MabThera/MabThera SC Dosage/Direction for Use

General: MabThera/MabThera SC: Substitution by any other biological medicinal product requires the consent of the prescribing physician.
It is important to check the product labels to ensure that the appropriate formulation (IV or SC) and strength is being given to the patient, as prescribed.
MabThera/Rituxan should always be administered in an environment where full resuscitation facilities are immediately available and under the close supervision of an experienced healthcare professional.
The safety and efficacy of alternating or switching between MabThera/Rituxan and products that are biosimilar but not deemed interchangeable has not been established. Therefore, the benefit-risk of alternating or switching needs to be carefully considered.
Premedication and Prophylactic Medications: Premedication consisting of an analgesic/anti-pyretic (e.g., paracetamol /acetaminophen) and an anti-histaminic drug (e.g., diphenhydramine) should always be given before each administration of MabThera/Rituxan.
Premedication with glucocorticoids should be administered in order to reduce the frequency and severity of infusion-related reactions. Patients with RA, PV or adult and pediatric GPA/MPA should receive 100 mg IV methylprednisolone to be completed 30 minutes prior to each MabThera/Rituxan IV infusion (see Precautions).
In patients with NHL or CLL premedication with glucocorticoids should also be considered, particularly if MabThera/Rituxan is not given in combination with steroid-containing chemotherapy (see Precautions).
Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for adult and pediatric patients with GPA/MPA or PV prior to and following MabThera/Rituxan IV treatment, as appropriate according to local clinical practice guidelines.
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 x10⁹/L it is recommended to administer prednisone/ prednisolone 100 mg intravenously shortly before administration with MabThera/Rituxan to decrease the rate and severity of acute infusion reactions and/or cytokine release syndrome.
Dosage adjustments during treatment: No dose reductions of MabThera/Rituxan are recommended. When MabThera/Rituxan is given in combination with chemotherapy, standard dose reductions for the chemotherapeutic drugs should be applied.
Mabthera: MabThera/Rituxan IV formulation is not intended for subcutaneous administration (see Cautions for Usage).
Do not administer the prepared infusion solutions as an intravenous push or bolus (see Cautions for Usage).
Intravenous Formulation Infusion Rate: First intravenous infusion: The recommended initial infusion rate is 50 mg/hour; after the first 30 minutes, the rate can be escalated in 50 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
Subsequent intravenous infusions: Subsequent infusions of MabThera/Rituxan IV can be started at a rate of 100 mg/hour and increased by 100 mg/hour increments every 30 minutes to a maximum of 400 mg/hour.
MabThera SC: MabThera/Rituxan SC formulation is not intended for intravenous administration (see Cautions for Usage).
MabThera/Rituxan SC 1400 mg is intended for use in non-Hodgkin's lymphoma (NHL) only.
MabThera/Rituxan SC should be injected subcutaneously into the abdominal wall and never into areas where the skin is red, bruised, tender, or hard or areas where there are moles or scars. No data are available on performing the injection in other sites of the body therefore injections should be restricted to the abdominal wall.
During the treatment course with MabThera/Rituxan SC, other medications for subcutaneous administration should preferably be administered at different sites.
MabThera/Rituxan SC 1400 mg injection should be administered over approximately 5 minutes.
If an injection is interrupted it can be resumed or another location may be used, if appropriate.
Standard dosage: Low-grade or Follicular Non-Hodgkin's Lymphoma: MabThera: Initial treatment: Intravenous monotherapy: The recommended dosage of MabThera/Rituxan IV used as monotherapy for adult patients is 375 mg/m² body surface area (BSA), administered as an intravenous infusion (see "Intravenous Formulation Infusion Rate" in the previous text) once weekly for 4 weeks.
Intravenous combination therapy: The recommended dosage of MabThera/Rituxan IV (R-IV) in combination with any chemotherapy is 375 mg/m² BSA per cycle for a total of: ­ 8 cycles R-IV with CVP (21 days/cycle).
8 cycles R-IV with MCP (28 days/cycle).
8 cycles R-IV with CHOP (21 days/cycle); 6 cycles if a complete remission is achieved after 4 cycles.
6 cycles R-IV with CHVP-Interferon (21 days/cycle).
MabThera/Rituxan IV should be administered on day 1 of each chemotherapy cycle after intravenous administration of the glucocorticoid component of the chemotherapy, if applicable.
