Posology : מינונים

4.2   Posology and method of administration

Truxima 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 Truxima.


Non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia
In patients with non-Hodgkin’s lymphoma and CLL, premedication with glucocorticoids should be considered if Truxima 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 Truxima to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome.

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris

In patients with granulomatosis with polyangiitis (Wegener’s) or microscopic polyangiitis, methylprednisolone given intravenously for 1 to 3 days at a dose of 1000 mg per day is recommended prior to the first infusion of Truxima (the last dose of methylprednisolone may be given on the same day as the first infusion of Truxima). 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 Truxima treatment.

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

Posology
Dose adjustments during treatment
No dose reductions of Truxima are recommended. When Truxima 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 Truxima 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.

Truxima 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 Truxima 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 Truxima 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 Truxima 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 retreatment with Truxima monotherapy for patients who have responded to previous treatment with Truxima 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

Truxima 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 Truxima 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 Truxima 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 Truxima infusion.

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) 
The recommended dosage of Truxima 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 Truxima 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 months 12 and 18, 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 Truxima 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

Truxima is for intravenous use. The prepared Truxima 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, 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 Truxima 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.