Presentation and Status in Health Basket
Pre-filled Syringe (solution for injection)
4 X 162 mg/0.9 ml
Tocilizumab SC formulation is administered with a single-use PFS+NSD.
A patient can self-inject Actemra only if the physician determines that it is appropriate and the patient agrees to medical follow-up as necessary and has been trained in proper injection technique.
Patients who transition from tocilizumab IV therapy to SC administration should administer the first SC dose at the time of the next scheduled IV dose under the supervision of a qualified health care professional.
Suitability of the patient for subcutaneous home use should be assessed and patients instructed to inform a healthcare professional before administering the next dose if they experience symptoms of an allergic reaction. Patients should seek immediate medical attention if developing symptoms of serious allergic reactions.
RA Patients: The recommended posology is subcutaneous 162mg once every week.
Limited information is available regarding switching patients from Actemra intravenous formulation to Actemra subcutaneous fixed dose formulation. The once every week dosing interval should be followed.
Patients transitioning from intravenous to subcutaneous formulation should administer their first subcutaneous dose instead of the next scheduled intravenous dose under the supervision of a qualified healthcare professional.
GCA Patients: The recommended posology is subcutaneous 162 mg once every week in combination with a tapering course of glucocorticoids. Actemra can be used alone following discontinuation of glucocorticoids.
Actemra monotherapy should not be used for the treatment of acute relapses.
Based upon the chronic nature of GCA, treatment beyond 52 weeks should be guided by disease activity, physician discretion, and patient choice.
Dose adjustments due to laboratory abnormalities:
Liver enzyme abnormalities:
> 1 to 3 x Upper Limit of Normal (ULN): Dose modify concomitant DMARDs (RA) or immunomodulatory agents (GCA) if appropriate.
For persistent increases in this range, reduce Actemra dose frequency to every other week injection or interrupt Actemra until alanine aminotransferase (ALT) or aspartate aminotransferase (AST) have normalised.
Restart with weekly or every other week injection, as clinically appropriate.
> 3 to 5 x ULN: Interrupt Actemra dosing until < 3 x ULN and follow recommendations above for > 1 to 3 x ULN.
For persistent increases > 3 x ULN (confirmed by repeat testing), discontinue Actemra.
> 5 x ULN: Discontinue Actemra.
Low absolute neutrophil count (ANC): In patients not previously treated with Actemra, initiation is not recommended in patients with an absolute neutrophil count (ANC) below 2 x 10^9/L.
ANC > 1 (cells x 10^9/ L ): Maintain dose.
ANC 0.5 to 1 (cells x 10^9/ L ): Interrupt Actemra dosing.
When ANC increases > 1 x 10^9/ L resume Actemra dosing every other week and increase to every week injection, as clinically appropriate.
ANC < 0.5 (cells x 10^9/ L ): Discontinue Actemra.
Low platelet count:
50 to 100 (cells x 10³/ μL): Interrupt Actemra dosing.
When platelet count > 100 x 10³/ μL resume Actemra dosing every other week
and increase to every week injection as clinically appropriate.
< 50 (cells x 10³/ μL): Discontinue Actemra.
Missed dose: If a patient misses a subcutaneous weekly injection of Actemra within 7 days of the scheduled dose, he/she should be instructed to take the missed dose on the next scheduled day. If a patient misses a subcutaneous once every other week injection of Actemra within 7 days of the scheduled dose, he/she should be instructed to take the missed dose immediately and the next dose on the next scheduled day.
Elderly patients: No dose adjustment is required in patients aged 65 years and older.
Renal impairment: No dose adjustment is required in patients with mild renal impairment. Actemra has not been studied in patients with moderate to severe renal impairment. Renal function should be monitored closely in these patients.
Hepatic impairment: Actemra has not been studied in patients with hepatic impairment. Therefore, no dose recommendations can be made.
Paediatric patients: The safety and efficacy of Actemra subcutaneous formulation in children from birth to less than 18 years have not been established. No data are available.
Method of administration: Actemra is for subcutaneous use.
After proper training in injection technique, patients may self-inject with Actemra if their physician determines that it is appropriate. The total content (0.9 ml) of the pre-filled syringe should be administered as a subcutaneous injection. The recommended injection sites (abdomen, thigh and upper arm) should be rotated and injections should never be given into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.
The pre-filled syringe should not be shaken.
Comprehensive instructions for the administration of Actemra in a pre-filled syringe are given in the package leaflet.
Actemra, in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult 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. In these patients, Actemra can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate.
Actemra has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with methotrexate.
