Skip to content
Inciteful Med
Resources About us Ask a Question

Restasis vs Xiidra: Which is Better for Sjögren's?

Published: | Updated:

Restasis (cyclosporine) and Xiidra (lifitegrast) are prescription eye drops that treat severe Sjögren's dry eye by reducing inflammation. Both require twice-daily use and can take weeks to months to work, though Xiidra may cause an unusual taste and Restasis is known for initial stinging.

Key Takeaways

  • • Restasis and Xiidra treat severe dry eye by reducing the inflammation that stops your eyes from making enough tears.
  • • Both medications typically require twice-daily use and can take several weeks to a few months to reach their full effect.
  • • You can continue using artificial tears for comfort, but wait 5 to 10 minutes between drops to avoid washing out the prescription medication.
  • • Mild burning or stinging is common when starting these drops, but usually improves as your eye surface heals.
  • • Xiidra can cause an unusual metallic taste, which can be minimized by pressing the inner corner of your eye after applying the drop.

When over-the-counter artificial tears are not enough to manage the severe dry eyes—medically known as keratoconjunctivitis sicca (severe dryness and inflammation of the cornea and conjunctiva)—caused by Sjögren’s syndrome, your doctor may recommend a prescription eye drop like Restasis (cyclosporine) or Xiidra (lifitegrast) [1]. Both are effective at reducing the underlying inflammation that stops your eyes from making enough tears, but they work in slightly different ways [2][3]. Restasis blocks the activation of inflammatory immune cells, while Xiidra prevents those cells from binding to the surface of your eye [2][3]. Although both medications typically require twice-daily use and can take weeks or even months to reach their full effect, many patients eventually experience significant relief from dryness [1][4].

How They Work

Primary Sjögren’s syndrome causes your immune system to mistakenly attack your moisture-producing glands. The resulting inflammation damages the tear glands, reducing tear production.

  • Cyclosporine (Restasis and Cequa): The active ingredient in these twice-daily drops is an immunosuppressant called cyclosporine. It works by inhibiting calcineurin, an enzyme that activates T-cells (a type of white blood cell that drives immune responses and inflammation) [3][5]. By blocking T-cell activation, cyclosporine lowers the production of inflammatory signals, allowing your tear glands to recover and produce more of your own natural tears [3][5]. While Restasis is the most common oil-based emulsion, newer versions like Cequa use a nanomicellar (tiny particle) technology to help the medicine penetrate the eye better [6][7].
  • Lifitegrast (Xiidra): Xiidra takes a different approach, though it is also used twice a day. It belongs to a class of drugs called LFA-1 antagonists (medications that block specific proteins on the surface of white blood cells) [2][1]. In a dry eye, certain proteins are overexpressed on the eye’s surface. Xiidra works by blocking inflammatory T-cells from binding to these proteins, effectively short-circuiting the inflammation cycle [2][8].

Time to Relief & Using Artificial Tears

Patience is essential when starting either of these medications. Unlike artificial tears, which provide immediate but temporary moisture, prescription drops treat the underlying disease and take time to work.

  • Delayed Relief: Both conventional cyclosporine (Restasis) and lifitegrast (Xiidra) have a delayed onset of action. It typically takes several weeks to a few months of twice-daily use to experience the full therapeutic benefit [1][4][9].
  • Faster Options: Newer formulations of cyclosporine, such as Cequa, are designed to improve how well the drug is absorbed and may offer a faster onset of action for some patients compared to traditional Restasis [1][10][11].
  • What to do while you wait: Because relief is not immediate, many patients get frustrated and stop taking the medication within the first few months [9][12]. However, you can and should continue using your over-the-counter artificial tears for comfort during this waiting period. Just be sure to wait at least 5 to 10 minutes between using your prescription drop and any artificial tears so you don’t wash the medication out of your eye [13][14][15].

Common Side Effects & Practical Tips

Because these drops go directly onto an already irritated eye, side effects are very common, especially when you first start treatment. They often come in single-use vials, and your doctor or pharmacist will explain exactly how to handle them.

  • Burning and Stinging: Mild to moderate burning, stinging, or redness upon putting the drops in is the most common complaint for both Restasis and Xiidra [16][4]. This often improves as your eye surface heals over time [17][18]. Using a preservative-free artificial tear 10 to 15 minutes before your prescription drop can sometimes help soothe the eye first [13][14].
  • Unusual Taste (Dysgeusia): Xiidra specifically is known to cause dysgeusia (an unusual, metallic, or salty taste in the back of the throat) shortly after using the drops [16][4][19]. This happens because the tear ducts naturally drain down into the nasal cavity and throat. To minimize this, you can practice punctal occlusion: gently press on the inner corner of your closed eye for a minute immediately after applying the drop. This blocks the drainage duct and keeps the medicine on your eye instead of in your throat [20].

