Actemra (tocilizumab)
Monoclonal Antibody, Human Interleukin 6 Inhibitors Intravenous Vial (Ml); Subcutaneous Syringe (Ml)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Tocilizumab, tocilizumab-aazg, and tocilizumab-bavi, recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibodies specific for the interleukin-6 (IL-6) receptor, are biologic response modifiers and disease-modifying antirheumatic drugs (DMARDs).
Tocilizumab-aazg (Tyenne(R)) and tocilizumab-bavi (Tofidence(R)) are biosimilar to tocilizumab (Actemra(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 alteration 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 tocilizumab biosimilars has interchangeable data at this time.
In this monograph, unless otherwise stated, the term ''tocilizumab products'' refers to tocilizumab (the reference drug) and its biosimilars (tocilizumab-aazg and tocilizumab-bavi).
Tocilizumab, a recombinant humanized monoclonal antibody specific for interleukin-6 (IL-6) receptor, is a biologic response modifier and a disease-modifying antirheumatic drug (DMARD). Tocilizumab is an IgG1 kappa immunoglobulin that binds to both soluble and membrane-bound IL-6 receptors and inhibits IL-6-mediated signaling through these receptors, thereby resulting in a reduction in inflammatory mediator production. The drug is produced in mammalian (Chinese hamster ovary) cells.
IL-6, a pleiotropic proinflammatory cytokine, is produced by various cell types, including T-cells, B-lymphocytes, monocytes, fibroblasts, synoviocytes, and endothelial cells, and has a broad spectrum of biologic activities. IL-6 is involved in T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, stimulation of hematopoietic precursor cell proliferation and differentiation, and induction of osteoclast differentiation and activation. While the causes of rheumatoid arthritis have not been fully elucidated, proinflammatory cytokines, including IL-6, appear to play critical roles in the disease process.
IL-6 is overexpressed in synovial tissue in patients with rheumatoid arthritis and is thought to contribute to synovial proliferation and joint destruction in patients with the disease. Elevated levels of IL-6 in serum and synovial fluid have been shown to correlate with clinical and laboratory measures of disease activity in patients with rheumatoid arthritis. IL-6 also is elevated in serum and synovial fluid in patients with polyarticular or systemic juvenile idiopathic arthritis (JIA), and the elevated levels of IL-6 have been correlated with disease activity.
The pharmacokinetics of tocilizumab are characterized by nonlinear elimination that is a combination of linear clearance and Michaelis-Menten elimination. The nonlinear part of the drug's elimination leads to an increase in drug exposure that is more than dose proportional. The pharmacokinetics of tocilizumab do not change with time.
Because of the dependence of total clearance on tocilizumab serum concentrations, the half-life of the drug is also concentration dependent and varies depending on the serum concentration. Population pharmacokinetic analyses in patient populations tested to date do not suggest any relationship between clearance of tocilizumab and the presence of anti-drug antibodies. The apparent steady-state half-life of tocilizumab in adults with rheumatoid arthritis is up to 11 or up to 13 days following IV administration of tocilizumab 4 or 8 mg/kg, respectively, every 4 weeks and up to 13 or up to 5 days after subcutaneous administration of tocilizumab 162 mg every week or every other week, respectively.
In patients with giant cell arteritis (GCA), the effective half-life of tocilizumab at steady state was 18.3-18.9 days in patients receiving 162 mg subcutaneously once weekly and 4.2-7.9 days in those receiving 162 mg subcutaneously every other week. For intravenous administration in GCA patients, the effective half-life of tocilizumab at steady state was 13.2 days in patients receiving 6 mg/kg every 4 weeks. The reported half-life in pediatric patients with polyarticular or systemic juvenile idiopathic arthritis (JIA) following IV administration is up to 17 or up to 16 days, respectively, at steady state.
Population pharmacokinetic analyses in adult rheumatoid arthritis and GCA patients indicate that age, gender, and race do not affect the pharmacokinetics of tocilizumab. However, linear clearance was found to increase with body size. In rheumatoid arthritis patients, systemic drug exposure was substantially greater (86%) in patients weighing more than 100 kg than in those weighing less than 60 kg following administration of a weight-based IV dose of 8 mg/kg.
At a fixed subcutaneous dosage, tocilizumab exposure is inversely related to body weight.
Two tocilizumab biosimilars are currently available. Biosimilarity of these products has been demonstrated for the indications described in Table 1. Biosimilarity to originator tocilizumab is additionally supported by comparative clinical studies in patients with rheumatoid arthritis.
Generic name: tocilizumab
Pronunciation: (TOE-si-LIZ-ue-mab)
Drug class: Monoclonal Antibody, Human Interleukin 6 Inhibitors
Therapeutic class: Analgesic, Anti-inflammatory or Antipyretic
Reference product & biosimilars
Today’s intelligence on Actemra
Indications
The following indications are listed for Actemra:
- Giant Cell Arteritis
- Polyarticular Juvenile Idiopathic Arthritis
- Rheumatoid Arthritis
- Systemic Sclerosis-Associated Interstitial Lung Disease
- Systemic-Onset Juvenile Idiopathic Arthritis
Also known as: Arthritis Deformans, Arthrosis Deformans, Cranial Arteritis, Extracranial Arteritis, Giant-Cell Arteritis, Granulomatous Arteritis, Horton's Arteritis, Juvenile-Onset Still's Disease, Lung Disease With Systemic Sclerosis, Nodose Rheumatism, Polyarticular Jia, Polyarticular Jra, Polyarticular Juvenile Chronic Arthritis, Polyarticular Juvenile Rheumatoid Arthritis, Rheumatic Arthritis, Rheumatic Gout, Systemic Juvenile Idiopathic Arthritis, Systemic-Onset Jia, Systemic-Onset Jra, Systemic-Onset Juvenile Chronic Arthritis, Systemic-Onset Juvenile Rheumatoid Arthritis, Temporal Arteritis.
Dosing
If a serious infection, an opportunistic infection, or sepsis develops, tocilizumab products should be discontinued until the infection is controlled.
