Zymfentra (infliximab-dyyb)
Antipsoriatics Subcutaneous Pen Injector Kit (EA); Subcutaneous Syringe Kit (EA)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Infliximab, infliximab-abda, infliximab-axxq, and infliximab-dyyb are chimeric human-murine immunoglobulin G1 kappa (IgG1 kappa) monoclonal antibodies that have a high affinity for human tumor necrosis factor (TNF; TNF-alpha).
Infliximab-abda, infliximab-axxq, and infliximab-dyyb are biosimilar to infliximab (Remicade(R)). FDA defines a biosimilar as a biological product that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency. The claim of biosimilarity is based on a totality-of-evidence approach, which includes consideration of data from analytical, animal, and clinical studies (e.g., human pharmacokinetic and pharmacodynamic studies, clinical immunogenicity assessment, additional comparative clinical studies).
Therefore, biosimilarity may be established even when there are formulation or minor structural differences as long as these differences are not clinically meaningful. Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between the proposed biological and the reference biological but does not independently establish safety and effectiveness of the proposed biological. In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product; these requirements include demonstrating that the biological product can be expected to produce the same clinical results as the reference product in any given patient and, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is no greater than the risk of using the reference product without such alternation or switch.
Biosimilar products that are interchangeable can be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. None of the currently available infliximab biosimilars have interchangeable data at this time.
In this monograph, unless otherwise stated, the term ''infliximab products'' refers to infliximab (the reference drug) and its biosimilars (infliximab-abda, infliximab-axxq, infliximab-dyyb).
Infliximab and its biosimilars are chimeric human-murine immunoglobulin G1 kappa (IgG1 kappa) monoclonal antibodies that have a high affinity for tumor necrosis factor (TNF-alpha). Infliximab products consist of the constant region of human IgG1 kappa coupled to the variable region of a high-affinity neutralizing murine anti-human TNF antibody. Because of the presence of human constant region sequences, the chimeric antibody is less immunogenic, has a longer half-life, and is more potent in binding and neutralizing human TNF compared with the murine antibody.
Infliximab is produced by continuous fermentation of a mouse myeloma cell line that has been transfected with cloned DNA coding for the chimeric antibody. The drug is purified from the culture supernatant using column chromatography and undergoes measures to inactivate and remove viruses.
Infliximab products have a high affinity for and bind specifically to soluble and transmembrane forms of TNF thereby inhibiting binding of TNF to cell surface tumor necrosis factor receptors (TNFRs). By binding to TNF, infliximab and infliximab products neutralize the cytokine. Although the exact mechanism(s) of the anti-inflammatory effects of infliximab products in the management of Crohn disease or rheumatoid arthritis remains to be more fully determined, binding and neutralization of TNF appears to be the principal mechanism.
There also is some evidence that infliximab may inhibit expression of TNF by binding soluble TNF attached to TNF receptors present on activated macrophages and T cells.
While it is clear that chronic inflammatory processes are not due solely to overexpression of TNF, the regulatory cytokine plays a critical role in the control of the production of other cytokines involved in the pathogenesis of inflammation of Crohn disease and rheumatoid arthritis. A variety of physiologic and pathologic functions have been ascribed to TNF-TNF receptor interactions and the effects of TNF include induction of proinflammatory cytokines such as interleukin 1(IL-1), IL-6 and IL-8, enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase proteins (C-reactive protein, serum amyloid A (SAA) haptoglobin, fibrinogen) and tissue degrading enzymes produced by synoviocytes and/or chondrocytes. TNF blocks the action of lipoprotein lipase, causing severe cachexia in experimental models of chronic infection.
In addition, TNF induces programmed cell death (apoptosis), stimulates the release matrix metalloproteinases from fibroblasts, chondrocytes, and neutrophils, and up-regulates the expression of endothelial adhesion molecules, leading to the migration of leukocytes into extravascular tissues. TNF also mediates pain, fever, shock, and anemia.
The complex interactions of paracrine or autocrine pathways mediated by networks of pro- and anti-inflammatory cytokines are implicated in many chronic inflammatory disorders and TNF plays a prominent role in the pathogenesis of Crohn disease, rheumatoid arthritis, multiple sclerosis, systemic vasculitis, allograft rejection, and graft-versus-host disease. Mucosal biopsies from patients with Crohn disease demonstrate increased TNF concentrations and intestinal mononuclear cell infiltrates in the lamina propria. Increased concentrations of TNF have been measured in fecal samples from Crohn disease patients and in the joints of patients with rheumatoid arthritis and levels correlated with disease manifestations in these patients.
Increased concentrations of TNF also have been reported in involved tissues and fluids of patients with ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis.
The ability of infliximab and its biosimilars to inhibit the functional activity of TNF has been demonstrated in a variety of in vitro bioassays utilizing human fibroblasts, endothelial and epithelial cells, neutrophils, and B and T cells. The relationship of these biological response markers to the mechanism(s) of infliximab products' clinical effects is not known. In addition, cell lysis by complement or effector cells has been observed in vitro in cells that express transmembrane TNF and are bound by infliximab.
In vivo studies have shown that anti-TNF antibodies reduce GI manifestations in a nonhuman primate model of colitis (cotton-top tamarin) and reduce synovitis and joint erosions in a murine model of collagen-induced arthritis.
In patients with Crohn disease, infliximab products have been shown to reduce inflammatory cell migration, reduce TNF production in areas of intestinal inflammation, and reduce the proportion of lamina propria mononuclear cells able to express TNF and interferon.
In patients with rheumatoid arthritis, infliximab products reduce infiltration of inflammatory cells into inflamed areas of the joint and downregulate expression of molecules that mediate cellular adhesion (E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1)), chemoattraction (IL-8 and monocyte chemotactic protein (MCP-1)), and tissue degradation (MMP 1 and 3). Infliximab also has been shown to inhibit pannus neoangiogenesis and proliferation through down-regulation of vascular endothelial growth factor (VEGF). Results of studies in transgenic mice that develop polyarthritis as the result of constitutive expression of TNF indicate that infliximab products can prevent such disease in these mice and, if administered after disease onset, allow eroded joints to heal.
There is evidence that infliximab can prevent or inhibit progression of structural damage in patients with rheumatoid arthritis.
In patients with Crohn disease or rheumatoid arthritis, therapy with infliximab products may result in decreases in proinflammatory cytokines (IL-1, IL-6) and decreases in systemic measures of inflammation, including C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR). Peripheral blood lymphocytes from patients treated with infliximab products exhibit a normal proliferative response to in vitro mitogenic stimulation and lymphocyte counts are not decreased in patients who receive the drugs.
In patients with psoriatic arthritis, therapy with infliximab products results in a reduction in the number of T-cells and blood vessels in the synovium and psoriatic skin lesions and a reduction of macrophages in the synovium. In patients with plaque psoriasis, therapy with infliximab products may reduce the epidermal thickness and infiltration of inflammatory cells.
Pharmacokinetic similarity between infliximab and its biosimilars has been demonstrated, and FDA considers that the pharmacokinetic data provide support for a totality-of-evidence determination of biosimilarity for infliximab-abda, infliximab-axxq, and infliximab-dyyb.
Data from adults who received single IV infusions of 1-20 mg/kg of infliximab indicate a predictable and linear relationship between the dose administered and the maximum serum concentration and AUC. In one study in adults with rheumatoid arthritis who received single 5-, 10-, or 20-mg/kg doses of infliximab given by IV infusion over 2 hours, peak serum concentrations were achieved 1-4 hours after the start of the infusion; serum concentrations of the drug then decreased exponentially from day 3 through week 12 and were still detectable in most patients at week 10. Systemic accumulation of infliximab does not appear to occur in adults receiving multiple doses of the drug given by IV infusion once every 4 or 8 weeks following an initial 3-dose induction regimen (doses at 0, 2, and 6 weeks).
