Tocilizumab

Tocilizumab is a prescription medication used to treat moderate to severe rheumatoid arthritis, giant cell arteritis, or inflammation of the lining of your arteries, severe or life-threatening cytokine release syndrome (CRS), and polyarticular juvenile idiopathic arthritis and systemic juvenile idiopathic arthritis ("Still disease") in adults and children aged 2 years or older. 

• Tocilizumab is available under the following different brand names: Actemra, Tofidence, and Tyenne.

Adult dosages:

Injectable solution

• 20mg/mL (4-,10-, and 20-mL single dose vials)

Injection, single-use autoinjector (ACTPen) for SC

• 162mg/0.9mL

Injection, single-use prefilled syringe for SC

• 162mg/0.9mL

Pediatric dosages:

Injectable solution

• 20mg/mL (4-, 10-, and 20-mL single dose vials)

Injection, single-use prefilled syringe for SC

• 162mg/0.9mL 

Rheumatoid Arthritis 

• IV Infusion: 4 mg/kg IV every 4 weeks initially, may increase to 8 mg/kg every 4 weeks based on clinical response
• SC Injection: Weight less than 100 kg: 162mg SC every other week, followed by an increase to weekly based on clinical response
• SC Injection: Weight greater than 100 kg: 162mg SC weekly

Giant Cell Arteritis

• 162mg SC weekly in combination with a tapering course of glucocorticoids

Interstitial Lung Disease 

• 162mg SC weekly

Cytokine Release Syndrome

• 8 mg/kg once by IV, may administer up to 3 additional doses, allow 8 hours between consecutive doses
• Safety not established for children younger than 2 years of age. 
• Children weighing less than 66 lbs or 30 kg: 12 mg/kg via IV once, not to exceed 800 mg/dose. 
• Children weighing 66 lbs or 30 kg or more: 8 mg kg via IV once, not to exceed 800 mg/dose.

COVID-19 (Emergency Use Authorization)

• 8 mg/kg via IV, not to exceed 800 mg/dose in hospitalized adults and pediatric patients aged 2 years or older
• Children weighing less than 66 lbs or 30 kg: 12 mg/kg via IV. 

Systemic Juvenile Idiopathic Arthritis

• Safety not established for children younger than 2 years of age. 
• IV Infusion: Children weighing less than 66 lbs or 30 kg: 12mg/kg every 2 weeks
• IV Infusion: Children weighing 66 lbs or 30 kg or more: 8 mg/kg every 2 weeks
• SC Injection: Children weighing less than 66 lbs or 30 kg: 162mg SC every 2 weeks
• SC Injection: Children weighing 66 lbs or 30 kg or more: 162mg SC every week

Polyarticular Juvenile Idiopathic Arthritis

• Safety not established for children younger than 2 years of age 
• IV Infusion: Children weighing less than 66 lbs or 30 kg: 10 mg/kg every 4 weeks
• IV Infusion: Children weighing 66 lbs or 30 kg or more: 8 mg/kg every 4 weeks 
• SC Injection: Children weighing less than 66 lbs or 30 kg: 162 mg SC every 3 weeks
• SC Injection: Children weighing 66 lbs or 30 kg or more: 162 mg SC every 2 weeks

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Tocilizumab include:

• runny or stuffy nose, 
• sinus pain, 
• store throat, 
• headache, 
• increased blood pressure, 
• abnormal liver function tests, and
• pain, swelling, burning, or irritation at the injection site

Serious side effects of Tocilizumab include:

• hives, 
• difficult breathing, 
• swelling in your face, lips, tongue, or throat, 
• chest pain, 
• lightheadedness, 
• severe stomach cramps, 
• bloating, 
• diarrhea, 
• constipation, 
• nosebleeds, 
• bleeding gums, 
• abnormal vaginal bleeding, 
• any bleeding that will not stop, 
• blood in urine or stools, 
• coughing up blood, 
• vomit that looks like coffee grounds, 
• loss of appetite, 
• right-sided stomach pain, 
• vomiting, 
• tiredness, 
• dark urine, 
• clay-colored stools, 
• yellowing of the skin or eyes (jaundice), 
• fever, 
• chills, 
• aches, 
• tiredness, 
• cough, 
• skin sores, 
• diarrhea, 
• weight loss, 
• burning while urinating, 
• ongoing stomach pain, and
• change in bowel habits 

