Bexxar

tositumomab

Dosage Form: injection
Bexxar®

(Tositumomab and Iodine I 131 Tositumomab)

WARNINGS

Hypersensitivity Reactions, including Anaphylaxis: Serious hypersensitivity reactions, including some with fatal outcome, have been reported with the Bexxar therapeutic regimen. Medications for the treatment of severe hypersensitivity reactions should be available for immediate use. Patients who develop severe hypersensitivity reactions should have infusions of the Bexxar therapeutic regimen discontinued and receive medical attention (see WARNINGS).

Prolonged and Severe Cytopenias: The majority of patients who received the Bexxar therapeutic regimen experienced severe thrombocytopenia and neutropenia. The Bexxar therapeutic regimen should not be administered to patients with >25% lymphoma marrow involvement and/or impaired bone marrow reserve (see WARNINGS and ADVERSE REACTIONS).

Pregnancy Category X: The Bexxar therapeutic regimen can cause fetal harm when administered to a pregnant woman.

Special requirements: The Bexxar therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) contains a radioactive component and should be administered only by physicians and other health care professionals qualified by training in the safe use and handling of therapeutic radionuclides. The Bexxar therapeutic regimen should be administered only by physicians who are in the process of being or have been certified by GlaxoSmithKline in dose calculation and administration of the Bexxar therapeutic regimen.

Bexxar Description

The Bexxar therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) is an anti-neoplastic radioimmunotherapeutic monoclonal antibody-based regimen composed of the monoclonal antibody, Tositumomab, and the radiolabeled monoclonal antibody, Iodine I 131 Tositumomab.

Tositumomab

Tositumomab is a murine IgG2a lambda monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Tositumomab is produced in an antibiotic-free culture of mammalian cells and is composed of two murine gamma 2a heavy chains of 451 amino acids each and two lambda light chains of 220 amino acids each. The approximate molecular weight of Tositumomab is 150 kD.

Tositumomab is supplied as a sterile, pyrogen-free, clear to opalescent, colorless to slightly yellow, preservative-free liquid concentrate. It is supplied at a nominal concentration of 14 mg/mL Tositumomab in 35 mg and 225 mg single-use vials. The formulation contains 10% (w/v) maltose, 145 mM sodium chloride, 10 mM phosphate, and Water for Injection, USP. The pH is approximately 7.2.

Iodine I 131 Tositumomab

Iodine I 131 Tositumomab is a radio-iodinated derivative of Tositumomab that has been covalently linked to Iodine-131. Unbound radio-iodine and other reactants have been removed by chromatographic purification steps. Iodine I 131 Tositumomab is supplied as a sterile, clear, preservative-free liquid for IV administration. The dosimetric dosage form is supplied at nominal protein and activity concentrations of 0.1 mg/mL and 0.61 mCi/mL (at date of calibration), respectively. The therapeutic dosage form is supplied at nominal protein and activity concentrations of 1.1 mg/mL and 5.6 mCi/mL (at date of calibration), respectively. The formulation for the dosimetric and the therapeutic dosage forms contains 4.4%−6.6% (w/v) povidone, 1−2 mg/mL maltose (dosimetric dose) or 9−15 mg/mL maltose (therapeutic dose), 8.5−9.5 mg/mL sodium chloride, and 0.9−1.3 mg/mL ascorbic acid. The pH is approximately 7.0.

Bexxar Therapeutic Regimen

The Bexxar therapeutic regimen is administered in two discrete steps: the dosimetric and therapeutic steps. Each step consists of a sequential infusion of Tositumomab followed by Iodine I 131 Tositumomab. The therapeutic step is administered 7-14 days after the dosimetric step. The Bexxar therapeutic regimen is supplied in two distinct package configurations as follows:

Bexxar Dosimetric Packaging

• A carton containing two single-use 225 mg vials and one single-use 35 mg vial of Tositumomab supplied by McKesson BioServices and

• A package containing a single-use vial of Iodine I 131 Tositumomab (0.61 mCi/mL at calibration), supplied by MDS Nordion.

