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Class: EENT Drugs, Miscellaneous
ATC Class: S01EA03
VA Class: OP900
Molecular Formula: C9H10Cl2N4•HCl
CAS Number: 73218-79-8
Brands: Iopidine

Medically reviewed by Last updated on Sep 14, 2020.


Relatively selective α2-adrenergic agonist;1 4 7 12 19 43 62 65 imidazoline-derivative sympathomimetic amine.a

Uses for Apraclonidine

Inhibition of Perioperative IOP Increases

Apraclonidine 1% is used prophylactically to prevent or reduce intraoperative and postoperative increases in intraocular pressure (IOP) before and after ocular laser surgery (e.g., argon laser trabeculoplasty, argon laser iridotomy, neodymium yttrium aluminum garnet [Nd:YAG] laser posterior capsulotomy).1 2 16 17 18 19 20


Apraclonidine 0.5% is used for short-term (<1 month) adjunctive therapy in patients with open-angle glaucoma receiving maximally tolerated drug therapy (i.e., a topical β-adrenergic blocking agent in conjunction with a systemically administered carbonic anhydrase inhibitor and a sympathomimetic and/or a parasympathomimetic agent) who require additional reduction in IOP.62 65

Apraclonidine Dosage and Administration


For topical ophthalmic use only.62 Not for injection or oral use.62

Ophthalmic Administration

Apply topically to the affected eye(s) as an ophthalmic solution.1 2 16 17 18 19 20 54 62

Avoid contamination of the solution container.34 62

If more than one topical ophthalmic drug is used, administer the drugs at least 5 minutes apart.c

1% solution is for single use only; use a separate container for each single-drop dose of 1% solution and discard each container after use.b


Available as apraclonidine hydrochloride; dosage expressed in terms of apraclonidine.1 a


Inhibition of Perioperative IOP Increases

Apraclonidine 1% solution: 1 drop in the eye undergoing surgery 1 hour before surgery; instill 1 drop in the same eye immediately upon completion of surgery.1 16 17 18 19


Apraclonidine 0.5% solution: 1 or 2 drops in the affected eye(s) 3 times daily.62 65 Benefit of therapy for most patients is <1 month.62 65 (See Tachyphylaxis under Cautions.)

Special Populations

No special population dosage recommendations at this time.b c

Cautions for Apraclonidine


Concomitant use with an MAO inhibitor.62 (See Specific Drugs under Interactions.)

Known hypersensitivity to apraclonidine, clonidine, or to any ingredient in the formulation.1 62


Sensitivity Reactions

Hypersensitivity Reactions

Topical hypersensitivity reactions (e.g., hyperemia, pruritus, discomfort, tearing, foreign body sensation, eyelid swelling) reported.36 62 65 c If hypersensitivity reaction occurs, discontinue apraclonidine.c

General Precautions

Systemic Effects

Perioperative use of apraclonidine hydrochloride ophthalmic solution to date has been associated with a low potential for causing adverse systemic effects;1 2 16 17 18 19 29 36 48 however, continuous (e.g., up to 12 weeks) use of apraclonidine ophthalmic solution has been associated with a higher incidence of adverse systemic effects.62

Cardiovascular Effects

Possible adverse cardiovascular effects (e.g., bradycardia,1 29 chest heaviness or burning,1 palpitation,1 reduced systolic and diastolic BP,2 29 orthostatic hypotension).1 57

Use with caution in patients with severe uncontrolled cardiac disease (e.g., hypertension), coronary insufficiency, recent MI, cerebrovascular disease, Raynaud’s disease, or thromboangitis obliterans.1 62 65

Use with caution in patients with a history of vasovagal attacks; 1 possible vasovagal attacks during laser surgery.1 17

Depressive Episodes

Carefully supervise patients with a history of mental depression; may be subject to further depressive episodes.62

CNS Effects

Possible dizziness and somnolence; performance of activities requiring mental alertness and physical coordination may be impaired.62


IOP-lowering efficacy may diminish during therapy with 0.5% ophthalmic solution; careful monitoring recommended.c

