Ixifi

In combination w/ MTX for reduction of signs & symptoms as well as improvement in physical function in adult patients w/ active disease when response to DMARDs including MTX has been inadequate; w/ severe, active & progressive disease not previously treated w/ MTX or other DMARDs. Moderately to severely active Crohn's disease in adult patients not responsive to full & adequate course of therapy w/ corticosteroid & immunosuppressant; or who are intolerant to or have medical CI for such therapies. Fistulizing Crohn's disease in adult patients not responsive to full & adequate course of conventional treatment including antibiotics, drainage & immunosuppressive therapy. Moderately to severely active ulcerative colitis (UC) in adult patients who have had inadequate response to conventional therapy including corticosteroids & 6-mercaptopurine or azathioprine, or who are intolerant to or have medical CI for such therapies. Ankylosing spondylitis in adult patients who have severe axial symptoms, elevated serological markers of inflammatory activity & who have responded inadequately to conventional therapy. In combination w/ MTX for active & progressive psoriatic arthritis in adult patients who have responded inadequately to DMARDs. Moderate to severe plaque psoriasis in adults who failed to respond to, or who have a CI to, or are intolerant to other systemic therapy including cyclosporine, MTX or PUVA. Severe, active Crohn's disease in ped patients (6-17 yr) not responsive to conventional therapy including corticosteroid, immunomodulator & primary nutrition therapy; or who are intolerant to or have CI for such therapies. Reducing signs & symptoms; inducing & maintaining clinical remission in ped patients (≥6 yr) w/ moderately to severely active UC who have had inadequate response to conventional therapy.

IV Adult ≥18 yr RA 3 mg/kg infusion over a 2-hr period followed by additional 3 mg/kg infusion doses at 2 & 6 wk after 1st infusion then every 8 wk thereafter. To be given concomitantly w/ MTX. Moderately to severely active Crohn's disease 5 mg/kg infusion over a 2-hr period. Maintenance: Additional 5 mg/kg infusions at 2 & 6 wk after initial dose followed by infusions every 8 wk. Fistulizing Crohn's disease Initially 5 mg/kg infusion over a 2-hr period followed w/ additional 5 mg/kg infusion doses at 2 & 6 wk after 1st infusion. Responding patient: Additional 5 mg/kg infusions every 8 wk or re-administration if signs & symptoms of the disease recur followed by 5 mg/kg infusions every 8 wk. UC, psoriatic arthritis & psoriasis 5 mg/kg infusion over a 2-hr period followed by additional 5 mg/kg infusion doses at 2 & 6 wk after 1st infusion then every 8 wk thereafter. Ankylosing spondylitis 5 mg/kg infusion over a 2-hr period followed by additional 5 mg/kg infusion doses at 2 & 6 wk after 1st infusion then every 6-8 wk. Re-administration for Crohn's disease & RA Re-administer w/in 16 wk following last infusion if signs & symptoms recur. Ped 6-17 yr Crohn's disease & UC 5 mg/kg infusion over a 2-hr period followed by additional 5 mg/kg infusion doses at 2 & 6 wk after 1st infusion then every 8 wk thereafter.

Previous severe hypersensitivity reaction to infliximab or any murine proteins. Moderate or severe heart failure (NYHA functional class III/IV). TB or other severe infections (eg, sepsis, abscesses & opportunistic infections).

