Rituximab (Mabthera) is an anti-CD 20 monoclonal antibody that is used to treat the following conditions:

• For the treatment of CD 20 positive chronic lymphocytic leukemia in combination with fludarabine and cyclophosphamide.
• Treatment of Wegener's granulomatosis (Granulomatosis with polyangiitis) in combination with steroids.
• Microscopic polyangiitis along with steroids
• Treatment of CD-20 positive Non-Hodgkin lymphoma
  • Follicular B cell lymphoma (relapsed or refractory)
  • Diffuse large B-cell lymphoma (in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone)
• Moderate to severe pemphigus vulgaris
• Treatment of moderate to severely active Rheumatoid arthritis in combination with methotrexate in patients not responsive to one or more TNF antagonist therapies.

Off-label uses of Rituximab include:

• Antibody-mediated cardiac transplant rejection
• Refractory autoimmune hemolytic anemia
• Burkitt lymphoma
• CNS lymphoma
• Chronic refractory Graft-vs-host disease
• Advanced Nodular lymphocyte predominant Hodgkin's lymphoma
• Resistant idiopathic membranous nephropathy
• Refractory immune thrombocytopenia
• Refractory Lupus nephritis
• Advanced gastric mucosa-associated lymphoid tissue lymphoma
• Refractory myasthenia gravis
• For the prevention of relapse of Neuromyelitis Optica
• Refractory pemphigus vulgaris
• Post-transplant lymphoproliferative disorder
• Splenic marginal zone lymphoma
• Acquired thrombotic thrombocytopenic purpura, and
• Waldenstrom's macroglobulinemia

Rituximab (Mabthera) Dose in Adults

Pretreatment considerations and the use of prophylactic medications:​​​​​​​

• Patients should be administered acetaminophen and antihistamines prior to the infusion.
• When rituximab is used as a chemotherapeutic agent, patients should be well hydrated and treatment for hyperuricemia should be given, especially if the lymphocyte counts are more than 25000/ul, to prevent tumor lysis syndrome.
• Pneumocystis jirovecii pneumonia (PCP) and prophylaxis for herpes virus infection is recommended during the treatment and up to 12 months following the treatment in patients with chronic lymphocytic leukemia.
• Similarly, PCP prophylaxis is also recommended during therapy and up to 6 months following treatment after rituximab treatment in patients with granulomatosis with polyangiitis
• Patients treated for pemphigus vulgaris should also be considered for PCP prophylaxis.
• All patients with resolved hepatitis B virus infection receiving rituximab should be considered for antiviral prophylaxis [Ref].

Rituximab Dosing:

• Off label use in antibody-mediated rejection in cardiac transplant patients:
  • Intravenous 375 mg/m2 once weekly ( for 1 to 4 doses) or 1000 mg after one and three weeks (Antibody-mediated rejection - AHA statement)

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• Off label use in refractory autoimmune hemolytic anemia:
  • Intravenous 375 mg/m2 once weekly (for 4 doses) with or without steroids.

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• Off label use in Burkitt lymphoma:
  • 375 mg/m2 intravenous on
    • Days 1 and 11 of cycle number 1 and 3, and
    • Days 2 and 8 of cycles number 2 and 4, or
    • 375 mg/m2 at the start of each chemotherapy cycle, followed by 2 additional doses 3 and 6 weeks after the completion of chemotherapy, or
    • 50 mg/m2 on day 8 and 375 mg/m2 on days 10 and 12 of cycle 2 followed by 375 mg/m2 on day 8 of cycles 3 to 7.

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• Chronic lymphocytic leukemia:
  • Intravenous 375 mg/m2 on the day prior to fludarabine & cyclophosphamide in cycle 1, then 500 mg/m2 on day 1 (every 28 days) of cycles 2 to 6 (in combination with fludarabine and cyclophosphamide).

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• Off label use in Chronic lymphocytic leukemia:
  • 375 mg/m2 on the day prior to bendamustine in cycle 1, then 500 mg/m on day 1 (every 28 days) of cycles 2 to 6 (in combination with bendamustine) in previously untreated patients or
  • 375 mg/m2 on days 1 and 4 of cycle 1 (or 50 mg/m2 on day 1, followed by 325 mg/m2 on day 3, followed by 375 mg/m2 on day 5 of cycle 1), then 375 mg/m2 on day 1 (every 28 days) of cycles 2 to 6 in combination with fludarabine.