Actemra in combination with methotrexate (MTX) is indicated for the treatment of severe, active and progressive rheumatoid arthritis (RA) in adults not previously treated with MTX.
Actemra (tocilizumab) is indicated for the treatment of giant cell arteritis (GCA) in adult patients.
Hypersensitivity to the active substance or to any of the excipients. Active, severe infections.
Infections: Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents including tocilizumab. Tocilizumab treatment must not be initiated in patients with active infections. Administration of Tocilizumab should be interrupted if a patient develops a serious infection until the infection is controlled . Healthcare professionals should exercise caution when considering the use of tocilizumab in patients with a history of recurring or chronic infections or with underlying conditions (e.g. diverticulitis, diabetes and interstitial lung disease which may predispose patients to infections).
Vigilance for the timely detection of serious infection is recommended for patients receiving biological treatments for moderate to severe RA as signs and symptoms of acute inflammation may be lessened, associated with suppression of the acute phase reactants. The effects of tocilizumab on C-reactive protein (CRP), neutrophils and signs and symptoms of infection should be considered when evaluating a patient for a potential infection. Patients should be instructed to contact their healthcare professional immediately when any symptoms suggesting infection appear, in order to assure rapid evaluation and appropriate treatment.
Vaccinations: Live and live attenuated vaccines should not be given concurrently with Tocilizumab as clinical safety has not been established. In a randomized open-label study, adult RA patients treated with Tocilizumab and MTX were able to mount an effective response to both the 23-valent pneumococcal polysaccharide and tetanus toxoid vaccines which was comparable to the response seen in patients on MTX only. It is recommended that all patients, particularly sJIA and pJIA patients, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating Tocilizumab therapy. The interval between live vaccinations and initiation of Tocilizumab therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.
See prescribing information for full details.
The most commonly reported Adverse Drug Reactions (ADRs) were upper respiratory tract infections, nasopharyngitis, headache, hypertension and increased ALT.
The most serious ADRs were serious infections, complications of diverticulitis, and hypersensitivity reactions.
See prescribing information for full details.
Interaction studies have only been performed in adults.
Concomitant administration of a single dose of 10 mg/kg Actemra with 10-25 mg MTX once weekly had no clinically significant effect on MTX exposure.
Population pharmacokinetic analyses did not detect any effect of MTX, non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids on Actemra clearance in RA patients. In GCA patients, no effect of cumulative corticosteroid dose on Actemra exposure was observed.
The expression of hepatic CYP450 enzymes is suppressed by cytokines, such as IL-6, that stimulate chronic inflammation. Thus, CYP450 expression may be reversed when potent cytokine inhibitory therapy, such as Actemra, is introduced.
In vitro studies with cultured human hepatocytes demonstrated that IL-6 caused a reduction in CYP1A2, CYP2C9, CYP2C19, and CYP3A4 enzyme expression. Actemra normalises expression of these enzymes.
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 to, or slightly higher than, those observed in healthy subjects.
When starting or stopping therapy with tocilizumab, patients taking medicinal products which are individually adjusted and are metabolised via CYP450 3A4, 1A2 or 2C9 (e.g. methylprednisolone, dexamethasone, (with the possibility for oral glucocorticoid withdrawal syndrome), atorvastatin, calcium channel blockers, theophylline, warfarin, phenprocoumon, phenytoin, ciclosporin, or
benzodiazepines) should be monitored as doses may need to be increased to maintain therapeutic effect. Given its long elimination half-life (t1/2), the effect of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy.
Pregnancy and Lactation
Pregnancy: Women of childbearing potential must use effective contraception during and up to 3 months after treatment.
There are no adequate data from the use of tocilizumab in pregnant women. A study in animals has shown an increased risk of spontaneous abortion/embryo-foetal death at a high dose. The potential risk for humans is unknown.
Actemra should not be used during pregnancy unless clearly necessary.
Breast-feeding: It is unknown whether tocilizumab is excreted in human breast milk. The excretion of tocilizumab in milk has not been studied in animals. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Actemra should be made taking into account the benefit of breast-feeding to the child and the benefit of Actemra therapy to the woman.
There are limited data available on overdose with Actemra. One case of accidental overdose was reported in which a patient with multiple myeloma received a single dose of 40 mg/kg administered intravenously. No adverse reactions were observed.
No serious adverse reactions were observed in healthy volunteers who received a single dose up to 28 mg/kg, although dose limiting neutropenia was observed.
Incompatibilitiess: In the absence of compatability studies, this medicinal product must not be mixed with other medicinal products.
Shelf life: Once removed from the refrigerator, Actemra must be administered within 8 hours and should not be kept above 30°C.