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Special Alerts
Tumor Necrosis Factor (TNF) Blockers: Surveillance of Malignancies in Pediatric, Adolescent, and Young Adult Patients
November 2011
The U.S. Food and Drug Administration (FDA) is updating the public about an ongoing surveillance program of reported cases of malignancy in patients ≤30 years of age treated with TNF blockers, including adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab. The FDA is requiring enhanced safety surveillance by the manufacturers of TNF blockers to include:
- In-depth follow-up on all reported malignancy cases
- Expedited reporting of all malignancy cases to the FDA
- Yearly summary and assessment of malignancies and TNF blocker usage data
Collected data will be re-evaluated periodically by the FDA over the next 10 years. Healthcare professionals should continue to be alert for possible malignancies in patients being treated with TNF blockers and report positive findings to the FDA's MedWatch program (1-800-332-1088 or https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm) or to the manufacturer.
For additional information, please refer to http://www.fda.gov/Drugs/DrugSafety/ucm278267.htm
Tumor Necrosis Factor-alpha (TNFα) Blockers: Risk of Infection from Legionella and Listeria
September 2011
The U.S. Food and Drug Administration (FDA) is notifying healthcare professionals of an update to the Boxed Warning for the entire class of tumor necrosis factor-alpha (TNFα) blockers including Remicade® (infliximab), Enbrel® (etanercept), Humira® (adalimumab), Cimzia® (certolizumab pegol), and Simponi® (golimumab). The Boxed Warning will include the risk of infection from two bacterial pathogens, Legionella and Listeria.
For additional information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm270977.htm
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(in FLIKS e mab)
Generic Available (U.S.)
No
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.remicade.com/remicade/assets/Med_Guide.pdf, must be dispensed with this medication.
REMS Components
Remicade®: Released from REMS requirement 8/1/2011
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of moderately- to severely-active rheumatoid arthritis (with methotrexate)
Treatment of moderately- to severely-active Crohn's disease with inadequate response to conventional therapy (to reduce signs/symptoms and induce and maintain clinical remission) or to reduce the number of draining enterocutaneous and rectovaginal fistulas and maintain fistula closure
Treatment of psoriatic arthritis (to reduce signs/symptoms of active arthritis and inhibit progression of structural damage and improve physical function)
Treatment of chronic severe plaque psoriasis
Treatment of active ankylosing spondylitis (reduce signs/symptoms)
Treatment of moderately- to severely-active ulcerative colitis with inadequate response to conventional therapy (reduce signs/symptoms and induce and maintain clinical remission, mucosal healing and eliminate corticosteroid use)
Pregnancy Risk Factor
B
Pregnancy Considerations
Reproduction studies have not been conducted. Use during pregnancy only if clearly needed. A Rheumatoid Arthritis and Pregnancy Registry has been established for women exposed to infliximab during pregnancy (Organization of Teratology Information Services, 877-311-8972).
Lactation
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
It is not known whether infliximab is secreted in human milk. Because many immunoglobulins are secreted in milk and the potential for serious adverse reactions exists, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Contraindications
Hypersensitivity to infliximab, murine proteins or any component of the formulation; doses >5 mg/kg in patients with moderate or severe heart failure (NYHA Class III/IV)
Canadian labeling: Additional contraindications (not in U.S. labeling): Severe infections (eg, sepsis, abscesses, tuberculosis, and opportunistic infections)
Warnings/Precautions
Boxed warnings:
• Infections: See “Concerns related to adverse effects” below.
• Malignancy: See “Concerns related to adverse effects” below.
• Tuberculosis: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Autoimmune disorder: Positive antinuclear antibody titers have been detected in patients (with negative baselines). Rare cases of autoimmune disorder, including lupus-like syndrome, have been reported; monitor and discontinue if symptoms develop.
• Hematologic disorders: Hematologic toxicities (eg, leukopenia, neutropenia, thrombocytopenia, pancytopenia) have been reported. Patients must be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias; discontinue if significant hematologic abnormalities are confirmed. Use with caution in patients with history of hematologic abnormalities.
