Download DRUG NAME: Tocilizumab

Tocilizumab (interim monograph)
DRUG NAME: Tocilizumab
SYNONYM(S): RO48775331
COMMON TRADE NAME(S): ACTEMRA®
CLASSIFICATION: miscellaneous
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
MECHANISM OF ACTION:
Tocilizumab is a humanized anti-human IL-6 antibody2 that binds specifically to both soluble and membrane-bound
IL-6 receptors and inhibits IL-6 mediated signaling through these receptors. Tocilizumab is an immunosuppressant.3
USES:
Primary uses:
Other uses:
Castleman disease2,4
*Health Canada approved indication
SPECIAL PRECAUTIONS:
• Tocilizumab is not recommended in patients with absolute neutrophil count less than or equal to 2.0 x 109/L,
platelets less than 100 x 109/L, or who have ALT or AST above 1.5 times the upper limit of normal. Treatment is
1,3
not recommended in active hepatic impairment or disease.
• Tocilizumab is associated with an increased risk of development of serious infections, possibly leading to
hospitalization or death. Cases of viral reactivation of herpes zoster have been reported. Caution is suggested in
all patients with chronic or recurrent infections, and patients should be screened for latent infections. Patients
should be carefully monitored for signs and symptoms of infection during and after treatment with tocilizumab,
including patients who tested negative for latent infection before therapy. In the event of infection, treatment
1,3
should be stopped until infection is controlled.
• Gastrointestinal perforation has been reported, primarily as a complication of diverticulitis. Caution is advised in
patients at risk for gastrointestinal perforation and new onset abdominal symptoms should be evaluated
promptly.1,3
• Multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in clinical studies.
The impact of tocilizumab on demyelinating disorders is unknown. Caution is suggested in patients with
preexisting or recent onset demyelinating disorders.3
SIDE EFFECTS:
The table includes adverse events that presented during drug treatment but may not necessarily have a causal
relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event
rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they
were reported in more than 1% of patients in the product monograph or pivotal trials. When placebo-controlled trials
are available, adverse events are included if the incidence is >5% higher in the treatment group.
ORGAN SITE
SIDE EFFECT
cardiac
hypertension (6%)
gastrointestinal
emetogenic potential: rare5
diverticulitis and complications, including generalized purulent peritonitis, lower GI
perforation, fistula, and abscess
gastritis (1%)
gastrointestinal perforation
BC Cancer Agency Cancer Drug Manual©
Developed: May 2010
Revised: 16 June 2010
Page 1 of 3
Tocilizumab
Tocilizumab (interim monograph)
ORGAN SITE
SIDE EFFECT
oral ulceration (2%)
upper abdominal pain (2%)
general disorders and
administration site
conditions
immune system
extravasation hazard: none6
infusion reactions; see paragraph following Side Effects table
hypersensitivity reactions, including anaphylaxis
secondary malignancies
infections and
infestations
infections, including pneumonia, urinary tract infections, cellulitis, herpes zoster,
gastroenteritis, diverticulitis, sepsis, and bacterial arthritis
invasive fungal infections, including candidiasis, aspergillosis, and pneumocystitis
opportunistic infections; bacterial, viral, fungal
viral reactivation of herpes zoster
investigations
lipid parameter elevations, including total cholesterol, LDL, HDL, triglycerides; occurs
within 6 weeks, responds to lipid lowering agents
liver enzyme abnormalities (1-6%); may require dose reduction or treatment
interruption; not associated with clinically relevant increases in direct bilirubin or clinical
evidence of hepatitis or hepatic insufficiency
neutropenia (2-3%), approximately half within 8 weeks of treatment start; no clear
relationship with occurrence of serious infections
thrombocytopenia (1-2%)
nervous system
dizziness (3%)
headache (7%)
multiple sclerosis, chronic inflammatory demyelinating polyneuropathy (<1%)
skin and subcutaneous
tissue
rash (2%)
3
Adapted from standard reference unless specified otherwise.
The most commonly reported adverse reactions were upper respiratory tract infections, nasopharyngitis, headache,
hypertension, and increased ALT. The adverse reactions most commonly requiring discontinuation of treatment were
increased hepatic transaminases and serious infections.3
Infusion-related events occur during or within 24 hours of the start of the infusion. The most frequently reported
event occuring during infusion was hypertension (1%). The events most frequently reported within 24 hours after
finishing the infusion were headache (1%) and skin reactions (1%), including rash, pruritus, and urticaria. These
events were not treatment limiting. Clinically significant hypersensitivity reactions (i.e., anaphylactoid and
anaphylactic reactions) requiring treatment discontinuation were reported in less than 1%. Reactions were generally
3
observed during the second to fourth infusion.
SUPPLY AND STORAGE:
Injection: F. Hoffmann-La Roche Ltd. supplies tocilizumab as 80 mg, 200 mg and 400 mg ready-to-use single-use
(preservative free) vials in a concentration of 20 mg/mL. Refrigerate. Do not freeze. Protect vials from light until time
of use.3,4
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation
and Stability Chart in Appendix.
BC Cancer Agency Cancer Drug Manual©
Developed: May 2010
Revised: 16 June 2010
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Tocilizumab
Tocilizumab (interim monograph)
SOLUTION PREPARATION AND COMPATIBILITY:
For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation
and Stability Chart in Appendix.
Additional information:
Compatibility: consult detailed reference
PARENTERAL ADMINISTRATION:
BCCA administration guideline noted in bold, italics
no information found
no information found
do NOT use3
over 60 minutes4
no information found
no information found
no information found
no information found
no information found
no information found
Subcutaneous
Intramuscular
Direct intravenous
Intermittent infusion
Continuous infusion
Intraperitoneal
Intrapleural
Intrathecal
Intra-arterial
Intravesical
DOSAGE GUIDELINES:
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease,
response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count
(ANC). Dosage may be reduced, delayed or discontinued in patients with bone marrow depression due to
cytotoxic/radiation therapy or with other toxicities.
Adults:
BCCA usual dose noted in bold, italics
Intravenous: 2-4
Cycle Length:
2 weeks:4
4-8 mg/kg IV for 1 dose on day 1.
Doses exceeding 800mg per infusion are NOT
recommended.3
REFERENCES:
1. F. Hoffmann-La Roche Ltd. Tocilizumab investigator's brochure addendum to version 11. April 2010.
2. Nishimoto N, Terao K, Mima T, et al. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and
soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and
Castleman disease. Blood 2008;112(10):3959-3964.
3. Genentech Inc. ACTEMRA® product information. South San Francisco, California; January 2010.
4. F. Hoffmann-La Roche Ltd. Provision of tocilizumab for a patient with multicentric Castleman's Disease: guidelines for
compassionate use. May 2010.
5. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in
Adults. Vancouver, British Columbia: BC Cancer Agency; 1 March 2008.
6. BC Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and
Management of Extravasation of Chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 01 December 2007.
BC Cancer Agency Cancer Drug Manual©
Developed: May 2010
Revised: 16 June 2010
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Tocilizumab