XIIDRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XIIDRA (XIIDRA).
Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist that binds to the I domain of LFA-1, blocking its interaction with intercellular adhesion molecule-1 (ICAM-1). This inhibits T-cell adhesion and migration, reducing inflammation in dry eye disease.
| Metabolism | Lifitegrast is not metabolized; it is eliminated primarily via renal excretion of unchanged drug. |
| Excretion | Primarily hepatic metabolism with biliary excretion; renal excretion accounts for <1% of unchanged drug. |
| Half-life | Terminal half-life is approximately 1.5 hours; supports twice-daily dosing for sustained ocular surface effects. |
| Protein binding | ~99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Not well characterized in systemic circulation; due to ocular administration, systemic Vd is not clinically relevant; estimated at 0.6 L/kg based on IV studies in animals. |
| Bioavailability | Ophthalmic: Low systemic bioavailability due to local administration (negligible systemic exposure). |
| Onset of Action | Ocular: Improvement in tear production observed as early as 2 weeks of twice-daily dosing. |
| Duration of Action | Duration of action supports twice-daily dosing; continued treatment required to maintain increased tear production. |
| Molecular Weight | 615.5 |
1 drop of 5% ophthalmic solution in each eye twice daily (approximately 12 hours apart).
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | No dose adjustment required for any Child-Pugh class. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; same as adult dosing. |
| 1st trimester | No adequate and well-controlled studies in pregnant women. Animal studies have not revealed fetal harm at doses >30 times the human exposure. Use only if potential benefit justifies risk. |
| 2nd trimester | Limited data; no evidence of teratogenicity in animal studies. Caution advised. |
| 3rd trimester | Limited data; consider risk-benefit. Avoid use near term if possible. |
Clinical note
Comprehensive clinical and safety monograph for XIIDRA (XIIDRA).
| Placental transfer | Based on molecular weight and animal data, minimal placental transfer is expected. No human data available. |
| Breastfeeding | Unknown if XIIDRA (lifitegrast) is excreted in human milk. Due to low systemic absorption (plasma concentrations <1 ng/mL), risk to infant likely negligible. However, caution is advised until more data available. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to lifitegrast or any component of the formulation
| Precautions | Instillations may cause transient blurred vision or eye irritation, Contains benzalkonium chloride; caution with contact lens use, Not for injection, Discontinue if hypersensitivity occurs |
| Food/Dietary | No known food-drug interactions specific to ophthalmic Xiidra. Systemic absorption is minimal; therefore, dietary restrictions are not required. |
| Clinical Pearls | Xiidra (lifitegrast) is a lymphocyte function-associated antigen-1 (LFA-1) antagonist indicated for treating dry eye disease. Administer one drop in each eye twice daily, approximately 12 hours apart. If using other topical ophthalmic medications, wait at least 5 minutes between instillations. Discontinue contact lens wear during treatment if lenses are not indicated for dry eye. Onset of effect may take several weeks; maximum benefit often seen after 12 weeks. Common side effects include dysgeusia (bad taste) and instillation site irritation. No dosage adjustment needed for hepatic or renal impairment. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Xiidra (lifitegrast) is classified as FDA Pregnancy Category B. Animal reproduction studies did not demonstrate fetal harm at doses up to 600 times the human ophthalmic dose. There are no adequate and well-controlled studies in pregnant women; however, systemic exposure is negligible due to low bioavailability (plasma concentrations below the limit of quantitation 0.5 ng/mL after topical ocular administration). Therefore, risk is considered minimal across all trimesters. |
| Fetal Monitoring | No specific maternal or fetal monitoring is required due to negligible systemic absorption. Standard prenatal care is sufficient. |
| Fertility Effects | In animal studies, lifitegrast did not impair fertility in male or female rats at oral doses up to 1000 mg/kg/day (approximately 4200 times the human ophthalmic dose). No human data on reproductive impact are available, but systemic exposure from topical use is minimal, suggesting no clinically significant effect on fertility. |
| Patient Advice | Use exactly as prescribed: one drop in each eye twice daily, about 12 hours apart. · Remove contact lenses before instilling and wait at least 15 minutes before reinserting. · Do not touch the dropper tip to any surface, including the eye, to avoid contamination. · Wait at least 5 minutes between Xiidra and other eye drops. · Temporary blurred vision or bad taste in the mouth may occur; if blurred vision persists, consult your doctor. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Store the bottle upright at room temperature (20°C–25°C) with the cap tightly closed. · Do not use if the solution changes color or becomes cloudy. · Report any eye pain, swelling, or vision changes to your healthcare provider promptly. |