Dapiprazole (Ophthalmic)


VA CLASSIFICATION
Primary: OP900

Commonly used brand name(s): Rev-Eyes.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antimydriatic—

Indications

Accepted

Mydriasis, reversal of—Indicated in the treatment of pharmacologically induced mydriasis produced by sympathomimetic (phenylephrine) or parasympatholytic (tropicamide) agents. {01} {07} {08} {09} {12} {13} {14}

Unaccepted
Dapiprazole is not indicated for the reduction of intraocular pressure, in the treatment of open angle glaucoma, {01} or for any indication other than reversal of induced mydriasis. {12}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    361.93


Description
    Dapiprazole hydrochloride is a sterile, white, lyophilized powder soluble in water {01}.
    Dapiprazole hydrochloride solution is a clear, colorless, slightly viscous solution {01}.


Other characteristics
    Reconstituted solution has a pH between 4.5 and 6 {06} and an osmolarity of approximately 415 mOsm {01}.

Mechanism of action/Effect:

Dapiprazole is an alpha-adrenergic blocking agent {01} {07} {08} and acts by blocking the alpha-adrenergic receptors in smooth muscle. Dapiprazole produces miosis through an effect on the dilator muscle of the iris. {01}

Dapiprazole has demonstrated safe and rapid reversal of mydriasis produced by phenylephrine and, to a lesser degree, of that produced by tropicamide. {07} {08} It has not been tested against other mydriatics. {12}In patients with decreased accommodative amplitude due to treatment with tropicamide, the miotic effect of dapiprazole may partially increase the accommodative amplitude. {01}


Other actions/effects:

Dapiprazole does not significantly alter intraocular pressure in normotensive eyes or in eyes with elevated intraocular pressure. {01}

Dapiprazole does not have any significant effect on ciliary muscle contraction, and therefore does not induce a significant change in the anterior chamber depth or in the thickness of the lens. {01}

Onset of action:

Eye color affects the rate of pupillary constriction. {01} In individuals with brown irides, the rate of pupillary constriction may be slightly slower than in individuals with blue or green irides. {01} Eye color does not appear to affect the final pupil size. {01}


Precautions to Consider

Carcinogenicity

Dapiprazole has been shown to significantly increase the incidence of liver tumors in rats after continuous dietary administration for 104 weeks. This effect was found only in male rats treated with the highest dose administered in the study, i.e., 300 mg per kg of body weight (mg/kg) per day (80,000 times the human dose). The effect was not observed in male and female rats at doses of 30 and 100 mg/kg per day or in female rats at doses of 300 mg/kg per day. {01}

Mutagenicity

Dapiprazole has not been shown to be mutagenic. {01}

Pregnancy/Reproduction
Fertility—
Studies have not shown that dapiprazole impairs fertility. {01}

Pregnancy—
Adequate and well-controlled studies have not been done in pregnant women. {01}

Reproduction studies have been performed in rats and rabbits at doses up to 128,000 and 27,000 times the human ophthalmic dose, respectively, and have revealed no evidence of harm to the fetus due to dapiprazole. {01}

FDA Pregnancy Category B. {01}

Breast-feeding

It is not known whether dapiprazole is distributed into human milk. {01} However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of dapiprazole have not been performed in the pediatric population. Safety and efficacy have not been established. {01}


Geriatrics


Appropriate studies on the relationship of age to the effects of dapiprazole have not been performed in the geriatric population. However, geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected. {12}

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Iritis, acute, or other conditions where miosis{12} is undesirable{01}
Risk-benefit should be considered when the following medical problem exists
Sensitivity to dapiprazole{01}


Side/Adverse Effects

Note: Miosis produced by dapiprazole may cause difficulty in dark adaptation, may reduce the field of vision, {01} or may reduce central visual acuity. {12}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Edema of cornea{01}{12} (swelling of the clear part of the eye)—incidence 10 to 40%
    
punctate keratitis{01}{12} (severe irritation of the clear part of the eye)—incidence 10 to 40%



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Burning of eye upon administration of medication{01} —incidence 50%
    
conjunctival injection, usually lasting 20 minutes{01}{12} (redness of the white part of the eye)—incidence 80%

