Acoltremon
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anum Ijaz M.B.B.S., M.D.[2]
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
Overview
Acoltremon is a TRPM8 thermoreceptor agonist that is FDA approved for the treatment of the signs and symptoms of dry eye disease. Common adverse reactions include instillation site pain (50%).
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
FDA-labeled Indications
- TRYPTYR is indicated for the treatment of the signs and symptoms of dry eye disease.
Recommended Dosage
- Instill one drop in each eye twice daily (approximately 12 hours apart).
Dosage Forrms and Strengths
TRYPTYR is a clear to slightly opalescent, colorless ophthalmic solution containing 0.003% acoltremon in a single-dose vial.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Acoltremon in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Acoltremon in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Acoltremon FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Acoltremon in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Acoltremon in pediatric patients.
Contraindications
None.
Warnings
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.
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.
Adverse Reactions
Clinical Trials Experience
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.
Postmarketing Experience
There is limited information regarding Acoltremon Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Acoltremon Drug Interactions in the drug label.
Use in Specific Populations
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.
- 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 (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/m2 basis.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Acoltremon in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Acoltremon during labor and delivery.
Nursing Mothers
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.
Pediatric Use
The safety and effectiveness of TRYPTYR have not been established in pediatric patients.
Geriatic Use
No clinically relevant differences in safety have been observed between elderly and younger patients.
Gender
There is no FDA guidance on the use of Acoltremon with respect to specific gender populations.
Race
There is no FDA guidance on the use of Acoltremon with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Acoltremon in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Acoltremon in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Acoltremon in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Acoltremon in patients who are immunocompromised.
Administration and Monitoring
Administration
- Wash hands before use.
- The single-dose vials are to be used immediately after opening and can be used to dose both eyes. Discard the single-dose vial, including any remaining contents, immediately after use.
- TRYPTYR can be used concomitantly with other topical ophthalmic eye drops. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.
- Contact lenses should be removed prior to the administration of TRYPTYR and may be reinserted 15 minutes following administration.
- If one dose is missed, treatment should continue with the next dose.
Monitoring
There is limited information regarding Acoltremon Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Acoltremon and IV administrations.
Overdosage
There is limited information regarding Acoltremon overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Acoltremon Pharmacology in the drug label.
Mechanism of Action
- 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.
Structure
TRYPTYR (acoltremon ophthalmic solution) 0.003% contains an agonist of TRPM8 ion channels. Acoltremon’s chemical name is (1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide. The molecular formula of acoltremon is C18H27NO2 and has a molecular weight of 289.42 g/mol.
Add structure image
Pharmacodynamics
There is limited information regarding Acoltremon Pharmacodynamics in the drug label.
Pharmacokinetics
- PK was assessed in 25 patients with dry eye disease receiving TRYPTYR administration (1 drop twice daily) on Days 1, 14, and 90.
- A total of three (3) (12.0%) had plasma concentrations above 20 pg/mL (the lower limit of quantification), with the highest plasma concentration of 213 pg/mL.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
- 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 Studies
- The efficacy of TRYPTYR for the treatment of dry eye disease was supported by two randomized, multi-center, double-masked, vehicle-controlled studies (COMET-2 [NCT-05285644] and COMET-3 [NCT-05360966]) enrolling a total of 931 dry eye patients (462 of which received TRYPTYR).
- Patients were randomized to TRYPTYR or vehicle (placebo) in a 1:1 ratio and dosed twice a day for 90 days. Use of artificial tears was not allowed during the studies. The mean age was 61 years (range, 30-93 years). The majority of patients were female (74.8%).
- Enrollment criteria included signs (i.e., corneal fluorescein staining score [2-15] and anesthetized Schirmer tear test [2-9 mm]) and symptoms (i.e., SANDE Score [≥ 50] and Ocular Discomfort Score [≥ 50]) of dry eye disease.
Efficacy
- Tear film production was measured by unanesthetized Schirmer tear test assessed using a Schirmer strip (0 - 35 mm).
- The average baseline unanesthetized Schirmer scores for TRYPTYR and Vehicle treated patients was 6.2 mm and 5.9 mm in the COMET-2 study, and 6.8 mm and 6.4 mm in the COMET-3 study, respectively. Of the patients treated at Day 14 (primary endpoint) with TRYPTYR, 42.6% achieved ≥ 10 mm increase in Schirmer score from baseline in the COMET-2 study and 53.2% achieved ≥ 10 mm increase in Schirmer score from baseline at Day 14 in the COMET-3 study, compared to 8.2% and 14.4% of vehicle-treated patients in the COMET-2 study and the COMET-3 study, respectively.
- A statistically significant improvement in tear production favoring TRYPTYR (p<0.01) was observed in both studies
How Supplied
- TRYPTYR (acoltremon ophthalmic solution) 0.003% is supplied as a sterile, clear to slightly opalescent, and colorless solution in a low-density polyethylene (LDPE), single-dose vial with a 0.4 mL fill.
- One strip of 5 single-dose vials is packaged in a foil pouch with twelve (12) pouches in a carton.
NDC 0065-8595-02; Carton of 60 Single-Dose Vials.
Storage
- Store refrigerated at 2°C to 8°C (36°F to 46°F). After opening the carton, TRYPTYR may be stored refrigerated or at room temperature at 2°C to 25°C (36°F to 77°F).
- If stored at room temperature, TRYPTYR should be used within 30 days, not to exceed the expiration date printed on the carton and foil pouch.
- After opening each foil pouch, the single-dose vials should be used within 7 days, not to exceed the expiration date printed on the vial.
- Store unopened single-dose vials in the original foil pouch until ready to use.
Images
Drug Images
{{#ask: Page Name::Acoltremon |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
Add Display Panel {{#ask: Label Page::Acoltremon |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
- Advise patients to read the FDA-approved patient labeling (Instructions for Use).
- Potential for Eye Injury and Contamination
Advise patients not to touch the tip of the single-dose vial to their eye or to any surface in order to avoid eye injury or contamination of the solution. Advise patients that one single-dose vial can be used to dose both eyes immediately after opening. Discard the single-dose vial, including any remaining contents, after use
- Use With Contact Lenses
Advise patients that contact lenses should be removed prior to administration of TRYPTYR and can be reinserted 15 minutes after administration.
- Use with Other Ophthalmic Drugs
Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.
- Storage Information
Instruct patients to store unopened single-dose vials in the original foil pouch until ready to use [see How Supplied/Storage and Handling
Precautions with Alcohol
Alcohol-Acoltremon interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
TRYPTYR® [trip’tir]
Look-Alike Drug Names
There is limited information regarding Acoltremon Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.