Apraclonidine

What it is used for

Apraclonidine Ophthalmic Solution, USP 0.5% as base is indicated for short-term adjunctive therapy in patients on maximally tolerated medical therapy who require additional IOP reduction. Patients on maximally tolerated medical therapy who are treated with Apraclonidine Ophthalmic Solution, USP 0.5% as base to delay surgery should have frequent follow-up examinations and treatment should be discontinued if the intraocular pressure rises significantly.

The addition of Apraclonidine Ophthalmic Solution, USP 0.5% as base to patients already using two aqueous suppressing drugs (i.e., beta-blocker plus carbonic anhydrase inhibitor) as part of their maximally tolerated medical therapy may not provide additional benefit. This is because Apraclonidine Ophthalmic Solution, USP 0.5% as base is an aqueous suppressing drug and the addition of a third aqueous suppressant may not significantly reduce IOP.

The IOP lowering efficacy of Apraclonidine Ophthalmic Solution, USP 0.5% as base diminishes over time in some patients. This loss of effect, or tachyphylaxis, appears to be an individual occurrence with a variable time of onset and should be closely monitored. The benefit for most patients is less than one month.

How to take it

One to two drops of apraclonidine ophthalmic solution should be instilled in the affected eye(s) three times daily. Since apraclonidine ophthalmic solution will be used with other ocular glaucoma therapies, an approximate 5 minute interval between instillation of each medication should be practiced to prevent washout of the previous dose. NOT FOR INJECTION INTO THE EYE. NOT FOR ORAL INGESTION.

Side effects, and when to stop

In clinical studies the overall discontinuation rate related to apraclonidine ophthalmic solution was 15%. The most commonly reported events leading to discontinuation included (in decreasing order of frequency) hyperemia, pruritus, tearing, discomfort, lid edema, dry mouth, and foreign body sensation.

The following adverse reactions (incidences) were reported in clinical studies of apraclonidine ophthalmic solution as being possibly, probably, or definitely related to therapy:

Who should not take it

Apraclonidine ophthalmic solution is contraindicated in patients with hypersensitivity to apraclonidine or any other component of this medication, as well as systemic clonidine. It is also contraindicated in patients receiving monoamine oxidase inhibitors (MAO inhibitors).

Warnings

Not for injection or oral ingestion. FOR TOPICAL OPHTHALMIC USE ONLY.

Other medicines and interactions

Apraclonidine should not be used in patients receiving MAO inhibitors (see CONTRAINDICATIONS ). Although no specific drug interactions with topical glaucoma drugs or systemic medications were identified in clinical studies of apraclonidine ophthalmic solution, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, anesthetics) should be considered. Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with apraclonidine can lead to a reduction in IOP lowering effect. No data on the level of circulating catecholamines after apraclonidine withdrawal are available. Caution, however, is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

An additive hypotensive effect has been reported with the combination of systemic clonidine and neuroleptic therapy. Systemic clonidine may inhibit the production of catecholamines in response to insulin-induced hypoglycemia and mask the signs and symptoms of hypoglycemia.

Since apraclonidine may reduce pulse and blood pressure, caution in using drugs such as beta-blockers (ophthalmic and systemic), antihypertensives, and cardiac glycosides is advised. Patients using cardiovascular drugs concurrently with apraclonidine ophthalmic solution should have pulse and blood pressure frequently monitored. Caution should be exercised with simultaneous use of clonidine and other similar pharmacologic agents.

Storing it

Storage: Store at 20° to 25°C (68° to 77°F).

Protect from freezing and light.

Retain in carton until time of use.

Rx Only

AKORN Distributed by: Akorn Operating Company LLC Gurnee, IL 60031

AC00N Rev. 01/22

General

Glaucoma patients on maximally tolerated medical therapy who are treated with apraclonidine ophthalmic solution to delay surgery should have their visual fields monitored periodically.

Although the topical use of apraclonidine ophthalmic solution has not been studied in renal failure patients, structurally related clonidine undergoes a significant increase in half -life in patients with severe renal impairment. Close monitoring of cardiovascular parameters in patients with impaired renal function is advised if they are candidates for topical apraclonidine therapy. Close monitoring of cardiovascular parameters in patients with impaired liver function is also advised as the systemic dosage form of clonidine is partly metabolized in the liver.

While the topical administration of apraclonidine ophthalmic solution had minimal effect on heart rate or blood pressure in clinical studies evaluating glaucoma patients, the preclinical pharmacology profile of this drug suggests that caution should be observed in treating patients with severe, uncontrolled cardiovascular disease, including hypertension. The possibility of a vasovagal attack should be considered and caution should be exercised in patients with a history of such episodes.

Apraclonidine ophthalmic solution should be used with caution in patients with coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, Raynaud's disease, or thromboangiitis obliterans. Caution and monitoring of depressed patients are advised since apraclonidine has been infrequently associated with depression.

Apraclonidine can cause dizziness and somnolence. Patients who engage in hazardous activities requiring mental alertness should be warned of the potential for a decrease in mental alertness while using apraclonidine.

Topical ocular administration of two drops of 0.5, 1.0 and 1.5% apraclonidine ophthalmic solution to New Zealand albino rabbits three times daily for one month resulted in sporadic and transient instances of minimal corneal edema in the 1.5% group only; no histopathological changes were noted in those eyes.

Use of apraclonidine ophthalmic solution can lead to an allergic-like reaction characterized wholly or in part by the symptoms of hyperemia, pruritus, discomfort, tearing, foreign body sensation, and edema of the lids and conjunctiva. If ocular allergic-like symptoms occur, apraclonidine ophthalmic solution therapy should be discontinued.