Restasis (Cyclosporine): Side Effects, Uses, Dosage, Interactions, Warnings (2025)

Description for Restasis

RESTASIS®(cyclosporine ophthalmic emulsion) 0.05% contains a topical calcineurin inhibitor immunosuppressant with anti-inflammatory effects. Cyclosporine's chemical name is Cyclo[[(E)-(2S,3R,4R)-3hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl-N-methylglycyl-N-methyl-L-leucyl-L-valylN-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl] and it has the following structure:

Structural Formula

Cyclosporine is a fine white powder. RESTASIS® appears as a white opaque to slightly translucent homogeneous emulsion. It has an osmolality of 230 to 320 mOsmol/kg and a pH of 6.5-8.0. Each mL of RESTASIS® ophthalmic emulsion contains: Active: cyclosporine 0.05%. Inactives: glycerin; castor oil; polysorbate 80; carbomer copolymer type A; purified water; and sodium hydroxide to adjust pH.

Uses for Restasis

RESTASIS® ophthalmic emulsion is indicated toincrease tear production in patients whose tear production is presumed to besuppressed due to ocular inflammation associated with keratoconjunctivitissicca. Increased tear production was not seen in patients currently takingtopical anti-inflammatory drugs or using punctal plugs.

Dosage for Restasis

Invert the unit dose vial a few times to obtain auniform, white, opaque emulsion before using. Instill one drop of RESTASIS®ophthalmic emulsion twice a day in each eye approximately 12 hours apart. RESTASIS®can be used concomitantly with lubricant eye drops, allowing a 15-minuteinterval between products. Discard vial immediately after use.

HOW SUPPLIED

Dosage Forms And Strengths

Ophthalmic emulsion containing cyclosporine 0.5 mg/mL

Storage And Handling

RESTASIS® ophthalmic emulsion is packaged insterile, preservative-free single-use vials. Each vial contains 0.4 mL fill ina 0.9 mL LDPE vial; 30 or 60 vials are packaged in a polypropylene tray with analuminum peelable lid. The entire contents of each tray (30 vials or 60 vials)must be dispensed intact.

30 Vials 0.4 mL each - NDC 0023-9163-30
60 Vials 0.4 mL each - NDC 0023-9163-60

Storage

Store at 15°-25 °C (59°-77 °F).

Allergan., Irvine, CA 92612, U.S.A. See www.allergan.com/patents. Revised: 2017

Side Effects for Restasis

The following serious adverse reactions are describedelsewhere in the labeling:

• Potential for Eye Injury and Contamination [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widelyvarying conditions, adverse reaction rates observed in the clinical trials of adrug cannot be directly compared to rates in the clinical trials of anotherdrug and may not reflect the rates observed in practice.

In clinical trials, the most common adverse reactionfollowing the use of RESTASIS®was ocular burning (17%).

Other reactions reported in 1% to 5% of patients includedconjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation,pruritus, stinging, and visual disturbance (most often blurring).

Post-marketing Experience

The following adverse reactions have been identifiedduring post approval use of RESTASIS®. Because these reactions arereported voluntarily from a population of uncertain size, it is not alwayspossible to reliably estimate their frequency or establish a causalrelationship to drug exposure.

Reported reactions have included: hypersensitivity (includingeye swelling, urticaria, rare cases of severe angioedema, face swelling, tongueswelling, pharyngeal edema, and dyspnea); and superficial injury of the eye(from the vial tip touching the eye during administration).

Drug Interactions for Restasis

No information provided.

Warnings for Restasis

Included as part of the PRECAUTIONS section.

Precautions for Restasis

Potential For Eye Injury And Contamination

Be careful not to touch the vial tip to your eye or othersurfaces to avoid potential for eye injury and contamination.

Use With Contact Lenses

RESTASIS® should not be administered while wearingcontact lenses. Patients with decreased tear production typically should notwear contact lenses. If contact lenses are worn, they should be removed priorto the administration of the emulsion. Lenses may be reinserted 15 minutesfollowing administration of RESTASIS® ophthalmic emulsion.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Systemic carcinogenicitystudies were conducted in male and female mice and rats. In the 78-week oral(diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of astatistically significant trend was found for lymphocytic lymphomas in females,and the incidence of hepatocellular carcinomas in mid-dose males significantlyexceeded the control value.

In the 24-month oral (diet) rat study, conducted at 0.5,2, and 8 mg/kg/day, pancreatic islet cell adenomas significantly exceeded thecontrol rate in the low dose level. The hepatocellular carcinomas andpancreatic islet cell adenomas were not dose related. The low doses in mice andrats are approximately 80 times greater (normalized to body surface area) thanthe daily recommended human dose of one drop (approximately 28 mcL) of 0.05% RESTASIS®twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming thatthe entire dose is absorbed.

Mutagenesis

Cyclosporine has not been found to be mutagenic/genotoxicin the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinesehamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, themouse dominant lethal assay, and the DNA-repair test in sperm from treatedmice. A study analyzing sister chromatid exchange (SCE) induction bycyclosporine using human lymphocytes in vitro gave indication of a positiveeffect (i.e., induction of SCE).

