Litfulo

Warnings and Precautions ( 5.7 ) 6/2026

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 ).

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 (5.8) ] . • Update immunizations according to current immunization guidelines [see Warnings and Precautions (5.9) ] . 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 (5.8) ] .

3 DOSAGE FORMS AND STRENGTHS Capsules: 50 mg of ritlecitinib, size 3, opaque capsules with yellow body and blue cap. The body is printed with “RCB 50” and the cap is printed with “Pfizer” in black. Capsules: 50 mg of ritlecitinib ( 3 )

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 )

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 (5.8) ] 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 …

7 DRUG INTERACTIONS • Certain CYP3A substrates : Additional monitoring and dose adjustment of CYP3A substrate should be considered. ( 7.1 ) • Certain CYP1A2 substrates : Additional monitoring and dose adjustment of CYP1A2 substrate should be considered. ( 7.1 ) • Certain CYP3A inducers: Coadministration with strong inducers of CYP3A is not recommended. ( 7.2 ) 7.1 Effects of LITFULO on Other Drugs Table 3 includes clinically significant drug interactions affecting other drugs. Table 3. Clinically Significant Interactions Affecting Other Drugs CYP3A Substrates Where Small Concentration Changes May Lead to Serious Adverse Reactions Clinical Impact Ritlecitinib is a CYP3A inhibitor. Concomitant use of ritlecitinib increases AUC and C max of CYP3A substrates [see Clinical Pharmacology (12.3 )] , which may increase the risk of adverse reactions of these substrates. Intervention Consider additional monitoring and dosage adjustment in accordance with approved product labeling of CYP3A substrates where small concentration changes may lead to serious adverse reactions when used with LITFULO. CYP1A2 Substrates Where Small Concentration Changes May Lead to Serious Adverse Reactions Clinical Impact Ritlecitinib is a CYP1A2 inhibitor. Concomitant use of ritlecitinib increases AUC and C max of CYP1A2 substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions of these substrates. Intervention Consider additional monitoring and dosage adjustment in accordance with the approved product labeling of CYP1A2 substrates where small concentration changes may lead to serious adverse reactions when used concomitantly with LITFULO. 7.2 Effects of Other Drugs on LITFULO Table 4 includes clinically significant drug interactions affecting LITFULO. Table 4. Clinically Significant Interactions Affecting LITFULO CYP3A Inducers Clinical Impact Concomitant use of strong CYP3A inducer (e.g., rifampin) may decrease AUC and C max of ritlecitinib [see Clinical Pharmacology (12.3) ] , which may result in loss of or reduced clinical response. Intervention Coadministration with strong inducers of CYP3A is not recommended.

8 USE IN SPECIFIC POPULATIONS • Lactation : Breastfeeding not recommended. ( 8.2 ) • Severe Hepatic Impairment: Not recommended. ( 8.6 ) 8.1 Pregnancy Pregnancy Exposure Registry If a patient becomes pregnant while receiving LITFULO, healthcare providers should report LITFULO exposure by calling 1-877-390-2940. Risk Summary Available data from clinical trials with LITFULO use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of ritlecitinib to pregnant rats and rabbits during organogenesis caused fetotoxicity and fetal malformations at exposures 49 and 55 times the maximum recommended human dose (MRHD) based on area under the curve (AUC) comparison, respectively (see Animal Data ) . The background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The estimated background risks in the U.S. general population of major birth defects and miscarriages are 2-4% and 15-20% of clinically recognized pregnancies, respectively. Data Animal Data In an embryo-fetal development study in pregnant rats, oral administration of ritlecitinib from gestation days 6 to 17 decreased fetal body weights and caused fetal skeletal malformations (malformed vertebrae and ribs) and variations (delayed ossification) at doses ≥175 mg/kg/day (49 times the MRHD based on AUC comparison). Maternal toxicity (lower body weights) was noted at 325 mg/kg/day (102 times the MRHD based on AUC comparison). There was no developmental toxicity at 75 mg/kg/day (16 times the MRHD based on AUC comparison). In an embryo-fetal development study in pregnant rabbits, oral administration of ritlecitinib from gestation days 7 to 19 decreased mean fetal body weights and increased visceral malformations (malpositioned kidneys), skeletal malformations (supernumerary sternebrae, absent thoracic arch, and/or fused thoracic centra), and skeletal variations (delayed ossification) at 75 mg/kg/day (55 times the MRHD based on AUC comparison). There was no developmental toxicity at doses up to 25 mg/kg/day (12 times the MRHD based on AUC comparison). In a pre- and postnatal development study in rats, oral administration of ritlecitinib from gestation day 6 through lactation day 20 had no effects on pre- and postnatal development at doses up to 75 mg/kg/day (14 times the MRHD based on AUC comparison). At 175 mg/kg/day (41 times the MRHD based on AUC comparison), ritlecitinib caused adverse lower postnatal survival and lower offspring body weights, which correlated with delayed sexual maturation in both sexes. Bred females in the F 1 generation also exhibited lower mean numbers of corpora lutea at 175 mg/kg/day. 8.2 Lactation Risk Summary There are no data on the presence of ritlecitinib in human milk, the effects on the breastfed infant, or the effects on milk production. Ritlecitinib is present in the milk of lactating rats (see Data ) . When a drug is present in animal milk, it is likely that it will be present in human milk. Because of the serious adverse effects in adults, including risks of serious infection and malignancy, advise women not to breastfeed during treatment with LITFULO and for approximately 14 hours after the last dose (approximately 6 elimination half-lives). Data After a single oral 30 mg/kg dose of ritlecitinib to lactating rats, ritlecitinib concentrations in milk over time were higher than those in plasma. The mean milk to plasma AUC ratio was 2.2. 8.4 Pediatric Use The safety and effectiveness of LITFULO for the treatment of alopecia areata have been established in pediatric patients ages 12 years and older. A total of 181 pediatric patients ages 12 to <18 years were enrolled in alopecia areata clinical trials, with 105 pediatric patients ages 12 to <18 years with alopecia areata randomized in a piv …

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.

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-{(2 S ,5 R )-2-Methyl-5-[(7 H -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

10 OVERDOSAGE LITFULO was administered in clinical trials up to a single oral dose of 800 mg. Adverse reactions were comparable to those seen at lower doses and no specific toxicities were identified. Pharmacokinetics (PK) data up to and including a single oral dose of 800 mg in healthy adult volunteers indicate that more than 90% of the administered dose is expected to be eliminated within 48 hours. There is no specific antidote for overdose with LITFULO. Treatment should be symptomatic and supportive, and monitor patients for signs and symptoms of adverse reactions [see Clinical Trials Experience (6.1) ] . In case of an overdose, call Poison Control Center at 1-800-222-1222 for latest recommendations.

16 HOW SUPPLIED/STORAGE AND HANDLING LITFULO capsules are packaged in child-resistant, white, high-density polyethylene (HDPE) bottles with polypropylene (PP) cap with a foil heat induction seal liner. The bottles contain 1g of desiccant in a high-density polyethylene (HDPE) canister. Do not eat the desiccant. Dosage Form Strength Description Bottle Size (number of capsules) NDC Number Capsules 50 mg of ritlecitinib Size 3, opaque capsules with yellow body and blue cap. The body is printed with “RCB 50” and the cap is printed with “Pfizer” in black. 28 count bottle 0069-0334-28 Store LITFULO at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep in original package.