Note: While both medications are heavily prescribed for the dry eyes associated with Sjögren’s, large clinical trials directly comparing the two specifically within the Sjögren’s patient population are currently limited [21][22]. These drops can also be quite expensive; always ask your doctor about trial samples, manufacturer savings cards, or prior authorization help if insurance coverage is an issue. Your doctor will help you choose based on your specific symptoms and how you tolerate the drops.

Frequently Asked Questions

How long does it take for Restasis or Xiidra to work?
Both Restasis and Xiidra take several weeks to a few months of twice-daily use to provide full therapeutic relief. During this waiting period, you can continue using over-the-counter artificial tears for temporary comfort.
Can I use artificial tears with Restasis or Xiidra?
Yes, you can use over-the-counter artificial tears along with your prescription drops. Just remember to wait at least 5 to 10 minutes between using your prescription drop and the artificial tears so the medication doesn't wash out of your eye.
Why does Xiidra leave a bad taste in my mouth?
Xiidra can cause a metallic or salty taste because the tear ducts naturally drain down into the nasal cavity and throat. Gently pressing on the inner corner of your closed eye for a minute after applying the drop can help keep the medicine on your eye instead.
Which is better for Sjögren's dry eye: Restasis or Xiidra?
Both medications effectively reduce the inflammation that causes severe dry eye, but they work in slightly different ways. Your eye doctor will help you choose the best option based on your specific eye surface, symptoms, and how you tolerate the side effects.

Questions for Your Doctor

  • • Which specific formulation (Restasis, Cequa, or Xiidra) makes the most sense for my specific eye surface and severity of dryness?
  • • How long should I commit to trying this prescription before we decide whether it is working for me?
  • • What is your recommended routine for spacing out my prescription drops, artificial tears, and nighttime ointments?
  • • Can your office provide trial samples or assist with manufacturer savings programs if my insurance doesn't cover the full cost?

Questions for You

  • • Am I prepared to commit to a twice-daily routine for several months, even if I don't feel immediate relief?
  • • Have I had a bad reaction to preservatives in eye drops in the past, or do I have a history of ocular rosacea?
  • • Which side effect am I most concerned about managing (like stinging vs. a metallic taste), and have I discussed this with my doctor?

Want personalized information?

Type your question below to get evidence-based answers tailored to your situation.

References

  1. 1

    The Role of Topical Cyclosporine A in Ocular Surface Inflammatory Disorders.

    Doctor MB, Kate A, Tallapelly HG, Basu S

    Seminars in ophthalmology 2026; (41(1)):119-130 doi:10.1080/08820538.2025.2512759.

    PMID: 40468687
  2. 2

    Quintessence of currently approved and upcoming treatments for dry eye disease.

    Patil S, Sawale G, Ghuge S, Sathaye S

    Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2025; (263(2)):269-278 doi:10.1007/s00417-024-06587-7.

    PMID: 39215848
  3. 3

    Cyclosporine a in the treatment of dry eye disease: a narrative review.

    Bian X, Ma J, Liu Y, et al.

    Frontiers in ophthalmology 2025; (5()):1700163 doi:10.3389/fopht.2025.1700163.

    PMID: 41346949
  4. 4

    Physician Satisfaction with Anti-Inflammatory Topical Medications for the Treatment of Dry Eye Disease.

    White DE, Zhao Y, Jayapalan H, et al.

    Clinical ophthalmology (Auckland, N.Z.) 2020; (14()):931-938 doi:10.2147/OPTH.S237832.

    PMID: 32273677
  5. 5

    Efficacy of topical cyclosporine 0.05% and osmoprotective lubricating eye drops in treating dry eye disease and inflammation.

    Mullick R, Annavajjhala S, Thakur P, et al.

    Indian journal of ophthalmology 2021; (69(12)):3473-3477 doi:10.4103/ijo.IJO_3822_20.

    PMID: 34826977
  6. 6

    Efficacy and safety of 0.05% micellar nano-particulate (MNP) cyclosporine ophthalmic emulsion in the treatment of moderate-to-severe keratoconjunctivitis sicca: a 12-week, multicenter, randomized, active-controlled trial.

    Rao AT, Gupta A, Chauhan T, et al.

    BMC ophthalmology 2023; (23(1)):121 doi:10.1186/s12886-023-02838-z.

    PMID: 36973703
  7. 7

    Prolonged Ocular Retention of Mucoadhesive Nanoparticle Eye Drop Formulation Enables Treatment of Eye Diseases Using Significantly Reduced Dosage.

    Liu S, Dozois MD, Chang CN, et al.

    Molecular pharmaceutics 2016; (13(9)):2897-905 doi:10.1021/acs.molpharmaceut.6b00445.

    PMID: 27482595
  8. 8

    [Topical cyclosporine in ophthalmology: Pharmacology and clinical indications].

    Levy O, Labbé A, Borderie V, et al.

    Journal francais d'ophtalmologie 2016; (39(3)):292-307.

    PMID: 26997607
  9. 9

    Real-World Treatment Patterns Of Cyclosporine Ophthalmic Emulsion And Lifitegrast Ophthalmic Solution Among Patients With Dry Eye.

