What Is the Most Important Safety Information I Should Know About ZEVALIN Treatment?

The following section provides an overview of the most important safety information you should know about ZEVALIN, including side effects. Not all of the safety information about ZEVALIN treatment is included here. For complete safety information, please click here to see the full prescribing information for ZEVALIN. Additional information may also be found on www.zevalin.com or by speaking with your health care provider. Because ZEVALIN treatment includes the use of rituximab, please see the rituximab medication guide (www.rituxan.com).

• Leukemia and Myelodysplastic Syndrome (MDS): Among 204 patients who received Y-90 ZEVALIN, following anticancer therapy, 2 patients (1%) were diagnosed with Acute Myelogenous Leukemia (a type of cancer of the blood, AML) within 3 years of receiving ZEVALIN treatment. MDS (another type of cancer in the bone marrow) and/or AML were reported in 5.2% (11/211) of patients with recurring non-Hodgkin's lymphoma (NHL) in clinical studies, and 1.5% (8/535) of all patients included in the expanded-access trial, with median follow-up of 6.5 and 4.4 years, respectively. Among the 19 reported cases, the median time to diagnosis of MDS or AML was 1.9 years following the ZEVALIN therapy; however, the total incidence continues to increase.
• ZEVALIN therapy may cause harm to an unborn baby, please tell your doctor if you are pregnant or plan to become pregnant.
• ZEVALIN may leak from your vein or infusion site. Your doctor will monitor you during treatment and will stop the infusion and switch to another vein, if this occurs during treatment.
• Do not get a vaccine that contains live virus for at least 12 months following ZEVALIN treatment.
• Your doctor will need to monitor your blood weekly to watch for dropping blood counts and platelet counts.
• Your doctor will discuss precautions with you to minimize radiation exposure.
• Creutzfeldt-Jakob Disease (CJD): CJD is a form of brain damage that leads to rapid decrease of mental function and movement. The ZEVALIN therapeutic regimen contains a protein made from human blood. Based on effective donor screening and product manufacturing processes, ZEVALIN carries a very low risk for transmission of viral diseases. The risk for getting CJD is also very low. No cases of transmission of viral diseases or CJD have ever been identified.
• Impairment of Fertility: There is a risk that ZEVALIN therapy will affect the male and female reproductive organs. Use birth control during treatment and for up to 12 months following ZEVALIN therapy.
• Nursing: Patients should be advised to discontinue nursing during and after ZEVALIN treatment.

Adverse Reactions (Side Effects):

• The most common adverse reactions of ZEVALIN are: decreases in blood counts, tiredness, abdominal (stomach) pain, nausea (upset stomach), inflammation of the nose and upper throat, weakness, diarrhea, cough, and fever. Common adverse reactions (≥40%) in clinical trials were: low neutrophil count (a type of white blood cell), decrease in number of white blood cells, decrease in platelets, decrease in red blood cells or hemoglobin, infection, lack of body strength and energy, muscles and bones symptoms, and stomach and intestinal symptoms.
• The most serious adverse reactions of ZEVALIN are prolonged and severe reduction in the number of blood counts and secondary cancers.
• When administered following initial anticancer therapy, grade 3/4 adverse reactions of ZEVALIN include prolonged and severe decrease in blood counts (decrease in platelets [51%], decrease in neutrophils [41%], decrease in white blood cells [36%], decrease in lymphocytes [18%], and decrease in red blood cells or hemoglobin [5%]), and secondary cancers. Reductions in blood cells were more severe and more prolonged among eleven (5%) patients who received ZEVALIN after first-line fludarabine or a fludarabine-containing anticancer regimen as compared to patients receiving non–fludarabine-containing regimens. Grade 3/4 infections occurred in 8% of ZEVALIN-treated patients and in 2% of controls and included neutropenic sepsis (fever and infection due to decrease in the number of neutrophils [1%]), bronchitis, catheter sepsis (bacterial infection in the blood related to catheter), diverticulitis (inflammation in the intestines), shingles or blistering skin rash caused from herpes virus reactivation, flu, lower air passage infection, sinusitis (swelling of the sinuses), and upper air passage infection.
• Grade 3/4 adverse reactions of ZEVALIN in recurring NHL patients include prolonged and severe reduction of blood cells (decrease in platelets [63%], decrease in neutrophils [60%], decrease in red blood cells or hemoglobin [17%], and ecchymosis (small blue or purple patch on the skin or mucous membrane [<1%])) and secondary cancers. Serious infections occurred in 3% of patients (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis (type of skin infection), colitis (swelling of the large intestine), diarrhea, osteomyelitis (bone infection), and upper-air passage infection). Life-threatening infections were reported in 2% of patients (sepsis, empyema (collection of pus), pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis (bile duct infection)).

Please click here to see the full Prescribing Information, including BOXED WARNINGS, for ZEVALIN. Because ZEVALIN treatment includes the use of rituximab, please see the rituximab medication guide (www.rituxan.com).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

IMPORTANT SAFETY INFORMATION

Contraindications
• FUSILEV is contraindicated for patients who have had previous allergic reactions attributed to folic acid or folinic acid.

Warnings and Precautions
• Due to Ca++ content, no more than 16 mL (160 mg) of levoleucovorin solution should be injected intravenously per minute
• FUSILEV enhances the toxicity of fluorouracil.
• Concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in HIV patients was associated with increased rates of treatment failure in a placebo-controlled study.

Adverse Reactions
Allergic reactions were reported in patients receiving FUSILEV.
Vomiting (38%), stomatitis (38%) and nausea (19%) were reported in patients receiving FUSILEV as rescue after high dose methotrexate therapy.
The most common adverse reactions (>50%) in patients with advanced colorectal cancer receiving Fusilev in combination with 5-FU were diarrhea, nausea and stomatitis.

Drug Interactions
FUSILEV may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible patients.

Reporting of Suspected Adverse Reactions
You are encouraged to report side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see the FUSILEV (levoleucovorin) for injection full prescribing information for complete safety information.