Rituximab-Hyaluronidase

Rituximab-Hyaluronidase is a combination medication used for the treatment of Follicular Lymphoma (FL), Diffuse Large B-cell Lymphoma (DLBCL), and Chronic Lymphocytic Leukemia (CLL) in adult patients.

• Rituximab-Hyaluronidase is available under the following different brand names: Rituxan Hycela

Common side effects of Rituximab-Hyaluronidase include:

• infections
• low white blood cell count (neutropenia)
• nausea
• constipation
• cough
• fatigue
• hair loss
• anemia
• low platelet count (thrombocytopenia)
• fever
• vomiting
• injection site redness

Serious side effects of Rituximab-Hyaluronidase include:

• painful sores or ulcers on the skin, lips, or mouth
• blisters
• peeling skin
• rash
• pustules
• liver problems 
• confusion
• dizziness or loss of balance
• difficulty walking or talking
• decreased strength or weakness on one side of the body
• vision problems, such as blurred vision or loss of vision
• serious allergic reactions 
• hives (red itchy welts) 
• itching
• swelling of lips, tongue, throat, or face
• sudden cough
• shortness of breath, difficulty breathing, or wheezing
• weakness
• palpitations 
• chest pain
• fever
• chills or shaking chills
• bacterial, fungal, and viral infections

Rare side effects of Rituximab-Hyaluronidase include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to the FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution

• (120 mg/2,000 units)/mL
• Ready-to-use SC solution contains rituximab and hyaluronidase human

Follicular Lymphoma

Adult dosage

• All patients must receive at least 1 full dose of rituximab IV infusion before starting rituximab/hyaluronidase SC
• Relapse or refractory follicular lymphoma
  • Rituximab 1,400/hyaluronidase 23,400 units SC every week for 3 or 7 weeks following a full dose of rituximab IV at week 1 (that is 4 or 8 weeks total)
• Retreatment relapse/refractory FL
  • Rituximab 1,400/hyaluronidase 23,400 units SC every week for 3 weeks following a full dose of rituximab by IV infusion at week 1 (that is 4 weeks in total)
• Previously untreated FL
  • 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 (that is up to 8 cycles in total)
  • Maintenance after complete or partial response
  • Single-agent maintenance: Rituximab 1,400/hyaluronidase 23,400 SC every 8 weeks x 12 doses
  • Initiate 8 weeks after complete or partial response to rituximab in combination with chemotherapy
• Nonprogressing FL
  • Following completion of 6-8 cycles of cyclophosphamide, vincristine, and prednisone chemotherapy and a full dose of rituximab by IV infusion at week 1, rituximab 1,400 mg/hyaluronidase 23,400 units SC every week for 3 weeks (that is 4 weeks in total) at 6-month intervals for a maximum of 16 doses

Diffuse Large B-cell lymphoma

Adult dosage

• Rituximab 1,400 mg/hyaluronidase 23,400 on Day 1 of cycles 2-8 in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (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

Adult dosage

• Rituximab 1,600 mg/hyaluronidase 26,800 units SC on Day 1 of a 28-day cycle in cycles 2-6 (in combination with fludarabine and cyclophosphamide (FC)) for a total of 5 cycles, following a full IV rituximab dose (Day 1 of cycle 1) of FC (that is 6 cycles in total)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Rituximab-Hyaluronidase has severe interactions with no other drugs
• Rituximab-Hyaluronidase has serious interactions with 22 other drugs
• Rituximab-Hyaluronidase has moderate interactions with 38 other drugs
• Rituximab-Hyaluronidase has minor interactions with the following drug:
  • methotrexate

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Rituximab-Hyaluronidase?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Rituximab-Hyaluronidase?”

Cautions

• Tumor lysis syndrome (TLS) can occur within 12-24 hours after administration; administer aggressive IV hydration and anti-hyperuricemic 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
• The 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 more than 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 outcomes 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 hours 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 hours 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 and more )
  • Premedicate patients with an antihistamine and acetaminophen before each administration; also consider glucocorticoids

Pregnancy and Lactation

• 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 women of reproductive potential before initiating therapy
• 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 in human milk, the effect on the breastfed infant, or milk production
  • However, rituximab is detected in the milk of lactating cynomolgus monkeys, and IgG is present in human milk
  • Rituximab is 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 the last dose due to the potential for serious adverse reactions in breastfed children