Table 2. Recommended Dosage Adjustment for Tocilizumab Products Based on Liver Enzyme Abnormalities in Adults with Rheumatoid Arthritis, SSc-ILD, or GCA
ALT or AST Value Recommendation for RA Recommendation for GCA and SSc-ILD >1 to 3 times ULN Modify dosage of Modify dosage of concomitant DMARDs if concomitant appropriate immunomodulatory agents if appropriate For persistent increases For persistent increases within this range in within this range in patients receiving IV patients receiving IV tocilizumab, reduce dose tocilizumab, withhold of tocilizumab to 4 therapy until ALT/AST mg/kg or withhold values normalize therapy until ALT/AST values normalize For persistent increases For persistent increases within this range in within this range in patients receiving sub-Q patients receiving sub-Q tocilizumab, reduce tocilizumab, reduce frequency of tocilizumab frequency of tocilizumab administration to every administration to every other week or withhold other week or withhold therapy until ALT/AST therapy until ALT/AST values normalize; resume values normalize; resume tocilizumab at every tocilizumab at every other week and increase other week and increase frequency to every week frequency to every week as clinically indicated as clinically indicated >3 to 5 times ULN Interrupt tocilizumab Interrupt tocilizumab (confirmed by repeat therapy until ALT/AST <3 therapy until ALT/AST <3 testing) times ULN and follow times ULN and follow recommendations for recommendations for ALT/AST >1 to 3 times ALT/AST >1 to 3 times ULN ULN For persistent increases For persistent increases of >3 times ULN, of >3 times ULN, discontinue tocilizumab discontinue tocilizumab >5 times ULN Discontinue tocilizumab Discontinue tocilizumab
Table 3. Recommended Dosage Adjustment for Tocilizumab Products Based on Absolute Neutrophil Count (ANC) in Adults with Rheumatoid Arthritis, GCA, or SSc-ILD
ANC (cells/mm3) Recommendation for RA Recommendation for GCA and SSc-ILD >1000 Maintain current dosage Maintain current dosage 500-1000 Interrupt tocilizumab Interrupt tocilizumab therapy therapy When ANC >1000/mm3 in When ANC >1000/mm3 in patients receiving IV patients receiving IV tocilizumab, resume tocilizumab, resume tocilizumab at a dose of tocilizumab at a dose of 4 mg/kg and increase to 6 mg/kg 8 mg/kg as clinically indicated When ANC >1000/mm3 in When ANC >1000/mm3 in patients receiving sub-Q patients receiving sub-Q tocilizumab, resume tocilizumab, resume tocilizumab at every tocilizumab at every other week and increase other week and increase frequency to every week frequency to every week as clinically indicated as clinically indicated <500 Discontinue tocilizumab Discontinue tocilizumab
Table 4. Recommended Dosage Adjustment for Tocilizumab Products Based on Platelet Count in Adults with Rheumatoid Arthritis, GCA, or SSc-ILD
Platelet Count Recommendation for RA Recommendation for GCA (cells/mm3) and SSc-ILD 50,000-100,000 Interrupt tocilizumab Interrupt tocilizumab therapy therapy When platelet count When platelet count >100,000/mm3 in patients >100,000/mm3 in patients receiving IV receiving IV tocilizumab, resume tocilizumab, resume tocilizumab at a dose of tocilizumab at a dose of 4 mg/kg and increase to 6 mg/kg 8 mg/kg as clinically indicated When platelet count When platelet count >100,000/mm3 in patients >100,000/mm3 in patients receiving sub-Q receiving sub-Q tocilizumab, resume tocilizumab, resume tocilizumab at every tocilizumab at every other week and increase other week and increase frequency to every week frequency to every week as clinically as clinically appropriate appropriate <50,000 Discontinue tocilizumab Discontinue tocilizumab
For the management of rheumatoid arthritis, GCA, and systemic or polyarticular JIA, tocilizumab and tocilizumab-aazg may be administered either by IV infusion (after dilution) over 60 minutes or by subcutaneous injection. Tocilizumab-bavi is only approved for IV administration for these indications. The drug should not be administered by rapid IV injection (e.g., IV push or bolus).
For the management of SSc-ILD, tocilizumab is administered by subcutaneous injection. The drug currently is not FDA-labeled for IV administration for this indication. The use of the prefilled pen has not been studied in patients with SSc-ILD.
For the management of CAR T cell-induced CRS, tocilizumab is administered only by IV infusion over 60 minutes. The drug should not be administered by rapid IV injection (e.g., IV push or bolus). Tocilizumab currently is not FDA-labeled for subcutaneous use for this indication.
For the management of COVID-19, tocilizumab and tocilizumab-bavi are administered only by IV infusion over 60 minutes. The drug should not be administered by rapid IV injection (e.g., IV push or bolus). Tocilizumab and tocilizumab-bavi currently are not FDA-labeled for subcutaneous use for this indication.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Actemra 80 Mg/4 Ml Vial | Maintenance | Infuse 8 mg/kg over 60 minute(s) by intravenous route every 4 weeks not to exceed 800 mg per infusion. |
| Actemra 200 Mg/10 Ml Vial | Maintenance | Infuse 8 mg/kg over 60 minute(s) by intravenous route every 4 weeks not to exceed 800 mg per infusion. |
| Actemra 400 Mg/20 Ml Vial | Maintenance | Infuse 8 mg/kg over 60 minute(s) by intravenous route every 4 weeks not to exceed 800 mg per infusion. |
| Actemra 162 Mg/0.9 Ml Syringe | Maintenance | Inject 0.9 milliliter (162 mg) by subcutaneous route once weekly. |
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
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)
Sarilumab; Tocilizumab/Biologic Dmards
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.
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)
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)
Myelosuppressives; Immunomodulators/Sodium Iodide I 131
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)
DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)
Selected Immunosuppressants/Leflunomide; Teriflunomide
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use of leflunomide or teriflunomide and potent immunosuppressants may result in additive or synergistic effects on the immune system.(1,2) Leflunomide is a prodrug and is converted to its active metabolite teriflunomide.(1)
CLINICAL EFFECTS: Concurrent use of leflunomide or teriflunomide with immunosuppressants may result in an increased risk of serious infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis.
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: If leflunomide or teriflunomide is used concurrently with immunosuppressive agents, chronic CBC monitoring should be performed more frequently, every month instead of every 6 to 8 weeks. If bone marrow suppression or a serious infection occurs, leflunomide or teriflunomide should be stopped and rapid drug elimination procedure should be performed.(1,2)
DISCUSSION: Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide or teriflunomide alone, but most frequently in patients taking concurrent immunosuppressants.(1,2) Severe and potentially fatal infections, including sepsis, have been reported in patients receiving leflunomide or teriflunomide, especially Pneumocystis jiroveci pneumonia and aspergillosis. Tuberculosis has also been reported.(1,2)
Selected Myelosuppressive Agents/Clozapine
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2)
CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal.
PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia.
PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent absolute neutrophil count (ANC) monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. The U.S. Food and Drug Administration (FDA) recommends that prescribers monitor patients' ANC according to the monitoring frequencies described in the prescribing information. Severe neutropenia remains a serious, potentially fatal risk that is greatest in the first several months of clozapine treatment. ANC monitoring can help identify neutropenia early to allow for timely intervention.(1-2) Australia, Canada, and U.K.: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing. For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(2)
DISCUSSION: Concurrent use of clozapine and selected myelosuppressive agents may require more frequent ANC monitoring or consideration of treatment alternatives secondary to neutropenic episodes. Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26)
Selected Myelosuppressive Agents/Deferiprone
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1)
CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal.
PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2)
PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1)
DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3)
Selected Myelosuppressive Agents/Dipyrone
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Concurrent use of dipyrone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1-29)
CLINICAL EFFECTS: Concurrent use of dipyrone with agents that cause bone marrow depression, including myelosuppressives, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding. Undetected severe neutropenia or agranulocytosis may be fatal.(1-29)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Concurrent use of dipyrone and myelosuppressive agents should be avoided. The European Medicines Agency states dipyrone is contraindicated in patients with a prior medical history of dipyrone-induced agranulocytosis (or from other pyrazolones/pyrazolidines), impaired bone marrow function or diseases of the hematopoietic system.(3) International labeling for dipyrone and methotrexate state that co-administration may increase the hematotoxicity of methotrexate, especially in elderly patients, and therefore should be avoided.(1-2) The European Medicines Agency advises if agranulocytosis is suspected with dipyrone, a complete blood count (including differential blood count) should be performed immediately, and treatment must be stopped while waiting for the results. If confirmed, treatment must not be reintroduced.(1-3)
DISCUSSION: A retrospective cohort study analyzed new users of dipyrone (n=444,972), non-steroidal anti-inflammatory drugs (n=3,814,367) which served as a reference cohort, and opioids-paracetamol (n=3,129,221) which was the negative control. During continuous treatment over a median of 37-40 days, 26 cases of hospitalized agranulocytosis occurred. With the assumption that agranulocytosis onset was 7 days prior to admission, the hazard ratio of agranulocytosis associated with dipyrone was 4.40 [0.90-21.57] compared to NSAIDs and 2.45 [0.68-8.83] compared to opioid-paracetamol. HR of neutropenia from dipyrone was 2.98 [1.57-5.65] compared to NSAIDs and not statistically significant compared to opioids-paracetamol. In a sensitivity analysis assuming that the onset of agranulocytosis was the date of hospitalization, the HR of dipyrone-induced agranulocytosis was 7.20 [95% confidence interval: 1.92-26.99] compared to NSAIDs and 3.31 [1.17-9.34] compared to opioids-paracetamol. Agranulocytosis was very rare but more than 4 times more common with dipyrone than other analgesics.(4) In a review of 1,448 reports of agranulocytosis attributed to dipyrone, patients with fatal outcomes were older and more often had also received methotrexate compared to those with non-fatal outcomes (odds ratio: 5.18; 95% confidence interval: 3.06-8.78).(5) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(2,6-26)
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)
Tocilizumab/Immunosuppressives; Immunomodulators
SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.
MECHANISM OF ACTION: Tocilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of tocilizumab 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 tocilizumab recommends caution because the concurrent use of tocilizumab 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: Tocilizumab was studied as monotherapy and in combination with methotrexate, non-biologic DMARDs or corticosteroids, depending on the indication. Tocilizumab has not been studied with biological DMARDs and concurrent use should be avoided. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by tocilizumab treated patients in the clinical trial periods included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving tocilizumab. Cases of tuberculosis, cryptococcus, aspergillosis, candidiasis, and pneumocystosis have been reported.(1)
Contraindications
*Known hypersensitivity to the drug.
There are no contraindication contraindications for this drug.
- Active tuberculosis
- Demyelinating disorder
- Disease of liver
- Diverticulitis of gastrointestinal tract
- Gastrointestinal perforation
- Inactive tuberculosis
- Infection
- Neutropenic disorder
- Opportunistic fungal infection
- Opportunistic viral infection
- Pneumocystis jirovecii pneumonia
- Thrombocytopenic disorder
- Hypercholesterolemia
- Hypertriglyceridemia
- Multiple sclerosis
Adverse reactions
Adverse effects reported in 5% or more of patients receiving tocilizumab products include upper respiratory tract infection, nasopharyngitis, headache, hypertension, increased ALT concentrations, and injection site reactions (e.g., erythema, pruritus, pain, hematoma).
More Frequent
- Abnormal hepatic function tests
- Hypercholesterolemia
- Hypertension
Less Frequent
- Increased alanine transaminase
- Increased aspartate transaminase
- Infection
- Neutropenic disorder
- Pneumonia
Rare or Very Rare
- Active tuberculosis
- Acute hepatic failure
- Anaphylaxis
- Aspergillosis
- Bacterial sepsis
- Blastomycosis
- Candidiasis
- Cellulitis
- Coccidioidomycosis
- Diverticulitis of gastrointestinal tract
- DRESS syndrome
- Drug-induced hepatitis
- Gastric ulcer
- Gastroenteritis
- Gastrointestinal perforation
- Hepatitis
- Hepatocellular damage
- Herpes zoster
- Histoplasmosis
- Hyperbilirubinemia
- Hypersensitivity drug reaction
- Hypofibrinogenemia
- Hypothyroidism
- Jaundice
- Kidney stone
- Leukopenia
- Malignancy
- Multiple sclerosis
- Opportunistic fungal infection
- Pancreatitis
- Peripheral demyelinating neuropathy
- Pneumocystis jirovecii pneumonia
- Reactivated tuberculosis
- Septic arthritis
- Stevens-johnson syndrome
- Thrombocytopenic disorder
- Urticaria
More Frequent
- Headache disorder
- Injection site sequelae
- Pharyngitis
- Upper respiratory infection
- Urinary tract infection
Less Frequent
- Acute abdominal pain
- Bronchitis
- Constipation
- Diarrhea
- Dizziness
- Gastritis
- Hyperlipidemia
- Hypertriglyceridemia
- Hypokalemia
- Insomnia
- Nausea
- Pruritus of skin
- Skin rash
- Stomatitis
- Symptoms of anxiety
- Upper abdominal pain
Rare or Very Rare
- Conjunctivitis
- Cough
- Dyspnea
- Erythema
- Herpes simplex infection
- Peripheral edema
- Weight gain
Precautions
No enhanced messaging available.
