Ritlecitinib

Ritlecitinib
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rithish Nimmagadda,MBBS.[2]

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Black Box Warning

Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events (MACE), and Thrombosis See full prescribing information for complete Boxed Warning. Increased risk of serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death, including tuberculosis (TB). Interrupt treatment if serious infection occurs until the infection is controlled. Ritlecitinib should not be given to patients with active tuberculosis. Test for latent TB before and during therapy; start treating latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.Monitor all patients for signs and symptoms of infection during and after treatment with ritlecitinib. Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) versus TNF blockers in rheumatoid arthritis (RA) patients. Ritlecitinib is not approved for use in RA patients. Malignancies were reported in patients treated with ritlecitinib. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. Thrombosis has occurred in patients treated with ritlecitinib. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers.

Overview

Ritlecitinib is a janus kinase 3 (JAK3) inhibitor and also an inhibitor of the tyrosine kinase that is FDA approved for the treatment of severe alopecia areata in adults and adolescents 12 years of age and older. There is a Black Box Warning for this drug as shown here. Common adverse reactions include Most common adverse reactions (incidence ≥1%) are headache, diarrhea, acne, rash, urticaria, folliculitis, pyrexia, atopic dermatitis, dizziness, increased blood creatine phosphokinase, herpes zoster, decreased red blood cell count, and stomatitis.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Recommended dosage of ritlecitinib in adults is 50 mg orally once daily.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Recommended dosage of ritlecitinib in adolescents 12 years of age and older is 50 mg orally once daily

Off-Label Use and Dosage (Pediatric)

Contraindications

atients with known hypersensitivity to ritlecitinib or any of its excipients

Warnings

Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events (MACE), and Thrombosis See full prescribing information for complete Boxed Warning. Increased risk of serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death, including tuberculosis (TB). Interrupt treatment if serious infection occurs until the infection is controlled. Ritlecitinib should not be given to patients with active tuberculosis. Test for latent TB before and during therapy; start treating latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.Monitor all patients for signs and symptoms of infection during and after treatment with ritlecitinib. Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) versus TNF blockers in rheumatoid arthritis (RA) patients. Ritlecitinib is not approved for use in RA patients. Malignancies were reported in patients treated with ritlecitinib. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. Thrombosis has occurred in patients treated with ritlecitinib. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers.

-Serious Infections

Serious infections have been reported in patients receiving ritlecitinib. The most frequent serious infections have been appendicitis, COVID-19 infection (including pneumonia), and sepsis. Among opportunistic infections, multi-dermatomal herpes zoster was reported with ritlecitinib.

Avoid use of ritlecitinib in patients with an active, serious infection. Consider the risks and benefits of treatment prior to initiating ritlecitinib in patients with chronic or recurrent infection, patients who have been exposed to tuberculosis (TB), patients with a history of serious infection or an opportunistic infection, patients who have resided or traveled in areas of endemic TB or mycosis, or patients 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 ritlecitinib. Interrupt therapy if a patient develops a serious or opportunistic infection. A patient who develops a new infection during treatment with ritlecitinib 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. Ritlecitinib may be resumed once the infection is controlled.

-TB activation , Viral infections

-Mortality

In a large, randomized, postmarketing safety study of another JAK inhibitor in rheumatoid arthritis 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. [ref] Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with ritlecitinib. [ref]

Malignancy and Lymphoproliferative Disorders

Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical trials of ritlecitinib. [ref]

In a large, randomized, postmarketing safety study of another JAK inhibitor in rheumatoid arthritis 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. [ref] A higher rate of lymphomas was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. [ref] 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. [ref] In this study, current or past smokers had an additional increased risk of overall malignancies. [ref]

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. [ref]

Periodic skin examination is recommended for patients who are at increased risk for skin cancer. [ref]

Major Adverse Cardiovascular Events (MACE)

In a large, randomized, postmarketing safety study of another JAK inhibitor in rheumatoid arthritis 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. [ref] Patients who are current or past smokers are at additional increased risk. [ref]

