Version May 2024
Patients treated with abrocitinib may be at increased risk for developing serious infections that may lead to hospitalization or death. The most frequent serious infections reported with abrocitinib were herpes simplex, herpes zoster, and pneumonia. If a serious or opportunistic infection develops, discontinue abrocitinib and control the infection.
Reported infections from Janus kinase (JAK) inhibitors used to treat inflammatory conditions include:
Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease; 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.
Invasive fungal infections, including cryptococcosis and pneumocystosis; patients with invasive fungal infections may present with disseminated, rather than localized, disease.
Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.
Avoid use of abrocitinib in patients with an active, serious infection, including localized infections. The risks and benefits of treatment with abrocitinib should be carefully considered prior to initiating therapy in patients with chronic or recurrent infections. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with abrocitinib, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients ≥50 years of age with at least 1 cardiovascular risk factor comparing another JAK inhibitor to tumor necrosis factor (TNF) blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. Abrocitinib is not approved for use in RA patients.
Malignancies were reported in patients treated with abrocitinib. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding nonmelanoma skin cancer) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk.
Major adverse cardiovascular events were reported in patients treated with abrocitinib. In RA patients ≥50 years of age with at least 1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (defined as cardiovascular death, myocardial infarction [MI], and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue abrocitinib in patients that have experienced a MI or stroke.
Deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients treated with abrocitinib. Thrombosis, including PE, DVT, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In RA patients ≥50 years of age with at least 1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid abrocitinib in patients at risk. If symptoms of thrombosis occur, discontinue abrocitinib and treat appropriately.
Dosage guidance:
Safety: Do not initiate therapy in patients with active serious infection (including localized infection, tuberculosis, hepatitis B and/or C), a platelet count <150,000/mm3, an absolute lymphocyte count <500 cells/mm3, an ANC <1,000 cells/mm3, or Hb <8 g/dL. Complete all age-appropriate immunizations before initiating therapy; avoid administering live vaccines immediately prior to, during, and immediately after therapy.
Atopic dermatitis, refractory, moderate to severe: Note: Not recommended for use with biologic immunomodulators, other Janus kinase inhibitors, or other systemic immunosuppressants (Ref). May be used with or without topical corticosteroids.
Oral:
US labeling: Initial: 100 mg once daily. For insufficient response, may increase dose to 200 mg once daily. Discontinue treatment if inadequate response is seen after dose increase.
Canadian labeling: Initial: Adults <65 years of age: 100 to 200 mg once daily; in patients taking 200 mg once daily, consider decreasing dose to 100 mg once daily if symptom control is achieved by week 12; may increase back to 200 mg once daily if symptom control cannot be maintained. Maximum dose: 200 mg/day.
Dosage recommendations for CYP2C19 poor metabolizers: Oral: Initial: 50 mg once daily. For insufficient response, may increase dose to 100 mg once daily. Discontinue treatment if inadequate response is seen after dose increase.
Missed doses: Administer missed dose as soon as possible within 12 hours of scheduled dose. If <12 hours until the next scheduled dose, skip the missed dose and resume dosing at regular scheduled time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Renal function estimated using the MDRD formula for dose adjustment purposes.
US labeling:
eGFR ≥60 mL/minute: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute: 50 mg once daily. For insufficient response, may increase dose to 100 mg once daily. Discontinue treatment if inadequate response is seen after dose increase.
eGFR <30 mL/minute, end-stage renal disease: Use is not recommended.
Patients on renal replacement therapy: Use is not recommended (has not been studied).
Canadian labeling:
eGFR ≥60 mL/minute: No dosage adjustment necessary.
eGFR <60 mL/minute: Reduce dose by 50%.
Mild to moderate impairment (Child-Turcotte-Pugh class A and B): No dosage adjustment necessary.
Severe impairment (Child-Turcotte-Pugh class C): Avoid use (has not been studied).
Hematologic toxicity:
Platelet count <50,000/mm3: Discontinue use and monitor CBC until platelet count >100,000/mm3.
Absolute lymphocyte count <500/mm3: Interrupt therapy until absolute lymphocyte count ≥500/mm3.
ANC <1,000/mm3: Interrupt therapy until ANC ≥1,000/mm3.
Hemoglobin <8 g/dL: Interrupt therapy until hemoglobin ≥8 g/dL.