Alternative 90-minute subsequent intravenous infusions: Patients who do not experience a Grade 3 or 4 infusion-related adverse event with Cycle 1 are eligible for an alternative 90-minute subsequent infusion in Cycle 2. The alternative infusion rate can be started at a rate of 20% of the total dose given in the first 30 minutes and the remaining 80% of the total dose given over the next 60 minutes for a total infusion time of 90 minutes. Patients who tolerate the first 90-minute MabThera/Rituxan IV infusion (Cycle 2) can continue to receive subsequent MabThera/Rituxan IV infusions at the 90-minute rate for the remainder of the treatment regimen (through Cycle 6 or Cycle 8). Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count > 5000/mm³ before Cycle 2 should not receive the 90-minute infusion (see Clinical Trials under Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions.
Re-treatment following relapse: Patients who have responded to MabThera/Rituxan IV initially may receive MabThera/Rituxan IV at a dose of 375 mg/m² BSA, administered as an IV infusion once weekly for 4 weeks (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies: Re-treatment, weekly for 4 doses under Actions).
Maintenance treatment: Previously untreated patients after response to induction treatment may receive maintenance therapy with MabThera/Rituxan IV given at 375 mg/m² BSA once every 2 months until disease progression or for a maximum period of two years (12 infusions in total).
Relapsed/refractory patients after response to induction treatment may receive maintenance therapy with MabThera/Rituxan IV given at 375 mg/m² BSA once every 3 months until disease progression or for a maximum period of two years (8 infusions in total).
MabThera SC (1400 mg): All patients must always receive their first dose of MabThera/Rituxan by intravenous administration. During their first cycle the patient is at the highest risk of experiencing an infusion/administration related reaction. Beginning therapy with MabThera/Rituxan IV infusion allows management of infusion/administration related reactions by slowing or stopping the intravenous infusion (see Precautions). The subcutaneous formulation must only be given at the second or subsequent cycles (see "First administration: Intravenous formulation" and "Subsequent administrations: Subcutaneous formulation" as follows).
First administration: Intravenous formulation: The first administration of MabThera/Rituxan must always be given by intravenous infusion at a dose of 375 mg/m² BSA (see "Intravenous Formulation Infusion Rate" as previously mentioned).
Subsequent administrations: Subcutaneous formulation: Patients unable to receive the full MabThera/Rituxan intravenous infusion dose should continue to receive subsequent cycles with MabThera/Rituxan IV until a full IV dose is successfully administered.
For patients who are able to receive the full MabThera/Rituxan IV infusion dose the second or subsequent MabThera/Rituxan dose can be given subcutaneously using the MabThera/Rituxan SC formulation (see Precautions).
Initial treatment: Subcutaneous monotherapy: The recommended dosage of MabThera/Rituxan SC used as monotherapy for adult patients is subcutaneous injection at a fixed dose of 1400 mg irrespective of the patient's BSA, once weekly for 3 weeks following MabThera/Rituxan IV at week 1 (1st week R-IV then 3 weeks R-SC; 4 weeks in total).
Subcutaneous combination therapy: MabThera/Rituxan SC should be administered on day 0 or day 1 of each chemotherapy cycle after administration of the glucocorticoid component of the chemotherapy, if applicable.
The recommended dosage in combination with any chemotherapy is MabThera/Rituxan IV (R-IV) 375 mg/m² BSA intravenously for the first cycle followed by subcutaneous injection of MabThera/Rituxan SC (R-SC) at a fixed dose of 1400 mg, irrespective of the patient's BSA.
1st cycle R-IV with CVP + 7 cycles R-SC with CVP (21 days/ cycle).
1st cycle R-IV with MCP + 7 cycles R-SC with MCP (28 days/ cycle).
1st cycle R-IV with CHOP + 7 cycles R-SC with CHOP (21 days/ cycle); or a total of 6 cycles (1st cycle R-IV then 5 cycles R-SC) if complete remission is achieved after 4 cycles.
1st cycle R-IV with CHVP-Interferon + 5 cycles R-SC with CHVP-Interferon (21 days/ cycle).
