Diquas/Diquas-S

Diquafosol sodium.

Diquafosol Sodium (DIQUAS/DIQUAS-S) is a sterile aqueous ophthalmic solution containing 30 mg of Diquafosol Sodium in each mL (3%).
Diquas: It also contains Dibasic sodium phosphate hydrate, Disodium edetate hydrate, Sodium chloride, Potassium chloride, Chlorhexidine gluconate solution (preservative), Dilute hydrochloric acid, and Sodium hydroxide as excipients. Its pH is 7.2-7.8 and its osmolar ratio is 1.0-1.1.
Diquas-S: It also contains Dibasic sodium phosphate hydrate, Disodium edetate hydrate, Sodium chloride, Potassium chloride, Hydrochloric acid, and Sodium hydroxide as excipients. Its pH is 7.2-7.8 and its osmolar ratio is 1.0-1.1.

P₂Y₂ Receptor Agonist.
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.
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.
Diquas-S: 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.
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 and its metabolites were measured. Those of diquafosol were below the lower limit of quantitation (2 ng/mL) at every time point in all of the volunteers. The plasma concentrations 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 was hardly detected in the ocular tissues, and instead UTP, UDP, UMP, uridine and uracil were detected.

Treatment of dry eye.

Usually, instill 1 drop a time 6 times daily.

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: For ophthalmic use only.
At the time of administration: Instruct the patient to be careful not to touch the tip of the bottle 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-S: Discard first 1-2 drops without administration. (To eliminate possible foreign particle from opening the container.)
After opening, use only once and discard the remaining product and the container.
Effects on ability to drive and use machines: 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 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%), eye itching in 16 patients (2.4%), foreign body sensation in eyes in 14 patients (2.1%) and ocular discomfort in 7 patients (1.1%), etc.
Adverse reactions were reported in 202 of 3,196 patients (6.3%) in post marketing observational study 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.
If an adverse drug reaction is observed, appropriate measures including discontinuing administration should be taken. (See table.)

Click on icon to see table/diagram/image

Diquas-S: Incidence was calculated based on the clinical study results up to the approval of diquafosol ophthalmic solution 3% (multidose bottles containing preservative).

No interaction studies have been performed with diquafosol.

Store at temperatures not exceeding 30°C.
Diquas: After opening, use within one month.

Ophthalmic Lubricants

S01XA - Other ophthalmologicals ; Used in ophthalmic preparations.

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