Before taking Litfulo(Ritlecitinib)

I. Serious Infections

Serious infections have been reported in patients receiving ritlecitinib (LITFULO). The most common serious infections are appendicitis, COVID-19 infection (including infectious pneumonia), and sepsis [see Adverse Reactions]. Among opportunistic infections, herpes zoster in multiple skin areas was reported in the ritlecitinib (LITFULO) group.

Patients with active serious infections should avoid using ritlecitinib (LITFULO). Before initiating ritlecitinib (LITFULO) in the following patients, the risks and benefits of treatment should be considered:

1. With chronic or recurrent infections

2. Previously exposed to TB

3. With a history of serious or opportunistic infections

4. Living in or traveling to areas endemic for TB or fungal diseases

5. With underlying diseases that may predispose them to infections

Closely monitor patients for signs and symptoms of infection during and after ritlecitinib (LITFULO) treatment. If a patient develops a serious or opportunistic infection, interrupt ritlecitinib (LITFULO) treatment. For patients who develop new infections during ritlecitinib (LITFULO) treatment, comprehensive diagnostic testing for immunocompromised patients should be performed promptly, appropriate antibacterial therapy should be initiated, and patients should be closely monitored. Ritlecitinib (LITFULO) may be restarted once the infection is controlled.

Tuberculosis

Screen patients for tuberculosis (TB) before starting treatment. Patients with active TB should not receive ritlecitinib (LITFULO). In patients with newly diagnosed latent TB or previously untreated latent TB, anti-tubercular therapy should be initiated before starting ritlecitinib (LITFULO) treatment. In patients with negative latent TB tests, consider anti-tubercular therapy before starting ritlecitinib (LITFULO) treatment for high-risk patients, and consider screening high-risk patients for TB during ritlecitinib (LITFULO) treatment.

Virus Reactivation

Virus reactivation, including cases of herpesvirus reactivation (e.g., herpes zoster), was reported in clinical trials [see Adverse Reactions]. If a patient develops herpes zoster, consider interrupting treatment until the event resolves.

Screen for viral hepatitis according to clinical guidelines before starting ritlecitinib (LITFULO) treatment. Patients with evidence of HIV infection or hepatitis B or C infection were excluded from clinical trials.

II. Mortality

In a large, randomized, post-marketing safety study of another JAK inhibitor in patients with rheumatoid arthritis (RA) aged 50 years and older with at least one cardiovascular risk factor, the use of JAK inhibitors was associated with a higher rate of all-cause mortality, including sudden cardiovascular death, compared to TNF blockers.

Consider the benefits and risks for individual patients before initiating or continuing ritlecitinib (LITFULO) treatment.

III. Malignancy and Lymphoproliferative Disorders

Malignancies, including non-melanoma skin cancer (NMSC), were observed in ritlecitinib (LITFULO) clinical trials [see Adverse Reactions].

For patients at increased risk of skin cancer, regular skin examinations are recommended.

IV. Major Adverse Cardiovascular Events (MACE)

In a large, randomized, post-marketing safety study of another JAK inhibitor in RA patients aged 50 years and older with at least one cardiovascular risk factor, a higher incidence of major adverse cardiovascular events (MACE) (defined as cardiovascular death, non-fatal myocardial infarction [MI], and non-fatal stroke) was observed with JAK inhibitors compared to patients receiving TNF blockers. The risk was increased in current or former smokers.

Before initiating or continuing ritlecitinib (LITFULO) treatment, consider the benefits and risks for individual patients, especially in current or former smokers and those with other cardiovascular risk factors.

Instruct patients about the symptoms of serious cardiovascular events and steps to take if they occur. Discontinue ritlecitinib (LITFULO) in patients who experience a myocardial infarction or stroke.

V. Thromboembolism

In a large, randomized, post-marketing safety study of another JAK inhibitor in RA patients aged 50 years and older with at least one cardiovascular risk factor, the overall incidence of thrombosis, deep vein thrombosis (DVT), and pulmonary embolism (PE) was higher with JAK inhibitors compared to patients receiving TNF blockers.

Avoid use of ritlecitinib (LITFULO) in patients at increased risk of thrombosis.

If symptoms of thrombosis or embolism occur, patients should interrupt ritlecitinib (LITFULO) treatment and promptly receive evaluation and appropriate treatment.

VI. Hypersensitivity

Serious reactions, including anaphylaxis, urticaria, and rash, were observed in patients receiving ritlecitinib (LITFULO) in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue ritlecitinib (LITFULO) and institute appropriate treatment.

VII. Laboratory Abnormalities

Ritlecitinib (LITFULO) treatment is associated with lymphopenia and thrombocytopenia.

Perform absolute lymphocyte count (ALC) and platelet count before starting ritlecitinib (LITFULO) treatment [see Dosage and Administration].

After starting ritlecitinib (LITFULO) treatment, interrupt or discontinue treatment based on ALC and platelet count abnormalities [see Dosage and Administration].

VIII. Vaccination

Data on vaccine response in patients receiving ritlecitinib (LITFULO) are not available. Avoid use of live attenuated vaccines during or shortly before treatment. Before starting ritlecitinib (LITFULO) treatment, advise patients to be up-to-date on all immunizations, including prophylactic herpes zoster vaccination, according to current immunization guidelines.