Class: beta-Adrenergic Blocking Agents
VA Class: OP101
Chemical Name: (-)-5-(3-tert-Butylamino-2-hydroxypropoxy)-1,2,3,4-tetrahydronaphthalen-1-one hydrochloride
Molecular Formula: C17H25NO3•ClH [Molecular Formula]
CAS Number: 27912-14-7[CAS number]
Uses for Levobunolol Hydrochloride
Ocular Hypertension and Glaucoma
Used alone2 51 52 53 54 55 56 57 58 92 a b c or in conjunction wth a topical miotic (e.g., pilocarpine), topical dipivefrin, topical epinephrine, and/or a systemic carbonic anhydrase inhibitor.2 101 a b c
Levobunolol Hydrochloride Dosage and Administration
Avoid contamination of the solution container.80
Ocular Hypertension and Glaucoma
Initially, 1 or 2 drops of a 0.5% ophthalmic solution in the affected eye(s) once daily2 51 52 53 54 55 56 58 92 93 a b c or, alternatively, 1 or 2 drops of a 0.25% ophthalmic solution twice daily.b c
Ocular Hypertension and Glaucoma
Cautions for Levobunolol Hydrochloride
Levobunolol may be absorbed systemically following topical application to the eye;2 a b c consider the usual precautions associated with systemic use of nonselective β-adrenergic blocking agents when using topical levobunolol.a b c
Severe cardiac reactions, including death associated with cardiac failure, have been reported in patients receiving topical (ocular) levobunolol.a b c May precipitate more severe cardiac failure in patients with preexisting heart failure and may cause cardiac failure in patients without a history of heart failure.a b c (See Actions.)
Avoid use in patients with cardiogenic shock or with overt cardiac failurea b c that is not adequately compensated (e.g., treated with cardiac glycosides and/or diuretics).98 99 In patients without a history of cardiac failure, discontinue therapy at the first sign or symptom of cardiac failure.a b c
Patients with mild or moderately severe COPD (e.g., chronic bronchitis, emphysema), bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma, in which levobunolol is contraindicated) generally should not receive β-adrenergic blocking agents.a b c (See Contraindications.) If levobunolol is required, use with caution in such patients since it may antagonize bronchodilation produced by endogenous and exogenous catecholamines.a b c
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.a b c
Need for withdrawal of β-adrenergic blocking agents prior to major surgery controversial; in some patients, gradual withdrawal of β-adrenergic blocking agents prior to elective surgery may be appropriate.60 93 a b c
β-Adrenergic blocking agents may mask signs 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.64 a b c
History of Anaphylactic or Hypersensitivity Reactions
Patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-adrenergic blocking agents; such patients may be unresponsive to usual doses of epinephine used to treat anaphylactic reactions.a b c
Levobunolol hydrochloride ophthalmic solution contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.82 83 84 85 86 87 88 89 110 a b c d
Levobunolol has little or no effect on pupil size.2 51 52 53 54 55 56 58 a b c Do not use alone in patients with angle-closure glaucoma; use only in combination with a miotic in these patients.7 98 104 105 106 107 108 a b c
Common Adverse Effects
Interactions for Levobunolol Hydrochloride
β-Adrenergic blocking agents, systemic or topical
Calcium-channel blocking agents
Catecholamine-depleting drugs (e.g., reserpine)
Ocular hypotensive agents (e.g., topical miotic and/or systemically administered carbonic anhydrase inhibitor)
Levobunolol Hydrochloride Pharmacokinetics
Following topical application in rabbits, rapidly distributed throughout ocular tissues and fluids (e.g., cornea, iris, ciliary body, aqueous humor).2
Nonselective β-adrenergic blocking agent that has some direct myocardial depressant activity2 3 10 11 12 13 14 15 16 17 19 20 21 22 23 27 28 a b c but does not have substantial local anesthetic activity2 23 a b c or intrinsic sympathomimetic activity.2 14 20 21 23 a b c
May block endogenous catecholamine-stimulated increases in cyclic adenosine monophosphate (AMP) concentrations within the ciliary processes and subsequent formation of aqueous humor.2 6 7 8 30 32 34 59
Advice to Patients
Importance of learning and adhering to proper administration techniques to avoid contamination of the product.80
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease, bronchospastic disease).a b c
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Betagan (with benzalkonium chloride and sodium metabisulfite)
Levobunolol Hydrochloride Ophthalmic Solution
Apotex, Bausch & Lomb, Falcon
Betagan (with benzalkonium chloride and sodium metabisulfite)
Levobunolol Hydrochloride Ophthalmic Solution
Apotex, Bausch & Lomb, Falcon
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Betagan 0.5% Solution (ALLERGAN): 10/$69.99 or 30/$199.98
Betagan 0.5% Solution (ALLERGAN): 15/$99.74 or 45/$285.57
Levobunolol HCl 0.25% Solution (PACIFIC PHARMA): 5/$15.99 or 15/$29.97
Levobunolol HCl 0.25% Solution (PACIFIC PHARMA): 10/$22.99 or 30/$45.97
Levobunolol HCl 0.5% Solution (BAUSCH & LOMB): 5/$29.99 or 15/$75.97
Levobunolol HCl 0.5% Solution (BAUSCH & LOMB): 10/$47.99 or 30/$135.97
Levobunolol HCl 0.5% Solution (BAUSCH & LOMB): 15/$65.99 or 45/$175.97
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions October 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Allergan Pharmaceuticals, Inc. Betagan prescribing information. Irvine, CA; 1989 Jun.
