Remicade

Antipsoriatic Monoclonal Antibodies and Others
Anti-Rheumatic Monoclonal Antibodies
Tumor Necrosis Factor (TNF)-Alpha Inhibitors

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Infliximab is administered as an intravenous infusion only.
Prior to initiating infliximab therapy, patients must be evaluated for latent tuberculosis infection.[27994] [60724] [61891] [62698]
 
Reconstitution of infliximab vials
Upon removal of an unopened vial from refrigerated storage in preparation for reconstitution, infliximab cannot be returned to refrigerated storage. However, unopened vials may be stored at temperatures up to a maximum of 30 degrees C (86 degrees F) for a single period of up to 6 months but not exceeding the original expiration date.
Reconstitute each vial (100 mg) with 10 mL of Sterile Water for Injection. Use a syringe equipped with a 21-gauge or smaller needle.
Insert the syringe needle into the vial and direct the stream of Sterile Water for Injection to the glass wall of the vial.
Gently swirl the solution by rotating the vial to dissolve the lyophilized powder. Avoid prolonged or vigorous agitation. Do not shake.
Allow the reconstituted solution to stand for 5 minutes.
The solution should be colorless to light yellow and opalescent; a few translucent particles may develop. Do not use if opaque particles, discoloration, or other foreign particles are present. Do not use if the lyophilized powder is not fully dissolved.
The reconstituted solution in the vials must be further diluted prior to administration. Do not store unused reconstituted solution.[27994] [60724] [61891] [62698]
 
Dilution for Infusion
Further dilute the total dose of the reconstituted solution to 250 mL with 0.9% Sodium Chloride Injection. Do not dilute the reconstituted infliximab solution with any other diluent.
Withdraw a volume of 0.9% Sodium Chloride Injection equal to the total dosage volume of reconstituted infliximab from a 250 mL glass bottle or bag containing 0.9% Sodium Chloride Injection.
Slowly add the total dosage volume of reconstituted infliximab solution to the 250 mL infusion bottle or bag. Gently mix.
The final infusion concentration should be 0.4 mg/mL to 4 mg/mL. For volumes greater than 250 mL, a larger infusion bag (e.g. 500 mL) or multiple 250 mL infusion bags may be used to ensure that the final concentration does not exceed 4 mg/mL.[27994] [60724] [61891] [62698]
 
Intravenous Infusion Administration
Prior to IV infusion, premedication may be administered at the prescriber's discretion. Premedication could include antihistamines, acetaminophen and/or corticosteroids.
The IV infusion should begin within 3 hours of reconstitution and dilution.
Do not administer the solution if visibly opaque particles, discoloration, or other foreign particles are observed.
Do not infuse the infliximab solution concomitantly in the same intravenous line with other agents.
Infuse IV over a period of not less than 2 hours. Use an infusion set with an in-line, sterile, non-pyrogenic, low-protein-binding filter (pore size of 1.2 microns or less). Discard any unused portion.[27994] [60724] [61891] [62698]
 
If Infusion Reactions Occur During Administration [27994] [60724] [61891] [62698]
During infusion, mild to moderate infusion reactions may improve if the infusion rate is slowed or the infusion is temporarily discontinued.
Upon resolution of the reaction, reinitiate administration at a lower infusion rate and/or the prescriber may order treatment with antihistamines, acetaminophen, and/or corticosteroids.
For patients that do not tolerate the infusion following these interventions, infliximab should be discontinued.
Discontinue infliximab if severe hypersensitivity reactions occur. Most such reactions occur within 2 hours of an infusion. Medications for the treatment of hypersensitivity reactions (e.g., acetaminophen, antihistamines, corticosteroids and/or epinephrine) should be available for immediate use in the event of a serious reaction.

anaphylactoid reactions / Rapid / 0-1.0
serum sickness / Delayed / 0.2-1.0
GI obstruction / Delayed / 0.2
pulmonary edema / Early / 0.2
bradycardia / Rapid / 0.2
hemolytic anemia / Delayed / 0.2
hepatic encephalopathy / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
stroke / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
lupus-like symptoms / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
Guillain-Barre syndrome / Delayed / Incidence not known
optic neuritis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
seizures / Delayed / Incidence not known
myelitis / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
cervical cancer / Delayed / Incidence not known
lymphoma / Delayed / Incidence not known
skin cancer / Delayed / Incidence not known
Merkel cell carcinoma / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known

