RESTASIS MULTIDOSE
Clinical safety rating
cautionComprehensive clinical and safety monograph for RESTASIS MULTIDOSE (RESTASIS MULTIDOSE).
Cyclosporine A is a calcineurin inhibitor immunosuppressant. It binds to cyclophilin, forming a complex that inhibits calcineurin, thereby blocking dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T-cells). This reduces transcription of pro-inflammatory cytokines (e.g., IL-2) and T-cell activation, decreasing ocular surface inflammation.
| Metabolism | Primarily hepatic via CYP3A4 isoenzyme; cyclosporine is extensively metabolized with minimal renal excretion of parent drug. |
| Excretion | Primarily biliary/fecal: ~85% of absorbed dose excreted in feces. Renal excretion minimal (<5%) as unchanged drug or metabolites. |
| Half-life | Terminal half-life approximately 24 hours (range 18–36 h) following ocular administration, reflecting slow elimination from ocular tissues and systemic circulation. |
| Protein binding | Approximately 90% bound to plasma proteins (primarily albumin and lipoproteins). |
| Volume of Distribution | Volume of distribution not well defined after ocular use; systemically, Vd is low (<2 L/kg) indicating limited tissue distribution due to high protein binding. |
| Bioavailability | Ocular: systemic bioavailability <0.5% of instilled dose; negligible due to low corneal penetration and rapid clearance. |
| Onset of Action | Clinical effect (increased tear production) observed after 4–8 weeks of twice-daily dosing; peak effect by 3–6 months. |
| Duration of Action | Duration of action supports twice-daily dosing; reduction in tear production returns if therapy discontinued; sustained effect with continuous use. |
| Molecular Weight | 1202.61 |
One drop in each eye twice daily, approximately 12 hours apart. Administered as an ophthalmic emulsion.
| Dosage form | EMULSION |
| Renal impairment | No dose adjustment required for renal impairment. Drug undergoes minimal systemic absorption. |
| Liver impairment | No dose adjustment required for hepatic impairment. Not metabolized hepatically to a significant extent. |
| Pediatric use | Safety and efficacy not established in pediatric patients; off-label use may consider adult dosing if indicated, but supported data are limited. |
| Geriatric use | Elderly patients may use the same dosing as adults; no specific geriatric dose adjustment is required. |
| 1st trimester | Cyclosporine crosses the placenta. Use only if potential benefit justifies risk; no well-controlled studies, but animal studies show embryotoxicity at high doses. |
| 2nd trimester | Use only if clearly needed; limited human data, but no increase in major malformations reported in small studies. |
| 3rd trimester | May cause neonatal immunosuppression, hyperkalemia, or renal dysfunction; monitor infant. Use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for RESTASIS MULTIDOSE (RESTASIS MULTIDOSE).
| Placental transfer | Cyclosporine crosses the placenta; fetal blood concentrations are about 30-50% of maternal levels. |
| Breastfeeding | Cyclosporine is excreted into breast milk in low concentrations. Breastfeeding is generally not recommended due to potential for immunosuppression and adverse effects in the nursing infant, though some sources consider use compatible if maternal levels are low. Monitor infant for infections, jaundice, or renal function changes. |
| Lactation Rating | L4 (Probably Hazardous) or 'Avoid' per most sources |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, cyclosporine (0.2-2 times the human topical ocular dose) caused embryotoxic and fetotoxic effects (increased pre- and postnatal mortality, reduced fetal weight) at maternal toxic doses. No adequate studies in pregnant women. Risk cannot be ruled out in first, second, or third trimester; use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | No specific maternal or fetal monitoring required due to minimal systemic absorption. However, monitor for signs of ocular adverse effects (e.g., eye pain, visual changes) and systemic immunosuppression (rare). If used in pregnancy, assess fetal growth and well-being per routine obstetrical care. |
| Fertility Effects | No human data on fertility impairment. Animal studies: cyclosporine at oral doses ≥ 12 mg/kg/day (approximately 200 times the human topical ocular dose) caused transient reduction in sperm motility and pregnancy rates in rats. Relevance to topical ocular use unknown. |
■ FDA Black Box Warning
None. Restasis Multidose does not carry a black box warning; however, cyclosporine systemic formulations have warnings for increased risk of infection, lymphomas, and hypertension.
| Common Effects | Dryness in mouth Constipation Lightheadedness Drowsiness |
| Serious Effects |
Hypersensitivity to cyclosporine or any excipientConcurrent use with PUVA or UVB therapy (due to increased risk of skin cancer)Concurrent use with other immunosuppressants (except corticosteroids) unless specifically indicated
| Precautions | Ocular infections should be resolved before initiating therapy., May cause ocular burning, stinging, or discomfort; transient blurred vision., Use with caution in patients with active herpes keratitis or other infections., Long-term safety in patients with history of ocular herpes is not established., Contains microemulsion vehicle; contact lens wearers should remove lenses prior to application and wait 15 minutes before reinsertion. |
| Food/Dietary | No known food interactions with topical ophthalmic cyclosporine. Grapefruit juice may increase systemic levels, but systemic absorption is minimal with eye drops. |
| Clinical Pearls | Restasis Multidose contains cyclosporine 0.05% ophthalmic emulsion. Shake well before each use. Tear function may improve after 3-6 months of continuous use. Do not administer while wearing contact lenses; remove lenses before instillation and wait 15 minutes before reinserting. May cause temporary blurred vision. If used with other ophthalmic drops, separate by at least 15 minutes. |
| Patient Advice | Shake the bottle vigorously for 15 seconds before each use. · Remove contact lenses before applying and wait 15 minutes before reinserting. · Tilt head back, pull down lower eyelid, and instill one drop in each eye twice daily, about 12 hours apart. · Do not touch the tip of the bottle to your eye or any surface to avoid contamination. · Temporary blurring or stinging may occur; do not perform other tasks until vision clears. · Store upright at room temperature, 15-25°C (59-77°F). Do not freeze. · Do not use if the emulsion looks separated or if the bottle is damaged. · Report any signs of eye infection, pain, redness, or vision changes to your doctor. · It may take several weeks to months to feel the full benefit; consistent use is important. · Avoid sharing the bottle with others. |
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