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• Relapsed or refractory CLL:
  • 375 mg/m2 on day 1, followed by 500 mg/m2 every 14 days for 4 doses and then 500 mg/m2 every 28 days for 3 doses (in combination with idelalisib) or
  • 375 mg/m2 on the day prior to bendamustine in cycle 1, then 500 mg/m2 on day 1 (every 28 days) of cycles 2 to 6 (in combination with bendamustine), or
  • 375 mg/m2 on day 1 in cycle 1, then 500 mg/m2 on day 1 (every 28 days) of cycles 2 to 6 (in combination with bendamustine and ibrutinib), or
  • 375 mg/m2 on day 1 of cycle 1 (following completion of dose ramp-up for venetoclax), then 500 mg/m2 on day 1 (every 28 days) of cycles 2 to 6 (in combination with venetoclax)

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• Off label use in CNS lymphoma:
  • Newly diagnosed patients: 375 mg/m2 on day 3 every 14 days (in combination with high-dose methotrexate) until disease progression or unacceptable toxicity, or
  • for 2 doses beyond a complete response followed by monthly treatments for up to a total of 1 year, or
  • 500 mg/m on day 1 of each cycle for 5 to 7 induction cycles (in combination with high-dose methotrexate, vincristine, and procarbazine, followed by whole-brain radiotherapy and cytarabine consolidation)
  • 375 mg/m2 on day 1 every 28 days (in combination with temozolomide) for 4 cycles, then followed by temozolomide monotherapy.

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• Off label use in chronic refractory Graft-versus-host disease (GVHD):
  • 375 mg/m2 intravenously once weekly for 4 doses. A second course of 4 weekly doses may be administered after 8 weeks of initial therapy if required because of incomplete response or
  • 375 mg/m once weekly for 4 to 8 doses

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• Granulomatosis with polyangiitis (Wegener granulomatosis):
  • Induction therapy for active Wegener's granulomatosis:
    • 375 mg/m2 intravenous once weekly for 4 doses. In severe cases, Rituximab should be administered in combination with methylprednisolone intravenous for 1 to 3 days followed by daily prednisone. (Corticosteroid therapy should begin with rituximab therapy or 14 days prior to the therapy)

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  • Maintenance therapy after the initial induction therapy:
    • Two infusions of 500 mg separated by 2 weeks, followed by 500 mg once every 6 months thereafter if indicated.
    • Follow-up therapy should begin within 24 weeks of the last dose of rituximab dose but no sooner than 16 weeks of the last dose.
    • Follow-up treatment with rituximab may begin within 4 weeks if rituximab was not used for induction.
    • Methylprednisolone at a dose of 100 mg should be given 30 minutes prior to each dose.

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• Advanced Hodgkin lymphoma (nodular lymphocyte-predominate):
  • 375 mg/m2 intravenous once weekly for 4 weeks, or
  • 375 mg/m once weekly for 4 weeks followed by maintenance dosing of 375 mg/m2 once weekly for 4 weeks every 6 months for 2 years.
  • It may be administered as monotherapy or in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP], or, in combination with ifosfamide, carboplatin, and etoposide [RICE]) for a relapsed disease.

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• Off-label use in patients with resistant idiopathic membranous nephropathy:
  • 375 mg/m2 intravenous once weekly for 4 doses. A similar course of 4 doses may be repeated at 6 months, or
  • 1,000 mg on days 1 and 15. The cycle may be repeated at 6 months, or
  • 375 mg/m2 once weekly for 2 doses, or
  • 375 mg/m2 once weekly for 4 doses, or
  • 375 mg/m2 as a single dose and repeated at least 1 week later (only if circulating B-cells >5/mm3 were detected).

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• Off label use in refractory Immune thrombocytopenia:
  • 375 mg/m2 intravenous once weekly for 4 doses or
  • 100 mg once weekly for 4 weeks (Low-dose regimen in patients with ITP

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• Off-label use in refractory Lupus nephritis:
  • 375 mg/m2 once weekly for 4 doses or
  • 1,000 mg on days 0 and 15 or
  • 500 to 1,000 mg on days 1 and 15

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• Microscopic polyangiitis (MPA):
  • Induction therapy for active MPA:
    • 375 mg/m2 intravenous once weekly for 4 doses. It may be given with intravenous methylprednisolone for 1 to 3 days followed by prednisone in severe cases. (Corticosteroid therapy should be initiated with rituximab therapy or may be initiated 14 days prior to the therapy.