antibody formation / Delayed / 7.0-62.0
elevated hepatic enzymes / Delayed / 17.0-51.0
infusion-related reactions / Rapid / 18.0-20.0
hypertension / Early / 0-7.0
neutropenia / Delayed / 7.0-7.0
candidiasis / Delayed / 5.0-5.0
hypotension / Rapid / 0.2-1.0
chest pain (unspecified) / Early / 1.0-1.0
dyspnea / Early / 1.0-1.0
dehydration / Delayed / 0.2
constipation / Delayed / 0.2
edema / Delayed / 0.2
thrombocytopenia / Delayed / 0.2
anemia / Delayed / 0.2
phlebitis / Rapid / 0.2
leukopenia / Delayed / 0.2
lymphadenopathy / Delayed / 0.2
hepatitis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
angina / Early / Incidence not known
dysphagia / Delayed / Incidence not known
psoriaform rash / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known

infection / Delayed / 5.3-56.0
abdominal pain / Early / 12.0-26.0
nausea / Early / 21.0-21.0
headache / Early / 5.0-18.0
sinusitis / Delayed / 14.0-14.0
diarrhea / Early / 12.0-12.0
cough / Delayed / 12.0-12.0
pharyngitis / Delayed / 12.0-12.0
dyspepsia / Early / 10.0-10.0
fatigue / Early / 9.0-9.0
flushing / Rapid / 9.0-9.0
arthralgia / Delayed / 1.0-8.0
fever / Early / 3.0-7.0
rash / Early / 3.0-3.0
chills / Rapid / 3.0-3.0
pruritus / Rapid / 0-1.0
urticaria / Rapid / 0-1.0
myalgia / Early / 0-1.0
dizziness / Early / 0.2
hyperhidrosis / Delayed / 0.2
lichen planus-like eruption / Delayed / Incidence not known
weight loss / Delayed / Incidence not known

Patients who receive infliximab are at increased risk for developing serious infection that may result in hospitalization and/or death. Do not administer infliximab to patients with a clinically important active infection like influenza or sepsis. If a patient develops a serious infection or sepsis, discontinue infliximab. Many of the serious infections in patients treated with infliximab have occurred in patients receiving concurrent immunosuppression therapy (e.g., methotrexate and corticosteroid therapy) that, in addition to their underlying conditions, may predispose them to infections. These infections involve multiple organ systems and include bacterial infection (Legionella and Listeria), mycobacterial infection (disseminated tuberculosis or extrapulmonary tuberculosis), fungal infection (histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, listeriosis, pneumocystis jiroveci pneumonia, cryptococcosis), parasitic infection, viral infection (hepatitis B, herpes infection), and other opportunistic infections. Patients with invasive fungal infections (specifically histoplasmosis) may present with disseminated rather than localized disease. Health care providers should be aware that antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Carefully consider the risks associated with infliximab prior to initiating therapy in patients who reside in histoplasmosis, blastomycosis, or coccidioidomycosis endemic zones. In patients who develop severe systemic illness, consider administering empiric antifungal therapy. Patients need to be evaluated for tuberculosis risk factors and for latent or active tuberculosis infection with a tuberculin skin test both before and during treatment. The possibility of anergy needs to be considered when interpreting the test result. If tuberculin skin testing is performed for latent tuberculosis infection, an induration size of 5 mm or greater should be considered positive even if the patient was vaccinated previously with Bacille Calmette-Guerin. Cases of new tuberculosis and reactivation of tuberculosis have occurred in patients who received infliximab, including patients who have previously received treatment for latent or active tuberculosis. Cases of tuberculosis also have been reported in patients being treated with infliximab during treatment for latent tuberculosis. Treatment of latent tuberculosis infection prior to initiation of infliximab has been shown to reduce the risk of tuberculosis reactivation during infliximab therapy. Consider antituberculosis therapy before infliximab initiation in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed and in patients who have several or highly significant risk factors for tuberculosis infection and have a negative test for latent tuberculosis. Some patients who tested negative for latent tuberculosis before infliximab receipt have developed active tuberculosis. Patients with a history of recurrent infections with underlying conditions that may predispose them to infections (e.g., elderly and patients with advanced or uncontrolled diabetes mellitus, malignancy, or immunosuppression) may not be appropriate candidates for infliximab. Educate patients about the symptoms of infection, and closely monitor patients for signs and symptoms of infection during and after infliximab treatment. Patients who develop a new infection during treatment should be closely monitored and evaluated for appropriate antimicrobial therapy. Safety and efficacy in patients with bone marrow suppression or other types of immunosuppression are not known.[27994] [61891]