Patient Monitoring

Closely monitor patients who develop excessive IOP reduction.1

Periodic visual field tests and frequent follow-up examinations recommended in patients receiving maximally tolerated drug therapy and 0.5% apraclonidine for glaucoma to delay surgery;62 discontinue therapy if IOP increases substantially.62

Ocular Effects

Abnormal vision, pain, keratitis, keratopathy, blepharitis, blepharoconjunctivitis, photophobia, corneal staining, corneal erosion, corneal infiltrate, and irritation reported rarely.62 65

Specific Populations


Category C.b c


Not known whether apraclonidine is distributed into milk.1 62 Caution advised if 0.5% ophthalmic solution is used.62 Temporarily discontinue nursing during the day that 1% ophthalmic solution is used for inhibition of perioperative IOP increases.1

Pediatric Use

Safety and efficacy not established in children <21 years of age.1 57

Geriatric Use

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

Hepatic Impairment

Closely monitor cardiovascular parameters in patients with impaired liver function.c

Renal Impairment

Elimination may be decreased; closely monitor cardiovascular parameters in severe renal impairment.62

Use with caution in patients with chronic renal impairment.c

Common Adverse Effects

0.5% solution: Discomfort, hyperemia, pruritus, tearing, lid edema, dry mouth, foreign body sensation, blanching, blurred vision, conjunctivitis, discharge, dry eye.c

1% solution: Ocular injection, upper lid elevation, irregular heart rate, nasal decongestion, ocular inflammation, conjunctival blanching, mydriasis.b

Interactions for Apraclonidine

Specific Drugs




Antidepressants, tricyclic (imipramine, desipramine)

Potential decrease in IOP-lowering effect62

Use concomitantly with caution62

Antipsychotic agents

Possible additive hypotensive effects62

Reported with concomitant systemic clonidine therapy; not evaluated with concomitant apraclonidine therapy1 62

Cardiac glycosides

Possible decrease in heart rate and BP62

Use concomitantly with caution62

CNS depressants (e.g., barbiturates, opiates, anesthetics, sedatives, alcohol)

Possible additive CNS effects62

Hypotensive agents

Possible decrease in heart rate and BP62

Use concomitantly with caution62

MAO inhibitors

Possible excess of circulating catecholamines with withdrawal of apraclonidine62

Concomitant use contraindicatedb c

No data available on the circulating plasma concentrations of catecholamines following apraclonidine withdrawal62

Ocular hypotensive agents

Additive IOP-lowering effect16 17

Used to therapeutic advantage16 17 18

Apraclonidine Pharmacokinetics



Some systemic absorption occurs following topical administration.1 2 15 29 62


Following topical application of a 1% solution, reduction in IOP usually occurs within 1 hour and reaches a maximum within 3–5 hours.1 2 16 17 62


Reduction in IOP persists for at least 12 hours.1 2 16 17 62



Distribution into both ocular and systemic human tissues is unknown.52

Not known whether apraclonidine crosses the placenta or is distributed into milk.1 57 62



Metabolic fate not fully elucidated.57 58 62

Elimination Route

Elimination characteristics not fully elucidated.57 58 62


0.5% solution: 8 hours.62 65





0.5% solution: Tight, light-resistant container at 2–27°C; do not freeze.62

1% solution: Tight, light-resistant container at 2–25°C.1 b


  • Stimulates α2-receptors; also may stimulate, to a lesser extent, α1-receptors.2 13

  • Inhibits the production of cyclic adenosine monophosphate (AMP) by inhibition of adenylate cyclase.4 6 13 43

  • Reduces both elevated1 16 17 18 19 48 54 62 65 and normal2 29 36 62 65 IOP in patients with or without glaucoma1 16 17 18 19 48 54 via peripheral (e.g., local) effects.2 61

  • Exact mechanism(s) of action not clearly established,1 3 8 9 10 19 56 65 but predominant effect appears to be reduced aqueous humor formation.1 3 10 19 55 56 62 65 resulting from constriction of afferent ciliary process vessels.2 3 10 53 56

  • Produces local vasoconstriction and reduction in blood flow in the eye.2 33 62

Advice to Patients

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the solution container.c If more than one topical ophthalmic drug is used, importance of administering at least 5 minutes apart.c

