Cyclosporine (Page 2 of 2)
12 CLINICAL PHARMACOLOGY
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.
12.3 Pharmacokinetics
Blood cyclosporine A concentrations were measured using a specific high pressure liquid chromatography-mass spectrometry assay. Blood concentrations of cyclosporine, in all the samples collected, after topical administration of cyclosporine ophthalmic emulsion 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 drug accumulation in blood during 12 months of treatment with cyclosporine ophthalmic emulsion.
13 NONCLINICAL TOXICOLOGY
13.1 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 0.05% cyclosporine ophthalmic emulsion 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 vitr o 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.
14 CLINICAL STUDIES
Four multicenter, randomized, adequate and well-controlled clinical studies were performed in approximately 1,200 patients with moderate to severe keratoconjunctivitis sicca. Cyclosporine ophthalmic emulsion 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-treated patients versus approximately 5% of vehicle-treated patients. Increased tear production was not seen in patients currently taking topical anti-inflammatory drugs or using punctal plugs.
No increase in bacterial or fungal ocular infections was reported following administration of cyclosporine ophthalmic emulsion.
16 HOW SUPPLIED/STORAGE AND HANDLING
Cyclosporine ophthalmic emulsion, 0.05% is packaged in sterile, preservative-free single-use vials. Each vial contains 0.4 mL fill in a 0.5 mL natural colored low density polyethylene vial; five vials are packaged in an aluminum pouch and six pouches are packaged in a carton. The entire contents of each carton (30 vials) must be dispensed intact. Cyclosporine ophthalmic emulsion is also provided in a 60 count carton that must be dispensed intact.
NDC 0378-8760-58
carton of 30 vials
NDC 0378-8760-91
carton of 60 vials
Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature.]
17 PATIENT COUNSELING 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 Precautions (5.1)]
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. 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.
Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.
Made in U.S.A.
JANUARY 2022
PRINCIPAL DISPLAY PANEL – 0.05%
NDC 0378-8760-58
CycloSPORINE
Ophthalmic Emulsion
0.05%
FOR USE IN THE EYES
Sterile, Preservative-Free
Rx only 30 Single-Use Vials (0.4 mL Each)
Each mL contains:
Active: Cyclosporine, USP 0.05%
Inactives: anhydrous glycerin, carbomer copolymer type
A, castor oil, polysorbate 80, water for injection, and
sodium hydroxide to adjust pH.
Usual Dosage: Twice daily approximately 12 hours apart.
Invert the vial before using. Use immediately after
opening and then discard. See accompanying prescribing
information.
Keep this and all medication out of the reach of
children.
Store at 20° to 25°C (68° to 77°F). [See USP Controlled
Room Temperature.] Store vials in the carton until use.
The entire contents of the carton (30 vials) must be
dispensed intact.
Manufactured for:
Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.
Made in U.S.A.
PRINCIPAL DISPLAY PANEL – 0.05%
NDC 0378-8760-91
CycloSPORINE
Ophthalmic Emulsion
0.05%
FOR USE IN THE EYES
Sterile, Preservative-Free
Rx only 60 Single-Use Vials (0.4 mL Each)
Each mL contains:
Active: Cyclosporine, USP 0.05%
Inactives: anhydrous glycerin, carbomer copolymer type
A, castor oil, polysorbate 80, water for injection, and
sodium hydroxide to adjust pH.
Usual Dosage: Twice daily approximately 12 hours apart.
Invert the vial before using. Use immediately after
opening and then discard. See accompanying prescribing
information.
Keep this and all medication out of the reach of
children.
Store at 20° to 25°C (68° to 77°F). [See USP Controlled
Room Temperature.] Store vials in the carton until use.
The entire contents of the carton (60 vials) must be
dispensed intact.
Manufactured for:
Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A.
Made in U.S.A.
| CYCLOSPORINE cyclosporine emulsion | |||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||
| Labeler — Mylan Pharmaceuticals Inc. (059295980) |
Revised: 01/2022 Mylan Pharmaceuticals Inc.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.