RESTASIS
Clinical safety rating
cautionComprehensive clinical and safety monograph for RESTASIS (RESTASIS).
Calcineurin phosphatase inhibitor; inhibits T-cell activation and inflammatory cytokine production by blocking dephosphorylation of nuclear factor of activated T-cells (NFAT).
| Metabolism | Primarily hepatic via CYP3A4. Major metabolites are inactive. Elimination half-life: ~8.6 hours (systemic). |
| Excretion | Primarily fecal elimination (approximately 94% of the dose), with less than 1% excreted unchanged in urine. Renal elimination is a minor pathway. |
| Half-life | Terminal elimination half-life is approximately 24 hours, supporting once-daily dosing in clinical use for chronic dry eye disease. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin and lipoproteins. |
| Volume of Distribution | Volume of distribution is approximately 2.5 L/kg, indicating extensive tissue distribution beyond total body water. |
| Bioavailability | After topical ophthalmic administration, systemic bioavailability is less than 0.1% (essentially negligible) due to low corneal permeability and rapid local clearance. |
| Onset of Action | Clinical effect (improvement in Schirmer test and ocular surface staining) begins after 4–6 weeks of twice-daily ophthalmic administration. |
| Duration of Action | Duration of action is approximately 12 hours after topical ophthalmic dosing, allowing twice-daily administration. Continuous use is required to maintain efficacy. |
| Molecular Weight | 33.3 |
One drop of 0.05% ophthalmic emulsion in each eye twice daily (approximately 12 hours apart).
| Dosage form | EMULSION |
| Renal impairment | No clinically significant renal excretion; dose adjustment not required for renal impairment. |
| Liver impairment | No hepatic metabolism; dose adjustment not required for hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients below 16 years have not been established. |
| Geriatric use | No specific dose adjustment; use same as younger adults. Caution with concomitant dry eye therapies. |
| 1st trimester | Insufficient data in pregnant women; animal studies show no evidence of fetal harm at relevant doses. Use only if potential benefit justifies potential risk. |
| 2nd trimester | Same as T1; no known teratogenic effects in animal studies, but human data lacking. |
| 3rd trimester | Same as T1; minimal systemic absorption minimizes fetal exposure. |
Clinical note
Comprehensive clinical and safety monograph for RESTASIS (RESTASIS).
| Placental transfer | Placental transfer is negligible due to low systemic absorption after topical ocular administration. |
| Breastfeeding | Transfer into breast milk is negligible due to low systemic absorption (<0.1 ng/mL) after ocular application. Considered compatible with breastfeeding. |
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | Category C. No adequate studies in pregnant women. In animal studies, cyclosporine (active ingredient) was embryotoxic and fetotoxic at doses toxic to dams. No evidence of teratogenicity in rats or rabbits. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | Monitor for systemic effects of cyclosporine (e.g., nephrotoxicity, hypertension) if used extensively. Baseline and periodic blood pressure, renal function, and serum cyclosporine levels if systemic absorption suspected. |
| Fertility Effects | No specific studies on fertility with ophthalmic cyclosporine. In animal studies, no impairment of fertility was observed at oral doses up to 30 mg/kg/day. Clinical relevance unknown. |
■ FDA Black Box Warning
None.
| Common Effects | Blurred vision Burning sensation in eye Headache High blood pressure Renal dysfunction Tremors Increased glucose level in blood Paresthesia tingling or pricking sensation Acne Decreased white blood cell count Increased levels of blood fat Decreased appetite Increased uric acid level in blood Electrolyte imbalance Convulsion Flushing sense of warmth in the face ears neck and trunk Gastrointestinal disturbance Gingival hyperplasia Stomach ulcer Abnormal liver function Excessive hair growth on face Hypertrichosis excessive hair growth Muscle cramp Muscle pain Fever Fatigue |
| Serious Effects |
Hypersensitivity to cyclosporine or any component of the formulationActive ocular infectionsPrior herpes simplex keratitis
| Precautions | May cause nephrotoxicity and hypertension if significant systemic absorption occurs (rare with ophthalmic use). Ocular infections (e.g., herpes simplex) should be treated prior to therapy. Avoid with concurrent ocular surgery. May cause hypersensitivity reactions including anaphylaxis (rare). Monitor for development of lymphoproliferative disorders and skin malignancies (theoretical risk with systemic absorption). |
| Food/Dietary | No specific food interactions documented for ophthalmic cyclosporine. Systemic absorption is minimal. |
| Clinical Pearls | Restasis (cyclosporine ophthalmic emulsion) 0.05% is an immunomodulator used for dry eye disease. It requires at least 3-6 months for maximal effect; do not expect immediate relief. Warn patients about transient stinging or burning upon instillation. Contact lenses should be removed before application and may be reinserted after 15 minutes. Restasis does not contain preservatives; each single-use vial should be discarded immediately after use. It is pregnancy category C. |
| Patient Advice | Restasis may take up to 6 months to show full benefit for dry eye symptoms. · Apply one drop in each eye twice daily, about 12 hours apart. · Remove contact lenses before using and wait 15 minutes before reinserting. · Do not touch the tip of the vial to your eye or any surface. · Use each single-use vial immediately after opening; discard any unused portion. · You may experience temporary burning or stinging upon application. |
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