Safety and efficacy of IV and subcutaneous tocilizumab for the management of active polyarticular or systemic JIA and safety and efficacy of IV tocilizumab for the management of severe or life-threatening chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome (CRS) have been established in pediatric patients 2 years of age and older. Safety and efficacy of the drug in children younger than 2 years of age or for the management of conditions other than polyarticular or systemic JIA and CAR T cell-induced CRS in children have not been established.
A multicenter, open-label, single-arm study to evaluate the pharmacokinetics, safety, pharmacodynamics, and efficacy of tocilizumab over 12 weeks in 11 patients with systemic JIA under 2 years of age was conducted. Patients received IV tocilizumab 12 mg/kg every 2 weeks, and concurrent use of stable background treatment with corticosteroids, methotrexate, and/or nonsteroidal anti-inflammatory agents was permitted. Patients who completed the 12-week phase of the study could continue to an optional extension phase for a total of 52 weeks or until the age of 2 years, whichever was longer. The primary pharmacokinetic parameters (peak and trough concentrations and AUC) of tocilizumab at steady state in these patients under 2 years of age were within the ranges of these parameters observed in patients 2-17 years of age with systemic JIA. In patients under 2 years of age with systemic JIA, serious adverse effects, adverse effects leading to drug discontinuance, and infectious adverse effects were reported in 27.3, 36.4, and 81.8% of patients, respectively. Six patients (54.5%) experienced hypersensitivity reactions and 3 of these patients experienced serious hypersensitivity reactions and were withdrawn from the study. Three of the patients who developed hypersensitivity reactions (two with serious hypersensitivity reactions) developed treatment-induced anti-tocilizumab antibodies after the event. There were no cases of macrophage activation syndrome (MAS) based on the study protocol-specified criteria, but there were 2 cases of suspected MAS based on Ravelli criteria.
In a retrospective analysis of pooled outcome data for patients treated with IV tocilizumab for CAR T cell-induced CRS, 25 patients were children (2-12 years of age) and 17 patients were adolescents (12-18 years of age). There were no differences in safety or efficacy between the pediatric patients and the adults.
Clinical data regarding tocilizumab use in pregnant women are not sufficient to determine whether there is a drug-associated risk for major birth defects and miscarriage. Monoclonal antibodies such as tocilizumab is actively transported across the placenta during the third trimester of pregnancy and may affect immune response in infants exposed to the drugs in utero.
In animal reproduction studies, IV administration of tocilizumab to cynomolgus monkeys during organogenesis caused abortion/embryofetal death at dosages of 1.25 (or more) times the maximum recommended human IV dosage of 8 mg/kg every 2-4 weeks. Evidence in animals suggests that inhibition of interleukin-6 (IL-6) signaling may interfere with cervical ripening and dilatation and myometrial contractile activity, which could potentially result in parturition delays. Based on animal data, there may be a potential risk to the fetus.
As pregnancy progresses, monoclonal antibodies are increasingly transported across the placenta, with the largest amount transferred during the third trimester. The risks and benefits of administering live or live attenuated vaccines to infants exposed to tocilizumab in utero should be considered, since the safety of such vaccines in infants exposed to the drug in utero is unknown.
It is not known whether tocilizumab is distributed into milk, and the effects of the drug on the breast-fed infant and on milk production also are not known. Maternal immunoglobulin G (IgG) is distributed into human milk. If tocilizumab is distributed into human milk, the effects of local exposure in the GI tract and potential limited systemic exposure in the infant are unknown. The lack of clinical data during lactation precludes a clear determination of the risk of tocilizumab exposure to nursing infants. Therefore, the manufacturers state that the developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for tocilizumab and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Approximately 16% of patients with rheumatoid arthritis who received IV tocilizumab in clinical trials were >=65 years of age and about 2% were >=75 years of age. Approximately 28% of patients with rheumatoid arthritis who received subcutaneous tocilizumab in clinical trials were >=65 years of age and about 4% were >=75 years of age. Serious infection occurred with greater frequency in those >=65 years of age relative to younger adults. Because the geriatric population in general may have a higher incidence of infections than younger adults, tocilizumab should be used with caution in this age group.
Clinical studies that evaluated tocilizumab for CAR T cell-induced CRS did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently than younger adults.
Clinical studies that evaluated tocilizumab for COVID-19 noted no overall differences in efficacy or safety between patients >=65 years of age and those <65 years of age.
Population pharmacokinetic analyses indicate that age does not affect the pharmacokinetics of tocilizumab.