Bexxar Therapeutic Packaging

• A carton containing two single-use 225 mg vials and one single-use 35 mg vial of Tositumomab, supplied by McKesson BioServices and

• A package containing one or two single-use vials of Iodine I 131 Tositumomab (5.6 mCi/mL at calibration), supplied by MDS Nordion.

Physical/Radiochemical Characteristics of Iodine-131

Iodine-131 decays with beta and gamma emissions with a physical half-life of 8.04 days. The principal beta emission has a mean energy of 191.6 keV and the principal gamma emission has an energy of 364.5 keV (Ref 1).

External Radiation

The specific gamma ray constant for Iodine-131 is 2.2 R/millicurie hour at 1 cm. The first half-value layer is 0.24 cm lead (Pb) shielding. A range of values is shown in Table 1 for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb. To facilitate control of the radiation exposure from this radionuclide, the use of a 2.55 cm thickness of Pb will attenuate the radiation emitted by a factor of about 1,000.

Table 1: Radiation Attenuation by Lead Shielding

Shield Thickness (Pb) cm	Attenuation Factor
0.24	0.5
0.89	10-1
1.60	10-2
2.55	10-3
3.7	10-4

The fraction of Iodine-131 radioactivity that remains in the vial after the date of calibration is calculated as follows:

Fraction of remaining radioactivity of Iodine-131 after x days = 2-(x/8.04).

Physical decay is presented in Table 2.

Table 2: Physical Decay Chart: Iodine-131: Half-Life 8.04 Days

Days	Fraction Remaining
0*	1.000
1	0.917
2	0.842
3	0.772
4	0.708
5	0.650
6	0.596
7	0.547
8	0.502
9	0.460
10	0.422
11	0.387
12	0.355
13	0.326
14	0.299

* (Calibration day)

Bexxar - Clinical Pharmacology

General Pharmacology

Tositumomab binds specifically to the CD20 (human B-lymphocyte−restricted differentiation antigen, Bp 35 or B1) antigen. This antigen is a transmembrane phosphoprotein expressed on pre-B lymphocytes and at higher density on mature B lymphocytes (Ref. 2). The antigen is also expressed on >90% of B-cell non-Hodgkin’s lymphomas (NHL) (Ref. 3). The recognition epitope for Tositumomab is found within the extracellular domain of the CD20 antigen. CD20 does not shed from the cell surface and does not internalize following antibody binding (Ref. 4).

Mechanism of Action

Possible mechanisms of action of the Bexxar therapeutic regimen include induction of apoptosis (Ref. 5), complement-dependent cytotoxicity (CDC) (Ref. 6), and antibody-dependent cellular cytotoxicity (ADCC) (Ref. 5) mediated by the antibody. Additionally, cell death is associated with ionizing radiation from the radioisotope.

Pharmacokinetics/Pharmacodynamics

The phase 1 study of Iodine I 131 Tositumomab determined that a 475 mg predose of unlabeled antibody decreased splenic targeting and increased the terminal half-life of the radiolabeled antibody. The median blood clearance following administration of 485 mg of Tositumomab in 110 patients with NHL was 68.2 mg/hr (range: 30.2−260.8 mg/hr). Patients with high tumor burden, splenomegaly, or bone marrow involvement were noted to have a faster clearance, shorter terminal half-life, and larger volume of distribution. The total body clearance, as measured by total body gamma camera counts, was dependent on the same factors noted for blood clearance. Patient-specific dosing, based on total body clearance, provided a consistent radiation dose, despite variable pharmacokinetics, by allowing each patient’s administered activity to be adjusted for individual patient variables. The median total body effective half-life, as measured by total body gamma camera counts, in 980 patients with NHL was 67 hours (range: 28-115 hours).

Elimination of Iodine-131 occurs by decay (see Table 2) and excretion in the urine. Urine was collected for 49 dosimetric doses. After 5 days, the whole body clearance was 67% of the injected dose. Ninety-eight percent of the clearance was accounted for in the urine.