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  • Maintenance therapy after induction:
    • 500 mg as 2 infusions separated at 2 weeks interval, followed by 500 mg once every 6 months thereafter if clinically indicated. Follow-up therapy should begin within 24 weeks of the last rituximab induction dose if indicated, but no sooner than 16 weeks following the last rituximab induction dose.
    • In case, induction therapy is other than rituximab, maintenance therapy with rituximab may be initiated within the 4 weeks after achieving disease remission.
    • Premedication with 100 mg intravenous methylprednisolone is recommended 30 minutes prior to each dose.

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• Off-label use in advanced gastric mucosa-associated lymphoid tissue lymphoma
  • 375 mg/m2 once weekly for 4 doses

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• Off-label use in Severe refractory Myasthenia gravis:
  • 375 mg/m2 once weekly for 4 weeks, then monthly for 2 months or
  • 375 mg/m once weekly for 4 weeks.

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• Off-label use in the prevention of Neuromyelitis Optica:
  • 1,000 mg once every 2 weeks for 2 doses, repeat 6 monthly or when CD19 cells counts are >0.1% of total lymphocytes or
  • 375 mg/m2 once weekly for 4 weeks, repeat after 6 months.

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• Refractory or relapsed low-grade or follicular CD 20 positive C cells Non-Hodgkin lymphoma:
  • 375 mg/m2 intravenous once weekly for 4 or 8 doses
  • For maintenance therapy after induction therapy:
    • 375 mg/m2 as a single agent 3 monthly until disease progression or for a total duration of 2 years.

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• Diffuse large B-cell lymphoma:
  • 375 mg/m2 given on day 1 of each chemotherapy cycle for a total of 8 doses (in combination with CHOP chemotherapy

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• Follicular CD 20 positive previously untreated follicular lymphoma:
  • 375 mg/m2 given on day 1 of each chemotherapy cycle for up to 8 doses (in combination with first-line chemotherapy)
  • Maintenance therapy should begin after 8 weeks of the induction therapy:
    • 375 mg/m2 once every 8 weeks for 12 doses as monotherapy or in combination with chemotherapy.

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• CD 20 positive low-grade B cell lymphoma after 6 - 8 cycles of the first line CVP are completed:
  • 375 mg/m2 once weekly for 4 doses every 6 months for a maximum of 16 doses as monotherapy

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• NHL in Combination therapy with ibritumomab:
  • 250 mg/m2 intravenous on day 1; repeat in 7 to 9 days with ibritumomab.

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• Pemphigus vulgaris:
  • 1,000 mg once every 2 weeks for 2 doses in combination with glucocorticoids followed by maintenance of rituximab 500 mg at months 12 and 18, and every 6 months thereafter or as clinically indicated. Relapse should be treated with rituximab 1,000 mg and glucocorticoids. Subsequent rituximab should not be given until 16 weeks of the last infusion.
  • Patients should be premedicated with intravenous 100 mg of methylprednisolone 30 minutes prior to the infusion.

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• Refractory Pemphigus vulgaris (off-label):
  • 375 mg/m2 intravenous once weekly for 4 doses. The dose may be repeated if indicated. or
  • 375 mg/m2 intravenous once weekly of weeks 1, 2, and 3 of a 4-week cycle. Repeat for 1 additional cycle, then 1 dose per month for 4 months (total of 10 doses in 6 months), in combination with IV immune globulin or
  • 1,000 mg once every 2 weeks for 2 doses.

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• Off-label use in Posttransplant lymphoproliferative disorder:
  • 375 mg/m2 once weekly for 4 doses or
  • 375 mg/m once weekly for 4 doses, followed 4 weeks later with 4 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy.

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• Rheumatoid arthritis:
  • 1,000 mg intravenous on days 1 and 15 in combination with methotrexate; subsequent courses may be administered every 24 weeks if indicated. It may be repeated no sooner than every 16 weeks.
  • Patients should be premedicated with 100 mg of methylprednisolone intravenous 30 minutes prior to each dose.

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• Off-label use in splenic marginal zone lymphoma:
  • 375 mg/m2 intravenous once weekly for 6 weeks followed by 375 mg/m2 once every 2 months for 1 to 2 years or
  • 375 mg/m2 once weekly for 4 weeks as monotherapy or
  • 375 mg/m on day 1 of each chemotherapy cycle for up to 6 cycles. Additional 1 to 2 cycles of rituximab monotherapy may be administered to improve response.

