DIPIVEFRIN HCL
DESCRIPTION:
PROPINE(R) contains dipivefrin hydrochloride in a sterile, isotonic solution.
Dipivefrin HCl is a white, crystalline powder, freely soluble in water.
EMPIRICAL FORMULA: C19H29O5N.HCl
CHEMICAL NAME: (+/-)-3,4-Dihydroxy-alpha- ((methylamino)methyl)benzyl alcohol
3,4-dipivalate hydrochloride.
CONTAINS:
Active: dipivefrin HCL* 0.1%
Preservative: benzalkonium chloride 0.005%
Inactives: edetate disodium; sodium chloride; hydrochloric acid to adjust pH;
and purified water.
ACTIONS/CLINICAL PHARMACOLOGY:
PROPINE(R) (dipivefrin HCl) 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(R) 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(R) 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(R) 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(R) 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(R) 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(R)
reported discomfort due to photophobia, glare or light sensitivity.
INDICATIONS AND USAGE:
PROPINE(R) (dipivefrin HCl) 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(R).
In controlled and open-label studies of glaucoma, PROPINE(R) demonstrated a
statistically significant intraocular pressure-lowering effect. Patients using
PROPINE(R) twice daily in studies with mean durations of 76-146 days experienced
mean pressure reductions ranging from 20-24%.
Therapeutic response to PROPINE(R) twice daily is somewhat less than 2%
epinephrine twice daily. Controlled studies showed statistically significant
differences in lowering of intraocular pressure between PROPINE(R) and 2%
epinephrine. In controlled studies in patients with a history of epinephrine
intolerance, only 3% of patients treated with PROPINE(R) exhibited intolerance,
while 55% of those treated with epinephrine again developed intolerance.
Therapeutic response to PROPINE(R) twice daily therapy is comparable to 2%
pilocarpine 4 times daily. In controlled clinical studies comparing PROPINE(R)
and 2% pilocarpine, there were no statistically significant differences in the
maintenance of IOP levels for the two medications. PROPINE(R) does not produce
miosis or accommodative spasm which cholinergic agents are known to produce.
Night blindness often associated with miotic agent is not present with
PROPINE(R) therapy. Patients with cataracts avoid the inability to see around
lenticular opacities caused by constricted pupil.
CONTRAINDICATIONS:
PROPINE(R) 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.
PRECAUTIONS:
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 (5mg/kg in
teratogenicity studies), and have revealed no evidence of impaired fertility or
harm to the fetus due to dipivefrin HCl. 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(R) is administered to a nursing woman.
PEDIATRIC USE. Safety and effectiveness in pediatric patients have not been
established.
ANIMAL PHARMACOLOGY:
ANIMAL STUDIES. Rabbit studies indicated a dose- related incidence of meibomian
gland retention cysts following topical administration of both dipivefrin
hydrochloride and epinephrine.
ADVERSE REACTIONS:
CARDIOVASCULAR EFFECTS. Tachycardia, arrhythmias and hypertension have been
reported with ocular administration of epinephrine.
LOCAL EFFECTS. The most frequent side effects reported with PROPINE(R) alone
were injection in 6.5% of patients and burning and stinging in 6%. Follicular
conjunctivitis, mydriasis, blurry vision, headache and allergic reactions to
PROPINE(R) have been reported. Epinephrine therapy can lead to adrenochrome
deposits in the conjunctiva and cornea.
DOSAGE AND ADMINISTRATION:
INITIAL GLAUCOMA THERAPY. The usual dosage of PROPINE(R) is one drop in the
eye(s) every 12 hours.
REPLACEMENT WITH PROPINE(R). When patients are being transferred to PROPINE(R)
from antiglaucoma agents other than epinephrine, on the first day continue the
previous medication and add one drop of PROPINE(R) in each eye every 12 hours.
On the following day, discontinue the previously used antiglaucoma agent and
continue with PROPINE(R).
In transferring patients from conventional epinephrine therapy to PROPINE(R),
simply discontinue the epinephrine medication and institute the PROPINE(R)
regimen.
ADDITION OF PROPINE(R). When patients on other antiglaucoma agents require
additional therapy, add one drop of PROPINE(R) every 12 hours.
CONCOMITANT THERAPY. For difficult to control patients, the addition of
PROPINE(R) to other agents such as pilocarpine, carbachol, echothiophate iodide
or acetazolamide has been shown to be effective.
NOTE: Not for injection.
C CAP(R) Compliance Cap Patient Instructions
INSTRUCTIONS FOR USE:
1. On the first usage, make sure the number "1" appears in the window. If not,
click the cap to the right station.
2. Remove the cap and apply medication.
3. Replace the cap. Hold the C CAP(R) between your thumb and forefinger. Now
rotate the bottle until the cap clicks to the next station.
4. When it's time to take your next dose, repeat steps 2 and 3.
IMPORTANT NOTES: Don't try to catch up on missed doses by applying more than one
dose at a time.
Each time you replace the cap, turn it until you hear the click.
The number in the window specifies your Next dosage.
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