Dosing & Uses
Dosage Forms & Strengths
rituximab/hyaluronidase
injectable solution
- (120mg/2,000 units)/mL
- Ready-to-use SC solution contains rituximab and hyaluronidase human
Follicular Lymphoma
All patients must receive at least 1 full dose of rituximab IV infusion before starting rituximab/hyaluronidase SC
Relapse or refractory follicular lymphoma
- Indicated for relapsed or refractory follicular lymphoma (FL) as a single agent
- Rituximab 1,400/hyaluronidase 23,400 units SC qWeek for 3 or 7 weeks following a full dose of rituximab IV at Week 1 (ie, 4 or 8 weeks total)
Retreatment relapse/refractory FL
- Rituximab 1,400/hyaluronidase 23,400 units SC qWeek for 3 weeks following a full dose of a rituximab by IV infusion at Week 1 (ie, 4 weeks in total)
Previously untreated FL
- Indicated for previously untreated FL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to rituximab in combination with chemotherapy, as single-agent maintenance therapy
- Rituximab 1,400/hyaluronidase 23,400 units SC on day 1 of a 21-day cycle in cycles 2-8, for up to 7 cycles, following a full IV rituximab dose on Day 1 of cycle 1 of chemotherapy (ie, up to 8 cycles in total)
Maintenance after complete or partial response
- Single agent maintenance: Rituximab 1,400/hyaluronidase 23,400 SC q8Weeks x 12 doses
- Initiate 8 weeks after complete or partial response to rituximab in combination with chemotherapy
Nonprogressing FL
- Indicated for nonprogressing (eg, stable disease) FL as a single agent after first-line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy
- Following completion of 6-8 cycles of CVP chemotherapy and a full dose of a rituximab by IV infusion at Week 1, rituximab 1,400 mg/hyaluronidase 23,400 units SC qWeek for 3 weeks (ie, 4 weeks in total) at 6-month intervals for maximum of 16 doses
Diffuse Large B-Cell Lymphoma
Indicated for previously untreated diffuse large B-cell lymphoma (DLBCL) in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens
Rituximab 1,400 mg/hyaluronidase 23,400 on Day 1 of cycles 2-8 in combination with CHOP for up to 7 cycles, following a full IV rituximab dose (Day 1, cycle 1) of CHOP (up to 6-8 cycles)
Chronic Lymphocytic Leukemia
Indicated, in combination with fludarabine and cyclophosphamide (FC), for treatment of adults with previously untreated and previously treated CLL
Rituximab 1,600 mg/hyaluronidase 26,800 units SC on Day 1 of a 28-day cycle in cycles 2-6 (in combination with FC) for a total of 5 cycles, following a full IV rituximab dose (Day 1 of cycle 1) of FC (ie, 6 cycles in total)
Dosing Considerations
Initiate treatment only after patients have received at least 1 full dose of rituximab IV infusion
Not indicated for nonmalignant conditions
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (15)
- adenovirus types 4 and 7 live, oral
rituximab-hyaluronidase, adenovirus types 4 and 7 live, oral. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- baricitinib
baricitinib, rituximab-hyaluronidase. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Baricitinib is not recommended in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressives.
- certolizumab pegol
rituximab-hyaluronidase and certolizumab pegol both increase immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Avoid combination because of an increased risk of serious infection.
