DOSAGE FORMS & STRENGTHS SECTION.
3 DOSAGE FORMS AND STRENGTHS Bottle filled with 15 mL of 1% (10 mg/mL), 2% (20 mg/mL) or 4% (40 mg/mL) pilocarpine hydrochloride sterile ophthalmic solution. Solution containing 1% (10 mg/mL), 2% (20 mg/mL) or 4% (40 mg/mL) pilocarpine hydrochloride ( 3 )
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.
PRINCIPAL DISPLAY PANEL NDC 0998-0206-15 Alcon Isopto Carpine 4% (pilocarpine hydrochloride ophthalmic solution) 15 mL Sterile Rx Only
ADVERSE REACTIONS SECTION.
6 ADVERSE REACTIONS Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect exposure in four controlled clinical trials of 90 days to 2 years duration in 317 patients diagnosed with open-angle glaucoma or ocular hypertension. In the four clinical trials, patients were treated with Isopto Carpine 2%, two to four times daily or with pilocarpine 1%, 1.75% or 2% in fixed combination with betaxolol 0.25%, two or three times daily.The most frequently reported adverse reactions occurring in 5% of patients in the pilocarpine 2% populations were: headache/browache, accommodative change, blurred vision, eye irritation, visual impairment (dim, dark, or jumping vision), and eye pain. The adverse reaction profile reported for the use of Isopto Carpine in pediatric patients is comparable to that seen in adult patients. Most common adverse reactions are headache/browache, accommodative change, eye irritation, eye pain, blurred vision, and/or visual impairment ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories, Inc. at 1-800-757-9195 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
INDICATIONS & USAGE SECTION.
1 INDICATIONS AND USAGE Isopto Carpine is indicated for the: Isopto Carpine is a muscarinic cholinergic agonist indicated for The reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension ( 1.1 ) The management of acute angle-closure glaucoma ( 1.2 ) The prevention of postoperative elevated IOP associated with laser surgery ( 1.3 ) The induction of miosis ( 1.4 ) 1.1 Reduction of Elevated Intraocular Pressuare (IOP) in Patients with Open-Angle Glaucoma or Ocular Hypertension 1.2 Management of Acute Angle-Closure Glaucoma 1.3 Prevention of Postoperative Elevated IOP Associated with Laser Surgery 1.4 Induction of Miosis
DOSAGE & ADMINISTRATION SECTION.
2 DOSAGE AND ADMINISTRATION Instill one drop in the eye(s) up to four times daily ( 2 ). 2.1 Reduction of Elevated Intraocular Pressure (IOP) in Patients with Open-Angle Glaucoma or Ocular Hypertension One drop of Isopto Carpine 1%, 2% or 4% should be applied topically in the eye(s) up to four times daily. Pilocarpine-nave patients should be started on the 1% concentration as higher concentrations are often not tolerated initially. The frequency of instillation and concentration of Isopto Carpine are determined by the severity of the elevated intraocular pressure and miotic response of the patient. To limit systemic exposure to pilocarpine, patients may be instructed to perform punctal occlusion for 2 minutes after instillation of Isopto Carpine ophthalmic solution. 2.2 Management of Acute Angle-Closure Glaucoma Prior to Isopto Carpine use, treatment with secretory suppressants and hyperosmotic agents may be needed to lower IOP below 50 mmHg and relieve iris ischemia. For initial management of acute angle-closure glaucoma, one drop of Isopto Carpine 1% or 2% may be applied topically in the eye(s) up to three times over a 30-minute period. If laser iridoplasty or iridomy is used to break the attack, one drop of Isopto Carpine 4% should be administered prior to the procedure. Following laser iridoplasty, one drop of Isopto Carpine 1% should be administered four times daily until an iridotomy can be performed. 2.3 Prevention of Postoperative Elevated IOP Associated with Laser Surgery One drop of Isopto Carpine 1%, 2% or 4% (or two drops administered five minutes apart) should be applied topically in the eye(s) 15 to 60 minutes prior to surgery. 2.4 Induction of Miosis One drop of Isopto Carpine 1%, 2% or 4% (or two drops administered five minutes apart) should be applied topically in the eye(s). 2.5 Use with Other Topical Ophthalmic Medications Isopto Carpine may be used in combination with beta-blockers, carbonic anhydrase inhibitors, sympathomimetics or hyperosmotic agents. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. 2.6 Use in Pediatric Patients In children under 2 years of age, one drop of Isopto Carpine 1% should be applied topically in the eye(s) three times daily. Children 2 years of age and over should be dosed as for adults. For the induction of miosis prior to goniotomy or trabeculotomy in children, one drop of Isopto Carpine 1% or 2% should be applied topically in the eye 15 to 60 minutes prior to surgery.
