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tofacitinib (Rx)Brand and Other Names:Xeljanz, Xeljanz XR

 
 
 

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet (Xeljanz)

  • 5mg

tablet, extended-release (Xeljanz XR)

  • 11mg
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Rheumatoid Arthritis

Indicated as second-line treatment for moderate-to-severe active rheumatoid arthritis in patients with an inadequate response or intolerance to methotrexate; may be used as monotherapy or in combination with methotrexate or other nonbiologic DMARDs

5 mg PO BID or 11 mg PO qDay

Dosage Modifications

Coadministration with strong CYP3A4 inhibitors: Not to exceed 5 mg qDay

Coadministration with 1 or more drugs that result in both moderate CYP3A4 inhibition and strong CYP2C19 inhibition (eg, fluconazole): Not to exceed 5 mg qDay

Coadministration with strong CYP3A4 inducers: May result in loss of or reduced clinical response; coadministration is not recommended

Coadministration with methotrexate: No dosage adjustment required

Coadministration with P-gp inhibitors: No dosage adjustment required

Renal impairment

  • Mild: No dosage adjustment required
  • Moderate-to-severe: Not to exceed 5 mg qDay

Hepatic impairment

  • Mild: No dosage adjustment required
  • Moderate: Not to exceed 5 mg qDay
  • Severe: Not recommended

Serious infection

  • Interrupt treatment if serious infection develops until infection is controlled
  • Lymphocytes ≥500/mm³: Maintain dose
  • Lymphocytes <500/mm³: Discontinue until infection controlled

Neutropenia

  • ANC >1000/mm³: Maintain dose
  • ANC 500-1000/mm³: Interrupt dosing for persistent decreases; when ANC >1000/mm³, resume dose at 5 mg BID
  • ANC <500/mm³: Discontinue

Anemia

  • Hgb ≤2 g/dL decrease and level ≥9.0 g/dL: Maintain dose
  • Hgb >2g/dL decrease or level <8.0 g/dL: Interrupt treatment until Hgb levels have normalized

Dosing Considerations

Should not be used in combination with biologic DMARDs or potent immunosuppressive agents (eg, azathioprine, cyclosporine)

Structural joint damage progression

  • Radiographic response data from the ORAL Scan and ORAL Start studies evaluated the efficacy of tofacitinib on structural joint damage progression as measured by mean change from baseline in van der Heijde modified Total Sharp Score (mTSS) and its components, erosion score, and joint space narrowing (JSN) score
  • In ORAL Scan, 74% of patients in the placebo/methotrexate group experienced no radiographic progression at Month 6 compared to 84% of patients treated with tofacitinib 5mg BID plus methotrexate
  • In ORAL Start, 55% of patients in the methotrexate group experienced no radiographic progression at Month 6 compared to 73% of patients treated with tofactinib 5mg BID

Safety and efficacy not established

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Interactions

Interaction Checker

tofacitinib and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Overall infections (20-22%)

            1-10%

            URTI (4.5%)

            Headache (4.3%)

            Diarrhea (4%)

            Nasopharyngitis (3.8%)

            UTI (2%)

            Hypertension (1.6%)

            <1%

            ANC <500/mm³ (0.07%)

            Lymphocytes <500/mm³ (0.04%)

            Frequency Not Defined

            Serious infections: 1.7 events per 100 patient-years

            Malignancies: 0.3 events per 100 patient-years

            Postmarketing reports

            Diverticulitis

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            Warnings

            Black Box Warnings

            Serious infections

            • Increased risk for developing serious infections that may lead to hospitalization or death; most patients who developed these infections were taking concomitant immunosuppressants (eg, methotrexate, corticosteroid)
            • If serious infection develops, interrupt until infection controlled
            • Reported infections include active TB, invasive fungal infections, and bacterial, viral, or other opportunistic pathogens
            • Test patients for latent TB before and during tofacitinib treatment; treatment for latent TB infection should be initiated prior to tofacitinib treatment

            Malignancies

            • Lymphoma and other malignancies reported
            • Epstein Barr virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with tofacitinib and concomitant immunosuppressive medications

            Contraindications

            None

            Cautions

            Serious and sometimes fatal infections reported due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens (see Black Box Warnings)

            Malignancy and lymphoproliferative disorders reported (see Black Box Warnings)

            GI perforation reported, although role of JAK inhibition in these events is unknown; caution in patients at increased risk for gastrointestinal perforation (eg, diverticulitis)

            Associated with gradual decrease in lymphocyte and neutrophils counts, and hemoglobin levels that may require treatment interruption (see Dosage Modifications)

            Associated with increased LFTs

            Associated with increase lipid parameters including total cholesterol, LDL, and HDL

            Avoid coadministration with live virus vaccines

            Not recommended with severe hepatic impairment

            Strong CYP3A4 inducers may decrease clinical response

            Decreased dose required if coadministered with strong CYP3A4 inhibitors, or moderate CYP3A4 inhibitors plus CYP2C19 inhibitors (see Dosage Modifications)

            Avoid use in patients with active, serious infection, including localized infections

            Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), reported; impact on chronic viral hepatitis reactivation unknown; perform screening for viral hepatitis in accordance with clinical guidelines before starting therapy

            Non-melanoma skin cancers (NMSCs) reported; periodic skin examination recommended for patients at increased risk for skin cancer

            Decreased dose required with moderate hepatic impairment or moderate-to-severe renal impairment (see Dosage Modifications)

            Use caution when treating patients with diabetes; higher incidence of infection in diabetic population in general reported

            Diverticulitis reported

            Extended-release tablet

            • Patients may notice an inert tablet shell passing in the stool or via colostomy
            • Caution when administering the extended-release tablet to patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic); rare reports of obstructive symptoms with strictures in association with the ingestion of other drugs utilizing a non-deformable extended release formulation
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            Pregnancy & Lactation

            Pregnancy Category: C

            Lactation: Unknown whether distributed in human breast milk; decision should be made whether to discontinue nursing or the drug, taking into account the importance of therapy to the mother

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Janus kinases (JAKs) pathways inhibitor; JAK consists of a group of intracellular tyrosine kinases that transmit signals from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoieses and immune cell function

            Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression; tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs

            These signals are essential in maintaining the inflammatory condition in rheumatoid arthritis (RA); inhibition of JAKs reduces production of and modulates proinflammatory cytokines central to RA

            Absorption

            Bioavailability: 74%

            Peak Plasma Time: 0.5-1 hr

            Distribution

            Protein Bound: ~40% (predominately to albumin)

            Vd: 87 L (following IV administration)

            Distributes equally between RBCs and plasma

            Metabolism

            Clearance mechanisms: ~70% hepatic metabolism and 30% renal excretion

            Primarily metabolized by CYP3A4 (accounting for ~53% of total clearance) and by CYP2C19 (accounting for ~17% of total clearance)

            Metabolites: Potency <10% of parent compound

            Elimination

            Half-life: 3 hr

            Renal clearance: 30%

            Excretion: 30% urine

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            Administration

            Oral Administration

            May take with or without food

            Extended-release tablets: Swallow whole; do not crush, split, or chew

            Switching from regular tablets to extended-release

            • 5 mg BID may be switched to extended-release 11 mg once daily the day following the last dose of 5 mg BID
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            Images

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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