Administration of the Bexxar therapeutic regimen results in sustained depletion of circulating CD20 positive cells. The impact of administration of the Bexxar therapeutic regimen on circulating CD20 positive cells was assessed in two clinical studies, one conducted in chemotherapy naïve patients and one in heavily pretreated patients. The assessment of circulating lymphocytes did not distinguish normal from malignant cells. Consequently, assessment of recovery of normal B cell function was not directly assessed. At seven weeks, the median number of circulating CD20 positive cells was zero (range: 0-490 cells/mm3). Lymphocyte recovery began at approximately 12 weeks following treatment. Among patients who had CD20 positive cell counts recorded at baseline and at 6 months, 8 of 58 (14%) chemotherapy naïve patients had CD20 positive cell counts below normal limits at six months and 6 of 19 (32%) heavily pretreated patients had CD20 positive cell counts below normal limits at six months. There was no consistent effect of the Bexxar therapeutic regimen on post-treatment serum IgG, IgA, or IgM levels.

Radiation Dosimetry

Estimations of radiation-absorbed doses for Iodine I 131 Tositumomab were performed using sequential whole body images and the MIRDOSE 3 software program. Patients with apparent thyroid, stomach, or intestinal imaging were selected for organ dosimetry analyses. The estimated radiation-absorbed doses to organs and marrow from a course of the Bexxar therapeutic regimen are presented in Table 3.

Table 3: Estimated Radiation-Absorbed Organ Doses

		Bexxar	Bexxar
		mGy/MBq	mGy/MBq
		Median	Range
From Organ ROIs
	Thyroid	2.71	1.4 - 6.2
	Kidneys	1.96	1.5 - 2.5
	ULI Wall	1.34	0.8 - 1.7
	LLI Wall	1.30	0.8 - 1.6
	Heart Wall	1.25	0.5 - 1.8
	Spleen	1.14	0.7 - 5.4
	Testes	0.83	0.3 - 1.3
	Liver	0.82	0.6 - 1.3
	Lungs	0.79	0.5 - 1.1
	Red Marrow	0.65	0.5 - 1.1
	Stomach Wall	0.40	0.2 - 0.8
From Whole Body ROIs
	Urine Bladder Wall	0.64	0.6 - 0.9
	Bone Surfaces	0.41	0.4 - 0.6
	Pancreas	0.31	0.2 - 0.4
	Gall Bladder Wall	0.29	0.2 - 0.3
	Adrenals	0.28	0.2 - 0.3
	Ovaries	0.25	0.2 - 0.3
	Small Intestine	0.23	0.2 - 0.3
	Thymus	0.22	0.1 - 0.3
	Uterus	0.20	0.2 - 0.2
	Muscle	0.18	0.1 - 0.2
	Breasts	0.16	0.1 - 0.2
	Skin	0.13	0.1 - 0.2
	Brain	0.13	0.1 - 0.2
	Total Body	0.24	0.2 - 0.3

Clinical Studies

The efficacy of the Bexxar therapeutic regimen was evaluated in 2 studies conducted in patients with low-grade, transformed low-grade, or follicular large-cell lymphoma. Determination of clinical benefit of the Bexxar therapeutic regimen was based on evidence of durable responses without evidence of an effect on survival. All patients had received prior treatment without an objective response or had progression of disease following treatment. Patients were required to have a granulocyte count >1500 cells/mm3, a platelet count ≥100,000/mm3, an average of ≤25% of the intratrabecular marrow space involved by lymphoma, and no evidence of progressive disease arising in a field irradiated with >3500 cGy within 1 year of completion of irradiation.

Study 1 was a multicenter, single-arm study of 40 patients whose disease had not responded to or had progressed after at least four doses of Rituximab therapy. The median age was 57 (range: 35−78); the median time from diagnosis to protocol entry was 50 months (range: 12−170); and the median number of prior chemotherapy regimens was 4 (range: 1−11). The efficacy outcome data from this study, as determined by an independent panel that reviewed patient records and radiologic studies, are summarized in Table 4.