A new primary malignancy has been reported among children, adolescents and young adults who received treatment with TNF-blocking agents (initiation of therapy 18 years of age or less), including infliximab. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months (range 1 to 84 months) after the first dose of TNF blocker therapy. Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources, including registries and spontaneous post-marketing reports. In the controlled portions of clinical trials of all the TNF-blocking agents, more cases of lymphoma have been observed among patients receiving a TNF blocker compared with control patients. In the controlled and open-label portions of infliximab clinical trials, 5 patients developed lymphomas among 5,707 patients treated with infliximab (median duration of follow-up 1 year) vs. 0 lymphomas in 1,600 control patients (median duration of follow-up 0.4 years). In rheumatoid arthritis patients, 2 lymphomas were observed for a rate of 0.08 cases per 100 patient-years of follow-up, which is approximately 3-fold higher than expected in the general population. In the combined clinical trial population for rheumatoid arthritis, Crohn's disease, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and plaque psoriasis, 5 lymphomas were observed for a rate of 0.10 cases per 100 patient-years of follow-up, which is approximately 4-fold higher than expected in the general population. Patients with Crohn's disease, rheumatoid arthritis or plaque psoriasis, particularly patients with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF-blocking therapy. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use in rheumatoid arthritis and other indications. Even in the absence of TNF blocker therapy, patients with rheumatoid arthritis may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including infliximab. These cases have had a very aggressive disease course and have been fatal. Almost all patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. The majority of reported infliximab cases have occurred in patients with Crohn's disease or ulcerative colitis and most were in adolescent and young adult males. It is uncertain whether the occurrence of HSTCL is related to TNF-blockers or TNF-blockers in combination with these other immunosuppressants. When treating patients, consideration of whether to use infliximab alone or in combination with other immunosuppressants such as azathioprine or 6-mercaptopurine should take into account a possibility that there is a higher risk of HSTCL with combination therapy versus an observed increased risk of immunogenicity and hypersensitivity reactions with infliximab monotherapy from the clinical trial data. Skin cancer, including melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy, including infliximab. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Psoriasis patients should be monitored for nonmelanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. In the maintenance portion of clinical trials for infliximab, NMSCs were more common in patients with previous phototherapy. In the controlled portions of clinical trials of some TNF-blocking agents including infliximab, more malignancies (excluding lymphoma and nonmelanoma skin cancer [NMSC]) have been observed in patients receiving those TNF-blockers compared with control patients. In a population-based retrospective cohort study, invasive cervical cancer was reported as a 2- to 3-fold increase in women, particularly those over 60 years of age, with rheumatoid arthritis treated with infliximab compared to patients not receiving biologics. Periodic cervical cancer screening should continue in women treated with infliximab. During the controlled portions of infliximab trials for labeled indications, 14 patients were diagnosed with malignancies (excluding lymphoma and NMSC) among 4,019 infliximab-treated patients vs. 1 among 1,597 control patients (at a rate of 0.52/100 patient-years among infliximab-treated patients vs. a rate of 0.11/100 patient-years among control patients), with median duration of follow-up 0.5 years for infliximab-treated patients and 0.4 years for control patients. Of these, the most common malignancies were breast, colorectal, and melanoma. The rate of malignancies among infliximab-treated patients was similar to that expected in the general population whereas the rate in control patients was lower than expected. The potential role of TNF-blocking therapy in the development of malignancies is not known. Rates in clinical trials for infliximab cannot be compared to rates in clinical trials of other TNF-blockers and may not predict rates observed in a broader patient population. Caution should be exercised in considering infliximab treatment in patients with a history of neoplastic disease or in continuing treatment in patients who develop malignancy while receiving infliximab.[27994] [61891]

AVSOLA, INFLECTRA, IXIFI, Remicade, RENFLEXIS

Rx

TNF blocker; given as an intravenous infusion
Used for Crohn's disease and ulcerative colitis in adult and pediatric patients 6 years and older; also used in adults with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis
Boxed warnings for increased risk of serious infections and potential risk of malignancy

5 mg/kg IV at weeks 0, 2, and 6, then 5 mg/kg IV every 8 weeks. May increase dose to 10 mg/kg IV infusion every 8 weeks for persons who initially respond and then lose response. The median time to response is 7 days. Maximum response is usually observed within 2 to 4 weeks. Persons who do not respond by week 14 are unlikely to respond with continued treatment; consider discontinuing therapy. Guidelines strongly recommend the use of infliximab to treat Crohn's disease that is resistant to treatment with corticosteroids. Combination therapy of infliximab with thiopurines is more effective than treatment with either agent alone in patients who are naive to those agents. In the ACCENT I trial, significantly more patients receiving maintenance therapy (5 mg/kg) achieved a clinical remission at week 30 (39%) compared to those receiving placebo (25%). In addition, 25% of subjects in remission and receiving maintenance therapy were able to discontinue corticosteroid therapy as opposed to 11% of subjects given placebo. Doses of up to 20 mg/kg IV have been studied but are not more effective in magnitude or duration of clinical response than doses of 5 mg/kg.

