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Tocilizumab (including biosimilars): Drug information

Tocilizumab (including biosimilars): Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
ALERT: US Boxed Warning
Risk of serious infections:

Patients treated with tocilizumab are at an increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.

If a serious infection develops, interrupt tocilizumab until the infection is controlled.

Reported infections include:

Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before tocilizumab use and during therapy. Treatment for latent infection should be initiated prior to tocilizumab use.

Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated rather than localized disease.

Bacterial, viral, and other infections caused by opportunistic pathogens.

The risks and benefits of treatment with tocilizumab should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection.

Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with tocilizumab, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.

Brand Names: US
  • Actemra;
  • Actemra ACTPen;
  • Tofidence;
  • Tyenne
Brand Names: Canada
  • Actemra
Pharmacologic Category
  • Antirheumatic, Disease Modifying;
  • Interleukin-6 Receptor Antagonist;
  • Monoclonal Antibody
Dosing: Adult

Dosage guidance:

Dosage form information: In the United States, Tofidence (tocilizumab-bavi) and Tyenne (tocilizumab-aazg) have been approved as biosimilars to Actemra.

COVID-19, hospitalized patients

COVID-19, hospitalized patients (Actemra only): Note: For use in hospitalized patients with significant oxygen requirements (eg, high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation) and those with lower but increasing oxygen requirements and evidence of systemic inflammation (Ref). Do not initiate if ANC <1,000/mm3, platelets <50,000/mm3, or ALT or AST >10 times ULN.

IV: 8 mg/kg once (maximum dose: 800 mg) as part of an appropriate combination regimen (Ref). If clinical signs or symptoms worsen or do not improve, a second dose may be considered ≥8 hours after the first dose (Ref).

Cytokine release syndrome

Cytokine release syndrome:

Bi-specific T-cell engaging therapy-associated (off-label use): Note: Some experts reserve for patients with severe cytokine release syndrome (CRS) who do not respond to initial measures.

IV: 8 mg/kg once (maximum dose: 800 mg); if clinical improvement does not occur within 8 to 24 hours after, up to 3 additional doses may be administered (with at least an 8-hour interval between consecutive doses) (Ref).

Chimeric antigen receptor T-cell therapy-associated (Actemra only): IV: 8 mg/kg once (maximum dose: 800 mg). May give with or without glucocorticoids (Ref); some experts suggest using in combination with a glucocorticoid for grades 3 and 4 CRS (Ref). If clinical improvement does not occur after the first dose, up to 3 additional doses may be administered (with at least an 8-hour interval between consecutive doses) (Ref).

Giant cell arteritis

Giant cell arteritis (adjunctive agent) (Actemra and Tyenne [tocilizumab biosimilar] only):

Note: Do not initiate if ANC is <2,000/mm3, platelets are <100,000/mm3, or if ALT or AST are >1.5 times ULN. If a patient develops a serious infection, interrupt therapy until the infection is controlled.

IV: 6 mg/kg (maximum dose: 600 mg) once every 4 weeks in combination with glucocorticoids (Ref); some experts use 8 mg/kg once every 4 weeks in combination with glucocorticoids (or as monotherapy following discontinuation of glucocorticoids) and do not exceed 800 mg per dose (Ref).

SUBQ: 162 mg once every week; based on clinical considerations, may consider 162 mg once every other week; to be administered in combination with glucocorticoids (or as monotherapy following discontinuation of glucocorticoids) (Ref).

Kidney transplant, antibody-mediated rejection

Kidney transplant, antibody-mediated rejection (off-label use): Note: Optimal dose, frequency, and duration of therapy have not been established and vary based on institutional protocols. Administer as part of an appropriate combination regimen.

IV: 8 mg/kg (maximum: 800 mg per dose) once every 4 weeks until resolution (Ref).

Kidney transplant, pretransplant desensitization

Kidney transplant, pretransplant desensitization (adjunctive agent) (off-label use): Note: Optimal dose, frequency, and duration of therapy have not been established and vary based on institutional protocols.

IV: Months prior to transplant: 8 mg/kg once monthly as part of a combination regimen (eg, immune globulin) (Ref).

Neuromyelitis optica, relapse prevention

Neuromyelitis optica, relapse prevention (alternative agent) (off-label use):

Note: For long-term therapy to prevent attacks; optimal immunotherapy selection has not been established (Ref). Do not initiate if ANC is <2,000/mm3, platelets are <100,000/mm3, or if ALT or AST are >1.5 times ULN. If a patient develops a serious infection, interrupt therapy until the infection is controlled.

IV: 8 mg/kg once every 4 weeks (Ref); maximum dose has not been established; some experts do not exceed 800 mg per dose (Ref).

Rheumatoid arthritis

Rheumatoid arthritis (Actemra and tocilizumab biosimilars):

Note: May be administered in combination with methotrexate, another conventional synthetic disease-modifying antirheumatic drug, or as monotherapy if other treatment options are not tolerated (Ref). Patients should be under the care of a clinician experienced with use of tocilizumab for this condition. Do not initiate if ANC is <2,000/mm3, platelets are <100,000/mm3, or if ALT or AST are >1.5 times ULN. If a patient develops a serious infection, interrupt therapy until the infection is controlled.

IV: Initial: 4 mg/kg once every 4 weeks; may be increased to 8 mg/kg once every 4 weeks based on clinical response (maximum dose: 800 mg) (Ref).

SUBQ:

<100 kg: 162 mg once every other week; may increase to 162 mg once every week based on clinical response.

≥100 kg: 162 mg once every week.

Systemic sclerosis–associated interstitial lung disease

Systemic sclerosis (scleroderma)–associated interstitial lung disease (alternative agent) (Actemra only) :

Note: For initial and/or maintenance therapy in patients who cannot take other preferred agents. Do not initiate if ANC is <2,000/mm3, platelets are <100,000/mm3, or if ALT or AST are >1.5 times ULN. If a patient develops a serious infection, interrupt therapy until the infection is controlled.

SUBQ: 162 mg once every week (Ref).

Transitioning from IV therapy to SUBQ therapy: Administer the first SUBQ dose instead of the next scheduled IV dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, based on tocilizumab's molecular weight (148 kDa), it is unlikely to be significantly renally eliminated (Ref).

Dosing: Hepatic Impairment: Adult

Hepatic impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Initiation of therapy in patients with active hepatic disease or hepatic impairment or with the following baseline ALT or AST elevation is usually not recommended:

ALT or AST >1.5 × ULN: rheumatoid arthritis (RA), giant cell arteritis, or systemic sclerosis (scleroderma)-associated interstitial lung disease (SSc-ILD).

ALT or AST >10 × ULN: COVID-19.

Hepatotoxicity during treatment: RA, giant cell arteritis, and SSc-ILD:

>1 to 3 × ULN: Note: Adjust concomitant disease-modifying antirheumatic drugs (for RA and SSc-ILD) or immunomodulatory agents (for GCA) as appropriate.

For persistent increases >1 to 3 × ULN, adjust dose as follows:

Giant cell arteritis:

IV: Interrupt therapy until ALT/AST have normalized.

SUBQ: Reduce injection frequency to every other week or interrupt therapy until ALT/AST have normalized; resume therapy at every other week, then increase frequency to every week as clinically appropriate.

Rheumatoid arthritis:

IV: Reduce dose to 4 mg/kg or interrupt therapy until ALT/AST have normalized.

SUBQ: Reduce injection frequency to every other week or interrupt therapy until ALT/AST have normalized; resume therapy at every other week, then increase frequency to every week as clinically appropriate.

Systemic sclerosis (scleroderma)-associated interstitial lung disease: SUBQ: Reduce injection frequency to every other week or interrupt therapy until ALT/AST have normalized; resume therapy at every other week, then increase frequency to every week as clinically appropriate.

>3 to 5 × ULN (confirmed with repeat testing): Interrupt until ALT/AST <3 × ULN and follow dosage adjustments recommended for liver enzyme abnormalities >1 to 3 × ULN. For persistent increases >3 × ULN, discontinue.

>5 × ULN: Discontinue.

Dosing: Adjustment for Toxicity: Adult

Hypersensitivity (anaphylaxis or other clinically significant hypersensitivity reaction): Stop immediately and discontinue permanently.

Infection (serious infection, opportunistic infection, or sepsis): Interrupt treatment until the infection is controlled.

Rheumatoid arthritis, giant cell arteritis, and systemic sclerosis (scleroderma)-associated interstitial lung disease:

Neutropenia:

ANC >1,000/mm3: Maintain dose.

ANC 500 to 1,000/mm3: Interrupt therapy; when ANC >1,000/mm3, may resume as follows:

Giant cell arteritis:

IV: 6 mg/kg IV once every 4 weeks.

SUBQ: 162 mg every other week, then may increase to every week as clinically appropriate.

Rheumatoid arthritis:

IV: 4 mg/kg once every 4 weeks, then may increase to 8 mg/kg once every 4 weeks as clinically appropriate.

SUBQ: 162 mg every other week, then may increase to every week as clinically appropriate.

Systemic sclerosis (scleroderma)-associated interstitial lung disease: SUBQ: 162 mg every other week, then may increase to every week as clinically appropriate.

ANC <500/mm3: Discontinue.

Thrombocytopenia:

Platelets 50,000 to 100,000/mm3: Interrupt therapy; when platelet count is >100,000/mm3, may resume as follows:

Giant cell arteritis:

IV: 6 mg/kg IV once every 4 weeks.

SUBQ: 162 mg every other week, then may increase to every week as clinically appropriate.

Rheumatoid arthritis:

IV: 4 mg/kg once every 4 weeks, then may increase to 8 mg/kg once every 4 weeks as clinically appropriate.

SUBQ: 162 mg every other week, then may increase to every week as clinically appropriate.

Systemic sclerosis (scleroderma)-associated interstitial lung disease: SUBQ: 162 mg every other week, then may increase to every week as clinically appropriate.

Platelets <50,000/mm3: Discontinue.

Dosing: Older Adult

Refer to adult dosing; use with caution.

Dosing: Pediatric

(For additional information see "Tocilizumab (including biosimilars): Pediatric drug information")

COVID-19, treatment

COVID-19 (hospitalized patients who are receiving systemic corticosteroids), treatment:

Note: Emergency authorization in pediatric patients for COVID-19 is supported by efficacy data from adult patients and pediatric safety and dosing data extrapolated from other indications (Ref); very limited pediatric retrospective data are available (Ref). Not recommended for use in patients with ANC <1,000/mm3, platelets <50,000/mm3, or in patients with active hepatic disease or hepatic impairment (Ref).

Children ≥2 years and Adolescents: Very limited data available:

<30 kg: IV: 12 mg/kg/dose once; if clinical signs or symptoms worsen or do not improve after initial dose, may repeat dose once ≥8 hours after initial dose (Ref).

≥30 kg: IV: 8 mg/kg/dose once; maximum dose: 800 mg/dose; if clinical signs or symptoms worsen or do not improve after initial dose, may repeat dose once ≥8 hours after initial dose (Ref).

Cytokine release syndrome due to chimeric antigen receptor T-cell therapy; severe or life-threatening

Cytokine release syndrome (CRS) due to chimeric antigen receptor T-cell therapy; severe or life-threatening:

Children ≥2 years and Adolescents: May be used alone or in combination with corticosteroids.

