Alcoltremon (TRYPTYR)

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Article initiated by:

Inês Coelho da Costa, M.D

All contributors:

Mário Lima Fontes, Inês Coelho da Costa, M.D

Assigned editor:

Review:

Assigned status Update Pending

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Medical Therapy

Description

TRYPTYR® (acoltremon ophthalmic solution) 0.003% is a prescription eye drop developed and marketed by Alcon® approved by the FDA in May 2025 for the treatment of dry eye disease (DED). It is the first-in-class TRPM8 receptor agonist, developed to stimulate basal tear production via cold-sensitive corneal receptors. It represents a novel neurosensory approach to DED, distinct from known anti-inflammatory therapies.

In pivotal trials (COMET‑2 and COMET‑3), 42.6% and 53.2% of patients, respectively, achieved ≥10 mm increase in Schirmer score at Day 14, versus 8.2% and 14.4% in vehicle arms (p < 0.0001). These effects were sustained through at least Day 90.

Patient Selection

Indications

Indicated for the treatment of the signs and symptoms of dry eye disease. In pivotal trials (COMET-2 and COMET-3), patients showed significant improvements in Schirmer test scores and subjective symptom relief.

Contraindications

No contraindications have been identified to date.

Clinical Pharmacology

Acoltremon is a potent and selective agonist of the Transient Receptor Potential Melastatin 8 (TRPM8) ion channel, a cold-sensitive, non-selective cation channel highly expressed on corneal sensory neurons, including C-fibers and Aδ-fibers. These channels are typically activated by cooling temperatures, evaporative stimuli, and compounds such as menthol and icilin. Upon activation by acoltremon, TRPM8 channels open to allow sodium and calcium ion influx, depolarizing the neuron and generating action potentials. These signals are transmitted via the ophthalmic branch of the trigeminal nerve to central nervous system pathways that regulate lacrimal gland activity. The result is a reflex increase in basal tear production, independent of inflammatory cascades.

This neurosensory mechanism distinguishes acoltremon from traditional treatments for dry eye disease (DED), such as cyclosporine and lifitegrast, which act primarily by suppressing ocular surface inflammation. By targeting the afferent limb of the lacrimal functional unit, acoltremon exerts a rapid effect, with clinical studies showing measurable increases in tear production as early as Day 1. However, the exact mechanism by which TRYPTYR exerts its therapeutic effect in DED remains unknown, as noted in the FDA-approved prescribing information.

Warnings/Precautions

General

• Avoid contact between the dropper tip and any surface, including the eye.

• Contact lenses should be removed before instillation and can be reinserted after 15 minutes

Drug Interactions

No known drug interactions. Can be used with other topical eye medications if spaced appropriately.

Carcinogenesis/Mutagenesis/Impairment of Fertility

In animal studies, acoltremon showed no evidence of carcinogenicity, mutagenicity, or impaired fertility, even at doses far exceeding human exposure.

Pregnancy

There are no adequate studies in pregnant women. Animal studies showed no teratogenic effects. The systemic absorption in humans is negligible, so fetal exposure is expected to be minimal.

Nursing Mothers

It is unknown whether acoltremon is excreted in human milk. The potential benefit for the mother should be weighed against any possible risk to the infant.

Pediatric Use

Safety and efficacy have not been established in pediatric populations.

Adverse Reactions

The most common adverse reaction is burning or stinging at the instillation site, reported in approximately 50% of patients. Less than 1% of patients discontinued the drug due to discomfort.

Overdosage

No cases of overdose have been reported. Due to the negligible systemic absorption, the risk of systemic toxicity is low. In case of overdose, monitor for ocular irritation and manage supportively.

Dosage and Administration

Instill one drop in each eye twice daily, approximately 12 hours apart. Use only the contents of a single-use vial immediately after opening; discard after use.

How Supplied

• Supplied as sterile, preservative-free, single-use LDPE vials, each containing 0.4 mL.
• Packaged in foil pouches of 5 vials; boxes contain 60 vials (12 pouches).
• Store refrigerated (2–8 °C). Once opened, the outer carton may be kept at room temperature (up to 25 °C) for up to 30 days.

• Once a pouch is opened, use the vials within 7 days.

Patient’s Instructions for Use

• Wash hands before use.
• Do not touch the dropper tip.
• Tilt head back, instill one drop in the lower conjunctival sac, and close the eye gently.
• Discard the vial after one use.
• Wait at least 5 minutes between multiple eye drops.

• Reinsert contact lenses after 15 minutes.