  • Importance of delaying insertion of soft contact lenses for at least 15 minutes after apraclonidine instillation, since benzalkonium chloride preservative in the solution may be absorbed by soft lenses.c

  • Risk of dizziness or fatigue; use caution when driving or operating machinery.62

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

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

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


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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Apraclonidine Hydrochloride


Dosage Forms


Brand Names




0.5% (of apraclonidine)

Iopidine (with benzalkonium chloride)


1% (of apraclonidine)

Iopidine (with benzalkonium chloride)


AHFS DI Essentials™. © Copyright 2021, Selected Revisions September 22, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Alcon Laboratories. Iopidine (apraclonidine hydrochloride) 1% prescribing information. Fort Worth, TX; 1995 Sep.

2. Alcon Laboratories. Iopidine product monograph. Fort Worth, TX; 1988 Feb.

3. Havener WH. Ocular pharmacology. 5th ed. St. Louis: The CV Mosby Co.; 1983:262-417.

4. Atlas D, Sabol SL. Interaction of clonidine and clonidine analogues with α-adrenergic receptors of neuroblastoma × glioma hybrid cells and rat brain. Eur J Biochem. 1981; 113:521-9.

5. Rudd P, Blaschke T. Antihypertensive agents and the drug therapy of hypertension. 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; 1985:784-805.

6. Weiner N, Taylor P. Neurohumoral transmission: the autonomic and somatic motor nervous systems. 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; 1985:66-99.

7. Forster BA, Ferrari-Dileo G, Anderson DR. Adrenergic alpha1 and alpha2 binding sites are present in bovine retinal blood vessels. Invest Ophthalmol Vis Sci. 1987; 28:1741-6.

8. Harrison R, Kaufmann CS. Clonidine: effects of a topically administered solution on intraocular pressure and blood pressure in open-angle glaucoma. Arch Ophthalmol. 1977; 95:1368-73.

9. Krieglstein GK, Langham ME, Leydhecker W. The peripheral and central neural actions of clonidine in normal and glaucomatous eyes. Invest Ophthalmol Vis Sci. 1978; 17:149-58.

10. Macri FJ, Cevario SJ. Clonidine: effects on aqueous humor formation and intraocular pressure. Arch Ophthalmol. 1978; 96:2111-3.

11. Rouot BR, Snyder SH. [3H]Para-Amino-clonidine: a novel ligand which binds with high affinity to α-adrenergic receptors. Life Sci. 1979; 25:769-74.

12. Sripanidkulchai B, Dawson R, Oparil S et al. Two renal α2-adrenergic receptor sites revealed by p-aminoclonidine binding. Am J Physiol. 1987; 252:(2 Part 2):F283-90.

13. Stump DC, Macfarlane DE. Clonidine and para-aminoclonidine, partial agonists for the alpha2-adrenergic receptor on intact human blood platelets. J Lab Clin Med. 1983; 102:779-87.

14. Hodapp E, Kolker AE, Kass MA et al. The effect of topical clonidine on intraocular pressure. Arch Ophthalmol. 1981; 99:1208-11.

15. Hernandez Y, Hernandez H, Cervantes R, Frati A et al. J. Toxicol. 1983; 2:99-106.

16. Robin AL, Pollack IP, House B et al. Effects of ALO 2145 on intraocular pressure following argon laser trabeculoplasty. Arch Ophthalmol. 1987; 105:646-50.

17. Robin AL, Pollack IP, deFaller JM. Effects of topical ALO 2145 (p-aminoclonidine hydrochloride) on the acute intraocular pressure rise after argon laser iridotomy. Arch Ophthalmol. 1987; 105:1208-11.

18. Pollack IP, Brown RH, Crandall AS et al. Prevention of the rise in intraocular pressure following neodymium-YAG posterior capsulotomy using topical 1% apraclonidine. Arch Ophthalmol. 1988; 106:754-7.

19. Brown RH, Stewart RH, Lynch MG et al. ALO 2145 reduces the intraocular pressure elevation after anterior segment laser surgery. Ophthalmology. 1988; 95:378-384.

