Tocilizumab
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: RISK OF SERIOUS INFECTIONS Patients treated with tocilizumab products including TYENNE are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 )] . Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. If a serious infection develops, interrupt TYENNE until the infection is controlled. Reported infections include: • Active tuberculosis, which may present with pulmonary or extrapulmonary disease.
Patients, except those with COVID-19, should be tested for latent tuberculosis before TYENNE use and during therapy. Treatment for latent infection should be initiated prior to TYENNE 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 due to opportunistic pathogens. The risks and benefits of treatment with TYENNE 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 TYENNE including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions ( 5.1 )] . WARNING: RISK OF SERIOUS INFECTIONS See full prescribing information for complete boxed warning. • Serious infections leading to hospitalization or death including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections have occurred in patients receiving tocilizumab products.
( 5.1 ) • If a serious infection develops, interrupt TYENNE until the infection is controlled. ( 5.1 ) • Perform test for latent TB (except patients with COVID-19); if positive, start treatment for TB prior to starting TYENNE. ( 5.1 ) • Monitor all patients for active TB during treatment, even if initial latent TB test is negative. ( 5.1 )
Interleukin-6 Receptor Antagonist
Dosing in kidney impairment
Renal Impairment No dose adjustment is required in patients with mild or moderate renal impairment. Tocilizumab products have not been studied in patients with severe renal impairment [see Clinical Pharmacology] .
Dosing in liver impairment
Hepatic Impairment The safety and efficacy of tocilizumab products have not been studied in patients with hepatic impairment, including patients with positive HBV and HCV serology [see Warnings and Precautions 5.8 )] .
Preparation and administration
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Your numbers for tocilizumab. Take vial strength, diluent, and limits from the label below.
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General Considerations for Administration Not Recommended for Concomitant Use with Biological DMARDs Tocilizumab products have not been studied in combination with biological DMARDs such as TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies and selective co-stimulation modulators because of the possibility of increased immunosuppression and increased risk of infection.
Avoid using TYENNE with biological DMARDs. Baseline Laboratory Evaluation Prior to Treatment Obtain and assess baseline complete blood count (CBC) and liver function tests prior to treatment. RA, GCA, PJIA and SJIA – It is recommended that TYENNE not be initiated in patients with an absolute neutrophil count (ANC) below 2,000 per mm 3 , platelet count below 100,000 per mm 3 , or ALT or AST above 1.5 times the upper limit of normal (ULN) [see Warnings and Precautions ( 5.3 , 5.4 )] .
CRS – Patients with severe or life-threatening CRS frequently have cytopenias or elevated ALT or AST due to the lymphodepleting chemotherapy or the CRS. The decision to administer TYENNE should take into account the potential benefit of treating the CRS versus the risks of short-term treatment with TYENNE. COVID-19 – It is recommended that TYENNE not be initiated in patients with an absolute neutrophil count (ANC) below 1,000 per mm 3 , platelet count below 50,000 mm 3 , or ALT or AST above 10 times ULN [see Warnings and Precautions ( 5.3 , 5.4 )] .
Recommended Dosage for Systemic Juvenile Idiopathic Arthritis TYENNE may be used as an intravenous infusion or as a subcutaneous injection alone or in combination with methotrexate. Do not change a dose based solely on a single visit body weight measurement, as weight may fluctuate. Recommended Intravenous Dosage Regimen: The recommended dose of TYENNE for SJIA patients given once every 2 weeks as a 60-minute single intravenous drip infusion is: [See table below.] Recommended Subcutaneous Dosage Regimen: [See table below.] When transitioning from TYENNE intravenous therapy to subcutaneous administration, administer the first subcutaneous dose when the next scheduled intravenous dose is due.
Interruption of dosing may be needed for management of dose-related laboratory abnormalities including elevated liver enzymes, neutropenia, and thrombocytopenia [see Dosage and Administration] .
Recommended Dosage for Coronavirus Disease 2019 (COVID-19) Administer TYENNE by intravenous infusion only. The recommended dosage of TYENNE for treatment of patients with COVID-19 given as a single 60-minute intravenous infusion is: [See table below.] If clinical signs or symptoms worsen or do not improve after the first dose, one additional infusion of TYENNE may be administered at least 8 hours after the initial infusion.
