Diquas/Diquas-S

Diquafosol sodium.

Diquas: Each mL contains 30 mg of diquafosol sodium. It also contains potassium chloride, sodium chloride, chlorhexidine gluconate solution, dibasic sodium phosphate hydrate, disodium edetate hydrate and pH adjuster as additives. Its pH is 7.2 - 7.8 and its osmolar ratio is 1.0 - 1.1.
Diquas-S: Each mL contains 30 mg of diquafosol sodium. It also contains dibasic sodium phosphate hydrate, disodium edetate hydrate, sodium chloride, potassium chloride, hydrochloric acid and sodium hydroxide as additives. The product has pH 7.2 - 7.8 and osmolar ratio 1.0 - 1.1.

Pharmacology: Pharmacodynamics: Mechanism of action: Diquafosol sodium stimulated water and mucin secretion by acting on P2Y₂ receptors on the conjunctival epithelial and goblet cell membrane and elevating intracellular calcium ion concentrations.
Stimulatory action on secretion of tear fluid including mucin: A single dose administration of diquafosol sodium into the eyes of normal animals (rabbits and rats) promoted tear fluid secretion and mucin secretion from the conjunctival cells.
A single dose administration of diquafosol sodium into the eyes of dry eye model rats promoted tear fluid secretion. Repeated dose administration increased mucin contents in the conjunctival tissues.
Stimulatory action on mucin production in corneal epithelial cells: Diquafosol sodium stimulated gene expression and protein production of membrane-associated mucin in corneal epithelial cells.
Improvement of corneal epithelial damage: Repeated dose administration of diquafosol sodium 6 times daily for 4 weeks improved corneal epithelial damage in rat dry eye model in a dose-dependent manner, and exhibited the maximal effect at the concentration of 1% or higher. Repeated dose of 1% diquafosol sodium for 2 weeks exhibited the maximal improvement effect when daily administration exceeded 6 times.
Pharmacokinetics: Plasma concentrations: After topical administration of diquafosol sodium solution either at concentrations of 0.3%, 1%, 3% or 5% to the eye of healthy adult volunteers one drop, once daily for one day, 6 times daily for one day or 6 times daily for 7 days, the plasma concentrations of diquafosol sodium and its metabolites were measured. Those of diquafosol sodium were below the lower limit of quantitation (2ng/mL) at every time point in all of the volunteers. The plasma concentration of metabolites (UTP, UDP, UMP and uridine) did not affect physiological concentrations derived from the endogenous components.
(Note: The approved concentration of this product is 3%.)
Ocular tissue distribution in animals: (Rabbits): Following a single topical administration of 3% ¹⁴C-diquafosol sodium ophthalmic solution to rabbit eyes, the radioactivity was distributed in the extraocular tissues including the conjunctiva and cornea, and reached the maximum radioactive concentrations in the cornea and conjunctiva at 5 minutes after administration. Thereafter, the radioactivity reduced to 4 to 30% of the maximum concentrations at 24 hours after administration.
Metabolism: (Human in vitro): In vitro metabolism reaction using human plasma and human liver microsome demonstrated that diquafosol sodium was rapidly metabolized, and UMP, uridine and uracil were produced.
(Rabbits): At 30 minutes after instillation of 3% ¹⁴C-diquafosol sodium ophthalmic solution to rabbit eyes, diquafosol sodium was hardly detected in the ocular tissues, and instead UTP, UDP, UMP, uridine and uracil were detected.

Dry eye.
Precautions related to Indications: This product should be used in patients diagnosed with dry eye, associated with keratoconjunctival epithelium disorders that accompany lacrimal fluid abnormality.

Recommended dose: Usually, instill 1 drop a time 6 times daily.
Mode of Administration: For ophthalmic use only.

Overdose is unlikely to occur after ocular administration. If overdose occurs, treatment should be symptomatic.

Patients with a history of hypersensitivity to any of the ingredients of this product.

Precautions concerning Use: Route of administration: Ophthalmic use only.
At the time of administration: Instruct the patient to be careful not to touch the tip of the bottle/container to the eye directly in order to avoid the contamination of the drug.
When more than one ophthalmic solution is used, at least 5 minutes of intervals should be taken.
Diquas: Discard contents one month after opening the bottle/sachet.
Diquas-S: Discard first 1~2 drops without administration (to eliminate possible foreign particle from opening the container).
After opening the single dose container, use only once and discard the remaining product and the container.
Effects on Ability to Drive and Use Machine: As with any ocular treatment, if transient blurred vision occurs at instillation, patients should be advised not to drive or use machines until their vision has cleared.
Use in Children: The safety of this product to low birth weight infants, neonates, infants or children has not been established. (No clinical experience.)

There are no adequate data for the use of diquafosol in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
It is unknown whether diquafosol and/or its metabolites are excreted in human milk.

Adverse drug reactions (including abnormal changes in laboratory test values) were reported in 155 of 655 patients (23.7%) in clinical trials for diquafosol sodium ophthalmic solution 3% (multidose bottles containing preservative) conducted in Japan before approval. The major adverse reactions were eye irritation in 44 patients (6.7%), eye discharge in 31 patients (4.7%), conjunctival hyperaemia in 24 patients (3.7%), eye pain in 18 patients (2.7%), itching in 16 patients (2.4%), foreign body sensation in 14 patients (2.1%) and ocular discomfort in 7 patients (1.1%), etc (upon approval - for Diquas only).
Adverse reactions were reported in 202 of 3,196 patients (6.3%) in post marketing observational study for diquafosol sodium ophthalmic solution 3% (multidose bottles containing preservative) in Japan. The major adverse reactions were eye irritation in 30 patients (0.9%), eye discharge in 30 patients (0.9%), eye pain in 22 patients (0.7%), lacrimation increased in 20 patients (0.6%) and blepharitis in 19 patients (0.6%), etc (Post marketing surveillance, at the time of 6th periodic safety update report - for Diquas only).
If adverse reactions are observed, appropriate measures such as discontinuing administration should be taken. (See table.)

Click on icon to see table/diagram/image

No interaction studies have been performed with diquafosol.

Diquas: Keep below 30°C.
Diquas-S: Store below 30°C in a tight container.

Other Eye Preparations

S01XA - Other ophthalmologicals ; Used in ophthalmic preparations.

E-D