Cyclosporine

Capsule, Liquid Filled · Oral, Ophthalmic

Prescription (Rx) Calcineurin Inhibitor Immunosuppressant 2 recalls

Uses

Cyclosporine ophthalmic emulsion, 0.05% is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs. Cyclosporine ophthalmic emulsion, 0.05% is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs. ( 1 )

Dosage and administration

Invert the unit dose vial a few times to obtain a uniform, white, opaque emulsion before using. Instill one drop of cyclosporine ophthalmic emulsion, 0.05% twice a day in each eye approximately 12 hours apart. Cyclosporine ophthalmic emulsion can be used concomitantly with lubricant eye drops, allowing a 15-minute interval between products. Discard vial immediately after use. Instill one drop of cyclosporine ophthalmic emulsion, 0.05% twice a day in each eye approximately 12 hours apart. ( 2 )

Dosage forms and strengths

Ophthalmic emulsion containing cyclosporine 0.5 mg/mL Cyclosporine ophthalmic emulsion 0.5 mg/mL ( 3 )

Contraindications

Cyclosporine ophthalmic emulsion is contraindicated in patients with known or suspected hypersensitivity to any of the ingredients in the formulation. Hypersensitivity ( 4 )

Warnings and precautions

To avoid the potential for eye injury and contamination, be careful not to touch the vial tip to your eye or other surfaces. ( 5.1 ) 5. 1 Potential for Eye Injury and Contamination Be careful not to touch the vial tip to your eye or other surfaces to avoid potential for eye injury and contamination. 5. 2 Use with Contact Lenses Cyclosporine ophthalmic emulsion 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 cyclosporine ophthalmic emulsion.

Side effects

The following serious adverse reactions are described elsewhere in the labeling: Potential for Eye Injury and Contamination [ see Warnings and Precautions ( 5.1 ) ] The most common adverse reaction following the use of -cyclosporine ophthalmic emulsion was ocular burning (17%). ( 6.1 ) To Report SUSPECTED ADVERSE REACTIONS, contact KVK-Tech, Inc. at 1-800-862-3895 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, the most common adverse reaction following the use of cyclosporine ophthalmic emulsion was ocular burning (17%). Other reactions reported in 1% to 5% of patients included conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbance (most often blurring). 6.2 Post-marketing Experience The following adverse reactions have been identified during post approval use of cyclosporine ophthalmic emulsion. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Reported reactions have included: hypersensitivity (including eye swelling, urticaria, rare cases of severe angioedema, face swelling, tongue swelling, pharyngeal edema, and dyspnea); and superficial injury of the eye (from the vial tip touching the eye during administration).

Use in specific populations

8.1 Pregnancy Risk Summary Clinical administration of cyclosporine ophthalmic emulsion 0.05% is not detected systemically following topical ocular administration [ see Clinical Pharmacology ( 12.3 ) ], 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). 8. 2 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 [see Clinical Pharmacology ( 12.3 )] , caution should be exercised when cyclosporine ophthalmic emulsion is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for cyclosporine ophthalmic emulsion and any potential adverse effects on the breast-fed child from cyclosporine. 8.4 Pediatric Use Safety and efficacy have not been established in pediatric patients below the age of 16. 8.5 Geriatric Use No overall difference in safety or effectiveness has been observed between elderly and younger patients.

Pregnancy

8.1 Pregnancy Risk Summary Clinical administration of cyclosporine ophthalmic emulsion 0.05% is not detected systemically following topical ocular administration [ see Clinical Pharmacology ( 12.3 ) ], 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).

Pediatric use

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

Geriatric use

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

Description

Cyclosporine ophthalmic emulsion, 0.05% contains a topical calcineurin inhibitor immunosuppressant with anti-inflammatory effects. Cyclosporine’s chemical name is Cyclo[[( E )-(2 S ,3 R ,4 R )-3-hydroxy-4-methyl-2-(methylamino)-6-octenoyl]-L-2-aminobutyryl- N -methylglycyl- N -methyl-L-leucyl-L-valyl- N -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 Formula: C 62 H 111 N 11 O 12 Mol. Wt.: 1202.6 Cyclosporine is a fine white powder. Cyclosporine ophthalmic emulsion 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 cyclosporine ophthalmic emulsion, 0.05% contains: Active: cyclosporine 0.05%. Inactives : glycerin; castor oil; polysorbate 80; carbomer copolymer type A; purified water; and sodium hydroxide to adjust pH. cyclosporine

Mechanism of action

12.1 Mechanism of Action Cyclosporine is an immunosuppressive agent when administered systemically. In patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca, cyclosporine emulsion is thought to act as a partial immunomodulator. The exact mechanism of action is not known.

How supplied

Cyclosporine ophthalmic emulsion, 0.05% is packaged in sterile, preservative-free single-use vials. Each vial contains 0.4 mL fill in a 0.9 mL LDPE vial; 30 or 60 vials are packaged in a polypropylene tray with an aluminum peelable lid. The entire contents of each tray (30 vials or 60 vials) must be dispensed intact. 30 Vials 0.4 mL each - NDC 10702-808-03 60 Vials 0.4 mL each - NDC 10702-808-06 Storage: Store at 15°-25°C (59°-77°F).