Infection (severe or opportunistic): Discontinue abrocitinib and treat infection. Consider risks and benefits of continuing abrocitinib prior to reinitiating therapy.
US labeling: Refer to adult dosing.
Canadian labeling: ≥65 years of age: Initial dose: 100 mg once daily.
(For additional information see "Abrocitinib: Pediatric drug information")
Note: Do not initiate therapy in patients with active serious infection (including localized infection, tuberculosis, hepatitis B and/or C), a platelet count <150,000/mm3, an absolute lymphocyte count (ALC) <500 cells/mm3, an ANC <1,000 cells/mm3, or Hb <8 g/dL. Complete all age-appropriate immunizations before initiating therapy; avoid administering live vaccines immediately prior to, during, and immediately after therapy.
Atopic dermatitis, refractory, moderate to severe: Children ≥12 years and Adolescents: Oral: 100 mg once daily; for insufficient response after 12 weeks of therapy, may increase dose to 200 mg once daily. Maximum daily dose: 200 mg/day. If response remains inadequate after dose increase to 200 mg, discontinue therapy. Note: May be used in combination with topical steroids (Ref).
Dosage recommendations for CYP2C19 poor metabolizers: Children ≥12 years and Adolescents: Oral: Initial: 50 mg once daily; for insufficient response after 12 weeks of therapy, may increase dose to 100 mg once daily. If response remains inadequate after dose increase to 100 mg, discontinue therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Children ≥12 years and Adolescents: Oral:
Hematologic toxicity:
Platelet count <50,000/mm3: Discontinue use and monitor CBC until platelet count >100,000/mm3.
ALC <500/mm3: Interrupt therapy until ALC ≥500/mm3.
ANC <1,000/mm3: Interrupt therapy until ANC ≥1,000/mm3.
Hemoglobin <8 g/dL: Interrupt therapy until hemoglobin ≥8 g/dL.
Infection (severe or opportunistic): Discontinue abrocitinib and treat infection. Consider risks and benefits of continuing abrocitinib prior to reinitiating therapy.
Altered kidney function: Children ≥12 years and Adolescents: Oral:
eGFR ≥60 mL/minute: No dosage adjustment necessary.
eGFR 30 to <60 mL/minute: Initial: 50 mg once daily. For insufficient response after 12 weeks, may increase dose to 100 mg once daily. If response remains inadequate after dose increase, discontinue therapy.
eGFR <30 mL/minute, end-stage renal disease: Use is not recommended.
Patients on renal replacement therapy: Use is not recommended (has not been studied).
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: Use is not recommended (has not been studied).
Major cardiovascular/thrombotic events, including acute myocardial infarction, cerebrovascular accident, deep vein thrombosis, and pulmonary embolism (PE) have been reported in patients receiving abrocitinib.
Mechanism: Dose-related; unknown. Dose-related events of venous thromboembolism occurred in patients treated with abrocitinib (Ref) though Janus kinase (JAK) inhibitors may reduce the risk for cardiovascular disease via inhibition of JAK-dependent cytokines (Ref)
Risk factors:
• Current or past smokers
• Existing cardiovascular or thrombotic risk factors (ie, previous PE, recent hospitalization) (Ref)
• Higher doses (ie, 200 mg) (Ref)
An increased incidence of infection (including serious infection [eg, pneumonia]) has been demonstrated with abrocitinib. Opportunistic infection, including herpes simplex infection and herpes zoster infection have also been reported, including herpes virus reactivation. Invasive fungal infections, tuberculosis, and other bacterial and viral infections have been reported with other nonselective Janus kinase (JAK) inhibitors, although JAK1-selective inhibitors are thought to be less likely to result in opportunistic infections (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Abrocitinib inhibits activity of the JAK1 enzymes, which block signaling of type 1 and type 2 interferons and cytokines which are necessary for lymphocyte development (Ref).
Risk factors:
• Higher doses (ie, 200 mg) (Ref)
• Chronic infection, recurrent infection, or history of serious or opportunistic infection (ie, tuberculosis, hepatitis B virus, herpes virus)
• Underlying conditions that may predispose to infection
Abrocitinib is a Janus kinase inhibitor; therefore, use may result in malignancies, including lymphomas. Nonmelanoma skin cancer (NMSC) has been rarely reported with abrocitinib.
