Trifluridine

L01B - Antimetabolites ATC L01BC59 Small molecule approved 1980 Oral Topical

JFDA label: lonsurf

Mechanism of Action

Inhibitor of DNA — DNA inhibitor

Target	Action	Gene / class
DNA efficacy	INHIBITOR

Indications

Approved

Herpes keratoconjunctivitis, keratitis

Contraindications

Source: Lexicomp

Known hypersensitivity to trifluridine or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Immune system disorders (1)

Not Known Local ocular hypersensitivity reaction

Eye disorders (10)

Common Burning sensation of eyes · eyelid edema · stinging of eyes

Not Known Epithelial keratopathy · eye irritation · hyperemia · increased intraocular pressure · keratoconjunctivitis sicca · ocular stromal edema · superficial punctate keratitis

Dosing

Source: Lexicomp

Herpes keratoconjunctivitis, keratitis: Ophthalmic: Instill 1 drop into affected eye(s) every 2 hours while awake, to a maximum of 9 drops/day, until re-epithelialization of corneal ulcer occurs; then use 1 drop every 4 hours while awake for another 7 days (minimum daily dosage of 5 drops is recommended). Do not exceed 21 days of treatment; if improvement has not taken place in 7 to 14 days, consider another form of therapy.

(For additional information see "Trifluridine: Pediatric drug information") Children ≥6 years and Adolescents: Ophthalmic: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Irritation

Mild local irritation of conjunctival and cornea may occur when instilled; effects are usually transient.

Pregnancy & Lactation

Pregnancy

Adverse effects have not been observed during animal reproduction studies of the ophthalmic solution.

Lactation

The amount of trifluridine available systemically following topical application of the ophthalmic drops is negligible.

Chemistry & Properties

Formula	C10H11F3N2O5
Molecular weight	296.2 g/mol
IUPAC name	1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione
CAS	70-00-8
PubChem CID	6256
InChIKey	`VSQQQLOSPVPRAZ-RRKCRQDMSA-N`
logP	-0.8 (XLogP -0.5)
Polar surface area	104.55 Å²
H-bond acceptors / donors	6 / 3
Drug-likeness (QED)	0.66
Lipinski violations	0

SMILES

O=c1[nH]c(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1C(F)(F)F

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.477 h
Volume of distribution	2.232 L/kg
Protein binding	48.7%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OAT1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (81, DDInter)

Interacting drug	Severity	Management
Adalimumab	major
Bacillus calmette-guerin substrain tice live antigen	major
Baricitinib	major
Certolizumab pegol	major
Cladribine	major
Clozapine	major
Deferiprone	major
Etanercept	major
Fingolimod	major
Golimumab	major
Infliximab	major
Leflunomide	major
Measles virus vaccine live attenuated	major
Mumps virus strain B level jeryl lynn live antigen	major
Natalizumab	major
Ozanimod	major
Rotavirus vaccine	major
Rubella virus vaccine	major
Samarium (153Sm) lexidronam	major
Siponimod	major
Smallpox (Vaccinia) Vaccine, Live	major
Talimogene laherparepvec	major
Teriflunomide	major
Tofacitinib	major
Typhoid vaccine (live)	major
Upadacitinib	major
Varicella Zoster Vaccine (Recombinant)	major
Yellow Fever Vaccine	major
Alefacept	moderate
Alemtuzumab	moderate
Anakinra	moderate
Anthrax vaccine	moderate
Azathioprine	moderate
Bifidobacterium longum infantis	moderate
Canakinumab	moderate
Candida albicans	moderate
Chloramphenicol	moderate
Chloramphenicol (ophthalmic)	moderate
Clostridium tetani toxoid antigen (formaldehyde inactivated)	moderate
Coccidioides immitis spherule	moderate

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Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
lonsurf	Tablet 15 mg, 6.14 mg	20 tab	The Jordan Drugstore Co	—
lonsurf	Tablet 20 mg, 8.19 mg	20 tab	The Jordan Drugstore Co	—