[Posted 09/25/2013] ISSUE: FDA approved changes to the prescribing information of the immune-suppressing and anti-cancer drugs Arzerra (ofatumumab) and Rituxan (rituximab) to add new Boxed Warning information about the risk of reactivation of hepatitis B virus (HBV) infection. The revised labels also will include additional recommendations for screening, monitoring, and managing patients on these drugs to decrease this risk.
In patients with prior HBV infection, HBV reactivation may occur when the body's immune system is impaired. HBV reactivation has occurred in patients with prior HBV exposure who are later treated with drugs classified as CD20-directed cytolytic antibodies, including Arzerra (ofatumumab) and Rituxan (rituximab). Some cases have resulted in fulminant hepatitis, hepatic failure, and death.
See the FDA Drug Safety Communication for additional information, including a Data Summary.
BACKGROUND: Arzerra is used to treat chronic lymphocytic leukemia (CLL) in patients who have further disease after treatment with the anti-cancer drugs fludarabine and alemtuzumab. Rituxan is used to treat non-Hodgkin's lymphoma and CLL. It is also used to treat other medical conditions, including rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.
Screen all patients for HBV infection before starting treatment with Arzerra or Rituxan 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 Arzerra or Rituxan therapy and for several months thereafter, since reactivations have occurred several months following completion of therapy with these drugs
In patients who develop reactivation of HBV while on Arzerra or Rituxan, immediately discontinue the drug and start appropriate treatment for HBV. Also discontinue any chemotherapy the patient is receiving until the HBV infection is controlled or resolved. Because of insufficient data, no recommendation can be made regarding the resumption of Arzerra or Rituxan in patients who develop HBV reactivation hepatitis
Before receiving Arzerra or Rituxan, tell your health care professional if you have or have had any severe infections, including HBV
If you have had HBV infection, your health care professional should monitor you for HBV infection during treatment and for several months after you stop treatment with Arzerra or Rituxan
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Some people who received rituximab experienced severe reactions to the medication. Some of these people died within 24 hours after they received a dose of rituximab. Most of these deaths happened after the first dose of rituximab. Tell your doctor if you have or have ever had chronic lymphocytic leukemia (CLL; a type of cancer that begins in the white blood cells), mantle cell lymphoma (a fast-growing cancer that begins in the cells of the immune system), an irregular heartbeat, or heart or lung disease. If you have any of these conditions, or if you are female, there is a greater chance that you will experience a serious reaction to rituximab. If you experience any of the following symptoms, tell your doctor or other health care provider immediately: hives; swelling of the lips, tongue, or throat; difficulty breathing or swallowing; dizziness; fainting; shortness of breath, wheezing; blurred vision; headache; pounding or irregular heartbeat; fast or weak pulse; loss of consciousness, fast breathing; pale or bluish skin; pain in the chest that may spread to other parts of the upper body; weakness; excessive tiredness; sweating; or anxiety.
When rituximab is used to treat non-Hodgkin's lymphoma (NHL; a type of cancer that begins in a type of white blood cells that normally fight infection) it may cause a condition called tumor lysis syndrome (TLS; a group of symptoms caused by the fast breakdown of cancer cells). TLS may cause kidney failure and the need for dialysis treatment. Tell your doctor if you are also receiving cisplatin (Platinol). If you notice that you need to urinate less often than usual or that you produce less urine than usual, tell your doctor immediately.
Rituximab has caused severe skin reactions. These reactions have caused death. If you experience any of the following symptoms, tell your doctor immediately: painful sores, ulcers, blisters, rash, or peeling skin.
Some people who received rituximab developed progressive multifocal leukoencephalopathy (PML; a rare infection of the brain that cannot be treated, prevented, or cured and that usually causes death or severe disability) during or after their treatment. If you experience any of the following symptoms, call your doctor immediately: difficulty thinking clearly or walking, loss of strength, vision problems, or any other unusual symptoms that develop suddenly.
Talk to your doctor about the risks of using rituximab.
Rituximab is used alone or with other medications to treat certain types of non-Hodgkin's lymphoma (NHL; a type of cancer that begins in a type of white blood cells that normally fights infection). Rituximab is also used with another medication to treat the symptoms of rheumatoid arthritis (RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) in people who have already been treated with a certain type of medication called a tumor necrosis factor (TNF) inhibitor. Rituximab is in a class of medications called biologic antineoplastic agents. It treats NHL by causing the death of blood cells that have multiplied abnormally. It treats rheumatoid arthritis by causing the death of certain blood cells that may cause the immune system to attack the joints.
Rituximab comes as a solution (liquid) to be injected into a vein. Rituximab is administered by a doctor or nurse in a medical office or infusion center. When rituximab is used to treat rheumatoid arthritis, it is usually given as 2 doses spaced 2 weeks apart. When rituximab is used to treat NHL it is either given once a week for 4 to 8 weeks or on the first day of each chemotherapy cycle. Your dosing schedule will depend on the condition that you have, the other medications you are using, and how well your body responds to treatment.
Rituximab must be given slowly. It may take several hours or longer to receive your first dose of rituximab, so you should plan to spend most of the day at the medical office or infusion center. After the first dose, you may receive your medication more quickly, depending on how you respond to treatment.
You may experience symptoms such as fever, shaking chills, tiredness, headache, or nausea while you are receiving a dose of rituximab, especially the first dose. Tell your doctor or other healthcare provider if you experience these symptoms while you are receiving your medication. Your doctor may prescribe other medications to help prevent or relieve these symptoms. Your doctor may tell you to take these medications before you receive each dose of rituximab.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Unless your doctor tells you otherwise, continue your normal diet.
If you miss an appointment to receive rituximab, call your doctor right away.
muscle or back pain
numbness, burning or tingling in the hands or feet
stomach area pain
unusual bruising or bleeding
sore throat, fever, chills, or other signs of infection
joint pain or soreness
Rituximab may cause other side effects. Call your doctor if you have any unusual problems while using this medication.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to rituximab.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Last Revised - 10/15/2013
AHFS® Consumer Medication Information. © Copyright, 2013. The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.