Dipivefrin

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.

No information provided.

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® (dipivefrin) 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® (dipivefrin) 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® (dipivefrin) 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® (dipivefrin) 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® (dipivefrin) reported discomfort due to photophobia, glare or light sensitivity.

General

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.

Information for patients

To avoid contamination, do not touch tip of container to the eye, eyelid or any surface.

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. 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 Dipivefrin hydrochloride is administered to a nursing woman.

Pediatric use

Clinical studies for safety and efficacy in pediatric patients have not been done.

Animal Studies

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