Distribution of infliximab into body tissues and fluids, including joints, has not been characterized. The volume of distribution of infliximab at steady state is independent of dose, indicating that the drug is distributed principally within the vascular compartment. The terminal elimination half-life of infliximab in adults with Crohn disease, rheumatoid arthritis, or plaque psoriasis has been reported to be about 8-12 days.
After a single subcutaneous dose of infliximab-dyyb 120 mg in healthy subjects, the median time to maxium serum concentration was 7 days; the mean half-life was 332 hours.
The metabolic fate of infliximab has not been determined to date, but the drug may be eliminated by the reticuloendothelial system. Infliximab is not metabolized by hepatic cytochrome P-450 (CYP) enzymes. While differences in clearance of infliximab have not been observed in patient subgroups defined by age, weight, or gender, clearance of infliximab is increased in patients who have developed antibodies to the drug.
Whether renal or hepatic impairment affects infliximab clearance has not been determined.
Several infliximab biosimilars are available. Biosimilarity of these products has been demonstrated for the indications described in the table below (see Table 1).
Generic name: infliximab-dyyb
Pronunciation: (in-FLIX-i-mab)
Drug class: Antipsoriatics
Therapeutic class: Analgesic, Anti-inflammatory or Antipyretic
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Zymfentra
Indications
The following indications are listed for Zymfentra:
- Crohn's Disease
- Ulcerative Colitis
Also known as: Colitis Ulcerativa, Regional Enteritis, Regional Ileocolitis.
Dosing
No dosing information is available for this tab.
No dosing information is available for this tab.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Zymfentra 120 Mg/Ml Pen Kit | Maintenance | Inject 120 mg by subcutaneous route every 2 weeks. |
| Zymfentra 120 Mg/Ml Syringe Kt | Maintenance | Inject 120 mg by subcutaneous route every 2 weeks. |
No dosing information is available for this tab.
Drug interactions
Although specific drug interaction studies evaluating concomitant use of infliximab or its biosimilars and other drugs have not been conducted to date, most patients in clinical studies evaluating infliximab received one or more concomitant drugs. Patients with Crohn disease usually received infliximab concomitantly with corticosteroids, mesalamine or sulfasalazine, azathioprine or mercaptopurine, and/or anti-infective agents; patients with rheumatoid arthritis usually received infliximab concomitantly with methotrexate and may also have received corticosteroids, nonsteroidal anti-inflammatory agents (NSAIAs), folic acid, or narcotics.
In patients with Crohn disease, serum concentrations of infliximab do not appear to be affected by baseline use of corticosteroids, 5-aminosalicylates, or anti-infectives (ciprofloxacin, metronidazole). There is some evidence from studies of infliximab that the incidence of some adverse immunologic reactions to infliximab products (e.g., infusion reactions, formation of antibodies to infliximab) is lower in patients receiving infliximab products concomitantly with immunosuppressive agents (e.g., corticosteroids, azathioprine, mercaptopurine, methotrexate) compared with those receiving infliximab products without such agents.
When deciding whether infliximab products should be used alone or in combination with other immunosuppressive agents, clinicians should consider both the possibility of an increased risk of hepatosplenic T-cell lymphoma with combination therapy and the observed (in infliximab studies) increase in immunogenicity and hypersensitivity reactions associated with infliximab products given as monotherapy.
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Biologic Dmards/Sarilumab; Tocilizumab
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Concurrent use of sarilumab(1) or tocilizumab(2) with other biologic DMARDs may result in additive or synergistic effects on the immune system.
CLINICAL EFFECTS: Concurrent use of sarilumab(1) or tocilizumab(2) with other biologic DMARDs may increase the risk of serious infections.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The concurrent use of sarilumab(1) or tocilizumab(2) with other biologic DMARDs should be avoided.
DISCUSSION: Concurrent use of sarilumab(1) or tocilizumab(2) and other biologic DMARDs may increase the risk of infection.
Immunosuppressive; Immunomod/Cladribine Onc Inj (10 MG/5 ML)
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Cladribine in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-2)
CLINICAL EFFECTS: Concurrent use of cladribine with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections.(1-2)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: Recommendations for cladribine regarding this interaction differ between regulatory approving agencies. The UK and AU manufacturers of Litak state that concomitant use of other myelosuppressive medicinal products with cladribine is contraindicated.(1-2) The Israeli manufacturer of Litak states that cladribine should not be used concomitantly with other myelosuppressive medicinal products.(3)
DISCUSSION: The risk of severe myelotoxicity and long-lasting immunosuppression is increased in patients with a disease-related bone marrow infiltration or a previous myelosuppressive treatment.(1-3)
Immunosuppressives; Immunomodulators/Efalizumab; Natalizumab
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Natalizumab,(1-3) efalizumab,(4) immunosuppressives, and immunomodulators all suppress the immune system.
CLINICAL EFFECTS: Concurrent use of natalizumab(1-3) or efalizumab(4) with immunosuppressives or immunomodulators may result in an increased risk of infections, including progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).
PREDISPOSING FACTORS: Previous JCV infection, longer duration of natalizumab treatment - especially if greater than 2 years, and prior or concomitant treatment with immunosuppressant medication are all independent risk factors which increase the risk for PML.(1,5) The FDA has estimated PML incidence stratified by risk factors: If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment less than 25 months, incidence <1/1,000. If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment less than 25 months, incidence 2/1,000 If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 4/1,000 If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 11/1,000.
PATIENT MANAGEMENT: The US manufacturer of natalizumab states patients with Crohn's disease should not receive concurrent immunosuppressants, with the exception of limited overlap of corticosteroids, due to the increased risk for PML. For new natalizumab patients currently receiving chronic oral corticosteroids for Crohn's Disease, begin corticosteroid taper when therapeutic response to natalizumab has occurred. If corticosteroids cannot be discontinued within six months of starting natalizumab, discontinue natalizumab.(3) The US manufacturer of natalizumab states that natalizumab should not ordinarily be used in multiple sclerosis patients receiving immunosuppressants or immunomodulators due to the increased risk for PML. Immunosuppressives include, but are not limited to azathioprine, cyclophosphamide, cyclosporine, mercaptopurine, methotrexate, mitoxantrone, mycophenolate, and corticosteroids.(3,6) The UK manufacturer of natalizumab states that concurrent use with immunosuppressives or antineoplastic agents is contraindicated.(1) The Canadian manufacturer of natalizumab states that natalizumab should not be used with immunosuppressive or immunomodulatory agents.(2) The US manufacturer of certolizumab states that concurrent therapy with natalizumab is not recommended.(7)
DISCUSSION: Progressive multifocal leukoencephalopathy has been reported in patients receiving concurrent natalizumab were recently or concomitantly taking immunomodulators or immunosuppressants.(1-5,8,9) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(10)
Selected Biologic Dmards/Abatacept
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Possibly additive or synergistic effects on the immune system.
CLINICAL EFFECTS: Concurrent use of abatacept with anakinra, rituximab, or a tumor necrosis factor (TNF) blocking agent may increase the risk of severe infections without providing any clinical benefit.(1-5)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of abatacept states that abatacept should not be used with TNF blocking agents or other biologic DMARDs. Patients transitioning from TNF blocking agent therapy to abatacept should be closely monitored for signs of infection.(1) The US manufacturers of adalimumab,(2) certolizumab,(3) golimumab,(4) and infliximab(5) state that concurrent therapy with abatacept is not recommended.
