Dofnac

  
     
 

DESCRIPTION

Dofnac (diclofenac sodium) is a sterile topical, nonsteroidal, anti-inflammatory product for ophthalmic use containing diclofenac sodium 0.1%, and Boric acid, disodium edetate (1 mg/mL), polyoxyl 35 castor oil, purified water, sorbic acid (2 mg/mL), and tromethamine. Diclofenac sodium is 2-((2,6-di-chlorophenyl)amino) benzeneacetic acid, monosodium salt. Its empirical formula is C14H10Cl2NO2Na. Its molecular weight is 318.14. Diclofenac sodium is a faintly yellow-white to light-beige, slightly hygroscopic crystalline powder. It is freely soluble in methanol, sparingly soluble in water, very slightly soluble in acetonitrile, and insoluble in chloroform and in 0.1N hydrochloric acid.

Dofnac is an iso-osmotic physiologically compatible solution with an osmolality of about 300 mOsmol/1000g, buffered at approximately pH 7.2. Dofnac solution has a faint characteristic odor of castor oil.

 

ACTIONS/CLINICAL PHARMACOLOGY
* Diclofenac sodium is one of a series of phenylacetic acids that have demonstrated anti-
inflammatory and analgesic properties in pharmacological studies. It is thought to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure. Prostaglandins also appear to play a role in the miotic response produced during ocular surgery by constricting the iris sphincter independently of cholinergic mechanisms. In clinical studies, Voltaren Ophthalmic has been shown to decrease the signs and symptoms of inflammation resulting from cataract surgery.

* Results from clinical studies indicate that Dofnac has no significant effect upon intraocular pressure; however, elevations in intraocular pressure may occur following cataract surgery.

* Results from a bioavailability study established that plasma levels of diclofenac following ocular instillation of two drops of Dofnac to each eye were below the limit of quantitation (10 ng/mL) over a 4-hour period. This study suggests that limited, if any, systemic absorption occurs with Dofnac.

* Efficacy studies of postoperative inflammation, favored Dofnac for the clinical assessments of inflammation (anterior chamber cells and flare, conjunctival erythema and ciliary flush). Patients safely continued on Dofnac for a period of up to 6 weeks.

* In comparative studies the effects of Dofnac and prednisolone sodium phosphate 1% on the blood-aqueous humor barrier were examined by anterior chamber fluorophotometry at 1 week postsurgery. Dofnac was found statistically more effective than prednisolone in expediting reestablishment of the blood-aqueous humor barrier disrupted by cataract extraction. However, the clinical benefit or harm in the reestablishment of the blood-aqueous barrier is unknown. The efficacy of Dofnac given before and shortly after surgery for photophobia is favored.

* Dofnac has been safely administered in conjunction with other ophthalmic medications such as antibiotics, beta blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics.
 

INDICATIONS AND USAGE
Dofnac is indicated for the treatment of postoperative inflammation in patients who have undergone cataract extraction and for the treatment of photophobia in patients undergoing incisional refractive surgery.
 

CONTRAINDICATIONS
Dofnac is contraindicated in patients concurrently wearing soft contact lenses and in patients who are hypersensitive to any component of the medication. Patients wearing hydrogel soft contact lenses who have used Dofnac concurrently have experienced ocular irritation manifested by redness and burning.
 

WARNINGS
There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti- inflammatory agents. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs. With some nonsteroidal anti-inflammatory drugs, there exists the potential for increased bleeding time due to interference with thrombocyte aggregation. There have been reports that ocularly applied nonsteroidal anti-inflammatory drugs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.
 

PRECAUTIONS

General

It is recommended that Dofnac be used with caution in surgical patients with known bleeding tendencies or who are receiving other medications that may prolong bleeding time.

Dofnac may slow or delay healing.

Carcinogenesis, mutagenesis, impairment of fertility Long-term carcinogenicity studies in rats given oral diclofenac sodium up to 2 mg/kg/day (approximately the human oral dose) revealed no significant increases in tumor incidence.

There was a slight increase in benign rat mammary fibroadenomas in mid-dose females (high-dose females had excessive mortality) but the increase was not significant for this common rat tumor. A 2-year carcinogenicity study conducted in mice employing oral diclofenac sodium up to 2 mg/kg/day did not reveal any oncogenic potential. Diclofenac sodium did not show mutagenic potential in various mutagenicity studies including the Ames test. Diclofenac sodium administered to male and female rats at 4 mg/kg/day did not affect fertility.

Pregnancy, T teratogenic effects

Pregnancy Category B: Reproduction studies performed in mice at oral doses up to 5000 times (20 mg/kg/day) and in rats and rabbits at oral doses up to 2500 times (10 mg/kg/day) the human topical dose have revealed no evidence of teratogenicity due to diclofenac sodium, despite the induction of maternal toxicity and fetal toxicity. In rats, maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival.
Diclofenac sodium has been shown to cross the placental barrier in mice and rats.
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.

Non-teratogenic effects

Because of the known effects of prostaglandin-inhibiting drugs on the fetal cardiovascular system (closure of the ductus arteriosus), the use of Dofnac during late pregnancy should be avoided.

Pediatric use

Safety and effectiveness in pediatric patients have not been established.
 

ADVERSE REACTIONS

* Transient burning and stinging were reported in approximately 15% of patients across all studies with the use of Dofnac. In ocular surgery studies, keratitis has been reported in up to 28% of patients receiving Dofnac, although in many of these cases keratitis was initially noted prior to the initiation of treatment. Elevated intraocular pressure following cataract surgery has been reported in approximately 15% of patients undergoing cataract surgery. Dry eye complaints have been reported in approximately 12% of case studies undergoing incisional refractive surgery.

* The following adverse reactions were reported in less than 3% of the patients; discharge, corneal deposits, corneal lesions, ocular allergy, itching, irritation, and blurred vision. The following adverse reactions were reported in less than 1% of the patients; corneal edema, corneal opacity, eyelid disorder, iritis, injection, and lacrimation disorder.

* Overdosage will not ordinarily cause acute problems. If accidentally ingested, fluids should be taken to dilute the medication.
 

DOSAGE AND ADMINISTRATION
Cataract surgery
One drop of Dofnac should be applied to the affected eye four times daily beginning 24 hours after cataract surgery and continuing throughout the first 2 weeks of the postoperative period.

Incisional refractive surgery