Patient information

Handling the Container Advise patients to not allow the tip of the vial to touch the eye or any surface, as this may contaminate the emulsion. Advise patients to not touch the vial tip to their eye to avoid the potential for injury to the eye [ see Warnings and Preca u tions ( 5.1 ) ]. Use with Contact Lens es Cyclosporine ophthalmic emulsion 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 cyclosporine ophthalmic emulsion [ see Warnings and Precautions ( 5.2 ) ]. Administration Advise patients that the emulsion from one individual single-use vial is to be used immediately after opening for administration to one or both eyes, and the remaining contents should be discarded immediately after administration. Distributed by: KVK-Tech, INC. Newtown, PA 18940 © 2024 AbbVie. All rights reserved. v2.0USPI10702AG

Label text from the FDA structured product label by KVK-TECH, INC. (revised Sep 23, 2024). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Cyclosporine NDC products (29)

NDCStrength & formLabelerType
68084-921Cyclosporine 100 mg/1
Capsule, Gelatin Coated		American Health PackagingANDA
68084-879Cyclosporine 25 mg/1
Capsule, Gelatin Coated		American Health PackagingANDA
60505-0134Cyclosporine 100 mg/1
Capsule, Gelatin Coated		Apotex Corp.ANDA
60505-0133Cyclosporine 25 mg/1
Capsule, Gelatin Coated		Apotex Corp.ANDA
59651-929Cyclosporine 100 mg/1
Capsule, Liquid Filled		Aurobindo Pharma LimitedANDA
59651-928Cyclosporine 50 mg/1
Capsule, Liquid Filled		Aurobindo Pharma LimitedANDA
59651-927Cyclosporine 25 mg/1
Capsule, Liquid Filled		Aurobindo Pharma LimitedANDA
69097-292Cyclosporine .5 mg/mL
Emulsion		Cipla USA Inc.ANDA
73043-005Cyclosporine .5 mg/mL
Emulsion		Devatis Inc.ANDA
75907-048Cyclosporine 100 mg/1
Capsule, Liquid Filled		Dr. Reddy's Laboratories IncANDA
75907-047Cyclosporine 25 mg/1
Capsule, Liquid Filled		Dr. Reddy's Laboratories IncANDA
23155-839Cyclosporine 100 mg/1
Capsule, Liquid Filled		Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
23155-838Cyclosporine 50 mg/1
Capsule, Liquid Filled		Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
23155-837Cyclosporine 25 mg/1
Capsule, Liquid Filled		Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.ANDA
0378-8760Cyclosporine .5 mg/mL
Emulsion		Mylan Pharmaceuticals Inc.ANDA
71656-012Cyclosporine .5 mg/mL
Emulsion		Saptalis Pharmaceuticals, LLCANDA
64380-129Cyclosporine 100 mg/1
Capsule, Liquid Filled		Strides Pharma Science LimitedANDA
64380-128Cyclosporine 50 mg/1
Capsule, Liquid Filled		Strides Pharma Science LimitedANDA
64380-127Cyclosporine 25 mg/1
Capsule, Liquid Filled		Strides Pharma Science LimitedANDA
0172-7313Cyclosporine 100 mg/mL
Solution		Teva Pharmaceuticals USA, Inc.ANDA
0093-9020Cyclosporine 100 mg/1
Capsule, Liquid Filled		Teva Pharmaceuticals USA, Inc.ANDA
0093-9019Cyclosporine 50 mg/1
Capsule, Liquid Filled		Teva Pharmaceuticals USA, Inc.ANDA
0093-9018Cyclosporine 25 mg/1
Capsule, Liquid Filled		Teva Pharmaceuticals USA, Inc.ANDA
0480-4076Cyclosporine .5 mg/mL
Emulsion		Teva Pharmaceuticals, Inc.ANDA
24979-126Cyclosporine .5 mg/mL
Emulsion		Upsher-Smith Laboratories, LLCANDA
17088-0362Cyclosporine 50 mg/mL
Injection		Novartis Pharma Stein AGDRUG FOR FURTHER PROCESSING
60505-6202Cyclosporine .5 mg/mL
Emulsion		Apotex CorpNDA AUTHORIZED GENERIC
10702-808Cyclosporine .5 mg/mL
Emulsion		KVK-TECH, INC.NDA AUTHORIZED GENERIC
68180-214Cyclosporine .5 mg/mL
Emulsion		Lupin Pharmaceuticals, Inc.NDA AUTHORIZED GENERIC

Cyclosporine recalls

Frequently asked questions

What is Cyclosporine used for?

Cyclosporine ophthalmic emulsion, 0.05% is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs. Cyclosporine ophthalmic emulsion, 0.05% is a calcineurin…

What are the side effects of Cyclosporine?

The following serious adverse reactions are described elsewhere in the labeling: Potential for Eye Injury and Contamination [ see Warnings and Precautions ( 5.1 ) ] The most common adverse reaction following the use of -cyclosporine ophthalmic emulsion was ocular burning (17%). ( 6.1 ) To Report SUSPECTED ADVERSE REACTIONS, contact KVK-Tech, Inc. at 1-800-862-3895 or FDA at 1-800-FDA-1088 or… See the full label for the complete list.

Who makes Cyclosporine?

Cyclosporine is listed by 17 labelers in the FDA NDC directory, including American Health Packaging, Apotex Corp., Aurobindo Pharma Limited, Cipla USA Inc..

Has Cyclosporine been recalled?

The FDA enforcement database lists 2 recalls for Cyclosporine, most recently D-0490-2017 (class ii): Failed Impurities/Degradations Specifications; out of specification results for Maximum Unknown Impurities and Total Impurities