ICD codes
| Code | Type | Description |
|---|---|---|
| Cytokine release syndrome | ||
| D89.83 | ICD10CM | Cytokine release syndrome |
| D89.831 | ICD10CM | Cytokine release syndrome, grade 1 |
| D89.832 | ICD10CM | Cytokine release syndrome, grade 2 |
| D89.833 | ICD10CM | Cytokine release syndrome, grade 3 |
| D89.834 | ICD10CM | Cytokine release syndrome, grade 4 |
| D89.835 | ICD10CM | Cytokine release syndrome, grade 5 |
| D89.839 | ICD10CM | Cytokine release syndrome, grade unspecified |
| Giant cell arteritis | ||
| M31.5 | ICD10CM | Giant cell arteritis with polymyalgia rheumatica |
| M31.6 | ICD10CM | Other giant cell arteritis |
| Polyarticular juvenile idiopathic arthritis | ||
| M08.0 | ICD10CM | Unspecified juvenile rheumatoid arthritis |
| M08.00 | ICD10CM | Unspecified juvenile rheumatoid arthritis of unspecified site |
| M08.01 | ICD10CM | Unspecified juvenile rheumatoid arthritis, shoulder |
| M08.011 | ICD10CM | Unspecified juvenile rheumatoid arthritis, right shoulder |
| M08.012 | ICD10CM | Unspecified juvenile rheumatoid arthritis, left shoulder |
| M08.019 | ICD10CM | Unspecified juvenile rheumatoid arthritis, unspecified shoulder |
| M08.02 | ICD10CM | Unspecified juvenile rheumatoid arthritis of elbow |
| M08.021 | ICD10CM | Unspecified juvenile rheumatoid arthritis, right elbow |
| M08.022 | ICD10CM | Unspecified juvenile rheumatoid arthritis, left elbow |
| M08.029 | ICD10CM | Unspecified juvenile rheumatoid arthritis, unspecified elbow |
| M08.03 | ICD10CM | Unspecified juvenile rheumatoid arthritis, wrist |
| M08.031 | ICD10CM | Unspecified juvenile rheumatoid arthritis, right wrist |
| M08.032 | ICD10CM | Unspecified juvenile rheumatoid arthritis, left wrist |
| M08.039 | ICD10CM | Unspecified juvenile rheumatoid arthritis, unspecified wrist |
| M08.04 | ICD10CM | Unspecified juvenile rheumatoid arthritis, hand |
| M08.041 | ICD10CM | Unspecified juvenile rheumatoid arthritis, right hand |
| M08.042 | ICD10CM | Unspecified juvenile rheumatoid arthritis, left hand |
| M08.049 | ICD10CM | Unspecified juvenile rheumatoid arthritis, unspecified hand |
| M08.05 | ICD10CM | Unspecified juvenile rheumatoid arthritis, hip |
| M08.051 | ICD10CM | Unspecified juvenile rheumatoid arthritis, right hip |
| M08.052 | ICD10CM | Unspecified juvenile rheumatoid arthritis, left hip |
| M08.059 | ICD10CM | Unspecified juvenile rheumatoid arthritis, unspecified hip |
| M08.06 | ICD10CM | Unspecified juvenile rheumatoid arthritis, knee |
| M08.061 | ICD10CM | Unspecified juvenile rheumatoid arthritis, right knee |
| M08.062 | ICD10CM | Unspecified juvenile rheumatoid arthritis, left knee |
| M08.069 | ICD10CM | Unspecified juvenile rheumatoid arthritis, unspecified knee |
| M08.07 | ICD10CM | Unspecified juvenile rheumatoid arthritis, ankle and foot |
| M08.071 | ICD10CM | Unspecified juvenile rheumatoid arthritis, right ankle and foot |
| M08.072 | ICD10CM | Unspecified juvenile rheumatoid arthritis, left ankle and foot |
| M08.079 | ICD10CM | Unspecified juvenile rheumatoid arthritis, unspecified ankle and foot |
| M08.08 | ICD10CM | Unspecified juvenile rheumatoid arthritis, vertebrae |
| M08.09 | ICD10CM | Unspecified juvenile rheumatoid arthritis, multiple sites |
| M08.0A | ICD10CM | Unspecified juvenile rheumatoid arthritis, other specified site |
| M08.2 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset |
| M08.20 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified site |
| M08.21 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, shoulder |
| M08.211 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right shoulder |
| M08.212 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left shoulder |
| M08.219 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified shoulder |
| M08.22 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, elbow |
| M08.221 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right elbow |
| M08.222 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left elbow |
| M08.229 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified elbow |
| M08.23 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, wrist |
| M08.231 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right wrist |
| M08.232 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left wrist |
| M08.239 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified wrist |
| M08.24 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, hand |
| M08.241 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right hand |
| M08.242 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left hand |
| M08.249 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified hand |
| M08.25 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, hip |
| M08.251 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right hip |
| M08.252 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left hip |
| M08.259 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified hip |
| M08.26 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, knee |
| M08.261 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right knee |
| M08.262 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left knee |
| M08.269 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified knee |
| M08.27 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, ankle and foot |
| M08.271 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right ankle and foot |
| M08.272 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left ankle and foot |
| M08.279 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified ankle and foot |
| M08.28 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, vertebrae |
| M08.29 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, multiple sites |
| M08.2A | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, other specified site |
| M08.3 | ICD10CM | Juvenile rheumatoid polyarthritis (seronegative) |
| M08.4 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis |
| M08.40 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified site |
| M08.41 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, shoulder |
| M08.411 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, right shoulder |
| M08.412 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, left shoulder |
| M08.419 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified shoulder |
| M08.42 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, elbow |
| M08.421 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, right elbow |
| M08.422 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, left elbow |
| M08.429 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified elbow |
| M08.43 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, wrist |
| M08.431 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, right wrist |
| M08.432 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, left wrist |
| M08.439 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified wrist |
| M08.44 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, hand |
| M08.441 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, right hand |
| M08.442 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, left hand |
| M08.449 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified hand |
| M08.45 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, hip |
| M08.451 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, right hip |
| M08.452 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, left hip |
| M08.459 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified hip |
| M08.46 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, knee |
| M08.461 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, right knee |
| M08.462 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, left knee |
| M08.469 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified knee |
| M08.47 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, ankle and foot |
| M08.471 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, right ankle and foot |
| M08.472 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, left ankle and foot |
| M08.479 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, unspecified ankle and foot |
| M08.48 | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, vertebrae |
| M08.4A | ICD10CM | Pauciarticular juvenile rheumatoid arthritis, other specified site |
| Rheumatoid arthritis | ||
| M05 | ICD10CM | Rheumatoid arthritis with rheumatoid factor |
| M05.0 | ICD10CM | Felty's syndrome |
| M05.00 | ICD10CM | Felty's syndrome, unspecified site |
| M05.01 | ICD10CM | Felty's syndrome, shoulder |
| M05.011 | ICD10CM | Felty's syndrome, right shoulder |
| M05.012 | ICD10CM | Felty's syndrome, left shoulder |
| M05.019 | ICD10CM | Felty's syndrome, unspecified shoulder |
| M05.02 | ICD10CM | Felty's syndrome, elbow |
| M05.021 | ICD10CM | Felty's syndrome, right elbow |
| M05.022 | ICD10CM | Felty's syndrome, left elbow |
| M05.029 | ICD10CM | Felty's syndrome, unspecified elbow |
| M05.03 | ICD10CM | Felty's syndrome, wrist |
| M05.031 | ICD10CM | Felty's syndrome, right wrist |
| M05.032 | ICD10CM | Felty's syndrome, left wrist |
| M05.039 | ICD10CM | Felty's syndrome, unspecified wrist |
| M05.04 | ICD10CM | Felty's syndrome, hand |
| M05.041 | ICD10CM | Felty's syndrome, right hand |
| M05.042 | ICD10CM | Felty's syndrome, left hand |
| M05.049 | ICD10CM | Felty's syndrome, unspecified hand |
| M05.05 | ICD10CM | Felty's syndrome, hip |
| M05.051 | ICD10CM | Felty's syndrome, right hip |
| M05.052 | ICD10CM | Felty's syndrome, left hip |
| M05.059 | ICD10CM | Felty's syndrome, unspecified hip |
| M05.06 | ICD10CM | Felty's syndrome, knee |
| M05.061 | ICD10CM | Felty's syndrome, right knee |
| M05.062 | ICD10CM | Felty's syndrome, left knee |
| M05.069 | ICD10CM | Felty's syndrome, unspecified knee |
| M05.07 | ICD10CM | Felty's syndrome, ankle and foot |
| M05.071 | ICD10CM | Felty's syndrome, right ankle and foot |