• Hepatic reactions: Severe hepatic reactions (including hepatitis, jaundice, acute hepatic failure, and cholestasis) have been reported during treatment; discontinue with jaundice or marked increase in liver enzymes (≥5 times ULN).
• Hepatitis B: Rare reactivation of hepatitis B (HBV) has occurred in chronic carriers of the virus, usually in patients receiving concomitant immunosuppressants; evaluate for HBV prior to initiation in all patients. Monitor during and for several months following discontinuation of treatment in HBV carriers; interrupt therapy if reactivation occurs and treat appropriately with antiviral therapy; if resumption of therapy is deemed necessary, exercise caution and monitor patient closely.
• Hypersensitivity or infusion reactions: Acute infusion reactions may occur. Hypersensitivity reaction may occur within 2 hours of infusion. Medication and equipment for management of hypersensitivity reaction should be available for immediate use. Interruptions and/or reinstitution at a slower rate may be required (consult protocols). Pretreatment may be considered, and may be warranted in all patients with prior infusion reactions. Serum sickness-like reactions have occurred; may be associated with a decreased response to treatment. The development of antibodies to infliximab may increase the risk of hypersensitivity and/or infusion reactions; concomitant use of immunosuppressants may lessen the development of anti-infliximab antibodies. The risk of infusion reactions may be increased with retreatment after an interruption or discontinuation of prior maintenance therapy. Retreatment in psoriasis patients should be resumed as a scheduled maintenance regimen without any induction doses; use of an induction regimen should be used cautiously for retreatment of all other patients.
• Infections: [U.S. Boxed Warning]: Patients receiving infliximab are at increased risk for serious infections which may result in hospitalization and/or fatality; infections usually developed in patients receiving concomitant immunosuppressive agents (eg, methotrexate or corticosteroids) and may present as disseminated (rather than local) disease. Active tuberculosis (or reactivation of latent tuberculosis), invasive fungal (including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and bacterial, viral or other opportunistic infections (including legionellosis and listeriosis) have been reported in patients receiving TNF-blocking agents, including infliximab. Monitor closely for signs/symptoms of infection. Discontinue for serious infection or sepsis. Consider risks versus benefits prior to use in patients with a history of chronic or recurrent infection. Consider empiric antifungal therapy in patients who are at risk for invasive fungal infection and develop severe systemic illness. Caution should be exercised when considering use in the elderly or in patients with conditions that predispose them to infections (eg, diabetes) or residence/travel from areas of endemic mycoses (blastomycosis, coccidioidomycosis, histoplasmosis), or with latent or localized infections. Do not initiate infliximab therapy with clinically important active infection. Patients who develop a new infection while undergoing treatment should be monitored closely.
• Malignancy: [U.S. Boxed Warning]: Lymphoma and other malignancies have been reported in children and adolescent patients receiving TNF-blocking agents including infliximab. Half the cases are lymphomas (Hodgkin's and non-Hodgkin's) and the other cases are varied but include malignancies not typically observed in this population. [U.S. Boxed Warning]: Hepatosplenic T-cell lymphoma has been reported in patients with Crohn's disease or ulcerative colitis treated with infliximab and concurrent or prior azathioprine or mercaptopurine use, usually reported in adolescent and young adult males. The impact of infliximab on the development and course of malignancies is not fully defined, but may be dose dependent. As compared to the general population, an increased risk of lymphoma has been noted in clinical trials; however, rheumatoid arthritis alone has been previously associated with an increased rate of lymphoma. Use caution in patients with a history of COPD, higher rates of malignancy were reported in COPD patients treated with infliximab. Psoriasis patients with a history of phototherapy had a higher incidence of nonmelanoma skin cancers.
• Tuberculosis: [U.S. Boxed Warning]: Infliximab treatment has been associated with active tuberculosis (may be disseminated or extrapulmonary) or reactivation of latent infections. Evaluate patients for tuberculosis risk factors and latent tuberculosis infection (with a tuberculin skin test) prior to and during therapy. Treatment of latent tuberculosis should be initiated before use. Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis throughout treatment. Most cases of reactivation have been reported within the first 3-6 months of treatment. Caution should be exercised when considering the use in patients who have been exposed to tuberculosis.
