Tocilizumab is an immunosuppressive drug, mainly for the treatment of rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis, a severe form of arthritis in children. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer.
Mechanism of action of Tocilizumab
Interleukin (IL)-6 plays essential roles not only in the immune response, but also in haematopoiesis and the central nervous system. Unregulated production of IL-6 has been found in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA), systemic onset juvenile idiopathic arthritis (soJIA), Crohn’s disease (CD), systemic lupus erythematosus (SLE) and vasculitis. Furthermore, IL-6 activities can explain many symptoms of these diseases. More importantly, serum levels of IL-6 are correlated with disease activity. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors.
Indications of Tocilizumab
- Giant cell arteritis
- Cytokine release syndrome
- Juvenile idiopathic arthritis
- Rheumatoid arthritis
- Systemic sclerosis
- Polyarticular juvenile idiopathic arthritis
- Severe aplastic anemia
- Systemic juvenile idiopathic arthritis
- Refractory aplastic anemia
Contra Indication of Tocilizumab
- Diabetes
- High cholesterol
- Low amount of magnesium in the blood
- Low amount of phosphate in the blood
- Low amount of calcium in the blood
- Low amount of sodium in the blood
- High amount of potassium in the blood
- Low amount of potassium in the blood
- Anemia
- Decreased blood Platelets
- Decreased neutrophils a type of white blood cell
- High blood pressure
- Very Rapid Heartbeat – torsades de Pointes
- prolonged QT interval on EKG
- Abnormal EKG with QT changes from Birth
- Hardening of the arteries due to plaque buildup
- Liver problems
- High Amount of Bilirubin in the Blood
- High Blood Sugar
- Abnormal liver function tests
- Pregnancy
- A mother who is producing milk and breastfeeding
- Relapse of Hepatitis B Infection Symptoms
- Pancreatitis
- past history of complete removal of stomach
- Reduced UGT1A1 Enzyme Activity due to 28 Polymorphism
- High Blood Levels of the Lipase Enzyme
- High Blood Levels of the Amylase Enzyme
Dosage of Tocilizumab
Strengths: 20 mg/mL; 162 mg/0.9 mL
Rheumatoid Arthritis
IV
- 4 mg/kg IV as a 60-minute single drip infusion once every 4 weeks, followed by an increase to 8 mg/kg IV given once every 4 weeks as a 60-minute single drip infusion based on clinical response
- Dose adjustment: Reduction from 8 mg/kg to 4 mg/kg is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia.
- Maximum dose: 800 mg per infusion
Subcutaneous
- Patients less than 100 kg: 162 mg subcutaneously every other week, followed by an increase to every week based on clinical response
- Patients 100 kg or greater: 162 mg subcutaneously every week
- Dose adjustment: Interruption of dose or reduction in frequency of administration from every week to every other week is recommended for management of certain dose-related laboratory changes including elevated liver enzymes, neutropenia, and thrombocytopenia.
Giant Cell Arteritis
- 162 mg subcutaneously once a week in combination with a tapering course of glucocorticoids
- Dose adjustment: 162 mg subcutaneously every other week in combination with a tapering course of glucocorticoids may be appropriate based on clinical considerations
Pediatric Juvenile Idiopathic Arthritis
Polyarticular Juvenile Idiopathic Arthritis (PJIA)
2 years or older
- Weight less than 30 kg: 10 mg/kg IV as a 60-minute single drip infusion
once every 4 weeks
- Weight 30 kg or more: 8 mg/kg as a 60-minute single drip infusion
once every 4 weeks
- Systemic Juvenile Idiopathic Arthritis (SJIA)
2 years or older
- Weight less than 30 kg: 12 mg/kg IV as a 60-minute single drip infusion
Once every 2 weeks
- Weight 30 kg or more: 8 mg/kg IV as a 60-minute single drip infusion
once every 2 weeks
Side Effects of Tocilizumab
The most common
- chest pain
- certainly hair loss
- headache
- joint painPain
- dizziness
- nausea and vomiting
- Severe stomach ache
- epigastric pain,
- diarrhoea,
- anorexia,
- flatulence,
- headache,
- dizziness,
- fainting, fast or pounding heartbeats.
More common
- Fast or irregular heartbeat
- appetite loss
- changes in nails
- constipation
- fatigue
- fever
- Back pain
- dizziness
- headache
- increased cough
- Acid or sour stomach
- decreased appetite
- Agitation
- chest congestion
- chest pain
- cold sweats
- confusion
- decreased sexual ability or desire
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Less common
- bleeding gums
- blood in the urine or stools
- chest pain
- diarrhea
- Burning, crawling, itching, numbness, prickling, “pins and needles“, or tingling feelings
- difficulty in moving
- muscle stiffness
- redness of the face, neck, arms and occasionally, upper chest
- lack or loss of strength
- muscle spasm
- difficult or labored breathing
- dry mouth
- headache
- irritability
- lack or loss of strength
- loose stools
- loss of interest or pleasure
- muscle stiffness
- night sweats
- passing gas
- stomach discomfort, upset, or pain
- swollen joints
- trouble concentrating
- increased blood pressure
Drug Interactions of Tocilizumab
Nilotinib may interact with following drugs ,suppliments & may chane the efficacy of drug
- alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
- anticancer medications (e.g., cabazitaxel, docetaxel, doxorubicin, etoposide, ifosfamide, irinotecan, vincristine)
- “azole” antifungal medications (e.g., fluconazole, itraconazole, ketoconazole)
- beta-blockers (e.g., atenolol, propranolol, metoprolol)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
- calcium channel blockers (e.g., nifedipine, diltiazem, verapamil, amlodipine, felodipine)
- carbamazepine
- chloroquine
- corticosteroids (e.g., dexamethasone, prednisone, methylprednisolone)
- cyclosporine
- dantrolene
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., delaviridine, efavirenz, etravirine, nevirapine)
- HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
- losartan
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- metronidazole
- mirtazapine
- modafinil
- montelukast
- norfloxacin
- ondansetron
- carbamazepine
- peginterferon alfa-2b
- phenytoin
- progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone)
- proton pump inhibitors (PPIs; e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline)
- sildenafil
- “statin” anticholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- tacrolimus
- tadalafil
- tamoxifen
- tetracycline
- theophylline
- tocilizumab
- tolterodine
- tramadol
- other selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, sertraline)
- 5-HT3 antagonists (e.g., granisetron, ondansetron)
- tamsulosin
- tapentadol
- thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
- tramadol
- tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine,
- other tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib)
- tetracycline
- tocilizumab
- vandetanib
- vemurafenib
- trimethoprim
- vaccines
- warfarin
Pregnancy & Lactation of Tocilizumab
FDA Pregnancy Category C
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. Effective birth control must be used to prevent pregnancy during treatment and for 3 months after the last dose of tocilizumab. If you become pregnant while receiving this medication, contact your doctor immediately.
Lactation
It is not known if tocilizumab passes into breast milk. If you are a breast-feeding mother and are receiving this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.