Among the forty patients in the study, twenty-four patients had disease that did not respond to their last treatment with Rituximab, 11 patients had disease that responded to Rituximab for less than 6 months, and five patients had disease that responded to Rituximab, with a duration of response of 6 months or greater. Overall, 35 of the 40 patients met the definition of “Rituximab refractory”, defined as no response or a response of less than 6 months duration. In this subset of patients the overall objective response was 63% (95% confidence interval 45%, 79%) with a median duration of 25 months (range of 4 - 38+ months). The complete response in this subset of patients was 29% (95% CI of 15%, 46%) with a median duration of response not yet reached (range of 4 - 38+ months).

Study 2 was a multicenter, single arm, open-label study of 60 chemotherapy refractory patients. The median age was 60 (range 38-82), the median time from diagnosis to protocol entry was 53 months (range: 9-334), and the median number of prior chemotherapy regimens was 4 (range 2-13). Fifty-three patients had not responded to prior therapy and 7 patients had responded with a duration of response of<6 months. The efficacy outcome data from this study, as determined by an independent panel that reviewed patient records and radiologic studies are also summarized in Table 4. Investigators continued to follow eight patients with complete response after the last independent review panel assessment. The updated duration of ongoing response as per investigators was reported to range from 42 to 85 months.

Table 4: Efficacy Outcomes in Bexxar Clinical Studies

	Study 1 (n = 40)	Study 2 (n = 60)
Overall Response
Rate 95% CI a	68% (51%, 81%)	47% (34%, 60%)
Response Duration (mos)
Median 95% CI a Range	16 (10, NRb) 1+ to 38+	12 (7, 47) 2 to 47
Complete Response c
Rate 95% CI a	33% (19%, 49%)	20% (11%, 32%)
Complete response c duration (mos)
Median 95% CI a Range	NR b (15, NR) 4 to 38+	47 (47, NR) 9 to 47

a CI = Confidence Interval

b NR = Not reached, Median duration of follow up: Study 1 = 26 months; Study 2 = 30 months

c Complete response rate = Pathologic and clinical complete responses

The results of these studies were supported by demonstration of durable objective responses in three single-arm studies. In these studies, 130 patients with Rituximab-naïve follicular non-Hodgkin’s lymphoma with or without transformation were evaluated for efficacy. All patients had relapsed following, or were refractory to, chemotherapy. The overall response rates ranged from 49% to 64% and the median durations of response ranged from 13 to 16 months. Due to small sample sizes in the supportive studies, as in studies 1 and 2, the 95% confidence intervals for the median durations of response are wide.

Indications and Usage for Bexxar

The Bexxar therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) is indicated for the treatment of patients with CD20 antigen-expressing relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with Rituximab-refractory non-Hodgkin’s lymphoma. Determination of the effectiveness of the Bexxar therapeutic regimen is based on overall response rates in patients whose disease is refractory to chemotherapy alone or to chemotherapy and Rituximab. The effects of the Bexxar therapeutic regimen on survival are not known.

The Bexxar therapeutic regimen is not indicated for the initial treatment of patients with CD20 positive non-Hodgkin’s lymphoma. (See ADVERSE REACTIONS, Immunogenicity.)

The Bexxar therapeutic regimen is intended as a single course of treatment. The safety of multiple courses of the Bexxar therapeutic regimen, or combination of this regimen with other forms of irradiation or chemotherapy, has not been evaluated.

Contraindications

The Bexxar therapeutic regimen is contraindicated in patients with known hypersensitivity to murine proteins or any other component of the Bexxar therapeutic regimen.