Disease-related concerns:
• Demyelinating CNS disease: Use with caution in patients with pre-existing or recent onset CNS demyelinating disorders; rare cases of optic neuritis and demyelinating disease (including multiple sclerosis, systemic vasculitis, and Guillain-Barré syndrome) have been reported; consider discontinuation of therapy if patient develops significant CNS reactions.
• Heart failure (HF): Use with caution in patients with mild HF (NYHA Class I, II) or decreased left ventricular function; worsening and new-onset HF has been reported; doses >5 mg/kg should not be administered in patients with moderate-to-severe heart failure (NYHA Class III/IV); discontinue therapy with onset of new or worsening symptoms.
• Seizure disorders: Use with caution in patients with a history of seizures; discontinue if significant CNS adverse reactions develop.
Concurrent drug therapy issues:
• Abatacept: Serious infections were reported when abatacept was used with other TNF-blocking agents; therefore, concurrent use of infliximab and abatacept is not recommended.
• Anakinra: Serious infections were reported when anakinra was used with another TNF-blocking agent (etanercept); therefore, concurrent use of infliximab and anakinra is not recommended.
• Biological disease-modifying antirheumatic drugs (DMARDs): Use caution when switching from one biologic DMARD to another; overlapping biological activities may further increase the risk of infection.
Special populations:
• Pediatrics: Malignancies have been reported among children and adolescents receiving TNF-blocking agents. Efficacy was not established in a study to evaluate infliximab use in juvenile idiopathic arthritis (JIA). Safety and efficacy for use in plaque psoriasis or ulcerative colitis have not been established in children. Note: For use in Crohn's disease: Safety and efficacy have not been established in children <6 years of age (U.S. labeling) and in children <9 years of age (Canadian labeling).
Other warnings/precautions:
• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
Adverse Reactions
Although profile is similar, frequency of adverse effects may vary with disease state. Except where noted, percentages reported in adults with rheumatoid arthritis:
>10%:
Central nervous system: Headache (18%)
Gastrointestinal: Nausea (21%), diarrhea (12%), abdominal pain (12%; Crohn's 26%)
Hepatic: ALT increased (risk increased with concomitant methotrexate)
Respiratory: Upper respiratory tract infection (32%), sinusitis (14%), cough (12%), pharyngitis (12%)
Miscellaneous: Development of antinuclear antibodies (~50%), infection (36%), infusion reactions (20%; severe <1%), development of antibodies to double-stranded DNA (20%), development of new abscess (Crohn's patients with fistulizing disease: 15%), anti-infliximab antibodies (variable; ~10% to 15% [range: 6% to 61%]; Mayer, 2006)
5% to 10%:
Cardiovascular: Hypertension (7%)
Central nervous system: Fatigue (9%), pain (8%), fever (7%)
Dermatologic: Rash (1% to 10%), pruritus (7%)
Gastrointestinal: Dyspepsia (10%)
Genitourinary: Urinary tract infection (8%)
Neuromuscular & skeletal: Arthralgia (1% to 8%), back pain (8%)
Respiratory: Bronchitis (10%), rhinitis (8%), dyspnea (6%)
Miscellaneous: Moniliasis (5%)
<5%: Abscess, adult respiratory distress syndrome, allergic reaction, anemia, arrhythmia, basal cell carcinoma, biliary pain, bradycardia, brain infarction, breast cancer, cardiac arrest, cellulitis, cholecystitis, cholelithiasis, circulatory failure, confusion, constipation, dehydration, delayed hypersensitivity (plaque psoriasis), diaphoresis increased, dizziness, edema, gastrointestinal hemorrhage, heart failure, hemolytic anemia, hepatitis, hypersensitivity reactions, hypotension, ileus, intervertebral disk herniation, intestinal obstruction, intestinal perforation, intestinal stenosis, leukopenia, lupus-like syndrome, lymphadenopathy, lymphoma, malignancies, meningitis, menstrual irregularity, MI, myalgia, neuritis, pancreatitis, pancytopenia, peripheral neuropathy, peritonitis, pleural effusion, pleurisy, proctalgia, pulmonary edema, pulmonary embolism, renal calculus, renal failure, respiratory insufficiency, seizure, sepsis, serum sickness, suicide attempt, syncope, tachycardia, tendon disorder, thrombocytopenia, thrombophlebitis (deep), ulceration