<30 kg: IV: 12 mg/kg/dose once; if no clinical improvement after initial dose, may repeat dose every 8 hours for up to 3 additional doses.

≥30 kg: IV: 8 mg/kg/dose once; if no clinical improvement after initial dose, may repeat dose every 8 hours for up to 3 additional doses; maximum single dose: 800 mg/dose.

Cytokine release syndrome due to bi-specific T-cell engaging therapy, severe or life-threatening

Cytokine release syndrome (CRS) due to bi-specific T-cell engaging therapy, severe or life-threatening: Very limited data available (Ref); optimal dose not established.

Children ≥2 years and Adolescents: IV: 8 mg/kg/dose once; some experts suggest may repeat the dose if clinical improvement does not occur within 24 to 48 hours (Ref); dosing based on expert recommendations and a case report of a 7-year-old who received blinatumomab as part of a Phase I clinical trial and developed CRS; a single 8 mg/kg dose of tocilizumab was used (patient weight was not provided) and within 12 hours a significant clinical response was observed (Ref); other reports of experience in pediatric patients are lacking.

Polyarticular juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis (PJIA):

Children ≥2 years and Adolescents: Note: Do not initiate if ANC is <2,000/mm3, platelets are <100,000/mm3, or if ALT or AST are >1.5 times ULN. Dose adjustment should not be made based solely on a single-visit body weight measurement due to fluctuations in body weight. May be used as monotherapy or in combination with methotrexate. Variable routes of administration (IV, SUBQ) and dosing; use precaution to ensure appropriate dose/route.

IV:

<30 kg: 10 mg/kg/dose every 4 weeks.

≥30 kg: 8 mg/kg/dose every 4 weeks; maximum dose: 800 mg/dose.

SUBQ:

<30 kg: 162 mg/dose once every 3 weeks.

≥30 kg: 162 mg/dose once every 2 weeks.

Conversion from IV to SUBQ dosing: Administer the first SUBQ dose instead of the next scheduled IV dose.

Systemic juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (SJIA):

Children ≥2 years and Adolescents: Note: Do not initiate if ANC is <2,000/mm3, platelets are <100,000/mm3, or if ALT or AST are >1.5 times ULN. Dose adjustment should not be made based solely on a single-visit body weight measurement due to fluctuations in body weight. May be used as monotherapy or in combination with methotrexate.

IV:

<30 kg: 12 mg/kg/dose every 2 weeks.

≥30 kg: 8 mg/kg/dose every 2 weeks; maximum dose: 800 mg/dose.

SUBQ:

<30 kg: 162 mg/dose once every 2 weeks.

≥30 kg: 162 mg/dose once every week.

Conversion from IV to SUBQ dosing: Administer the first SUBQ dose instead of the next scheduled IV dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity:

Polyarticular and systemic juvenile idiopathic arthritis (SJIA): Children ≥2 years and Adolescents:

Non-hematologic toxicity: Dose reductions have not been studied; however, dose interruptions are recommended for liver enzyme abnormalities (see Hepatic Impairment). In addition, consider interrupting or discontinuing concomitant methotrexate and/or other medications and hold tocilizumab dosing until the clinical situation has been assessed. For hypersensitivity reactions, stop the infusion immediately and discontinue permanently. For infection (serious, opportunistic, or sepsis), interrupt treatment until infection resolved.

Hematologic toxicity: Dose reductions have not been studied; however, dose interruptions are recommended for low neutrophil counts and low platelets similar to recommendations provided for adult rheumatoid arthritis patients (see the following):

Adults:

Neutropenia:

ANC >1,000/mm3: Maintain dose.

ANC 500 to 1,000/mm3: Interrupt therapy; when ANC >1,000/mm3, resume IV tocilizumab at 4 mg/kg (may increase to 8 mg/kg as clinically appropriate) or resume SUBQ tocilizumab at every other week dosing (increase frequency to every week as clinically appropriate).

ANC <500/mm3: Discontinue.

Thrombocytopenia:

Platelets 50,000 to 100,000/mm3: Interrupt therapy; when platelet count is >100,000/mm3, resume IV tocilizumab at 4 mg/kg (may increase to 8 mg/kg as clinically appropriate) or resume SUBQ tocilizumab at every other week dosing (increase frequency to every week as clinically appropriate).

Platelets <50,000/mm3: Discontinue.

Dosing: Kidney Impairment: Pediatric

Children ≥2 years and Adolescents:

Mild to moderate renal impairment: No dosage adjustment required.

Severe renal impairment: There are no dosage adjustments provided in the manufacturer's labeling (not studied).

Dosing: Hepatic Impairment: Pediatric

COVID-19: Children ≥2 years and Adolescents: There are no dosage adjustments provided in the fact sheet for health care providers; not recommended for use in patients with active hepatic disease or hepatic impairment (ie, ALT/AST >10 times ULN). Decision for use should balance potential risks and benefits (Ref).

Polyarticular and systemic juvenile idiopathic arthritis (SJIA): Children ≥2 years and Adolescents:

Baseline: There are no dosage adjustments provided in the manufacturer's labeling (not studied); not recommended for use in patients with active hepatic disease or hepatic impairment.

Hepatotoxicity during therapy: Dose reductions have not been studied in pediatric patients; however, dose interruptions and reductions are recommended for liver enzyme abnormalities similar to those for adult rheumatoid arthritis patients.

ALT/AST >1 to 3 times ULN (persistent): Consider dose reduction or interrupt until ALT/AST have normalized.

ALT/AST >3 to 5 times ULN (confirmed with repeat testing): Interrupt until ALT/AST <3 times ULN and then reinitiate at a reduced dose. For persistent increase in ALT/AST >3 times ULN, discontinue.

ALT/AST >5 times ULN: Discontinue.

Adverse Reactions (Significant): Considerations
GI perforation

GI perforation (most often lower GI) has been reported, typically secondary to diverticulitis. Tocilizumab is associated with a higher risk of GI perforation in patients with rheumatoid arthritis compared to other biologic or conventional disease-modifying antirheumatic drugs (Ref). GI perforation and diverticulitis may present with an atypical clinical picture (Ref).

Mechanism: Unknown; tocilizumab is an interleukin-6 (IL-6) receptor antagonist and is hypothesized that IL-6 is needed to maintain intestinal homeostasis; neutralization of IL-6 impairs healing of digestive epithelium in susceptible individuals (Ref).

Risk factors:

• History of diverticulitis (Ref)

• Older age (Ref)

• Concurrent glucocorticoids (current and cumulative use [prednisone dose >7.5 mg/day]) (Ref)

• Concurrent nonsteroidal anti-inflammatory drugs (Ref)

Hematologic effects

Neutropenia and thrombocytopenia may occur; treatment interruption, dose or interval modification, or discontinuation may be required. Neutropenia and thrombocytopenia do not appear to be associated with serious infections and bleeding, respectively (Ref).

Mechanism: Tocilizumab is an antagonist of the interleukin-6 (IL-6) receptor; IL-6 mobilizes neutrophils from the marginated pool into the circulating pool, therefore, neutropenia induced by tocilizumab may reflect a shift of neutrophils out of circulation rather than myelosuppression (Ref). Similarly, IL-6 increases thrombopoiesis and tocilizumab-induced reductions in platelet counts are typically not large enough to be associated with bleeding (Ref).

Onset: Varied; neutrophil counts typically decrease over the first 6 weeks and stabilize thereafter (Ref).

Risk factors:

• Neutropenia risk is increased in females and baseline neutrophils <2,000/mm3 (Ref)

Hepatic effects

Tocilizumab may cause increased serum alanine aminotransferase and increased serum aspartate aminotransferase. Increases are generally transient; however, some cases may require dose reduction (Ref). Cases of severe hepatitis and hepatic failure (including fatal) have been reported (Ref). Mild liver injury may resolve within 6 weeks, while severe cases may resolve within 2 to 3 months (Ref).

Mechanism: Unknown; may result from effects on interleukin-6, which helps protect against liver damage and increases liver regeneration (Ref).

Onset: Varied; has been reported months to years after initiation, although most cases occur within the first year (Ref).

Risk factors:

• Concurrent methotrexate, disease-modifying drugs, or other hepatotoxic medications (Ref)

Hypersensitivity reactions

Tocilizumab is associated with a variety of hypersensitivity reactions, including immediate (eg, anaphylaxis) (Ref) and delayed hypersensitivity reactions. Fatal anaphylactic reactions have been reported following repeated IV administration (Ref). Hypersensitivity reactions are rare, occurring at a rate of 0.1% to 0.7% (Ref). Delayed hypersensitivity reactions include non-specific cutaneous eruptions, urticaria, psoriasis, and hypersensitivity angiitis (Ref). In addition, serious cutaneous adverse reactions (SCARs) have been reported, including drug rash with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome (Ref).

Mechanism:

Immediate reactions: Unknown; possibly related to release of cytokines or IgE-mediated (Ref).

Delayed hypersensitivity reactions: Non–dose-related, immunologic (ie, T-cell–mediated) (Ref).

Onset:

Anaphylactic reactions: Rapid; occurs within 24 hours after infusion, typically between the second and ninth infusions (Ref).

Delayed reactions: Varied; range from 4 days after a single infusion to development of psoriatic lesions after 22 infusions (Ref).

SCARs: Varied; usually occur 1 to 8 weeks after initiation (Ref), although DRESS has been reported after 3 months (Ref).

Risk factors:

• Patients with systemic juvenile idiopathic arthritis with greater disease activity and younger age may be at higher risk for anaphylactic reactions (Ref)

• Patients with adult-onset Still disease may have a higher risk of anaphylaxis than patients with other rheumatic diseases (Ref)

• IV administration associated with higher risk of serious hypersensitivity reactions, including anaphylaxis, compared to SUBQ administration (Ref)

• Absence of concurrent synthetic disease-modifying antirheumatic drugs may increase the risk of anaphylactic reactions in patients with rheumatoid arthritis (Ref)

Infections

Serious and potentially fatal infections (including invasive fungal, bacterial, viral, protozoal, and other opportunistic infections) have been reported in patients receiving tocilizumab. Most serious infections have occurred in patients taking concurrent immunosuppressive therapy. Common serious infections have included pneumonia, urinary tract infections, cellulitis, herpes zoster, gastroenteritis, diverticulitis of the gastrointestinal tract, sepsis, and septic arthritis. Tuberculosis (pulmonary or extrapulmonary) has been reported, both reactivation of latent infection and new infections. Overall rate of infection with concurrent methotrexate is 30% higher than with monotherapy and serious infection may be doubled (Ref). In a multi-database study, the risk of serious infection with tocilizumab in adult patients with rheumatoid arthritis was not different from tumor necrosis factor (TNF) inhibitors (Ref). Overall risk of infection is similar to TNF inhibitors, with particular risks for mycobacterial and viral infections (Ref). Healthcare-associated infections in patients with COVID-19 were increased 5-fold with prior use of tocilizumab (Ref).

Mechanism: Dose-related, related to mechanism of action; immunosuppression increases risk for infection.

Onset: Delayed; may occur at any time. No difference noted for 0 to 12 months treatment versus 13 to 24 months of treatment (Ref).