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• Acquired Thrombotic thrombocytopenic purpura (off-label use):
  • 375 mg/m2 intravenous once weekly for 4 doses (in combination with plasma exchange). (additional four doses may be administered for ADAMTS13 levels remaining below normal or for persistently detectable anti-ADAMTS13 IgG antibodies.
  • Rituximab should be administered immediately after plasma exchange. The next plasma exchange should be delayed at least for allow 24 hours after rituximab infusion.

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• Waldenström macroglobulinemia (off-label use):
  • Rituximab monotherapy:
    • 375 mg/m2 once weekly for 4 weeks. Repeat the dose after 12 weeks.
  • Rituximab in combination with cyclophosphamide and dexamethasone:
    • 375 mg/m2 on day 1 every 21 days for 6 cycles.
  • In combination with bortezomib:
    • 375 mg/m2 on days 1, 8, 15, and 22 every 28 days during cycles 1 and 4. A total of 8 rituximab doses should be given in a 6 cycles treatment.
  • In combination with bortezomib and dexamethasone:
    • 375 mg/m2 on days 1, 8, 15, and 22 every 35 days during cycles 2 and 5. 8 rituximab doses should be given in the 6 cycles treatment regimen or
    • 375 mg/m2 on day 11 every 21 days for 4 cycles as induction therapy followed by 4 additional maintenance cycles given 12 weeks apart twelve weeks after the induction therapy.
  • In combination with bendamustine:
    • 375 mg/m2 on day 1 every 28 days for four cycles. ( Single rituximab doses were also administered 1 week prior to the first cycle and 4 weeks after the last cycles (for a total of 6 rituximab doses).
  • In combination with carfilzomib and dexamethasone:
    • 375 mg/m2 intravenous on days 2 and 9 every 21 days for six induction cycles, followed by 375 mg/m2 on day 2 every 8 weeks for eight maintenance cycles.
  • In combination with ibrutinib:
    • 375 mg/m2 intravenous once weekly during weeks 1 to 4 and weeks 17 to 20.

Rituximab (Mabthera) Dose in Childrens

Note: All patients should receive acetaminophen and an antihistamine prior to rituximab. Furthermore, patients using rituximab for cancers with a high tumor burden (or those with lymphocytes more than 25000/ul) should also add a uricosuric agent like allopurinol to avoid the risk of tumor lysis syndrome.

• CD 20 positive, mature B-cell Acute lymphoblastic leukemia:
  • Children 5 years of age or more and Adolescents:
    • 375 mg/m2 administered intravenous on days 1 and 3 of courses 1 and 2 and on day 1 only of course 3. It should be used in combination with ifosfamide, carboplatin, and etoposide (ICE).

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• Autoimmune hemolytic anemia:
  • Infants 4 months of age or more, Children, and Adolescents:
    • 375 mg/m2 intravenous infusion once weekly for 4 doses.

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• Chronic, steroid-refractory, Graft-versus-host disease (GVHD):
  • Children and Adolescents:
    • 375 mg/m2 intravenous once weekly for 4 doses followed by monthly infusions. (GVHD musculoskeletal and skin manifestations respond better than ophthalmic, hepatic, or gastrointestinal manifestations).

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• Chronic Immune thrombocytopenic purpura (ITP):
  • Children and Adolescents:
    • 375 mg/m2 intravenous infusions once weekly for 4 doses

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• Stage III/ IV, CD 20 + Acute B-cell leukemia:
  • Children and Adolescents:
    • 375 mg/m2 administered every 14 days for 4 doses.

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• Steroid-dependent Nephrotic syndrome:
  • Children and Adolescents:
    • 375 mg/m2 once weekly for 1 to 4 doses. (Use should b limited to patients who do not respond to steroids and steroid-sparing agents or are intolerant to the first line therapy)

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• CD 20 + B-cell Non-Hodgkin lymphoma (relapsed or refractory disease):
  • Children 11 years of age or more and Adolescents:
    • 375 mg/m2 intravenous infusion administered on days 1 and 3 of courses 1 and 2 and on day 1 only of course 3. Use in combination with ICE.

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• Mature B-cell stage III/ IV Non-Hodgkin lymphoma:
  • Children and Adolescents:
    • 375 mg/m2 intravenous infusion (maximum dose of 500 mg/dose).
    • Data is limited but the following regimen may be used in combination with multi-agent chemotherapy.
      • Induction 1 and 2: On days 2 and 0 of each phase (4 doses);
      • Consolidation 1 and 2: On day 1 of each phase (2 doses).