The following adverse events were reported in children with Crohn's disease and were found more frequently in children than adults:
>10%:
Hepatic: Liver enzymes increased (18%; ≥5 times ULN: 1%)
Hematologic: Anemia (11%)
Miscellaneous: Infections (56%; more common with every 8-week versus every 12-week infusions)
1% to 10%:
Central nervous system: Flushing (9%)
Gastrointestinal: Blood in stool (10%)
Hematologic: Leukopenia (9%), neutropenia (7%)
Neuromuscular & skeletal: Bone fracture (7%)
Respiratory: Respiratory tract allergic reaction (6%)
Miscellaneous: Viral infection (8%), bacterial infection (6%), antibodies to infliximab (3%)
Postmarketing and/or case reports (adults or children): Agranulocytosis, anaphylactic reactions, anaphylactic shock, angina, angioedema, autoimmune hepatitis, bronchospasm, central demyelinating disorders (eg, multiple sclerosis, optic neuritis); cholestasis, drug-induced lupus-like syndrome, erythema multiforme, heart failure (worsening), hepatic carcinoma, hepatitis B reactivation, hepatocellular damage, hepatosplenic T-cell lymphoma (HSTCL), Hodgkin's disease, idiopathic thrombocytopenia purpura, interstitial fibrosis, interstitial pneumonitis, jaundice, laryngeal/pharyngeal edema, latent tuberculosis reactivation, leiomyosarcoma, leukemias, liver failure, liver function tests increased, melanoma, neuropathy, numbness, opportunistic infection, pericardial effusion, peripheral demyelinating disorders (eg, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy); pneumonia, psoriasis (including new onset, palmoplantar, pustular, or exacerbation), renal cell carcinoma, seizure, Stevens-Johnson syndrome, thrombotic thrombocytopenia purpura, taste abnormal, tingling, toxic epidermal necrolysis, transverse myelitis, tuberculosis, urticaria, vasculitis (systemic and cutaneous)
Metabolism/Transport Effects
None known.
Drug Interactions
Abatacept: Anti-TNF Agents may enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Abciximab: May enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Risk C: Monitor therapy
Anakinra: Anti-TNF Agents may enhance the adverse/toxic effect of Anakinra. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Risk X: Avoid combination
Canakinumab: Anti-TNF Agents may enhance the adverse/toxic effect of Canakinumab. Specifically, the risk for serious infections and/or neutropenia may be increased. Risk X: Avoid combination
Certolizumab Pegol: Anti-TNF Agents may enhance the immunosuppressive effect of Certolizumab Pegol. Risk X: Avoid combination
Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Rilonacept: Anti-TNF Agents may enhance the adverse/toxic effect of Rilonacept. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid echinacea (may diminish the therapeutic effect of infliximab).
Storage
Store vials at 2°C to 8°C (36°F to 46°F).
Reconstitution
Reconstitute vials with 10 mL sterile water for injection. Swirl vial gently to dissolve powder; do not shake. Allow solution to stand for 5 minutes. Total dose of reconstituted product should be further diluted to 250 mL of 0.9% sodium chloride injection to a final concentration of 0.4-4 mg/mL. Infusion of dose should begin within 3 hours of preparation.
Compatibility
Stable in NS; do not infuse with other agents.
Mechanism of Action
Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha (TNFα), thereby interfering with endogenous TNFα activity. Elevated TNFα levels have been found in involved tissues/fluids of patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis. Biological activities of TNFα include the induction of proinflammatory cytokines (interleukins), enhancement of leukocyte migration, activation of neutrophils and eosinophils, and the induction of acute phase reactants and tissue degrading enzymes. Animal models have shown TNFα expression causes polyarthritis, and infliximab can prevent disease as well as allow diseased joints to heal.