Risk factors:

• Higher doses (Ref)

• Prednisone dose ≥5 mg/day or equivalent (Ref)

• Age ≥65 years (Ref)

• Previous or concurrent respiratory disease (Ref)

• Chronic or recurrent infections, tuberculosis exposure, and/or underlying conditions predisposing to infection

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling and the FDA issued emergency use authorization (EUA), unless otherwise specified. Incidences are reported for monotherapy, combination therapy, and adults, unless otherwise noted. Refer to EUA for information regarding reporting adverse reactions (FDA 2021).

>10%:

Endocrine & metabolic: Increased serum cholesterol (19% to 20%; children and adolescents: ≤2%)

Gastrointestinal: Constipation (6% to 13%)

Hematologic & oncologic: Neutropenia (children and adolescents <30 kg: 26%; children and adolescents ≥30 kg and adults: 3% to 4%)

Hepatic: Increased serum alanine aminotransferase (≤36%) (table 1), increased serum aspartate aminotransferase (≤22%) (table 2)

Tocilizumab: Adverse Reaction: Increased Serum Alanine Aminotransferase

Drug (Tocilizumab)

Comparator (Methotrexate)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Methotrexate)

Number of Patients (Placebo)

Comments

5%

N/A

0%

Children and adolescents

8 or 12 mg per kg

IV

Systemic juvenile idiopathic arthritis

75

N/A

N/A

≥3 × ULN

3%

N/A

1%

Adults

Single infusion of 8 mg/kg (maximum dose: 800 mg)

IV

Patients hospitalized with COVID-19 pneumonia

295

N/A

143

N/A

36%

33%

N/A

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

N/A

> ULN to 3 × ULN

7%

N/A

N/A

Adults

162 mg administered every week

SUBQ

Rheumatoid arthritis

N/A

N/A

N/A

≥3 × ULN

3%

N/A

N/A

Adults

162 mg administered every other week

SUBQ

Rheumatoid arthritis

N/A

N/A

N/A

≥3 × ULN

1%

4%

N/A

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

N/A

>3 × ULN to 5 × ULN

0.7%

1%

N/A

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

N/A

>5 × ULN

Tocilizumab: Adverse Reaction: Increased Serum Aspartate Aminotransferase

Drug (Tocilizumab)

Comparator (Methotrexate)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Methotrexate)

Comments

3%

N/A

0%

Children and adolescents

8 or 12 mg per kg

IV

Systemic juvenile idiopathic arthritis

75

N/A

≥3 × ULN

22%

26%

N/A

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

> ULN to 3 × ULN

1%

N/A

N/A

Adults

162 mg administered every week

SUBQ

Rheumatoid arthritis

N/A

N/A

≥3 × ULN

0.7%

0.4%

N/A

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

>5 × ULN

0.7%

N/A

N/A

Adults

162 mg administered every other week

SUBQ

Rheumatoid arthritis

N/A

N/A

≥3 × ULN

0.3%

2%

N/A

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

>3 × ULN to 5 × ULN

Hypersensitivity: Infusion-related reaction (4% to 20%)

Local: Injection site reaction (SUBQ: Children and adolescents: 15% to 44% [higher incidence occurred in weight ≥30 kg]; adults: 7% to 10%)

1% to 10%:

Cardiovascular: Deep vein thrombosis (3%), hypertension (4% to 7%), peripheral edema (<2%), septic shock (6%)

Dermatologic: Skin rash (2%) (table 3)

Tocilizumab: Adverse Reaction: Skin Rash

Drug (Tocilizumab)

Comparator (Methotrexate)

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Methotrexate)

2%

1%

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

Endocrine & metabolic: Hyperglycemia (5%), hypoglycemia (3%), hypokalemia (4% to 5%), hypothyroidism (<2%), increased LDL cholesterol (9% to 10%; children and adolescents: ≤2%), weight gain (<2%)

Gastrointestinal: Diarrhea (children, adolescents, and adults: ≥4%), gastric ulcer (<2%), gastritis (1%), nausea (3% to 4%), oral mucosa ulcer (2%), stomatitis (<2%), upper abdominal pain (2%)

Genitourinary: Urinary tract infection (5% to 8%) (table 4)

Tocilizumab: Adverse Reaction: Urinary Tract Infection

Drug (Tocilizumab)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Placebo)

8%

3%

Adults

Single infusion of 8 mg/kg (maximum dose: 800 mg)

IV

Patients hospitalized with COVID-19 pneumonia

295

143

5%

4%

Adults

Single infusion of 8 mg/kg (maximum dose: 800 mg). Possible second dose if clinical signs or symptoms worsened or did not improve after first dose.

IV

Patients hospitalized with COVID-19

974

483

Hematologic & oncologic: Leukopenia (<2%), thrombocytopenia (children, adolescents, and adults: 1% to 4%) (table 5)

Tocilizumab: Adverse Reaction: Thrombocytopenia

Drug (Tocilizumab)

Placebo

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Placebo)

Comments

1%

3%

Children and adolescents

8 or 12 mg per kg

IV

Systemic juvenile idiopathic arthritis

75

N/A

N/A

4%

1%

Adults

Single infusion of 8 mg/kg (maximum dose: 800 mg)

IV

Patients hospitalized with COVID-19 pneumonia

295

143

N/A

3%

1%

Adults

Single infusion of 8 mg/kg (maximum dose: 800 mg)

IV

Patients hospitalized with COVID-19 pneumonia

429

213

In combination with remdesivir

Hepatic: Increased serum bilirubin (<2%)

Immunologic: Antibody development (children and adolescents: ≤6%; adults: ≤2%, including neutralizing)

Infection: Herpes simplex infection (<2%)

Nervous system: Anxiety (3% to 6%), delirium (5%), dizziness (3%), headache (3% to 7%), insomnia (4% to 5%), pain (3%)

Ophthalmic: Conjunctivitis (<2%)

Renal: Acute kidney injury (7%), nephrolithiasis (<2%)

Respiratory: Bronchitis (3%) (table 6), cough (<2%), dyspnea (<2%), nasopharyngitis (7%) (table 7), pneumonia (8%) (table 8), upper respiratory tract infection (7%) (table 9)

Tocilizumab: Adverse Reaction: Bronchitis

Drug (Tocilizumab)

Comparator (Methotrexate)

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Methotrexate)

3%

2%

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

Tocilizumab: Adverse Reaction: Nasopharyngitis

Drug (Tocilizumab)

Comparator (Methotrexate)

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Methotrexate)

7%

6%

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

Tocilizumab: Adverse Reaction: Pneumonia

Drug (Tocilizumab)

Placebo + Remdesivir

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Placebo + Remdesivir)

Comments

8%

5%

Single infusion of 8 mg/kg (maximum dose: 800 mg)

IV

Patients hospitalized with COVID-19 pneumonia

429

213

In combination with remdesivir

Tocilizumab: Adverse Reaction: Upper Respiratory Tract Infection

Drug (Tocilizumab)

Comparator (Methotrexate)

Population

Dose

Dosage Form

Indication

Number of Patients (Tocilizumab)

Number of Patients (Methotrexate)

7%

5%

Adults

8 mg per kg

IV

Rheumatoid arthritis

288

284

<1%: Hypersensitivity: Anaphylaxis (Park 2020)

Frequency not defined:

Cardiovascular: Hypotension

Dermatologic: Pruritus

Nervous system: Chronic inflammatory demyelinating polyneuropathy

Otic: Otitis media

Postmarketing:

Dermatologic: Cellulitis, psoriasis (Grasland 2013), Stevens-Johnson syndrome (Venkateswaran 2020), urticaria (Erdogan 2018)

Gastrointestinal: Diverticulitis of the gastrointestinal tract (Stangfeld 2017), gastroenteritis, gastrointestinal perforation (Stangfeld 2017), pancreatitis (Kamath 2021), ulcerative bowel lesion (Ohkubo 2022)

Hematologic & oncologic: Malignant neoplasm (Finet 2012)

Hepatic: Hepatic failure (Genovese 2017), hepatic injury (Genovese 2017), hepatitis (Genovese 2017), jaundice (Genovese 2017)

Hypersensitivity: Angioedema (Erdogan 2018), drug reaction with eosinophilia and systemic symptoms (Zuelgaray 2017), hypersensitivity angiitis (Wu 2015)

Infection: Aspergillosis, atypical mycobacterial infection, candidiasis, cryptococcosis, herpes zoster infection, infection (Campbell 2011), sepsis

Nervous system: Multiple sclerosis (Beauchemin 2016)

Neuromuscular & skeletal: Septic arthritis

Respiratory: Infection due to an organism in genus Pneumocystis, tuberculosis

Contraindications

Known hypersensitivity to tocilizumab or any component of the formulation.

Canadian labeling: Additional contraindications (not in the US labeling): Active infections.

Warnings/Precautions

Concerns related to adverse effects:

• Herpes zoster reactivation: Herpes zoster reactivation has been reported.

• Hyperlipidemia: Therapy is associated with increases in total cholesterol, triglycerides, low-density lipoprotein, and/or high-density lipoprotein.

• Malignancy: Use of tocilizumab may affect defenses against malignancies; impact on the development and course of malignancies is not fully defined; however, malignancies were observed in clinical trials.

Disease-related concerns:

• Demyelinating CNS disease: Use with caution in patients with preexisting or recent onset CNS demyelinating disorders; rare cases of CNS demyelinating disorders (multiple sclerosis and chronic inflammatory demyelinating polyneuropathy) have occurred.

• Hepatic impairment: Use with caution in hepatic impairment; see "Dosage: Hepatic Function Impairment" for additional information.

• Tuberculosis: Consider anti-tuberculosis (TB) treatment in patients with a history of latent or active TB infection or disease (latent or active TB) if adequate treatment course cannot be confirmed, and for patients with risk factors for TB despite a negative test.

Concurrent drug therapy issues:

• Biological disease-modifying antirheumatic drugs: Concomitant use with other biological disease-modifying antirheumatic drugs (DMARDs) (eg, tumor necrosis factor blockers, IL-1 receptor blockers, anti-CD20 monoclonal antibodies, selective costimulation modulators) has not been studied and should be avoided due to the increased risk of infection.

Special populations:

• Patients with rheumatic musculoskeletal disease undergoing hip or knee replacement surgery: Hold biologic disease-modifying antirheumatic drugs (DMARDs) prior to surgery and plan surgery after the next dose is due. Surgery can occur after holding medication for 1 full dosing cycle (eg, for medications administered every 4 weeks, schedule surgery 5 weeks from last administered dose); therapy can be restarted once surgical wound shows evidence of healing (eg, no swelling, erythema, or drainage), sutures/staples are removed, and no ongoing nonsurgical site infections (typically ~14 days to reduce infection risk). Decisions to withhold therapy should be based on shared decision making; ensure the patient and their provider weigh risks of interrupting therapy and disease control versus risks of continuing therapy and surgical complications (ACR/AAHKS [Goodman 2022]).