HOW SUPPLIED SECTION.
16 HOW SUPPLIED/STORAGE AND HANDLING Isopto Carpine (pilocarpine hydrochloride ophthalmic solution) 1%, 2% and 4% is supplied sterile in natural low density polyethylene plastic ophthalmic DROP-TAINER dispensers and green low density polyethylene tips with green polypropylene caps. 15 mL in 15 mL bottles 1%: NDC 0998-0203-15 2%: NDC 0998-0204-15 4%: NDC 0998-0206-15 STORAGE: Store at 15- 25C (59 - 77F) and protect from freezing.
11 DESCRIPTION Isopto Carpine (pilocarpine hydrochloride ophthalmic solution) is a cholinergic agonist prepared as a sterile topical ophthalmic solution. The active ingredient is represented by the chemical structure: Established name: pilocarpine hydrochloride Chemical name: 2(3H)-furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)-methyl]- monohydrochloride, (3S-cis)-. Molecular Formula: C11H16N2O2 HCl Molecular Weight: 244.72. Each mL of Isopto Carpine (pilocarpine hydrochloride ophthalmic solution) contains: Active: pilocarpine hydrochloride 1% (10 mg/mL), 2% (20 mg/mL), or 4% (40 mg/mL). Preservative: benzalkonium chloride 0.01%. Inactives: hypromellose 2910, boric acid, sodium citrate, sodium chloride (present in 1% only); hydrochloric acid and/or sodium hydroxide (to adjust pH); purified water. Isopto Carpine has a pH of 3.5 to 5.5 and an osmolality of 290 to 350 mOsm/kg (1% and 2% products) and 550 to 600 mOsm/kg (4% product).
10 OVERDOSAGE Systemic toxicity following topical ocular administration of pilocarpine is rare, but occasionally patients who are sensitive may develop sweating and gastrointestinal overactivity following the suggested dosage and administration. Overdosage can produce sweating, salivation, nausea, tremors and slowing of the pulse and a decrease in blood pressure. In moderate overdosage, spontaneous recovery is to be expected and is aided by intravenous fluids to compensate for dehydration. For patients demonstrating severe poisoning, atropine, the pharmacologic antagonist to pilocarpine, should be used.
WARNINGS AND PRECAUTIONS SECTION.
5 WARNINGS AND PRECAUTIONS Poor illumination: Exercise caution in night driving and other hazardous occupations in poor illumination ( 5.1 ). Pre-existing retinal disease: Rare cases of retinal detachment have been reported; a thorough examination of the retina including funduscopy is advised in all patients prior to the initiation of therapy ( 5.2 ). Iritis: Caution is advised in patients with iritis. ( 5.3 ) Congenital glaucoma: Caution is advised in pediatric patients with primary congenital glaucoma for control of IOP as cases of a paradoxical increase in IOP have been reported. ( 5.4 ) 5.1 Poor Illumination Patients should be advised to exercise caution in night driving and other hazardous occupations in poor illumination. In addition, miotics may cause accommodative spasm. Patients should be advised not to drive or use machinery if vision is not clear. 5.2 Pre-existing Retinal Disease As with all miotics, rare cases of retinal detachment have been reported when used in certain susceptible individuals and those with pre-existing retinal disease; therefore, a thorough examination of the retina including funduscopy is advised in all patients prior to the initiation of therapy. 5.3 Iritis Isopto Carpine is not recommended to be used when iritis is present. 5.4 Primary Congenital Glaucoma Caution is advised when using Isopto Carpine in pediatric patients with primary congenital glaucoma for control of intraocular pressure (IOP) as cases of a paradoxical increase in IOP have been reported. In addition, the use of Isopto Carpine is not recommended in pediatric patients diagnosed with glaucoma secondary to anterior segment dysgenesis or uveitis (especially if uveitis is active). 5.5 Contact Lens Wear Contact lens wearers should be advised to remove their lenses prior to the instillation of Isopto Carpine ophthalmic solution and to wait 10 minutes after dosing before reinserting their contact lenses.