Pharmacodynamics/Kinetics
Onset of action: Crohn's disease: ~2 weeks
Distribution: Vd: 3-6 L
Half-life elimination: 7-12 days
Dosage
I.V.: Note: Premedication with antihistamines (H1-antagonist +/- H2-antagonist), acetaminophen, and/or corticosteroids may be considered to prevent and/or manage infusion-related reactions:
Children: U.S. labeling ≥6 years, Canadian labeling ≥9 years: Crohn's disease: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter; if no response by week 14, consider discontinuing therapy
Children ≥6 years: Ulcerative colitis: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter
Adults:
Crohn's disease: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter; dose may be increased to 10 mg/kg in patients who respond but then lose their response. If no response by week 14, consider discontinuing therapy.
Psoriatic arthritis (with or without methotrexate): 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter
Rheumatoid arthritis (in combination with methotrexate therapy): 3 mg/kg at 0, 2, and 6 weeks, followed by 3 mg/kg every 8 weeks thereafter; doses have ranged from 3-10 mg/kg repeated at 4- to 8-week intervals
Ankylosing spondylitis: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 6 weeks thereafter (Canadian labeling recommends every 6-8 weeks thereafter)
Plaque psoriasis: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter
Ulcerative colitis: 5 mg/kg at 0, 2, and 6 weeks, followed by 5 mg/kg every 8 weeks thereafter
Dosage adjustment with heart failure (HF): Weigh risk versus benefits for individual patient:
Moderate-to-severe HF (NYHA Class III or IV): ≤5 mg/kg
Dosage adjustment in renal impairment: No specific adjustment is recommended
Dosage adjustment in hepatic impairment: No specific adjustment is recommended
Administration: I.V.
Infuse over at least 2 hours; do not infuse with other agents; use in-line low protein binding filter (≤1.2 micron). Temporarily discontinue or decrease infusion rate with infusion-related reactions. Antihistamines (H1-antagonist +/- H2-antagonist), acetaminophen and/or corticosteroids may be used to manage reactions. Infusion may be reinitiated at a lower rate upon resolution of mild-to-moderate symptoms.
Canadian labeling (not approved in U.S. labeling): Infusion of doses ≤6 mg/kg over not less than 1 hour may be considered in patients treated for rheumatoid arthritis who have initially tolerated 3 infusions each over 2 hours. Safety of shortened infusion has not been studied with doses >6 mg/kg.
Guidelines for the treatment and prophylaxis of infusion reactions: (Note: Limited to adult patients and dosages used in Crohn's; prospective data for other populations [pediatrics, other indications/dosing] are not available).
A protocol for the treatment of infusion reactions, as well as prophylactic therapy for repeat infusions, has been published (Mayer, 2006).
Treatment of infusion reactions: Medications for the treatment of hypersensitivity reactions should be available for immediate use. For mild reactions, the rate of infusion should be decreased to 10 mL/hour. Initiate a normal saline infusion (500-1000 mL/hour) and appropriate symptomatic treatment (eg, acetaminophen and diphenhydramine); monitor vital signs every 10 minutes until normal. After 20 minutes, the infusion may be increased at 15-minute intervals, as tolerated, to completion (initial increase to 20 mL/hour, then 40 mL/hour, then 80 mL/hour, etc [maximum of 125 mL/hour]). For moderate reactions, the infusion should be stopped or slowed. Initiate a normal saline infusion (500-1000 mL/hour) and appropriate symptomatic treatment. Monitor vital signs every 5 minutes until normal. After 20 minutes, the infusion may be reinstituted at 10 mL/hour; then increased at 15-minute intervals, as tolerated, to completion (initial increase 20 mL/hour, then 40 mL/hour, then 80 mL/hour, etc [maximum of 125 mL/hour]). For severe reactions, the infusion should be stopped with administration of appropriate symptomatic treatment (eg, hydrocortisone/methylprednisolone, diphenhydramine and epinephrine) and frequent monitoring of vitals (consult institutional policies, if available). Retreatment after a severe reaction should only be done if the benefits outweigh the risks and with appropriate prophylaxis. Delayed infusion reactions typically occur 1-7 days after an infusion. Treatment should consist of appropriate symptomatic treatment (eg. acetaminophen, antihistamine, methylprednisolone).
