Tocilizumab
Indications
Tocilizumab is used for:
Juvenile idiopathic arthritis, Rheumatoid Arthritis (RA)
Adult Dose
Parenteral
Adult:
Rheumatoid Arthritis
Indicated for adults with moderate-to-severe active rheumatoid arthritis with inadequate response to 1 or more DMARDs as an IV infusion or SC injection
May use alone or in combination with methotrexate or other DMARDs
IV infusion
4 mg/kg IV q4wk initially; may increase to 8 mg/kg q4wk based on clinical response
Not to exceed 800 mg/dose q4wk
SC injection
Weight <100 kg: 162 mg SC every other week, followed by an increase to every week based on clinical response
Weight >100 kg: 162 mg SC every week
Hepatic impairment
Not recommended with active hepatic disease or hepatic impairment
Child Dose
Systemic Juvenile Idiopathic Arthritis (SJIA, Still's Disease)
<2 years: Safety and efficacy not established
>2 years or older (<30 kg): 12 mg/kg IV q2weeks
(>30 kg): 8 mg/kg IV q2weeks
May be administered as monotherapy or with methotrexate
Polyarticular Juvenile Idiopathic Arthritis (PJIA)
<2 years: Safety and efficacy not established
>2 years or older (<30 kg): 10 mg/kg IV q4weeks
(>30 kg or more): 8 mg/kg IV q4weeks
May be administered as monotherapy or with methotrexate
Renal Dose
Renal impairment
Mild: No dosage adjustment required
Moderate-to-severe: Has not been studied
Administration
IV Preparation
Withdraw a volume of 0.9% NaCl from bag/bottle equal to volume of the solution required for the patient's dose
Adults and children weighing >30 kg: Dilute to 100 mL in 0.9% NaCl
Children <30 kg: Dilute to 50 mL in 0.9% NaCl
Slowly add dose to infusion bag or bottle and gently invert to mix (prevent foaming)
IV Administration
Administer as single IV infusion over 1 hr
Do NOT administer as bolus or push
Do not infuse with any other drugs as no compatibility studies have been conducted
SC Preparation
Remove prefilled SC syringe from refrigerator 30 minutes before administration
SC Administration
Indicated only in adults with rheumatoid arthritis
Rotate SC injection sites (ie, thighs, abdomen, outer area of upper arm [caregiver only]) and inject full amount of the syringe (0.9 mL)
Transition from IV to SC: Administer first SC dose instead of next scheduled IV dose
Contra Indications
Hypersensitivity
Precautions
Serious infections leading to hospitalization or death (ie, tuberculosis; bacterial, invasive fungal, viral, or other opportunistic infections) have occurred with use
Stop therapy if serious infection occurs; can restart if infection is controlled
Test for latent tuberculosis before initiating; if positive, initiate tuberculosis therapy before starting tocilizumab
Continue to monitor all patients for active tuberculosis during therapy
Lactation: unknown whether distributed in breast milk, do not breast feed
Pregnancy-Lactation
Interactions
Interactions with Other Medications and Other Forms of Interaction: Population pharmacokinetic analyses did not detect any effect of MTX, nonsteroidal anti-inflammatory drugs or corticosteroids on tocilizumab clearance. Tocilizumab has not been studied in combination with other biological DMARDs.
The expression of hepatic CYP450 enzymes is suppressed by cytokines, eg, IL-6, that stimulate chronic inflammation. Thus, CYP450 expression may be reversed when potent cytokine inhibitory therapy, eg, tocilizumab is introduced.
In vitro studies with cultured human hepatocytes demonstrated that IL-6 caused a reduction in CYP1A2, CYP2C9, CYP2C19, and CYP3A4 enzyme expression. Tocilizumab normalizes expression of these enzymes.
The effect of tocilizumab on CYP enzymes (except CYP2C19 and CYP2D6) is clinically relevant for CYP450 substrates with a narrow therapeutic index, and/or where the dose is individually adjusted. In a study in RA patients, levels of simvastatin (CYP3A4) were decreased by 57% one week following a single dose of tocilizumab, to the level similar or slightly higher than those observed in healthy subjects.
When starting or stopping therapy with tocilizumab, patients taking medications, which are individually dose-adjusted and are metabolised via CYP450 3A4, 1A2, or 2C9 (eg, atorvastatin, calcium channel blockers, theophylline, warfarin, phenytoin, ciclosporin, or benzodiazepines) should be monitored as doses of these products may need to be adjusted to maintain their therapeutic effect. Given its long elimination t½, the effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy.
Adverse Effects
Side effects of Tocilizumab :
>10%
SC injection site reactions (7.1-10.1%)
1-10%
Upper respiratory tract infections,Nasopharyngitis,Headache,Hypertension,Increased ALT,Infusion related skin reactions (eg, rash, pruritus, urticaria),Dose related adverse reactions including decreased neutrophil count <1000/cu.mm, decreased platelets <100,000/cu.mm,Lipid elevations,Mouth ulcerations,Gastritis,Upper abdominal pain
Mechanism of Action
Interleukin-6 receptor antagonist; changes in clinical trials observed include decreased C-reactive protein level to within normal range, decreased values in other pharmacodynamic parameters (eg, rheumatoid factor, erythrocyte sedimentation rate, amyloid A), and increased hemoglobin value