| M05.072 | ICD10CM | Felty's syndrome, left ankle and foot |
| M05.079 | ICD10CM | Felty's syndrome, unspecified ankle and foot |
| M05.09 | ICD10CM | Felty's syndrome, multiple sites |
| M05.1 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis |
| M05.10 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified site |
| M05.11 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of shoulder |
| M05.111 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of right shoulder |
| M05.112 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of left shoulder |
| M05.119 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified shoulder |
| M05.12 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of elbow |
| M05.121 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of right elbow |
| M05.122 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of left elbow |
| M05.129 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified elbow |
| M05.13 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of wrist |
| M05.131 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of right wrist |
| M05.132 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of left wrist |
| M05.139 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified wrist |
| M05.14 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of hand |
| M05.141 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of right hand |
| M05.142 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of left hand |
| M05.149 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified hand |
| M05.15 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of hip |
| M05.151 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of right hip |
| M05.152 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of left hip |
| M05.159 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified hip |
| M05.16 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of knee |
| M05.161 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of right knee |
| M05.162 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of left knee |
| M05.169 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified knee |
| M05.17 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of ankle and foot |
| M05.171 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of right ankle and foot |
| M05.172 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of left ankle and foot |
| M05.179 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of unspecified ankle and foot |
| M05.19 | ICD10CM | Rheumatoid lung disease with rheumatoid arthritis of multiple sites |
| M05.2 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis |
| M05.20 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified site |
| M05.21 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of shoulder |
| M05.211 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of right shoulder |
| M05.212 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of left shoulder |
| M05.219 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified shoulder |
| M05.22 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of elbow |
| M05.221 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of right elbow |
| M05.222 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of left elbow |
| M05.229 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified elbow |
| M05.23 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of wrist |
| M05.231 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of right wrist |
| M05.232 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of left wrist |
| M05.239 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified wrist |
| M05.24 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of hand |
| M05.241 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of right hand |
| M05.242 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of left hand |
| M05.249 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified hand |
| M05.25 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of hip |
| M05.251 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of right hip |
| M05.252 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of left hip |
| M05.259 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified hip |
| M05.26 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of knee |
| M05.261 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of right knee |
| M05.262 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of left knee |
| M05.269 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified knee |
| M05.27 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of ankle and foot |
| M05.271 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of right ankle and foot |
| M05.272 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of left ankle and foot |
| M05.279 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of unspecified ankle and foot |
| M05.29 | ICD10CM | Rheumatoid vasculitis with rheumatoid arthritis of multiple sites |
| M05.3 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis |
| M05.30 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified site |
| M05.31 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of shoulder |
| M05.311 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of right shoulder |
| M05.312 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of left shoulder |
| M05.319 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified shoulder |
| M05.32 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of elbow |
| M05.321 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of right elbow |
| M05.322 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of left elbow |
| M05.329 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified elbow |
| M05.33 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of wrist |
| M05.331 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of right wrist |
| M05.332 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of left wrist |
| M05.339 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified wrist |
| M05.34 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of hand |
| M05.341 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of right hand |
| M05.342 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of left hand |
| M05.349 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified hand |
| M05.35 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of hip |
| M05.351 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of right hip |
| M05.352 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of left hip |
| M05.359 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified hip |
| M05.36 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of knee |
| M05.361 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of right knee |
| M05.362 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of left knee |
| M05.369 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified knee |
| M05.37 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of ankle and foot |
| M05.371 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of right ankle and foot |
| M05.372 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of left ankle and foot |
| M05.379 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of unspecified ankle and foot |
| M05.39 | ICD10CM | Rheumatoid heart disease with rheumatoid arthritis of multiple sites |
| M05.4 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis |
| M05.40 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified site |
| M05.41 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of shoulder |
| M05.411 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of right shoulder |
| M05.412 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of left shoulder |
| M05.419 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified shoulder |
| M05.42 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of elbow |
| M05.421 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of right elbow |
| M05.422 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of left elbow |
| M05.429 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified elbow |
| M05.43 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of wrist |
| M05.431 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of right wrist |
| M05.432 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of left wrist |
| M05.439 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified wrist |
| M05.44 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of hand |
| M05.441 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of right hand |
| M05.442 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of left hand |
| M05.449 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified hand |
| M05.45 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of hip |
| M05.451 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of right hip |
| M05.452 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of left hip |
| M05.459 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified hip |
| M05.46 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of knee |
| M05.461 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of right knee |
| M05.462 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of left knee |
| M05.469 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified knee |
| M05.47 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of ankle and foot |
| M05.471 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of right ankle and foot |
| M05.472 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of left ankle and foot |
| M05.479 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of unspecified ankle and foot |
| M05.49 | ICD10CM | Rheumatoid myopathy with rheumatoid arthritis of multiple sites |
| M05.5 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis |
