About This Medication
11 DESCRIPTION LITFULO (ritlecitinib) capsules are formulated with ritlecitinib tosylate, a kinase inhibitor. Ritlecitinib tosylate is a white to off white to pale pink solid which is freely soluble in water. The chemical name is 1-{(2S,5R)-2-Methyl-5-[(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}prop-2-en-1-one 4 methylbenzene-1-sulfonic acid. The molecular formula for ritlecitinib tosylate is C 22 H 27 N 5 O 4 S. The molecular weight is 457.55 g/mol and its structural formula is: LITFULO is supplied for oral administration as a 50 mg immediate-release capsule. Each capsule contains 50 mg ritlecitinib (equivalent to 80.13 mg ritlecitinib tosylate) and the following inactive ingredients: crospovidone, glyceryl dibehenate, lactose monohydrate, microcrystalline cellulose, and hypromellose (HPMC) capsule shells. The yellow/blue, opaque capsule shells contain Brilliant blue FCF – FD&C Blue, hypromellose, titanium dioxide, and yellow iron oxide. Chemical Structure
유효 성분
| 성분 |
함량 |
| Ritlecitinib Tosylate |
- |
적응증 및 용법
1 INDICATIONS AND USAGE LITFULO is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older. Limitations of Use : Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants. LITFULO is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older. ( 1 ) Limitations of Use : Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants ( 1 ).
작용 원리
12.1 Mechanism of Action LITFULO is a kinase inhibitor. Ritlecitinib irreversibly inhibits Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family by blocking the adenosine triphosphate (ATP) binding site. In cellular settings, ritlecitinib inhibits cytokine induced STAT phosphorylation mediated by JAK3-dependent receptors. Additionally, ritlecitinib inhibits signaling of immune receptors dependent on TEC kinase family members. The relevance of inhibition of specific JAK or TEC family enzymes to therapeutic effectiveness is not currently known.
용량 및 투여 방법
2 DOSAGE AND ADMINISTRATION • For recommended testing, evaluations and immunizations prior to LITFULO initiation, see Full Prescribing Information. ( 2.1 ) • Recommended dosage is 50 mg orally once daily. ( 2.2 ) • For dosage interruption for certain adverse reactions, see Full Prescribing Information. ( 2.4 ) 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation Perform the following evaluations prior to LITFULO initiation: • Tuberculosis (TB) infection evaluation: LITFULO initiation is not recommended in patients with active TB. For patients with latent TB or those with a negative latent TB test who are at high risk for TB, start preventive therapy for latent TB prior to initiation of LITFULO [see Warnings and Precautions (5.1) ] . • Viral hepatitis screening in accordance with clinical guidelines: LITFULO initiation is not recommended in patients with hepatitis B or hepatitis C [see Warnings and Precautions (5.1) ] . • Treatment with LITFULO should not be initiated in patients with an absolute lymphocyte count (ALC) <500/mm 3 or a platelet count <100,000/mm 3 [see Warnings and Precautions (5.7) ] . • Update immunizations according to current immunization guidelines [see Warnings and Precautions (5.8) ] . 2.2 Recommended Dosage The recommended dosage of LITFULO is 50 mg orally once daily with or without food [see Clinical Pharmacology (12.3) ] . Swallow capsules whole. Do not crush, split, or chew LITFULO capsules. If a dose is missed, administer the dose as soon as possible unless it is less than 8 hours before the next dose, in which case, skip the missed dose. Thereafter, resume dosing at the regular scheduled time. 2.3 Patients with Severe Hepatic Impairment LITFULO is not recommended in patients with severe (Child Pugh C) hepatic impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . 2.4 Treatment Interruption or Discontinuation If treatment interruption is indicated, a temporary treatment interruption for less than 6 weeks is not expected to result in significant loss of regrown scalp hair. Hematologic Abnormalities Recommendations for LITFULO treatment interruption or discontinuation for hematologic abnormalities are summarized in Table 1. Table 1. Laboratory Monitoring Guidance Laboratory Measure Recommendation ALC = absolute lymphocyte count. Platelet Count Treatment should be discontinued if platelet count is <50,000/mm 3 Lymphocytes Treatment should be interrupted if ALC is <500/mm 3 and may be restarted once ALC return above this value. ALC and platelet counts are recommended before treatment initiation and at 4 weeks after treatment initiation, and thereafter according to routine patient management [see Warnings and Precautions (5.7) ] .