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and kidney and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Appropriate use: SUBQ administration is only indicated for adult patients with rheumatoid arthritis, giant cell arteritis, and systemic sclerosis (scleroderma)-associated interstitial lung disease (SSc-ILD), and pediatric patients with polyarticular juvenile idiopathic arthritis. Do not use SUBQ injection for IV infusion. Do not administer IV for the treatment of SSc-ILD. SUBQ administration with the prefilled ACTPen autoinjector has not been studied in SSc-ILD.

• Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently; there are no data available concerning secondary transmission of infection from live vaccines in patients receiving therapy.

Warnings: Additional Pediatric Considerations

Reactivation of TB has been reported in pediatric patients receiving biologic response modifiers (infliximab and etanercept); prior to therapy, patients with no TB risk factors should be screened for latent TB infection (LTBI) with an age appropriate test (ie, <5 years of age: Tuberculin skin test, and ≥5 years of age: IGRA [interferon gamma release assay]); if any TB risk factors are present or symptoms, both LTBI screening tests should be performed (AAP [Davies 2016])

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Tyenne: Tocilizumab-aazg 200 mg/10 mL (10 mL); Tocilizumab-aazg 400 mg/20 mL (20 mL) [contains polysorbate 80]

Solution, Intravenous [preservative free]:

Actemra: 80 mg/4 mL (4 mL); 200 mg/10 mL (10 mL); 400 mg/20 mL (20 mL) [contains polysorbate 80]

Tofidence: Tocilizumab-bavi 80 mg/4 mL (4 mL); Tocilizumab-bavi 400 mg/20 mL (20 mL); Tocilizumab-bavi 200 mg/10 mL (10 mL) [contains polysorbate 80]

Tyenne: Tocilizumab-aazg 80 mg/4 mL (4 mL) [contains polysorbate 80]

Solution Auto-injector, Subcutaneous [preservative free]:

Actemra ACTPen: 162 mg/0.9 mL (0.9 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Actemra: 162 mg/0.9 mL (0.9 mL) [contains polysorbate 80]

Generic Equivalent Available: US

No

Pricing: US

Solution (Actemra Intravenous)

80 mg/4 mL (per mL): $159.35

200 mg/10 mL (per mL): $159.35

400 mg/20 mL (per mL): $159.35

Solution (Tofidence Intravenous)

80 mg/4 mL (per mL): $133.20

200 mg/10 mL (per mL): $133.20

400 mg/20 mL (per mL): $133.20

Solution (Tyenne Intravenous)

80 mg/4 mL (per mL): $117.51

200 mg/10 mL (per mL): $117.50

400 mg/20 mL (per mL): $117.50

Solution Auto-injector (Actemra ACTPen Subcutaneous)

162 mg/0.9 mL (per 0.9 mL): $1,409.77

Solution Prefilled Syringe (Actemra Subcutaneous)

162 mg/0.9 mL (per 0.9 mL): $1,409.77

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Actemra: 80 mg/4 mL (4 mL); 200 mg/10 mL (10 mL); 400 mg/20 mL (20 mL) [contains polysorbate 80]

Solution Auto-injector, Subcutaneous:

Actemra: 162 mg/0.9 mL (0.9 mL) [contains polysorbate 80]

Solution Prefilled Syringe, Subcutaneous:

Actemra: 162 mg/0.9 mL (0.9 mL) [contains polysorbate 80]

Administration: Adult

IV : Allow diluted solution for infusion to reach room temperature prior to administration; infuse over 60 minutes using a dedicated IV line. Do not infuse other agents through same IV line. Do not administer IV push or IV bolus. If additional doses are necessary for the management of cytokine-release syndrome, the interval between doses should be at least 8 hours. Do not use if opaque particles or discoloration is visible.

Note: In response to tocilizumab use for COVID-19, the possibility that supplies of the IV formulation may become limited or unavailable prompted the manufacturer of Actemra, Genentech, to evaluate use of the SUBQ formulation for IV administration. Though Genentech does not recommend the use of the SUBQ formulation diluted in IV bags for infusion, they have provided the following stability information; no information is available on safety and efficacy of the SUBQ formulation administered as an IV infusion (Ref):

No physicochemical incompatibilities were observed with the following investigational study conditions using tocilizumab prefilled syringes (PFS):

• Tocilizumab PFS diluted in a 100 mL NS IV bag made of materials such as PVC, polyolefin, polyethylene (PE), and polypropylene (PP). No NS was removed prior to injecting tocilizumab PFS.

• Two doses were tested: Low dose (1 PFS injected into a 100 mL NS bag, leading to a protein concentration of 1.6 mg/mL [total dose: 162 mg]) and high dose (6 PFS injected into a 100 mL NS bag leading to a concentration of 9.2 mg/mL [total dose: 972 mg]). Note: Tocilizumab doses exceeding 800 mg/infusion are not recommended in patients with rheumatoid arthritis or cytokine-release syndrome.

• IV solutions were stored for 24 hours at room temperature.

• Simulated infusions were conducted over 2 hours using an infusion rate of 19.6 mL/hour (infusion volume of 40 mL) with infusion administration sets made of PVC, PE, polybutadiene, or polyurethane equipped with a 0.2 or 0.22 micrometer polyethersulfone or polysulfone inline filter.

• Compatibility with other drugs and indwelling catheters, such as peripherally inserted central catheters and central venous access devices, were not tested.

SUBQ: Allow to reach room temperature (30 minutes for prefilled syringe; 45 minutes for autoinjector) prior to use. Do not use if particulate matter or discoloration is visible; solution should be clear and colorless to pale yellow. Administer the full amount in the prefilled syringe or autoinjector. Rotate injection sites; avoid injecting into moles, scars, or tender, bruised, red, or hard skin. After proper training, patients may self-inject, or the patient's caregiver may administer tocilizumab.

Giant cell arteritis, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis: When transitioning from IV administration to SUBQ administration, give the first SUBQ dose instead of the next scheduled IV dose.

Systemic sclerosis (scleroderma)-associated interstitial lung disease: Should only be administered SUBQ using prefilled syringe (IV administration is not approved for systemic sclerosis (scleroderma)-associated interstitial lung disease); use with the ACTPen autoinjector has not been studied.

Administration: Pediatric

IV: Allow diluted solution to reach room temperature prior to administration; infuse over 60 minutes using a dedicated IV line. Do not administer IV push or IV bolus. Do not use if opaque particles or discoloration are visible.

SUBQ: Administer the full amount (162 mg/0.9 mL) in the prefilled syringe. Allow to reach room temperature prior to use. Do not use if particulate matter or discoloration is visible; solution should be clear and colorless to pale yellow. Rotate injection sites; avoid injecting into moles, scars, or tender, bruised, red, or hard skin. After proper training, patients may self-inject, or the patient's caregiver may administer tocilizumab using prefilled syringe. Use of the autoinjector in pediatric patients has not been studied.

Note: In response to tocilizumab use for COVID-19, the possibility that supplies of the IV formulation may become limited or unavailable prompted the manufacturer, Genentech, to evaluate use of the SUBQ formulation for IV administration. Though Genentech does not recommend the use of the SUBQ formulation diluted in IV bags for infusion, they have provided the following stability information; no information is available on safety and efficacy of the SUBQ formulation administered as an IV infusion (Ref):

No physicochemical incompatibilities were observed with the following investigational study conditions using tocilizumab prefilled syringes (PFS):

• Tocilizumab PFS diluted in a 100 mL NS IV bag made of materials such as PVC, polyolefin, polyethylene (PE), and polypropylene (PP). No NS was removed prior to injecting tocilizumab PFS.

• Two doses were tested: Low dose (1 PFS injected into a 100 mL NS bag, leading to a protein concentration of 1.6 mg/mL [total dose: 162 mg]) and high dose (6 PFS injected into a 100 mL NS bag leading to a concentration of 9.2 mg/mL [total dose: 972 mg]). Note: Tocilizumab doses exceeding 800 mg/infusion are not recommended in patients with rheumatoid arthritis or cytokine-release syndrome.

• IV solutions were stored for 24 hours at room temperature.

• Simulated infusions were conducted over 2 hours using an infusion rate of 19.6 mL/hour (infusion volume of 40 mL) with infusion administration sets made of PVC, PE, polybutadiene, or polyurethane equipped with a 0.2 or 0.22 micrometer polyethersulfone or polysulfone inline filter.

• Compatibility with other drugs and indwelling catheters, such as peripherally inserted central catheters and central venous access devices, were not tested.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Atemra: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125472s046lbl.pdf#page=50

Tyenne: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761275s000lbl.pdf#page=46

Use: Labeled Indications

COVID-19, hospitalized patients (Actemra only): Treatment of COVID-19 in adult, hospitalized patients who are receiving systemic glucocorticoids and require supplemental oxygen, noninvasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.

Cytokine release syndrome, chimeric antigen receptor T-cell therapy-associated (Actemra only): Treatment of chimeric antigen receptor T-cell–induced severe or life-threatening cytokine release syndrome in patients ≥2 years of age.

Giant cell arteritis (Actemra and Tyenne [tocilizumab biosimilar] only): Treatment of giant cell arteritis in adult patients.

Polyarticular juvenile idiopathic arthritis (Actemra and tocilizumab biosimilars): Treatment of active polyarticular juvenile idiopathic arthritis in patients ≥2 years of age.

Rheumatoid arthritis (Actemra and tocilizumab biosimilars): Treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs.

Systemic juvenile idiopathic arthritis (Actemra and tocilizumab biosimilars): Treatment of active systemic juvenile idiopathic arthritis in patients ≥2 years of age.

Systemic sclerosis (scleroderma)-associated interstitial lung disease (Actemra only): Indicated to slow the rate of decline in pulmonary function in adult patients with systemic sclerosis (scleroderma)-associated interstitial lung disease.

Note: In the United States, Tofidence (tocilizumab-bavi) and Tyenne (tocilizumab-aazg) have been approved as biosimilars to Actemra.

Use: Off-Label: Adult

Cytokine release syndrome, bi-specific T-cell engaging therapy-associated; Kidney transplant, antibody-mediated rejection, treatment; Kidney transplant, pretransplant desensitization; Neuromyelitis optica, relapse prevention

Medication Safety Issues
Sound-alike/look-alike issues:

Tocilizumab may be confused with sarilumab.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Anifrolumab: Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) may enhance the immunosuppressive effect of Anifrolumab. Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Management: Consider alternatives to the use of belimumab with other biologic therapies. Monitor closely for increased toxicities related to additive immunosuppression (ie, infection, malignancy) if combined. Risk D: Consider therapy modification

Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CycloSPORINE (Systemic): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

HMG-CoA Reductase Inhibitors (Statins): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Theophylline: Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of Theophylline. Risk C: Monitor therapy

Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification

Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Based on limited data, tocilizumab may be considered for use in patients with rheumatic and musculoskeletal diseases who are planning to become pregnant; however, treatment should be discontinued once pregnancy is confirmed. Conception should be planned during a period of quiescent/low disease activity (ACR [Sammaritano 2020]).

Data related to paternal use of tocilizumab are limited (Hoeltzenbein 2016). Therefore, recommendations are not available for use in patients with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).

