infliximab

REMS

Moderately to severely active rheumatoid arthritis (in combination with methotrexate).
Moderately to severely active Crohn's disease in patients with an inadequate response to conventional therapy.
Active psoriatic arthritis.
Active ankylosing spondylitis.
Moderately to severely active ulcerative colitis in patients with an inadequate response to conventional therapy.
Chronic severe plaque psoriasis in patients who are candidates for systemic therapy and when other systemic therapies are less appropriate.

Action ⬆ ⬇

Neutralizes and prevents the activity of tumor necrosis factor-alpha (TNF-alpha), resulting in anti-inflammatory and antiproliferative activity.

Therapeutic effects:

Decreased signs and symptoms, decreased rate of joint destruction, and improved physical function in rheumatoid arthritis and psoriatic arthritis.
Decreased signs and symptoms and induction and maintenance of clinical remission in Crohn's disease.
Reduction in number of fistulas and maintenance of closure of fistulae in Crohn's disease.
Decreased signs and symptoms in ankylosing spondylitis.
Decreased signs and symptoms, maintenance of clinical remission and mucosal healing, and eliminating corticosteroid use in ulcerative colitis.
Decreased induration, scaling, and erythema of psoriatic lesions.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Predominantly distributed within the vascular compartment.

Metabolism/Excretion: Unknown.

Half-Life: 9.5 days.

Time/Action Profile ⬆ ⬇

(symptoms of Crohn’s disease)

ROUTE	ONSET	PEAK	DURATION
IV	1–2 wk	unknown	12–48 wk‡

‡After infusion.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to infliximab, murine (mouse) proteins, or other components in the formulation;
Moderate to severe HF (doses >5 mg/kg);
Concurrent anakinra or abatacept.

Use Cautiously in:

History of chronic or recurrent infection or underlying illness/treatment predisposing to infection;
Patients being retreated after 2 yr without treatment (↑ risk of adverse reactions);
History of tuberculosis or exposure (latent tuberculosis should be treated prior to infliximab therapy);
History of opportunistic infection;
Moderate to severe HF (doses ≤5 mg/kg);
Patients residing, or who have resided, where tuberculosis, histoplasmosis, coccidioidomycoses, or blastomycosis is endemic;
Chronic obstructive pulmonary disease (↑ risk of malignancy);
OB: Use only if potential maternal benefit justifies potential fetal risk; infants exposed in utero may be at ↑ risk for infection or agranulocytosis;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children <6 yr (safety not established); ↑ risk of lymphoma (including hepatosplenic T-cell lymphoma [HSTCL] in patients with Crohn's disease or ulcerative colitis), leukemia, and other malignancies;
Geri: ↑risk of adverse reactions, including serious infections, in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIAS, chest pain, edema, HF, hypertension, hypotension, MYOCARDIAL ISCHEMIA/INFARCTION, pericardial effusion, tachycardia, vasculitis

Derm: acne, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS (AGEP), alopecia, dry skin, ecchymosis, eczema, erythema, flushing, hematoma, hot flushing, pruritus, psoriasis, rash, STEVENS-JOHNSON SYNDROME, sweating, TOXIC EPIDERMAL NECROLYSIS, urticaria

EENT: conjunctivitis, vision loss

GI: abdominal pain, nausea, vomiting, constipation, diarrhea, dyspepsia, flatulence, hepatotoxicity, intestinal obstruction, oral pain, tooth pain, ulcerative stomatitis

GU: dysuria, urinary frequency, urinary tract infection

Hemat: neutropenia

MS: arthralgia, arthritis, back pain, involuntary muscle contractions, myalgia

Neuro: fatigue, headache, anxiety, depression, dizziness, insomnia, paresthesia, STROKE

Resp: upper respiratory tract infection, bronchitis, cough, dyspnea, laryngitis, pharyngitis, respiratory tract allergic reaction, rhinitis, sinusitis

Misc: fever, infusion reactions, chills, flu-like syndrome, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), INFECTION (INCLUDING REACTIVATION TUBERCULOSIS AND OTHER OPPORTUNISTIC INFECTIONS DUE TO BACTERIAL, INVASIVE FUNGAL, VIRAL, MYCOBACTERIAL, AND PARASITIC PATHOGENS), lupus-like syndrome, MALIGNANCY (INCLUDING LYMPHOMA, HSTCL, LEUKEMIA, SKIN CANCER, AND CERVICAL CANCER), pain, SARCOIDOSIS

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with anakinra or abatacept↑ risk of serious infections (not recommended).
Concurrent use with azathioprine and/or methotrexate may ↑ risk of HSTCL.
Use of live virus vaccines or therapeutic infectious agents may ↑ risk of infection; avoid concurrent use; wait for ≥6 mo before administering any live vaccines to infants exposed in utero.

Route/Dosage ⬆ ⬇

Rheumatoid Arthritis

IV (Adults ): 3 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then repeat every 8 wk; dose may be adjusted in partial responders up to 10 mg/kg or treatment as often as every 4 wk (to be used with methotrexate).

Crohn's Disease

IV (Adults ): 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg every 8 wk; dose may be adjusted up to 10 mg/kg in patients who initially respond and then lose their response.
IV (Children ): 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg every 8 wk.

