Class: EENT Drugs, Miscellaneous
ATC Class: S01EA03
VA Class: OP900
Molecular Formula: C9H10Cl2N4•HCl
CAS Number: 73218-79-8
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
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
For topical ophthalmic use only.62 Not for injection or oral use.62
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.)
No special population dosage recommendations at this time.b c
Cautions for Apraclonidine Hydrochloride
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
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
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
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
Carefully supervise patients with a history of mental depression; may be subject to further depressive episodes.62
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
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
Abnormal vision, pain, keratitis, keratopathy, blepharitis, blepharoconjunctivitis, photophobia, corneal staining, corneal erosion, corneal infiltrate, and irritation reported rarely.62 65
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
Safety and efficacy not established in children <21 years of age.1 57
No substantial differences in safety and efficacy relative to younger adults.b c
Closely monitor cardiovascular parameters in patients with impaired liver function.c
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
Antidepressants, tricyclic (imipramine, desipramine)
Potential decrease in IOP-lowering effect62
Use concomitantly with caution62
Possible additive hypotensive effects62
Reported with concomitant systemic clonidine therapy; not evaluated with concomitant apraclonidine therapy1 62
Possible decrease in heart rate and BP62
Use concomitantly with caution62
CNS depressants (e.g., barbiturates, opiates, anesthetics, sedatives, alcohol)
Possible additive CNS effects62
Possible decrease in heart rate and BP62
Use concomitantly with caution62
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
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 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.
0.5% (of apraclonidine)
Iopidine (with benzalkonium chloride)
1% (of apraclonidine)
Iopidine (with benzalkonium chloride)
AHFS DI Essentials. © Copyright 2017, Selected Revisions September 22, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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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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