LIFITEGRAST
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LIFITEGRAST (LIFITEGRAST).
Integrase inhibitor; inhibits the strand transfer step of HIV-1 integration by binding to the integrase active site and blocking the covalent integration of viral DNA into host chromosomal DNA.
| Metabolism | Primarily glucuronidation via UGT1A1 and UGT1A3; minor metabolism by CYP3A4. |
| Excretion | Primarily biliary/fecal elimination (approximately 80% of absorbed dose excreted in feces as parent drug and metabolites). Renal excretion accounts for less than 5% of the dose. |
| Half-life | Terminal elimination half-life of approximately 5.5 hours in healthy subjects; supports twice-daily dosing for sustained tear production. |
| Protein binding | Approximately 55% bound to human plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.75 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Low systemic bioavailability after ophthalmic administration (<5% of ocular dose) due to limited corneal penetration and rapid clearance from systemic circulation. |
| Onset of Action | Ocular (topical): Increased tear production observed within 2 weeks; maximum effect may require 6–12 weeks of continuous therapy. |
| Duration of Action | Duration of enhanced tear production persists as long as treatment continues; effect wanes over several days to weeks after discontinuation. |
25 mg orally twice daily, with or without food.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended for patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended for moderate or severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. No approved pediatric dosing. |
| Geriatric use | No specific dose adjustment recommended based on age alone. Geriatric patients may have age-related renal impairment; refer to renal adjustment guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LIFITEGRAST (LIFITEGRAST).
| Breastfeeding | No data on presence in human milk; excreted in rat milk at concentrations similar to plasma. M/P ratio unknown. Caution advised; consider developmental benefits of breastfeeding versus risk of infant exposure. |
| Teratogenic Risk | Lifitegrast is an integrin antagonist with no adequate and well-controlled studies in pregnant women. Animal studies show no teratogenicity at doses up to 20 mg/kg/day (rabbit) and 100 mg/kg/day (rat), with maternal toxicity at high doses. Risk cannot be ruled out; use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with dofetilide or other drugs that inhibit UGT1A1","Severe hepatic impairment (Child-Pugh Class C)","Coadministration with rifampin, carbamazepine, phenytoin, phenobarbital, St. John's wort"]
| Precautions | ["Post-treatment exacerbations of HBV in HIV/HBV coinfected patients who discontinue bictegravir/emtricitabine/tenofovir alafenamide (if liftegrast is part of such a combo)","Risk of immune reconstitution syndrome","Decreased renal function (if used with tenofovir alafenamide; monitor serum creatinine and urine glucose)"] |
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| Fetal Monitoring |
| No specific monitoring required beyond standard prenatal care. Monitor for ocular adverse effects if systemic absorption occurs (rare). |
| Fertility Effects | No human data on fertility; animal studies (rat) at doses up to 50 mg/kg/day showed no impairment of fertility. Theoretical risk due to integrin antagonism but no evidence in clinical use. |