PREGNANCY CATEGORY X

Iodine I 131 Tositumomab (a component of the Bexxar therapeutic regimen) is contraindicated for use in women who are pregnant. Iodine-131 may cause harm to the fetal thyroid gland when administered to pregnant women. Review of the literature has shown that transplacental passage of radioiodide may cause severe, and possibly irreversible, hypothyroidism in neonates. While there are no adequate and well-controlled studies of the Bexxar therapeutic regimen in pregnant animals or humans, use of the Bexxar therapeutic regimen in women of childbearing age should be deferred until the possibility of pregnancy has been ruled out. If the patient becomes pregnant while being treated with the Bexxar therapeutic regimen, the patient should be apprised of the potential hazard to the fetus (see BOXED WARNING, Pregnancy Category X).

Warnings

Prolonged and Severe Cytopenias (see BOXED WARNINGS; ADVERSE REACTIONS, Hematologic Events)

The most common adverse reactions associated with the Bexxar therapeutic regimen were severe or life-threatening cytopenias (NCI CTC grade 3 or 4) with 71% of the 230 patients enrolled in clinical studies experiencing grade 3 or 4 cytopenias. These consisted primarily of grade 3 or 4 thrombocytopenia (53%) and grade 3 or 4 neutropenia (63%). The time to nadir was 4 to 7 weeks and the duration of cytopenias was approximately 30 days. Thrombocytopenia, neutropenia, and anemia persisted for more than 90 days following administration of the Bexxar therapeutic regimen in 16 (7%), 15 (7%), and 12 (5%) patients respectively (this includes patients with transient recovery followed by recurrent cytopenia). Due to the variable nature in the onset of cytopenias, complete blood counts should be obtained weekly for 10-12 weeks. The sequelae of severe cytopenias were commonly observed in the clinical studies and included infections (45% of patients), hemorrhage (12%), a requirement for growth factors (12% G- or GM-CSF; 7% Epoetin alfa) and blood product support (15% platelet transfusions; 16% red blood cell transfusions). Prolonged cytopenias may also influence subsequent treatment decisions.

The safety of the Bexxar therapeutic regimen has not been established in patients with >25% lymphoma marrow involvement, platelet count<100,000 cells/mm3 or neutrophil count <1,500 cells/mm3.

Hypersensitivity Reactions Including Anaphylaxis (see BOXED WARNINGS; ADVERSE REACTIONS, Hypersensitivity Reactions and Immunogenicity)

Serious hypersensitivity reactions, including some with fatal outcome, were reported during and following administration of the Bexxar therapeutic regimen. Emergency supplies including medications for the treatment of hypersensitivity reactions, e.g., epinephrine, antihistamines and corticosteroids, should be available for immediate use in the event of an allergic reaction during administration of the Bexxar therapeutic regimen. Patients who have received murine proteins should be screened for human anti-mouse antibodies (HAMA). Patients who are positive for HAMA may be at increased risk of anaphylaxis and serious hypersensitivity reactions during administration of the Bexxar therapeutic regimen.

Secondary Malignancies

Myelodysplastic syndrome (MDS) and/or acute leukemia were reported in 10% (24/230) of patients enrolled in the clinical studies and 3% (20/765) of patients included in expanded access programs, with median follow-up of 39 and 27 months, respectively. Among the 44 reported cases, the median time to development of MDS/leukemia was 31 months following treatment; however, the cumulative rate continues to increase.

Additional non-hematological malignancies were also reported in 54 of the 995 patients enrolled in clinical studies or included in the expanded access program. Approximately half of these were non-melanomatous skin cancers. The remainder, which occurred in 2 or more patients, included colorectal cancer (7), head and neck cancer (6), breast cancer (5), lung cancer (4), bladder cancer (4), melanoma (3), and gastric cancer (2). The relative risk of developing secondary malignancies in patients receiving the Bexxar therapeutic regimen over the background rate in this population cannot be determined, due to the absence of controlled studies (see ADVERSE REACTIONS).

Pregnancy Category X

(see BOXED WARNINGS; CONTRAINDICATIONS).

