Posology : מינונים

4.2   Posology and method of administration

Ruxience should be administered under the close supervision of an experienced healthcare professional, and in an environment where full resuscitation facilities are immediately available (see section 4.4).

Premedication and prophylactic medications

All indications
Premedication consisting of an anti-pyretic and an antihistaminic, e.g. paracetamol and diphenhydramine, should always be given before each administration of Ruxience.

Non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia

In patients with non-Hodgkin’s lymphoma and CLL, premedication with glucocorticoids should be considered if Ruxience is not given in combination with glucocorticoid-containing chemotherapy.

Prophylaxis with adequate hydration and administration of uricostatics starting 48 hours prior to start of therapy is recommended for CLL patients to reduce the risk of tumour lysis syndrome. For CLL patients whose lymphocyte counts are > 25 x 109/L, it is recommended to administer prednisone/prednisolone 100 mg intravenous shortly before infusion with Ruxience to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome.

Rheumatoid arthritis, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris

In patients with rheumatoid arthritis or pemphigus vulgaris, premedication with 100 mg intravenous methylprednisolone should be completed 30 minutes prior to Ruxience infusion to decrease the incidence and severity of infusion-related reactions (IRRs).

In patients with GPA or MPA, methylprednisolone given intravenously for 1 to 3 days at a dose of 1000 mg per day is recommended prior to the first infusion of Ruxience (the last dose of methylprednisolone may be given on the same day as the first infusion of Ruxience). This should be followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, and tapered as rapidly as possible based on clinical need) during and after the 4-week induction course of Ruxience treatment.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis is recommended for patients with GPA/MPA or PV during and following Ruxience treatment, as appropriate according to local clinical practice guidelines.

Posology

It is important to check the medicinal product labels to ensure that the appropriate formulation is being given to the patient, as prescribed.

Dose adjustments during treatment

No dose reductions of Ruxience are recommended. When Ruxience is given in combination with chemotherapy, standard dose reductions for the chemotherapeutic medicinal products should be applied.

Non-Hodgkin’s lymphoma

Follicular non-Hodgkin's lymphoma
Combination therapy
The recommended dose of Ruxience in combination with chemotherapy for induction treatment of previously untreated or relapsed/refractory patients with follicular lymphoma is: 375 mg/m2 body surface area per cycle, for up to 8 cycles.

Ruxience should be administered on Day 1 of each chemotherapy cycle, after intravenous administration of the glucocorticoid component of the chemotherapy if applicable.

Maintenance therapy
• Previously untreated follicular lymphoma
The recommended dose of Ruxience used as a maintenance treatment for patients with previously untreated follicular lymphoma who have responded to induction treatment is: 375 mg/m2 body surface area once every 2 months (starting 2 months after the last dose of induction therapy) until disease progression or for a maximum period of two years (12 infusions in total).

• Relapsed/refractory follicular lymphoma
The recommended dose of Ruxience used as a maintenance treatment for patients with relapsed/refractory follicular lymphoma who have responded to induction treatment is: 375 mg/m2 body surface area once every 3 months (starting 3 months after the last dose of induction therapy) until disease progression or for a maximum period of two years (8 infusions in total).

Monotherapy
• Relapsed/refractory follicular lymphoma
The recommended dose of Ruxience monotherapy used as induction treatment for adult patients with stage III-IV follicular lymphoma who are chemoresistant or are in their second or subsequent relapse after chemotherapy is: 375 mg/m2 body surface area, administered as an intravenous infusion once weekly for four weeks.

For re-treatment with Ruxience monotherapy for patients who have responded to previous treatment with rituximab monotherapy for relapsed/refractory follicular lymphoma, the recommended dose is: 375 mg/m2 body surface area, administered as an intravenous infusion once weekly for four weeks (see section 5.1).

Diffuse large B cell non-Hodgkin's lymphoma

Ruxience should be used in combination with CHOP chemotherapy. The recommended dosage is 375 mg/m2 body surface area, administered on Day 1 of each chemotherapy cycle for 8 cycles after intravenous infusion of the glucocorticoid component of CHOP. Safety and efficacy of rituximab have not been established in combination with other chemotherapies in diffuse large B cell non-Hodgkin’s lymphoma.