Pregnancy Considerations

Tocilizumab crosses the placenta (Moriyama 2020; Saito 2018; Saito 2019a; Tada 2019). Tocilizumab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Tocilizumab was not detected in umbilical cord blood, infant serum, or maternal serum at delivery in a patient who received her last dose 23 weeks prior to delivery (Saito 2021). Postmarketing data reviewed through 2014 have not shown an increased rate of congenital malformations or a pattern of specific malformations following in utero exposure to tocilizumab. The review included pregnancy outcome data from 288 women who received tocilizumab for rheumatic disorders; the majority received a dose during the first trimester or within 6 weeks of conception. Using these data, the incidence of preterm birth and spontaneous abortion may be increased when compared to the background rate, but these outcomes may also be influenced by maternal disease and concomitant medications (Hoeltzenbein 2016). Additional outcome data are limited (Akira 2023; Dalkilic 2019; Dernoncourt 2023; Ghalandari 2022; Imaizumi 2022; Jorgensen 2022; Khan 2023; Konagai 2023; Sugisaki 2023; Tada 2019).

Until additional data are available, tocilizumab is not currently recommended for the treatment of rheumatic and musculoskeletal diseases during pregnancy. Tocilizumab should be discontinued once pregnancy is confirmed (ACR [Sammaritano 2020]).

Outcome data specific to use of tocilizumab in pregnancy for COVID-19 are limited (Isaac 2023; Jorgensen 2022; Péju 2022). In general, the treatment of COVID-19 infection during pregnancy is the same as in nonpregnant patients. However, because data for most therapeutic agents in pregnant patients are limited, treatment options should be evaluated as part of a shared decision-making process. Use of tocilizumab for the treatment of COVID-19 is recommended in hospitalized pregnant patients (NIH 2023). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.

The risk of severe morbidity and mortality from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID-19. Symptomatic pregnant patients may require ICU admission, mechanical ventilation, or ventilatory support (ECMO). Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG 2023; NIH 2023). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.

Data collection to monitor pregnancy and infant outcomes following exposure to tocilizumab is ongoing. Health care providers or pregnant patients are encouraged to enroll exposed pregnancies in the registry (1-877-311-8972).

Breastfeeding Considerations

Tocilizumab is present in colostrum and breast milk (Moriyama 2020; Saito 2018; Saito 2019a; Saito 2019b; Saito 2021; Tada 2019).

In a report of 2 cases, breast milk concentrations peaked ~3 days after an IV maternal dose, then gradually decreased (Saito 2018). In a third case, tocilizumab was detected in the serum of 1 infant at birth following in utero exposure; however, concentrations rapidly decreased and were not detectable by 4 weeks of age, even though the infant was exclusively breastfed (Saito 2019a).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Although data related to use in lactating patients are limited, adverse events have not been reported in breastfed infants (Nakajima 2016; Saito 2018; Saito 2019a). Concentrations of tocilizumab are expected to be limited in breast milk due to large molecular weight. Also, because tocilizumab is unlikely to be absorbed via the infant GI tract, use of tocilizumab may be considered in patients who are breastfeeding (ACR [Sammaritano 2020]).

Breast milk has not been found to be a source of COVID-19 infection and maternal infection is not a contraindication to breastfeeding. The decision to breastfeed during treatment for COVID-19 should be evaluated as part of a shared decision-making process. Breastfeeding can continue if tocilizumab is needed for the management of COVID-19. However, lactating patients with COVID-19 infection can transmit the virus through respiratory droplets and all precautions should be taken to avoid spreading the virus to the infant (eg, hand hygiene, mask wearing); alternatively, breast milk can be expressed and fed to the infant by someone without confirmed or suspected COVID-19 (ACOG 2023; NIH 2023).

Information related to COVID-19 and breastfeeding is available from the World Health Organization (https://www.who.int/news/item/28-04-2020-new-faqs-address-healthcare-workers-questions-on-breastfeeding-and-covid-19).

Monitoring Parameters

COVID-19: ALT/AST, neutrophils, platelets (per current standard clinical practice); signs and symptoms of demyelinating disorders and new infections.

Chronic therapy: Latent TB screening prior to therapy initiation (all patients); neutrophils, platelets (prior to therapy, 4 to 8 weeks after start of therapy, and every 3 months thereafter [rheumatoid arthritis {RA}, giant cell arteritis {GCA}, systemic sclerosis (scleroderma)-associated interstitial lung disease {SSC-ILD}]); ALT/AST, alkaline phosphatase, and total bilirubin (prior to therapy, every 4 to 8 weeks after start of therapy for the first 6 months, and every 3 months thereafter [RA, GCA, SSc-ILD]); neutrophils, platelets, ALT/AST (prior to therapy, at second administration, and every 2 to 4 weeks [systemic juvenile idiopathic arthritis] or 4 to 8 weeks [polyarticular juvenile idiopathic arthritis] thereafter); additional liver function tests (eg, bilirubin) as clinically indicated; lipid panel (prior to and 4 to 8 weeks following initiation of therapy, then subsequently according to current guidelines); monitor all patients for signs and symptoms of infection (prior to, during, and after therapy); signs and symptoms of CNS demyelinating disorders; new onset abdominal symptoms.

Mechanism of Action

Tocilizumab is an antagonist of the interleukin-6 (IL-6) receptor. Endogenous IL-6 is induced by inflammatory stimuli and mediates a variety of immunological responses. Inhibition of IL-6 receptors by tocilizumab leads to a reduction in cytokine and acute phase reactant production.

Pharmacokinetics (Adult Data Unless Noted)

Onset (cytokine release syndrome [CRS]): Median time to defervescence: 4 hours (Fitzgerald 2017); Fever and hypotension often resolve within a few hours (Lee 2014); Blood pressure stabilization: 1 to 3 days (Abboud 2016; Maude 2014b). A median of 1 dose (range: 1 to 4) was required for management of CRS due to chimeric antigen receptor T-cell therapy.

Distribution: Vdss: Children and Adolescents: Systemic juvenile idiopathic arthritis (SJIA): 4.01 L; Polyarticular juvenile idiopathic arthritis (PJIA): 4.08 L; Adults: Rheumatoid arthritis (RA): 6.4 L; Giant cell arteritis (GCA): 7.46 L; Systemic sclerosis (scleroderma)-associated interstitial lung disease (SSc-ILD): 6.74 L.

Bioavailability: SUBQ: 80% (GCA, RA, SSc-ILD); 95% (SJIA); 96% (PJIA).

Half-life elimination:

IV: Concentration dependent: Steady state: Children and Adolescents: SJIA: Up to 16 days; PJIA: Up to 17 days; Adults: RA: Up to 11 to 13 days; GCA: 13.2 days.

SUBQ: Concentration dependent: Children and Adolescents: SJIA: Up to 14 days; PJIA: Up to 10 days; Adults: RA: Up to 5 days (every-other-week dosing) or up to 13 days (every-week dosing); GCA: 4.2 to 7.9 days (every other week dosing) or 18.3 to 18.9 days (every-week dosing); SSc-ILD: 12.1 to 13 days (every-week dosing).

Time to peak: SUBQ: ~3 days (for every-week dosing); ~4.5 days (for every-2-week dosing).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Body weight:

Rheumatoid arthritis: For IV administration, the body weight-based dose (8 mg/kg) resulted in ~86% higher exposure in patients who weighed >100 kg in comparison with patients who weighed <60 kg.