    White DE, Zhao Y, Ogundele A, et al.

    Clinical ophthalmology (Auckland, N.Z.) 2019; (13()):2285-2292 doi:10.2147/OPTH.S226168.

    PMID: 31819353
  10. 10

    Ocular Pharmacokinetics of a Topical Ophthalmic Nanomicellar Solution of Cyclosporine (Cequa®) for Dry Eye Disease.

    Mandal A, Gote V, Pal D, et al.

    Pharmaceutical research 2019; (36(2)):36 doi:10.1007/s11095-018-2556-5.

    PMID: 30617777
  11. 11

    Efficacy and Safety of a Water-Free Topical Cyclosporine, 0.1%, Solution for the Treatment of Moderate to Severe Dry Eye Disease: The ESSENCE-2 Randomized Clinical Trial.

    Akpek EK, Wirta DL, Downing JE, et al.

    JAMA ophthalmology 2023; (141(5)):459-466 doi:10.1001/jamaophthalmol.2023.0709.

    PMID: 37022717
  12. 12

    Real-world treatment patterns of OTX-101 ophthalmic solution, cyclosporine ophthalmic emulsion, and lifitegrast ophthalmic solution in patients with dry eye disease: a retrospective analysis.

    Karpecki P, Barghout V, Schenkel B, et al.

    BMC ophthalmology 2023; (23(1)):443 doi:10.1186/s12886-023-03174-y.

    PMID: 37919692
  13. 13

    Personalized Management of Dry Eye Disease: Beyond Artificial Tears.

    Matossian C, Crowley M, Periman L, Sorkin S

    Clinical ophthalmology (Auckland, N.Z.) 2022; (16()):3911-3918 doi:10.2147/OPTH.S384819.

    PMID: 36452043
  14. 14

    Analyze interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in dry eye and the therapeutic effect of cyclosporine A.

    Wu J, Li GJ, Niu J, et al.

    World journal of clinical cases 2024; (12(25)):5665-5672 doi:10.12998/wjcc.v12.i25.5665.

    PMID: 39247746
  15. 15

    Physicochemical Properties and Rheological Behavior of Artificial Tears for Dry Eye Syndrome.

    Montmeat D, Thouvenin A, Rasamison R, Boudy V

    Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 2025; (41(10)):604-610 doi:10.1177/10807683251364169.

    PMID: 40762066
  16. 16

    Safety, adherence and discontinuation in varenicline solution nasal spray clinical trials for dry eye disease.

    Hauswirth SG, Kabat AG, Hemphill M, et al.

    Journal of comparative effectiveness research 2023; (12(6)):e220215 doi:10.57264/cer-2022-0215.

    PMID: 37096956
  17. 17

    A randomized study of the efficacy and safety of 0.1% cyclosporine A cationic emulsion in treatment of moderate to severe dry eye.

    Baudouin C, Figueiredo FC, Messmer EM, et al.

    European journal of ophthalmology 2017; (27(5)):520-530 doi:10.5301/EJO.5000952.

    PMID: 28362054
  18. 18

    Impact of Topical Cyclosporine-A or Topical Chloroquine on Post-LASIK Ocular Surface Stability - A Randomized Controlled Trial.

    Titiyal JS, Goswami A, Kaur M, et al.

    Current eye research 2023; (48(6)):557-563 doi:10.1080/02713683.2023.2182747.

    PMID: 36800492
  19. 19

    Dry Eye Disease: Focus on Prescription Therapy.

    Marshall LL, Hayslett RL

    The Senior care pharmacist 2023; (38(6)):239-251 doi:10.4140/TCP.n.2023.239.

    PMID: 37231571
  20. 20

    Efficacy of Topical Cyclosporine Combined with Punctal Plugs in Treating Dry Eye Disease and Inflammation.

    Feng C, Wang W, Gong L, Lin T

    Current eye research 2025; (50(2)):148-161 doi:10.1080/02713683.2024.2411699.

    PMID: 39373208
  21. 21

    Renal Disease in Primary Sjögren's Syndrome.

    Aiyegbusi O, McGregor L, McGeoch L, et al.

    Rheumatology and therapy 2021; (8(1)):63-80 doi:10.1007/s40744-020-00264-x.

    PMID: 33367966
  22. 22

    Recommendations from the Brazilian society of rheumatology for the diagnosis of Sjögren's syndrome (Part I): glandular manifestations (systematic review).

    Trevisani VFM, Pasoto SG, Fernandes MLMS, et al.

    Advances in rheumatology (London, England) 2019; (59(1)):58 doi:10.1186/s42358-019-0102-8.

    PMID: 31852541

This page compares prescription eye drops for Sjögren's dry eye for informational purposes only. Always consult your ophthalmologist or rheumatologist before starting or changing your eye care routine.

Stay up to date

Get notified when new research about Primary Sjögren's Syndrome is published.

No spam. Unsubscribe anytime.