Chronic lymphocytic leukaemia
The recommended dosage of Ruxience in combination with chemotherapy for previously untreated and relapsed/refractory patients is 375 mg/m2 body surface area administered on Day 0 of the first treatment cycle followed by 500 mg/m2 body surface area administered on Day 1 of each subsequent cycle for 6 cycles in total. The chemotherapy should be given after Ruxience infusion.

Rheumatoid arthritis

A course of Ruxience consists of two 1000 mg intravenous infusions. The recommended dosage of Ruxience is 1000 mg by intravenous infusion followed by a second 1000 mg intravenous infusion two weeks later.

Subsequent courses should be administrated every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks.


Available data suggest that clinical response is usually achieved within 16 - 24 weeks of an initial treatment course. Continued therapy should be carefully reconsidered in patients who show no evidence of therapeutic benefit within this time period.

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) 

The recommended dosage of Ruxience for induction of remission therapy of GPA and MPA is 375 mg/m2 body surface area, administered as an intravenous infusion once weekly for 4 weeks (four infusions in total).


Pemphigus vulgaris
The recommended dosage of Ruxience for the treatment of pemphigus vulgaris is 1000 mg administered as an IV infusion followed two weeks later by a second 1000 mg IV infusion in combination with a tapering course of glucocorticoids.

Maintenance treatment
A maintenance infusion of 500 mg IV should be administered at month 12 and then every 6 months thereafter based on clinical evaluation.

Treatment of relapse
In the event of relapse, patients may receive 1000 mg IV. The healthcare provider should also consider resuming or increasing the patient’s glucocorticoid dose based on clinical evaluation.

Subsequent infusions may be administered no sooner than 16 weeks following the previous infusion.

Special populations
Paediatric population

The safety and efficacy of Ruxience in children below 18 years has not been established. No data are available.

Elderly
No dose adjustment is required in patients aged 65 years and above.

Method of administration
All indications

The prepared Ruxience solution should be administered as an intravenous infusion through a dedicated line. It should not be administered as an intravenous push or bolus.

Patients should be closely monitored for the onset of cytokine release syndrome (see section 4.4).
Patients who develop evidence of severe reactions, especially severe dyspnoea, bronchospasm or hypoxia should have the infusion interrupted immediately. Patients with non-Hodgkin’s lymphoma should then be evaluated for evidence of tumour lysis syndrome including appropriate laboratory tests and, for pulmonary infiltration, with a chest X-ray. In all patients, the infusion should not be restarted until complete resolution of all symptoms, and normalisation of laboratory values and chest X-ray findings. At this time, the infusion can be initially resumed at not more than one-half the previous rate.
If the same severe adverse reactions occur for a second time, the decision to stop the treatment should be seriously considered on a case by case basis.

Mild or moderate infusion-related reactions (IRR) (section 4.8) usually respond to a reduction in the rate of infusion. The infusion rate may be increased upon improvement of symptoms.

Non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis, pemphigus vulgaris, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) 
First infusion

The recommended initial rate for infusion is 50 mg/h; after the first 30 minutes, it can be escalated in 50 mg/h increments every 30 minutes, to a maximum of 400 mg/h.

Subsequent infusions

Subsequent doses of Ruxience can be infused at an initial rate of 100 mg/h, and increased by 100 mg/h increments at 30 minute intervals, to a maximum of 400 mg/h.


Rheumatoid arthritis
Alternative subsequent, faster, infusion schedule

If patients did not experience a serious infusion-related reaction with their first or subsequent infusions of a dose of 1000 mg Ruxience administered over the standard infusion schedule, a more rapid infusion can be administered for second and subsequent infusions using the same concentration as in previous infusions (4 mg/mL in a 250 mL volume). Initiate at a rate of 250 mg/hour for the first 30 minutes and then 600 mg/hour for the next 90 minutes. If the more rapid infusion is tolerated, this infusion schedule can be used when administering subsequent infusions.

Patients who have clinically significant cardiovascular disease, including arrhythmias, or previous serious infusion reactions to any prior biologic therapy or to rituximab, should not be administered the more rapid infusion.