Side Effects Overview
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Serious Infections [see Warnings and Precautions (5.1) ] • Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions (5.3) ] • Thromboembolic Events [see Warnings and Precautions (5.5) ] • Hypersensitivity [see Warnings and Precautions (5.6) ] • Laboratory Abnormalities [see Warnings and Precautions (5.7) ] Most common adverse reactions (incidence ≥1%) are headache, diarrhea, acne, rash, urticaria, folliculitis, pyrexia, atopic dermatitis, dizziness, blood creatine phosphokinase increased, herpes zoster, red blood cell count decreased, and stomatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of LITFULO was evaluated in three randomized, placebo-controlled clinical trials and one long-term trial in subjects with alopecia areata, including alopecia totalis and alopecia universalis, who were 12 years of age and older. A total of 1628 subjects were treated with LITFULO representing 2085 subject-years of exposure. There were 1011 subjects with at least 1 year of exposure to LITFULO. In the placebo-controlled period of clinical trials in alopecia areata, a total of 668 subjects were exposed to LITFULO with 130 receiving 50 mg once daily for up to 24 weeks. The median age of subjects was 33 years, 105 (11.9%) subjects were 12 to <18 years old and 22 (2.5%) subjects were 65 years of age or older. The majority of subjects were White (70.7%) and female (63.6%). Adverse reactions occurring at ≥1% in the treated groups and at a higher rate than placebo are presented in Table 2. A total of 2 (1.5%) subjects treated with LITFULO 50 mg were discontinued from the trials due to adverse reactions. Table 2. Adverse Reactions in Clinical Trials of LITFULO for the Treatment of Alopecia Areata Reported in ≥1% of subjects and at a higher rate than placebo for up to 24 weeks. LITFULO 50 mg N=130 n (%) Placebo N=213 n (%) Headache Headache includes headache and migraine. 14 (10.8) 18 (8.5) Diarrhea Diarrhea includes diarrhea and frequent bowel movements. 13 (10.0) 8 (3.8) Acne Acne includes acne and acne pustular. 8 (6.2) 10 (4.7) Rash Rash includes rash and dermatitis allergic. 7 (5.4) 2 (0.9) Urticaria 6 (4.6) 3 (1.4) Folliculitis 4 (3.1) 4 (1.9) Pyrexia 4 (3.1) 0 Dermatitis atopic 3 (2.3) 1 (0.5) Dizziness 3 (2.3) 3 (1.4) Blood creatine phosphokinase increased 2 (1.5) 0 Herpes zoster 2 (1.5) 0 Red blood cell count decreased 2 (1.5) 0 Stomatitis 2 (1.5) 0 Specific Adverse Reactions Exposure adjusted incidence rates were adjusted by clinical trial size for all adverse reactions reported in this section. Overall Infections In the placebo-controlled trials, for up to 24 weeks, overall infections were reported in 66 subjects (80.35 per 100 subject-years) treated with placebo and 43 subjects (74.53 per 100 subject-years) treated with LITFULO 50 mg. Across clinical trials, including the long-term trial, overall infections were reported in 645 subjects (50.71 per 100 subject-years) treated with LITFULO 50 mg or higher. Serious Infections In the placebo-controlled trials, for up to 24 weeks, 3 subjects reported serious infections across all ritlecitinib doses studied. Across clinical trials, including the long-term trial, serious infections were reported in 12 subjects (0.66 per 100 subject-years) treated with LITFULO 50 mg or higher. The most common serious infections were related to appendicitis, COVID-19 infection (including pneumonia), and sepsis. Herpes Zoster In the placebo-controlled trials, for up to 24 weeks, herpes zoster was reported in 4 subjects across all ritlecitinib doses studied and 0 subjects treated with placebo. Across clinical trials, including the long-term trial, herpes zoster was reported in 21 subjects (1.17 per 100 subject-years) treated with LITFULO 50 mg or higher. Opportunistic infections of multi-dermatomal herpes zoster were reported in 1 subject (0.50 per 100 subject-years) treated with the ritlecitinib higher dose in the placebo-controlled trials and 2 subjects (0.1 per 100 subject-years) treated with LITFULO 50 mg or higher in all clinical trials. Malignancy In the placebo-controlled trials, for up to 24 weeks, 1 malignancy (breast cancer) was reported in 1 subject (1.33 per 100 subject-years) treated with ritlecitinib higher dose and no malignancy was reported in subjects treated with placebo. Across clinical trials, including the long-term trial, malignancies excluding NMSC were reported in 7 subjects (0.37 per 100 subject-years) treated with LITFULO 50 mg or higher. Thromboembolic Events Across clinical trials, including the long-term trial, pulmonary embolism (PE) was reported in 1 subject (0.06 per 100 