Giant cell arteritis: Higher exposure was observed in patients with lower body weight. For the 162 mg SUBQ every week dosing regimen, the steady-state Cavg was 51% higher in patients with body weight <60 kg compared with patients weighing between 60 to 100 kg. For the 162 mg SUBQ every-other-week regimen, the steady-state Cavg was 129% higher in patients with body weight <60 kg compared with patients weighing between 60 to 100 kg.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Actemra;
  • (AR) Argentina: Actemra;
  • (AT) Austria: Roactemra;
  • (AU) Australia: Actemra | Roactemra;
  • (BE) Belgium: Roactemra;
  • (BG) Bulgaria: Roactemra;
  • (BR) Brazil: Actemra | Roactemra;
  • (CH) Switzerland: Actemra;
  • (CL) Chile: Actemra;
  • (CO) Colombia: Actemra;
  • (CZ) Czech Republic: Roactemra;
  • (DE) Germany: Roactemra | Tyenne;
  • (DO) Dominican Republic: Actemra;
  • (EC) Ecuador: Actemra;
  • (EE) Estonia: Roactemra;
  • (EG) Egypt: Actemra;
  • (ES) Spain: Roactemra;
  • (FI) Finland: Roactemra;
  • (FR) France: Roactemra;
  • (GB) United Kingdom: Roactemra;
  • (GR) Greece: Roactemra;
  • (HK) Hong Kong: Actemra;
  • (HR) Croatia: Roactemra;
  • (HU) Hungary: Roactemra;
  • (ID) Indonesia: Actemra;
  • (IE) Ireland: Roactemra;
  • (IN) India: Actemra | Tocira;
  • (IT) Italy: Roactemra;
  • (JO) Jordan: Actemra;
  • (JP) Japan: Actemra;
  • (KE) Kenya: Actemra;
  • (KR) Korea, Republic of: Actemra;
  • (KW) Kuwait: Actemra;
  • (LB) Lebanon: Actemra;
  • (LT) Lithuania: Roactemra;
  • (LU) Luxembourg: Roactemra;
  • (LV) Latvia: Roactemra;
  • (MA) Morocco: Actemra;
  • (MX) Mexico: Roactemra | Roactemra sc;
  • (MY) Malaysia: Actemra;
  • (NL) Netherlands: Roactemra;
  • (NO) Norway: Roactemra;
  • (NZ) New Zealand: Actemra;
  • (PE) Peru: Actemra | Roactemra;
  • (PH) Philippines: Actemra;
  • (PK) Pakistan: Actemra;
  • (PL) Poland: Roactemra;
  • (PR) Puerto Rico: Actemra;
  • (PT) Portugal: Roactemra;
  • (PY) Paraguay: Actemra;
  • (QA) Qatar: Actemra;
  • (RO) Romania: Roactemra;
  • (RU) Russian Federation: Actemra;
  • (SA) Saudi Arabia: Actemra;
  • (SE) Sweden: Roactemra;
  • (SG) Singapore: Actemra;
  • (SI) Slovenia: Roactemra;
  • (SK) Slovakia: Roactemra;
  • (TH) Thailand: Actemra;
  • (TN) Tunisia: Actemra;
  • (TR) Turkey: Actemra;
  • (TW) Taiwan: Actemra;
  • (UA) Ukraine: Actemra;
  • (UY) Uruguay: Actemra;
  • (ZA) South Africa: Actemra
  1. Abboud R, Keller J, Slade M, et al. Severe cytokine-release syndrome after T cell-replete peripheral blood haploidentical donor transplantation is associated with poor survival and anti-IL-6 therapy is safe and well tolerated. Biol Blood Marrow Transplant. 2016;22(10):1851-1860. [PubMed 27318038]
  2. Actemra (tocilizumab) [prescribing information]. South San Francisco, CA: Genentech Inc; December 2022.
  3. Actemra (tocilizumab) [product monograph]. Mississauga, Ontario, Canada: Hoffman-La Roche Limited; October 2022.
  4. Akira T, Shimazu Y, Hashimoto N, et al. Successful pregnancy outcome in a patient with juvenile idiopathic arthritis in adulthood, amyloid A amyloidosis, and chronic kidney disease using tocilizumab with strict blood pressure control. Intern Med. Published online Sep 29, 2023. doi:10.2169/internalmedicine.1951-23 [PubMed 37779073]
  5. Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  6. Alfreijat M, Habibi M, Bhatia P, Bhatia A. Severe hepatitis associated with tocilizumab in a patient with rheumatoid arthritis. Rheumatology (Oxford). 2013;52(7):1340-1341. doi:10.1093/rheumatology/kes397 [PubMed 23315786]
  7. American College of Obstetricians and Gynecologists (ACOG). COVID-19 FAQs for obstetricians-gynecologists, obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed December 4, 2023.
  8. Anger F, Wiegering A, Wagner J, et al. Toxic drug-induced liver failure during therapy of rheumatoid arthritis with tocilizumab subcutaneously: a case report. Rheumatology (Oxford). 2017;56(9):1628-1629. doi:10.1093/rheumatology/kex221 [PubMed 28575416]
  9. Barbulescu A, Delcoigne B, Askling J, Frisell T. Gastrointestinal perforations in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs in Sweden: a nationwide cohort study. RMD Open. 2020;6(2):e001201. doi:10.1136/rmdopen-2020-001201 [PubMed 32669452]
  10. Barrett DM, Teachey DT, Grupp SA. Toxicity management for patients receiving novel T-cell engaging therapies. Curr Opin Pediatr. 2014;26(1):43-49. [PubMed 24362408]
  11. Beauchemin P, Carruthers R. MS arising during tocilizumab therapy for rheumatoid arthritis. Mult Scler. 2016;22(2):254-256. doi:10.1177/1352458515623862 [PubMed 26743640]
  12. Ben Said B, Gerfaud-Valentin M, Seve P. Fatal DRESS syndrome under tocilizumab treatment for seronegative polyarthritis. J Allergy Clin Immunol Pract. 2018;6(3):1048-1049. doi:10.1016/j.jaip.2017.08.041 [PubMed 29126664]
  13. Bhimraj A, Morga RL, Snumaker AH, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. https://www.idsociety.org/COVID19guidelines. Updated May 15, 2023. Accessed May 18, 2023.
  14. Boonpheng B, De Castro ICC, Ng YH, et al. Tocilizumab for treatment of chronic active antibody-mediated rejection in kidney transplant recipients. Clin Transplant. 2023;37(5):e14936. doi:10.1111/ctr.14936 [PubMed 36787372]
  15. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
  16. Burmester GR, Choy E, Kivitz A, et al. Low immunogenicity of tocilizumab in patients with rheumatoid arthritis. Ann Rheum Dis. 2017;76(6):1078-1085. doi:10.1136/annrheumdis-2016-210297 [PubMed 28007755]
  17. Campbell L, Chen C, Bhagat SS, Parker RA, Östör AJ. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford). 2011;50(3):552-562. doi:10.1093/rheumatology/keq343 [PubMed 21078627]
  18. Cansever M, Şahin N, Dursun I, et al Successful slow desensitization to tocilizumab in a 15-year-old patient. J Investig Allergol Clin Immunol. 2018;28(6):436-438. doi:10.18176/jiaci.0314 [PubMed 30530397]
  19. Centers for Disease Control and Prevention (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm. [PubMed 6423951]
  20. China National Health Commission. Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th edition). Published March 4, 2020. Accessed March 23, 2020. http://kjfy.meetingchina.org/msite/news/show/cn/3337.html
  21. Choi J, Aubert O, Vo A, et al. Assessment of tocilizumab (anti-interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients. Am J Transplant. 2017;17(9):2381-2389. doi:10.1111/ajt.14228 [PubMed 28199785]
  22. Clements T, Rice TF, Vamvakas G, et al. Update on transplacental transfer of IgG subclasses: impact of maternal and fetal factors. Front Immunol. 2020;11:1920. doi:10.3389/fimmu.2020.01920 [PubMed 33013843]
  23. Cortellini G, Mascella F, Simoncelli M, et al. Effective desensitization to tocilizumab in delayed hypersensitivity reaction. Pharmacology. 2018;102(1-2):114-116. doi:10.1159/000490419 [PubMed 29953985]
  24. Curtis JR, Xie F, Chen L, et al. The incidence of gastrointestinal perforations among rheumatoid arthritis patients. Arthritis Rheum. 2011;63(2):346-351. doi:10.1002/art.30107 [PubMed 20967860]
  25. Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(10):1843-1847. doi:10.1136/annrheumdis-2016-209131 [PubMed 27113415]
  26. Dalkilic E, Coskun BN, Yağız B, Pehlivan Y. A successful pregnancy in a patient with Takayasu's arteritis under tocilizumab treatment: A longitudinal case study. Int J Rheum Dis. 2019;22(10):1941-1944. doi:10.1111/1756-185X.13687 [PubMed 31482664]
  27. Davies HD, Committee on Infectious Diseases. Infectious complications with the use of biologic response modifiers in infants and children. Pediatrics. 2016;138(2);e20161209. [PubMed 27432853]
  28. Dernoncourt A, Liabeuf S, Bennis Y, et al. Fetal and neonatal adverse drug reactions associated with biologics taken during pregnancy by women with autoimmune diseases: insights from an analysis of the World Health Organization Pharmacovigilance Database (VigiBase®). BioDrugs. 2023;37(1):73-87. doi:10.1007/s40259-022-00564-4 [PubMed 36401769]
  29. DeWitt EM, Kimura Y, Beukelman T, et al. Consensus Treatment Plans for New-Onset Systemic Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken). 2012;64(7):1001-1010. [PubMed 22290637]
  30. Emery P, Keystone E, Tony HP, et al. IL-6 Receptor Inhibition With Tocilizumab Improves Treatment Outcomes in Patients With Rheumatoid Arthritis Refractory to Anti-Tumour Necrosis Factor Biologicals: Results from a 24-Week Multicentre Randomised Placebo-Controlled Trial. Ann Rheum Dis. 2008;67(11):1516-1523. [PubMed 18625622]
  31. Erdogan T, Yasar Bilge NS, Kasifoglu T. Successful slow tocilizumab desensitization in a patient with adult onset Still disease. Biologicals. 2018;55:17-18. doi:10.1016/j.biologicals.2018.07.002 [PubMed 30017556]
  32. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  33. Finet A, Amini-Adle M, Balme B, Colson F, Thomas L. Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cause or coincidence? Clin Rheumatol. 2013;32(2):277-280. doi:10.1007/s10067-012-2114-1 [PubMed 23138884]
  34. Fitzgerald JC, Weiss SL, Maude SL, et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med. 2017;45(2):e124-e131. [PubMed 27632680]
  35. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939. doi:10.1002/acr.24596 [PubMed 34101387]
  36. Galvão VR, Castells MC. Hypersensitivity to biological agents-updated diagnosis, management, and treatment. J Allergy Clin Immunol Pract. 2015;3(2):175-185. doi:10.1016/j.jaip.2014.12.006 [PubMed 25754718]
  37. Genentech Inc. Actemra use in coronavirus disease 2019 (COVID-19) [press release]. South San Francisco, CA: Genentech, a member of the Roche Group; March 18, 2020.
  38. Genentech manufacturer communication. Actemra Prefilled Syringe for Intravenous Infusion. April 3, 2020. Data on file.
  39. Genovese MC, Kremer JM, van Vollenhoven RF, et al. Transaminase levels and hepatic events during tocilizumab treatment: pooled analysis of long-term clinical trial safety data in rheumatoid arthritis. Arthritis Rheumatol. 2017;69(9):1751-1761. [PubMed 28597609]
  40. Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 Receptor Inhibition With Tocilizumab Reduces Disease Activity in Rheumatoid Arthritis With Inadequate Response to Disease-Modifying Antirheumatic Drugs: The Tocilizumab in Combination With Traditional Disease-Modifying Antirheumatic Drug Therapy Study. Arthritis Rheum. 2008;58(10):2968-2980. [PubMed 18821691]
  41. Ghalandari N, Crijns HJMJ, Bergman JEH, Dolhain RJEM, van Puijenbroek EP, Hazes JMW. Reported congenital malformations after exposure to non-tumour necrosis factor inhibitor biologics: a retrospective comparative study in EudraVigilance. Br J Clin Pharmacol. 2022;88(12):5378-5388. doi:10.1111/bcp.15471 [PubMed 35894810]
  42. Glisson CC. Neuromyelitis optica spectrum disorders (NMOSD): treatment and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 11, 2022.
  43. Goodman SM, Springer BD, Chen AF, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. Arthritis Care Res (Hoboken). 2022;74(9):1399-1408. doi:10.1002/acr.24893 [PubMed 35718887]
  44. Gordon AC, Mouncey PR, Al-Beidh F; REMAP-CAP Investigators. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med. Published online February 25, 2021. doi:10.1056/NEJMoa2100433 [PubMed 33631065]
