Apraclonidine Hydrochloride

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

Introduction

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

Uses for Apraclonidine Hydrochloride

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

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Glaucoma

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 Hydrochloride Dosage and Administration

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

Dosage

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

Adults

Inhibition of Perioperative IOP Increases
Ophthalmic

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

Glaucoma
Ophthalmic

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 Hydrochloride

Contraindications

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

Warnings/Precautions

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

Tachyphylaxis

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

Pregnancy

Category C.b c

Lactation

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 Hydrochloride

Specific Drugs

Drug

Interaction

Comments

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 Hydrochloride Pharmacokinetics

Absorption

Bioavailability

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

Onset

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

Duration

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

Distribution

Extent

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

Elimination

Metabolism

Metabolic fate not fully elucidated.57 58 62

Elimination Route

Elimination characteristics not fully elucidated.57 58 62

Half-life

0.5% solution: 8 hours.62 65

Stability

Storage

Ophthalmic

Solution

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

Actions

  • 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.)

Preparations

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

Apraclonidine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.5% (of apraclonidine)

Iopidine (with benzalkonium chloride)

Alcon

1% (of apraclonidine)

Iopidine (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.

Iopidine 0.5% Solution (ALCON VISION): 5/$114.49 or 15/$322.74

Iopidine 0.5% Solution (ALCON VISION): 10/$207.08 or 30/$588.57

Iopidine 1% Solution (ALCON VISION): 24/$366.26 or 72/$1,035.58

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

References

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. [PubMed 6260485]

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. [PubMed 3667146]

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. [PubMed 889511]

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. [PubMed 24018]

10. Macri FJ, Cevario SJ. Clonidine: effects on aqueous humor formation and intraocular pressure. Arch Ophthalmol. 1978; 96:2111-3. [PubMed 718505]

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. [PubMed 40089]

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. [PubMed 6138385]

14. Hodapp E, Kolker AE, Kass MA et al. The effect of topical clonidine on intraocular pressure. Arch Ophthalmol. 1981; 99:1208-11. [IDIS 134902] [PubMed 7020658]

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. [PubMed 2887153]

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. [IDIS 234757] [PubMed 3307717]

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. [IDIS 242782] [PubMed 3369999]

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. [PubMed 3050686]

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. [PubMed 3345140]

21. Henry JC, Krupin T, Schultz J et al. Increased intraocular pressure following neodymium-YAG laser iridectomy. Arch Ophthalmol. 1986; 104:178. [PubMed 3753864]

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. [PubMed 3991123]

23. Ofner S, Samples JR, Van Buskirk EM. Pilocarpine and the increase in intraocular pressure after trabeculoplasty. Am J Ophthalmol. 1984; 97:647-9. [IDIS 185419] [PubMed 6720849]

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. [IDIS 229123] [PubMed 3566598]

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. [IDIS 192255] [PubMed 6497745]

26. Ruderman JM, Zweig KO, Wilensky JT et al. Effects of corticosteroid pretreatment on argon laser trabeculoplasty. Am J Ophthalmol. 1983; 96:84-9. [IDIS 173265] [PubMed 6869482]

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. [PubMed 6829673]

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. [IDIS 234756] [PubMed 3307716]

30. Stark WJ, Worthen D, Holladay JT et al. Neodymium:YAG lasers: an FDA report. Ophthalmology. 1985; 92:209-12. [PubMed 3982799]

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. [IDIS 201626] [PubMed 3839390]

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. [IDIS 244310] [PubMed 3390053]

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. [PubMed 6622019]

39. Thomas JV, Simmons RJ, Belcher CD III. Argon laser trabeculoplasty in the presurgical glaucoma patient. Ophthalmology. 1982; 89:187-97. [PubMed 7088501]

40. Krupin T, Stone RA, Cohen BH et al. Acute intraocular pressure response to argon laser iridotomy. Ophthalmology. 1985; 92:922-6. [PubMed 4022578]

41. Robin AL, Pollack IP. A comparison of neodymium: YAG and argon laser iridotomies. Ophthalmology. 1984; 91:1011-6. [PubMed 6387569]

42. Wise JB, Witter SL. Argon laser therapy for open-angle glaucoma: a pilot study. Arch Ophthalmol. 1979; 97:319-22. [PubMed 575877]

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. [PubMed 2836025]

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. [PubMed 3991124]

46. Channell MM, Beckman H. Intraocular pressure changes after neodymium-YAG laser posterior capsulotomy. Arch Ophthalmol. 1984; 102:1024-6. [PubMed 6547596]

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. [IDIS 244762] [PubMed 3041944]

49. Lowenstein J. Drugs five years later: clonidine. Ann Intern Med. 1980; 92:74-7. [IDIS 106637] [PubMed 6101302]

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. [PubMed 4038694]

53. Bill A, Heilmann K. Ocular effects of clonidine in cats and monkeys. Exp Eye Res. 1975; 21:481-8. [PubMed 812714]

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. [PubMed 3062536]

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. [PubMed 6547221]

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 3¼15.

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.

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