| M05.50 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified site |
| M05.51 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of shoulder |
| M05.511 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of right shoulder |
| M05.512 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of left shoulder |
| M05.519 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified shoulder |
| M05.52 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of elbow |
| M05.521 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of right elbow |
| M05.522 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of left elbow |
| M05.529 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified elbow |
| M05.53 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of wrist |
| M05.531 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of right wrist |
| M05.532 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of left wrist |
| M05.539 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified wrist |
| M05.54 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of hand |
| M05.541 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of right hand |
| M05.542 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of left hand |
| M05.549 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hand |
| M05.55 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of hip |
| M05.551 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of right hip |
| M05.552 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of left hip |
| M05.559 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hip |
| M05.56 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of knee |
| M05.561 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of right knee |
| M05.562 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of left knee |
| M05.569 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified knee |
| M05.57 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of ankle and foot |
| M05.571 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of right ankle and foot |
| M05.572 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of left ankle and foot |
| M05.579 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified ankle and foot |
| M05.59 | ICD10CM | Rheumatoid polyneuropathy with rheumatoid arthritis of multiple sites |
| M05.6 | ICD10CM | Rheumatoid arthritis with involvement of other organs and systems |
| M05.60 | ICD10CM | Rheumatoid arthritis of unspecified site with involvement of other organs and systems |
| M05.61 | ICD10CM | Rheumatoid arthritis of shoulder with involvement of other organs and systems |
| M05.611 | ICD10CM | Rheumatoid arthritis of right shoulder with involvement of other organs and systems |
| M05.612 | ICD10CM | Rheumatoid arthritis of left shoulder with involvement of other organs and systems |
| M05.619 | ICD10CM | Rheumatoid arthritis of unspecified shoulder with involvement of other organs and systems |
| M05.62 | ICD10CM | Rheumatoid arthritis of elbow with involvement of other organs and systems |
| M05.621 | ICD10CM | Rheumatoid arthritis of right elbow with involvement of other organs and systems |
| M05.622 | ICD10CM | Rheumatoid arthritis of left elbow with involvement of other organs and systems |
| M05.629 | ICD10CM | Rheumatoid arthritis of unspecified elbow with involvement of other organs and systems |
| M05.63 | ICD10CM | Rheumatoid arthritis of wrist with involvement of other organs and systems |
| M05.631 | ICD10CM | Rheumatoid arthritis of right wrist with involvement of other organs and systems |
| M05.632 | ICD10CM | Rheumatoid arthritis of left wrist with involvement of other organs and systems |
| M05.639 | ICD10CM | Rheumatoid arthritis of unspecified wrist with involvement of other organs and systems |
| M05.64 | ICD10CM | Rheumatoid arthritis of hand with involvement of other organs and systems |
| M05.641 | ICD10CM | Rheumatoid arthritis of right hand with involvement of other organs and systems |
| M05.642 | ICD10CM | Rheumatoid arthritis of left hand with involvement of other organs and systems |
| M05.649 | ICD10CM | Rheumatoid arthritis of unspecified hand with involvement of other organs and systems |
| M05.65 | ICD10CM | Rheumatoid arthritis of hip with involvement of other organs and systems |
| M05.651 | ICD10CM | Rheumatoid arthritis of right hip with involvement of other organs and systems |
| M05.652 | ICD10CM | Rheumatoid arthritis of left hip with involvement of other organs and systems |
| M05.659 | ICD10CM | Rheumatoid arthritis of unspecified hip with involvement of other organs and systems |
| M05.66 | ICD10CM | Rheumatoid arthritis of knee with involvement of other organs and systems |
| M05.661 | ICD10CM | Rheumatoid arthritis of right knee with involvement of other organs and systems |
| M05.662 | ICD10CM | Rheumatoid arthritis of left knee with involvement of other organs and systems |
| M05.669 | ICD10CM | Rheumatoid arthritis of unspecified knee with involvement of other organs and systems |
| M05.67 | ICD10CM | Rheumatoid arthritis of ankle and foot with involvement of other organs and systems |
| M05.671 | ICD10CM | Rheumatoid arthritis of right ankle and foot with involvement of other organs and systems |
| M05.672 | ICD10CM | Rheumatoid arthritis of left ankle and foot with involvement of other organs and systems |
| M05.679 | ICD10CM | Rheumatoid arthritis of unspecified ankle and foot with involvement of other organs and systems |
| M05.69 | ICD10CM | Rheumatoid arthritis of multiple sites with involvement of other organs and systems |
| M05.7 | ICD10CM | Rheumatoid arthritis with rheumatoid factor without organ or systems involvement |
| M05.70 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified site without organ or systems involvement |
| M05.71 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of shoulder without organ or systems involvement |
| M05.711 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of right shoulder without organ or systems involvement |
| M05.712 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of left shoulder without organ or systems involvement |
| M05.719 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified shoulder without organ or systems involvement |
| M05.72 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of elbow without organ or systems involvement |
| M05.721 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of right elbow without organ or systems involvement |
| M05.722 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of left elbow without organ or systems involvement |
| M05.729 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified elbow without organ or systems involvement |
| M05.73 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of wrist without organ or systems involvement |
| M05.731 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of right wrist without organ or systems involvement |
| M05.732 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of left wrist without organ or systems involvement |
| M05.739 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified wrist without organ or systems involvement |
| M05.74 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of hand without organ or systems involvement |
| M05.741 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of right hand without organ or systems involvement |
| M05.742 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of left hand without organ or systems involvement |
| M05.749 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified hand without organ or systems involvement |
| M05.75 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of hip without organ or systems involvement |
| M05.751 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of right hip without organ or systems involvement |
| M05.752 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of left hip without organ or systems involvement |
| M05.759 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified hip without organ or systems involvement |
| M05.76 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of knee without organ or systems involvement |
| M05.761 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of right knee without organ or systems involvement |
| M05.762 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of left knee without organ or systems involvement |
| M05.769 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified knee without organ or systems involvement |
| M05.77 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of ankle and foot without organ or systems involvement |
| M05.771 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of right ankle and foot without organ or systems involvement |
| M05.772 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of left ankle and foot without organ or systems involvement |
| M05.779 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot without organ or systems involvement |
| M05.79 | ICD10CM | Rheumatoid arthritis with rheumatoid factor of multiple sites without organ or systems involvement |
| M05.7A | ICD10CM | Rheumatoid arthritis with rheumatoid factor of other specified site without organ or systems involvement |
| M05.8 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor |
| M05.80 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified site |
| M05.81 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of shoulder |
| M05.811 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of right shoulder |
| M05.812 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of left shoulder |
| M05.819 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified shoulder |
| M05.82 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of elbow |
| M05.821 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of right elbow |
| M05.822 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of left elbow |