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with ritlecitinib, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. [ref] Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. [ref] Discontinue ritlecitinib in patients that have experienced a MI or stroke. [ref]

Thromboembolic Events

Pulmonary embolism (PE) was reported in a patient receiving ritlecitinib. [ref] In a higher dosing group, one patient reported an event of retinal artery occlusion. [ref]

In a large, randomized, postmarketing safety study of another JAK inhibitor in rheumatoid arthritis patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, deep-vein thrombosis (DVT), and PE were observed compared to those treated with TNF blockers. [ref]

Avoid ritlecitinib in patients who may be at increased risk of thrombosis. [ref] If symptoms of thrombosis or embolism occur, patients should interrupt therapy and be evaluated promptly and treated appropriately. [ref]

Hypersensitivity

Serious reactions including anaphylactic reactions, urticaria, and rash have been observed in patients receiving ritlecitinib in clinical trials. [ref] If a clinically significant hypersensitivity reaction occurs, discontinue the drug and institute appropriate therapy. [ref]

Laboratory Abnormalities

Treatment with ritlecitinib was associated with decreases in lymphocytes and platelets. [ref]

Prior to ritlecitinib initiation, perform absolute lymphocyte count (ALC) and platelet counts. [ref] After initiating treatment, treatment interruption or discontinuation are recommended based on ALC and platelet count abnormalities. [ref]

Liver Enzyme Elevations – Treatment with ritlecitinib was associated with increased incidence of liver enzyme elevation compared to placebo. [ref] Increases of ALT ≥5 times the upper limit of normal (ULN) and increases of AST ≥5 times the ULN were observed in patients receiving ritlecitinib clinical trials. [ref] Evaluate at baseline and thereafter according to routine patient management. [ref] Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. [ref] If increases in ALT or AST are observed and drug-induced liver injury is suspected, interrupt ritlecitinib until this diagnosis is excluded. [ref]

Creatine Phosphokinase (CPK) Elevations – Treatment with ritlecitinib was associated with increased incidence of CPK elevation compared to placebo. [ref]

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Ritlecitinib Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Ritlecitinib Postmarketing Experience in the drug label.

Drug Interactions

Certain CYP3A substrates: Additional monitoring and dose adjustment of CYP3A substrate should be considered.

Certain CYP1A2 substrates: Additional monitoring and dose adjustment of CYP1A2 substrate should be considered.

Certain CYP3A inducers: Coadministration with strong inducers of CYP3A is not recommended.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): If a patient becomes pregnant while receiving ritlecitinib, healthcare providers should report the exposure by calling 1-877-390-2940.

Available data from clinical trials with ritlecitinib 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 AUC comparison, respectively.

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.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ritlecitinib in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Ritlecitinib during labor and delivery.

Nursing Mothers

There are no data on the presence ritlecitinib in human milk, the effects on the breastfed infant, or the effects on milk production

Pediatric Use

There is no FDA guidance on the use of Ritlecitinib in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Ritlecitinib in geriatric settings.

Gender

There is no FDA guidance on the use of Ritlecitinib with respect to specific gender populations.

Race

There is no FDA guidance on the use of Ritlecitinib with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Ritlecitinib in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Ritlecitinib in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Ritlecitinib in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Ritlecitinib in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Ritlecitinib Administration in the drug label.

Monitoring

There is limited information regarding Ritlecitinib Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Ritlecitinib and IV administrations.

Overdosage

There is limited information regarding Ritlecitinib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Ritlecitinib Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Ritlecitinib Mechanism of Action in the drug label.

Structure

There is limited information regarding Ritlecitinib Structure in the drug label.

Pharmacodynamics

There is limited information regarding Ritlecitinib Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Ritlecitinib Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Ritlecitinib Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Ritlecitinib Clinical Studies in the drug label.

How Supplied

Oral Capsules

Storage

There is limited information regarding Ritlecitinib Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Ritlecitinib Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Ritlecitinib interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

Litfulo®

Look-Alike Drug Names

There is limited information regarding Ritlecitinib Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.