DISCUSSION: In clinical trials, patients who received concurrent abatacept and TNF blocking agents experienced more infections (63% versus 43%) and more serious infections (4.4% versus 0.8%) than patients who received TNF agents alone. There was no significant additional efficacy over use of TNF agents alone.(1) In other trials, infections and serious infections were reported in 54% and 3%, respectively, of patients who received abatacept alone.(1)
Selected Immunosuppressants/Nadofaragene Firadenovec
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Nadofaragene firadenovec may contain low levels of replication-competent adenovirus.(1)
CLINICAL EFFECTS: Concurrent use of nadofaragene firadenovec in patients receiving immunosuppressive therapy may cause disseminated adenovirus infection.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Individuals who are immunosuppressed or immune-deficient should not receive nadofaragene firadenovec.(1)
DISCUSSION: Nadofaragene firadenovec is a non-replicating adenoviral vector-based gene therapy but may contain low levels of replication-competent adenovirus. Immunocompromised persons, including those receiving immunosuppressant therapy, may be at risk for disseminated adenovirus infection.(1)
Selected Immunosuppressants/Talimogene Laherparepvec
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus.(1)
CLINICAL EFFECTS: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Talimogene laherparepvec is contraindicated in immunosuppressed patients.(1) The magnitude of immunocompromise and associated risks due to immunosuppressant drugs should be determined by a physician.
DISCUSSION: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1)
Selected Immunosuppressive Agents/Live Vaccines; Live Bcg
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: A variety of disease modifying agents suppress the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines or intravesicular BCG. Immune response to vaccines may be decreased during periods of immunocompromise.(1)
CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) After instillation of intravesicular BCG, immunosuppression may interfere with local immune response, or increase the severity of mycobacterial infection following inadvertent systemic exposure.(2)
PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency.
PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) Patients who receive anti-B cell therapies should not receive live vaccines for at least 6 months after such therapies due to a prolonged duration of immunosuppression. An exception is the Zoster vaccine, which can be given at least 1 month after receipt of anti-B cell therapies.(1) The US manufacturer of abatacept states live vaccines should not be given during or for up to 3 months after discontinuation of abatacept.(2) The US manufacturer of live BCG for intravesicular treatment of bladder cancer states use is contraindicated in immunosuppressed patients.(3) The US manufacturer of daclizumab states live vaccines are not recommended during and for up to 4 months after discontinuation of treatment.(4) The US manufacturer of guselkumab states that live vaccines should be avoided during treatment with guselkumab.(5) The US manufacturer of inebilizumab-cdon states that live vaccines are not recommended during treatment and after discontinuation until B-cell repletion. Administer all live vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon.(6) The US manufacturer of ocrelizumab states that live vaccines are not recommended during treatment and until B-cell repletion occurs after discontinuation of therapy. Administer all live vaccines at least 4 weeks prior to initiation of ocrelizumab.(7) The US manufacturer of ozanimod states that live vaccines should be avoided during and for up to 3 months after discontinuation of ozanimod.(8) The US manufacturer of siponimod states that live vaccines are not recommended during treatment and for up to 4 weeks after discontinuation of treatment.(9) The US manufacturer of ustekinumab states BCG vaccines should not be given in the year prior to, during, or the year after ustekinumab therapy.(10) The US manufacturer of satralizumab-mwge states that live vaccines are not recommended during treatment and should be administered at least four weeks prior to initiation of satralizumab-mwge.(11) The US manufacturer of ublituximab-xiiy states that live vaccines are not recommended during treatment and until B-cell recovery. Live vaccines should be administered at least 4 weeks prior to initiation of ublituximab-xiiy.(12) The US manufacturer of etrasimod states that live vaccines should be avoided during and for 5 weeks after treatment. Live vaccines should be administered at least 4 weeks prior to initiation of etrasimod.(13) The US manufacturer of emapalumab-lzsg states that live vaccines should not be administered to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.(14) The US manufacturer of sibeprenlimab-szsi states live vaccines should not be given within 30 days prior to initiation or during treatment with sibeprenlimab-szsi.(15)
DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1)
Tumor Necrosis Factor (TNF) Inhibitors/Vedolizumab
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Possibly additive or synergistic effects on the immune system.
CLINICAL EFFECTS: Concurrent use of vedolizumab and a tumor necrosis factor (TNF) inhibitor may increase the risk of severe infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of vedolizumab states that concurrent use of vedolizumab with tumor necrosis factor (TNF) blocking agents should be avoided.(1)
DISCUSSION: Patients receiving or who had received a TNF inhibitor in the past 60 days were excluded from clinical trials for vedolizumab.(1)
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Biologic Therapies/Anifrolumab
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use of anifrolumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1)
CLINICAL EFFECTS: Concurrent use of anifrolumab with other biologic therapies may increase the risk of serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The concurrent use of anifrolumab with other biologic therapies is not recommended.(1)
DISCUSSION: The combination of anifrolumab with other biologic therapies has not been studied and is not recommended.(1)
Igg Antibodies And Derivatives/Efgartigimod-Alfa
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)
CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)
DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)
Igg Antibodies And Derivatives/Nipocalimab-Aahu
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)
CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)
DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)
Immunosuppres;Immunomodul/Selected Multiple Sclerosis Agents
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Ocrelizumab or ofatumumab in combination with immunosuppressives and immune-modulators all suppress the immune system.(1,2)
CLINICAL EFFECTS: Concurrent use of ocrelizumab or ofatumumab with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1,2)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: The ocrelizumab US prescribing information states: - Ocrelizumab and other immune-modulating or immunosuppressive therapies, (including immunosuppressant doses of corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with ocrelizumab. When switching from drugs with prolonged immune effects, such as daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating ocrelizumab.(1) The ofatumumab US prescribing information states: - Ofatumumab and other immunosuppressive therapies (including systemic corticosteroids) may have the potential for increased immunosuppressive effects and increase the risk of infection. When switching between therapies, the duration and mechanism of action of each therapy should be considered due to the potential for additive immunosuppressive effects. Ofatumumab for MS therapy has not been studied in combination with other MS agents that suppress the immune system.(2)
DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1,2) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(3)
Immunosuppressives; Immunomodulators/Baricitinib
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use of baricitinib with other biologic disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine or cyclosporine may result in additive or synergistic effects on the immune system.
CLINICAL EFFECTS: Concurrent use of baricitinib with other biologic DMARDs or potent immunosuppressants such as azathioprine or cyclosporine may increase the risk of serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of baricitinib states that concurrent use of baricitinib with biologic DMARDs or potent immunosuppressants is not recommended.(1)
DISCUSSION: Most patients who developed serious infections while being treated with baricitinib were on concomitant immunosuppressants like methotrexate and corticosteroids. The combination of baricitinib with other biologic DMARDs has not been studied.(1)
Immunosuppressives; Immunomodulators/Cladribine Oral
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Cladribine in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-2)
CLINICAL EFFECTS: Concurrent use of cladribine with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-2)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: Recommendations for cladribine regarding this interaction differ between regulatory approving agencies. The cladribine US prescribing information states: -Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short-term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of cladribine.(1) The cladribine Canadian prescribing information states: -Use of cladribine in immunocompromised patients is contraindicated because of a risk of additive effects on the immune system. Acute short-term therapy with corticosteroids can be administered during cladribine treatment.(2)
DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-2)
Immunosuppressives; Immunomodulators/Deuruxolitinib
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Deuruxolitinib, immunosuppressives, and immunomodulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of deuruxolitinib and potent immunosuppressants may increase the risk of serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of deuruxolitinib states that concurrent use of deuruxolitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1) If concurrent use cannot be avoided, patients should be monitored for signs and symptoms of infection. If a patient develops a serious or opportunistic infection, interrupt deuruxolitinib treatment until the infection is controlled.
DISCUSSION: Serious infections have been reported in patients receiving treatment with deuruxolitinib.(1)
Immunosuppressives; Immunomodulators/Etrasimod
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Etrasimod causes reversible sequestration of lymphocytes in lymphoid tissues, resulting in a mean 55% decrease in peripheral blood lymphocyte count at 52 weeks.(1) Other immunosuppressives and immune-modulators also suppress the immune system.
CLINICAL EFFECTS: Concurrent use of etrasimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious and fatal infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML).(1)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications increases the risk of adverse effects.