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• Posttransplant lymphoproliferative disorder (PTLD):
  • Infants 11 months of age or older, Children, and Adolescents:
    • 375 mg/m2 once weekly for 3 to 4 doses.

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• Primary mediastinal large B-cell lymphoma (PMBCL):
  • Children and Adolescents:
    • 375 mg/m2 every 21 to 28 days for 6 to 8 doses in combination with multiagent chemotherapy

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• Refractory Systemic lupus erythematosus (SLE):
  • Rituximab may be used in patients with refractory lupus who have failed more than one initial therapy.
  • Children 6 years of age or older and Adolescents:
    • Initial dose is 187.5 mg/m2 once on day one, followed by 375 mg/m2 once weekly for 1 to 3 doses (days 8, 15, 22).

Pregnancy Risk Factor C

• Rituximab crosses over the placental boundary and can be detected in large amounts in newborns. 
• This could cause B-cell lymphocytopenia, which can last up to six weeks.
• Pregnancy with Rituximab has been linked to premature births, severe and frequent infections, and other blood disorders. 
• However, no specific birth defects have been observed. Limited data suggests that pregnancy could be allowed to continue even though rituximab is being withheld.
• Furthermore, because of the risk of progression of maternal disease, rituximab use in pregnancy is not discouraged.
• In patients with aggressive lymphomas, rituximab may be administered as a part of the R-CHOP therapy in the second and third trimesters. 
• The cytotoxic component of the regimen should be stopped 3 weeks before the expected delivery. SLE in pregnant women may be treated using other preferred agents.
• Pregnant patients with Rheumatoid Arthritis should be switched to other safer alternative medications.
• After treatment with Rituximab, females in their reproductive years should continue to use effective contraception for 12 consecutive months.

Rituximab during breastfeeding

• Breast milk contains small amounts of Rituximab. 
• The manufacturer doesn't recommend rituximab being used during breastfeeding or for more than six months after the last dose.
• Breastfeeding should not be discouraged if other suitable medicines are not available.
• Breastfeeding should not be allowed when Rheumatoid-related arthritis patients are being treated. Instead, safer options should be considered.  

Rituximab (Mabthera) Dose in Renal Disease:

• No dose adjustment mentioned in the manufacturer's labeling

Rituximab (Mabthera) Dose in Liver Disease:

• No dose adjustment mentioned in the manufacturer's labeling

Side effects of Rituximab (Mabthera):

Very few side effects were observed when patients were treated with Rituximab montherapy. Most of the patients who devloped side effects were on combination chemotherapeutic agents, steroids, and methotrexate.

Common side effects of Rituximab:

• Cardiovascular effects: Peripheral edema, flushing, and hypertension
• Central nervous system: Fatigue, chills, peripheral sensory neuropathy, headache, insomnia, and pain.
• Dermatologic: Pruritus, skin rash, and night sweats.
• Endocrine & metabolic: Hypophosphatemia and weight gain
• Gastrointestinal: Nausea, diarrhea, and abdominal pain
• Genitourinary: Urinary tract infection
• Hematologic & oncologic: Hypogammaglobulinemia, neutropenia, lymphocytopenia, anemia, leukopenia, and thrombocytopenia
• Hepatic: Hepatobiliary disease and increased serum alanine aminotransferase
• Hypersensitivity: Angioedema
• Immunologic: Antibody development
• Infection: Infections
• Neuromuscular & skeletal: Asthenia, muscle spasm, and arthralgia
• Respiratory: Pulmonary disease, pulmonary toxicity, cough, rhinitis, epistaxis, bronchitis, and nasopharyngitis
• Miscellaneous: Infusion related reaction and fever

Less common side effects:

• Cardiovascular: Hypotension, chest tightness, and significant cardiovascular events
• Central nervous system: Dizziness, rigors, anxiety, migraine, and paresthesias
• Dermatologic: Urticaria
• Endocrine & metabolic: Hyperglycemia, increased lactate dehydrogenase, and hyperuricemia.
• Gastrointestinal: Vomiting, dyspepsia, and upper abdominal pain.
• Hematologic & oncologic: Pancytopenia
• Hepatic: Hepatitis B activation
• Infection: Viral and fungal infection
• Neuromuscular & skeletal: Back pain and myalgia
• Respiratory: Dyspnea, throat irritation, bronchospasm, upper respiratory tract infection, and sinusitis.

