Lipivir is indicated for the treatment of severe alopecia areata in adolescents and adults aged 12 years and above.

Lipofectinib Instructions

Product Name: LuciRit

Manufacturer: Lucius Pharmaceuticals

Chinese name: Litxitinib English name: Ritlecitinib

Drug approval number: 10 L 1035/23

 

 

【Summary】

Ritlecitinib is a kinase inhibitor indicated for the treatment of severe alopecia areata in adults and adolescents aged 12 years and older.

 

【Indications】

Indicated for the treatment of severe alopecia areata in adults and adolescents aged 12 years and above.

Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants.

 

【Specification】

50mg/capsule, 28 capsules/box.

 

【Storage】

Store at 20°C to 25°C (68°C to 77°F); short-distance transport is permitted at a temperature range of 15 to 30°C (59–86°F).

 

【Usage and Dosage】

Before using Ritlecitinib for treatment:

1. Tuberculosis (TB) infection: It is not recommended to start treatment with LuciRit in patients with active TB. For patients with latent TB or patients with negative latent TB test and high risk of TB, start preventive treatment for latent TB before starting LuciRit treatment [see Warnings and Precautions].

2. Screen for viral hepatitis according to clinical guidelines: It is not recommended that patients with hepatitis B or hepatitis C start treatment with LuciRit [see Warnings and Precautions].

3. Patients with an absolute lymphocyte count (ALC) < 500/mm3 or a platelet count < 100,000/mm3 should not start treatment with LuciRit [see Warnings and Precautions].

4. Update immunizations according to current immunization guidelines [see WARNINGS AND PRECAUTIONS].

1. Recommended Dosage

1. The recommended dose of Ritlecitinib is 50 mg, taken orally, once a day, with or without food.

2. Swallow the capsule whole. Do not crush, break or chew the capsule.

3. If you miss a dose, take it as soon as possible, unless it is less than 8 hours before the next dose, in which case you skip the missed dose. After that, resume taking the medicine at your normal schedule.

2. Patients with severe liver damage

LuciRit is not recommended for use in patients with severe (Child Pugh C) hepatic impairment [see Use in Specific Populations].

3. Treatment interruption or discontinuation

If interruption of treatment is necessary, temporary interruptions of treatment for less than 6 weeks are not expected to result in significant loss of regrowth scalp hair.

Hematological abnormalities

Recommendations for interrupting or discontinuing LuciRit treatment due to hematologic abnormalities are summarized in the table below.

Laboratory Monitoring Guidelines

Laboratory indicators	suggestion
Platelet count	If platelet count is < 50,000/mm3, treatment should be stopped
Lymphocytes	If ALC < 500/mm3, treatment should be interrupted and can be restarted once ALC returns to above this value.

ALC = absolute lymphocyte count.

ALC and platelet counts are recommended prior to and 4 weeks after initiation of treatment and thereafter according to routine patient management [see WARNINGS AND PRECAUTIONS].

 

【Adverse Reactions】

1. Headache, diarrhea, acne, rash, stomatitis

2. Urticaria, folliculitis, fever, atopic dermatitis

3. Dizziness, increased blood creatine phosphokinase, herpes zoster, decreased red blood cell count

 

【Taboo】

LuciRit is contraindicated in patients with known hypersensitivity to LuciRit or any of its excipients.

 

【Notes】

1. Severe infection

Serious infections have been reported in patients treated with LuciRit. The most common serious infections were appendicitis, COVID-19 infection (including pneumonia), and sepsis [see Adverse Reactions]. Among opportunistic infections, multiple cutaneous herpes zoster was reported in the LuciRit group.

LuciRit should be avoided in patients with active serious infections. The risks and benefits of treatment should be considered before starting LuciRit in the following patients:

1) With chronic or recurrent infection

2) Previous exposure to TB

3) History of severe infection or opportunistic infection

4) Patients living in or traveling to TB-endemic areas or fungal disease-endemic areas

5) Having an underlying disease that may make them susceptible to infection

During and after treatment with LuciRit, monitor patients closely for signs and symptoms of infection. If a patient develops a serious or opportunistic infection, interrupt LuciRit treatment. For patients who develop a new infection during treatment with LuciRit, a comprehensive diagnostic workup for immunocompromised patients should be promptly performed and appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored. Once the infection is under control, LuciRit can be restarted.

 

tuberculosis

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

 

Virus reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster) have been reported in clinical trials [see ADVERSE REACTIONS]. If a patient develops herpes zoster, consider interrupting treatment until the event resolves.

Before starting LuciRit treatment, viral hepatitis screening should be performed according to clinical guidelines. Patients with evidence of HIV infection or hepatitis B or C infection were excluded from clinical trials.

 

2. Mortality

In a large, randomized, postmarketing safety study of RA patients aged 50 years and older with at least one cardiovascular risk factor treated with another JAK inhibitor, all-cause mortality, including sudden cardiovascular death, was higher in patients treated with a JAK inhibitor compared with a TNF blocker.

Consider the benefits and risks for the individual patient before initiating or continuing treatment with LuciRit.