Re-treatment following relapse: Patients who have responded to MabThera/Rituxan IV or SC initially may be treated again with MabThera/Rituxan SC at a fixed dose of 1400 mg, administered as a subcutaneous injection once weekly, following a first administration of MabThera/Rituxan given by intravenous infusion at a dose of 375 mg/m² BSA (1st week R-IV then 3 weeks R-SC; 4 weeks in total) (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies: Re-treatment, weekly for 4 doses under Actions).
Maintenance treatment: Previously untreated patients after response to induction treatment may receive maintenance therapy with MabThera/Rituxan SC given at a fixed dose of 1400 mg once every 2 months until disease progression or for a maximum period of two years (12 administrations in total).
Relapsed/refractory patients after response to induction treatment may receive maintenance therapy with MabThera/Rituxan SC given at a fixed dose of 1400 mg once every 3 months until disease progression or for a maximum period of two years (8 administrations in total).
Diffuse Large B-cell Non-Hodgkin's Lymphoma: MabThera: In patients with diffuse large B cell non-Hodgkin's lymphoma MabThera/Rituxan IV should be used in combination with CHOP (cyclophosphamide, doxorubicin, prednisone and vincristine) chemotherapy. The recommended dosage of MabThera/Rituxan IV is 375 mg/m² BSA, administered on day 1 of each chemotherapy cycle for 8 cycles after IV administration of the glucocorticoid component of CHOP (see "Intravenous Formulation Infusion Rate" as previously mentioned).
Alternative 90-minute subsequent intravenous infusions: Patients who do not experience a Grade 3 or 4 infusion-related adverse event with Cycle 1 are eligible for an alternative 90-minute subsequent infusion in Cycle 2. The alternative infusion rate can be started at a rate of 20% of the total dose given in the first 30 minutes and the remaining 80% of the total dose given over the next 60 minutes for a total infusion time of 90 minutes. Patients who tolerate the first 90-minute MabThera/Rituxan IV infusion (Cycle 2) can continue to receive subsequent MabThera/Rituxan IV infusions at the 90-minute rate for the remainder of the treatment regimen (through Cycle 6 or Cycle 8). Patients who have clinically significant cardiovascular disease or who have a circulating lymphocyte count > 5000/mm³ before Cycle 2 should not receive the 90-minute infusion (see Clinical Trials under Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions).
MabThera SC (1400 mg): All patients must always receive their first dose of MabThera/Rituxan by intravenous administration. During their first cycle the patient is at the highest risk of experiencing an infusion/administration related reaction. Beginning therapy with MabThera/Rituxan IV infusion allows management of infusion/administration related reactions by slowing or stopping the intravenous infusion (see Precautions). The subcutaneous formulation must only be given at the second or subsequent cycles (see "First administration: Intravenous formulation" and "Subsequent administrations: Subcutaneous formulation" as follows).
In patients with diffuse large B cell non-Hodgkin's lymphoma MabThera/Rituxan SC 1400 mg should be used in combination with CHOP (cyclophosphamide, doxorubicin, prednisone and vincristine) chemotherapy.
First administration: Intravenous formulation: The first administration of MabThera/Rituxan must always be given by intravenous infusion at a dose of 375 mg/m² BSA (see "Intravenous Formulation Infusion Rate" as previously mentioned).
Subsequent administrations: Subcutaneous formulation: Patients unable to receive the full MabThera/Rituxan intravenous infusion dose should continue to receive subsequent cycles with MabThera/Rituxan IV until a full IV dose is successfully administered.
For patients who are able to receive the full MabThera/Rituxan IV infusion dose, the second or subsequent MabThera/Rituxan doses can be given subcutaneously using the MabThera/Rituxan SC formulation (see Precautions).
The recommended dosage of MabThera/Rituxan SC is a fixed dose of 1400 mg, irrespective of the patient's BSA, administered on day 1 of each chemotherapy cycle for 8 cycles (1st cycle R-IV with CHOP + 7 cycles R-SC with CHOP; 8 cycles in total) after IV administration of the glucocorticoid component of CHOP.
Chronic Lymphocytic Leukaemia: MabThera: The recommended dosage of MabThera/Rituxan IV in combination with chemotherapy for previously untreated and relapsed/refractory CLL patients is 375 mg/m² BSA administered on day 1 of the first treatment cycle followed by 500 mg/m2 BSA administered on day 1 of each subsequent cycle for 6 cycles in total (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions).
The chemotherapy should be given after the MabThera/Rituxan IV infusion (see "Intravenous Formulation Infusion Rate" as previously mentioned).
