Apraclonidine

INDICATIONS AND USAGE Apraclonidine ophthalmic solution 0.5% 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 0.5% to delay surgery, should have frequent follow-up examinations and treatment should be discontinued if the IOP rises significantly. The addition of apraclonidine ophthalmic solution 0.5% 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 0.5% 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 0.5% 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.

DOSAGE AND ADMINISTRATION One to two drops of apraclonidine ophthalmic solution 0.5% should be instilled in the affected eye(s) three times daily. Since apraclonidine ophthalmic solution 0.5% 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.

WARNINGS Not for injection or oral ingestion. FOR EYE USE ONLY.

CONTRAINDICATIONS Apraclonidine ophthalmic solution 0.5% 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 (MAO) inhibitors.

Drug 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 0.5%, 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 0.5% should have pulse and blood pressures frequently monitored. Caution should be exercised with simultaneous use of clonidine and other similar pharmacologic agents.

Pregnancy Apraclonidine HCl has been shown to have an embryocidal effect in rabbits when given in an oral dose of 3.0 mg/kg (60 times the maximum recommended human dose). Dose related maternal toxicity was observed in pregnant rats at 0.3 mg/kg (6 times the maximum recommended human dose). There are no adequate and well controlled studies in pregnant women. Apraclonidine ophthalmic solution 0.5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when apraclonidine ophthalmic solution 0.5% is administered to a nursing woman.

ADVERSE REACTIONS In clinical studies the overall discontinuation rate related to apraclonidine ophthalmic solution 0.5% 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 0.5% as being possibly, probably, or definitely related to therapy: Ocular The following adverse reactions were reported in 5% to 15% of the patients: discomfort, hyperemia, and pruritus. The following adverse reactions were reported in 1% to 5% of the patients: blanching, blurred vision, conjunctivitis, discharge, dry eye, foreign body sensation, lid edema, and tearing. The following adverse reactions were reported in less than 1% of the patients: abnormal vision, blepharitis, blepharoconjunctivitis, conjunctival edema, conjunctival follicles, corneal erosion, corneal infiltrate, corneal staining, edema, irritation, keratitis, keratopathy, lid disorder, lid erythema, lid margin crusting, lid retraction, lid scales, pain, and photophobia. Nonocular Dry mouth occurred in approximately 10% of the patients. The following adverse reactions were reported in less than 3% of the patients: abnormal coordination, asthenia, arrhythmia, asthma, chest pain, constipation, contact dermatitis, depression, dermatitis, dizziness, dry nose, dyspnea, facial edema, headache, insomnia, malaise, myalgia, nausea, nervousness, paresthesia, parosmia, peripheral edema, pharyngitis, rhinitis, somnolence, and taste perversion. Clinical Practice The following events have been identified during postmarketing use of apraclonidine ophthalmic solution 0.5% in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to apraclonidine ophthalmic solution 0.5%, or a combination of these factors, include bradycardia and hypersensitivity.