Ankylosing Spondylitis

IV (Adults ): 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg every 6 wk.

Psoriatic Arthritis

IV (Adults ): 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg every 8 wk (to be used with or without methotrexate).

Ulcerative Colitis

IV (Adults and Children ≥6 yr): 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg every 8 wk.

Plaque Psoriasis

IV (Adults ): 5 mg/kg initially, then repeat at 2 and 6 wk after initial infusion, then maintenance dose of 5 mg/kg every 8 wk.

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 100 mg/vial

Assessment ⬆ ⬇

Assess for infusion-related reactions (fever, chills, urticaria, pruritus) during and for 2 hr after infusion. Symptoms usually resolve when infusion is discontinued. Reactions are more common after 1st or 2nd infusion. Frequency of reactions may be reduced with immunosuppressant agents.
Monitor patients who develop a new infection while taking infliximab closely. Discontinue therapy in patients who develop a serious infection or sepsis. Do not initiate therapy in patients with active infections.
Assess for signs and symptoms of systemic infections (fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock). Ascertain if patient lives in or has traveled to areas of endemic mycoses. Consider empiric antifungal treatment for patients at risk of histoplasmosis and other invasive fungal infections until the pathogens are identified. Consult with an infectious diseases specialist. Consider stopping infliximab until the infection has been diagnosed and adequately treated.
Assess for latent tuberculosis with a tuberculin skin test prior to initiation of and during therapy. Treatment of latent tuberculosis should be initiated prior to therapy with infliximab.
Monitor patient for hypersensitivity reactions (urticaria, dyspnea, hypotension) during infusion. Discontinue infliximab if severe reaction occurs. Have medications (antihistamines, acetaminophen, corticosteroids, epinephrine) and equipment readily available in the event of a severe reaction.
Rheumatoid Arthritis: Assess pain and range of motion prior to and periodically during therapy.
Crohn’s Disease and Ulcerative Colitis: Assess for signs and symptoms before, during, and after therapy.
Psoriasis: Assess lesions periodically during therapy.

Lab Test Considerations:

May cause ↑ in positive ANA. Frequency may be decreased with baseline immunosuppressant therapy.
- Monitor liver function tests periodically during therapy. May cause mild to moderate AST and ALT ↑ without progressing to liver dysfunction. If patient develops jaundice or liver enzyme elevations ≥5 times the upper limits of normal, discontinue infliximab.
- Monitor CBC with differential periodically during therapy. May cause leukopenia, neutropenia, thrombocytopenia, and pancytopenia. Discontinue infliximab if symptoms of blood dyscrasias (persistent fever) occur.

Implementation ⬆ ⬇

Do not confuse infliximab with rituximab.
Ensure vaccinations are brought up to date in adult and pediatric patients before starting therapy.

IV Administration:

Intermittent Infusion: Calculate the total number of vials needed. Reconstitution: Reconstitute each vial with 10 mL of sterile water for injection using a syringe with a 21-gauge needle or smaller. Direct stream to sides of vial. Do not use if vacuum is not present in vial. Gently swirl solution by rotating vial to dilute; do not shake. May foam on reconstitution; allow to stand for 5 min. Solution is colorless to light yellow and opalescent; a few translucent particles may develop because infliximab is a protein. Do not use if opaque particles, discoloration, or other particles occur. Diluent: Withdraw volume of total infliximab dose from infusion container containing 250 mL with 0.9% NaCl. Slowly add total dose of infliximab. Do not dilute with other solutions.Concentration: 0.4 to 4 mg/mL. Mix gently. Infusion should begin within 3 hr (4 hr for Renflexis) of preparation. Solution is incompatible with polyvinyl chloride equipment. Prepare in glass infusion bottle or polypropylene or polyolefin bags. Do not reuse or store any portion of infusion solution. Unopened vials are stable for 6 mo at room temperature; once removed from refrigerator, cannot be returned to the refrigerator. Diluted solution is stable for 4 hr at room temperature, 34 days if refrigerated, and 6 hr at room temperature when removed from refrigerator.
Rate: Administer over at least 2 hr through polyethylene-lined administration set with an in-line, sterile, nonpyrogenic, low protein-building filter with ≤1.2-micron pore size.
Y-Site Incompatibility: Do not administer concurrently in the same line with any other agents.

Patient/Family Teaching ⬆ ⬇

Explain purpose of infliximab to patient.
Advise patient that adverse reactions (myalgia, rash, fever, polyarthralgia, pruritus) may occur 3–12 days after delayed (>2 yr) retreatment with infliximab. Symptoms usually decrease or resolve within 1–3 days. Instruct patient to notify health care professional if symptoms occur.
May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional promptly if symptoms of fungal infection occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient of risk of malignancies such as hepatosplenic T-cell lymphoma. Instruct patient to report signs and symptoms (splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) to health care professional promptly.
Advise patient to examine skin periodically during therapy and notify health care professional of any changes in appearance of skin or growths on skin.
Instruct patient not to receive live vaccines during therapy.
Advise females to continue regular PAP smears for cervical cancer screening.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and or if breastfeeding. Infants exposed to infliximab in utero should wait at least 6 mo before receiving any live vaccine; may be at increased risk of infection.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