2. Allergan Pharmaceuticals, Inc. Betagan product monograph. Irvine, CA; 1985.
3. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:1341.
4. 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.
5. 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.
6. Remis LL, Epstein DL. Treatment of glaucoma. Annu Rev Med. 1984; 35:195-205. [PubMed 6426371]
7. Havener WH. Ocular pharmacology. 5th ed. St. Louis: CV Mosby Co; 1983:261-417,656-7.
8. Neufeld AH. Epinephrine and timolol: how do these drugs lower intraocular pressure? Ann Ophthalmol. 1981; 13:1109-11.
9. Schwender CF, Pike RE, Shavel J Jr. Derivatives of 3,4-dihydro-1(2H)-naphthalenone as β-adrenergic blocking agents: 2. Aromatic-substituted analogs of bunolol. J Med Chem. 1973; 16:254-7. [PubMed 4147388]
10. Rzeszotarski WJ, Gibson RE, Eckelman WC et al. Cardioselectivity of β-adrenoceptor blocking agents: 1. 1-[(4-hydroxyphenethyl)amino]-3-(aryloxy)propan-2-ols. J Med Chem. 1979; 22:735-7. [PubMed 37339]
11. Commarato MA, Giardino EC, Kopia GA et al. Levo-bunolol and propranolol: further evaluation of oral β-blocking activity in conscious dogs. Arch Int Pharmacodyn Ther. 1977; 226:205-13. [PubMed 327960]
12. Shapiro W, Park J. The effect of a new beta-blocking agent, levo-bunolol, on exercise-induced or augmented ventricular arrhythmias. Am Heart J. 1978; 96:417-8. [IDIS 117233] [PubMed 356571]
13. Kaplan HR, Commarato MA. Relative beta adrenergic receptor blocking activity in dogs after intravenous and intraportal vein administration: bunolol, propranolol, their levo isomers and sotalol. J Pharmacol Exp Ther. 1973; 185:395-405. [PubMed 4145046]
14. Robson RD, Kaplan HR. The cardiovascular pharmacology of bunolol, a new beta adrenergic blocking agent. J Pharmacol Exp Ther. 1970; 175:157-67. [PubMed 4394301]
15. Kaplan HR, LaSala SA, Robson RD. Oral β-adrenoceptor blocking activity of bunolol and its optical isomers. Eur J Pharmacol. 1971; 16:237-40. [PubMed 4405784]
16. Kaplan HR, LaSala SA. Oral and intravenous beta adrenergic blocking potency of bunolol d,1-5-[3-tert.-butylamino)-2-hydroxypropoxy)-3,4 dihydro-1-(2H) naphthalenone hydrochloride, the isomers and propranolol. Fed Proc. 1970; 29:477.
17. Kaplan HR, Commarato MA, Lattime EC. l-Bunolol and propranolol: oral and intravenous β-adrenoceptor blocking activity in rats compared to dogs and humans. J Pharm Sci. 1978; 67:132-3. [PubMed 22739]
18. Hammer RH. Cardiovascular drugs. In: Foye WO, ed. Principles of medicinal chemistry. 2nd ed. Philadelphia: Lea & Febiger; 1981:395-429.