Discontinue infusion if mild to moderate reactions reoccur or severe hypersensitivity reactions occur during infusion. Closely monitor signs & symptoms of delayed hypersensitivity if retreated after prolonged period. Evaluate for active & inactive (latent) TB before starting treatment. Patients w/ mild heart failure (NYHA class I/II). Immediately interrupt infusion if acute infusion reactions occur; may be pretreated w/ antihistamine, hydrocortisone &/or paracetamol to prevent mild & transient effects. Greater risk of developing Abs in patients who discontinue immunosuppressants prior to or during treatment. Carefully consider the benefit-risk of re-administration after a period of no-treatment especially as re-induction regimen given at wk 0, 2 & 6. Closely monitor for infections including TB before, during & after treatment; not to be given further treatment if patient develops serious infection or sepsis. Not to be given in patient w/ clinically important, active infection. Patients w/ chronic infection or history of recurrent infections including use of concomitant immunosuppressants. Suppression of tumor necrosis factor-α (TNF-α) may mask symptoms of infection (eg, fever). Patients taking TNF-blockers are more susceptible to serious infections. Perform appropriate screening test (eg, tuberculin skin test & chest x-ray); risk of false -ve tuberculin skin test results especially in severely ill or immunocompromised patients. Consider anti-TB therapy before treatment initiation in patients who have several or significant risk factors for TB & have -ve test for latent TB; w/ history of latent or active TB in whom adequate course of treatment cannot be confirmed. Patients who have resided in or traveled to regions where invasive fungal infections (eg, histoplasmosis, coccidioidomycosis or blastomycosis) are endemic; consider appropriate empiric antifungal therapy while diagnostic workup is being performed. Not to be initiated in patients w/ fistulizing Crohn's disease w/ acute suppurative fistulas until source for possible infection specifically abscess has been excluded. Discontinue use if HBV reactivation develops. Evaluate patients at risk for HBV infection before initiating therapy. Evaluate for evidence of liver injury in patients w/ symptoms or signs of liver dysfunction. Discontinue use if jaundice &/or ALT elevations ≥5 times ULN develops. Not recommended to be used concurrently w/ etanercept, anakinra; abatacept; other biological products; live vaccines; therapeutic infectious agents eg, live attenuated bacteria (eg, BCG bladder instillation for cancer treatment). Monitor patients when switching from one biological DMARD to another. Not to be given further treatment if patient develops symptoms suggestive of lupus-like syndrome & +ve for Ab against double-stranded DNA. Patients w/ neurologic disorders; consider discontinuation if seizure & new onset or exacerbation of clinical symptoms &/or radiographic evidence of CNS demyelinating disorders develop. Risk of malignancies & lymphoproliferative disorders. Patients w/ increased risk of malignancy due to heavy smoking; w/ psoriasis & medical history of extensive immunosuppressant therapy or prolonged PUVA treatment. Monitor psoriasis patients for non-melanoma skin cancers particularly those who have had prior prolonged phototherapy treatment. Risk of developing of hepatosplenic T-cell lymphoma. Screen patients w/ UC who are at increased risk or who had prior history of dysplasia or colon carcinoma at regular intervals prior to therapy & throughout disease course. Possible acute & chronic leukemia; melanoma & Merkel cell carcinoma. Periodic skin exam is recommended for all patients particularly those w/ risk factors for skin cancer. Increased incidence of cervical cancer in women w/ RA treated w/ infliximab; periodic screening in women treated w/ Ixifi including those >60 yr. Patients w/ history of malignancy or when considering continuing treatment in patients who develop malignancy. Consider discontinuation in patients who develop significant hematologic abnormalities. Closely monitor for infections in patient who requires surgery while on Ixifi. Patients who have undergone arthroplasty. Not recommended in patients w/ intestinal strictures due to Crohn's disease. Re-administration for UC & psoriatic arthritis other than every 8 wk; for ankylosing spondylitis other than every 6 to 8 wk; for psoriasis. May affect ability to drive or use machinery. Renal & hepatic impairment. Women of childbearing potential should use adequate contraception & continue its use for at least 6 mth after last infliximab treatment. Increased risk of adverse pregnancy outcomes in women w/ inflammatory bowel disease or RA-associated w/ increased disease activity. Pregnancy & lactation. Potential ped malignancy. Potentially fatal outcome in infant who received BCG vaccine after in utero exposure to infliximab; 12-mth waiting period following birth is recommended prior to live vaccine administration. Consider benefit-risk of live vaccine administration prior to 12 mth of age. Childn <6 yr w/ Crohn's disease or UC. Elderly.

Viral infection (eg, flu, herpes infections); serum sickness-like reactions; headache, vertigo/dizziness; flushing; upper & lower resp tract infections (eg, bronchitis, pneumonia), dyspnea, sinusitis; nausea, diarrhea, abdominal pain, dyspepsia, vomiting; abnormal hepatic function, cholecystitis; rash, pruritus, urticaria, increased sweating, dry skin; fatigue, chest pain, infusion-related reactions, fever; elevated hepatic transaminases.

Formation of Abs may be reduced & plasma conc may be increased w/ MTX & other immunomodulators. Not recommended in combination w/ other biological therapeutics used to treat the same conditions including anakinra & abatacept. Not to be given concurrently w/ live vaccines; therapeutic infectious agents.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs) / Immunosuppressants

L04AB02 - infliximab ; Belongs to the class of tumor necrosis factor alpha (TNF-alpha) inhibitors. Used as immunosuppressants.

POM