  45. Grasland A, Mahé E, Raynaud E, Mahé I. Psoriasis onset with tocilizumab. Joint Bone Spine. 2013;80(5):541-542. doi:10.1016/j.jbspin.2013.03.014 [PubMed 23731639]
  46. Grøn KL, Arkema EV, Glintborg B, et al. Risk of serious infections in patients with rheumatoid arthritis treated in routine care with abatacept, rituximab and tocilizumab in Denmark and Sweden. Ann Rheum Dis. 2019;78(3):320-327. doi:10.1136/annrheumdis-2018-214326 [PubMed 30612115]
  47. Healthy Canadians Recalls & Alerts. Important safety information on ACTEMRA (tocilizumab) – risk of fatal anaphylaxis - for health professionals. Health Canada website. https://recalls-rappels.canada.ca/en/alert-recall/actemra-tocilizumab-risk-fatal-anaphylaxis-health-professionals. Published September 13, 2010. Accessed September 9, 2022. [PubMed HealthCanada.1]
  48. Healthy Canadians Recalls & Alerts. Important safety information on ACTEMRA (tocilizumab) – risk of hepatoxicity. Health Canada website. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/69991a-eng.php. Published May 21, 2019. Accessed May 28, 2019. [PubMed HealthCanada.2]
  49. Hoeltzenbein M, Beck E, Rajwanshi R, et al. Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data. Semin Arthritis Rheum. 2016;46(2):238-245. doi:10.1016/j.semarthrit.2016.05.004 [PubMed 27346577]
  50. Imagawa T, Yokota S, Mori M, et al. Safety and Efficacy of Tocilizumab, an Anti-IL-6-Receptor Monoclonal Antibody, in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis. Mod Rheumatol. 2012;22(1):109-115. [PubMed 21667343]
  51. Imaizumi C, Saito M, Abe F, et al. Adult-onset Still's disease during pregnancy treated with tocilizumab. Intern Med. 2022;61(20):3137-3140. doi:10.2169/internalmedicine.8886-21 [PubMed 35283384]
  52. Isaac B, Hazari K, Harb DK, et al. Maternal and fetal outcome in pregnant women with critical COVID-19 treated with tocilizumab in a tertiary care hospital in Dubai. Cureus. 2023;15(1):e34395. doi:10.7759/cureus.34395 [PubMed 36874696]
  53. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. [PubMed 12534540]
  54. Jones G, Sebba A, Gu J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010;69(1):88-96. doi:10.1136/ard.2008.105197 [PubMed 19297346]
  55. Jorgensen SCJ, Lapinsky SE. Tocilizumab for coronavirus disease 2019 in pregnancy and lactation: a narrative review. Clin Microbiol Infect. 2022;28(1):51-57. doi:10.1016/j.cmi.2021.08.016 [PubMed 34438068]
  56. Jouve T, Daligault M, Noble J, et al. Tocilizumab evaluation in HLA-desensitization before kidney transplantation as an add-on therapy to apheresis: the TETRA study. J Clin Med. 2023;12(2):424. doi:10.3390/jcm12020424 [PubMed 36675353]
  57. Jouve T, Laheurte C, Noble J, et al. Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates. Am J Transplant. 2022;22(1):71-84. doi:10.1111/ajt.16709 [PubMed 34080291]
  58. Justet A, Neukirch C, Poubeau P, et al. Successful rapid tocilizumab desensitization in a patient with Still disease. J Allergy Clin Immunol Pract. 2014;2(5):631-632. doi:10.1016/j.jaip.2014.04.015 [PubMed 25213064]
  59. Kamath A, Acharya SD, Rao RR, Ullal SD. Assessment of pancreatitis associated with tocilizumab use using the United States Food and Drug Administration Adverse Event Reporting System database. Sci Rep. 2021;11(1):18818. doi:10.1038/s41598-021-98325-w [PubMed 34552181]
  60. Khairallah P, Robbins-Juarez S, Patel S, et al. Tocilizumab for the treatment of chronic antibody mediated rejection in kidney transplant recipients. Clin Transplant. 2023;37(1):e14853. doi:10.1111/ctr.14853 [PubMed 36398915]
  61. Khan B, David T, Sussman J, et al. A successful antenatal outcome in a patient with refractory Takayasu's arteritis treated with tocilizumab throughout pregnancy-a case report. Oxf Med Case Reports. 2023;2023(5):omad046. doi:10.1093/omcr/omad046 [PubMed 37260724]
  62. Khanna D, Lin CJF, Furst DE, et al; focuSSced Investigators. Tocilizumab in systemic sclerosis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2020;8(10):963-974. doi:10.1016/S2213-2600(20)30318-0 [PubMed 32866440]
  63. Kim AY, Gandhi RT. COVID-19: management in hospitalized adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 9, 2022.
  64. Koike T, Harigai M, Inokuma S, et al. Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with rheumatoid arthritis in Japan. J Rheumatol. 2014;41(1):15-23. doi:10.3899/jrheum.130466 [PubMed 24187110]
  65. Koike T, Harigai M, Inokuma S, et al. Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann Rheum Dis. 2011;70(12):2148-2151. doi:10.1136/ard.2011.151092 [PubMed 21852254]
  66. Konagai N, Kamiya CA, Nakanishi A, et al. Safe use of tocilizumab in pregnant women with Takayasu arteritis: three case studies. RMD Open. 2023;9(1):e002996. doi:10.1136/rmdopen-2023-002996 [PubMed 36754550]
  67. Kourbeti IS, Ziakas PD, Mylonakis E. Biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis. Clin Infect Dis. 2014;58(12):1649-1657. doi:10.1093/cid/ciu185. [PubMed 24647016]
  68. Kumar G, Adams A, Hererra M, et al. Predictors and outcomes of healthcare-associated infections in COVID-19 patients. Int J Infect Dis. 2021;104:287-292. doi:10.1016/j.ijid.2020.11.135 [PubMed 33207271]
  69. Lavacca A, Presta R, Gai C, et al. Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation. Clin Transplant. 2020;34(8):e13908. doi:10.1111/ctr.13908 [PubMed 32415711]
  70. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195. [PubMed 24876563]
  71. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  72. Ludwig H, Terpos E, van de Donk N, et al. Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Lancet Oncol. 2023;24(6):e255-e269. doi:10.1016/S1470-2045(23)00159-6 [PubMed 37269857]
  73. Maini RN, Taylor PC, Szechinski J, et al. Double-Blind Randomized Controlled Clinical Trial of the Interleukin-6 Receptor Antagonist, Tocilizumab, in European Patients With Rheumatoid Arthritis Who had an Incomplete Response to Methotrexate. Arthritis Rheum. 2006;54(9):2817-2829. [PubMed 16947782]
  74. Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014a;20(2):119-122. [PubMed 24667956]
  75. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014b;371(16):1507-1517. [PubMed 25317870]
  76. Maus MV, Alexander S, Bishop MR, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events. J Immunother Cancer. 2020;8(2):e001511. doi:10.1136/jitc-2020-001511 [PubMed 33335028]
  77. Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021;73(8):1349-1365. doi:10.1002/art.41774 [PubMed 34235884]
  78. Moots RJ, Sebba A, Rigby W, et al. Effect of tocilizumab on neutrophils in adult patients with rheumatoid arthritis: pooled analysis of data from phase 3 and 4 clinical trials. Rheumatology (Oxford). 2017;56(4):541-549. doi:10.1093/rheumatology/kew370 [PubMed 28013198]
  79. Moriyama M, Wada Y, Minamoto T, Kondo M, Honda M, Murakawa Y. Unexpectedly lower proportion of placental transferred tocilizumab relative to whole immunoglobulin G: a case report. Scand J Rheumatol. 2020;49(2):165-166. doi:10.1080/03009742.2019.1639821 [PubMed 31436129]
  80. Nakajima K, Watanabe O, Mochizuki M, Nakasone A, Ishizuka N, Murashima A. Pregnancy outcomes after exposure to tocilizumab: a retrospective analysis of 61 patients in Japan. Mod Rheumatol. 2016;26(5):667-671. doi:10.3109/14397595.2016.1147405 [PubMed 26873562]
  81. Nam SH, Lim DH, Heo HM, et al. Anaphylaxis to tocilizumab in patients with rheumatic disease. Immunotherapy. 2021;13(18):1483-1489. doi:10.2217/imt-2020-0307 [PubMed 34657472]
  82. National Institute for Health and Care Excellence. Drug allergy: diagnosis and management. Published September 3, 2014. Accessed October 23, 2020. https://www.nice.org.uk/guidance/cg183
  83. National Institutes of Health (NIH). COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. https://www.covid19treatmentguidelines.nih.gov/. Updated August 8, 2022. Accessed August 9, 2022.
  84. National Institutes of Health (NIH). COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. https://www.covid19treatmentguidelines.nih.gov/. Updated April 20, 2023. Accessed May 15, 2023.
  85. Nishimoto N, Hashimoto J, Miyasaka N, et al. Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, and IL-6 Inhibitor (SAMURAI): Evidence of Clinical and Radiographic Benefit from an X-Ray Reader-Blinded Randomised Controlled Trial of Tocilizumab. Ann Rheum Dis. 2007;66(9):1162-1167. [PubMed 17485422]
  86. Nishimoto N, Miyasaka N, Yamamoto K, et al. Long-Term Safety and Efficacy of Tocilizumab, an Anti-IL-6 Receptor Monoclonal Antibody, in Monotherapy, in Patients With Rheumatoid Arthritis (the STREAM study): Evidence of Safety and Efficacy in a 5-Year Extension Study. Ann Rheum Dis. 2009;68(10):1580-1584. [PubMed 19019888]
  87. Nishimoto N, Miyasaka N, Yamamoto K, et al. Study of Active Controlled Tocilizumab Monotherapy for Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate (SATORI): Significant Reduction in Disease Activity and Serum Vascular Endothelial Growth Factor by IL-6 Receptor Inhibition Therapy. Mod Rheum. 2009;19(1):12-19. [PubMed 18979150]
  88. Noble J, Giovannini D, Laamech R, et al. Tocilizumab in the treatment of chronic antibody-mediated rejection post kidney transplantation: clinical and histological monitoring. Front Med (Lausanne). 2021;8:790547. doi:10.3389/fmed.2021.790547 [PubMed 35004757]
  89. Ogata A, Kato Y, Higa S, Yoshizaki K. IL-6 inhibitor for the treatment of rheumatoid arthritis: a comprehensive review. Mod Rheumatol. 2019;29(2):258-267. doi:10.1080/14397595.2018.1546357 [PubMed 30427250]
  90. Ohkubo A, Osoegawa T, Harada N, et al. A rare case of rheumatoid arthritis with tocilizumab-induced intestinal mucosal injury. Intern Med. 2022;61(7):1011-1014. doi:10.2169/internalmedicine.8031-21 [PubMed 34544951]
  91. Oldfield V, Dhillon S, Plosker GL. Tocilizumab: A Review of its Use in the Management of Rheumatoid Arthritis. Drugs. 2009;69(5):609-632. [PubMed 19368420]
  92. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. [PubMed 22235228]
  93. Pardeo M, Wang J, Ruperto N, et al. Neutropenia during tocilizumab treatment is not associated with infection risk in systemic or polyarticular-course juvenile idiopathic arthritis. J Rheumatol. 2019;46(9):1117-1126. doi:10.3899/jrheum.180795 [PubMed 30824645]
  94. Park EH, Lee EY, Shin K, Kim HA. Tocilizumab-induced anaphylaxis in patients with adult-onset Still's disease and systemic juvenile idiopathic arthritis: a case-based review. Rheumatol Int. 2020;40(5):791-798. doi:10.1007/s00296-019-04456-9 [PubMed 31598752]
  95. Pawar A, Desai RJ, Solomon DH, et al. Risk of serious infections in tocilizumab versus other biologic drugs in patients with rheumatoid arthritis: a multidatabase cohort study. Ann Rheum Dis. 2019;78(4):456-464. doi:10.1136/annrheumdis-2018-214367 [PubMed 30679153]
  96. Péju E, Belicard F, Silva S, et al; COVIDPREG Study Group. Management and outcomes of pregnant women admitted to intensive care unit for severe pneumonia related to SARS-CoV-2 infection: the multicenter and international COVIDPREG study. Intensive Care Med. 2022;48(9):1185-1196. doi:10.1007/s00134-022-06833-8 [PubMed 35978137]