- influenza virus vaccine quadrivalent, intranasal
rituximab-hyaluronidase, influenza virus vaccine quadrivalent, intranasal. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- measles (rubeola) vaccine
rituximab-hyaluronidase, measles (rubeola) vaccine. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- measles mumps and rubella vaccine, live
rituximab-hyaluronidase, measles mumps and rubella vaccine, live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- measles, mumps, rubella and varicella vaccine, live
rituximab-hyaluronidase, measles, mumps, rubella and varicella vaccine, live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- palifermin
palifermin increases toxicity of rituximab-hyaluronidase by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- poliovirus vaccine live oral trivalent
rituximab-hyaluronidase, poliovirus vaccine live oral trivalent. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- rotavirus oral vaccine, live
rituximab-hyaluronidase, rotavirus oral vaccine, live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- rubella vaccine
rituximab-hyaluronidase, rubella vaccine. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- smallpox (vaccinia) vaccine, live
rituximab-hyaluronidase, smallpox (vaccinia) vaccine, live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- varicella virus vaccine live
rituximab-hyaluronidase, varicella virus vaccine live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- yellow fever vaccine
rituximab-hyaluronidase, yellow fever vaccine. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
- zoster vaccine live
rituximab-hyaluronidase, zoster vaccine live. immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Safety of immunization with live viral vaccines following rituximab therapy has not been studied and vaccination with live virus vaccines is not recommended.
Monitor Closely (33)
- amphotericin B deoxycholate
amphotericin B deoxycholate and rituximab-hyaluronidase both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Caution should be exercised when concurrent therapy is used. Patients should be monitored for signs of renal failure.
- belatacept
belatacept and rituximab-hyaluronidase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.
- cholera vaccine
rituximab-hyaluronidase, cholera vaccine. immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.
- cisplatin
cisplatin and rituximab-hyaluronidase both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Potential for renal toxicity when used in combination with cisplatin.
- dengue vaccine
rituximab-hyaluronidase decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- denosumab
rituximab-hyaluronidase, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- fingolimod
rituximab-hyaluronidase increases effects of fingolimod by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Concomitant therapy is expected to increase the risk of immunosuppression. Use caution when switching patients from long-acting therapies with immune effects. .
- hepatitis A vaccine inactivated
rituximab-hyaluronidase, hepatitis A vaccine inactivated. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- hepatitis a/b vaccine
rituximab-hyaluronidase, hepatitis a/b vaccine. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- hepatitis b vaccine
rituximab-hyaluronidase, hepatitis b vaccine. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- HIV vaccine
rituximab-hyaluronidase, HIV vaccine. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- human papillomavirus vaccine, bivalent
rituximab-hyaluronidase, human papillomavirus vaccine, bivalent. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- human papillomavirus vaccine, nonavalent
rituximab-hyaluronidase, human papillomavirus vaccine, nonavalent. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- human papillomavirus vaccine, quadrivalent
rituximab-hyaluronidase, human papillomavirus vaccine, quadrivalent. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- influenza A (H5N1) vaccine
rituximab-hyaluronidase, influenza A (H5N1) vaccine. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- influenza virus vaccine (H5N1), adjuvanted
rituximab-hyaluronidase, influenza virus vaccine (H5N1), adjuvanted. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- influenza virus vaccine quadrivalent
rituximab-hyaluronidase, influenza virus vaccine quadrivalent. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- influenza virus vaccine quadrivalent, adjuvanted
rituximab-hyaluronidase, influenza virus vaccine quadrivalent, adjuvanted. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- influenza virus vaccine quadrivalent, cell-cultured
rituximab-hyaluronidase, influenza virus vaccine quadrivalent, cell-cultured. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- influenza virus vaccine trivalent
rituximab-hyaluronidase, influenza virus vaccine trivalent. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- influenza virus vaccine trivalent, adjuvanted
rituximab-hyaluronidase, influenza virus vaccine trivalent, adjuvanted. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- ioversol
ioversol and rituximab-hyaluronidase both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.
- Japanese encephalitis virus vaccine
rituximab-hyaluronidase, Japanese encephalitis virus vaccine. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- mechlorethamine
mechlorethamine, rituximab-hyaluronidase. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration with mechlorethamine may increase the risk of immunosuppression and myelosuppression.
- poliovirus vaccine inactivated
rituximab-hyaluronidase decreases effects of poliovirus vaccine inactivated by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Avoid vaccination during chemotherapy or radiation therapy if possible because antibody response may be suboptimal. Patients on chemotherapy with anti-B cell antibodies should wait =6 months after therapy before being vaccinated with inactivated vaccines.