Prophylaxis of infusion reactions: Premedication with acetaminophen and diphenhydramine 90 minutes prior to infusion may be considered in all patients with prior infusion reactions, and in patients with severe reactions corticosteroid administration is recommended. Steroid dosing may be oral (prednisone 50 mg orally every 12 hours for 3 doses prior to infusion) or intravenous (a single dose of hydrocortisone 100 mg or methylprednisolone 20-40 mg administered 20 minutes prior to the infusion). On initiation of the infusion, begin with a test dose at 10 mL/hour for 15 minutes. Thereafter, the infusion may be increased at 15-minute intervals, as tolerated, to completion (initial increase 20 mL/hour, then 40 mL/hour, then 80 mL/hour, etc). A maximum rate of 125 mL/hour is recommended in patients who experienced prior mild-moderate reactions and 100 mL/hour is recommended in patients who experienced prior severe reactions. In patients with cutaneous flushing, aspirin may be considered (Becker, 2004). For delayed infusion reactions, premedicate with acetaminophen and diphenhydramine 90 minutes prior to infusion. On initiation of the infusion, begin with a test dose at 10 mL/hour for 15 minutes. Thereafter, the infusion may be increased to infuse over 3 hours. Postinfusion therapy with acetaminophen for 3 days and an antihistamine for 7 days is recommended.
Administration: I.V. Detail
Do not infuse with other agents. Use in-line low protein binding filter (≤1.2 micron).
pH ~7.2
Monitoring Parameters
Monitor improvement of symptoms and physical function assessments. During infusion, if reaction is noted, monitor vital signs every 2-10 minutes, depending on reaction severity, until normal. Latent TB screening prior to initiating and during therapy; signs/symptoms of infection (prior to, during, and following therapy); CBC with differential; signs/symptoms/worsening of heart failure; HBV screening prior to initiating (all patients), HBV carriers (during and for several months following therapy); signs and symptoms of hypersensitivity reaction; symptoms of lupus-like syndrome; LFTs (discontinue if >5 times ULN); signs and symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss).
Psoriasis patients with history of phototherapy should be monitored for nonmelanoma skin cancer.
Patient Education
This drug can only be administered by infusion. You will be more prone to infection. Report immediately any headache or unusual fatigue; increased nausea or abdominal pain; bruising or bleeding easily; cough, runny nose, or respiratory difficulty; chest pain or persistent dizziness; mouth sores; vaginal itching or discharge; and frequent infections or unhealed sores. Common reactions include fatigue, muscle pain or weakness, back pain, fever, or chills. Do not receive live vaccines such as BCG or influenza during treatment.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Fatigue is common; may cause dizziness
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Infusion reactions may occur. Premedication may be helpful. Treatment for hypersensitivity reactions should be available. Place and read PPD before initiation of therapy. Treatment of latent TB infection should be initiated prior to treatment with infliximab. Monitor for signs or symptoms of infection. Assess for signs of liver dysfunction (eg, unusual fatigue, dark urine, decreased urine output, abdominal pain, easy bruising or bleeding, jaundice). Monitor labs throughout treatment. Do not use with live vaccines, such as BCG or influenza, or past allergies to mouse proteins.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Remicade®: 100 mg [contains polysorbate 80, sucrose 500 mg]
Pricing: U.S. (www.drugstore.com)
Solution (reconstituted) (Remicade)
100 mg (1): $756.96
References
Antoni CE, Kavanaugh A, Kirkham B, et al, “Sustained Benefits of Infliximab Therapy for Dermatologic and Articular Manifestations of Psoriatic Arthritis: Results from the Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT),” Arthritis Rheum, 2005, 52(4):1227-36.
Becker M, Rose CD, and McIlvain-Simpson G, “Niacin-Like Reaction to Infliximab Infusion in Systemic Juvenile Rheumatoid Arthritis,” J Rheumatol, 2004, 31(12):2529-30.