19. Arce-Gomez E, Alcocer L. Aspe J. Antihypertensive effect of L-bunolol a new beta-adrenergic blocking agent. Curr Ther Res. 1976; 19:386-96. [PubMed 817869]
20. Covi G, Capuzzo MG, Corsato M et al. Comparison of levo-bunolol and atenolol in the treatment of mild or moderate hypertension. Curr Ther Res. 1984; 36:516-21.
21. Gavras H, Gavras I, Brunner HR et al. Effect of a new beta-adrenergic blocker, l-bunolol, on blood pressure and on the renin-aldosterone system. J Clin Pharmacol. 1977; 17:350-7. [PubMed 323300]
22. Podrid PJ, Lown B, Graboys TB. Effect of levo-bunolol on ventricular arrhythmia. Circulation. 1977; 56(Suppl III):III-8. [PubMed 902386]
23. Kaplan HR, Robson RD. Antiarrhythmic activity of bunolol, a new beta adrenergic blocking agent. J Pharmacol Exp Ther. 1970; 175:168-77. [PubMed 4394302]
24. Bray JS. Pilot single-blind evaluation of the effects of levo-bunolol on exercise tolerance and angina attack rate in patients with proven ischemic heart disease. Clin Res. 1977; 25:544A.
25. Shapiro W, Park J. Comparison of duration of action of levo-bunolol and propranolol at rest and during exercise in angina pectoris. Clin Res. 1978; 26:47A.
26. Palmieri G, Nazzari M, Ambrosi G et al. A crossover randomized comparison of levobunolol and propranolol in the treatment of angina of effort. Curr Ther Res. 1985; 37:524-9.
27. Giles RE, Finkel MP. Effects of alprenolol, bunolol and propranolol on pulmonary resistance in the anaesthetized dog. Eur J Pharmacol. 1971; 16:156-63.
28. Quast U, Vollmer KO. Binding of β-adrenergic antagonists to rat and rabbit lung: special reference to levobunolol. Arzneimittelforschung. 1984; 34:579-84. [PubMed 6147147]
29. Coakes RL, Brubaker RF. The mechanism of timolol in lowering intraocular pressure: in the normal eye. Arch Ophthalmol. 1978; 96:2045-8. [IDIS 118812] [PubMed 363105]
30. Watanabe K, Chiou GCY. Action mechanism of timolol to lower the intraocular pressure in rabbits. Ophthalmic Res. 1983; 15:160-7. [PubMed 6314218]
31. Boger WP III. Timolol: short term “escape” and long term “drift.” Ann Ophthalmol. 1979; 11:1239-42. Editorial.
32. Remis LL, Epstein DL. Treatment of glaucoma. Glaucoma. 1984; 35:195-205.
33. Chiou GCY. Recent advances in antiglaucoma drugs. Biochem Pharmacol. 1981; 30:103-6. [PubMed 7248025]
34. 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]
35. Polack BCP. Drugs used in ocular treatment. In: Dukes MNG, ed. Side effects of drugs. New York: Elsevier/North Holland Inc; 1981:425-9.
36. Leinweber FJ, Szpiech JM, DiCarlo FJ. l-Bunolol metabolites in human urine. Pharmacology. 1978; 16:70-7. [PubMed 339235]
37. Leinweber FJ, Greenough RC, DiCarlo FJ. Bunolol metabolism by dogs: urinary excretion of 5-hydroxytetralone. Xenobiotica. 1978; 8:239-43. [PubMed 347724]
38. Leinweber FJ, Greenough RC, Schwender CF et al. Bunolol metabolism by cell-free preparations of human liver: biosynthesis of dihydrobunolol. Xenobiotica. 1972; 2:191-202. [PubMed 4560367]
39. Leinweber FJ, Szpiech JM, DiCarlo FJ. l-Bunolol metabolism in rats: identification of urinary metabolites. J Pharm Sci. 1978; 67:129-31. [PubMed 338886]
40. Leinweber FJ, Greenough RC, DiCarlo FJ. Bunolol metabolism by dogs: identification of basic metabolites and their conjugates. J Pharm Sci. 1977; 66:1570-5. [PubMed 335043]
41. Leinweber FJ, Greenough RC, Schwender CF et al. Bunolol metabolism by dogs: isolation and identification of two acidic metabolites. J Pharm Sci. 1971; 60:1516-9. [PubMed 4399678]
42. Leinweber FJ, Greenough RC, Schwender CF et al. Bunolol metabolism by cell-free preparations of human liver: biosynthesis of dihydrobunolol. Fed Proc. 1972; 31:537.