Impairment Of Fertility

No impairment in fertility was demonstrated in studies inmale and female rats receiving oral doses of cyclosporine up to 15 mg/kg/day(approximately 2,000 times the human daily dose of 0.001 mg/kg/day normalizedto body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating.

Use In Specific Populations

Pregnancy

Risk Summary

Clinical administration of cyclosporine ophthalmicemulsion 0.05% is not detected systemically following topical ocularadministration [see CLINICAL PHARMACOLOGY], and maternal use is notexpected to result in fetal exposure to the drug. Oral administration ofcyclosporine to pregnant rats or rabbits did not produce teratogenicity atclinically relevant doses [see Data].

Data

Animal Data

At maternally toxic doses (30 mg/kg/day in rats and 100mg/kg/day in rabbits), cyclosporine oral solution (USP) was teratogenic asindicated by increased pre- and postnatal mortality, reduced fetal weight andskeletal retardations. These doses (normalized to body surface area) are 5,000and 32,000 times greater, respectively, than the daily recommended human doseof one drop (approximately 28 mcL) of cyclosporine ophthalmic emulsion 0.05%twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming thatthe entire dose is absorbed. No evidence of embryofetal toxicity was observedin rats or rabbits receiving cyclosporine during organogenesis at oral doses upto 17 mg/kg/day or 30 mg/kg/day, respectively. These doses in rats and rabbitsare approximately 3,000 and 10,000 times greater, respectively, than the dailyrecommended human dose. An oral dose of 45 mg/kg/day cyclosporine administeredto rats from Day 15 of pregnancy until Day 21 postpartum produced maternaltoxicity and an increase in postnatal mortality in offspring. This dose is7,000 times greater than the daily recommended human dose. No adverse effectsin dams or offspring were observed at oral doses up to 15 mg/kg/day (2,000times greater than the daily recommended human dose).

Lactation

Risk Summary

Cyclosporine is known to appear in human milk followingsystemic administration, but its presence in human milk following topicaltreatment has not been investigated. Although blood concentrations areundetectable following topical administration of RESTASIS® ophthalmic emulsion [seeCLINICAL PHARMACOLOGY], caution should be exercised when RESTASIS® isadministered to a nursing woman. The developmental and health benefits ofbreastfeeding should be considered along with the mother's clinical need for RESTASIS®and any potential adverse effects on the breast-fed child from cyclosporine.

Pediatric Use

Safety and efficacy have not been established inpediatric patients below the age of 16.

Geriatric Use

No overall difference in safety or effectiveness has beenobserved between elderly and younger patients.

Warnings for Restasis

Included as part of the PRECAUTIONS section.

Precautions for Restasis

Potential For Eye Injury And Contamination

Be careful not to touch the bottle tip to your eye or other surfaces to avoid potential for eye injury and contamination.

Uses With Contact Lenses

RESTASIS MULTIDOSE™ should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. If contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS MULTIDOSE™ ophthalmic emulsion.

Patient Counseling Information

Handling The Container

Advise patients to not allow the tip of the bottle to touch the eye or any surface, as this may contaminate the emulsion. Advise patients to not touch the bottle tip to their eye to avoid the potential for injury to the eye [see WARNINGS AND PRECAUTIONS].

Use With Contact Lenses

RESTASIS MULTIDOSE™ should not be administered while wearing contact lenses. Patients with decreased tear production typically should not wear contact lenses. Advise patients that if contact lenses are worn, they should be removed prior to the administration of the emulsion. Lenses may be reinserted 15 minutes following administration of RESTASIS MULTIDOSE™ ophthalmic emulsion [see WARNINGS AND PRECAUTIONS].

Administration

Advise patients to read the “Instructions for Use” for detailed first-time use instructions.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Systemic carcinogenicity studies were conducted in male and female mice and rats. In the 78-week oral (diet) mouse study, at doses of 1, 4, and 16 mg/kg/day, evidence of a statistically significant trend was found for lymphocytic lymphomas in females, and the incidence of hepatocellular carcinomas in mid-dose males significantly exceeded the control value.

In the 24-month oral (diet) rat study, conducted at 0.5, 2, and 8 mg/kg/day, pancreatic islet cell adenomas significantly exceeded the control rate in the low dose level. The hepatocellular carcinomas and pancreatic islet cell adenomas were not dose related. The low doses in mice and rats are approximately 80 times greater (normalized to body surface area) than the daily recommended human dose of one drop (approximately 28 mcL) of cyclosporine ophthalmic emulsion, 0.05% twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed.

Mutagenesis

Cyclosporine has not been found to be mutagenic/genotoxic in the Ames Test, the V79-HGPRT Test, the micronucleus test in mice and Chinese hamsters, the chromosome-aberration tests in Chinese hamster bone-marrow, the mouse dominant lethal assay, and the DNA-repair test in sperm from treated mice. A study analyzing sister chromatid exchange (SCE) induction by cyclosporine using human lymphocytes in vitro gave indication of a positive effect (i.e., induction of SCE).

