RESTASIS MULTIDOSE
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RESTASIS MULTIDOSE (RESTASIS MULTIDOSE).
| Breastfeeding | Cyclosporine is excreted in human milk after systemic administration. However, topical ocular administration results in negligible systemic absorption (blood concentrations below 100 ng/mL). M/P ratio not established. Caution is advised; consider developmental and health benefits of breastfeeding along with mother's clinical need for Restasis. |
| 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. |
■ 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 component of the formulation.","Active ocular infections (bacterial, viral, fungal)."]
| 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."] |
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| 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. |