Version May 2024
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. Ritlecitinib should not be given to patients with active TB. 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.
Higher rate of all-cause mortality, including sudden cardiovascular death, with another Janus kinase inhibitor (JAK) vs. tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients. Ritlecitinib is not approved for use in RA patients.
Malignancies have occurred 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 major adverse cardiovascular events (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.
Note: Do not initiate therapy in patients with active serious infection (including localized infection, tuberculosis, hepatitis B and/or C), a platelet count <100,000/mm3, or an absolute lymphocyte count (ALC) <500 cells/mm3. Complete all age-appropriate immunizations before initiating therapy; avoid administering live vaccines immediately prior to and during therapy.
Alopecia areata, severe: Children ≥12 years and Adolescents: Oral: 50 mg once daily.
Dosing adjustment for toxicity:
Children ≥12 years and Adolescents:
Cardiovascular (myocardial infarction or stroke): Discontinue treatment.
Hematologic:
ALC <500 cells/mm3: Interrupt therapy until ALC ≥500/mm3.
Platelet count <50,000/mm3: Discontinue treatment.
Hypersensitivity reactions: Discontinue treatment.
Infection, serious or opportunistic: Interrupt therapy; may resume once infection is controlled. For herpes zoster, the manufacturer recommends interrupting treatment until episode resolves.
Thromboembolic events: Interrupt treatment.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
Children ≥12 years and Adolescents:
Baseline hepatic impairment:
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended.
Hepatoxicity during treatment: If ritlecitinib-induced liver injury is suspected, interrupt therapy until diagnosis is excluded.
(For additional information see "Ritlecitinib: Drug information")
Note: Do not use in combination with other Janus kinase inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants; do not initiate in patients with an absolute lymphocyte count <500 cells/mm3 or platelet count <100,000 cells/mm3.
Alopecia areata, severe: Oral: 50 mg once daily.
Missed doses: Administer missed dose as soon as possible. If <8 hours until the next scheduled dose, skip the missed dose and resume dosing at regular scheduled time.
There are no dosage adjustments provided in the manufacturer's labeling.
Hepatic impairment prior to treatment initiation:
Mild to moderate impairment (Child-Turcotte-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Turcotte-Pugh class C): Use is not recommended.
Acute hepatotoxicity during treatment: If ritlecitinib-induced liver injury is suspected, interrupt therapy.
Ritlecitinib is a Janus kinase inhibitor; therefore, use may result in malignancies. Malignant neoplasm, including nonmelanoma skin cancer (NMSC) and one case of breast cancer, has been reported with ritlecitinib therapy (Ref).
Onset: Delayed; breast cancer diagnosis was on day 195 of ritlecitinib therapy (Ref).
Risk factors:
• Known malignancy (other than successfully treated NMSC or cervical cancer)
An increased incidence of infection has been demonstrated with ritlecitinib. Serious infection, including appendicitis, sepsis, and pneumonia, has been reported. Opportunistic infection, including herpes zoster infection and herpes virus reactivation, has also been reported.
Mechanism: Related to pharmacologic action; Janus kinase inhibitors cause immune suppression (Ref).
Risk factors:
• Active or chronic infections especially those requiring hospitalization and IV antimicrobial administration within the last 6 months (Ref)
• Active or latent hepatitis or tuberculosis (TB) (Ref)
• Recurrent or disseminated herpes zoster (Ref)
• Underlying conditions that may predispose infection
• Known TB exposure or ongoing risk factors for TB exposure (eg, travel to areas with high TB prevalence)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Nervous system: Headache (11%)
1% to 10%:
Dermatologic: Acne vulgaris (6%), atopic dermatitis (2%), folliculitis (3%), skin rash (5%), urticaria (5%)
Gastrointestinal: Diarrhea (10%), stomatitis (2%)
Hematologic & oncologic: Decreased red blood cells (2%)
Infection: Herpes zoster infection (2%) (table 1)
|
Drug (Ritlecitinib) |
Placebo |
Population |
Number of Patients (Ritlecitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
2% |
0% |
Adolescents and adults |
130 |
213 |
Nervous system: Dizziness (2%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (2%)
Miscellaneous: Fever (3%)
Frequency not defined:
Cardiovascular: Acute myocardial infarction, pulmonary embolism
Hematologic & oncologic: Decreased platelet count, lymphocytopenia, malignant neoplasm (including skin carcinoma [non-melanoma])
Hepatic: Increased liver enzymes
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis)
Infection: Infection, serious infection (including appendicitis, pneumonia, and sepsis)
Hypersensitivity to ritlecitinib or any component of the formulation.
Concerns related to adverse effects:
• CPK effects: Increased CPK may occur.
• Hematological toxicity: Hematological toxicities, including lymphopenia and thrombocytopenia, may occur; generally reversible with treatment interruption or discontinuation.