43. Leinweber FJ, Haynes LJ, Crew MC et al. Absorption, tissue distribution, and excretion of bunolol-14C by dogs. J Pharm Sci. 1971; 60:1512-5. [PubMed 4399677]
44. DiCarlo FJ, Leinweber FJ, Szpiech JM et al. Metabolism of l-bunolol in man. Fed Proc. 1976; 35:566.
45. Kölle EU, Hengy H, Thomann P. Pharmacokinetics of levobunolol and dihydrolevobunolol in man. Naunyn-Schmiedeberg’s Arch Pharmacol. 1983; 322:R9.
46. Hengy H, Kölle EU. Determination of levobunolol and dihydrolevobunolol in blood and urine by high-performance liquid chromatography using fluorescence detection. J Chromatogr. 1985; 338:444-9. [PubMed 3889026]
47. DiCarlo FJ, Leinweber FJ, Szpiech JM et al. Metabolism of l-bunolol. Clin Pharmacol. 1977; 22:858-63.
48. Schwender CF, Farber S, Blaum C et al. Derivatives of 3,4-dihydro-1(2H)-naphthalenone as β-adrenergic blocking agents: 1. bunolol and related analogs. J Med Chem. 1970; 13:684-8. [PubMed 4393796]
49. Shell JW. Pharmacokinetics of topically applied ophthalmic drugs. Surv Ophthalmol. 1982; 26:207-18. [PubMed 7041308]
50. Zimmerman TJ. Timolol maleate—a new glaucoma medication? Invest Ophthalmol Visual Sci. 1977; 16:687-8. Editorial.
51. Levobunolol Study Group. Levobunolol: a beta-adrenoceptor antagonist effective in the long-term treatment of glaucoma. Ophthalmology. 1985; 92:1271-6. [PubMed 2865710]
52. Berson FG, Cohen HB, Foerster RJ et al. Levobunolol compared with timolol for the long-term control of elevated intraocular pressure. Arch Ophthalmol. 1985; 103:379-82. [IDIS 196928] [PubMed 3883972]
53. Bensinger RE, Keates EU, Gofman JD et al. Levobunolol: a three-month efficacy study in the treatment of glaucoma and ocular hypertension. Arch Ophthalmol. 1985; 103:375-8. [IDIS 196927] [PubMed 3883971]
54. Ober M, Scharrer A, David R et al. Long-term ocular hypotensive effect of levobunolol: results of a one-year study. Br J Ophthalmol. 1985; 69:593-9. [PubMed 3893528]
55. Duzman E, Ober M, Scharrer A et al. A clinical evaluation of the effects of topically applied levobunolol and timolol on increased intraocular pressure. Am J Ophthalmol. 1982; 94:318-27. [IDIS 157783] [PubMed 6751091]
56. Long D, Zimmerman T, Spaeth G et al. Minimum concentration of levobunolol required to control intraocular pressure in patients with primary open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 1985; 99:18-22. [IDIS 195698] [PubMed 3881033]
57. Partamian LG, Kass MA, Gordon M. A dose-respone study of the effect of levobunolol on ocular hypertension Am J Ophthalmol. 1983; 95:229-32.
58. Cinotti A, Cinotti D, Grant W et al. Levobunolol vs timolol for open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 1985; 99:11-7. [IDIS 195697] [PubMed 3881032]
59. Thomas JV, Epstein DL. Timolol and epinephrine in primary open angle glaucoma. Arch Ophthalmol. 1981; 99:91-5. [IDIS 130036] [PubMed 7006581]
60. Martin DE, Kammerer WS. The hypertensive surgical patient: controversies in management. Surg Clin North Am. 1983; 63:1017-33. [PubMed 6138862]
61. 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]
62. Van Buskirk M. Adverse reactions from timolol administration. Ophthalmology. 1980; 87:447-50. [PubMed 7402590]
63. 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]
64. Jackson JE, Bressler R. Clinical pharmacology of sulphonylurea hypoglycaemic agents: part 2. Drugs. 1981; 22:295-320. [IDIS 143257] [PubMed 7030708]
65. Anon. Additions to Timoptic contraindications. FDA Drug Bull. 1981; 11:17-8. [PubMed 7319166]
66. 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]
67. Hernandez y Hernandez HH, Cervantes R, Frati A et al. Cardiovascular effects of topical glaucoma therapies in normal subjects. J Toxicol Cutaneous Ocul Toxicol. 1983; 2:99-106.
