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ASCRS NEWS PI 14 continued from page 12 BRIEF SUMMARY: Please see the DEXTENZA Package Insert for full prescribing information for DEXTENZA (11/2018) 1 INDICATIONS AND USAGE DEXTENZA ® (dexamethasone ophthalmic insert) is a corticosteroid indicated for the treatment of ocular pain following ophthalmic surgery (1). 4 CONTRAINDICATIONS DEXTENZA is contraindicated in patients with active corneal, conjunctival or canalicular infections, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella; mycobacterial infections; fungal diseases of the eye, and dacryocystitis. 5 WARNINGS AND PRECAUTIONS 5.1 Intraocular Pressure Increase Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be monitored during the course of the treatment. 5.2 Bacterial Infection Corticosteroids may suppress the host response and thus increase the hazard for secondary ocular infections. In acute purulent conditions, steroids may mask infection and enhance existing infection [see Contraindications (4)]. 5.3 Viral Infections Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex) [see Contraindications (4)]. 5.4 Fungal Infections Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal culture should be taken when appropriate [see Contraindications (4)]. 5.5 Delayed Healing The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: • Intraocular Pressure Increase [see Warnings and Precautions (5.1)] • Bacterial Infection [see Warnings and Precautions (5.2)] • Viral Infection [see Warnings and Precautions (5.3)] • Fungal Infection [see Warnings and Precautions (5.4)] • Delayed Healing [see Warnings and Precautions (5.5)] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation; delayed wound healing; secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera [see Warnings and Precautions (5)]. DEXTENZA was studied in three randomized, vehicle-controlled studies (n = 351). The mean age of the population was 68 years (range 43 to 87 years), 62% were female, and 85% were white. Forty-six percent had brown iris color and 31% had blue iris color. The most common ocular adverse reactions that occurred in patients treated with DEXTENZA were: anterior chamber inflammation including iritis and iridocyclitis (9%); intraocular pressure increased (5%); visual acuity reduced (2%); eye pain (1%); cystoid macular edema (1%); corneal edema (1%); and conjunctival hyperemia (1%). The most common non-ocular adverse reaction that occurred in patients treated with DEXTENZA was headache (1%). 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate or well-controlled studies with DEXTENZA in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, administration of topical ocular dexamethasone to pregnant mice and rabbits during organogenesis produced embryofetal lethality, cleft palate and multiple visceral malformations [see Animal Data]. Data Animal Data Topical ocular administration of 0.15% dexamethasone (0.75 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in a mouse study. A daily dose of 0.75 mg/kg/day in the mouse is approximately 5 times the entire dose of dexamethasone in the DEXTENZA product, on a mg/m 2 basis. In a rabbit study, topical ocular administration of 0.1% dexamethasone throughout organogenesis (0.36 mg /day, on gestational day 6 followed by 0.24 mg/day on gestational days 7-18) produced intestinal anomalies, intestinal aplasia, gastroschisis and hypoplastic kidneys. A daily dose of 0.24 mg/day is approximately 6 times the entire dose of dexamethasone in the DEXTENZA product, on a mg/m 2 basis. 8.2 Lactation Systemically administered corticosteroids appear in human milk and could suppress growth and interfere with endogenous corticosteroid production; however the systemic concentration of dexamethasone following administration of DEXTENZA is low [see Clinical Pharmacology (12.3)]. There is no information regarding the presence of DEXTENZA in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production to inform risk of DEXTENZA to an infant during lactation. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DEXTENZA and any potential adverse effects on the breastfed child from DEXTENZA. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients. 17 PATIENT COUNSELING INFORMATION Advise patients to consult their surgeon if pain, redness, or itching develops. MANUFACTURED FOR: Ocular Therapeutix, Inc. Bedford, MA 01730 USA PP-US-DX-0072 at the podium when it came to defending their positions. Dr. Ahmed led his argument with a case. A 52-year-old female with mild to moderate glaucoma was showing signs of progression despite "normal" IOPs in office visits. She was on prostaglandins and was compliant. This patient underwent the water drinking test and used Icare Home (Icare USA) tonometry. These tests showed significantly elevated peak IOP and fluctuations. "This changed our mind that we need to do something for this patient, and it explained progression when she had normal pressure in the office," Dr. Ahmed said He went on to highlight several studies that he said pro- vide strong evidence that peak and fluctuation are very important for progression, though he noted other long-term studies suggest the opposite. Taking to the podium, Dr. Rhee said that while it's alluring to believe diurnal IOP is important, it's really mean IOP that affects progression. Dr. Ahmed, Dr. Rhee accused, mixed and matched terms in his presentation. Diurnal IOP variability is different than intervisit variations, the latter of which can result from patient in- compliance, procedures, and other factors. Some of the studies men- tioned by Dr. Ahmed, Dr. Rhee said, deal with intervisit variability. Circadian variations of IOP is normal, Dr. Rhee said, yet only 2 to 5% of people have glaucoma. Just forced blinking, he noted, can cause a pressure of 20 to 60 mm Hg, but that doesn't seem to cause damage. Studies have shown that when you have higher pressure you have more IOP variability, but the percentage of variability is similar. High variability is just a marker for higher mean IOP, Dr. Rhee said. In the literature, Dr. Rhee said there are only four papers that measure true circadian IOP; the others study intervisit variabil- ity. If you look at the circadian rhythm IOP studies, do they show a correlation between fluctuation and progression? "Maybe," Dr. Rhee said, also noting a body of literature against IOP fluctuation being correlated with disease pro- gression. "It's really the mean IOPs that ended up being important," Dr. Rhee said. He also said that if IOP fluctuations were really influencing progression, wouldn't trabeculec- tomy be curative? Trab, he said, virtually eliminates fluctuation, and yet it's certainly not a cure. "It's the level of IOP that's the problem," he said. "Too high is too high." Editors' note: Drs. Ahmed and Rhee have financial interests with various ophthalmic companies. Dr. Ahmed takes on the position supporting 24-hour IOP monitoring.

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