Other differences include how they are formulated (e.g. one is a solution and the other is an emulsion) and their cost. I'll describe these in more detail below.
The next sections contain a general overview of the differences between Cequa and Restasis and cover:
As stated, both Cequa and Restasis contain cyclosporine, an immunosuppressive/anti-inflammatory agent, but in different concentrations:
Restasis (cyclosporin 0.05%) Cequa (cyclosporin 0.09%)
Whether this increased concentration of cyclosporine contained in Cequa translates to it being
more effective in treating dry eyes isn't definitively known.
There are no head-to-head or comparison studies to draw from, unfortunately. I do discuss their clinical trial data in one of the following sections, however.
While both Restasis and Cequa are in liquid dosage forms, they are formulated differently:
Restasis is an emulsion Cequa is a solution
There likely isn't a huge difference in effect based on the type of formulation used alone.
Nevertheless, the manufacturer of Cequa, Sun Pharma, in a news release, stated this regarding their formulation in particular:
"...[Cequa] is the first and only approved CsA [cyclosporin] product that incorporates a nanomicellar technology. The innovative nanomicellar formulation allows the CsA molecule to overcome solubility challenges, penetrate the eye’s aqueous layer and prevents the release of the active lipophilic molecule prior to penetration."
What this is basically saying is that Cequa is formulated in a way that allows the drug (cyclosporine) to be delivered to the site of action (corneal and conjunctival cells) without significant degradation or loss of active ingredient in other parts of the eye. This feature is one of its (Cequa) main marketing claims.
There is no indication, however, that Cequa delivers a higher percentage of cyclosporine to the site of action when compared to Restasis.
The full ingredient list for each drug is as follows:
Cyclosporine 0.05% Glycerin Castor oil Polysorbate 80 Carbomer copolymer type A Purified water Sodium hydroxide
Restasis appears as a white opaque to slightly translucent homogeneous emulsion.
Cyclosporine 0.09% Polyoxyl hydrogenated castor oil Octoxynol-40 Polyvinylpyrrolidone Sodium phosphate monobasic dihydrate Sodium phosphate dibasic anhydrous Water for injection Sodium hydroxide
Cequa appears as a clear, colorless ophthalmic solution.
How these drugs are packaged and available to consumers represents a significant difference between two.
Firstly, both are available as single-use, preservative-free vials. However, Cequa contains a lower volume of liquid: Cequa contains 0.25 mL liquid per single-use vial. Restasis contains 0.4 mL liquid per single-use vial.
vial the liquid comes in for each product is the same size (0.9 mL), but Cequa contains less liquid.
Below are excerpts from each of their respective prescription information inserts:
Restasis: RESTASIS® ophthalmic emulsion is packaged in sterile, preservative-free single-use vials. Each vial contains 0.4 mL fill in a 0.9 mL LDPE [Low-density polyethylene] vial. Cequa:
CEQUA ophthalmic solution is packaged in sterile, preservative-free, single-use vials. Each vial contains 0.25 mL fill in a 0.9 mL LDPE vial.
It is important to note that while Restasis was originally only available as single-use vials (as described above), it
now is also available in a 'MultiDose' bottle.
Just like the single-use vials, the MultiDose bottle contains
no preservatives. One bottle contains a one-month supply. The MultiDose bottle looks like this:
If you find single-use vials cumbersome (and wasteful due to the plastic packaging), the MultiDose bottle may be a better option for you.
only available in single-use plastic vials. It does not come in a Multi-use bottle like Restasis.
Both Restasis and Cequa use the same data endpoint in their clinical trials for determining the effectiveness of each. The test they use is known as the 'Schirmer wetting test'
The 'Schirmer wetting test' is used to determine whether or not your tear glands produce enough tears to moisturize the eyes.
To perform the test, a calibrated, vertical paper strip inserted into the lower eyelid of each eye. The eyes are then closed for 5 minutes and the amount of moisture that has traveled down the strip (from the eye) is measured.
The benchmark for 'normal' moisture production is 10 mm of moistened paper (i.e. moisture from tear production has traveled 10 millimeters down the paper strip from the eye).
less than 10mm of the paper has been moistened, you likely have some sort of problem producing tears and may be diagnosed as having dry eye syndrome.