PATIENT MANAGEMENT: The etrasimod US prescribing information states etrasimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Concomitant administration of these therapies with etrasimod should be avoided because of the risk of additive immune effects during therapy and in the weeks following administration. Etrasimod's effect on peripheral lymphocytes may persist for up to 5 weeks after discontinuation.(1) When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects.(1)
DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients treated with other sphingosine-1 phosphate receptor modulators.(1)
Immunosuppressives; Immunomodulators/Filgotinib
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use of filgotinib with other immunosuppressants or immunomodulators including azathioprine, cyclosporine, tacrolimus, biologic disease-modifying antirheumatic drugs (DMARDs), or other Janus kinase (JAK) inhibitors may result in additive or synergistic effects on the immune system.(1)
CLINICAL EFFECTS: Concurrent use of filgotinib with other immunosuppressants or immunomodulators including azathioprine, cyclosporine, tacrolimus, biologic DMARDs, or other JAK inhibitors may increase the risk of serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The UK manufacturer of filgotinib states that concurrent use of filgotinib with other immunosuppressants or immunomodulators including azathioprine, cyclosporine, tacrolimus, biologic DMARDs, or other JAK inhibitors is not recommended.(1)
DISCUSSION: Serious infections have been reported in patients receiving filgotinib. Caution should be used in patients with a higher incidence of serious infection, including elderly patients aged 75 years and older.(1)
Immunosuppressives; Immunomodulators/Fingolimod
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Fingolimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-3)
CLINICAL EFFECTS: Concurrent use of fingolimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-3)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: Recommendations for fingolimod regarding this interaction differ between regulatory approving agencies. The fingolimod US prescribing information states: - Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with fingolimod. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating fingolimod.(1) The fingolimod Canadian prescribing information states: - Concurrent use with immunosuppressive or immunomodulatory agents is contraindicated due to the risk of additive immune system effects. However, co-administration of a short course of corticosteroids (up to 5 days) did not increase the overall rate of infection in patients participating Phase III clinical trials.(2) The fingolimod UK specific product characteristics states: - Fingolimod is contraindicated in patients currently receiving immunosuppressive therapies or those immunocompromised by prior therapies. When switching patients from another disease modifying therapy to Gilenya, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time minimizing the risk of disease activation.(3)
DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-3)
Immunosuppressives; Immunomodulators/Inebilizumab
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Inebilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of inebilizumab with immunosuppressive or immunomodulating agents may result in myelosuppression including neutropenia resulting in an increased risk for serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of inebilizumab states that the concurrent use of inebilizumab with immunosuppressive agents, including systemic corticosteroids, may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1)
DISCUSSION: Inebilizumab has not been studied in combination with other immunosuppressants. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents. The most common infections reported by inebilizumab treated patients in the randomized and open-label clinical trial periods included urinary tract infections (20%), nasopharyngitis (13%), upper respiratory tract infections (8%), and influenza (7%). Although there been no cases of Hepatitis B virus reactivation or progressive multifocal leukoencephalopathy reported in patients taking inebilizumab, these infections have been observed in patients taking other B-cell-depleting antibodies.(1)
Immunosuppressives; Immunomodulators/Ozanimod
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Ozanimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of ozanimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: The ozanimod US prescribing information state this information regarding this interaction: -Ozanimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ozanimod after alemtuzumab is not recommended. However, ozanimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1)
DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1)
Immunosuppressives; Immunomodulators/Ponesimod
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Ponesimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of ponesimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: The ponesimod US prescribing information states ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ponesimod after alemtuzumab is not recommended. However, ponesimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1)
DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1)
Immunosuppressives; Immunomodulators/Ritlecitinib
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Ritlecitinib, immunosuppressives, and immunomodulators all suppress the immune system.
CLINICAL EFFECTS: Concurrent use of ritlecitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of ritlecitinib states that concurrent use of ritlecitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1)
DISCUSSION: Serious infections have been reported in patients receiving ritlecitinib. Reported infections included appendicitis, COVID-19 infection (including pneumonia), and sepsis. Reports of viral reactivation, including herpes virus reactivation was reported in clinical studies with ritlecitinib.(1)
Immunosuppressives; Immunomodulators/Siponimod
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Siponimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of siponimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: The siponimod US prescribing information state this information regarding this interaction: -Siponimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with siponimod after alemtuzumab is not recommended. However, siponimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1)
DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1)
Immunosuppressives; Immunomodulators/Tofacitinib
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use of tofacitinib and azathioprine, other biologic disease-modifying antirheumatic drugs (DMARDs), or potent immunosuppressants may result in additive or synergistic effects on the immune system.(1)
CLINICAL EFFECTS: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants use may increase the risk of serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Tofacitinib should not be used concurrently with azathioprine, other biologic DMARDs, or cyclosporine.(1) Patient should be monitored for decreases in lymphocytes and neutrophils. Therapy should be adjusted based on the indication. - For all indications: If absolute neutrophil count (ANC) or lymphocyte count is less than 500 cells/mm3, discontinue tofacitinib. - For rheumatoid arthritis or psoriatic arthritis and absolute neutrophil count (ANC) 500 to 1000 cells/mm3: interrupt dosing. When ANC is greater than 1000 cells/mm3, resume Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily. - For ulcerative colitis and ANC 500 to 1000 cells/mm3: -If taking Xeljanz 10 mg twice daily, decrease to 5 mg twice daily. When ANC is greater than 1000 cells/mm3, increase to 10 mg twice daily based on clinical response. -If taking Xeljanz 5 mg twice daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 5 mg twice daily. -If taking Xeljanz XR 22 mg once daily, decrease to 11 mg once daily. When ANC is greater than 1000 cells/mm3, increase to 22 mg once daily based on clinical response. -If taking Xeljanz XR 11 mg once daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 11 mg once daily. - For polyarticular course juvenile idiopathic arthritis (pcJIA) and ANC 500 to 1000 cells/mm3: interrupt dosing until ANC is greater than 1000 cells/mm3.(1)
DISCUSSION: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants may increase the risk of infection.(1) Serious infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving tofacitinib. Some patients presented with disseminated disease and were often taking concomitant immunomodulating agents. In the ulcerative colitis population, a greater risk of serious infections was seen with a higher tofacitinib dose. In 7 placebo-controlled rheumatoid arthritis trials (0-3 months exposure), the overall frequency of infections was 20% in the tofacitinib 5 mg twice daily group and 22% in the tofacitinib 10 mg twice daily group compared to 18% in the placebo group. Serious infections were reported in 11 patients (1.7 events per 100 patient-years) with a rate difference between treatment groups of 1.1 (-0.4, 2.5) events per 100 patient-years for both tofacitinib 5 mg twice daily and 10 mg twice daily. During 0-12 months exposure, serious infections were reported in 34 patients (2.7 events per 100 patient years) in the tofacitinib 5 mg twice daily group and 33 patients (2.7 events per 100 patient years) in the tofacitinib 10 mg twice daily group.(1)
Immunosuppressives; Immunomodulators/Upadacitinib
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Upadacitinib, immunosuppressives, and immunomodulators all suppress the immune system.
CLINICAL EFFECTS: Concurrent use of upadacitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of upadacitinib states that concurrent use of upadacitinib with immunosuppressives or immunomodulators is not recommended.
DISCUSSION: Serious infections have been reported in patients receiving upadacitinib. Reported infections included pneumonia, cellulitis, tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, cryptococcosis. Reports of viral reactivation, including herpes virus reactivation and hepatitis B reactivation, were reported in clinical studies with upadacitinib.(1)
Slt Immunosuppress; Immunomodulator/Ropeginterferon Alfa-2B
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Ropeginterferon alfa-2b and immunosuppressives both suppress the immune system.
CLINICAL EFFECTS: Concurrent use of ropeginterferon alfa-2b with immunosuppressives may result in an increased risk of serious infections.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Avoid concurrent use of myelosuppressive agents.(1-2) If concurrent use cannot be avoided, monitor for effects of excessive immunosuppression.