5 mg/kg IV at weeks 0, 2 and 6 weeks, then 5 mg/kg IV every 8 weeks. In clinical trials, children on a stable dose of 6-mercaptopurine, azathioprine, or methotrexate received infliximab according to this regimen. At week 10, of 112 patients, 88% had a clinical response defined as at least a 15 point reduction in their Pediatric Crohn's Disease Activity Index (PCDAI) score from baseline and a total score of 30 or less. Further, of 52 patients who received infliximab 5 mg/kg IV every 8 weeks as maintenance therapy, 60% had a clinical remission defined as a total PCDAI score of 10 or less at week 30; 56% met the endpoint at week 54.

5 mg/kg IV at weeks 0, 2, and 6, then 5 mg/kg IV every 8 weeks. May increase dose to 10 mg/kg IV infusion every 8 weeks for persons who initially respond and then lose response. Persons who do not respond by week 14 are unlikely to respond with continued treatment; consider discontinuing therapy. In a placebo-controlled study, closure of at least 50% of perianal or abdominal fistulae was obtained in 68% of subjects treated with infliximab and 26% of subjects given placebo. Among those receiving infliximab, the median time to response and duration of response was 2 weeks and 12 weeks, respectively. Closure of all fistulas was seen in 52% of those receiving infliximab compared to 13% of those in the placebo group.[27994] [60724] [61891] [62698] Guidelines state that infliximab is effective and should be considered in treating perianal fistulas due to Crohn's disease; the addition of antibiotics to infliximab is more effective than infliximab alone for treating perianal fistulas and should be considered. Infliximab may be effective and should be considered for the treatment of enterocutaneous and rectovaginal fistulas.[64397]

5 mg/kg/dose IV at weeks 0, 2, and 6, then 5 mg/kg/dose IV every 8 weeks. Guidelines strongly recommend infliximab in combination with a thiopurine for the induction of remission in persons with moderately to severely active ulcerative colitis and for maintenance of remission.

5 mg/kg/dose IV at weeks 0, 2, and 6, then 5 mg/kg/dose IV every 8 weeks.[27994] [60724] [61891]

3 mg/kg/dose IV at 0, 2, and 6 weeks, then 3 mg/kg/dose IV every 8 weeks. May consider increasing the dose up to 10 mg/kg/dose and/or treating as often as every 4 weeks for persons with an incomplete response. In clinical trials, maximal doses were 6 mg/kg/dose or 10 mg/kg/dose IV every 4 weeks in some patients. The risk of serious infections is increased at higher doses or more frequent dosing. Infliximab reduces signs and symptoms, inhibits the progression of joint structural damage (erosions and the degree of joint space narrowing), and improves the physical functioning of patients when added to methotrexate therapy. In methotrexate-naive patients with a disease duration 3 or fewer years, concurrent use of infliximab with methotrexate improved these disease parameters to a greater extent than methotrexate alone. Guidelines recommend infliximab plus methotrexate as an option for patients with a disease duration less than 6 months and high disease activity with poor prognostic feature presence. For established disease, adding or switching to an anti-TNF biologic is an option for patients with moderate or high disease activity after 3 months of methotrexate monotherapy or DMARD combination therapy. A switch to a different anti-TNF biologic is an option for patients with moderate or high disease activity after greater than or equal to 3 months of a TNF blocker or with a non-serious adverse event. Also, a switch to an anti-TNF biologic is an option for patients with moderate or high disease activity after greater than or equal to 6 months of a non-TNF biologic or with a serious or non-serious adverse event to the drug. The goal is low disease activity or remission.

5 mg/kg IV infusion at 0, 2, and 6 weeks for induction. Thereafter, a maintenance dose of 5 mg/kg IV infusion every 6 weeks. Infliximab improves the signs and symptoms of disease (a 20% or greater improvement in the Assessment in SpondyloArthritis International Society (ASAS) response criteria, or ASAS 20). The ASAS guidelines state that anti-TNF therapy should be given to patients with persistently high disease activity despite conventional treatments.

