Rotarac

Rotarac (bromfenac ophthalmic solution) 0.09% is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery.

Xibrom (bromfenac ophthalmic solution) 0.09% is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery.

Recommended Dosing

One drop of Rotarac ophthalmic solution should be applied to the affected eye two times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period.

Use With Other Topical Ophthalmic Medications

Rotarac ophthalmic solution may be administered in conjunction with other topical ophthalmic medications such as alpha-agonists, beta-blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 minutes apart.

Recommended Dosing

One drop of Xibrom ophthalmic solution should be applied to the affected eye two times daily beginning 24 hours after cataract surgery and continuing through the first 2 weeks of the postoperative period.

Use With Other Topical Ophthalmic Medications

Xibrom ophthalmic solution may be administered in conjunction with other topical ophthalmic medications such as alpha-agonists, beta-blockers, carbonic anhydrase inhibitors, cycloplegics, and mydriatics. Drops should be administered at least 5 minutes apart.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Sulfite Allergic Reactions

Contains sodium sulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Slow Or Delayed Healing

All topical nonsteroidal anti-inflammatory drugs (NSAIDs) may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.

Potential For Cross-Sensitivity

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.

Increased Bleeding Time

With some NSAIDs, there exists the potential for increased bleeding time due to interference with platelet aggregation. There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.

It is recommended that Rotarac ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

Keratitis And Corneal Reactions

Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients.

Post-marketing experience with topical NSAIDs also suggests that use more than 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events.

Contact Lens Wear

Rotarac should not be administered while wearing contact lenses. Remove contact lenses prior to instillation of Rotarac. The preservative in Rotarac, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of Rotarac.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and 5 mg/kg/day (340 times the predicted human systemic exposure), respectively revealed no significant increases in tumor incidence. Bromfenac did not show mutagenic potential in various mutagenicity studies, including the reverse mutation, chromosomal aberration, and micronucleus tests.

Bromfenac did not impair fertility when administered orally to male and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (systemic exposure 90 and 30 times the predicted human exposure, respectively).

Use In Specific Populations

Pregnancy - Pregnancy Category C

Risk Summary

There are no adequate and well-controlled studies with Rotarac in pregnant women. No malformations were observed in reproduction studies in rats and rabbits with oral doses of bromfenac at exposures up to 150 times (rats) and 90 times (rabbits) the predicted human systemic exposure; however, both embryolethality and maternal toxicity were observed at the highest dose exposures. The systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans, following ocular administration. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations

Premature closure of the ductus arteriosus in the fetus has occurred with third trimester use of oral and injectable NSAIDs. Measurable maternal and fetal plasma drug levels are available with oral and injectable routes of NSAID administration. The maternal plasma level of Rotarac following ocular administration is unknown.

Animal Data

Reproduction studies performed in rats at oral doses of bromfenac up to 0.9 mg/kg/day (systemic exposure 90 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and rabbits at oral doses up to 7.5 mg/kg/day (150 times the predicted human systemic exposure) produced no drug-related malformations in reproduction studies. However, embryo-fetal lethality and maternal toxicity were produced in rats and rabbits at 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted human exposure), and caused dystocia, increased neonatal mortality and reduced postnatal growth at 0.9 mg/kg/day.

Nursing Mothers

It is not known if Rotarac is present in human milk. The systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans, following ocular administration. Based on the low level of systemic exposure, it is unlikely that Rotarac would be detected in human milk using available assays. Caution should be exercised when Rotarac ophthalmic solution is administered to a nursing woman.

Pediatric Use

Safety and efficacy in pediatric patients below the age of 18 have not been established.

Geriatric Use

There is no evidence that the efficacy or safety profiles for Rotarac differ in patients 65 years of age and older compared to younger adult patients.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Sulfite Allergic Reactions

Contains sodium sulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Slow Or Delayed Healing

All topical nonsteroidal anti-inflammatory drugs (NSAIDs) may slow or delay healing. Topical corticosteroids are also known to slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.