DISCUSSION: In clinical trials, 20% of patients experienced leukopenia. Interferon alfa products may cause fatal or life-threatening infections.(1-2)
Tnf Blockers/Azathioprine; Mercaptopurine
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: The exact mechanism is unknown, but may involve additive or synergistic effects on the immune system.
CLINICAL EFFECTS: Concurrent use of a TNF blocker with either azathioprine or mercaptopurine may increase the risk of hepatosplenic T-cell lymphoma (HSTCL), a rare but usually fatal cancer.(1-3)
PREDISPOSING FACTORS: The majority of reports of hepatosplenic T cell lymphoma in patients receiving concurrent TNF blockers with either azathioprine or mercaptopurine have occurred in patients with Crohn's disease or ulcerative colitis; however, there is one report in a psoriasis patient and two reports in rheumatoid arthritis patients.(1) The majority of patients were adolescent or young males.(2)
PATIENT MANAGEMENT: Patients receiving concurrent therapy with TNF blockers and either azathioprine or mercaptopurine should be counseled on the risk of developing hepatosplenic T-cell lymphoma, a rare but usually fatal cancer. They should be counseled on the signs and symptoms of malignancies such as HSTCL, which may include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.
DISCUSSION: From initiation of TNF marketing to December 31, 2010, the FDA has received 28 reports of hepatosplenic T-cell lymphoma (HSTCL) in patients receiving TNF blockers: infliximab (20), etanercept (1), adalimumab (2), infliximab/adalimumab (5), certolizumab (0), golimumab (0). In 22 of these cases, the patients were also receiving azathioprine or mercaptopurine (18 with infliximab, 4 with infliximab/adalimumab).(1)
Tumor Necrosis Factor (TNF) Inhibitors/Interleukin-1 Blocker
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Possibly additive or synergistic effects on the immune system.
CLINICAL EFFECTS: Concurrent use of anakinra, canakinumab, or rilonacept and a tumor necrosis factor (TNF) inhibitor may increase the risk of severe infection and/or neutropenia(1-9) without providing any clinical benefit.(4-6)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of anakinra states that concurrent use of anakinra with tumor necrosis factor (TNF) blocking agents certolizumab, etanercept, and infliximab is not recommended.(1) The Canadian(2) and US(3) manufacturers of adalimumab, the US manufacturer of certolizumab,(4) and the US manufacturer of golimumab,(4) and the US manufacturer of infliximab(7) state that concurrent therapy with anakinra is not recommended. The Australian manufacturers of infliximab, adalimumab, etanercept, and golimumab state that concurrent use with anakinra is contraindicated.(11-14) The Australian manufacturer of anakinra states that concurrent therapy with TNF inhibitors is contraindicated.(15) The US manufacturers of rilonacept(8) and canakinumab(9) state that concurrent use with TNF blocking agents is not recommended. Patients receiving concurrent therapy should be closely monitored for signs of infection and neutropenia.(10)
DISCUSSION: Preliminary data suggest a higher rate of serious infections (7%) in patients treated concurrently with anakinra and etanercept compared to when anakinra is administered alone (2%)(1) or when etanercept is administered alone (0%).(5,8) The most common infections were bacterial pneumonia (4 cases) and cellulitis (4 cases). One patient with pulmonary fibrosis and pneumonia died from respiratory failure.(6) Preliminary data also suggest a higher rate of neutropenia (2-3%) when anakinra is administered with etanercept.(1,6) Data also suggest that the combination provides no added clinical benefit.(6)
Moderate Interaction: Assess the risk to the patient and take action as needed.
Biologic Therapies/Belimumab
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Concurrent use of belimumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1)
CLINICAL EFFECTS: Concurrent use of belimumab with other biologic therapies may increase the risk of serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The concurrent use of belimumab with other biologic therapies should be approached with caution.(1)
DISCUSSION: In a randomized, double-blind, placebo-controlled trial, more patients who received belimumab and rituximab experienced serious adverse events, serious infections, and post-injection systemic reactions (22.2%, 9%, and 13.2%, respectively) than patients who received belimumab with placebo (13.9%, 2.8%, 9.7%) or standard therapy (19.7%, 5.3%, 5.3%).(1) The combination of belimumab with other biologic therapies has not been studied and should be used cautiously.(1)
Igg Antibodies And Derivatives/Rozanolixizumab-Noli
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)
CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)
DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)
Immunosuppressives; Immunomodulators/Cladribine Oncology Inj
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Cladribine in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-4)
CLINICAL EFFECTS: Concurrent use of cladribine with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections.(1-4)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: Recommendations for cladribine regarding this interaction differ between regulatory approving agencies. The cladribine US, UK, and Australian prescribing information state: -Caution should be exercised if cladribine injection is administered before, after, or in conjunction with other drugs known to cause immunosuppression or myelosuppression.(1-3) The cladribine Canadian prescribing information states: -Proceed carefully in patients with severe bone marrow impairment of any etiology since further suppression of bone marrow function should be anticipated.(4)
DISCUSSION: Severe bone marrow suppression, including neutropenia, anemia and thrombocytopenia, has been commonly observed in patients treated with cladribine injection, especially at high doses.(1-4)
Immunosuppressives; Immunomodulators/Covid-19 Vaccines
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Immunosuppressants and immunomodulators may prevent the immune system from properly responding to the COVID-19 vaccine.(1-3)
CLINICAL EFFECTS: Administration of a COVID-19 vaccine with immunosuppressants or immunomodulators may interfere with vaccine-induced immune response and impair the efficacy of the vaccine. However, patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted.(1-3)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The Centers for Disease Control and Prevention (CDC),(1) Infectious Diseases Society of America (IDSA),(2) and the American College of Rheumatology (ACR)(3) have published guidances for COVID-19 vaccination in patients on immunosuppressants. The CDC states that all immunocompromised patients over 6 months of age should receive at least 1 dose of COVID-19 vaccine if eligible. See the CDC's Interim Clinical Considerations for Use of COVID-19 Vaccines for specific recommendations based on age, vaccination history, and vaccine manufacturer.(1) The CDC advises planning for vaccination at least 2 weeks before starting or resuming immunosuppressive therapy.(1) IDSA recommends timing COVID-19 vaccination at least 2 weeks before starting or at least 3 months after completing immunosuppressive therapy.(2) The ACR states that in general, immunosuppressants and immunomodulators should be held for 1-2 weeks after each vaccine dose.(3) Patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted, though the immune response will likely be blunted. COVID-19 vaccines should not be delayed in patients taking immunosuppressive therapies.(1-2) See below for specific recommendations for certain agents. B-cell depleting agents, including rituximab: The CDC states that the utility of B-cell quantification to guide clinical care is not known and is not recommended. Patients who receive B-cell depleting therapy on a continuing basis should receive COVID-19 vaccines about 4 weeks before the next scheduled dose. For patients who received 1 or more doses of COVID-19 vaccine during treatment with B-cell-depleting therapies that were administered over a limited period (e.g., as part of a treatment regimen for certain malignancies), revaccination may be considered according to the current CDC recommendations for unvaccinated patients. The suggested interval to start revaccination is about 6 months after completion of the B-cell-depleting therapy.(1) IDSA recommends waiting for at least 3-6 months after the last infusion of B-cell depleting therapy before administering COVID-19 vaccines.(2) The ACR recommends consulting with the rheumatologist to determine optimal timing of COVID-19 vaccination. Measuring CD19 B cells may be considered to determine need for a booster vaccine dose. If B cell levels are not measured, a supplemental vaccine dose 2-4 weeks before the next scheduled dose of rituximab is recommended.(3) Recipients of hematopoietic cell transplant or CAR-T-cell therapy who received one or more doses of COVID-19 vaccine prior to or during treatment should undergo revaccination following the current CDC recommendations for unvaccinated patients. Revaccination should start at least 3 months (12 weeks) after transplant or CAR-T-cell therapy.(1,2) The CDC includes abatacept, cyclophosphamide, and TNF-alpha and cytokine inhibitors in their general recommendation to hold therapy for at least 2 weeks following vaccination (1) while the ACR provides different recommendations:(3) *Abatacept: - Subcutaneous abatacept should be withheld for 1-2 weeks after each vaccine dose, as disease activity allows. - For intravenous abatacept, time administration so that vaccination will occur 1 week before the next abatacept infusion. *Cyclophosphamide: When feasible, administer cyclophosphamide 1 week after each COVID-19 vaccine dose. *TNF-alpha inhibitors and cytokine inhibitors: The ACR was not able to reach consensus on whether to modify dosing or timing of these agents with COVID-19 vaccination.