Mechanism: Dose-related; related to the pharmacologic action. Janus kinase (JAK) inhibition interferes with T and NK cells and interferon function (Ref).
Onset: Delayed; most cases of NMSC occurred in the first 3 months of abrocitinib treatment (Ref).
Risk factors:
• Known malignancy (other than successfully treated NMSC)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adolescents and adults.
>10%:
Gastrointestinal: Nausea (6% to 15%)
Infection: Infection (35%; serious infection: ≤1% [including pneumonia]) (table 1)
|
Drug (Abrocitinib) |
Placebo |
Dose |
Number of Patients (Abrocitinib) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
35% |
26% |
200 mg once daily |
590 |
342 |
|
35% |
26% |
100 mg once daily |
608 |
342 |
|
Serious infection: 1% |
0.6% |
100 mg once daily |
608 |
342 |
|
Serious infection: 0.3% |
0.6% |
200 mg once daily |
590 |
342 |
Respiratory: Nasopharyngitis (9% to 12%)
1% to 10%:
Cardiovascular: Hypertension (1%)
Dermatologic: Acne vulgaris (2% to 5%), contact dermatitis (1%), impetigo (2%)
Gastrointestinal: Abdominal distress (1%), gastroenteritis (1%), upper abdominal pain (≤2%), vomiting (2% to 3%)
Genitourinary: Urinary tract infection (2%)
Hematologic & oncologic: Thrombocytopenia (2%)
Infection: Herpes simplex infection (3% to 4%, including reactivation of disease), herpes zoster infection (≤1%, including reactivation of disease), influenza (1%)
Nervous system: Dizziness (2% to 3%), fatigue (1% to 2%), headache (6% to 8%)
Neuromuscular & skeletal: Increased creatinine phosphokinase in blood specimen (3%)
Respiratory: Oropharyngeal pain (1%)
<1%:
Cardiovascular: Acute myocardial infarction, deep vein thrombosis, pulmonary embolism
Endocrine & metabolic: Hyperlipidemia
Hematologic & oncologic: Lymphocytopenia, malignant neoplasm (including nonmelanoma skin cancer [basal cell carcinoma of skin, cutaneous T-cell lymphoma, squamous cell carcinoma]) (Simpson 2021)
Nervous system: Cerebrovascular accident
Ophthalmic: Retinal detachment
Concomitant use of antiplatelet therapy, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to abrocitinib or any component of the formulation.
Concerns related to adverse effects:
• Hematologic toxicity: Hematologic toxicity, including thrombocytopenia and lymphopenia, has been observed in patients treated with abrocitinib.
• Lipid abnormalities: Dose-dependent increases in lipid parameters (eg, total cholesterol, low-density lipoprotein cholesterol, triglycerides) have been observed in patients treated with abrocitinib.
Disease-related concerns:
• Hepatic impairment: Avoid use in patients with severe hepatic impairment or those with active hepatitis B or hepatitis C.
• Renal impairment: Avoid use in patients with severe renal impairment or end-stage renal disease.
Special populations:
• CYP2C19 poor metabolizers: Dose reduction recommended in patients who are known or suspected to be CYP2C19 poor metabolizers due to reduced metabolic clearance of abrocitinib.
Other warnings/precautions:
• Immunizations: Complete all age-appropriate immunizations before initiating therapy; avoid administration of live vaccines immediately prior to, during, and immediately after therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Cibinqo: 50 mg, 100 mg, 200 mg
No
Tablets (Cibinqo Oral)
50 mg (per each): $222.69
100 mg (per each): $222.69
200 mg (per each): $222.69
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Cibinqo: 50 mg, 100 mg, 200 mg
Oral: Administer with or without food. Swallow tablet whole; do not crush, split, or chew.
Oral: Administer with or without food. Swallow tablet whole; do not crush, split, or chew.
Missed doses: Administer missed dose as soon as possible within 12 hours of scheduled dose. If <12 hours until the next scheduled dose, skip the missed dose and resume dosing at regular scheduled time.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Cibinqo: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213871s004lbl.pdf#page=27
Atopic dermatitis, refractory, moderate to severe: Treatment of refractory, moderate to severe atopic dermatitis in adults and pediatric patients ≥12 years of age whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.
Limitations of use: Not recommended for use in combination with other Janus kinase inhibitors, biologic immunomodulators, or other immunosuppressants.