Incidence less frequent
    
Blurring of vision{01} —incidence <10%
    
browache{01} —incidence 10 to 40%
    
chemosis{01}{12} (swelling of the membrane covering the white part of the eye)—incidence 10 to 40%
    
dryness of eye{01} —incidence <10%
    
edema of eyelid{01} (swelling of eyelid)—incidence 10 to 40%
    
erythema of eyelid{01} (redness of eyelid)—incidence 10 to 40%
    
headache{01} —incidence 10 to 40%
    
itching of eye{01} —incidence 10 to 40%
    
photophobia{01} (increased sensitivity of eye to light)—incidence 10 to 40%
    
ptosis{01} (drooping of upper eyelid)—incidence 10 to 40%
    
tearing of eye{01} —incidence <10%





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Dapiprazole (Ophthalmic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Other medical problems, especially acute iritis or other conditions where miosis {12} is undesirable

Proper use of this medication

» Proper dosing

Precautions while using this medication
» Medication causes blurred vision or other vision problems; not driving, using machines, or doing anything else that could be dangerous if unable to see well

Possible eye photosensitivity; wearing sunglasses that block ultra-violet light


Side/adverse effects
Signs of potential side effects, especially edema of cornea and punctate keratitis


Ophthalmic Dosage Forms

DAPIPRAZOLE HYDROCHLORIDE FOR OPHTHALMIC SOLUTION

Usual adult dose
Antimydriatic
Topical, to the conjunctiva, 1 drop, followed by another 1 drop after five minutes; administration to start immediately following the retinal examination, to reverse the diagnostic mydriasis. {01} {12}


Usual adult prescribing limits
Dapiprazole should not be used more frequently than once a week. {01}

Usual pediatric dose
Safety and efficacy have not been established. {01}

Strength(s) usually available
U.S.—


0.5% (5 mg of dapiprazole HCl per mL when reconstituted) (Rx) [Rev-Eyes{01} (hydroxypropyl methylcellulose 0.4%) (benzalkonium chloride 0.01%) (mannitol 2%) (sodium chloride) (edetate sodium 0.01%) (sodium phosphate dibasic) (sodium phosphate monobasic) (water for injection)]

Canada—


0.5% (5 mg of dapiprazole HCl per mL when reconstituted) (Rx) [Rev-Eyes{14}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
Dapiprazole is supplied in a kit consisting of one vial of dapiprazole hydrochloride (25 mg), one vial of diluent (5 mL), and one dropper for dispensing. {01}

To prepare the solution, pour diluent into medication vial, attach dropper assembly to vial, and shake vial for several minutes to dissolve powder. {01}

Stability:
Once the eyedrops have been reconstituted they may be stored at room temperature (15 to 30 °C [59 to 86 °F]) for 21 days. {01} The solution should be discarded if it is not clear and colorless. {01}

Auxiliary labeling:
   • For the eye. {01}



Revised: 08/16/1993



References
  1. PI (US)—Rev-Eyes, Storz: Rev 1/91, Rec 7/91.
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  1. Manufacturer's drug monographs for: Dapiprazole Hydrochloride - drug substance and Dapiprazole Hydrochloride for Ophthalmic Solution dosage form.
  1. Nyman N, Keates EU. Effects of dapiprazole on the reversal of pharmacologically induced mydriasis. Optom Vis Sci 1990 Sep; 67(9): 705-9.
  1. Allinson RW et al. Reversal of mydriasis by dapiprazole. Ann Ophthalmol 1990 Apr; 22(4): 131-3, 138.
  1. Prosdocimo G, DeMarco D. Intraocular dapiprazole to reverse mydriasis during extracapsular cataract extraction. Am J Ophthalmol 1988 Mar 15; 105(3): 321-2.
  1. Open.
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  1. Panel comments: sent 11/8, due 11/29, processed 12/5/91.
  1. Panel Ballot Comments: sent 1/8/92, due 1/29/92, processed 2/7/92.
  1. Rev-Eyes package insert (Storz—Canada), CPS 1993: 1043.
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