  97. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
  98. Pfeil J, Grulich-Henn J, Wenning D, Breil T, Günther P, Lutz T. Multiple upper gastrointestinal perforations in a 15-year-old patient treated with tocilizumab. Rheumatology (Oxford). 2014;53(9):1713-1714. doi: 10.1093/rheumatology/keu032 [PubMed 24625503]
  99. Picard M, Galvão VR. Current knowledge and management of hypersensitivity reactions to monoclonal antibodies. J Allergy Clin Immunol Pract. 2017;5(3):600-609. doi:10.1016/j.jaip.2016.12.001 [PubMed 28110056]
  100. Plushner SL. Tocilizumab: An Interleukin-6 Receptor Inhibitor for the Treatment of Rheumatoid Arthritis. Ann Pharmacother. 2008;429(11):1660-1668. [PubMed 18957621]
  101. Porter DL, Maloney DG. Cytokine release syndrome (CRS). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 10, 2024.
  102. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-1645. doi:10.1016/S0140-6736(21)00676-0 [PubMed 33933206]
  103. Refer to manufacturer's labeling.
  104. Rempenault C, Lukas C, Combe B, et al. Risk of diverticulitis and gastrointestinal perforation in rheumatoid arthritis treated with tocilizumab compared to rituximab or abatacept. Rheumatology (Oxford). 2022;61(3):953-962. doi:10.1093/rheumatology/keab438 [PubMed 33993216]
  105. Ringold S, Weiss PF, Beukelman T, et al. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013;65(10):2499-2512. [PubMed 24092554]
  106. Rocchi V, Puxeddu I, Cataldo G, et al. Hypersensitivity reactions to tocilizumab: role of skin tests in diagnosis. Rheumatology (Oxford). 2014;53(8):1527-1529. doi:10.1093/rheumatology/keu181 [PubMed 24899663]
  107. Roofeh D, Lin CJF, Goldin J, et al; focuSSced Investigators. Tocilizumab prevents progression of early systemic sclerosis-associated interstitial lung disease. Arthritis Rheumatol. 2021;73(7):1301-1310. doi:10.1002/art.41668 [PubMed 33538094]
  108. Rosas IO, Bräu N, Waters M, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med. Published online February 25, 2021. doi:10.1056/NEJMoa2028700 [PubMed 33631066]
  109. Saito J, Yakuwa N, Kaneko K, et al. Clinical application of the dried milk spot method for measuring tocilizumab concentrations in the breast milk of patients with rheumatoid arthritis. Int J Rheum Dis. 2019b;22(6):1130-1137. doi:10.1111/1756-185X.13557 [PubMed 30968569]
  110. Saito J, Yakuwa N, Takai C, et al. Tocilizumab concentrations in maternal serum and breast milk during breastfeeding and a safety assessment in infants: a case study. Rheumatology (Oxford). 2018;57(8):1499-1501. doi:10.1093/rheumatology/key091 [PubMed 29635528]
  111. Saito J, Yakuwa N, Kaneko K, et al. Tocilizumab drug levels during pregnancy and lactation: a woman who discontinued tocilizumab therapy until the end of the first trimester and resumed it after birth. Obstet Med. 2021;14(4):260-262. doi:10.1177/1753495X20966094 [PubMed 34880942]
  112. Saito J, Yakuwa N, Kaneko K, et al. Tocilizumab during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk and infant serum. Rheumatology (Oxford). 2019a;58(8):1505-1507. doi:10.1093/rheumatology/kez100 [PubMed 30945743]
  113. Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med. 2021;384(1):20-30. doi:10.1056/NEJMoa2030340 [PubMed 33332779]
  114. Salmon JH, Perotin JM, Morel J, et al. Serious infusion-related reaction after rituximab, abatacept and tocilizumab in rheumatoid arthritis: prospective registry data. Rheumatology (Oxford). 2018;57(1):134-139. doi:10.1093/rheumatology/kex403 [PubMed 29069471]
  115. Salvarani C, Muratore F. Treatment of giant cell arteritis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2022.
  116. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529-556. doi:10.1002/art.41191 [PubMed 32090480]
  117. Santomasso BD, Nastoupil LJ, Adkins S, et al. Management of immune-related adverse events in patients treated with chimeric antigen receptor T-cell therapy: ASCO guideline. J Clin Oncol. 2021;39(35):3978-3992. doi:10.1200/JCO.21.01992 [PubMed 34724386]
  118. Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi:10.1186/s13601-015-0073-8 [PubMed 26339470]
  119. Sethi S, Peng A, Najjar R, Vo A, Jordan SC, Huang E. Infectious complications in tocilizumab-treated kidney transplant recipients. Transplantation. 2021;105(8):1818-1824. doi:10.1097/TP.0000000000003512 [PubMed 33534530]
  120. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313. [PubMed 7746084]
  121. Shin BH, Everly MJ, Zhang H, et al. Impact of tocilizumab (anti-IL-6R) treatment on immunoglobulins and anti-HLA antibodies in kidney transplant patients with chronic antibody-mediated rejection. Transplantation. 2020;104(4):856-863. doi:10.1097/TP.0000000000002895 [PubMed 31385933]
  122. Shovman O, Shoenfeld Y, Langevitz P. Tocilizumab-induced neutropenia in rheumatoid arthritis patients with previous history of neutropenia: case series and review of literature. Immunol Res. 2015;61(1-2):164-168. doi:10.1007/s12026-014-8590-4 [PubMed 25403696]
  123. Singh JA, Furst DE, Bharat A, et al. 2012 Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease-Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639. [PubMed 22473917]
  124. Smolen JS, Beaulieu A, Rubbert-Roth A, et al; OPTION Investigators. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987-997. [PubMed 18358926]
  125. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-977. doi:10.1136/annrheumdis-2016-210715 [PubMed 28264816]
  126. Soyer O, Demir S, Bilginer Y, et al. Severe hypersensitivity reactions to biological drugs in children with rheumatic diseases. Pediatr Allergy Immunol. 2019;30(8):833-840. doi:10.1111/pai.13114 [PubMed 31419311]
  127. Strangfeld A, Richter A, Siegmund B, et al. Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. Ann Rheum Dis. 2017;76(3):504-510. doi:10.1136/annrheumdis-2016-209773 [PubMed 27405509]
  128. Stone JH, Spotswood H, Unizony SH, et al. New-onset versus relapsing giant cell arteritis treated with tocilizumab: 3-year results from a randomized controlled trial and extension. Rheumatology (Oxford). Published online October 29, 2021. doi:10.1093/rheumatology/keab780 [PubMed 34718434]
  129. Stone JH, Tuckwell K, Dimonaco S, et al. Trial of tocilizumab in giant-cell arteritis. N Engl J Med. 2017;377(4):317-328. doi:10.1056/NEJMoa1613849 [PubMed 28745999]
  130. Streetz KL, Luedde T, Manns MP, Trautwein C. Interleukin 6 and liver regeneration. Gut. 2000;47(2):309-312. doi:10.1136/gut.47.2.309 [PubMed 10896929]
  131. Sugisaki K, Sakauchi M. Tocilizumab treatment for Takayasu arteritis in pregnancy: a case report with positive maternal and neonatal outcomes. J Med Cases. 2023;14(4):118-123. doi:10.14740/jmc4083 [PubMed 37188300]
  132. Suwa T, Hogg JC, English D, Van Eeden SF. Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow. Am J Physiol Heart Circ Physiol. 2000;279(6):H2954-2960. doi:10.1152/ajpheart.2000.279.6.H2954 [PubMed 11087252]
  133. Tada Y, Sakai M, Nakao Y, Maruyama A, Ono N, Koarada S. Placental transfer of tocilizumab in a patient with rheumatoid arthritis. Rheumatology (Oxford). 2019;58(9):1694-1695. doi:10.1093/rheumatology/kez155 [PubMed 31329987]
  134. Teachey DT, Rheingold SR, Maude SL, et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 2013;121(26):5154-5157. [PubMed 23678006]
  135. Teoh Z, Danziger-Isakov L, Courter JD, et al. Tocilizumab for treatment of children and young adults with severe acute COVID-19: experience at a quaternary-care children's hospital. Pediatr Infect Dis J. 2023;42(2):119-121. doi:10.1097/INF.0000000000003763 [PubMed 36638396]
  136. Tétu P, Hamelin A, Moguelet P, Barbaud A, Soria A. Management of hypersensitivity reactions to Tocilizumab. Clin Exp Allergy. 2018;48(6):749-752. doi:10.1111/cea.13142 [PubMed 29603809]
  137. Tofidence (tocilizumab-bavi) [product information]. Cambridge, MA: Biogen MA Inc; September 2023.
  138. Tyenne (tocilizumab-aazg) [product information]. Lake Zurich, IL: Fresenius Kabi USA LLC; March 2024.
  139. US Food and Drug Administration (FDA). Fact sheet for healthcare providers emergency use authorization (EUA) for Actemra (tocilizumab). https://www.fda.gov/media/150321/download. Published June 24, 2021. Accessed June 25, 2021.
  140. US Food and Drug Administration (FDA). Fact sheet for healthcare providers emergency use authorization (EUA) for Actemra (tocilizumab). https://www.fda.gov/media/150321/download. Updated December 21, 2022. Accessed January 31, 2023.
  141. Varga J, Montesi S. Treatment and prognosis of interstitial lung disease in systemic sclerosis (scleroderma). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 11, 2022.
  142. Venkateswaran N, Khianey R, Generoso A. Stevens Johnson Syndrome in a patient with giant cell arteritis during short term tocilizumab therapy. Cureus. 2020;12(4):e7662. doi:10.7759/cureus.7662 [PubMed 32411563]
  143. Vikse J, Henry BM. Tocilizumab in COVID-19: beware the risk of intestinal perforation. Int J Antimicrob Agents. 2020;56(1):106009. doi:10.1016/j.ijantimicag.2020.106009 [PubMed 32389721]
  144. Villiger PM, Adler S, Kuchen S, et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10031):1921-1927. doi:10.1016/S0140-6736(16)00560-2 [PubMed 26952547]
  145. Vo AA, Choi J, Kim I, et al. A phase I/II trial of the interleukin-6 receptor-specific humanized monoclonal (tocilizumab) + intravenous immunoglobulin in difficult to desensitize patients. Transplantation. 2015;99(11):2356-2363. doi:10.1097/TP.0000000000000741 [PubMed 26018350]
  146. Wu CP, Hsieh CW, Chen DY, Lee BJ, Yang CS. Tocilizumab-associated cutaneous reactive endotheliomatosis in a patient with rheumatoid arthritis. Joint Bone Spine. 2015;82(2):132-134. doi:10.1016/j.jbspin.2014.04.004 [PubMed 25553831]
  147. Xie F, Yun H, Bernatsky S, Curtis JR. Brief report: risk of gastrointestinal perforation among rheumatoid arthritis patients receiving tofacitinib, tocilizumab, or other biologic treatments. Arthritis Rheumatol. 2016;68(11):2612-2617. doi:10.1002/art.39761 [PubMed 27213279]
  148. Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. http://www.chinaxiv.org/user/download.htm?id=30387&filetype=pdf. Updated March 2020. Accessed March 23, 2020.
  149. Yasuoka R, Iwata N, Abe N, et al. Risk factors for hypersensitivity reactions to tocilizumab introduction in systemic juvenile idiopathic arthritis. Mod Rheumatol. 2019;29(2):324-327. doi:10.1080/14397595.2018.1457490 [PubMed 29578355]
  150. Yoshiki R, Nakamura M, Tokura Y. Drug eruption induced by IL-6 receptor inhibitor tocilizumab. J Eur Acad Dermatol Venereol. 2010;24(4):495-496. doi:10.1111/j.1468-3083.2009.03437.x [PubMed 19754658]
  151. Zhang C, Zhang M, Qiu W, et al; TANGO Study Investigators. Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial. Lancet Neurol. 2020;19(5):391-401. doi:10.1016/S1474-4422(20)30070-3 [PubMed 32333897]
  152. Zuelgaray E, Domont F, Peiffer-Smadja N, Saadoun D, Cacoub P. Tocilizumab-induced drug reaction with eosinophilia and systemic symptoms syndrome in adult-onset still disease. Ann Intern Med. 2017;167(2):141-142. doi:10.7326/L16-0592 [PubMed 28531906]
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