5 mg/kg/dose IV at weeks 0, 2, and 6, then 5 mg/kg/dose IV every 8 weeks. May increase the dose to 5 mg/kg/dose IV every 6 weeks if an inadequate primary response may be due to insufficient drug exposure (e.g., known subtherapeutic drug concentrations, obesity, relapse during treatment); however, consider the increased risk for infection and adverse reactions.

5 mg/kg/dose IV at weeks 0, 2, and 6, then 5 mg/kg/dose IV every 8 weeks. Guidelines recommend infliximab as monotherapy or in combination with methotrexate for use in children with severe plaque or pustular psoriasis that is unresponsive to other systemic medications, rapidly progressive, unstable, and/or life-threatening.

5 mg/kg/dose IV at weeks 0, 2 and 6, then 5 mg/kg/dose IV every 8 weeks. Infliximab can be used with or without methotrexate.

3 to 10 mg/kg/dose IV at weeks 0, 2, and 6, then every 4 to 8 weeks.

5 mg/kg IV infusion as a single dose given over 2 hours may be considered as an alternative to a second infusion of IVIG or corticosteroids for IVIG-resistant patients.[61950]

5 to 10 mg/kg IV as a single dose in patients with refractory MIS-C who do not improve within 24 hours of initial immunomodulatory therapy. Do not use in patients with features of macrophage activation syndrome (MAS).

3 to 5 mg/kg/dose IV every 4 to 8 weeks has been evaluated as a third-line therapy in refractory cases. Optimal dosing has not been established; however, suggested regimens include induction doses administered at 0, 2, and 6 weeks followed by maintenance dosing every 4, 6, or 8 weeks. In 1 randomized study, patients with pulmonary sarcoidosis received 3 mg/kg (n = 46), 5 mg/kg (n = 47), or placebo (n = 45) at weeks 0, 2, 6, 12, 18, and 24. At week 24, a 2.5% increase in percentage predicted forced vital capacity (% pred FVC) was observed in the combined infliximab group compared to no change in the placebo group (p = 0.038). Similar treatment benefit was not observed in a smaller study in which patients were randomized to receive either 5 mg/kg given at weeks 0, 2, 6, and 14 (n = 13) or placebo (n = 6). The % pred VC increased 2-fold with infliximab at week 6, but this difference was not significant (15.22 vs. 8.39; p = 0.65). In addition to pulmonary sarcoidosis, data from non-randomized studies suggest efficacy and safety in cutaneous, ocular, neurologic, and multisystem sarcoidosis.

3 to 6 mg/kg/dose (Max: 20 mg/kg/dose) IV initially at intervals of 0, 2, and 6 weeks, and then administered every 4 to 8 weeks thereafter. Higher doses of 10 to 20 mg/kg/dose IV every 2 to 8 weeks have been reported in a study of pediatric patients (age 2 to 18 years) with recalcitrant or highly active JIA. A randomized, placebo-controlled trial in patients 4 to 17 years demonstrated no significant difference between patients receiving infliximab 3 mg/kg/dose (n = 60) or placebo (n = 62) in American College of Rheumatology Pediatric 30 (ACR Pedi 30) response criteria for improvement at week 14 (63.8% vs. 49.2%, respectively). Patients randomized to placebo were treated with infliximab 6 mg/kg/dose beginning at week 14. ACR Pedi 50 and ACR Pedi 70 responses were 69.6% and 51.8%, respectively, for all patients at week 52; there were no significant differences between the infliximab dose groups. Approximately 40% of patients in both dose groups had 0 joints with active arthritis. Initial therapy with a biologic, such as infliximab, is recommended in patients with involvement of high-risk joints, high disease activity, or patients at high risk of disabling joint damage. Infliximab may also be used as subsequent therapy in combination with a disease-modifying antirheumatic drug.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; use with caution. It is not known if there are differences in clearance or other pharmacokinetic parameters in patients with marked impairment of hepatic function. Specific guidelines for dosage adjustments in hepatic impairment are not available. During treatment, evaluate patients with signs or symptoms of hepatic dysfunction. Discontinue infliximab if jaundice or AST or ALT concentrations at least 5 times the upper limit of normal (ULN) develop.

It is not known if there are differences in clearance or other pharmacokinetic parameters in patients with marked impairment of renal function. Specific guidelines for dosage adjustments in renal impairment are not available.