subject-years) treated with LITFULO. There was 1 report of retinal artery occlusion and 1 report of acute myocardial infarction. Urticaria In the placebo-controlled trials, for up to 24 weeks, urticaria was reported in 28 subjects treated in all ritlecitinib doses studied and 3 subjects treated with placebo. The rate of urticaria was 8.23 per 100 subject-years in subjects treated with ritlecitinib 50 mg and 4.03 per 100 subject-years in subjects treated with placebo. Across clinical trials, including the long-term trial, urticaria was reported in 76 subjects treated with LITFULO 50 mg or higher. Among all subjects treated with ritlecitinib 50 mg or higher in the integrated safety analysis, the rate of urticaria was 4.10 per 100 subject-years. The median time to onset of an initial event was 8 weeks; median duration of urticaria was 7 days. Most of the cases were mild to moderate in severity. Decreased Lymphocyte Counts Across clinical trials, including the long-term trial confirmed ALC <500/mm 3 occurred in 1 subject (<0.1%) treated with LITFULO 50 mg. Age appeared to be a risk factor for lower ALC in subjects ≥65 years of age. Decreased Platelet Count In the placebo-controlled trials, for up to 24 weeks, treatment with LITFULO was associated with a decrease in platelet count. Maximum effects on platelets were observed within 4 weeks, after which platelet count remained stable at a lower level with continued therapy. Across clinical trials, including the long-term trial, 1 subject (<0.1%) had a confirmed platelet count <100,000/mm 3 . No subject had a confirmed platelet count <75,000/mm 3 . Creatine Phosphokinase (CPK) Elevations In the placebo-controlled trials, for up to 24 weeks, events of blood CPK increased were reported in 2 (1.5%) subjects treated with LITFULO 50 mg and 0 subjects treated with placebo. Liver Enzyme Elevations In the placebo-controlled trials, for up to 24 weeks, events of increases in liver enzymes ≥3 times the upper limit of normal (ULN) were observed in subjects treated with LITFULO [see Warnings and Precautions (5.7) ] .
경고 및 주의 사항
5 WARNINGS AND PRECAUTIONS • Hypersensitivity: Discontinue LITFULO if a clinically significant hypersensitivity reaction occurs. ( 5.6 ) • Laboratory Abnormalities: Perform ALC and platelet counts prior to LITFULO initiation. Treatment interruption or discontinuation are recommended based on ALC and platelet count abnormalities. ( 5.7 ) • Vaccinations: Avoid use of live vaccines during or shortly prior to LITFULO treatment. ( 5.8 ) 5.1 Serious Infections Serious infections have been reported in patients receiving LITFULO. The most frequent serious infections have been appendicitis, COVID-19 infection (including pneumonia), and sepsis [see Adverse Reactions (6.1) ] . Among opportunistic infections, multi-dermatomal herpes zoster was reported with LITFULO. Avoid use of LITFULO in patients with an active, serious infection. Consider the risks and benefits of treatment prior to initiating LITFULO in patients: • with chronic or recurrent infection • who have been exposed to TB • with a history of serious infection or an opportunistic infection • who have resided or traveled in areas of endemic TB or mycoses, or • with underlying conditions that may predispose them to infection Closely monitor patients for the development of signs and symptoms of infection during and after treatment with LITFULO. Interrupt LITFULO if a patient develops a serious or opportunistic infection. A patient who develops a new infection during treatment with LITFULO should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient, appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored. LITFULO may be resumed once the infection is controlled. Tuberculosis Screen patients for tuberculosis (TB) before starting therapy. LITFULO should not be given to patients with active TB. Anti-TB therapy should be started prior to initiating therapy with LITFULO in patients with a new diagnosis of latent TB or previously untreated latent TB. In patients with a negative latent TB test, consider anti-TB therapy before initiating treatment with LITFULO in those at high risk and consider screening patients at high risk for TB during treatment with LITFULO. Viral Reactivation Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), was reported in clinical trials [see Adverse Reactions (6.1) ] . If a patient develops herpes zoster, consider interrupting treatment until the episode resolves. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy with LITFULO. Patients with evidence of HIV infection or hepatitis B or C infection were excluded from clinical trials. 