Ingestion of IOPIDINE 0.5% Ophthalmic Solution has been reported to cause bradycardia, drowsiness, and hypothermia.
Accidental or intentional ingestion of oral clonidine has been reported to cause apnea, arrhythmias, asthenia, bradycardia, conduction defects, diminished or absent reflexes, dryness of the mouth, hypotension, hypothermia, hypoventilation, irritability, lethargy, miosis, pallor, respiratory depression, sedation or coma, seizure, somnolence, transient hypertension, and vomiting.
Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained. Hemodialysis is of limited value since a maximum of 5% of circulating drug is removed.
IOPIDINE 0.5% 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).
In clinical studies the overall discontinuation rate related to IOPIDINE 0.5% 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 IOPIDINE 0.5% (apraclonidine ophthalmic solution) as being possibly, probably, or definitely related to therapy:
OcularThe 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, photophobia.
NonocularDry 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 post-marketing use of IOPIDINE® 0.5% Ophthalmic Solution 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 IOPIDINE 0.5% Ophthalmic Solution, or a combination of these factors, include: bradycardia.
IOPIDINE 0.5% Ophthalmic Solution 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 IOPIDINE 0.5% Ophthalmic Solution to delay surgery should have frequent followup examinations and treatment should be discontinued if the intraocular pressure rises significantly.
The addition of IOPIDINE 0.5% Ophthalmic Solution 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 Reference ID: 4079501 IOPIDINE 0.5% Ophthalmic Solution is an aqueous suppressing drug and the addition of a third aqueous suppressant may not significantly reduce IOP.
The IOP lowering efficacy of IOPIDINE 0.5% Ophthalmic Solution 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.
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. IOPIDINE 0.5% Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
IOPIDINE 0.5% Ophthalmic Solution as base in a sterile, isotonic, aqueous solution containing apraclonidine hydrochloride.
Supplied in plastic ophthalmic DROP-TAINER® dispenser as follows: 5 mL NDC 0065-0665-05 10 mL NDC 0065-0665-10
StorageStore between 2 - 25°C (36 - 77°F). Protect from freezing and light.
Distributed by: ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA. Revised: n/a
Not for injection or oral ingestion. FOR TOPICAL OPHTHALMIC USE ONLY.
PRECAUTIONS GeneralGlaucoma patients on maximally tolerated medical therapy who are treated with IOPIDINE 0.5% Ophthalmic Solution to delay surgery should have their visual fields monitored periodically.
Although the topical use of IOPIDINE 0.5% 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 IOPIDINE 0.5% 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.
IOPIDINE 0.5% 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 IOPIDINE 0.5% 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, IOPIDINE 0.5% (apraclonidine ophthalmic solution) therapy should be discontinued.
One to two drops of IOPIDINE 0.5% Ophthalmic Solution should be instilled in the affected eye(s) three times daily. Since IOPIDINE 0.5% 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.
In clinical studies the overall discontinuation rate related to IOPIDINE 0.5% 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 IOPIDINE 0.5% (apraclonidine ophthalmic solution) as being possibly, probably, or definitely related to therapy:
OcularThe 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, photophobia.
NonocularDry 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 post-marketing use of IOPIDINE® 0.5% Ophthalmic Solution 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 IOPIDINE 0.5% Ophthalmic Solution, or a combination of these factors, include: bradycardia.
DRUG INTERACTIONSApraclonidine 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 IOPIDINE® 0.5% 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 IOPIDINE 0.5% Ophthalmic Solution should have pulse and blood pressures frequently monitored. Caution should be exercised with simultaneous use of clonidine and other similar pharmacologic agents.