Impairment Of Fertility

No impairment in fertility was demonstrated in studies in male and female rats receiving oral doses of cyclosporine up to 15 mg/kg/day (approximately 2,000 times the human daily dose of 0.001 mg/kg/day normalized to body surface area) for 9 weeks (male) and 2 weeks (female) prior to mating.

Use In Specific Populations

Pregnancy

Risk Summary

Clinical administration of cyclosporine ophthalmic emulsion 0.05% is not detected systemically following topical ocular administration [see CLINICAL PHARMACOLOGY], and maternal use is not expected to result in fetal exposure to the drug. Oral administration of cyclosporine to pregnant rats or rabbits did not produce teratogenicity at clinically relevant doses [see Data].

Data

Animal Data

At maternally toxic doses (30 mg/kg/day in rats and 100 mg/kg/day in rabbits), cyclosporine oral solution (USP) was teratogenic as indicated by increased pre- and postnatal mortality, reduced fetal weight and skeletal retardations. These doses (normalized to body surface area) are 5,000 and 32,000 times greater, respectively, than the daily recommended human dose of one drop (approximately 28 mcL) of cyclosporine ophthalmic emulsion 0.05% twice daily into each eye of a 60 kg person (0.001 mg/kg/day), assuming that the entire dose is absorbed. No evidence of embryofetal toxicity was observed in rats or rabbits receiving cyclosporine during organogenesis at oral doses up to 17 mg/kg/day or 30 mg/kg/day, respectively. These doses in rats and rabbits are approximately 3,000 and 10,000 times greater, respectively, than the daily recommended human dose.

An oral dose of 45 mg/kg/day cyclosporine administered to rats from Day 15 of pregnancy until Day 21 postpartum produced maternal toxicity and an increase in postnatal mortality in offspring. This dose is 7,000 times greater than the daily recommended human dose. No adverse effects in dams or offspring were observed at oral doses up to 15 mg/kg/day (2,000 times greater than the daily recommended human dose).

Lactation

Risk Summary

Cyclosporine is known to appear in human milk following systemic administration, but its presence in human milk following topical treatment has not been investigated. Although blood concentrations are undetectable following topical administration of cyclosporine ophthalmic emulsion 0.05% [see CLINICAL PHARMACOLOGY], caution should be exercised when RESTASIS MULTIDOSE™ is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RESTASIS MULTIDOSE™ and any potential adverse effects on the breast-fed child from cyclosporine.

Pediatric Use

Safety and efficacy have not been established in pediatric patients below the age of 16.

Geriatric Use

No overall difference in safety or effectiveness has been observed between elderly and younger patients.

Overdose Information for Restasis

No information provided.

Contraindications for Restasis

RESTASIS® is contraindicated in patients with known or suspectedhypersensitivity to any of the ingredients in the formulation.

Clinical Pharmacology for Restasis

Mechanism Of Action

Cyclosporine is animmunosuppressive agent when administered systemically.

In patients whose tearproduction is presumed to be suppressed due to ocular inflammation associatedwith keratoconjunctivitis sicca, cyclosporine emulsion is thought to act as apartial immunomodulator. The exact mechanism of action is not known.

Pharmacokinetics

Blood cyclosporine A concentrations were measured using aspecific high pressure liquid chromatography-mass spectrometry assay. Bloodconcentrations of cyclosporine, in all the samples collected, after topicaladministration of RESTASIS® 0.05%, twice daily, in humans for up to 12 months,were below the quantitation limit of 0.1 ng/mL. There was no detectable drugaccumulation in blood during 12 months of treatment with RESTASIS® ophthalmicemulsion.

Clinical Studies

Four multicenter, randomized, adequate andwell-controlled clinical studies were performed in approximately 1,200 patientswith moderate to severe keratoconjunctivitis sicca. RESTASIS® demonstratedstatistically significant increases in Schirmer wetting of 10 mm versus vehicleat six months in patients whose tear production was presumed to be suppresseddue to ocular inflammation. This effect was seen in approximately 15% of RESTASIS®ophthalmic emulsion-treated patients versus approximately 5% of vehicle-treatedpatients. Increased tear production was not seen in patients currently takingtopical anti-inflammatory drugs or using punctal plugs.

No increase in bacterial or fungal ocular infections wasreported following administration of RESTASIS®.

Patient Information for Restasis

Handling The Container

Advise patients to not allow the tip of the vial to touchthe eye or any surface, as this may contaminate the emulsion. Advise patientsto not touch the vial tip to their eye to avoid the potential for injury to theeye [see WARNINGS AND PRECAUTIONS].

Use With Contact Lenses

RESTASIS® should not be administered while wearingcontact lenses. Patients with decreased tear production typically should notwear contact lenses. Advise patients that if contact lenses are worn, theyshould be removed prior to the administration of the emulsion. Lenses may be reinserted15 minutes following administration of RESTASIS® ophthalmic emulsion [see WARNINGSAND PRECAUTIONS].

Administration

Advise patients that the emulsion from one individualsingle-use vial is to be used immediately after opening for administration toone or both eyes, and the remaining contents should be discarded immediatelyafter administration.