DISCUSSION: IDSA recommendations are based on cohort and case control studies in immunocompromised patients that found low to modest vaccine effectiveness (37-61%) but lower risks of COVID-19 association hospitalization, COVID-19 related mortality, and critical illness.(2) The ACR convened a COVID-19 Vaccine Guidance Task Force to provide guidance on optimal use of COVID-19 vaccines in rheumatology patients. These recommendations are based on limited clinical evidence of COVID-19 vaccines in patients without rheumatic and musculoskeletal disorders and evidence of other vaccines in this patient population.(3) The ACR recommendation for rituximab is based on studies of humoral immunity following receipt of other vaccines. These studies have uncertain generalizability to vaccination against COVID-19, as it is unknown if efficacy is attributable to induction of host T cells versus B cell (antibody-based) immunity.(3) The ACR recommendation for mycophenolate is based on preexisting data of mycophenolate on non-COVID-19 vaccine immunogenicity. Emerging data suggests that mycophenolate may impair SARS-CoV-2 vaccine response in rheumatic and musculoskeletal disease and transplant patients.(3) The ACR recommendation for methotrexate is based on data from influenza vaccines and pneumococcal vaccines with methotrexate.(3) The ACR recommendation for JAK inhibitors is based on concerns related to the effects of JAK inhibitors on interferon signaling that may result in a diminished vaccine response.(3) The ACR recommendation for subcutaneous abatacept is based on several studies suggesting a negative effect of abatacept on vaccine immunogenicity. The first vaccine dose primes naive T cells, naive T cell priming is inhibited by CTLA-4, and abatacept is a CTLA-4Ig construct. CTLA-4 should not inhibit boosts of already primed T cells at the time of the second vaccine dose.(3)
Immunosuppressives; Immunomodulators/Ublituximab
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Ublituximab, immunosuppressives, and immunomodulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of ublituximab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1)
PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications.
PATIENT MANAGEMENT: The US manufacturer of ublituximab recommends caution because the concurrent use of ublituximab with immunomodulating or immunosuppressive agents, including immunosuppressant doses of corticosteroids, may increase the risk of infection.(1) If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents. When switching from agents with immune effects, the half-life and mechanism of action of these drugs must be taken into consideration in order to prevent additive immunosuppressive effects.(1)
DISCUSSION: The most common infections reported by ublituximab-treated patients in the clinical trial periods included upper respiratory tract infections and urinary tract infections. Serious, including life-threatening or fatal, bacterial and viral infections were observed in patients receiving ublituximab.(1) Serious and/or fatal bacterial, fungal, and new or reactivated viral infections have been associated with other anti-CD20 B-cell depleting therapies. There were no cases of progressive multifocal leukoencephalopathy (PML) reported during the clinical trials; however, there have been reports of PML during or following completion of other anti-CD20 B-cell depleting therapies.(1)
Immunosuppressives; Immunomodulators/Ustekinumab
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Ustekinumab, immunosuppressives, and immunomodulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of ustekinumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of ustekinumab recommends caution because the concurrent use of ustekinumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1)
DISCUSSION: Ustekinumab has not been studied in combination with other immunosuppressants in psoriasis studies. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of ustekinumab. In Crohn's disease and ulcerative colitis studies, concomitant use of immunosuppressants or corticosteroids did not appear to influence the safety or efficacy of ustekinumab. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by ustekinumab treated patients in the clinical trial periods included nasopharyngitis(8%) and upper respiratory tract infection(5%). Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab. Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia resulting in respiratory failure or prolonged hospitalization have been reported in patients receiving ustekinumab.(1)
Contraindications
*Prior hypersensitivity reaction to infliximab products or any inactive ingredients in the formulations or any murine proteins.
*Doses greater than 5 mg/kg are contraindicated in patients with moderate or severe heart failure.
- Active tuberculosis
- Disseminated candidiasis
- Disseminated tuberculosis
- Extrapulmonary pneumocystosis
- Lupus-like syndrome
- Opportunistic fungal infection
- Pneumocystis jirovecii pneumonia
- Sepsis
- Chronic heart failure
- Demyelinating disorder
- Disease of liver
- Guillain-barre syndrome
- Hepatosplenic t-cell lymphoma
- Immunosuppression
- Inactive tuberculosis
- Infection
- Legionella pneumophila pneumonia
- Leukemia
- Leukopenia
- Listeriosis
- Malignancy
- Malignant lymphoma
- Multiple sclerosis
- Neutropenic disorder
- Opportunistic viral infection
- Optic neuritis
- Pancytopenia
- Seizure disorder
- Thrombocytopenic disorder
- Vasculitis
- Viral hepatitis B
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in greater than 10% of patients receiving IV infliximab products include infections (e.g., upper respiratory, sinusitis, pharyngitis), infusion-related reactions, headache, and abdominal pain.
Adverse effects reported in >=3% of patients receiving subcutaneous infliximab-dyyb for ulcerative colitis include COVID-19, anemia, arthralgia, injection site reaction, increased alanine aminotransferase, and abdominal pain.
Adverse effects reported in >=3% of patients receiving subcutaneous infliximab-dyyb for Crohn disease include COVID-19, headache, upper respiratory tract infection, injection site reaction, diarrhea, increased blood creatine phosphokinase, arthralgia, increased alanine aminotransferase, hypertension, urinary tract infection, neutropenia, dizziness, and leukopenia.
More Frequent
- Abnormal hepatic function tests
- Anemia
- Hypersensitivity drug reaction
- Hypotension
- Increased alanine transaminase
- Increased aspartate transaminase
- Urticaria
Less Frequent
- Candidiasis
- Hypertension
- Viral infection
Rare or Very Rare
- Abscess
- Active tuberculosis
- Acute hepatic failure
- Acute myocardial infarction
- Agranulocytosis
- Anaphylaxis
- Aspergillosis
- Autoimmune hepatitis
- Bacterial sepsis
- Blastomycosis
- Bradycardia
- Bronchospastic pulmonary disease
- Bullous dermatitis
- Carcinoma of cervix
- Cardiac arrhythmia
- Cellulitis
- Cerebrovascular accident
- Cholestasis
- Chronic inflammatory demyelinating polyneuropathy
- Coccidioidomycosis
- Cryptococcosis
- Cutaneous vasculitis
- Cytomegalovirus disease
- Dehydration
- Demyelinating disorder
- Drug-exacerbated psoriasis
- Erythema multiforme
- Gastrointestinal obstruction
- Guillain-barre syndrome
- Heart failure
- Hemolytic anemia
- Hepatitis
- Hepatosplenic t-cell lymphoma
- Histoplasmosis
- Idiopathic thrombocytopenic purpura
- Infection
- Interstitial pneumonitis
- Jaundice
- Laryngeal edema
- Legionnaires' disease
- Leukemia
- Leukopenia
- Linear immunoglobulin A bullous dermatosis
- Listeriosis
- Lupus-like syndrome
- Lymphadenopathy
- Malignancy
- Malignant lymphoma
- Malignant melanoma
- Merkel cell carcinoma
- Multiple sclerosis
- Mycosis fungoides
- Myelitis
- Neutropenic disorder
- Nocardiosis
- Opportunistic fungal infection
- Optic neuritis
- Pancytopenia
- Parasitic infection
- Pericardial effusion
- Peripheral motor neuropathy
- Pneumocystis jirovecii pneumonia
- Pneumonia
- Pulmonary edema
- Pulmonary fibrosis
- Reactivated tuberculosis
- Reactivation of hepatitis B
- Salmonella septicemia
- Seizure disorder
- Serum sickness
- Skin ulcer
- Squamous cell carcinoma
- Stevens-johnson syndrome
- Thrombocytopenic disorder
- Thrombotic thrombocytopenic purpura
- Toxic epidermal necrolysis
- Vasculitis
- Vision impairment
- Worsening of chronic heart failure
More Frequent
- Acute abdominal pain
- Chest pain
- Chills
- Dyspnea
- Fatigue
- Fever
- Flu-like symptoms
- Flushing
- Headache disorder
- Myalgia
- Nausea
- Pharyngitis
- Pruritus of skin
- Sinusitis
- Skin rash
- Upper respiratory infection
- Vomiting
Less Frequent
- Arthralgia
- Bronchitis
- Cough
- Diarrhea
- Dyspepsia
- Oral candidiasis
- Pain
- Urinary tract infection
Rare or Very Rare
- Basal cell carcinoma of skin
- Constipation
- Dizziness
- Edema
- Facial edema
- Hyperhidrosis
- Hyperlipidemia
- Thrombophlebitis
- Transient blindness
Precautions
No enhanced messaging available.