- ponesimod
ponesimod and rituximab-hyaluronidase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- rabies vaccine
rituximab-hyaluronidase, rabies vaccine. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- rabies vaccine chick embryo cell derived
rituximab-hyaluronidase, rabies vaccine chick embryo cell derived. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
- siponimod
siponimod and rituximab-hyaluronidase both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- sipuleucel-T
rituximab-hyaluronidase decreases effects of sipuleucel-T by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.
- trastuzumab
trastuzumab, rituximab-hyaluronidase. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.
- trastuzumab deruxtecan
trastuzumab deruxtecan, rituximab-hyaluronidase. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.
- zoster vaccine recombinant
rituximab-hyaluronidase, zoster vaccine recombinant. immunosuppressive effects; risk of infection. Use Caution/Monitor. When used for rheumatoid arthritis, follow current immunization guidelines and administer non-live vaccines at least 4 weeks prior to a course of rituximab.
Minor (1)
- methotrexate
methotrexate and rituximab-hyaluronidase both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
Adverse Effects
Percentages are for all grades of toxicity unless otherwise noted
>10% (FL)
Neutropenia (32%)
Nausea (31%)
Constipation (25%)
Cough (23%)
Fatigue (20%)
Diarrhea (18%)
Asthenia (17%)
Pyrexia (15%)
Anemia (15%)
Abdominal pain (14%)
Vomiting (14%)
Alopecia (14%)
Paresthesia (16%)
Injection site erythema (13%)
Arthralgia (13%)
Peripheral neuropathy (12%)
Dyspnea (11%)
Pneumonia (11%)
>10% (DLBCL)
Neutropenia (31%)
lopecia (24%)
Anemia (23%)
Nausea (22%)
Fatigue (19%)
Constipation (15%)
Diarrhea (14%)
Febrile neutropenia (14%)
Decreased neutrophil count (14%)
Pyrexia (13%)
Peripheral neuropathy (12%)
Cough (11%)
Asthenia (11%)
Vomiting (11%)
>10% (CLL)
Neutropenia (65%)
Nausea (38%)
Pyrexia (32%)
Injection site erythema (26%)
Thrombocytopenia (24%)
Vomiting (21%)
Leukopenia (19%)
Injection site pain (16%)
Erythema (15%)
Anemia (13%)
Chills (13%)
Cough (13%)
Upper respiratory tract infection (13%)
Rash (12%)
Diarrhea (12%)
Fatigue (11%)
Febrile neutropenia (11%)
1-10% (FL)
Bone pain (10%)
Extremity pain (10%)
Pruritus (10%)
Rash (10%)
Erythema (9%)
Back pain (9%)
Oropharyngeal pain (9%)
Insomnia (9%)
Dyspepsia (8%)
Chills (8%)
Injection site pain (8%)
Chills (8%)
Bronchitis (8%)
Urinary tract infection (8%)
Muscle spasms (8%)
Myalgia (8%)
Sinusitis (7%)
Dizziness (7%)
Insomnia (7%)
Stomatitis (6%)
Hypertension (6%)
Conjunctivitis (5%)
Upper abdominal pain (5%)
Peripheral edema (5%)
Mucosal inflammation (5%)
Influenza (4%)
Influenza-like illness (3%)
Peripheral neuropathy, Grade 3-4 (2%)
Diarrhea, Grade 3-4 (2%)
Asthenia, Grade 3-4 (1%)
Chest pain, Grade 3-4 (1%)
Dyspnea, Grade 3-4 (1%)
Hypertension, Grade 3-4 (1%)
1-10% (DLBCL)
Paresthesia (9%)
Mucosal inflammation (8%)
Peripheral edema (8%)
Decreased weight (8%)
Decreased appetite (8%)
Abdominal pain (7%)
Pneumonia (7%)
Leukopenia (7%)
Decreased WBC count (7%)
Insomnia (7%)
Stomatitis (6%)
Headache (6%)
Dyspnea (6%)
Dyspepsia (5%)
Lymphopenia (5%)
Decreased lymphocyte count (5%)
1-10% (CLL)
Abdominal pain (9%)
Arthralgia (9%)
Constipation (8%)
Asthenia (8%)
Respiratory tract infection (8%)
Pruritus (8%)
Bronchitis (7%)
Extremity pain (7%)
Headache (7%)
Bone pain (6%)
Oropharyngeal pain (6%)
Dyspnea (4%)
Urinary tract infection (2%)
Pneumonia (2%)
Insomnia (1%)
Hypotension (1%)
Postmarketing Reports
Skin: Severe mucocutaneous reactions, pyoderma gangrenosum (including genital presentation)
Warnings
Black Box Warnings
Severe mucocutaneous reactions
- Severe, including fatal, mucocutaneous reactions reported including paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis
- Discontinue drug if severe mucocutaneous reaction occurs
Progressive multifocal leukoencephalopathy