NONCLINICAL TOXICOLOGY SECTION.
13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility There have been no long-term studies done using pilocarpine hydrochloride in animals to evaluate carcinogenic potential.
USE IN SPECIFIC POPULATIONS SECTION.
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy. Category C. Animal reproduction studies have not been conducted with pilocarpine hydrochloride. It is also not known whether pilocarpine hydrochloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Isopto Carpine should be given to a pregnant woman only if clearly needed. 8.3 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 Isopto Carpine is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness of pilocarpine hydrochloride ophthalmic solution in pediatric patients have been established. 8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.
INFORMATION FOR PATIENTS SECTION.
17 PATIENT COUNSELING INFORMATION 17.1 Avoiding Contamination of the Product Do not touch dropper tip to any surface, as this may contaminate the contents. 17.2 Night Driving Caution is advised with night driving and when hazardous activities are undertaken in poor illumination. 17.3 Accommodative Spasm Isopto Carpine ophthalmic solution may cause problems when changing focus between near objects and distant objects. Do not drive or use machinery if vision is not clear. 17.4 Contact Lens Wear Contact lens should be removed prior to the instillation of Isopto Carpine ophthalmic solution. Wait 10 minutes after dosing before reinserting contact lenses. 17.5 Concomitant Topical Ocular Therapy If more than one topical ophthalmic medication is being used, the medicines must be administered at least 5 minutes apart. 17.6 Systemic Exposure To limit exposure to pilocarpine to the eye alone, close eyes gently and apply pressure with finger to the corner of eye by the nose for 2 minutes after instillation of Isopto Carpine ophthalmic solution. Rx Only Printed in USA 2009, 2010 Alcon, Inc. ALCON LABORATORIES, INC. 6201 South Freeway Fort Worth, Texas 76134 USA 1-800-757-9195 9005884-0910
CLINICAL STUDIES SECTION.
14 CLINICAL STUDIES In clinical trials reported in the medical literature, pilocarpine ophthalmic solution reduced intraocular pressure (IOP) by 3-7 mmHg in patients with open-angle glaucoma. Pilocarpine ophthalmic solution has also been shown to be effective in the induction of miosis, in the prevention of postoperative elevated IOP, and in the management of acute angle-closure glaucoma.
CLINICAL PHARMACOLOGY SECTION.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Pilocarpine hydrochloride is a direct acting cholinergic parasympathomimetic agent which acts through direct stimulation of muscarinic receptors and smooth muscle such as the iris and secretory glands.Pilocarpine contracts the ciliary muscle, causing increased tension on the scleral spur and opening of the trabecular meshwork spaces to facilitate outflow of aqueous humor. Outflow resistance is reduced, lowering intraocular pressure (IOP). Pilocarpine also produces miosis through contraction of the iris sphincter muscle. Miosis relieves appositional angle narrowing and closure, which lowers IOP in certain types of angle-closure glaucoma. 12.3 Pharmacokinetics Systemic exposure to pilocarpine was evaluated in 14 healthy subjects administered 2 drops of Isopto Carpine (pilocarpine hydrochloride ophthalmic solution) 4% to both eyes four times daily for eight days. A comparison of Cmax values on Days 5 and 8 indicated that pilocarpine concentrations in plasma reached steady-state following topical administration of Isopto Carpine 4%. The mean (SD) Cmax and AUC0-last values on Day 8 were 3.7 (3.2) ng/mL and 7.7 (8.4) nghour/mL, respectively. The Tmax values on Day 8 ranged from 0.5 to 1 hour.
4 CONTRAINDICATIONS None. None.