Rheumatoid Arthritis: MabThera: A course of MabThera/Rituxan IV consists of two 1000 mg IV infusions. The recommended dosage of MabThera/Rituxan is 1000 mg by IV infusion followed two weeks later by the second 1000 mg IV infusion (see "Intravenous Formulation Infusion Rate" as previously mentioned).
The need for further courses should be evaluated 24 weeks following the previous course with retreatment given based on residual disease or disease activity returning to a level above a DAS28-ESR of 2.6 (treatment to remission) (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies: Rheumatoid Arthritis under Actions). Patients may receive further courses no sooner than 16 weeks following the previous course.
Alternative 120-minute subsequent infusions with the concentration of 4 mg/mL in a 250 mL volume: If patients did not experience a serious infusion-related adverse event with their previous infusion administered over the original administration schedule, a 120-minute infusion can be administered for subsequent infusions. 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 120-minute infusion is tolerated, the same alternative 120-minute infusion rate can be used when administering subsequent infusions and courses.
Patients who have clinically significant cardiovascular disease including arrhythmias or previous serious infusion reactions to any prior biologic therapy or to MabThera/Rituxan, should not be administered the 120-minute infusion.
Adult Patients with Granulomatosis with Polyangiitis (Wegener's) (GPA) and Microscopic Polyangiitis (MPA): MabThera: Induction of Remission: The recommended dosage of MabThera/Rituxan IV for treatment of adult patients with severe active GPA and MPA is 375 mg/m² BSA, administered as an IV infusion (see "Intravenous Formulation Infusion Rate" as previously mentioned) once weekly for 4 weeks.
Methylprednisolone given IV for 1 to 3 days at a dose of 1000 mg per day is recommended in combination with MabThera/Rituxan IV to treat severe vasculitis symptoms, followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day, and tapered as rapidly as possible per clinical need) during and after the 4 week induction course of MabThera/Rituxan IV treatment.
Maintenance Treatment: Following induction of remission with MabThera/Rituxan IV, maintenance treatment should be initiated no sooner than 16 weeks after the last MabThera/Rituxan IV infusion.
Following induction of remission with other standard of care immunosuppressants, MabThera/Rituxan IV maintenance treatment should be initiated during the 4 week period that follows disease remission.
Administer MabThera/Rituxan IV as two 500 mg IV infusions separated by two weeks, followed by a 500 mg IV infusion at month 6, 12 and 18 and then every 6 months thereafter based on clinical evaluation.
Pediatric Patients with Granulomatosis with Polyangiitis (Wegener's) (GPA) and Microscopic Polyangiitis (MPA): MabThera: The recommended dosage of MabThera/Rituxan IV for the treatment of pediatric patients with active GPA/MPA is 375 mg/m² BSA, administered as an IV infusion once weekly for 4 weeks.
Prior to the first MabThera/Rituxan IV infusion, methylprednisolone should be given IV for three daily doses of 30 mg/kg/ (not to exceed 1 g/day) to treat severe vasculitis symptoms. Up to three additional daily doses of 30 mg/kg IV methylprednisolone can be given prior to the first MabThera/Rituxan IV infusion.
Following completion of IV methylprednisolone, patients should receive oral prednisone 1 mg/kg/day (not to exceed 60 mg/day) and tapered as rapidly as possible per clinical need (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions).
Maintenance treatment: Administer as two 250 mg IV infusions separated by 2 weeks, followed by 250 mg IV infusion every 6 months thereafter.
Pemphigus Vulgaris: MabThera: The recommended dosage of MabThera/Rituxan IV 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 (see General under Dosage & Administration).
Maintenance Treatment: Maintenance infusions 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 during the course of MabThera/Rituxan IV therapy, 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 Dosage Instructions: Pediatric use: No dose adjustments are recommended in pediatric patients (≥ 2 to < 18 years of age) with active GPA/MPA. Currently available data are described in Precautions, Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies and Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
The safety and efficacy of MabThera/Rituxan IV in children and adolescents (≥2 to <18 years) have not been established in indications other than active GPA/MPA.
MabThera/Rituxan IV should not be used in pediatric patients with active GPA/MPA < 2 years of age (see Precautions).
Geriatric use: No dose adjustment is required in patients aged ≥65 years of age.