| M05.829 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified elbow |
| M05.83 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of wrist |
| M05.831 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of right wrist |
| M05.832 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of left wrist |
| M05.839 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified wrist |
| M05.84 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of hand |
| M05.841 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of right hand |
| M05.842 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of left hand |
| M05.849 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified hand |
| M05.85 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of hip |
| M05.851 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of right hip |
| M05.852 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of left hip |
| M05.859 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified hip |
| M05.86 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of knee |
| M05.861 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of right knee |
| M05.862 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of left knee |
| M05.869 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified knee |
| M05.87 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of ankle and foot |
| M05.871 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of right ankle and foot |
| M05.872 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of left ankle and foot |
| M05.879 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot |
| M05.89 | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of multiple sites |
| M05.8A | ICD10CM | Other rheumatoid arthritis with rheumatoid factor of other specified site |
| M05.9 | ICD10CM | Rheumatoid arthritis with rheumatoid factor, unspecified |
| M05.A | ICD10CM | Abnormal rheumatoid factor and anti-citrullinated protein antibody with rheumatoid arthritis |
| M06 | ICD10CM | Other rheumatoid arthritis |
| M06.0 | ICD10CM | Rheumatoid arthritis without rheumatoid factor |
| M06.00 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified site |
| M06.01 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, shoulder |
| M06.011 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, right shoulder |
| M06.012 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, left shoulder |
| M06.019 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified shoulder |
| M06.02 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, elbow |
| M06.021 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, right elbow |
| M06.022 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, left elbow |
| M06.029 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified elbow |
| M06.03 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, wrist |
| M06.031 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, right wrist |
| M06.032 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, left wrist |
| M06.039 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified wrist |
| M06.04 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, hand |
| M06.041 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, right hand |
| M06.042 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, left hand |
| M06.049 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified hand |
| M06.05 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, hip |
| M06.051 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, right hip |
| M06.052 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, left hip |
| M06.059 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified hip |
| M06.06 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, knee |
| M06.061 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, right knee |
| M06.062 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, left knee |
| M06.069 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified knee |
| M06.07 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, ankle and foot |
| M06.071 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, right ankle and foot |
| M06.072 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, left ankle and foot |
| M06.079 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, unspecified ankle and foot |
| M06.08 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, vertebrae |
| M06.09 | ICD10CM | Rheumatoid arthritis without rheumatoid factor, multiple sites |
| M06.0A | ICD10CM | Rheumatoid arthritis without rheumatoid factor, other specified site |
| M06.8 | ICD10CM | Other specified rheumatoid arthritis |
| M06.80 | ICD10CM | Other specified rheumatoid arthritis, unspecified site |
| M06.81 | ICD10CM | Other specified rheumatoid arthritis, shoulder |
| M06.811 | ICD10CM | Other specified rheumatoid arthritis, right shoulder |
| M06.812 | ICD10CM | Other specified rheumatoid arthritis, left shoulder |
| M06.819 | ICD10CM | Other specified rheumatoid arthritis, unspecified shoulder |
| M06.82 | ICD10CM | Other specified rheumatoid arthritis, elbow |
| M06.821 | ICD10CM | Other specified rheumatoid arthritis, right elbow |
| M06.822 | ICD10CM | Other specified rheumatoid arthritis, left elbow |
| M06.829 | ICD10CM | Other specified rheumatoid arthritis, unspecified elbow |
| M06.83 | ICD10CM | Other specified rheumatoid arthritis, wrist |
| M06.831 | ICD10CM | Other specified rheumatoid arthritis, right wrist |
| M06.832 | ICD10CM | Other specified rheumatoid arthritis, left wrist |
| M06.839 | ICD10CM | Other specified rheumatoid arthritis, unspecified wrist |
| M06.84 | ICD10CM | Other specified rheumatoid arthritis, hand |
| M06.841 | ICD10CM | Other specified rheumatoid arthritis, right hand |
| M06.842 | ICD10CM | Other specified rheumatoid arthritis, left hand |
| M06.849 | ICD10CM | Other specified rheumatoid arthritis, unspecified hand |
| M06.85 | ICD10CM | Other specified rheumatoid arthritis, hip |
| M06.851 | ICD10CM | Other specified rheumatoid arthritis, right hip |
| M06.852 | ICD10CM | Other specified rheumatoid arthritis, left hip |
| M06.859 | ICD10CM | Other specified rheumatoid arthritis, unspecified hip |
| M06.86 | ICD10CM | Other specified rheumatoid arthritis, knee |
| M06.861 | ICD10CM | Other specified rheumatoid arthritis, right knee |
| M06.862 | ICD10CM | Other specified rheumatoid arthritis, left knee |
| M06.869 | ICD10CM | Other specified rheumatoid arthritis, unspecified knee |
| M06.87 | ICD10CM | Other specified rheumatoid arthritis, ankle and foot |
| M06.871 | ICD10CM | Other specified rheumatoid arthritis, right ankle and foot |
| M06.872 | ICD10CM | Other specified rheumatoid arthritis, left ankle and foot |
| M06.879 | ICD10CM | Other specified rheumatoid arthritis, unspecified ankle and foot |
| M06.88 | ICD10CM | Other specified rheumatoid arthritis, vertebrae |
| M06.89 | ICD10CM | Other specified rheumatoid arthritis, multiple sites |
| M06.8A | ICD10CM | Other specified rheumatoid arthritis, other specified site |
| M06.9 | ICD10CM | Rheumatoid arthritis, unspecified |
| Systemic sclerosis-associated interstitial lung disease | ||
| M34.81 | ICD10CM | Systemic sclerosis with lung involvement |
| Systemic-onset juvenile idiopathic arthritis | ||
| M08.2 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset |
| M08.20 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified site |
| M08.21 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, shoulder |
| M08.211 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right shoulder |
| M08.212 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left shoulder |
| M08.219 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified shoulder |
| M08.22 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, elbow |
| M08.221 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right elbow |
| M08.222 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left elbow |
| M08.229 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified elbow |
| M08.23 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, wrist |
| M08.231 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right wrist |
| M08.232 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left wrist |
| M08.239 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified wrist |
| M08.24 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, hand |
| M08.241 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right hand |
| M08.242 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left hand |
| M08.249 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified hand |
| M08.25 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, hip |
| M08.251 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right hip |
| M08.252 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left hip |
| M08.259 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified hip |
| M08.26 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, knee |
| M08.261 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right knee |
| M08.262 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left knee |
| M08.269 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified knee |
| M08.27 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, ankle and foot |
| M08.271 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, right ankle and foot |
| M08.272 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, left ankle and foot |
| M08.279 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, unspecified ankle and foot |
| M08.28 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, vertebrae |
| M08.29 | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, multiple sites |
| M08.2A | ICD10CM | Juvenile rheumatoid arthritis with systemic onset, other specified site |
ICD code information from First Databank (FDB).
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