Safety and efficacy of IV infliximab and its biosimilars (infliximab-abda, infliximab-axxq, infliximab-dyyb) have been established in pediatric patients 6 years of age and older with Crohn disease. The manufacturer states that infliximab has been studied in this population only in conjunction with conventional immunosuppressive therapy. Safety and efficacy of long-term therapy (exceeding 1 year) with infliximab products in pediatric patients with Crohn disease have not been established. Use of infliximab products for the management of Crohn disease in pediatric patients 6 years of age or older is supported by the results of a randomized, open-label study in 112 pediatric patients 6 years of age or older. Safety and efficacy for the management of Crohn disease have not been established in pediatric patients younger than 6 years of age.
Safety and efficacy of IV infliximab and its biosimilars (infliximab-abda, infliximab-axxq, infliximab-dyyb) have been established in pediatric patients 6 years of age and older with ulcerative colitis. Safety and efficacy of long-term infliximab therapy (exceeding 1 year) in pediatric patients with ulcerative colitis have not been established. Use of infliximab products for the management of ulcerative colitis in pediatric patients 6 years of age or older is supported by the results of adequate and well-controlled studies in adults with additional safety and pharmacokinetic data from an open-label study in 60 pediatric patients 6 years of age or older. Safety and efficacy for the management of ulcerative colitis have not been established in pediatric patients younger than 6 years of age.
Safety and efficacy of infliximab products in pediatric patients with plaque psoriasis have not been established.
Safety and efficacy of infliximab for the management of juvenile rheumatoid arthritis+ have been evaluated in children 4-17 years of age with juvenile arthritis who had not responded adequately to methotrexate. While infliximab in combination with methotrexate produced important and durable clinical effects in children, the primary efficacy end point (i.e., the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement) measured at week 14 did not differ between infliximab-treated children and placebo recipients. A 3-mg/kg dose of infliximab was associated with a higher risk of serious adverse events, infusion reactions, and development of antibodies to infliximab, antinuclear antibodies (ANAs), and antibodies to double stranded DNA (anti-ds DNA) compared with a 6-mg/kg dose. Further study is needed to evaluate the safety and efficacy of the drug for juvenile rheumatoid arthritis.
Malignancies, some fatal, have been reported in children and adolescents who received treatment with TNF blocking agents. It is unclear whether reported cases of hepatosplenic T-cell lymphoma in patients receiving infliximab products have been related to use of the TNF blocking agent or use of the TNF blocking agent in conjunction with other immunosuppressive agents. Therefore, carefully assess risks and benefits when deciding whether to use infliximab products alone or in combination with other immunosuppressive agents.
Pharmacokinetic values for infliximab in pediatric patients 6-17 years of age with Crohn disease or ulcerative colitis are similar to values in adults with these diseases.
All pediatric patients should be up to date with their vaccinations prior to initiating therapy with infliximab products.
Infliximab has been detected for up to 6 months in the serum of infants whose mothers received infliximab products during pregnancy. Infants who were exposed to infliximab products in utero may be at increased risk of infection. Fatal disseminated BCG infection has been reported in an infant who received BCG vaccine after having been exposed to infliximab in utero. Do not administer live vaccines to infants exposed to infliximab products in utero for at least 6 months following birth.
The safety and efficacy of infliximab-dyyb (Zymfentra(R)) in pediatric patients have not been established.
Available observational studies in pregnant women exposed to infliximab products showed no increased risk of major malformations among live births as compared to those exposed to non-biologics. In a study using data from an inflammatory bowel disease pregnancy registry, infliximab exposure was not associated with increased rates of major congenital malformations, miscarriage/stillbirth, infants of low birth weight, small for gestational age, or infection in the first year of life. In a second study of inflammatory bowel disease patients conducted in Sweden, Finland, and Denmark, exposure to infliximab was not associated with increased rates of congenital anomalies or infant death; however, when infliximab was given in combination with immunosuppressants (e.g., systemic corticosteroids, azathioprine), the combination therapy was associated with increased rates of preterm birth, small for gestational age, low birth weight, and infant hospitalization for infection compared to non-biologic systemic treatment. Methodological limitations may hinder interpretation of these study results. Women with inflammatory bowel disease or rheumatoid arthritis may have an increased risk of adverse pregnancy outcomes (e.g., preterm delivery, low birth weight, small for gestational age at birth) with increased disease activity.
Infliximab crosses the placenta during the third trimester of pregnancy and may affect immune responses in infants who were exposed in utero. Infliximab has been detected for up to 6 months in the serum of infants whose mothers received infliximab products during pregnancy.
Reproduction studies using infliximab products in animals have not been conducted since the drug only binds TNF from humans and other primates and does not cross-react with TNF from other species. In a developmental toxicity study conducted in mice using a murine anti-TNF antibody that selectively inhibits murine TNF, no evidence of maternal toxicity, fetal mortality, or structural abnormalities was observed. In pharmacodynamic animal models using an analogous anti-TNF antibody, doses of 10-15 mg/kg produced maximal pharmacologic effectiveness; in animal reproduction studies, doses up to 40 mg/kg produced no adverse effects.
Clinical studies indicate that IV infliximab is present in human milk at low levels. Systemic exposure in a breastfed infant is expected to be low, as infliximab is largely degraded in the GI tract. In a study of 168 women with inflammatory bowel disease treated with infliximab, infants exposed to infliximab through breast milk had no increase in infection rates and demonstrated normal development. There are no data on the effects of infliximab on milk production. Consider the developmental and health benefits of breastfeeding, along with the mother's clinical need for the infliximab product and any potential adverse effects on the breastfed infant from the infliximab product or from the underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Clinical studies evaluating infliximab for the management of Crohn disease, ulcerative colitis, ankylosing spondylitis, and psoriatic arthritis have included an insufficient number of patients 65 years of age and older to make a valid comparison of the drug's safety and efficacy in geriatric patients compared with younger adults. In clinical studies in adults with rheumatoid arthritis or plaque psoriasis, there were no overall differences in the safety and efficacy of infliximab in those 65 years of age or older compared with younger adults; however, the incidence of serious adverse effects was higher in infliximab-treated and control patients 65 years of age or older compared with younger adults. Because serious infectious complications have been reported in some patients receiving infliximab products and because the overall incidence of infection is higher in geriatric adults than in younger individuals, monitor geriatric patients who receive infliximab products closely for the development of serious infections..