68. 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]
69. Van Buskirk M. Adverse reactions from timolol administration. Ophthalmology. 1980; 87:447-50. [PubMed 7402590]
70. 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]
71. 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.
72. Munroe WP, Rindone JP, Kershner RM. Systemic side effects associated with the ophthalmic administration of timolol. Drug Intell Clin Pharm. 1985; 19:85-9. [IDIS 195453] [PubMed 3882377]
73. Leier CV, Baker ND, Weber PA. Cardiovascular effects of ophthalmic timolol. Ann Intern Med. 1986; 104:197-9. [IDIS 213654] [PubMed 3946944]
74. Schwender CF, Farber S, Blaum C et al. Derivatives of 3,4-dihydro-1(2H)-naphthalenone as β-adrenergic blocking agents. 1. bunolol and related analogs. J Med Chem. 1970; 13:684-8. [PubMed 4393796]
75. Gosselin RE, Smith RP, Hodge HC. Clinical toxicology of commercial products. 5th ed. Baltimore, MD: Williams & Wilkins; 1984:I-6.
76. Kitazawa Y, Horie T. Diurnal variation of intraocular pressure in primary open-angle glaucoma. Am J Ophthalmol. 1975; 79:557-66. [PubMed 1168023]
77. Caldwell DR, Salisbury CR, Guzek JP. Effects of topical betaxolol in ocular hypertensive patients. Arch Ophthalmol. 1984; 102:539-40. [IDIS 183932] [PubMed 6704008]
78. Radius RL. Use of betaxolol in the reduction of elevated intraocular pressure. Arch Ophthalmol. 1983; 101:898-900. [IDIS 171713] [PubMed 6860201]
79. Levy NS, Boone L. Effect of 0.25% betaxolol placebo. Glaucoma. 1985; 5:230-2.
80. American Society of Health-System Pharmacists, Inc.. Medication Teaching Manual. 2nd ed. Bethesda, MD: American Society of Hospital Pharmacists; 1980:300.
81. Fraunfelder FT. Extraocular fluid dynamics: how best to apply topical ocular medication. Trans Am Ophthalmol. 1976; 74:457-87.
82. Anon. Sulfites in foods and drugs. FDA Drug Bull. 1983; 13:12. [PubMed 6604672]
83. Sogn D. The ubiquitous sulfites. JAMA. 1984; 251:2986-7. [IDIS 185969] [PubMed 6716628]
84. Koepke JW, Christopher KL, Chai H et al. Dose-dependent bronchospasm from sulfites in isoetharine. JAMA. 1984; 251:2982-3. [IDIS 185966] [PubMed 6716626]
85. Twarog FJ, Leung DYM. Anaphylaxis to a component of isoetharine (sodium bisulfite). JAMA. 1982; 248:2030-1. [IDIS 158261] [PubMed 7120631]
86. Baker GJ, Collett P, Allen DH. Bronchospasm induced by metabisulphite-containing foods and drugs. Med J Aust. 1981; 2:614-7. [IDIS 146240] [PubMed 7334982]
87. Koepke JW, Selner JC, Dunhill AL. Presence of sulfur dioxide in commonly used bronchodilator solutions. J Allergy Clin Immunol. 1983; 72(5 Part 1):504-8. [IDIS 178793] [PubMed 6630799]
88. US Food and Drug Administration. Sulfiting agents; labeling in drugs for human use: warning statement (Docket No. 84N-0113). Fed Regist. 1985; 50:47558-63.
89. US Food and Drug Administration Center for Food Safety and Applied Nutrition. Tentative report on the reexamination of the GRAS status of sulfiting agents, October 1984. Bethesda, MD: FASEB Life Sciences Research Office. (in press)
90. 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]
91. 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.