5.2 Mortality In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with LITFULO. 5.3 Malignancy and Lymphoproliferative Disorders Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical trials of LITFULO [see Adverse Reactions (6.1) ] . In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this study, current or past smokers had an additional increased risk of overall malignancies. The risks and benefits of ritlecitinib treatment should be considered prior to initiating or continuing therapy in patients with a known malignancy other than a successfully treated NMSC or cervical cancer. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. 5.4 Major Adverse Cardiovascular Events (MACE) In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with LITFULO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. Discontinue LITFULO in patients that have experienced a myocardial infarction or stroke. 5.5 Thromboembolic Events An event of pulmonary embolism (PE) was reported in a patient receiving LITFULO [see Adverse Reactions (6.1) ] . In a ritlecitinib higher dosing group, 1 patient reported an event of retinal artery occlusion. In a large, randomized, postmarketing safety study of another JAK inhibitor in RA patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers. Avoid LITFULO in patients who may be at increased risk of thrombosis. If symptoms of thrombosis or embolism occur, patients should interrupt LITFULO and be evaluated promptly and treated appropriately. 5.6 Hypersensitivity Serious reactions including anaphylactic reactions, urticaria and rash have been observed in patients receiving LITFULO in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue LITFULO and institute appropriate therapy [see Adverse Reactions (6.1) ] . 5.7 Laboratory Abnormalities Treatment with LITFULO was associated with decreases in lymphocytes and platelets [see Adverse Reactions (6.1) ] . Prior to LITFULO initiation, perform ALC and platelet counts [see Dosage and Administration (2.1) ] . After initiating treatment with LITFULO, treatment interruption or discontinuation are recommended based on ALC and platelet count abnormalities [see Dosage and Administration (2.4) ] . Liver Enzyme Elevations – Treatment with LITFULO was associated with increased incidence of liver enzyme elevation compared to placebo. Increases of ALT ≥5 times the upper limit of normal (ULN) and increases of AST ≥5 times the ULN were observed in patients in LITFULO clinical trials. Evaluate at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt LITFULO until this diagnosis is excluded. Creatine Phosphokinase (CPK) Elevations – Treatment with LITFULO was associated with increased incidence of CPK elevation compared to placebo. 5.8 Vaccinations No data are available on the response to vaccination in patients receiving LITFULO. Use of live attenuated vaccines should be avoided during or shortly prior to initiating treatment. Prior to initiating LITFULO, it is recommended that patients be brought up to date with all immunizations, including prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines.
금기
4 CONTRAINDICATIONS LITFULO is contraindicated in patients with known hypersensitivity to ritlecitinib or any of its excipients [see Warnings and Precautions (5.6) ] . LITFULO is contraindicated in patients with known hypersensitivity to ritlecitinib or any of its excipients. ( 4 )
약동학
12.3 Pharmacokinetics Ritlecitinib AUC 0-tau and C max increase in an approximately dose-proportional manner up to 200 mg. Steady state was reached approximately by Day 4. Absorption The ritlecitinib absolute oral bioavailability is approximately 64%. Ritlecitinib peak plasma concentrations were reached within 1 hour following an oral dose. Effect of Food Food does not have a clinically significant impact on the systemic exposures of ritlecitinib. The coadministration of a 100 mg ritlecitinib capsule with a high-fat meal reduced the ritlecitinib C max by ~32% and AUC inf was increased by 11%. In clinical trials, ritlecitinib was administered without regard to meals [see Dosage and Administration (2.2) ] . Distribution Approximately 14% of circulating ritlecitinib is bound to plasma proteins. Elimination The ritlecitinib mean terminal half-life ranges from 1.3 to 2.3 hours. Metabolism The metabolism of ritlecitinib is mediated by multiple pathways with no single route contributing to more than 25% of the total metabolism. These pathways include: • Glutathione S-transferase (GST): cytosolic GST A1/3, M1/3/5, P1, S1, T2, Z1 and microsomal GST 1/2/3 • CYP enzymes (CYP3A, CYP2C8, CYP1A2, and CYP2C9) Excretion Approximately 66% of radiolabeled ritlecitinib dose is excreted in the urine and 20% in the