Abatacept: (Major) Concomitant use of abatacept with other biologic agents, such as tumor necrosis factor (TNF) inhibitors, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. In controlled clinical trials, patients receiving concomitant abatacept and TNF inhibitor therapy experienced more infections (63%) and serious infections (4.4%) as compared with patients treated with only TNF inhibitors (43% and 0.8%, respectively). These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of abatacept with a TNF inhibitor. Monitor patients for signs of infection during the transition from TNF antagonist therapy to abatacept therapy.
Adalimumab: (Contraindicated) Do not use infliximab in combination with other tumor necrosis factor (TNF) modifier therapy, including adalimumab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if infliximab is used concomitantly with adalimumab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Anakinra: (Major) Avoid the concomitant use of anakinra with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection with no additional clinical benefit. Data suggest a higher rate of serious infections when anakinra and a TNF inhibitor is used in combination with anakinra compared with either drug given alone. Neutropenia (1,000/mcL or less) was observed in 2% of patients receiving the combination. The use of anakinra with a TNF inhibitor in combination did not yield any additional clinical benefit as compared to the use of the TNF inhibitor alone.
Anifrolumab: (Major) Coadministration is not recommended. Anifrolumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Antithymocyte Globulin: (Moderate) Many serious infections during infliximab therapy have occurred in patients receiving concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposes patients to infections.
Azathioprine: (Moderate) Most infliximab recipients who developed serious infections were taking concomitant immunosuppressives such as methotrexate or corticosteroids. The concurrent use of infliximab and immunosuppressants may also contribute to malignancy risk. However, the use of concomitant immunosuppressives such as 6-mercaptopurine, azathioprine, or methotrexate with infliximab appeared to reduce the frequency of antibodies to infliximab. Patients with Crohn's disease receiving immunosuppressives tended to have fewer infusion-related reactions as compared to patients not receiving immunosuppressive therapy. Also, concomitant methotrexate use, for example, may increase infliximab concentrations. Patients who were antibody-positive were more likely to have higher rates of infliximab clearance and reduced efficacy than were patients who were antibody negative. For patients with inflammatory bowel disease especially adolescents and young adults, consider the possibility that there is a higher risk of hepatosplenic T-cell lymphoma with combination therapy versus an observed increased risk of immunogenicity and hypersensitivity reactions with infliximab monotherapy from the clinical trial data.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Belimumab: (Major) Avoid use together. Belimumab has not been studied in combination with other biologic therapies including tumor necrosis factor modifiers (TNF blockers). Therefore, belimumab use is not recommended in combination with TNF blockers. Potential concerns with use of these drugs together include an increased susceptibility to immunosuppression and serious infections, some of which might be fatal.
Canakinumab: (Major) Avoid concomitant administration of canakinumab with tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. An increased incidence of serious infections and an increased risk of neutropenia have been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Based upon the potential for similar interactions, concomitant administration of canakinumab and TNF inhibitors is not recommended.
Certolizumab pegol: (Contraindicated) Do not use certolizumab in combination with other tumor necrosis factor (TNF) modifier therapy, including infliximab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if certolizumab is used concomitantly with infliximab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cyclosporine: (Moderate) The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during infliximab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as cyclosporine. If infliximab is initiated or discontinued in a patient taking cyclosporine, monitor the cyclosporine concentration; cyclosporine dose adjustment may be needed.
Dexamethasone: (Moderate) Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
Etanercept: (Contraindicated) The combination of infliximab with other biologics used to treat the same conditions as infliximab is not recommended. Both infliximab and etanercept block the actions of TNF-alpha. It is unknown if any adverse effects would occur if infliximab was used concomitantly with etanercept. A potential exists for an increased risk for serious infection or an impact on the development of malignancies from increased activity toward TNF.
Golimumab: (Contraindicated) Do not use golimumab in combination with other tumor necrosis factor (TNF) modifier therapy, including infliximab, due to the potential for additive effects and drug toxicity. It is unknown if any adverse effects would occur if golimumab is used concomitantly with infliximab. A potential exists for increased risk of infection or an impact on the development of malignancies from increased activity toward TNF.