92. Silverstone DE, Arkfeld D, Cowan G et al. Long-term diurnal control of intraocular pressure with levobunolol and timolol. Glaucoma. 1985; 7:138-40.
93. Wandel T, Charap AD, Lewis RA et al. Glaucoma treatment with once-daily levobunolol. Am J Ophthalmol. 1986; 101:298-304. [IDIS 213261] [PubMed 3513594]
94. Matthys H, Pohl M, Braig H et al. The cardiopulmonary effects of celiprolol and propranolol in asymptomatic bronchial asthmatics. Br J Clin Pract. 1985; 40(Suppl):33.
95. Alcon Laboratories. Betoptic prescribing information. Fort Worth, TX; 1985 Nov.
96. Merck Sharpe & Dohme. Timoptic prescribing information. West Point, PA; 1985 Oct.
97. Schwartz HJ, Scher TH. Biosulfite intolerance manifest as bronchospasm following topical dipivefrin hydrochloride therapy for glaucoma. Arch Ophthalmol. 1985; 103:14-5. [IDIS 195001] [PubMed 3977669]
98. Reviewers’ comments (personal observations), 1986 Aug.
99. Novack G. (Allergan Pharmaceuticals, Inc, Irvine, CA): personal communication; 1986 Jul 17.
100. Meekins BB, Tsoy EA, Shields BM. Comparison of two treatment schedules for combined timolol and dipivefrin therapy. Invest Ophthalmol Vis Sci. 1986; 27(Suppl):161.
101. Allen R, Long D, Robin A et al. Efficacy and safety of levobunolol compared with timolol in combination with dipivefrin in glaucoma. Invest Ophthalmol Vis Sci. 1986; 27(Suppl):161.
102. Kass MA, Meltzer DW, Gordon M et al. Compliance with topical pilocarpine treatment. Am J Ophthalmol. 1986; 101:515-23. [IDIS 215291] [PubMed 3706455]
103. Goldberg I, Ashburn FS Jr, Palmberg PF et al. Timolol and epinephrine: a clinical study of ocular interactions. Arch Ophthalmol. 1980; 98:484-6. [IDIS 109845] [PubMed 7362504]
104. Goethals M, Missotten L. Long term trial of timolol in different forms of glaucoma. Bull Soc Belg Ophthalmol. 1977; 179:95-101.
105. Kramer P, Ritch R. The treatment of acute angle-closure glaucoma revisited. Ann Ophthalmol. 1984; 16:1101-3. [PubMed 6532284]
106. Phillips CI. Timolol in operated closed-angle glaucoma. Br J Ophthalmol. 1980: 64:240-6.
107. Airaksinen PJ, Saari KM, Tiainen TJ et al. Management of acute closed-angle glaucoma with miotics and timolol. Br J Ophthalmol. 1979; 63:822-5. [PubMed 526463]
108. Levine L. Clinical implications of reported timolol-induced side effects. Am J Optom Physiol Optics. 1982; 59:523-8.
109. Tang-Liu DDS, Liu S, Richman J et al. HPLC quantitation of levobunolol and its metabolite, dihydrolevobunolol, in biological fluids. J Liq Chromatogr. (in press)
110. Food and Drug Administration. Sulfiting agents; labeling in drugs for human use; warning statements. [21 CFR Part 201] Fed Regist. 1986; 51:43900-5.
111. Garbe D. (Allergan Pharmaceuticals, Inc, Irvine, CA): personal communication; 1990 Feb 13.
112. Alward WLM. Medical management of glaucoma. N Engl J Med. 1998; 339:1298-307. [IDIS 414110] [PubMed 9791148]
a. Falcon Pharmaceuticals, Ltd. Levobunolol hydrochloride ophthalmic solution prescribing information. Fort Worth, TX; 2002 Mar.
b. Apotex Corp. Levobunolol hydrochloride ophthalmic solution prescribing information. Weston, FL; 2004 Oct.
c. Allergan Pharmaceuticals, Inc. Betagan (levobunolol hydrochloride) ophthalmic solution prescribing information. Irvine, CA; 2004 Jan.
d. Food and Drug Administration Center for Food Safety and Applied Nutrition. The reexamination of the GRAS status of sulfiting agents. Jan. 1985. (Doc No. 223-83-2020). Bethesda, MD: FASEB Life Sciences Reasearch Office.