Propine

You should not use this medication if you are allergic to dipivefrin, or if you have narrow-angle glaucoma.

Before using dipivefrin, tell your doctor if you are allergic to any drugs, or if you have high blood pressure or a history of cataract surgery.

Do not use this medication while you are wearing contact lenses. This medication may contain a preservative that can be absorbed by soft contact lenses. Wait at least 15 minutes after using dipivefrin before putting your contact lenses in.

Do not allow the dropper tip to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

You should not use this medication if you are allergic to dipivefrin, or if you have narrow-angle glaucoma.

Before using dipivefrin, tell your doctor if you are allergic to any drugs, or if you have:

• high blood pressure; or
• a history of cataract surgery.

If you have any of these conditions, you may need a dose adjustment or special tests to safely use dipivefrin ophthalmic.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether dipivefrin ophthalmic passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

General

• Adjust dosage according to individual requirements and response of patient as determined by tonometric readings before and during therapy.7

• Because of diurnal variations in IOP, measure IOP at different times during the day to determine if an adequate hypotensive effect is maintained.7 Since IOP may not stabilize for a few weeks after initiating therapy, determine IOP after several weeks of therapy; thereafter, IOP should be determined as necessary.7 89 94

Administration

Ophthalmic Administration

Apply topically to the eye as an ophthalmic solution.1 4 Not for injection.1

Avoid contamination of the solution container.6

Dosage

Available as dipivefrin hydrochloride; dosage expressed in terms of the salt.1

Adults

1 drop of a 0.1% solution in affected eye(s) every 12 hours.1 4 5 10

In patients receiving several drugs for the treatment of glaucoma, adjustments to the regimen should involve one drug at a time and should usually occur at intervals of at least 1 week.89

Initially, 1 drop of a 0.1% solution every 12 hours while therapy with other drugs is continued.1 Beginning on the following day1 and continuing at intervals of at least 1 week until optimum response is achieved, reduce dosage of one of the other drugs or discontinue one of the other drugs.89 Adjust remaining regimen according to the IOP response of the patient.89

Conversion from monotherapy with epinephrine: Discontinue epinephrine and initiate dipivefrin at 1 drop of a 0.1% solution into affected eye(s) every 12 hours1 5 at the time of the next scheduled dose of epinephrine.89 94

Conversion from monotherapy with antiglaucoma agents other than epinephrine: On day 1, continue other antiglaucoma agent and add 1 drop of a 0.1% dipivefrin solution every 12 hours.1 On day 2, discontinue the other drug and continue dipivefrin.1

• Prodrug with little or no pharmacologic activity until hydrolyzed into epinephrine.1 7 9 12 14 22 35 89

• Lowers IOP1 4 5 10 13 25 26 27 28 34 36 37 52 in patients with glaucoma;1 4 5 10 13 25 26 27 28 34 36 37 52 lowers IOP to a lesser extent in the normal eye; causes mydriasis.27 77 Appears to lower IOP by stimulating α -and/or β2-adrenergic receptors, 7 11 23 24 67 90 93 95 96 resulting in an increase in pressure-independent (uveoscleral) and, to a lesser extent in pressure-dependent (trabecular) aqueous humor outflow.1 4

Dipivefrin is used to treat certain types of glaucoma.

This medicine is available only with your doctor's prescription.

Propine® contains dipivefrin hydrochloride in a sterile, isotonic solution. Dipivefrin HCI is a white, crystalline powder, freely soluble in water with an osmolality of approximately 250 - 330 mOsmol/kg.

Empirical Formula:

C19H29O5N•HCI

Chemical Name: (±) -3,4-Dihydroxy–α– [(methylamino) methyl] benzylalcohol 3,4-dipivalate hydrochloride.

STRUCTURAL FORMULA:

Contains: Active: dipivefrin HCI 0.1%

Preservative: benzalkonium chloride

Inactives: edetate disodium; purified water; sodium chloride; and hydrochloric acid to adjust pH. The pH during its shelf life ranges from 2.5 - 3.5.

Propine® (dipivefrin HCI ophthalmic solution, USP) is indicated as initial therapy for the control of intraocular pressure in chronic open-angle glaucoma. Patients responding inadequately to other antiglaucoma therapy may respond to addition of Propine®.

In controlled and open-label studies of glaucoma, Propine® ophthalmic solution demonstrated a statistically significant intraocular pressure-lowering effect. Patients using Propine® twice daily in studies with mean durations of 76-146 days experienced mean pressure reductions ranging from 20-24%.

Therapeutic response to Propine® ophthalmic solution twice daily is somewhat less than 2% epinephrine twice daily. Controlled studies showed statistically significant differences in lowering of intraocular pressure between Propine® and 2% epinephrine. In controlled studies in patients with a history of epinephrine intolerance, only 3% of patients treated with Propine® ophthalmic solution exhibited intolerance, while 55% of those treated with epinephrine again developed intolerance.

Therapeutic response to Propine® twice daily therapy is comparable to 2% pilocarpine 4 times daily. In controlled clinical studies comparing Propine® ophthalmic solution and 2% pilocarpine, there were no statistically significant differences in the maintenance of IOP levels for the two medications. Propine® does not produce miosis or accommodative spasm which cholinergic agents are known to produce. Night blindness often associated with miotic agents is not present with Propine® therapy. Patients with cataracts avoid the inability to see around lenticular opacities caused by constricted pupil.

Propine® should not be used in patients with narrow angles since any dilation of the pupil may predispose the patient to an attack of angle-closure glaucoma. This product is contraindicated in patients who are hypersensitive to any of its components.

Propine® (dipivefrin HCI ophthalmic solution, USP) 0.1%, is supplied sterile in opaque white low density polyethylene ophthalmic dispenser bottles and tips with purple polystyrene caps as follows:

Note: Store in a tight, light-resistant container at 15° to 25°C (59° to 77°F).

Rx Only

Revised December 2005
© 2006 Allergan, Inc.
Irvine, CA 92612, U.S.A.
® marks owned by Allergan, Inc.
7592X
71738US11T

Applies to dipivefrin ophthalmic: ophthalmic solution

Ocular

Ocular side effects have included injection (6.5%), stinging (6%), and burning (6%). Follicular conjunctivitis and mydriasis have been reported rarely. Corneal vascularization or vesicles, eyelid ectropion, papillary conjunctivitis, blepharoconjunctivitis, macular edema, corneal toxicity (dendritic keratitis, punctate keratitis, or epitheliopathy), and blurred vision have also been reported.

Ocular side effects associated with ocular administration of epinephrine have included conjunctival and corneal adrenochrome deposits.[Ref]

Some long-term studies have reported observations of follicular conjunctivitis in almost all patients with up to 40% classified as severe reactions.[Ref]

Cardiovascular

Cardiovascular side effects have included slight increases in heart rate and diastolic blood pressure.

Cardiovascular side effects associated with ocular epinephrine have included tachycardia, arrhythmias, and hypertension.[Ref]

Most placebo-controlled studies have reported mild average increases in heart rate (3 to 4 beats/min--with or without palpitations) or diastolic blood pressure (1 to 5 mm Hg) associated with dipivefrin.[Ref]

Nervous system

Nervous system side effects have included headache and dizziness.[Ref]

Hypersensitivity

Hypersensitivity reactions have included bronchospasm associated with a formulation containing bisulfite preservative.[Ref]

Some side effects of Propine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.