Isopto Carpine Ophthalmic Solution: Package Insert / Prescribing Info

1.1 Reduction of Elevated Intraocular Pressure (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

2.1 Reduction of Elevated 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-naïve 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 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.

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 Preexisting Retinal Disease

As with all miotics, rare cases of retinal detachment have been reported when used in certain susceptible individuals and those with preexisting 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 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.

6.1 Clinical Trials 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/brow ache, 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.

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.

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 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) ng×hour/mL, respectively. The Tmax values on Day 8 ranged from 0.5 to 1 hour.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

There have been no long-term studies done using pilocarpine hydrochloride in animals to evaluate carcinogenic potential.