ICD codes
| Code | Type | Description |
|---|---|---|
| Crohn's disease | ||
| K50 | ICD10CM | Crohn's disease [regional enteritis] |
| K50.0 | ICD10CM | Crohn's disease of small intestine |
| K50.00 | ICD10CM | Crohn's disease of small intestine without complications |
| K50.01 | ICD10CM | Crohn's disease of small intestine with complications |
| K50.011 | ICD10CM | Crohn's disease of small intestine with rectal bleeding |
| K50.012 | ICD10CM | Crohn's disease of small intestine with intestinal obstruction |
| K50.013 | ICD10CM | Crohn's disease of small intestine with fistula |
| K50.014 | ICD10CM | Crohn's disease of small intestine with abscess |
| K50.018 | ICD10CM | Crohn's disease of small intestine with other complication |
| K50.019 | ICD10CM | Crohn's disease of small intestine with unspecified complications |
| K50.1 | ICD10CM | Crohn's disease of large intestine |
| K50.10 | ICD10CM | Crohn's disease of large intestine without complications |
| K50.11 | ICD10CM | Crohn's disease of large intestine with complications |
| K50.111 | ICD10CM | Crohn's disease of large intestine with rectal bleeding |
| K50.112 | ICD10CM | Crohn's disease of large intestine with intestinal obstruction |
| K50.113 | ICD10CM | Crohn's disease of large intestine with fistula |
| K50.114 | ICD10CM | Crohn's disease of large intestine with abscess |
| K50.118 | ICD10CM | Crohn's disease of large intestine with other complication |
| K50.119 | ICD10CM | Crohn's disease of large intestine with unspecified complications |
| K50.8 | ICD10CM | Crohn's disease of both small and large intestine |
| K50.80 | ICD10CM | Crohn's disease of both small and large intestine without complications |
| K50.81 | ICD10CM | Crohn's disease of both small and large intestine with complications |
| K50.811 | ICD10CM | Crohn's disease of both small and large intestine with rectal bleeding |
| K50.812 | ICD10CM | Crohn's disease of both small and large intestine with intestinal obstruction |
| K50.813 | ICD10CM | Crohn's disease of both small and large intestine with fistula |
| K50.814 | ICD10CM | Crohn's disease of both small and large intestine with abscess |
| K50.818 | ICD10CM | Crohn's disease of both small and large intestine with other complication |
| K50.819 | ICD10CM | Crohn's disease of both small and large intestine with unspecified complications |
| K50.9 | ICD10CM | Crohn's disease, unspecified |
| K50.90 | ICD10CM | Crohn's disease, unspecified, without complications |
| K50.91 | ICD10CM | Crohn's disease, unspecified, with complications |
| K50.911 | ICD10CM | Crohn's disease, unspecified, with rectal bleeding |
| K50.912 | ICD10CM | Crohn's disease, unspecified, with intestinal obstruction |
| K50.913 | ICD10CM | Crohn's disease, unspecified, with fistula |
| K50.914 | ICD10CM | Crohn's disease, unspecified, with abscess |
| K50.918 | ICD10CM | Crohn's disease, unspecified, with other complication |
| K50.919 | ICD10CM | Crohn's disease, unspecified, with unspecified complications |
| Ulcerative colitis | ||
| K51 | ICD10CM | Ulcerative colitis |
| K51.0 | ICD10CM | Ulcerative (chronic) pancolitis |
| K51.00 | ICD10CM | Ulcerative (chronic) pancolitis without complications |
| K51.01 | ICD10CM | Ulcerative (chronic) pancolitis with complications |
| K51.011 | ICD10CM | Ulcerative (chronic) pancolitis with rectal bleeding |
| K51.012 | ICD10CM | Ulcerative (chronic) pancolitis with intestinal obstruction |
| K51.013 | ICD10CM | Ulcerative (chronic) pancolitis with fistula |
| K51.014 | ICD10CM | Ulcerative (chronic) pancolitis with abscess |
| K51.018 | ICD10CM | Ulcerative (chronic) pancolitis with other complication |
| K51.019 | ICD10CM | Ulcerative (chronic) pancolitis with unspecified complications |
| K51.2 | ICD10CM | Ulcerative (chronic) proctitis |
| K51.20 | ICD10CM | Ulcerative (chronic) proctitis without complications |
| K51.21 | ICD10CM | Ulcerative (chronic) proctitis with complications |
| K51.211 | ICD10CM | Ulcerative (chronic) proctitis with rectal bleeding |
| K51.212 | ICD10CM | Ulcerative (chronic) proctitis with intestinal obstruction |
| K51.213 | ICD10CM | Ulcerative (chronic) proctitis with fistula |
| K51.214 | ICD10CM | Ulcerative (chronic) proctitis with abscess |
| K51.218 | ICD10CM | Ulcerative (chronic) proctitis with other complication |
| K51.219 | ICD10CM | Ulcerative (chronic) proctitis with unspecified complications |
| K51.3 | ICD10CM | Ulcerative (chronic) rectosigmoiditis |
| K51.30 | ICD10CM | Ulcerative (chronic) rectosigmoiditis without complications |
| K51.31 | ICD10CM | Ulcerative (chronic) rectosigmoiditis with complications |
| K51.311 | ICD10CM | Ulcerative (chronic) rectosigmoiditis with rectal bleeding |
| K51.312 | ICD10CM | Ulcerative (chronic) rectosigmoiditis with intestinal obstruction |
| K51.313 | ICD10CM | Ulcerative (chronic) rectosigmoiditis with fistula |
| K51.314 | ICD10CM | Ulcerative (chronic) rectosigmoiditis with abscess |
| K51.318 | ICD10CM | Ulcerative (chronic) rectosigmoiditis with other complication |
| K51.319 | ICD10CM | Ulcerative (chronic) rectosigmoiditis with unspecified complications |
| K51.5 | ICD10CM | Left sided colitis |
| K51.50 | ICD10CM | Left sided colitis without complications |
| K51.51 | ICD10CM | Left sided colitis with complications |
| K51.511 | ICD10CM | Left sided colitis with rectal bleeding |
| K51.512 | ICD10CM | Left sided colitis with intestinal obstruction |
| K51.513 | ICD10CM | Left sided colitis with fistula |
| K51.514 | ICD10CM | Left sided colitis with abscess |
| K51.518 | ICD10CM | Left sided colitis with other complication |
| K51.519 | ICD10CM | Left sided colitis with unspecified complications |
| K51.8 | ICD10CM | Other ulcerative colitis |
| K51.80 | ICD10CM | Other ulcerative colitis without complications |
| K51.81 | ICD10CM | Other ulcerative colitis with complications |
| K51.811 | ICD10CM | Other ulcerative colitis with rectal bleeding |
| K51.812 | ICD10CM | Other ulcerative colitis with intestinal obstruction |
| K51.813 | ICD10CM | Other ulcerative colitis with fistula |
| K51.814 | ICD10CM | Other ulcerative colitis with abscess |
| K51.818 | ICD10CM | Other ulcerative colitis with other complication |
| K51.819 | ICD10CM | Other ulcerative colitis with unspecified complications |
| K51.9 | ICD10CM | Ulcerative colitis, unspecified |
| K51.90 | ICD10CM | Ulcerative colitis, unspecified, without complications |
| K51.91 | ICD10CM | Ulcerative colitis, unspecified, with complications |
| K51.911 | ICD10CM | Ulcerative colitis, unspecified with rectal bleeding |
| K51.912 | ICD10CM | Ulcerative colitis, unspecified with intestinal obstruction |
| K51.913 | ICD10CM | Ulcerative colitis, unspecified with fistula |
| K51.914 | ICD10CM | Ulcerative colitis, unspecified with abscess |
| K51.918 | ICD10CM | Ulcerative colitis, unspecified with other complication |
| K51.919 | ICD10CM | Ulcerative colitis, unspecified with unspecified complications |
ICD code information from First Databank (FDB).
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.