Substrate of CYP2B6 (minor), CYP2C19 (major), CYP2C9 (major), CYP3A4 (minor), OAT1/3; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein/ABCB1
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.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy
Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) may enhance the immunosuppressive effect of Anifrolumab. Risk X: Avoid combination
Aspirin: May enhance the antiplatelet effect of Abrocitinib. Management: Do not use aspirin at doses greater than 81 mg/day with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. Risk D: Consider therapy modification
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). 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
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. 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
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
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
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
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
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the immunosuppressive effect of Abrocitinib. Management: The use of abrocitinib in combination with other immunosuppressants is not recommended. Doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone (for persons over 10 kg) administered for 2 or more weeks are considered immunosuppressive. Risk D: Consider therapy modification
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
CYP2C19 Inducers (Moderate): May decrease the serum concentration of Abrocitinib. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May decrease the serum concentration of Abrocitinib. Risk X: Avoid combination
CYP2C19 Inhibitors (Moderate): May increase the serum concentration of Abrocitinib. Risk C: Monitor therapy
CYP2C9 Inducers (Moderate): May decrease the serum concentration of Abrocitinib. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
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
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Fluconazole: May increase the serum concentration of Abrocitinib. Risk X: Avoid combination
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Immunosuppressants (Cytotoxic Chemotherapy): Abrocitinib may enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): Abrocitinib may enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): Abrocitinib may enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). 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
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Risk C: Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C19 Substrates (High risk with Inducers). Risk C: Monitor therapy
Methotrexate: Abrocitinib may enhance the immunosuppressive effect of Methotrexate. Risk X: Avoid combination
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
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
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. 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
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
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
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
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
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
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
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
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
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. 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
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider therapy modification
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
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). 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.
Agents other than abrocitinib are preferred for the treatment of atopic dermatitis in pregnant patients (Vestergaard 2019).
Data collection to monitor pregnancy and infant outcomes following exposure to abrocitinib is ongoing. Health care providers are encouraged to enroll patients exposed to abrocitinib during pregnancy in the Pregnancy Registry (877-311-3770). Patients may also enroll themselves.
It is not known if abrocitinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 day after the last abrocitinib dose.
CBC (prior to initiating therapy, 4 weeks after initiation, 4 weeks after dose increase, and periodically thereafter in patients who develop hematologic abnormalities); lipid parameters (4 weeks after initiating therapy and periodically thereafter); tuberculosis (TB) screen (baseline and annually thereafter for patients in highly endemic areas for TB); viral hepatitis screening (prior to initiating therapy and periodically thereafter); clinical signs/symptoms of infection (including TB) during and after therapy; skin examinations (periodically, in patients at increased risk for skin cancer); signs/symptoms of thrombosis.
Abrocitinib reversibly inhibits the Janus kinase 1 (JAK1) enzyme by blocking the adenosine triphosphate binding site. Inhibition of JAK1 prevents signaling of interleukin-4, interleukin-13, and other cytokines involved in the pathogenesis of atopic dermatitis (Bieber 2021).
Absorption: >91%.
Distribution: Vd: ~100 L.
Protein binding: ~64% (primarily albumin).
Metabolism: Hepatic via CYP2C19 (~53%), CYP2C9 (~30%), CYP3A4 (~11%), and CYP2B6 (~6%). Metabolized to 2 active metabolites (3-hydroxypropyl [less active than parent] and 2-hydroxypropyl [as active as parent]).
Bioavailability: ~60%.
Half-life elimination: Abrocitinib and active metabolites: 3 to 5 hours.
Time to peak: ≤1 hour.
Excretion: Urine (<1% as unchanged drug; active metabolites predominantly excreted in urine).
Altered kidney function: In patients with moderate (eGFR 30 to 59 mL/minute) and severe (eGFR <30 mL/minute) renal impairment, AUC of abrocitinib and its active metabolites was increased by 110% and 191%, respectively, compared to subjects with normal renal function (eGFR ≥90 mL/minute).
Hepatic function: In patients with mild (Child-Pugh class A) and moderate (Child-Pugh class B) hepatic impairment, AUC of abrocitinib and its active metabolites was increased by ~4% and ~15%, respectively, compared to patients with normal hepatic function.
CYP2C19 poor metabolizers: AUC of abrocitinib was 2.3-fold higher in poor metabolizers compared to normal metabolizers.
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