Disease-related concerns:
• Cardiovascular: Consider the benefits and risks prior to initiating or continuing ritlecitinib therapy, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors.
• Hematologic: Treatment should not be initiated in patients with an absolute lymphocyte count <500/mm3 or a platelet count <100,000/mm3.
• Thromboembolic: Avoid use in patients who may be at increased risk of thrombosis.
• Tuberculosis: Initiation of ritlecitinib is not recommended in patients with tuberculosis (TB) disease (active TB). In patients with a new diagnosis of TB infection or previously untreated TB infection, anti-TB therapy should be started prior to initiating ritlecitinib. In patients with a negative TB test, consider anti-TB therapy before initiating ritlecitinib in those at high risk and consider screening patients at high risk for TB during treatment. Consider the risks and benefits of treatment prior to initiating ritlecitinib in patients who have been exposed to TB or who have resided or traveled in areas of endemic TB.
• Viral hepatitis: Use in patients with hepatitis B or C is not recommended.
Concurrent drug therapy issues:
• Immunosuppressant medications: Do not use in combination with other JAK inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants.
Other warnings/precautions:
• Immunizations: Immunization status should be current before initiating therapy with ritlecitinib. Live vaccines should not be given concomitantly with ritlecitinib; recommended interval between receipt of live vaccines and initiation of immunosuppressive agents such as ritlecitinib should follow current vaccination clinical guidelines.
• Interruption of therapy: Treatment interruptions of <6 weeks should not result in significant loss of regrown hair.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as tosylate:
Litfulo: 50 mg [contains fd&c blue #1 (brilliant blue)]
No
Capsules (Litfulo Oral)
50 mg (per each): $161.54
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Litfulo is only available through select specialty pharmacies within the Litfulo Defined Distribution Network or through an eligible Integrated Delivery Network specialty pharmacy. Further information is available by calling 1-833-956-3376 or via https://www.pfizerdermatologypatientaccess.com/hcp/specialty-pharmacy.
Oral: Swallow capsules whole; do not crush, split, or chew. Administer without regard to meals.
Missed dose: Administer the missed dose as soon as possible. If <8 hours until the next scheduled dose, skip the missed dose and resume dosing at the regular scheduled time.
Oral: Administer without regard to food. Swallow capsules whole; do not crush, split, or chew.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Store in original container.
Treatment of severe alopecia areata (FDA approved in ages ≥12 years and adults). Note: Not recommended for use in combination with other Janus kinase inhibitors, biologic immunomodulators, cyclosporine, or other potent immunosuppressants.
Substrate of CYP1A2 (minor), CYP2C8 (minor), CYP2C9 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Ritlecitinib may increase the serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Ritlecitinib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Ritlecitinib. Risk X: Avoid combination
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Ritlecitinib may increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Methotrexate: May enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Adverse events were observed in some animal reproduction studies.
Data collection to monitor pregnancy and infant outcomes following exposure to ritlecitinib is ongoing. Health care providers are encouraged to enroll patients exposed to ritlecitinib during pregnancy in the pregnancy registry (1-877-390-2940).
Absolute lymphocyte count and platelets (prior to and 4 weeks after initiation, then as clinically indicated); liver function (prior to initiation, then as clinically indicated); tuberculosis (TB) and viral hepatitis screening (prior to initiating therapy); clinical signs and symptoms of infection (including TB) during and after therapy; skin examinations (periodically, in patients at increased risk for skin cancer); signs and symptoms of thrombosis; signs and symptoms of hypersensitivity reactions.
Irreversibly inhibits Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family by blocking the adenosine triphosphate (ATP) binding site. Intracellularly, inhibits cytokine-induced STAT phosphorylation mediated by JAK3-dependent receptors. Also, inhibits signaling of immune receptors dependent on TEC kinase family members. Inhibition of JAK3 and TEC may result in inhibition of T cell activation (King 2023).
Onset: Initial: Within 4 to 8 weeks.
Protein binding: ~14% (plasma proteins).
Metabolism: Hepatic via glutathione S-transferase, CYP3A, CYP1A2, and CYP2C19.
Bioavailability: ~64%.
Half-life elimination: Terminal: 1.3 to 2.3 hours.
Time to peak: 1 hour.
Excretion: Urine: ~66% (~4% as unchanged drug); feces: ~20%.
Altered kidney function: Following multiple doses of 50 mg once daily, the steady state AUC increased ~55% and Cmax ~44.5% in persons with severe kidney impairment (eGFR <30 mL/minute) compared to those with normal kidney function (eGFR >90 mL/minute) (Purohit 2023).
Hepatic impairment: Following multiple doses of 30 mg once daily, the steady state AUC increased ~18.5% and Cmax ~4% in persons with moderate hepatic impairment (Child-Pugh class B) compared to those with normal hepatic function (Purohit 2023).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