feces. Approximately 4% of the ritlecitinib dose is excreted unchanged drug in urine. Specific Populations No clinically relevant differences in the pharmacokinetics of ritlecitinib were observed based on age (12-73 years), body weight, gender, GST genotype, and race. Patients with Renal Impairment The AUC 24 observed in patients with severe renal impairment (eGFR <30 mL/min) was 55.2% higher compared with the AUC 24 in matched participants with normal renal functions. These differences are not considered clinically significant. Ritlecitinib has not been studied in patients with mild (eGFR 60 to <90 mL/min) or moderate (eGFR 30 to <60 mL/min) renal impairment, as a clinically relevant increase in ritlecitinib exposure is not expected in these patients. The eGFR and classification of renal function status of patients was done using the Modification of Diet in Renal Disease (MDRD) formula. Ritlecitinib has not been studied in patients with ESRD or in renal transplant recipients. Patients with Hepatic Impairment Patients with moderate (Child Pugh B) hepatic impairment had an 18.5% increase in ritlecitinib AUC 24 compared to patients with normal hepatic function. Ritlecitinib has not been studied in patients with mild (Child Pugh A) hepatic impairment, as a clinically relevant increase in ritlecitinib exposure is not expected in these patients. Ritlecitinib has not been studied in patients with severe (Child Pugh C) hepatic impairment and is not recommended for use in these patients [see Dosage and Administration (2.3) and Use In Specific Populations (8.6) ] . Drug Interaction Studies Clinical Studies Effect of other drugs on ritlecitinib The effect of coadministered drugs on the pharmacokinetics of ritlecitinib is presented in Table 5. Table 5. Change in Pharmacokinetics of Ritlecitinib in the Presence of Coadministered Drugs Coadministered Drugs Regimen of Coadministered Drug Dose of Ritlecitinib Ratio Ratios for C max and AUC inf compare coadministration of ritlecitinib with the drug versus administration of ritlecitinib alone. (90% Confidence Interval) C max AUC inf Strong CYP3A inhibitor: Itraconazole Drug interaction with CYP3A inhibitor is not clinically significant. 200 mg once daily × 5 days 30 mg 1.03 (0.83, 1.27) 1.15 (1.05, 1.27) Strong CYP enzyme inducer: Rifampin 600 mg once daily × 8 days 50 mg 0.75 (0.63, 0.89) 0.56 (0.52, 0.60) Effect of ritlecitinib on other drugs The effect of ritlecitinib on the pharmacokinetics of coadministered drugs is presented in Table 6. Table 6. Change in Pharmacokinetics of Coadministered Drugs in the Presence of Ritlecitinib Coadministered Drugs Dose Regimen of Ritlecitinib Ratio Ratios for C max and AUC inf compare coadministration of the drug with ritlecitinib versus administration of the drug alone. (90% Confidence Interval) C max AUC inf Oral contraceptive: Ethinyl estradiol (EE) and levonorgestrel (LN) Drug interactions with ritlecitinib for oral contraceptives, CYP2B6 substrates, CYP2C substrates, and substrates of OATP1B1, BCRP, OAT3, and OCT1 transporters are not clinically significant. 50 mg once daily × 11 days EE: 0.92 (0.84, 1.01) LN: 0.80 (0.73, 0.88) EE: 0.98 (0.91, 1.06) LN AUC last of levonorgestrel was reported in lieu of AUC inf because the terminal phase of levonorgestrel was not well characterized. : 0.88 (0.83, 0.93) Sensitive CYP3A substrate: Midazolam [see Drug Interactions (7.1) ] 200 mg once daily × 11 days Ritlecitinib dosage 4 times the approved recommended dosage. 1.81 (1.48, 2.21) 2.69 (2.16, 3.36) Sensitive CYP1A2 substrate: Caffeine [see Drug Interactions (7.1) ] 200 mg once daily × 9 days 1.10 (1.04, 1.16) 2.65 (2.34, 3.00) Sensitive CYP2B6 substrate: Efavirenz 200 mg once daily × 11 days 0.88 (0.77, 1.01) 1.00 AUC 0-72 of efavirenz was reported (0.95, 1.04) Sensitive CYP2C substrate: Tolbutamide 200 mg once daily × 10 days 1.03 (0.97, 1.10) 0.99 (0.92, 1.07) Sensitive OATP1B1, BCRP and OAT3 substrate: Rosuvastatin 200 mg once daily × 10 days 0.73 (0.63, 0.83) 0.87 (0.75, 1.01) Sensitive OCT1 substrate: Sumatriptan 400 mg single dose coadministration Ritlecitinib dosage 8 times the approved recommended dosage. 0.87 (0.73, 1.03) 1.30 (1.17, 1.44) 400 mg single dose 8 hours prior to Sumatriptan 1.50 (1.26, 1.78) 1.50 (1.35, 1.66) In Vitro Studies CYP Related Pathways: Ritlecitinib is not an inhibitor of CYP2D6. Other Metabolic Pathways: Ritlecitinib is not an inhibitor of uridine 5’ diphospho glucuronosyltransferases (UGTs) (UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7), GSTs or sulfotransferases (SULTs). Transporter Systems: Ritlecitinib is not an inhibitor of P-glycoprotein (P-gp) or bile salt export pump (BSEP).