RITLECITINIB Drug Interactions: What You Need to Know

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.

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 )

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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . 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 <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> .

5.7 Laboratory Abnormalities Treatment with LITFULO was associated with decreases in lymphocytes and platelets <span class="opacity-50 text-xs">[see Adverse Reactions (6.1) ]</span> . Prior to LITFULO initiation, perform ALC and platelet counts <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span> . After initiating treatment with LITFULO, treatment interruption or discontinuation are recommended based on ALC and platelet count abnormalities <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> .

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.