Rare side effects of Tocilizumab include:

• none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first

• Tocilizumab has no known severe interactions with other drugs
• Tocilizumab has serious interactions with at least 64 other drugs.
• Tocilizumab has moderate interactions with at least 26 other drugs. 
• Tocilizumab has mild interactions with the following drugs:
  • cat's claw
  • lenalidomide

This information does not contain all possible interactions or adverse effects.  Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns

Keep out of reach of children.  In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• hypersensitivity

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Tocilizumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Tocilizumab?"

Cautions

• Not recommended with active hepatic disease or hepatic impairment. 
• May cause neutropenia, decreased platelets, elevated liver transaminases, and increased lipid parameters; monitor neutrophils, platelets, lipids, and liver function tests every 4-8 weeks
• Impact of treatment is unknown regarding development of malignancies, but malignancies were observed in clinical studies; treatment with immunosuppressants may increase risk of malignancies
• Anaphylaxis or serious hypersensitivity reactions have occurred, including fatalities, with or without concomitant arthritis therapies
• Impact of treatment with tocilizumab on demyelinating disorders is unknown, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in RA clinical studies; monitor for signs and symptoms potentially indicative of demyelinating disorders
• Caution if increased risk for GI perforation; gastrointestinal perforation reported, primarily as complications of diverticulitis; promptly evaluate patients presenting with new onset abdominal symptoms for early identification of gastrointestinal perforation
• Serious infections
  • Do not administer in patients with an active infection, including localized infections
  • Consider risk versus benefits before initiating in patients with chronic or recurrent infection, exposure to tuberculosis, history of serious or an opportunistic infection, have resided or traveled in areas of endemic tuberculosis or endemic mycoses, or who have underlying conditions predisposing them to infection
  • Not studied in combination with biological DMARDs (eg, TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, selective co-stimulation modulators); avoid in combination with these agents because of increased immunosuppression and infection risk
  • Viral reactivation reported; cases of herpes zoster exacerbation observed in clinical studies; unknown if associated with hepatitis B reactivation; not studied
• Hepatic injury - RA or GCA
  • Serious cases of hepatic injury with IV or SC therapy; some cases have resulted in liver transplant or death; onset for cases ranged from months to years after initiating Tocilizumab
  • For RA and GCA patients, obtain a liver test panel (ALT, AST, alkaline phosphatase, and total bilirubin) before initiating therapy, every 4-8 weeks after start of therapy for the first 6 months of treatment and every 3 months thereafter
  • Not recommended to initiate in RA or GCA patients with elevated transaminases ALT or AST greater than 1.5x ULN
  • In patients who develop elevated ALT or AST greater than 5x ULN, discontinue therapy; for recommended modifications based upon increase in transaminases
  • Measure liver tests promptly in patients who report symptoms that may indicate liver injury, such as fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice; if patient is found to have abnormal liver tests (eg, ALT >3x ULN, total bilirubin >2x ULN)
  • Interrupt treatment and establish probable cause; once liver tests normalize, restart in patients with another explanation for liver test abnormalities
• PJIA or SJIA
  • A similar pattern of liver enzyme elevation is noted within the PJIA and SJIA populations
  • Monitor liver test panel at the time of the second administration and thereafter every 4-8 weeks for PJIA and every 2-4 weeks for SJIA
• COVID-19
  • Patients hospitalized with COVID-19 may have elevated ALT or AST levels
  • Multiorgan failure with liver involvement has been recognized as a complication of severe COVID-19
  • During randomized, controlled studies, tocilizumab was associated with increased incidence of transaminase elevations
  • When deciding to administer tocilizumab, balance potential benefit against risks of acute treatment
  • Not recommended in patients with COVID-19 who have elevated ALT or AST >10x ULN
  • Monitor ALT/AST when used for COVID-19 according to current standard clinical practices

Pregnancy and Lactation

• Insufficient data available in pregnant women to determine whether there is a drug-associated risk for major birth defects and miscarriage. 
• No data available on the presence of Tocilizumab in human milk, effects of the drug on the breastfed infant, or effects on the drug on milk production.