Dosage & Administration
Litfulo Prescribing Information
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- Increased risk of serious bacterial, fungal, viral and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Interrupt treatment if serious infection occurs until the infection is controlled. LITFULO should not be given to patients with active tuberculosis. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test.
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- Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) vs. TNF blockers in rheumatoid arthritis (RA) patients. LITFULO is not approved for use in RA patients.
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- Malignancies have occurred in patients treated with LITFULO [see Warnings and Precautions (5.3)]. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients.
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- Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients.
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- Thrombosis has occurred in patients treated with LITFULO. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers.
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.
Recommended Evaluations and Immunizations Prior to Treatment Initiation
Perform the following evaluations prior to LITFULO initiation:
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- 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)].
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- 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)].
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- Treatment with LITFULO should not be initiated in patients with an absolute lymphocyte count (ALC) <500/mm3 or a platelet count <100,000/mm3[see Warnings and Precautions (5.7)].
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- Update immunizations according to current immunization guidelines [see Warnings and Precautions (5.8)].
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.
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)].
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.
| Laboratory Measure | Recommendation |
|---|---|
| ALC = absolute lymphocyte count. | |
Platelet Count | Treatment should be discontinued if platelet count is <50,000/mm3 |
Lymphocytes | Treatment should be interrupted if ALC is <500/mm3 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 (5.7)].
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.
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 F1 generation also exhibited lower mean numbers of corpora lutea at 175 mg/kg/day.
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.
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 pivotal, double-blind, placebo-controlled trial (Trial AA-I). Efficacy was consistent between the pediatric patients and adults [see Clinical Studies (14)]. The adverse reaction profile in the pediatric patients was similar to adults.
The safety and efficacy of LITFULO have not been established in pediatric patients under 12 years of age.
Geriatric Use
No dose adjustment is required for patients ≥65 years of age.
A total of 28 patients enrolled in alopecia areata trials were 65 years of age and older, and none were 75 years of age and older. Clinical trials of LITFULO did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.
Hepatic Impairment
No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment.
LITFULO is not recommended in patients with severe (Child Pugh C) hepatic impairment [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].
LITFULO is contraindicated in patients with known hypersensitivity to ritlecitinib or any of its excipients [see Warnings and Precautions (5.6)].