- Progressive multifocal leukoencephalopathy (PML), including fatal PML, reported
Reactivation of hepatitis B
- Reactivation of hepatitis B virus (HBV) infection reported, including deaths
- Screen all patients for HBV infection before initiating drug by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc)
- Consult with hepatitis experts regarding monitoring and use of HBV antiviral therapy when screening identifies patients at risk of HBV reactivation due to evidence of prior HBV infection
- Monitor patients with evidence of prior HBV infection for clinical and laboratory signs of hepatitis B or HBV reactivation during therapy and for several months thereafter, since reactivations have occurred several months following completion of therapy
- If HBV reactivation develops, discontinue drug immediately and start HBV treatment; also discontinue any chemotherapy until the HBV infection controlled/resolved
- Because of insufficient data, no recommendation can be made regarding the resumption of the drug in patients who develop HBV reactivation hepatitis
Contraindications
None
Cautions
Tumor lysis syndrome (TLS) can occur within 12-24 hr after administration; administer aggressive IV hydration and antihyperuricemic therapy in patients at high risk for TLS; correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated
Cardiac adverse reactions (eg, ventricular fibrillation, myocardial infarction, cardiogenic shock) may occur; discontinue treatment for serious or life-threatening cardiac arrhythmias; perform cardiac monitoring during and after all administrations for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina
Severe, including fatal, renal toxicity can occur after administration; closely monitor for signs of renal failure and discontinue treatment in patients with a rising serum creatinine or oliguria
Abdominal pain, bowel obstruction, and bowel perforation can occur in patients receiving rituximab-containing products, in combination with chemotherapy; in postmarketing reports, the mean time to documented gastrointestinal perforation was 6 days; evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur
Safety of immunization with live viral vaccines following rituximab-containing chemotherapy has not been studied, and vaccination with live virus vaccines is not recommended before or during treatment
Based on human data, rituximab-containing products can cause fetal harm due to B-cell lymphocytopenia in infants exposed to rituximab in utero (see Pregnancy)
Infections
- Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab
- Infections reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after rituximab exposure)
- New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella-zoster virus, West Nile virus, and hepatitis B and C viruses
- Discontinue treatment for serious infections and institute appropriate anti-infective therapy
Hypersensitivity
- Rituximab-containing products are associated with hypersensitivity and other administration reactions (eg, cytokine release syndrome, TLS, anaphylactic reactions)
- Severe infusion-related reactions (eg, pulmonary events, fever, chills, rigors, hypotension, urticaria, angioedema) with fatal outcome reported with IV use of rituximab, with an onset ranging within 30-120 minutes after starting the first IV infusion
- Cytokine release syndrome may occur within 1-2 hr of initiating infusion; severe cytokine release syndrome is characterized by severe dyspnea, often accompanied by bronchospasm and hypoxia, in addition to fever, chills, rigors, urticaria, and angioedema
- Local cutaneous reactions may occur more than 24 hr after administration
- During administration, interrupt treatment immediately when observing signs of a severe reaction, and initiate aggressive symptomatic treatment; closely monitor the following patients: those with preexisting cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm³ )
