Tocilizumab

Registered South African indications:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Systemic juvenile idiopathic arthritis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Active, severe infections

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment
• Hepatic impairment
• History of recurring or chronic infections or with underlying conditions which may predispose patients to infections
• Latent tuberculosis
• History of intestinal ulceration or diverticulitis
• Thrombocytopaenia
• Severe neutropenia
• Cardiovascular risk factors
• Controlled sodium diet (IV)

Forms avail. in SA and covered in this monograph: inj

Treatment should be initiated by medical practitioners experienced in the diagnosis and treatment of rheumatoid arthritis

Rheumatoid arthritis (Additional agent required)
- Severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate (MTX)
- Moderate to severe active rheumatoid arthritis in patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor (TNF) antagonists

• IV: 8mg/kg body weight, as an infusion over 1hr, every 4 weeks; For individuals whose body weight is >100kg: Doses exceeding 800mg/infusion are not recommended
• SC: 162mg, weekly

IV formulation: Doses above 1.2g have not been evaluated in clinical studies

Tocilizumab can be given as monotherapy in case of intolerance to methotrexate (MTX) or where continued treatment with MTX is inappropriate. Tocilizumab has been shown to reduce the rate of progression of joint damage as measured by modified total Sharp-Genant radiographic score and to improve physical function when given in combination with MTX

Patients transitioning from IV to SC administration should administer the first SC dose at the time of the next scheduled IV dose

SC formulation may be given as monotherapy in the case of intolerance to methotrexate or where continued treatment with methotrexate is inappropriate

Paed. forms avail. in SA and covered in this monograph: inj

Treatment should be initiated by medical practitioners experienced in the diagnosis and treatment of polyarticular juvenile idiopathic arthritis or systemic juvenile idiopathic arthritis

Polyarticular juvenile idiopathic arthritis (Additional agent required)
- In patients intolerant to methotrexate or where the treatment response with methotrexate is inadequate

Younger than 2 years

• Not established for use

Older than 2 years

• <30kg: IV: 10mg/kg infused over 1hr, every 4 weeks
• ≥30kg: IV: 8mg/kg infused over 1hr, every 4 weeks

Systemic juvenile idiopathic arthritis (Additional agent required)
- In patients who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs and systemic corticosteroids

Younger than 2 years

• Not established for use

Older than 2 years

• <30kg: IV: 12mg/kg infused over 1hr, every 2 weeks
• ≥30kg: IV: 8mg/kg infused over 1hr, every 2 weeks

Tocilizumab can be given as monotherapy (in case of intolerance to methotrexate or where treatment with methotrexate is inappropriate) or in combination with methotrexate

Pregnancy

• FDA Pregnancy Category Not Rated (NR)

Breastfeeding

• Caution; not recommended

Renal Impairment

• Moderate to severe: Caution; no information available

Hepatic Impairment

• Caution; no information available

Elderly

• No dose adjustment recommended

Central Nervous System Disorders

• Headache
• Dizziness

Cardiovascular Disorders

• Hypertension

Respiratory Disorders

• Upper respiratory tract infections
• Pneumonia
• Cough
• Dyspnoea

Gastrointestinal Disorders

• Diverticulitis
• Abdominal pain
• Mouth ulceration
• Gastritis
• Stomatitis
• Gastric ulcer

Hepatobiliary Disorders

• Increased hepatic transaminases 
• Increased total bilirubin

Genitourinary Disorders

• Nephrolithiasis

Endocrine and Metabolic Disorders

• Increased weight
• Hypercholesterolaemia
• Hypertriglyceridaemia
• Hypothyroidism

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Urticaria
• Oral herpes simplex 
• Herpes zoster
• Cellulitis
• Peripheral oedema

Immune, Blood and Lymphatic System Disorders

• Leukopenia
• Neutropenia
• Hypersensitivity reactions

Sensory Disorders

• Conjunctivitis

• Live and live attenuated vaccines 
• Other biological agents
• Cytokine inhibitory therapy
• Simvastatin
• CYP3A4 substrates
• CYP1A2 substrates
• CYP2C9 substrates

• Full blood count
• Lipid profile
• Hepatic function
• Tuberculosis screening

Specific cases may require

• Renal function

Tocilizumab binds specifically to both soluble and membrane-bound interleukin (IL)-6 receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T and B cells, lymphocytes, monocytes and fibroblasts. IL-6 is involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, induction of hepatic acute phase protein synthesis and stimulation of haematopoiesis. IL-6 has been implicated in the pathogenesis of diseases including inflammatory diseases, osteoporosis and neoplasia.

Injection (per 4ml) 80mg

• Actemra 80 (Roche) originator

Injection (per 10ml) 200mg

• Actemra 200 (Roche) originator

Injection (per 20ml) 400mg

• Actemra 400 (Roche) originator

Injection (per 0.9ml) 162mg

• Actemra SC (Roche) originator