Doses exceeding 800 mg per infusion are not recommended in patients with COVID-19.
Subcutaneous administration is not approved for COVID-19 .
Preparation and Administration Instructions for Intravenous Infusion TYENNE for intravenous infusion should be diluted by a healthcare professional using aseptic technique as follows:
Use a sterile needle and syringe to prepare TYENNE.
Patients less than 30 kg : use a 50 mL infusion bag or bottle of 0.9% or 0.45% Sodium Chloride Injection, USP, and then follow steps 1 and 2 below.
Patients at or above 30 kg weight : use a 100 mL infusion bag or bottle, and then follow steps 1 and 2 below. - Step 1. Withdraw a volume of 0.9% or 0.45% Sodium Chloride Injection, USP, equal to the volume of the TYENNE injection required for the patient's dose from the infusion bag or bottle [see Dosage and Administration ( 2.2 , 2.4 , 2.5 , 2.6 )] . [See table below.] - Step 2.
Withdraw the amount of TYENNE for intravenous infusion from the vial(s) and add slowly into the 0.9% or 0.45% Sodium Chloride Injection, USP infusion bag or bottle. To mix the solution, gently invert the bag to avoid foaming.
The prepared solution for infusion should be used immediately. If not used immediately, the diluted tocilizumab solutions may be refrigerated at 36°F to 46°F (2°C to 8°C) up to 24 hours, or stored at room temperature at or below 77°F (25°C) for up to 4 hours and should be protected from light. Administration of diluted TYENNE solution must be completed within this period of time.
TYENNE solutions do not contain preservatives; therefore, unused product remaining in the vials should not be used.
Allow the fully diluted TYENNE solution to reach room temperature prior to infusion.
The infusion should be administered over 60 minutes and must be administered with an infusion set. Do not administer as an intravenous push or bolus.
TYENNE should not be infused concomitantly in the same intravenous line with other drugs. No physical or biochemical compatibility studies have been conducted to evaluate the co-administration of TYENNE with other drugs.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulates and discolorations are noted, the product should not be used.
Fully diluted TYENNE solutions are compatible with polypropylene, polyethylene and polyvinyl chloride infusion bags and bottles, and glass infusion bottles.
Preparation and Administration Instructions for Subcutaneous Injection
TYENNE for subcutaneous injection is not intended for intravenous drip infusion.
Assess suitability of patient for subcutaneous home use and instruct patients to inform a healthcare professional before administering the next dose if they experience any symptoms of allergic reaction. Patients should seek immediate medical attention if they develop symptoms of serious allergic reactions. TYENNE subcutaneous injection is intended for use under the guidance of a healthcare practitioner.
After proper training in subcutaneous injection technique, a patient may self-inject TYENNE or the patient's caregiver may administer TYENNE if a healthcare practitioner determines that it is appropriate. PJIA and SJIA patients may self-inject with the TYENNE prefilled syringe or autoinjector, or the patient's caregiver may administer TYENNE if both the healthcare practitioner and the parent/legal guardian determine it is appropriate [see Use in Specific Populations] .
Patients, or patient caregivers, should be instructed to follow the directions provided in the Instructions for Use (IFU) for additional details on medication administration.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use TYENNE prefilled syringes (PFS) or prefilled autoinjectors exhibiting particulate matter, cloudiness, or discoloration. TYENNE for subcutaneous administration should be clear and colorless to pale yellow.
Do not use if any part of the PFS or autoinjector appears to be damaged.
Patients using TYENNE for subcutaneous administration should be instructed to inject the full amount in the syringe (0.9 mL) or full amount in the autoinjector (0.9 mL), which provides 162 mg of TYENNE, according to the directions provided in the IFU.