Contraindications & warnings to Rituximab (Mabthera):

The manufacturer's labeling does not mention any contraindications. It should not be used for the following patients:

• Patients who are allergic to any component of this formulation have a type 1 hypersensitivity reaction to murine protein and Chinese Hamster Ovary cell proteins.
• Multifocal leukoencephalopathy, (PML),
• Patients with active severe infections

Warnings/Precautions

These conditions should not be taken into consideration when using RItuximab:

Perforation or obstruction of the bowel

• Cardiovascular:
  • There are adverse effects such as ventricular fibrillation.Myocardial InfarctionCardiogenic shock.
  • Cardiac arrhythmias should be checked on patients before and after infusion. If life-threatening arrhythmias occur, the infusion should be stopped.
• Hematologic:
  • ​​​​​​​Rituximab can cause anemia, lymphopenia and leukopenia. Monitoring of blood CBC levels should be done during and after treatment.
• US Boxed Warning:
  • Reactivation of the hepatitis B virus may occur up to two years after last treatment. It can lead to liver failure, fulminant hepatitis and even death.
  • Before starting therapy, patients should be tested for Hepatitis B. Screening should include HBsAg, hepatitis B's surface antigen (anti-HBc) and Hepatitis B's core antibody (anti–HBc). Anti-HBc testing should include both IgG antibodies and IgM antibodies. 
  • Isolated IgM antibodies against HBc are not recommended as this only indicates recent infection. All patients with viral hepatitis must be treated with the appropriate antiviral treatment.
  • Patients who have a history of past infection as shown by positive anti-HBc antibodies should be started on prophylactic antiviral therapy. The American society of clinical oncology recommends initiating prophylactic antiviral therapy in patients who are HBsAg and anti-HBc positive.
  • Patients with HBsAg-negative and anti-HBc-positive patients should be closely monitored for HBV reactivation by HBV DNA and ALT testing 3 times per month during rituximab therapy.

• Rituximab use is associated with severe infections.
  • These include fatal bacterial infections, fungal and reactivation of viral infections.
  • Patients who have persistent hypogammaglobulinemia i.e. lasting greater than 11 months after rituximab therapy are especially prone to develop infections.
  • Patients treated with rituximab have reported viral infections such as cytomegalovirus and herpes simplex viruses, parvovirus B19 and varicella virus.
  • Patients who have been treated with rituximab for chronic lymphocyticleukemia (CLL) should be given prophylactic treatment for Pneumocystis Jirovecii pneumonia (PCP), and antiherpetic virus prophylaxis for the first 12 months. Patients being treated for pemphigus veritis (PV) should also receive PCP prophylaxis.

• US Boxed Warning - Infusion-related reactions, which may be fatal within 24 hours have been reported.
  • These reactions include hypotension, bronchospasm, angioedema, hypoxia, urticaria, pulmonary infiltrates, acute respiratory distress syndrome, Myocardial infarction, ventricular fibrillation, cardiogenic shock, and/or anaphylactoid events.

Premedicate patients with antihistamine and acetaminophen 30 minutes before the infusion. In severe reactions, the infusion should be stopped. However, mild to moderate reactions can be treated with half of the usual infusion rate.

• US Boxed Warning - Mucocutaneous reactions: Mucocutaneous reactions like Stevens-Johnson syndrome, toxic epidermal necrolysis, lichenoid dermatitis, paraneoplastic pemphigus, and vesiculobullous dermatitis have been reported with the use of rituximab.
  • The infusion may occur as early as within 24 hours of infusion and at times be fatal.

• US Boxed Warning - Progressive multifocal leukoencephalopathy: Fatal JC virus infection leading to progressive multifocal leukoencephalopathy has been reported with the use of rituximab.

Within 12 months of receiving their last dose of Rituximab, patients may be diagnosed. Patients present with progressive drowsiness, confusion, disorientation, motor weakness, altered speech, visual problems, and poor coordination. MRI, Lumbar puncture and neurological consultation should all be sought. Stop using Rituximab or other immunosuppressants or chemotherapeutics.

• Rituximab may cause severe and sometimes fatal renal toxicity in patients with NHL. Renal toxicity may be a result of tumor lysis syndrome or other nephrotoxic chemotherapeutic drugs like cisplatin. Rituximab should be discontinued when the patients develop oliguria or have a rising creatinine.