So, how Cequa and Restasis measure effectiveness is by reporting how many individuals who 'failed' the Schirmer wetting test (by producing less than 10mm of moisture)
improved to producing over 10mm of moisture after using the respective drug. Cequa Effectiveness
The following is reported from the prescribing information for Cequa:
To put this data into words:
In the first clinical trial (OTX-101-2014-001), 16.8% of individuals who previously had less than 10mm of tear production (via the Schirmer test) now produced over 10mm after 84 days of use of Cequa. This compares to only 8.6% of individuals who used the drug vehicle alone (i.e. non-drug containing liquid). This represents an 8.2% difference between Cequa and placebo (i.e. vehicle). In the second clinical trial (OTX-101-2016-001), 16.6% of individuals who previously had less than 10mm of tear production (via the Schirmer test) now produced over 10mm after 84 days of use of Cequa. This compares to only 9.2% of individuals who used the drug vehicle alone (i.e. non-drug containing liquid). This represents a 7.3% difference between Cequa and placebo (i.e. vehicle). Restasis Effectiveness
The prescribing information for Restasis doesn't provide a chart summarizing their clinical trial data as Cequa does. It does, however, state:
Cyclosporine ophthalmic emulsion, 0.05% demonstrated statistically significant increases in Schirmer wetting of 10 mm versus vehicle at six months in patients whose tear production was presumed to be suppressed due to ocular inflammation.
This effect was seen in approximately 15% of cyclosporine ophthalmic emulsion, 0.05%-treated patients versus approximately 5% of vehicle treated patients.
In other words, about 15% of individuals who previously had less than 10mm of tear production (via the Schirmer test) now produced over 10mm after 6 months (180 days) of use of Restasis.
On the surface, it appears that Cequa is more effective than Restasis based on the data that shows it increases tear production (based on the Schirmer test) in
more individuals (~16.6/16.8% for Cequa versus ~15% for Restasis).
However, it is important to point out that there have
not been any direct comparison studies between the two drugs, and clinical trial conditions between them were different. It therefore so it is impossible to definitively say one is better than the other without more evidence.
Preliminary data suggests that their onset of effect is the same, around four weeks or so after first starting. Full effects are both are seen between three to six months after starting therapy.
Side effects for Cequa and Restasis are quite similar. The two most common ones are:
Ocular burning/eye irritation upon installation of drops (22% for Cequa vs. 17% for Restasis) Conjunctival hyperemia (which manifests as bloodshot eyes and redness) (6% for Cequa vs. 1-5% for Restasis)
Other reported side effects include:
Blepharitis Headache Urinary tract infection
For the two most common side effects (burning/irritation), they occur more commonly with Cequa, most likely due to the fact that it contains a higher concentration of cyclosporine.
How To Use
Cequa and Restasis have the same recommended directions for use:
Instill 1 drop into the affected eye(s) twice daily, approximately 12 hours apart. Artificial tears may be used with these products, but allow a 15-minute interval between administration of products.
If using single-use vials, they must be discarded after one use. They do not contain preservatives and should not be saved for later use.
The Restasis MultiDose bottle contains a 30 day-supply if using 4 drops per day (one drop in each eye every 12 hours). It contains around 120 drops, with some overfill due to the need to prime to bottle before first use.
Neither product can be used if you are wearing contacts. Contact lenses should be removed before administration, and it is necessary to wait 15 minutes before inserting them back in.
The cost of each product will vary based on your insurance plan and copay structure. However, going off of a 'cash price', Cequa is slightly less expensive:
Restasis: ~$560 for a 30-day supply Cequa: ~$510 for a 30-day supply Restasis and Cequa contain the same active ingredients, cyclosporine, but Cequa is more highly concentrated (0.09% vs. 0.05% for Restasis). Overall, they have similar side effects and effectiveness but do have several differences including how they are formulated and how much they cost. Summary References Restasis Prescribing Information. AccessFDA Cequa Prescribing Information. AccessFDA Dry Eye Syndrome PPP - 2018. American Academy of Ophthalmology
Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review. PubMed Sun Pharma Announces U.S. FDA Approval of CEQUA™ to Treat Dry Eye Disease. BusinessWire