Injection sites should be rotated with each injection and should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.
| Recommended Intravenous COVID-19 Dosage | |
| Patients less than 30 kg weight | 12 mg per kg |
| Patients at or above 30 kg weight | 8 mg per kg |
| Administered by a 60-minute intravenous infusion | |
| For Intravenous Use: Volume of TYENNE Injection per kg of Body Weight | ||
| Dosage | Indication | Volume of TYENNE injection per kg of body weight |
| 4 mg/kg | Adult RA | 0.2 mL/kg |
| 6 mg/kg | Adult GCA | 0.3 mL/kg |
| 8 mg/kg | Adult RA SJIA, PJIA, CRS and COVID-19 (greater than or equal to 30 kg of body weight) | 0.4 mL/kg |
| 10 mg/kg | PJIA (less than 30 kg of body weight) | 0.5 mL/kg |
| 12 mg/kg | SJIA, CRS and COVID-19 (less than 30 kg of body weight) | 0.6 mL/kg |
Drug interactions
Check tocilizumab against a medication listLabel text (6 paragraphs)
7 DRUG INTERACTIONS
7.1 Concomitant Drugs for Treatment of Adult Indications In RA patients, population pharmacokinetic analyses did not detect any effect of methotrexate (MTX), non-steroidal anti-inflammatory drugs or corticosteroids on tocilizumab clearance. Concomitant administration of a single intravenous dose of 10 mg/kg tocilizumab with 10-25 mg MTX once weekly had no clinically significant effect on MTX exposure. Tocilizumab products have not been studied in combination with biological DMARDs such as TNF antagonists [see Dosage and Administration ( 2.2 )] . In GCA patients, no effect of concomitant corticosteroid on tocilizumab exposure was observed.
7.2 Interactions with CYP450 Substrates Cytochrome P450s in the liver are down-regulated by infection and inflammation stimuli including cytokines such as IL-6. Inhibition of IL-6 signaling in RA patients treated with tocilizumab products may restore CYP450 activities to higher levels than those in the absence of tocilizumab products leading to increased metabolism of drugs that are CYP450 substrates. In vitro studies showed that tocilizumab has the potential to affect expression of multiple CYP enzymes including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Its effect on CYP2C8 or transporters is unknown.
In vivo studies with omeprazole, metabolized by CYP2C19 and CYP3A4, and simvastatin, metabolized by CYP3A4, showed up to a 28% and 57% decrease in exposure one week following a single dose of tocilizumab, respectively. The effect of tocilizumab products on CYP enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of TYENNE, in patients being treated with these types of medicinal products, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) and the individual dose of the medicinal product adjusted as needed.
Exercise caution when coadministering TYENNE with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, etc. The effect of tocilizumab products on CYP450 enzyme activity may persist for several weeks after stopping therapy [see Clinical Pharmacology ( 12.3 )] .
7.3 Live Vaccines Avoid use of live vaccines concurrently with TYENNE [see Warnings and Precautions ( 5.9 )] .
Contraindications
4 CONTRAINDICATIONS TYENNE is contraindicated in patients with known hypersensitivity to tocilizumab products [see Warnings and Precautions ( 5.6 )]. Known hypersensitivity to tocilizumab products. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary The available data with tocilizumab products from a pregnancy exposure registry, retrospective cohort study, pharmacovigilance, and published literature are insufficient to draw conclusions about a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. These studies had methodological limitations, including small sample size of tocilizumab exposed groups, missing exposure and outcomes information, and lack of adjustment for confounders.
Monoclonal antibodies, such as tocilizumab products, are actively transported across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant [see Clinical Considerations ]. In animal reproduction studies, intravenous administration of tocilizumab to Cynomolgus monkeys during organogenesis caused abortion/embryo-fetal death at doses 1.25 times and higher than the maximum recommended human dose by the intravenous route of 8 mg per kg every 2 to 4 weeks.
The literature in animals suggests that inhibition of IL-6 signaling may interfere with cervical ripening and dilatation and myometrial contractile activity leading to potential delays of parturition [see Data ] . Based on the animal data, there may be a potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Fetal/Neonatal adverse reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to TYENNE in utero [see Warnings and Precautions 5.9 )]. Disease-associated Maternal Risk Published data suggest that the risk of adverse pregnancy outcomes in women with rheumatoid arthritis is associated with increased disease activity.
Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Data Animal Data An embryo-fetal developmental toxicity study was performed in which pregnant Cynomolgus monkeys were treated intravenously with tocilizumab at daily…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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