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. |
| Molecular Weight | 298.3 |
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 | Insufficient human data; animal studies show risk. Avoid use unless no alternative. |
| 2nd trimester | Insufficient human data; potential fetal harm. Use only if benefit justifies risk. |
| 3rd trimester | Insufficient human data; potential neonatal adverse effects. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for LITFULO (LITFULO).
| Placental transfer | Likely crosses placenta based on molecular weight and animal studies; specific human data not available. |
| Breastfeeding | It is unknown whether LITFULO is excreted in human milk. Due to potential serious adverse reactions in breastfeeding infants, advise patients not to breastfeed during treatment and for at least 2 weeks after last dose. |
■ 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 LITFULO or any excipientsCurrent or history of PEComa (tuberous sclerosis complex)
| 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) |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase drug levels. No other significant food interactions. |
Loading safety data…
| Lactation Rating |
| L5 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls |
| LITFULO (ritlecitinib) is a JAK3/TEC kinase inhibitor approved for alopecia areata. Monitor for infections, thrombosis, malignancy, and laboratory abnormalities (CBC, LFTs, lipids). Avoid live vaccines during treatment. Dose reduction may be needed in hepatic impairment. Not recommended with severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take LITFULO exactly as prescribed, with or without food. · Do not take if you have an active serious infection. · Report any signs of infection (fever, chills, cough), blood clots (leg pain, shortness of breath), or skin cancer (new lesions). · Avoid live vaccines while on LITFULO. · You may need regular blood tests to monitor cell counts and liver function. · Tell your doctor if you are pregnant, breastfeeding, or planning to become pregnant. |