LITFULO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LITFULO (LITFULO).
Litfulo (ritlecitinib) is a Janus kinase (JAK) inhibitor that selectively inhibits JAK3 and to a lesser extent TEC family kinases, thereby modulating the signaling pathways involved in the immune response.
| Metabolism | Litfulo is primarily metabolized by CYP3A4. |
| Excretion | Primarily excreted unchanged in feces (≈66%) via biliary secretion, with renal excretion accounting for ≈23% as unchanged drug and metabolites; <1% excreted in urine as unchanged parent compound. |
| Half-life | Terminal elimination half-life is approximately 50 hours (range 40–60 h), supporting once-daily or twice-daily dosing with steady-state achieved within 10–14 days. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 0.6 L/kg, indicating extensive distribution into total body water and tissues. |
| Bioavailability | Oral bioavailability is approximately 40–50% (range 35–60%); absorption is enhanced (≈1.5-fold) when taken with a high-fat meal. |
| Onset of Action | Oral: Onset of clinical effect (reduction in pruritus) observed within 2 weeks; maximal efficacy for skin clearance seen after 8–12 weeks of continuous dosing. |
| Duration of Action | Duration of therapeutic effect persists for the dosing interval (12–24 hours) with continuous drug exposure; after discontinuation, effects wane over 2–3 weeks. |
50 mg orally once daily, with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not studied in severe renal impairment (eGFR <30 mL/min) or ESRD. |
| Liver impairment | Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C). No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies included limited numbers of patients ≥65 years; no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LITFULO (LITFULO).
| Breastfeeding | No data available on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants from JAK inhibitors, advise women not to breastfeed during treatment and for at least 4 to 6 weeks after the last dose. |
| Teratogenic Risk | LITFULO (ritlecitinib) is a JAK inhibitor. In animal studies, maternal toxicity and fetal adverse effects including reduced fetal weight and skeletal variations were observed at exposures below the clinical dose. There are no adequate human studies. By trimester: First trimester: Potential risk of miscarriage and congenital anomalies; avoid use. Second and third trimesters: Risk of fetal myelosuppression, immunosuppression, and growth impairment. Considered contraindicated in pregnancy. |
■ FDA Black Box Warning
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS. See full prescribing information for complete boxed warning.
| Serious Effects |
["Hypersensitivity to ritlecitinib or any excipients"]
| Precautions | ["Serious infections","Mortality","Malignancies including lymphoma","Major adverse cardiovascular events","Thrombosis","Gastrointestinal perforations","Laboratory abnormalities (e.g., neutropenia, lymphopenia, elevated liver enzymes, elevated lipids)"] |
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| Fetal Monitoring | Monitor complete blood count (CBC) and liver function tests (LFTs) monthly during pregnancy if exposure occurs. Screen for infections, particularly herpes zoster, tuberculosis, and hepatitis B/C reactivation. Fetal ultrasound monitoring for growth restriction if used in second/third trimester. |
| Fertility Effects | Based on animal studies, LITFULO may impair female fertility (e.g., prolonged estrous cycles, reduced fertility indices). Effects on male fertility were not observed in animals. Human data are lacking; advise women of childbearing potential to use effective contraception during treatment and for at least 4 weeks after last dose. |