor JL et al. Dose-response study of betaxolol in hypertension. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:287-96.

80. Bianchetti G, Padovani P, Thiercelin JF et al. Pharmacokinetic studies on betaxolol—evaluation of the effects of age, hypertension, presence of food, and concomitant administration of hydrochlorothiazide on the disposition of the drug. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:123-31.

81. Barrett AM. Therapeutic applications of β-adrenoceptor antagonists. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:65-72.

82. Bergis SK. Long-term efficacy and safety of betaxolol and propranolol in hypertensive patients. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:353-7.

83. Beresford R, Heel RC. Betaxolol: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in hypertension. Drugs. 1986; 31:6-28. [IDIS 210401] [PubMed 2866947]

84. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. 5th ed. Baltimore: Williams & Wilkins; 1984:I-6.

85. Gomeni R, Kilborn JR, Morselli PL et al. The action of the new β-adrenoceptor blocker SL 75212 on the metabolic response to insulin-induced hypoglycaemia in man. Br J Clin Pharmacol. 1979; 8:404P. [IDIS 105839] [PubMed 41557]

86. Davies IB, Larribaud J, Thiercelin JF et al. Betaxolol does not modify hypoglycaemic actions on glibenclamide or metformin in normal subjects. Br J Clin Pharmacol. 1984; 17:622P.

87. Merck Sharp & Dohme. Timoptic prescribing information. West Point, PA; 1985 Oct.

88. Jackson JE, Bressler R. Clinical pharmacology of sulphonylurea hypoglycaemic agents: part 2. Drugs. 1981; 22:295-320. [IDIS 143257] [PubMed 7030708]

89. Brüugmann U, Blasini R. Comparative effects of long-acting beta-adrenergic receptor blockers with and without cardioselectivity: double-blind, randomized, cross-over and placebo-controlled study with betaxolol and nadolol. Circulation. 1983; 68(Suppl III):406. [IDIS 174045] [PubMed 6861316]

90. Saunders J, Prestwich SA, Avery AJ et al. The effect of non-selective and selective beta-1-blockade on the plasma potassium response to hypoglycaemia. Diabete Metab. 1981; 7:239-42. [PubMed 6120859]

91. Zimmerman TJ. Timolol maleate—a new glaucoma medication? Invest Ophthalmol Visual Sci. 1977; 16:687-8. Editorial.

92. Giudicelli JF, Chauvin M, Thuillez C et al. β-Adrenoceptor blocking effects and pharmacokinetics of betaxolol (SL-75212) in man. Br J Clin Pharmacol. 1980; 10:41-9. [IDIS 116851] [PubMed 6104973]

93. Stewart RH, Kimbrough RL, Ward RL. Betaxolol vs timolol: a six-month double-blind comparison. Arch Ophthalmol. 1986; 104:46-8. [IDIS 209945] [PubMed 3510612]

94. Feghali JG, Kaufman PL. Decreased intraocular pressure in the hypertensive human eye with betaxolol, a β1-adrenergic antagonist. Am J Ophthalmol. 1985; 100:777-82. [IDIS 209309] [PubMed 2866715]

95. Spiritus EM, Casciari R. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol. 1985; 100:492-3. [IDIS 206433] [PubMed 4037047]

96. Schoene RB, Abuan T, Ward RL et al. Effects of topical betaxolol, timolol, and placebo on pulmonary function in asthmatic bronchitis. Am J Ophthalmol. 1985; 100:493-4.

97. Dunn TL, Gerber MJ, Shen AS et al. Timolol-induced bronchospasm: utility of betaxolol as an alternative ocular hypotensive agent in patients with asthma. Clin Res. 1985; 33:20A.

98. Allen RC. Betaxolol in the treatment of glaucoma: multiclinic trials. Ophthalmology. 1984; 91:142.

99. Weinreb RN, Ritch R, Kushner FH. Effect of adding betaxolol to dipivefrin therapy. Am J Ophthalmol. 1986; 101:196-8. [IDIS 211580] [PubMed 3946535]

100. Martin DE, Kammerer WS. The hypertensive surgical patient: controversies in management. Surg Clin North Am. 1983; 63:1017-33. [PubMed 6138862]

101. Djian J. Clinical evaluation of betaxolol (Kerlone) as a once-daily treatment for hypertension in 4685 patients. Br J Clin Pract. 1985; 39:188-91. [IDIS 206468] [PubMed 2866790]

102. Jaillard J, Rouffy J, Sauvanet JP. Long-term influence of betaxolol on plasma lipids and lipoproteins. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:221-31.

103. American Society of Health-System Pharmacists, Inc.. Medication teaching manual: a guide for patient counseling. 2nd ed. Bethesda, MD: American Society of Hospital Pharmacists; 1980:300.