• Tumor lysis syndrome resulting in acute renal failure may occur within the first 24 hours and require dialysis. Patients may develop hyperkalemia, hypocalcemia, hyperuricemia, and hyperphosphatemia.

Patients at high risk, such as those with a high tumor burden or cell count of over 25000/ul, should receive prophylactic medicine and hydration before rituximab is initiated.

• Immunizations: Live vaccines should not be given prior to or during rituximab therapy.

• Elderly patients may develop cardiac toxicity resulting in arrhythmias, pulmonary toxicity resulting in pneumonitis, and may develop serious infections.

  Monitor patients for toxicity and adverse effects:

• Monitor CBC with differential and platelets prior to each treatment course and at weekly or monthly as indicated (frequently in hematologic malignancies and at 2 - 4 months interval in autoimmune diseases like Rheumatoid arthritis)
• Monitor serum electrolytes in patients at risk of developing tumor lysis syndrome
• Screen all patients for Hepatitis B virus infection prior to Rituximab therapy.
• Patients with an active infection should be treated.
• Reactivation of Hepatitis B virus infection should be monitored for up to 2 years following completion of treatment.
• HBsAg Negative and anti-HBC positive patients should be monitored at three monthly intervals and up to one year after treatment for reactivation.
• Monitor for cardiac adverse effects during and after infusion of rituximab in patients with preexisting cardiac disease
• Monitor for signs of bowel obstruction and perforation.
• Monitor for signs and symptoms of progressive multifocal leukoencephalopathy.
• Monitor for mucocutaneous reactions

How to Administer Rituximab (Mabthera)?

Note:

1. Do not administer as an intravenous push or bolus.
2. Do not administer subcutaneously.
3. The infusion may be stopped or given slowly if an infusion-related reaction occurs.
4. The infusion may be restarted slowly (50% of the previous rate) in mild to moderate reactions.
5. The infusion may be discontinued in life-threatening cardiac arrhythmias.

How to administer Rituximab?

• Start rituximab infusion at a rate of 50 mg/hour.
• If no infusion-related complications occur, increase the infusion rate by 50 mg/hour to a maximum of 400 mg/hour every 30 minutes.
• Subsequent infusions may be started at a standard rate of 100 mg/hour and increased to a maximum of 400 mg/hour in increments of 100 mg/hour every 30 minutes.
• Accelerated infusion rate over 90 minutes may be used in patients with previously untreated follicular NHL and diffuse large B-cell NHL who are on chemotherapy and receiving a corticosteroid as part of their combination chemotherapy regimen, have a circulating blood lymphocyte count <5,000/ul, or have no significant cardiovascular disease.
• The accelerated infusion rate may be used after tolerance has been established at the recommended infusion rate in cycle 1.
• 20% of the dose administered over the first 30 minutes and the remaining 80% is given over 60 minutes.

How to administer Rituximab in Children?

• Rituximab may be infused over 6 - 8 hours at a rate of 0.5 mg/kg/hour to a maximum rate of 400 mg/hour.

Mechanism of action of Rituximab (Mabthera):

• Rituximab, a monoclonal antigen against CD20 on the surface B lymphocytes, is called Rituximab.
• Rituximab binds with the CD 20 antigen at the cell surface and activates complement-dependent B cells cytotoxicity.
• It also binds with the Fc receptors of human cells, mediating cell death through antibody-dependent cellular toxicity.

The onset of action of Rituximab:

• Immune thrombocytopenia: Initial response is seen in 7 to 56 days. Peak response may take up to 14 to 180 days NHL: B-cell depletion is noted within 3 weeks.

Rheumatoid arthritis (RA): B-cell depletion is noted within 2 weeks.

Duration of action: up to six months (B-cell levels may take up to one year to return to normal)

Half-life elimination: 5 - 78 days  

International Brands of Rituximab (Mabthera):

Pricing in the US:

• Solution (Rituxan Intravenous)
  • 100 mg/10 mL (per mL): $112.74
  • 500 mg/50 mL (per mL): $112.74

International brand names

• Blitzima
• Mabthera
• Reditux
• Relito
• Ritemvia
• Rituxan
• Rituxim
• Rituzena
• Rixathon

Rituximab (Mabthera) Brands in Pakistan:

Ristova (Roche Pakistan LTD) Mabthera (Roche Pakistan LTD)