Potential For Cross-Sensitivity

There is the potential for cross-sensitivity to acetylsalicylic acid, phenylacetic acid derivatives, and other NSAIDs. Therefore, caution should be used when treating individuals who have previously exhibited sensitivities to these drugs.

Increased Bleeding Time

With some NSAIDs, there exists the potential for increased bleeding time due to interference with platelet aggregation. There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular surgery.

It is recommended that Xibrom ophthalmic solution be used with caution in patients with known bleeding tendencies or who are receiving other medications which may prolong bleeding time.

Keratitis And Corneal Reactions

Use of topical NSAIDs may result in keratitis. In some susceptible patients, continued use of topical NSAIDs may result in epithelial breakdown, corneal thinning, corneal erosion, corneal ulceration or corneal perforation. These events may be sight threatening. Patients with evidence of corneal epithelial breakdown should immediately discontinue use of topical NSAIDs and should be closely monitored for corneal health.

Post-marketing experience with topical NSAIDs suggests that patients with complicated ocular surgeries, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events which may become sight threatening. Topical NSAIDs should be used with caution in these patients.

Post-marketing experience with topical NSAIDs also suggests that use more than 24 hours prior to surgery or use beyond 14 days post surgery may increase patient risk for the occurrence and severity of corneal adverse events.

Contact Lens Wear

Xibrom should not be administered while wearing contact lenses. Remove contact lenses prior to instillation of Xibrom. The preservative in Xibrom, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of Xibrom.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and 5 mg/kg/day (340 times the predicted human systemic exposure), respectively revealed no significant increases in tumor incidence. Bromfenac did not show mutagenic potential in various mutagenicity studies, including the reverse mutation, chromosomal aberration, and micronucleus tests.

Bromfenac did not impair fertility when administered orally to male and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (systemic exposure 90 and 30 times the predicted human exposure, respectively).

Use In Specific Populations

Pregnancy - Pregnancy Category C

Risk Summary

There are no adequate and well-controlled studies with Xibrom in pregnant women. No malformations were observed in reproduction studies in rats and rabbits with oral doses of bromfenac at exposures up to 150 times (rats) and 90 times (rabbits) the predicted human systemic exposure; however, both embryolethality and maternal toxicity were observed at the highest dose exposures. The systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans, following ocular administration. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Clinical Considerations

Premature closure of the ductus arteriosus in the fetus has occurred with third trimester use of oral and injectable NSAIDs. Measurable maternal and fetal plasma drug levels are available with oral and injectable routes of NSAID administration. The maternal plasma level of Xibrom following ocular administration is unknown.

Animal Data

Reproduction studies performed in rats at oral doses of bromfenac up to 0.9 mg/kg/day (systemic exposure 90 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and rabbits at oral doses up to 7.5 mg/kg/day (150 times the predicted human systemic exposure) produced no drug-related malformations in reproduction studies. However, embryo-fetal lethality and maternal toxicity were produced in rats and rabbits at 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. In rats, bromfenac treatment caused delayed parturition at 0.3 mg/kg/day (30 times the predicted human exposure), and caused dystocia, increased neonatal mortality and reduced postnatal growth at 0.9 mg/kg/day.

Nursing Mothers

It is not known if Xibrom is present in human milk. The systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans, following ocular administration. Based on the low level of systemic exposure, it is unlikely that Xibrom would be detected in human milk using available assays. Caution should be exercised when Xibrom ophthalmic solution is administered to a nursing woman.

Pediatric Use

Safety and efficacy in pediatric patients below the age of 18 have not been established.

Geriatric Use

There is no evidence that the efficacy or safety profiles for Xibrom differ in patients 65 years of age and older compared to younger adult patients.

The plasma concentration of bromfenac following ocular administration of 0.09% Rotarac (bromfenac ophthalmic solution) in humans is unknown. Based on the maximum proposed dose of one drop to the eye (0.09 mg) twice a day and PK information from other routes of administration, the systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans.

The plasma concentration of bromfenac following ocular administration of 0.09% Xibrom (bromfenac ophthalmic solution) in humans is unknown. Based on the maximum proposed dose of one drop to the eye (0.09 mg) twice a day and PK information from other routes of administration, the systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans.