IOPIDINE

IOPIDINE 1% Ophthalmic Solution contains apraclonidine hydrochloride, an alpha adrenergic agonist, in a sterile isotonic solution for topical application to the eye. Apraclonidine hydrochloride is a white to off-white powder and is highly soluble in water. Its chemical name is 2-[(4-amino-2,6 dichlorophenyl)imino] imidazolidine monohydrochloride with an empirical formula of C₉H₁₁Cl₃N₄ and a molecular weight of 281.6.

The chemical structure of apraclonidine hydrochloride is:

Each mL of IOPIDINE 1% Ophthalmic Solution contains: Actives: apraclonidine hydrochloride 11.5 mg equivalent to apraclonidine base 10 mg. Inactives: sodium chloride, sodium acetate, sodium hydroxide and/or hydrochloric acid (pH 4.4-7.8), purified water and benzalkonium chloride 0.01% (preservative). Osmolality is 260-320 mOsm.

Apraclonidine is a relatively selective, alpha adrenergic agonist and does not have significant membrane stabilizing (local anesthetic) activity. When instilled into the eye, IOPIDINE 1% (apraclonidine hydrochloride ophthalmic solution) has the action of reducing intraocular pressure (IOP). Ophthalmic apraclonidine has minimal effect on cardiovascular parameters.

Optic nerve head damage and visual field loss may result from an acute elevation in IOP that can occur after argon or Nd:YAG laser surgical procedures. Elevated IOP, whether acute or chronic in duration, is a major risk factor in the pathogenesis of visual field loss. The higher the peak or spike of IOP, the greater the likelihood of visual field loss and optic nerve damage especially in patients with previously compromised optic nerves. The onset of action with IOPIDINE 1% Ophthalmic Solution can usually be noted within one hour and the maximum IOP reduction usually occurs three to five hours after application of a single dose. The precise mechanism of the ocular hypotensive action of IOPIDINE 1% Ophthalmic Solution is not completely established at this time. Aqueous fluorophotometry studies in man suggest that its predominant action may be related to a reduction of aqueous formation. Controlled clinical studies of patients requiring argon laser trabeculoplasty, argon laser iridotomy or Nd:YAG posterior capsulotomy showed that IOPIDINE 1% Ophthalmic Solution controlled or prevented the post-surgical IOP rise typically observed in patients after undergoing those procedures. After surgery, the mean IOP was 1.2 to 4 mmHg below the corresponding pre-surgical baseline pressure before IOPIDINE Ophthalmic Solution treatment. With placebo treatment, post-surgical pressures were 2.5 to 8.4 mmHg higher than their corresponding pre-surgical baselines. Overall, only 2% of patients treated with IOPIDINE* 1% Ophthalmic Solution had severe IOP elevations (spike greater than or equal to 10 mmHg) during the first three hours after laser surgery, whereas 23% of placebo-treated patients responded with severe pressure spikes (Table 1). Of the patients that experienced a pressure spike after surgery, the peak IOP was above 30 mmHg in most patients (Table 2) and was above 50 mmHg in seven placebo-treated patients and one IOPIDINE 1% Ophthalmic Solution-treated patient.

Table 1: Incidence of IOP Spikes Greater Than or Equal to 10 mmHg

^aN = Number Spikes/Number Eyes.

Table 2: Magnitude of Post-surgical IOP in Trabeculoplasty, Iridotomy and Nd:YAG Capsulotomy Patients With Severe Pressure Spikes Greater than or Equal to 10 mmHg

Maximum Postsurgical IOP (mmHg)

IOPIDINE 1% Ophthalmic Solution is indicated to control or prevent post-surgical elevations in IOP that occur in patients after argon laser trabeculoplasty, argon laser iridotomy or Nd:YAG posterior capsulotomy.

IOPIDINE 1% Ophthalmic Solution is contraindicated for patients receiving monoamine oxidase inhibitor therapy and for patients with hypersensitivity to any component of this medication or to clonidine.

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

It is not known if topically applied IOPIDINE 1% Ophthalmic Solution is excreted in human milk. Decision should be made to discontinue nursing temporarily for the one day on which IOPIDINE 1% Ophthalmic Solution is used.

Safety and effectiveness in pediatric patients have not been established.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

The following adverse events, occurring in less than 2% of patients, were reported in association with the use of IOPIDINE 1% Ophthalmic Solution in laser surgery: ocular injection, upper lid elevation, irregular heart rate, nasal decongestion, ocular inflammation, conjunctival blanching, and mydriasis.

The following adverse events were observed in investigational studies dosing IOPIDINE 1% Ophthalmic Solution once or twice daily for up to 28 days in non-laser studies:

Ocular

Conjunctival blanching, upper lid elevation, mydriasis, burning, discomfort, foreign body sensation, dryness, itching, hypotony, blurred or dimmed vision, allergic response, conjunctival microhemorrhage.

Gastrointestinal

Abdominal pain, diarrhea, stomach discomfort, emesis

Cardiovascular

Bradycardia, vasovagal attack, palpitations, orthostatic episode

Central Nervous System

Insomnia, dream disturbances, irritability, decreased libido.

Other

Taste abnormalities, dry mouth, nasal burning or dryness, headache, head cold sensation, chest heaviness or burning, clammy or sweaty palms, body heat sensation, shortness of breath, increased pharyngeal secretion, extremity pain or numbness, fatigue, paresthesia, pruritus not associated with rash.

Clinical Practice

The following events have been identified during postmarketing use of IOPIDINE 1% 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 1% Ophthalmic Solution, or a combination of these factors, include hypersensitivity.

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.

One drop of IOPIDINE* 1% Ophthalmic Solution should be instilled in the scheduled operative eye one hour before initiating anterior segment laser surgery and a second drop should be instilled to the same eye immediately upon completion of the laser surgical procedure. Use a separate container for each single-drop dose and discard each container after use.

IOPIDINE 1% Ophthalmic Solution as base is a sterile, isotonic, aqueous solution containing apraclonidine hydrochloride.

Supplied as follows: 0.1 mL in plastic ophthalmic dispensers, packaged two per pouch. These dispensers are enclosed in a foil overwrap as an added barrier to evaporation.

0.1 mL (packaged two per pouch) NDC 0065-0660-10

Storage: Store at 2°C to 25°C (36°F-77°F).

Protect from light.

Distributed by:
ALCON LABORATORIES, INC.
Fort Worth, Texas 76134 USA

Alcon®

a Novartis company

* a trademark of Novartis

© Novartis

T2018-17
March 2018

NDC 0065-0660-10

IOPIDINE^®
(apraclonide hydrochloride ophthalmic solution) 1% as base
Sterile

Alcon^®
a Novartis company
CONTENTS: 12 pouches containing
2 units, 0.1mL each