For the temporary relief of burning and irritation due to dryness of the eye

Adults and elderly
Instill 1-2 drops in the affected eye(s) as needed

Pediatric population
The safety and efficacy of SYSTANE* Lubricant Eye Drops in children has not been established.

Hepatic and Renal Disease
The safety and efficacy of SYSTANE* Lubricant Eye Drops in subjects with hepatic/renal disease has not been established.

Method of administration
- For ocular use only
- If solution changes color or becomes cloudy do not use.
- After cap is removed, if tamper evident snap collar is loose, remove before
using product.
- If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.
- Shake well before use
- May be used to treat dry eye associated with contact lens usage by instilling drops prior to inserting contact lenses and after the removal of contact lenses. Place drops on the eye and blink.
- To avoid contamination, do not touch tip of container to any surface. Replace
cap after using.

- If you experience persistent eye discomfort, excessive tearing, headache, vision changes, or redness of the eye, stop using SYSTANE* Lubricant Eye Drops and consult your eye care professional as the problem could become more serious.

- After cap is removed, if tamper evident snap collar is loose, remove before using product.

No clinically relevant interactions have been described.

Fertility
There are no adequate data regarding the impact of SYSTANE* Lubricant Eye Drops on fertility. All of the ingredients in this product are pharmacologically inert compounds, generally classified as non-toxic and non-irritating (See Section 5.3). Therefore, no effects on fertility are anticipated.

Pregnancy
There are no adequate data from the use of SYSTANE* Lubricant Eye Drops in pregnant women. All of the ingredients in this product are pharmacologically inert compounds, generally classified as non-toxic and non-irritating (See Section 5.3). Therefore, no effects during pregnancy are anticipated. This product can be used during pregnancy.

Breast-feeding
There are no adequate data regarding the impact of SYSTANE* Lubricant Eye Drops on lactation. All of the ingredients in this product are pharmacologically inert compounds, generally classified as non-toxic and non-irritating (See Section 5.3). Therefore, no effects on breast-feeding are anticipated. This product can be used during breastfeeding.

Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs after application, the patient must wait until the vision clears before driving or using machinery

Tabulated list of adverse reactions

The following adverse reactions have been reported following administration of SYSTANE* Lubricant Eye Drops. Frequency cannot be estimated from the available data.

--To reports any side effect(s):
       - Saudi Arabia:
--The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662
o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc
        Other GCC States:
-- Please contact the relevant competent authority.

Due to the characteristics of this preparation, no toxic effects are to be expected with an ocular overdose of this product, nor in the event of accidental ingestion of the contents of one bottle.

Pharmacodynamic studies with SYSTANE* Lubricant Eye Drops were not performed.

Absorption

Polyethylene Glycol 400
There is no data available following ocular administration; therefore all supporting information is derived from systemic exposures.

Polyethylene glycol (PEGs) has been shown to be absorbed from the gastrointestinal tract. The percentage absorbed is highly dependent on the molecular weight with low molecular weight (< 1000 Da) showing partial absorption in the small intestine following oral administration. Oral administration of PEG 400 in humans resulted in 50-65% absorbed. PEG’s with molecular weights greater than 4000 have minimal absorption through intact skin.

Propylene Glycol
There is no data available following ocular administration; therefore, all supporting information is derived from systemic exposures.

Studies in animals have shown that propylene glycol is rapidly absorbed following oral administration in cats, rats and rabbits.

Distribution

Polyethylene Glycol 400
Studies have been performed on the distribution of PEG 400 in the systemic circulation following oral, intravenous or topical administrations. It has been reported that PEG 400 diffuses intracellularly based on the calculated volume of distribution in dogs following intravenous administration.

Propylene Glycol
Studies have been performed on the distribution of propylene in the systemic circulation following oral or intravenous administrations in humans. Following IV administration of propylene glycol doses of 120-600 mg/m2 the average Vd was ~0.780 L/kg and following oral administrations the apparent volume of distribution is ~0.5 L/kg. These values are  pproximately the value of total body which indicates that propylene glycol is distributed uniformly in tissues.

Biotransformation

Polyethylene Glycol 400
Only low levels of detectable metabolic products were identified after oral administration. Metabolism studies of PEG have shown formation of carboxylic acid from oxidation of the terminal alcohol groups. The diacid and hydroxyl acid metabolites of PEG have been identified in plasma and urine in humans.

Propylene Glycol
Systemic propylene glycol has been reported to undergo oxidative metabolism to lactic and pyruvic acids and carbon dioxide. Studies in rats have shown increases in liver glycogen content following diets containing propylene glycol.

Elimination

Polyethylene Glycol 400
It has been shown that following oral administrations of PEG 400, systemic levels are excreted primarily unchanged in the urine and feces. Urinary excretion of PEG occurs through passive glomerular filtration and is therefore dependent on molecular weight. Human data shows urinary
clearance as the major excretory pathway for PEG 400. In the dog, PEGs with molecular weights in the range 400 to 4000 are cleared from plasma at a rate identical to the glomerular filtration rate, which suggests a passive filtration process.

Propylene Glycol
Propylene glycol eliminated from systemic blood is proportional to the concentration. It has been shown that elimination occurs through metabolism and renal excretion with approximately one third to one half of the administered dose recovered in urine.

Linearity/non-linearity

Polyethylene Glycol 400
No dose ranging studies have been reported regarding systemic exposures.
Propylene Glycol Nonlinear kinetics following increasing intravenous infusions in patients showed saturable clearance in the dose range of 3-15 g/m2 of propylene glycol.

Pharmacokinetic/pharmacodynamic relationship(s)

Polyethylene Glycol 400
No PK/PD studies have been reported for PEG 400.

Propylene Glycol
No PK/PD studies have been reported for propylene glycol.

Non-clinical data reveal no special hazard for humans based on conventional studies or risk assessment of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.

Not applicable

Store below 30°C.
Do not use this medicine after the expiry date which is stated on the packaging.
Discard 4 weeks after first opening.
Keep this medicine out of the sight and reach of children.

SYSTANE* Lubricant Eye Drops is supplied in plastic bottles in the size of 15 ml.

- To avoid contamination, never touch the tip of the vial to any surface.
- Use before the expiration date marked on the product.
- If the solution becomes discolored or cloudy, the product should not be used.
- TAMPER EVIDENT: Do not use if security seal is damaged or missing. Do not use if
                         package has been opened or damaged.
- If swallowed, get medical help.
- Keep out of the reach of children
- Replace cap after using.
- Keep container tightly closed when not in use.
- Can be used for up to six months after opening.
- Discard any remaining solution six months after first opening.