Acoltremon

Risk Summary

There are no adequate and well-controlled studies on acoltremon in pregnant women. Systemic exposure to acoltremon from ocular administration is negligible. 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/m² basis.

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.

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.

Carcinogenicity

Long term studies in animals have not been performed to evaluate the carcinogenic potential of acoltremon.

Mutagenicity

Acoltremon was not mutagenic or clastogenic in the standard battery of genotoxicity tests including a bacterial reverse mutation assay, an in vitro chromosomal aberration assay in human peripheral lymphocytes and micronucleus assay in rats.

Impairment of Fertility

Studies to evaluate the potential effects of acoltremon on male or female fertility in animals have not been performed.

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 acoltremon 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 acoltremon was instillation site pain (50%). Less than 1% of patients discontinued therapy due to burning or stinging sensation in the eyes.