Live Vaccines: (Contraindicated) Do not administer live vaccines to infliximab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving infliximab. Before initiation of infliximab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Infliximab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Mercaptopurine, 6-MP: (Moderate) Post-marketing fatal cases of hepatosplenic T-cell lymphoma have been reported, mostly in adolescent and young adult males with inflammatory bowel disease such as Crohn's disease or ulcerative colitis; almost all cases have occurred in patients who had received a TNF blocker such as infliximab concomitantly with either mercaptopurine, 6-MP or azathioprine at or before diagnosis. It is unknown whether the occurrence of hepatosplenic T-cell lymphoma is related to a TNF blocker or to a TNF blocker in combination with these other immunosuppressants. Use with caution.
Methotrexate: (Moderate) Rheumatoid arthritis patients who received methotrexate in combination with infliximab had higher serum concentrations of infliximab as compared to those who received infliximab alone. Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
Methylprednisolone: (Moderate) Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
Mycophenolate: (Moderate) Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
Natalizumab: (Major) Natalizumab for Crohn's disease should not be used in combination with tumor necrosis factor (TNF) modifiers. Coadministration may further increase the risk of serious infections, including progressive multifocal leukoencephalopathy and other opportunistic infections. Ordinarily, patients with mulitple sclerosis who are receiving chronic TNF-modifier therapy should not be treated with natalizumab.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with infliximab. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Prednisone: (Moderate) Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
Pretomanid: (Major) Avoid coadministration of pretomanid with infliximab, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Rilonacept: (Contraindicated) Concurrent use of rilonacept and tumor necrosis factor (TNF) modifiers is not advised, as the risk of serious infections may be increased. Although concurrent use has not been evaluated in clinical trials, an increased incidence of serious infections and neutropenia has been associated with administration of another drug that blocks IL-1 in combination with TNF inhibitors.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and infliximab. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Rituximab: (Major) Avoid the concomitant use of rituximab and infliximab if they are used to treat the same condition due to additive immunosuppression and an increased risk of infection. If coadministration is necessary for separate conditions, monitor patients closely for signs or symptoms of infection.
Rituximab; Hyaluronidase: (Major) Avoid the concomitant use of rituximab and infliximab if they are used to treat the same condition due to additive immunosuppression and an increased risk of infection. If coadministration is necessary for separate conditions, monitor patients closely for signs or symptoms of infection.
Sarilumab: (Major) Avoid the concomitant use of sarilumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tacrolimus: (Moderate) Many serious infections during infliximab therapy have occurred in patients who received concurrent immunosuppressives that, in addition to their underlying Crohn's disease or rheumatoid arthritis, predisposed patients to infections. The impact of concurrent infliximab therapy and immunosuppression on the development of malignancies is unknown. In clinical trials, the use of concomitant immunosuppressant agents appeared to reduce the frequency of antibodies to infliximab and appeared to reduce infusion reactions.
Theophylline, Aminophylline: (Moderate) The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during infliximab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as theophylline. If infliximab is initiated or discontinued in a patient taking theophylline, monitor the theophylline concentration; theophylline dose adjustment may be needed.
Tocilizumab: (Major) Avoid the concomitant use of tocilizumab with biological DMARDs, such as tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Infliximab may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of infliximab therapy.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as tumor necrosis factor (TNF) modifiers, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Vedolizumab: (Major) Vedolizumab should not be used in combination with tumor necrosis factor (TNF) modifiers because of the potential for increased risk of progressive multifocal leukoencephalopathy and other infections. Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy should not be treated with vedolizumab.
Warfarin: (Moderate) The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNF-alpha) during chronic inflammation. Thus, it is expected that the formation of CYP450 enzymes could be normalized during infliximab receipt. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as warfarin. If infliximab is initiated or discontinued in a patient taking warfarin, check the INR; warfarin dose adjustment may be needed.

