Actemra

/ Roche

Treatment should be initiated by healthcare professionals experienced in the diagnosis and treatment of RA, sJIA or pJIA.
RA Patients
Posology: The recommended posology is 8 mg/kg body weight, given once every four weeks. For individuals whose body weight is more than 100 kg, doses exceeding 800 mg per infusion are not recommended. See prescribing information for full details. Doses above 1.2 g have not been evaluated in clinical studies. See prescribing information for full details.
Dose adjustments due to laboratory abnormalities:
Liver enzyme abnormalities:
> 1 to 3 x Upper Limit of Normal (ULN): Modify the dose of the concomitant MTX if appropriate. For persistent increases in this range, reduce Tocilizumab dose to 4 mg/kg or interrupt Tocilizumab until alanine aminotransferase (ALT) or aspartate aminotransferase (AST) have normalized. Restart with 4 mg/kg or 8 mg/kg, as clinically appropriate.
> 3 to 5 x ULN (confirmed by repeat testing): Interrupt Tocilizumab,dosing until < 3 x ULN and follow recommendations above for > 1 to 3 x ULN. For persistent increases > 3 x ULN, discontinue Tocilizumab.
> 5 x ULN: Discontinue Tocilizumab.
Low absolute neutrophil count (ANC): In patients not previously treated with Tocilizumab, initiation is not recommended in patients with an absolute neutrophil count (ANC) below 2 x 109/l. See prescribing information for full details.
For dose adjustment due to low platelet count: See prescribing information for full details.
Paediatric patients:
sJIA Patients: The recommended posology in patients above 2 years of age is 8 mg/kg once every 2 weeks in patients weighing greater than or equal to 30 kg or 12 mg/kg once every 2 weeks in patients weighing less than 30 kg. The dose should be calculated based on the patient’s body weight at each administration. A change in dose should only be based on a consistent change in the patient’s body weight over time. The safety and efficacy of Tocilizumab in children below 2 years of age has not been established. No data are available. Dose interruptions of tocilizumab for the following laboratory abnormalities are recommended in sJIA patients in the tables below. If appropriate, the dose of concomitant MTX and/or other medications should be modified or dosing stopped and tocilizumab dosing interrupted until the clinical situation has been evaluated. As there are many co-morbid conditions that may affect laboratory values in sJIA, the decision to discontinue tocilizumab for a laboratory abnormality should be based upon the medical assessment of the individual patient.
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. Tocilizumab has not been studied in patients with moderate to severe renal impairment. Renal function should be monitored closely in these patients.
Hepatic impairment: Tocilizumab has not been studied in patients with hepatic impairment. Therefore, no dose recommendations can be made.
Method of administration: After dilution, Tocilizumab for RA, sJIA and pJIA patients should be administered as an intravenous infusion over 1 hour.
RA, sJIA and pJIAPatients ≥ 30 kg: Tocilizumab should be diluted to a final volume of 100 ml with sterile, non-pyrogenic sodium chloride 9 mg/ml (0.9%) solution for injection using aseptic technique.
sJIA and pJIA Patients < 30 kg: Tocilizumab should be diluted to a final volume of 50 ml with sterile, non-pyrogenic sodium chloride 9 mg/ml (0.9%) solution for injection using aseptic technique.
See prescribing information for full details.

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, Tocilizumab can be given as monotherapy in case of intolerance to 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 X-ray and to improve physical function when given in combination with methotrexate.

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.

Upper respiratory tract infections, hypercholesterolaemia, herpes zoster,  hepatic transaminases increased, weight increased, total bilirubin increased, headache, dizziness, cough, dyspnoea, rash, pruritus, urticaria, hypertension, leukopenia, neutropenia, conjunctivitis, abdominal pain, mouth ulceration, gastritis, peripheral oedema hypersensitivity reaction, injection site reaction, cellulitis, pneumonia, oral herpes simplex.
See prescribing information for full details.

Interaction studies have only been performed in adults.
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 tocilizumab, is introduced.
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. 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.
See prescribing information for full details.

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.
Lactation: It is unknown whether tocilizumab is excreted in human breast milk. See prescribing information for full details.

There are limited data available on overdose with Tocilizumab. One case of accidental overdose was reported in which a patient with multiple myeloma received a single dose of 40 mg/kg. 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.
Paediatric population: No case of an overdose in the paediatric population has been observed.

Fertility: Available non-clinical data do not suggest an effect on fertility under tocilizumab treatment.