Bexxar

No drug interactions have been studied. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Before receiving Bexxar injection,

• tell your doctor and pharmacist if you are allergic to Bexxar or any of the ingredients in Bexxar injection
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
• tell your doctor if you have or have ever had kidney or thyroid disease.
• tell your doctor if you are breastfeeding.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you have received Bexxar injection.
• do not have any vaccinations without talking to your doctor.
• you should know that the radioactive material in Bexxar injection may be present in your body for 1 to 2 weeks after you receive your last dose. You will need to take certain precautions to prevent the radiation from spreading to others who come in contact with you. Your doctor will explain these precautions to you and will also give you this information in writing. Follow these directions carefully, and ask your doctor if you have any questions.
• you should know that Bexxar injection may damage your thyroid gland. You will need to take medication to protect your thyroid gland beginning the day before you receive your first dose of Bexxar injection and continuing until 14 days after you receive the second dose of Bexxar injection. If you are unable to take the medication needed to protect your thyroid gland, your doctor will not give you Bexxar injection. After your treatment with Bexxar injection, you will need to visit your doctor once a year to check whether your thyroid gland has been damaged. If your thyroid gland is damaged, you will need to take a daily medication for the rest of your life.
• you should know that if you receive Bexxar injection, your body may develop antibodies (substances in the blood that help the immune system recognize and attack foreign substances) to murine proteins. If you develop these antibodies, you may have an allergic reaction when you take medications made from murine proteins, or these medications might not work well for you. After your treatment with Bexxar injection, be sure to tell all of your doctors that you have been treated with Bexxar injection.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain tests to check your body's response to Bexxar injection during your treatment and for at least 10 weeks after your treatment.

None

Pregnancy

Pregnancy: Category D [see Warnings and Precautions (5.6)]: There are no studies of the Bexxar therapeutic regimen in pregnant women or animals. Based on the transplacental passage of I-131, administration of the Bexxar therapeutic regimen to a pregnant woman can cause fetal harm including severe and possibly irreversible neonatal hypothyroidism. Limited data suggest an increased risk of miscarriage up to a year following I-131 treatment.

Inform patients who are pregnant or become pregnant after the Bexxar therapeutic regimen about the potential hazard to a fetus. Evaluate infants born to mothers treated with the Bexxar therapeutic regimen for hypothyroidism at the time of delivery and during the neonatal period.

Nursing Mothers

Because immunoglobulins are secreted in human milk, it is expected that tositumomab would be present in human milk. Radiolabeled iodine is excreted in breast milk and may reach concentrations equal to or greater than maternal plasma concentrations. Because of the potential for serious adverse reactions in nursing infants from the Bexxar therapeutic regimen, advise women to discontinue nursing or to consider alternative treatment, taking into account the importance of the Bexxar therapeutic regimen to the mother.

Pediatric Use

The safety and effectiveness of the Bexxar therapeutic regimen have not been established in children.

Geriatric Use

Clinical studies of the Bexxar therapeutic regimen did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects.

Renal Impairment

Use of the Bexxar therapeutic regimen has not been studied in patients with renal impairment [see Warnings and Precautions (5.6), Clinical Pharmacology (12.3)].

Females and Males of Reproductive Potential

Contraception: Females of reproductive potential should use effective contraception during treatment with the Bexxar therapeutic regimen and for 12 months after treatment ends to avoid the embryo-fetal effects of the radioisotope and the risk of increased pregnancy loss during that time period.

The Bexxar therapeutic regimen exposes the testes to radiation [see Dosage and Administration (2.9)]. Because of the potential for mutagenesis in male gametes, males of reproductive potential should use effective contraception during treatment with the Bexxar therapeutic regimen and for 12 months after treatment ends.

Infertility: The Bexxar therapeutic regimen results in radiation exposure of the ovaries and testes. Based on published studies examining patients treated with I-131, the Bexxar therapeutic regimen may cause transient ovarian or testicular dysfunction. Radiation effects may persist for up to 12 months following treatment.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of the Bexxar therapeutic regimen or to determine its effects on fertility in males or females. However, Iodine I-131 is a potential carcinogen and mutagen.

Administration of the Bexxar therapeutic regimen exposes the testes and ovaries to radiation [see Dosage and Administration (2.9)].

The clinical benefit of the Bexxar therapeutic regimen was established in a single-arm clinical trial conducted in 40 patients with low-grade, transformed low-grade, or follicular large-cell lymphoma. Patients had a Karnofsky performance status of at least 60%, a granulocyte count of 1,500 cells/mm3, a platelet count greater than or equal to 100,000/mm3, less than or equal to 25% of the intra-trabecular marrow space involved by lymphoma, and no evidence of progressive disease arising in a field irradiated with >3,500 cGy within one year of completion of irradiation.

This study enrolled 40 patients with low-grade or transformed low-grade or follicular large-cell lymphoma whose disease had not responded to, or had progressed following, at least 4 doses of rituximab therapy. The median age was 57 years (range: 35 to 78 years); the median time from diagnosis to protocol entry was 50 months (range: 12 to 170 months); and the median number of prior chemotherapy regimens was 4 (range: 1 to 11). Overall, 35 of the 40 patients were rituximab-refractory (defined as no response or a response of less than 6 months’ duration following rituximab therapy).

The main outcome measure in Study was overall response rate as determined by an independent panel that reviewed patient records and radiologic studies (Table 6).

a CI = confidence interval

b NR = not reached, median duration of follow-up = 26 months

c Complete response rate = pathologic and clinical complete responses

The results of this study were supported by demonstration of durable objective responses in 4 single-arm studies enrolling 190 patients evaluable for efficacy with rituximab-naïve, follicular non-Hodgkin’s lymphoma with or without transformation, who had relapsed following or were refractory to chemotherapy. In these studies, the overall response rates ranged from 47% to 64% and the median durations of response ranged from 12 to 18 months

You should not receive Bexxar if you are allergic to mouse proteins, or if you have ever had an allergic reaction to a monoclonal antibody.

To make sure Bexxar is safe for you, tell your doctor if you have:

• kidney disease; or

• severe bone marrow suppression.

Bexxar can cause damage to the thyroid gland of an unborn baby if the mother receives this medication during pregnancy. You should not receive this medication if you are pregnant.

Bexxar can be harmful to an unborn baby whether the father or the mother receives this medication at the time of conception. Use effective birth control to prevent pregnancy during your treatment, whether you are a man or a woman. Continue using birth control for at least 12 months after you have received Bexxar.

Tositumomab can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using Bexxar.

Some people treated with Bexxar later developed leukemia or other cancers. However, it has not been determined whether this medication actually increases the risk of causing other cancers. Talk with your doctor about your individual risk.

Other drugs may interact with tositumomab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.