 

3. Malignant Tumors and Lymphoproliferative Diseases

Malignancies, including non-melanoma skin cancer (NMSC), have been observed in clinical trials with LuciRit [see ADVERSE REACTIONS].

Regular skin examinations are recommended for patients at increased risk for skin cancer.

 

4. Major adverse cardiovascular events (MACE)

In a large, randomized, postmarketing 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, nonfatal myocardial infarction (MI), and nonfatal stroke) was observed with JAK inhibitors compared with patients treated with TNF blockers. Current or former smokers are at increased risk.

Before starting or continuing treatment with LuciRit, consider the benefits and risks for the individual patient, especially in current or former smokers and those with other cardiovascular risk factors. Patients should be informed of the symptoms of serious cardiovascular events and the steps to take if they occur. LuciRit should be discontinued in patients who develop a myocardial infarction or stroke.

 

5. Thromboembolism

In a large, randomized, postmarketing safety study, higher rates of overall thrombosis, DVT, and PE were observed in RA patients aged 50 years and older with at least one cardiovascular risk factor treated with another JAK inhibitor compared with those treated with a TNF blocker.

Patients who may be at increased risk for thrombosis should avoid the use of LuciRit. If thrombotic or embolic symptoms occur, patients should interrupt LuciRit treatment and receive prompt evaluation and appropriate treatment.

 

6. Allergies

Severe reactions, including anaphylaxis, urticaria, and rash, have been observed in patients receiving LuciRit in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue LuciRit and institute appropriate treatment.

 

7. Abnormal laboratory tests

Treatment with LuciRit is associated with lymphocytopenia and thrombocytopenia. Before starting treatment with LuciRit, perform ALC and platelet counts [see Dosage and Administration]. After starting treatment with LuciRit, interruption or discontinuation of treatment is recommended based on abnormal ALC and platelet counts [see Dosage and Administration].

 

8. Vaccination

There are no data on the response to vaccination in patients receiving LuciRit. The use of live attenuated vaccines during or shortly before starting treatment should be avoided. Prior to starting LuciRit treatment, it is recommended that patients be up to date on all immunizations, including prophylactic herpes zoster vaccination, according to current immunization guidelines.

 

【Use in special populations】

1. Pregnancy

If a patient becomes pregnant while receiving LuciRit, they should consult their doctor as soon as possible.

Available data from clinical trials using LuciRit in pregnant women are insufficient to determine. Drug-related risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of rituximab to pregnant rats and rabbits during the period of organogenesis resulted in fetotoxicity and fetal malformations at exposures 49 and 55 times the maximum recommended human dose (MRHD), respectively, based on area under the curve (AUC) comparisons.

 

2. Lactation

Because of serious adverse reactions in adults, including the risk of serious infections and malignancies, advise women not to breastfeed during treatment with LuciRit and for approximately 14 hours (approximately 6 elimination half-lives) after the last dose.

 

3. Medication for children

The safety and efficacy of LuciRit for the treatment of alopecia areata have been established in pediatric patients 12 years of age and older. The safety and efficacy of LuciRit in pediatric patients younger than 12 years of age have not been established.

 

4. Medication for elderly patients

No dose adjustment is required for patients ≥65 years of age. Clinical trials of LuciRit did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger adults. Because of the higher incidence of infection in the general elderly population, caution should be exercised when treating the elderly.

 

5. Liver damage

No dose adjustment is required for patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.

LuciRit is not recommended for use in patients with severe (Child Pugh Class C) hepatic impairment [see Dosage and Administration].

【Drug Interactions】

1. Effects of rituximab on other drugs

1. CYP3A substrates whose concentration changes may lead to serious adverse reactions

Liraconazole is a CYP3A inhibitor. Concomitant use of Liraconazole can increase the AUC and Cmax of CYP3A substrates, which may increase the risk of adverse reactions of these substrates.

Action: Consider additional monitoring and dose adjustments as per approved product labeling for CYP3A substrates where small changes in concentrations may result in serious adverse reactions.

2. CYP1A2 substrates for which small changes in concentration may lead to serious adverse reactions

Liraglutide is a CYP1A2 inhibitor. Concomitant use of Liraglutide can increase the AUC and Cmax of CYP1A2 substrates, which may increase the risk of adverse reactions of these substrates.

Action: If risk is small, consider additional monitoring and dose adjustment per approved product labeling for CYP1A2 substrates. When used concomitantly with rituximab, changes in concentrations may result in serious adverse reactions.

2. Effects of other drugs on rituximab

1. CYP3A inducers

Concomitant use of strong CYP3A inducers (e.g., rifampin) may decrease the AUC and Cmax of rituximab, potentially resulting in loss or reduction of clinical response.

Treatment measures: Co-administration with strong CYP3A inducers is not recommended.

 

【Overdose】

In clinical trials, single oral doses of rituximab were as high as 800 mg. Adverse reactions were comparable to those observed at lower doses, and no specific toxicities were found.

In healthy adult volunteers, single oral dosing of ≤800 mg demonstrated that more than 90% of the administered dose is expected to be eliminated within 48 hours.