20. Fourman S. Effects of topical ALO 2145 (p-aminoclonidine hydrochloride, aplonidine hydrochloride) on the acute intraocular pressure rise after argon laser iridotomy. Arch Ophthalmol. 1988; 106:307-9.

21. Henry JC, Krupin T, Schultz J et al. Increased intraocular pressure following neodymium-YAG laser iridectomy. Arch Ophthalmol. 1986; 104:178.

22. Brown SVL, Thomas JV, Belcher CD III et al. Effect of pilocarpine in treatment of intraocular pressure elevation following neodymium: YAG laser posterior capsulotomy. Ophthalmology. 1985; 92:354-9.

23. Ofner S, Samples JR, Van Buskirk EM. Pilocarpine and the increase in intraocular pressure after trabeculoplasty. Am J Ophthalmol. 1984; 97:647-9.

24. Migliori ME, Beckman H, Channell MM. Intraocular pressure changes after neodymium-YAG laser capsulotomy in eyes pretreated with timolol. Arch Ophthalmol. 1987; 105:473-475.

25. Weinreb RN, Robin AL, Baerveldt G et al. Flurbiprofen pretreatment in argon laser trabeculoplasty or primary open-angle glaucoma. Arch Ophthalmol. 1984; 102:1629-32.

26. Ruderman JM, Zweig KO, Wilensky JT et al. Effects of corticosteroid pretreatment on argon laser trabeculoplasty. Am J Ophthalmol. 1983; 96:84-9.

27. Schrems W, Eichelbronner O, Krieglstein GK. The immediate IOP response of Nd-YAG-laser iridotomy and its prophlactic treatability. Acta Ophthalmol. 1984; 62:673-80.

28. Weinreb RN, Ruderman J, Juster R et al. Immediate intraocular pressure response to argon laser trabeculoplasty. Am J Ophthalmol. 1983; 95:279-86.

29. Abrams DA, Robin AL, Pollack IP et al. The safety and efficacy of topical 1% ALO 2145 (p-aminoclonidine hydrochloride) in normal volunteers. Arch Ophthalmol. 1987; 105:1205-1207.

30. Stark WJ, Worthen D, Holladay JT et al. Neodymium:YAG lasers: an FDA report. Ophthalmology. 1985; 92:209-12.

31. Richter CV, Arzeno G, Pappas HR et al. Prevention of intraocular pressure elevation following neodymium-YAG laser posterior capsulotomy. Arch Ophthalmol. 1985; 103:912-5.

32. Cavero I, Depoortere H, LeFevre-Borg F. Pharmacological studies on para-aminoclonidine. Br J Pharmacol. 1980; 69:295P-6.

33. Chandler ML, DeSantis L. Studies of p-amino clonidine as a potential antiglaucoma agent. Invest Ophthalmol Vis Sci. 1985; 25(Suppl):227.

34. 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.

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

36. Robin AL. Short-term effects of unilateral 1% apraclonidine therapy. Arch Ophthalmol. 1988; 106:912-5.

37. Moster M, Simmons S, Feldman R et al. Cyclocryotherapy: acute intraocular pressure rise and long term results. Invest Ophthalmol Vis Sci. 1987; 28(Suppl):273.

38. Hoskins HD, Hetherington J Jr, Minckler DS et al. Complications of laser trabeculoplasty. Ophthalmology. 1983; 90:796-9.

39. Thomas JV, Simmons RJ, Belcher CD III. Argon laser trabeculoplasty in the presurgical glaucoma patient. Ophthalmology. 1982; 89:187-97.

40. Krupin T, Stone RA, Cohen BH et al. Acute intraocular pressure response to argon laser iridotomy. Ophthalmology. 1985; 92:922-6.

41. Robin AL, Pollack IP. A comparison of neodymium: YAG and argon laser iridotomies. Ophthalmology. 1984; 91:1011-6.

42. Wise JB, Witter SL. Argon laser therapy for open-angle glaucoma: a pilot study. Arch Ophthalmol. 1979; 97:319-22.

43. Simmons RMA, Jones DJ. Binding of [3H]prazosin and [3H]p-aminoclonidine to α-adrenoceptors in rat spinal cord. Brain Res. 1988; 445:338-49.