Bongartz T, Sutton AJ, Sweeting MJ, et al, “Anti-TNF Antibody Therapy In Rheumatoid Arthritis and the Risk of Serious Infections and Malignancies: Systematic Review and Meta-Analysis of Rare Harmful Effects in Randomized Controlled Trials,” JAMA, 2006, 295(19):2275-85.
Buch MH, Bryer D, Lindsay S, et al, “Shortening Infusion Times for Infliximab Administration,” Rheumatology (Oxford), 2006, 45(4):485-6.
Carpenter PA and Sanders JE, “Steroid-Refractory Graft-vs-Host Disease: Past, Present and Future,” Pediatr Transplant. 2003, 7(Suppl 3):19-31.
Centers for Disease Control, “Testing and Treatment of Latent Tuberculosis Infection,” MMWR Recomm Rep, 2000, 49(RR-6).
Chung ES, Packer M, Lo KH, et al, “Randomized, Double-Blind, Placebo-Controlled, Pilot Trial of Infliximab, a Chimeric Monoclonal Antibody to Tumor Necrosis Factor-Alpha, in Patients with Moderate-to-Severe Heart Failure: Results of the Anti-TNF Therapy Against Congestive Heart Failure (ATTACH) Trial,” Circulation, 2003, 107(25):3133-40.
Couriel D, Saliba R, Hicks K, et al, “Tumor Necrosis Factor-Alpha Blockade for the Treatment of Acute GVHD,” Blood, 2004, 104(3):649-54.
“Diagnostic Standards and Classification of Tuberculosis in Adults and Children. Official Statement of the American Thoracic Society and the Centers for Disease Control and Prevention,” Am J Respir Crit Care Med, 2000, 161:1376-95.
Dommasch E and Gelfand JM, “Is There Truly a Risk of Lymphoma From Biologic Therapies?” Dermatol Ther, 2009, 22 (5):418-30.
Gerloni V, Pontikaki I, Gattinara M, et al, “Efficacy of Repeated Intravenous Infusions of an Anti-Tumor Necrosis Factor Alpha Monoclonal Antibody, Infliximab, in Persistently Active, Refractory Juvenile Idiopathic Arthritis,” Arthritis Rheum, 2005, 52(2):548-53.
Klotz U, Teml A, and Schwab M, “Clinical Pharmacokinetics and Use of Infliximab,” Clin Pharmacokinet, 2007, 45(8):645-60.
Kornbluth A and Sachar DB, “Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee,” Am J Gastroenterol, 2010, 105(3):501-23.
Lichtenstein GR, Hanauer SB, and Sandborn WJ, “Management of Crohn's Disease in Adults,” Am J Gastroenterol, 2009, 104(2):465-83.
Mayer L and Young Y, “Infusion Reactions and Their Management,” Gastroenterol Clin North Am, 2006, 35(4):857-66.
Parakkal D, Sifuentes H, Semer R, et al, “Hepatosplenic T-Cell Lymphoma in Patients Receiving TNF-α Inhibitor Therapy: Expanding the Groups at Risk,” Eur J Gastroenterol Hepatol, 2011, 23(12):1150-6.
Ruperto N, Lovell DJ, Cuttica R, et al, “A Randomized, Placebo-Controlled Trial of Infliximab Plus Methotrexate for the Treatment of Polyarticular-Course Juvenile Rheumatoid Arthritis,” Arthritis Rheum, 2007, 56(9):3096-106.
Shergy WJ, Isern RA, Cooley DA, et al, “Open Label Study to Assess Infliximab Safety and Timing of Onset of Clinical Benefit among Patients With Rheumatoid Arthritis,” J Rheumatol, 2002, 29(4):667-77.
Thayu M, Markowitz JE, Mamula P, et al, “Hepatosplenic T-Cell Lymphoma in an Adolescent Patient After Immunomodulator and Biologic Therapy for Crohn Disease,” J Pediatr Gastroenterol Nutr, 2005, 40(2):220-2.
Van Vollenhoven RF, Gullstrom E, and Klareskog L, “Feasibility of 1 Hour Infliximab Infusions,” Ann Rheum Dis, 2005, 64(4):654.
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Last full review/revision March 2012
Content last modified March 2012
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