104. Poe RD (Alcon Laboratories, Fort Worth, TX): Personal communication; 1986 May 14.

105. Frances Y, Luccioni R, Vague P et al. Effects of betaxolol, propranolol, and acebutolol on the glycoregulation after oral glucose tolerance test in hypertensive patients. In: Morselli PL, ed. LERS monograph series. Vol 1. New York: Raven Press; 1983:213-20.

106. Bianchetti G, Blatrix C, Gomeni R et al. Pharmacokinetics of the new β-adrenoceptor blocking agent betaxolol (SL 75212) in man after repeated oral administration. Arzneimittelforschung. 1980; 30:1912-6. [PubMed 6109538]

107. Kitazawa Y, Horie T. Diurnal variation of intraocular pressure in primary open-angle glaucoma. Am J Ophthalmol. 1975; 79:557-66. [PubMed 1168023]

108. Buotroy M, Vert P, Bianchetti G et al. Betaxolol: pharmacokinetics and pharmacodynamic effects of a new cardioselective beta-blocker in pregnant women. Proceedings of World Conference on Clinical Pharmacology and Therapeutics. Washington, DC; 1983 July 31-August 5. Abstract No. N565.

109. Ganansia J, Bianchetti G, Bouchet JL et al. Protein binding of betaxolol in healthy volunteers and in patients with renal or hepatic disease. In: Aiache and Hirtz, eds. Proceedings of 2nd European Congress of Biopharmaceutics and Pharmacokinetics; Salamanca, Spain: 1984 April 24-27. Vol 3: Clinical Pharmacokinetics; 1984:440-7.

110. Dunn TL, Gerber MJ, Shen AS et al. The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects. Am Rev Respir Dis. 1986; 133:264-8. [IDIS 211744] [PubMed 3946922]

111. Anon. Two new beta-blockers for glaucoma. Med Lett Drugs Ther. 1986; 28:45-8. [PubMed 2870417]

112. Anon. The autonomic nervous system and the eye. Lancet. 1985; 2:591-2. [PubMed 2863600]

113. Reviewers’ comments (personal observations); 1986 Apr.

114. Durand A, Pauloin D, Bernard F et al. In vitro metabolism of betaxolol and metoprolol: influence of the structure. Proceedings of World Conference on Clinical Pharmacology and Therapeutics. Washington, DC; 1983 July 31-August 5. Abstract No. N568.

115. Neufeld AH. Epinephrine and timolol: how do these drugs lower intraocular pressure? Ann Ophthalmol. 1981; 13:1109-11.

116. Watanabe K, Chiou GCY. Action mechanism of timolol to lower the intraocular pressure in rabbits. Ophthalmic Res. 1983; 15:160-7. [PubMed 6314218]

117. Remis LL, Epstein DL. Treatment of glaucoma. Glaucoma. 1984; 35:195-205.

118. Schenker HI, Yablonski ME, Podos SM et al. Fluorophotometric study of epinephrine and timolol in human subjects. Arch Ophthalmol. 1981; 99:1212-6. [IDIS 134903] [PubMed 7259595]

119. Ball S. Congestive heart failure from betaxolol. Arch Ophthalmol. 1987; 105:320. [IDIS 226823] [PubMed 2881533]

120. Orlando RG. Clinical depression associated with betaxolol. Am J Ophthalmol. 1986; 102:275. [IDIS 219461] [PubMed 3740190]

121. Alcon Laboratories. Betoptic S (betaxolol hydrochloride) suspension prescribing information (dated 2000 Feb). In Physicians' desk reference for ophthalmology. 30th ed. Montvale, NJ: Medical Economics Inc; 2002:208-9.

122. Alcon Laboratories. Betoptic S (betaxolol hydrochloride) product monograph. Fort Worth, TX; 1990 Feb.

123. The United States pharmacopeia, 23rd rev, and The national formulary, 18th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1995:197-8.

124. The USP Drug Nomenclature Committee. Nomenclature policies and recommendations: I. Review and current proposals and decisions. Pharmacopeial Forum. 1991; 17:1509-11.

125. Alcon Laboratories. Betaxon (levobetaxolol hydrochloride ophthalmic suspension) prescribing information (dated 2000 May). In Physicians' desk reference for ophthalmology. 30th ed. Montvale, NJ: Medical Economics Inc; 2002:206-8.

126. Weinreb RN, Caldwell DR, Goode SM et al. A double-masked three-month comparison between 0.25% betaxolol suspension and 0.5% betaxolol ophthalmic solution. Am J Ophthalmol. 1990; 110:189-92. [IDIS 269118] [PubMed 2198812]

a. Alcon Laboratories. Betoptic S (betaxolol hydrochloride) suspension prescribing information. Ft. Worth, TX; 2003 Dec.

b. Falcon Pharmaceuticals. Betoptic (betaxolol hydrochloride) solution prescribing information. Ft. Worth, TX.

Hide
(web3)