- Premedicate patients with an antihistamine and acetaminophen prior to each administration; also consider glucocorticoids
Pregnancy & Lactation
Pregnancy
Based on human data, rituximab can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed to rituximab in utero
There are no available data on use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage
Verify pregnancy status in females of reproductive potential prior to initiating therapy
Animal data
- In animal reproduction studies, IV administration of a rituximab to pregnant cynomolgus monkeys during organogenesis caused lymphoid B-cell depletion in newborn offspring at doses resulting in 80% of the exposure (based on AUC) of those achieved following a dose of 2 g in humans
- Reduced fetal weight and increased fetal lethality were observed following SC administration of hyaluronidase human in mice at a dose >2700 times higher than the human dose
Contraception
- Females of childbearing potential should use effective contraception during treatment and for 12 months following treatment
Lactation
There are no data on the presence of rituximab or hyaluronidase human in human milk, the effect on the breastfed infant, or the effect on milk production
However, rituximab is detected in the milk of lactating cynomolgus monkeys, and IgG is present in human milk
Rituximab reported to be excreted at low concentrations in human breast milk; advise a lactating woman not to breastfeed during treatment and for at least 6 months after last dose due to potential for serious adverse reactions in breastfed children
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Monoclonal antibody targets CD20 antigen expressed on pre-B and mature B-lymphocytes’ surfaces
Upon binding to CD20, mediates B-cell lysis
Hyaluronidase human increases permeability of SC tissue by temporarily depolymerizing hyaluronan
In doses administered, hyaluronidase human acts locally; effects of hyaluronidase human are reversible and permeability of SC tissue is restored within 24-48 hr
Absorption
Bioavailability: 0.646 (FL); 0.634 (CLL)
Peak plasma concentration
- FL: 237 mcg/mL (cycle 7); 156 mcg/mL (cycle 18)
- CLL: 202 mcg/mL (cycle 6)
Peak trough concentration
- FL: 122.2 mcg/mL (cycle 7); 45.5 mcg/mL (cycle 18)
- CLL: 97.5 mcg/mL (cycle 6)
AUC
- FL: 3,779 mcg·d/mL (cycle 7); 5,000 mcg·d/mL (cycle 18)
- CLL: 4088 mcg·d/mL (cycle 5)
Distribution
Vd (steady-state): 8.09 L (FL); 8.52 (CLL)
Elimination
Half-life: 34.1 days (FL); 32 days (CLL)
Clearance: 0.18 L/day (FL); 0.204 (CLL)
Administration
SC Preparation
Solution for SC is ready to use
Visually inspect solution for particulates; solution should appear as a clear-to-opalescent and colorless-to-yellowish liquid
SC Administration
Consider premedication (ie, acetaminophen, diphenhydramine, and/or glucocorticoids)
Premedication with acetaminophen and diphenhydramine may attenuate infusion-related reactions
Observe patients for 15 minutes after SC administration
If administration is interrupted, administer at the same site or at a different site along the abdomen
Avoid coadministering other SC medications at the same site
Avoid injections into areas where skin appears red, bruised, tender, or hard
Avoid injections in areas where there are moles or scars No data available on other injection sites
SC injection rate
- Inject SC in abdomen
- 1,400 mg/23,400 IU/vial (1,400 mg rituximab and 23,400 Units hyaluronidase human): SC over ~5 minutes
- 1,600 mg/26,800 IU/vial (1,600 mg rituximab and 26,800 Units hyaluronidase human): SC over ~7 minutes
Storage
Unused vials: Refrigerate at 2-8°C (36-46°F)
Solution for SC injection: Refrigerate at 2-8°C (36-46°F) up to 48 hr and subsequently for 8 hr at room temperature up to 30°C (86°F)
Protect vials and solution from light
Images
Formulary
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- View the formulary and any restrictions for each plan.
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