propine

Description: PROPINE® contains dipivefrin hydrochloride in a sterile, isotonicsolution propine. Dipivefrin HCl is a white, crystalline powder, freely soluble in waterwith an osmolality of approx propine. 250-330 mOsmol/kg propine.

Empirical Formula: C 19 H 29 O 5 N · HCl

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

Contains:

Active: dipivefrin HCl 0.1%

Preservative: benzalkonium chloride

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

Clinical Pharmacology: PROPINE® (dipivefrin HCl ophthalmic solution, USP)is a member of a class of drugs known as prodrugs propine. Prodrugs are usually notactive in themselves and require biotransformation to the parent compound beforetherapeutic activity is seen propine. These modifications are undertaken to enhanceabsorption, decrease side effects and enhance stability and comfort, thus makingthe parent compound a more useful drug propine. Enhanced absorption makes the prodruga more efficient delivery system for the parent drug because less drug willbe needed to produce the desired therapeutic response propine.

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

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

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

Using a prodrug means that less drug is needed for therapeutic effect sinceabsorption is enhanced with the prodrug propine. PROPINE® ophthalmic solution at0.1% dipivefrin was judged less irritating than a 1% solution of epinephrinehydrochloride or bitartrate propine. In addition, only 8 of 455 patients (1.8%) treatedwith PROPINE® reported discomfort due to photophobia, glare or light sensitivity propine.

Indications: PROPINE® (dipivefrin HCl ophthalmic solution, USP) is indicatedas initial therapy for the control of intraocular pressure in chronic open-angleglaucoma propine. Patients responding inadequately to other antiglaucoma therapy mayrespond to addition of PROPINE® propine.

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

Therapeutic response to PROPINE® ophthalmic solution twice daily is somewhatless than 2% epinephrine twice daily propine. Controlled studies showed statisticallysignificant differences in lowering of intraocular pressure between PROPINE®and 2% epinephrine propine. In controlled studies in patients with a history of epinephrineintolerance, only 3% of patients treated with PROPINE® ophthalmic solutionexhibited intolerance, while 55% of those treated with epinephrine again developedintolerance propine.

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

Contraindications: PROPINE® should not be used in patients with narrow anglessince any dilation of the pupil may predispose the patient to an attack of angle-closureglaucoma propine. This product is contraindicated in patients who are hypersensitiveto any of its components propine.

Precautions: Aphakic Patients propine. Macular edema has been shown to occur in up to30% of aphakic patients treated with epinephrine propine. Discontinuation of epinephrinegenerally results in reversal of the maculopathy propine.

Pregnancy: Pregnancy Category B propine. Reproduction studies have been performed inrats and rabbits at daily oral doses up to 10 mg/kg body weight (5 mg/kg interatogenicity studies), and have revealed no evidence of impaired fertilityor harm to the fetus due to dipivefrin HCl propine. There are, however, no adequateand well-controlled studies in pregnant women propine. Because animal reproduction studiesare not always predictive of human response, this drug should be used duringpregnancy only if clearly needed propine.

Nursing Mothers propine. It is not known whether this drug is excreted in human milk propine. Because many drugs are excreted in human milk, caution should be exercised whenPROPINE® ophthalmic solution is administered to a nursing woman propine.

Pediatric Use: Safety and effectiveness in pediatric patients have not beenestablished propine.

Geriatric Use propine. No overall clinical differences in safety or effectiveness havebeen observed between elderly and other adult patients propine.

Animal Studies propine. Rabbit studies indicated a dose-related incidence of meibomiangland retention cysts following topical administration of both dipivefrin hydrochlorideand epinephrine propine.

Adverse Reactions:

Cardiovascular Effects propine. Tachycardia, arrhythmias and hypertension have beenreported with ocular administration of epinephrine propine.

Local Effects propine. The most frequent side effects reported with PROPINE® alonewere injection in 6.5% of patients and burning and stinging in 6% propine. Follicularconjunctivitis, eye pain, mydriasis, blurry vision, eye pruritus, headache,and allergic reaction to PROPINE® ophthalmic solution have been reported propine. Epinephrine therapy can lead to adrenochrome deposits in the conjunctiva andcornea propine.

Dosage and Administration:
Initial Glaucoma Therapy propine. The usual dosage of PROPINE® is one drop in theeye(s) every 12 hours propine.

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

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

Addition of PROPINE® propine. When patients on other antiglaucoma agents requireadditional therapy, add one drop of PROPINE® every 12 hours propine.

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

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