44. Petursson G, Cole R, Hanna C. Treatment of glaucoma: using minidrops of clonidine. Arch Ophthalmol. 1984;102:1180-1.

45. Flohr MJ, Robin AL, Kelley JS. Early complications following Q-switched neodymium:YAG laser posterior capsulotomy. Ophthalmology. 1985; 92:360-3.

46. Channell MM, Beckman H. Intraocular pressure changes after neodymium-YAG laser posterior capsulotomy. Arch Ophthalmol. 1984; 102:1024-6.

47. Pollack IP, Patz A. Argon laser iridotomy: an experimental and clinical study. Ophthalmol Surg. 1976; 7:22-30.

48. Jampel HD, Robin AL, Quigley HA et al. Apraclonidine: a one-week dose-response study. Arch Ophthalmol. 1988; 106:1069-73.

49. Lowenstein J. Drugs five years later: clonidine. Ann Intern Med. 1980; 92:74-7.

50. Innemee HC, van Zwieten PA. The central ocular hypotensive effect of clonidine. Albrecht von Graefes Arch Ophthalmol. 1979; 210:93-102.

51. Innemee HC, Hermans AJ, van Zwieten PA. The influence of clonidine on intraocular pressure after topical application to the eyes of anesthetized cats. Albrecht von Graefes Arch Ophthalmol. 1979; 212:19-27.

52. Liu JH, Neufeld AH. Study of central regulation of intraocular pressure using ventriculocisternal perfusion. Invest Ophthalmol Vis Sci. 1985; 26:136-43.

53. Bill A, Heilmann K. Ocular effects of clonidine in cats and monkeys. Exp Eye Res. 1975; 21:481-8.

54. Morrison JC, Robin AL. Adjunctive glaucoma therapy: a comparison of apraclonidine and dipivefrin when added to timolol maleate. Ophthalmology. (in press).

55. Gharagozloo NZ, Relf SJ, Brubaker RF. Aqueous flow is reduced by the alpha-adrenergic agonist, apraclonidine hydrochloride (ALO 2145). Ophthalmology. 1988; 95:1217-20.

56. Lee DA, Topper JE, Brubaker RF. Effect of clonidine on aqueous humor flow in normal human eyes. Exp Eye Res. 1984; 38:239-46.

57. Alcon Laboratories, Fort Worth, TX: Personal communication.

58. Reviewers’ comments (personal observations); 1988 Oct.

59. Vine AK. Ocular hypertension following Nd:YAG laser capsulotomy: a potentially blinding combination. Ophthalmic Surg. 1984; 15:283-4.

60. Innemee HC, van Zwieten PA. The distribution in the eye and the effect on intraocular pressure of clonidine. Albrecht von Graefes Arch Ophthalmol. 1979; 209:189-98.

61. York BM Jr, inventor; Alcon Laboratories Inc, assignee. Method for lowering intraocular pressure using phenylimino-imidazoles. US patent 4,517,199. 1985 May 14. Int C13 A61K 31/415.

62. Alcon. Iopidine 0.5% (apraclonidine ophthalmic solution) prescribing information. In: Physicians’ desk reference for ophthalmology. 24th ed. Montvale, NJ: Medical Economics Company Inc; 221-2.

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

64. The United States Pharmacopeia, 23rd rev, and The national formulary, 18th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1995:128-9.

65. Alcon Laboratories Inc. Iopidine 0.5% (apraclonidine ophthalmic solution) product monograph. Fort Worth, TX; 1993 Nov.

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

a. AHFS drug information 2006. McEvoy GK, ed. Apraclonidine. Bethesda, MD: American Society of Health-System Pharmacists; 2830-3.

b. Alcon Laboratories. Iopidine (apraclonidine hydrochloride ophthalmic solution) 1% prescribing information. Fort Worth, TX; 2004 Dec.

c. Alcon Laboratories. Iopidine (apraclonidine ophthalmic solution) 0.5% prescribing information. Fort Worth, TX; 2003 Dec.