PROPINE® contains dipivefrin hydrochloride in a sterile, isotonic solution. Dipivefrin HCI is a white, crystalline powder, freely soluble in water.

Empirical Formula:

C₁₉-H₂₉O₅N•HCI

Chemical Name: (±) -3,4-Dihydroxy-α-[(methyl-amino) methyl] benzyl-alcohol 3,4-dipivalate hydrochloride.

Contains: Active: dipivefrin HCI 0.1%

Preservative: benzalkonium chloride; Inactives: edetate disodium; sodium chloride; hydrochloric acid to adjust pH; and purified water.

Last updated on RxList: 12/9/2008

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.

Initial Glaucoma Therapy

The usual dosage of PROPINE® is one drop in the eye(s) every 12 hours.

Replacement with PROPINE® ophthalmic solution

When patients are being transferred to PROPINE® from antiglaucoma agents other than epinephrine, on the first day continue the previous medication and add one drop of PROPINE® ophthalmic solution in each eye every 12 hours. On the following day, discontinue the previously used antiglaucoma agent and continue with PROPINE®.

In transferring patients from conventional epinephrine therapy to PROPINE® ophthalmic solution, simply discontinue the epinephrine medication and institute the PROPINE® regimen.

Addition of PROPINE® ophthalmic solution

When patients on other antiglaucoma agents require additional therapy, add one drop of PROPINE® every 12 hours.

Concomitant Therapy

For difficult to control patients, the addition of PROPINE® ophthalmic solution to other agents such as pilocarpine, carbachol, echothiophate iodide or acetazolamide has been shown to be effective.

Note: Not for injection.

PROPINE® (dipivefrin HCI ophthalmic solution, USP) 0.1%, is supplied sterile in plastic dropper bottles as follows: 5 mL - 0023-9208-05; 10 mL - 0023-9208-10; 15 mL - 0023-9208-15.

Note: Store in tight, light-resistant containers.

Allergan, Inc. Irvine, CA 92612, U.S.A. Revised December 2000. FDA Rev date: 4/12/2002

Last updated on RxList: 12/9/2008

Cardiovascular Effects

Tachycardia, arrhythmias and hypertension have been reported with ocular administration of epinephrine.

Local Effects

The most frequent side effects reported with PROPINE® alone were injection in 6.5% of patients and burning and stinging in 6%. Follicular conjunctivitis, eye pain, mydriasis, blurry vision, eye pruritus, headache and allergic reaction to PROPINE® ophthalmic solution have been reported. Epinephrine therapy can lead to adrenochrome deposits in the conjunctiva and cornea.

No information provided.

Last updated on RxList: 12/9/2008

No information provided.

Aphakic Patients

Macular edema has been shown to occur in up to 30% of aphakic patients treated with epinephrine. Discontinuation of epinephrine generally results in reversal of the maculopathy.

Pregnancy

Pregnancy Category B

Reproduction studies have been performed in rats and rabbits at daily oral doses up to 10 mg/kg body weight (5 mg/kg in teratogenicity studies), and have revealed no evidence of impaired fertility or harm to the fetus due to dipivefrin HCI. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

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 PROPINE® ophthalmic solution is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Animal Studies

Rabbit studies indicated a dose-related incidence of meibomian gland retention cysts following topical administration of both dipivefrin hydrochloride and epinephrine.

Last updated on RxList: 12/9/2008

No information provided.

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.

Last updated on RxList: 12/9/2008

PROPINE® (dipivefrin HCI ophthalmic solution, USP) is a member of a class of drugs known as prodrugs. Prodrugs are usually not active in themselves and require biotransformation to the parent compound before therapeutic activity is seen. These modifications are undertaken to enhance absorption, decrease side effects and enhance stability and comfort, thus making the parent compound a more useful drug. Enhanced absorption makes the prodrug a more efficient delivery system for the parent drug because less drug will be needed to produce the desired therapeutic response.

PROPINE® ophthalmic solution is a prodrug of epinephrine formed by the diesterification of epinephrine and pivalic acid. The addition of pivaloyl groups to the epinephrine molecule enhances its lipophilic character and as a consequence, its penetration into the anterior chamber.

PROPINE® is converted to epinephrine inside the human eye by enzyme hydrolysis. The liberated epinephrine, an adrenergic agonist, appears to exert its action by decreasing aqueous production and by enhancing outflow facility. The PROPINE® prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine, with fewer side effects than are associated with conventional epinephrine therapy.

The onset of action with one drop of PROPINE® occurs about 30 minutes after treatment, with maximum effect seen at about one hour.

Using a prodrug means that less drug is needed for therapeutic effect since absorption is enhanced with the prodrug. PROPINE® ophthalmic solution at 0.1% dipivefrin was judged less irritating than a 1% solution of epinephrine hydrochloride or bitartrate. In addition, only 8 of 455 patients (1.8%) treated with PROPINE® reported discomfort due to photophobia, glare or light sensitivity.

Last updated on RxList: 12/9/2008

No information provided. Please refer to the PRECAUTIONS section.

Last updated on RxList: 12/9/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

DIPIVEFRIN SOLUTION - OPHTHALMIC

(dye-PI-ve-frin)

USES: Dipivefrin is used to treat high pressure inside the eye due to glaucoma (open-angle type) or other eye diseases (e.g., ocular hypertension). Lowering high pressure inside the eye can help prevent blindness. This medication works by regulating the flow of fluid within the eye to maintain a normal pressure.

HOW TO USE: Apply this medication in the affected eye(s), usually one drop every 12 hours or as directed by your doctor.

To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

This medication contains a preservative that may stain contact lenses. If you are wearing contact lenses, remove them before using your eye drops. Wait at least 15 minutes after each dose before putting your lenses back in.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 5 minutes before applying other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same times each day. It is important to continue using dipivefrin even if you feel well. Most people with glaucoma or high pressure in the eye do not feel sick.

SIDE EFFECTS: Burning/stinging/irritation/redness of the eye, blurred vision, headache, and increased sensitivity to light may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Although unlikely, this medication may cause dark staining on your eyes. Tell your doctor promptly if this occurs.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: eye pain/swelling, severe headaches, fast/irregular heartbeat.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using dipivefrin, tell your doctor or pharmacist if you are allergic to it; or to epinephrine, the preservative benzalkonium chloride, sulfites (found in some brands of this medication); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: narrow or closed-angle glaucoma.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: eye problems (e.g., macular edema, lens extraction/aphakia), high blood pressure, heart or blood vessel disease, irregular heartbeat.

If you develop an eye infection or injury, or have eye surgery, check with your doctor about whether you should continue to use your current bottle of dipivefrin. You may be advised to start using a new bottle.

Use caution while engaging in activities requiring clear vision such as driving or using machinery because your vision may be temporarily blurred or unstable after applying this drug.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature below 77 degrees F (25 degrees C) away from light and moisture. Keep the cap tightly closed. Discard the solution if it turns brown or cloudy or if it contains particles. Do not store in the bathroom and do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.