AVSOLA/INFLECTRA/Infliximab (Murine)/IXIFI/Remicade/RENFLEXIS Intravenous Inj Pwd F/Sol: 100mg

10 mg/kg/dose IV.

10 mg/kg/dose IV.

5 mg/kg/dose IV for Crohn's disease and ulcerative colitis; doses up to 20 mg/kg/dose IV have been used off-label for juvenile idiopathic arthritis.

6 to 12 years: 5 mg/kg/dose IV for Crohn's disease and ulcerative colitis; doses up to 20 mg/kg/dose IV have been used off-label for juvenile idiopathic arthritis.
1 to 5 years: Safety and efficacy have not been established; however, doses up to 20 mg/kg/dose IV have been used off-label for juvenile idiopathic arthritis.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Infliximab neutralizes the biological activity of the cytokine tumor necrosis factor-alpha (TNFalpha). Infliximab binds to high affinity soluble and transmembrane forms of TNFalpha and inhibits the binding of TNFalpha with its receptors. Infliximab does not neutralize TNFbeta, a related cytokine that utilizes the same receptors as TNFalpha. Biological activities attributed to TNFalpha include induction of pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6; enhancement of leukocyte migration by increasing endothelial layer permeability; expression of adhesion molecules by endothelial cells and leukocytes; activation of neutrophil and eosinophil functional activity; fibroblast proliferation; synthesis of prostaglandins; and induction of acute phase and other liver proteins. Infliximab inhibits the functional activity of TNFalpha in a wide variety of in vitro bioassays utilizing human fibroblasts, endothelial cells, neutrophils, B and T lymphocytes, and epithelial cells. Cells expressing transmembrane bound TNFalpha bound by infliximab can be lysed in vitro by complement or effector cells. In vitro models show that anti-TNFalpha antibodies reduce disease activity in colitis models and decrease synovitis and joint erosions in animal models. Infliximab prevents disease in transgenic mice that develop polyarthritis as a result of constitutive expression of human TNFalpha, and, when administered after disease onset, allows eroded joints to heal.
 
In patients with Crohn's disease, infliximab reduces infiltration of inflammatory cells and TNFalpha production in inflamed areas of the intestine. In addition, the proportion of mononuclear cells from the lamina propria able to express TNFalpha and interferon gamma is reduced. In patients with rheumatoid arthritis, infliximab treatment reduces inflammatory cell infiltration into inflamed areas of the joint and reduces the expression of molecules mediating adhesion [E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vacular adhesion molecule-1 (VCAM-1)], chemoattraction (monocyte chemotactic protein (MCP-1 and IL-8), and tissue degradation (matrix metalloproteinase (MMP) 1 and 3). After treatment with infliximab, patients with Crohn's disease or rheumatoid arthritis have decreased concentrations of IL-6 and C-reactive protein as compared to baseline.
 
In patients with plaque psoriasis, infliximab reduces infiltration of inflammatory cells within the plaques. In addition, infliximab may reduce epidermal thickness. The relationship between these pharmacodynamic effects and the mechanism of action of infliximab for the treatment of plaque psoriasis is unknown.

Infliximab is administered intravenously. Infliximab is predominantly distributed within the vascular compartment. No evidence of accumulation of infliximab has been observed after repeated dosing 3 mg/kg or 10 mg/kg IV at 4 or 8-week intervals. The median terminal half-life of infliximab is 7.7 to 9.5 days.
 
Currently, therapeutic monitoring of infliximab is not recommended. The relationship between the serum trough concentration of infliximab and clinical response has been studied in 105 patients with rheumatoid arthritis (RA) who received infliximab 3 mg/kg IV at baseline and at 2, 6, and 14 weeks; 86 patients also received concurrent methotrexate. The DAS28 (28 joint disease activity score) before each infliximab infusion was compared with the corresponding trough serum infliximab concentration. Response was based on European League Against Rheumatism (EULAR) criteria and was determined at week 14. Nonresponse was defined either as a DAS28 decrease of up to 0.6 or a decrease greater than 0.6 and up to 1.2 with an attained DAS of greater than 5.1. The clinical response to infliximab correlated with serum trough concentrations. Specifically, 88 to 90% of patients with a serum trough infliximab of at least 1.3 mg/L were EULAR responders whereas only 50% of RA patients with a lower serum trough infliximab concentration were EULAR responders. Correction for potential confounders such as baseline C-reactive protein concentrations, baseline DAS28 scores, and rheumatoid factor presence did not affect the observed relationship.

When single IV infusions of infliximab 3 to 20 mg/kg are given, a linear relationship exists between the dose administered and the maximal concentration (Cmax) observed.

Indication and patient-specific factors should be assessed before the use of infliximab during lactation. Data are limited regarding the use of infliximab during breast-feeding. No data are available on the effects of infliximab on the breast-fed infant or the effects on milk production. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for adverse reactions in nursing infants from infliximab products, the product labels state that women should not breast-feed their infants while taking infliximab. However, experts consider infliximab compatible with breast-feeding due to the low transfer to breast milk. It is estimated that less than 0.5% of mother's plasma concentration passes to the breast milk and that peak excretion occurs 1 to 4 days following an infusion, and that much of infliximab would be destroyed in the infant's gastrointestinal tract. In a multi-center study involving breast-feeding women with inflammatory bowel disease (IBD), infants exposed to infliximab through breast milk developed normally and did not have an increase in infection rate. In a small study (n = 3) designed to evaluate maternal transfer of infliximab, samples collected from breast milk and the infants' serum resulted in drug concentrations below the limits of detection (less than 0.1 mcg/mL).