Acoltremon

TRYPTYR is indicated for the treatment of the signs and symptoms of dry eye disease. TRYPTYR is a TRPM8 thermoreceptor agonist indicated for the treatment of the signs and symptoms of dry eye disease. ( 1 )

TRYPTYR is a clear to slightly opalescent, colorless ophthalmic solution containing 0.003% acoltremon in a single-dose vial. Ophthalmic solution: 0.003% acoltremon in a single-dose vial. ( 3 )

None. None. ( 4 )

To avoid the potential for eye injury and contamination, do not touch the vial tip to the eye or other surfaces. ( 5.1 )

5.1 Potential for Eye Injury and Contamination To avoid the potential for eye injury and contamination, do not touch the vial tip to the eye or other surfaces.

5.2 Use with Contact Lenses TRYPTYR should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of TRYPTYR.

The most common adverse reaction was instillation site pain (50%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories, Inc. at 1-800-757-9780, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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. In patients with dry eye disease, 766 patients received at least one dose of TRYPTYR in four randomized controlled clinical trials across 71 sites in the United States. The most common ocular adverse reaction observed in controlled clinical studies with TRYPTYR was instillation site pain (50%). Less than 1% of patients discontinued therapy due to burning or stinging sensation in the eyes.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies on TRYPTYR in pregnant women. Systemic exposure to acoltremon from ocular administration is negligible [see Clinical Pharmacology ( 12.3 )] . Intravenous administration of acoltremon to pregnant rats and rabbits during organogenesis did not produce embryofetal toxicity at 806- and 2151-fold the maximum recommended human ocular dose (MRHOD) of acoltremon on a mg/m 2 basis ( see Data ) . All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. Data Animal Data In embryofetal developmental studies in pregnant rats and rabbits dosed by intravenous injection daily during organogenesis from gestation days 6-17 and gestation days 7-19, respectively, no maternal or fetal toxicity was observed at 806- and 2151-fold the MRHOD of acoltremon on a mg/m 2 basis.

8.2 Lactation Risk Summary There are no data on the presence of acoltremon in human milk, the effects on the breastfed infant, or the effects on milk production. However, systemic exposure to acoltremon following topical ocular administration is low. The lack of clinical data during lactation precludes a clear determination of the risk of TRYPTYR to an infant during lactation; however, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TRYPTYR.

8.4 Pediatric Use The safety and effectiveness of TRYPTYR have not been established in pediatric patients.

8.5 Geriatric Use No clinically relevant differences in safety have been observed between elderly and younger patients.

Studies in animals suggest that acoltremon, the active substance in TRYPTYR, is an agonist of transient receptor potential melastatin 8 (TRPM8) thermoreceptors. TRPM8 thermoreceptor stimulation has been shown to activate trigeminal nerve signaling leading to increased basal tear production. The exact mechanism of action for TRYPTYR in dry eye disease is unknown.