Hypothyroidism

Administration of the Bexxar therapeutic regimen may result in hypothyroidism (see ADVERSE REACTIONS, Hypothyroidism). Thyroid-blocking medications should be initiated at least 24 hours before receiving the dosimetric dose and continued until 14 days after the therapeutic dose (see DOSAGE and ADMINISTRATION). All patients must receive thyroid-blocking agents; any patient who is unable to tolerate thyroid-blocking agents should not receive the Bexxar therapeutic regimen. Patients should be evaluated for signs and symptoms of hypothyroidism and screened for biochemical evidence of hypothyroidism annually.

Precautions

Radionuclide Precautions

Iodine I 131 Tositumomab is radioactive. Care should be taken, consistent with the institutional radiation safety practices and applicable federal guidelines, to minimize exposure of medical personnel and other patients.

Renal Function

Iodine I 131 Tositumomab and Iodine-131 are excreted primarily by the kidneys. Impaired renal function may decrease the rate of excretion of the radiolabeled iodine and increase patient exposure to the radioactive component of the Bexxar therapeutic regimen. There are no data regarding the safety of administration of the Bexxar therapeutic regimen in patients with impaired renal function.

Immunization

The safety of immunization with live viral vaccines following administration of the Bexxar therapeutic regimen has not been studied. The ability of patients who have received the Bexxar therapeutic regimen to generate a primary or anamnestic humoral response to any vaccine has not been studied.

Information for Patients

Prior to administration of the Bexxar therapeutic regimen, patients should be advised that they will have a radioactive material in their body for several days upon their release from the hospital or clinic. After discharge, patients should be provided with both oral and written instructions for minimizing exposure of family members, friends and the general public. Patients should be given a copy of the written instructions for use as a reference for the recommended precautionary actions.

The pregnancy status of women of childbearing potential should be assessed and these women should be advised of the potential risks to the fetus (see CONTRAINDICATIONS). Women who are breastfeeding should be instructed to discontinue breastfeeding and should be apprised of the resultant potential harmful effects to the infant if these instructions are not followed.

Patients should be advised of the potential risk of toxic effects on the male and female gonads following the Bexxar therapeutic regimen, and be instructed to use effective contraceptive methods during treatment and for 12 months following the administration of the Bexxar therapeutic regimen.

Patients should be informed of the risks of hypothyroidism and be advised of the importance of compliance with thyroid blocking agents and need for life-long monitoring.

Patients should be informed of the possibility of developing a HAMA immune response and that HAMA may affect the results of in vitro and in vivo diagnostic tests as well as results of therapies that rely on murine antibody technology.

Patients should be informed of the risks of cytopenias and symptoms associated with cytopenia, the need for frequent monitoring for up to 12 weeks after treatment, and the potential for persistent cytopenias beyond 12 weeks.

Patients should be informed that MDS, secondary leukemia, and solid tumors have also been observed in patients receiving the Bexxar therapeutic regimen.

Due to lack of controlled clinical studies, and high background incidence in the heavily pretreated patient population, the relative risk of development of myelodysplastic syndrome/acute leukemia and solid tumors due to the Bexxar therapeutic regimen cannot be determined.

Laboratory Monitoring

A complete blood count (CBC) with differential and platelet count should be obtained prior to, and at least weekly following administration of the Bexxar therapeutic regimen. Weekly monitoring of blood counts should continue for a minimum of 10 weeks or, if persistent, until severe cytopenias have completely resolved. More frequent monitoring is indicated in patients with evidence of moderate or more severe cytopenias (see BOXED WARNINGS and WARNINGS). Thyroid stimulating hormone (TSH) level should be monitored before treatment and annually thereafter. Serum creatinine levels should be measured immediately prior to administration of the Bexxar therapeutic regimen.

Drug Interactions

No formal drug interaction studies have been performed. Due to the frequent occurrence of severe and prolonged thrombocytopenia, the potential benefits of medications that interfere with platelet function and/or anticoagulation should be weighed against the potential increased risk of bleeding and hemorrhage.

Drug/Laboratory Test Interactions

Administration of the Bexxar therapeutic regimen may result in the development of HAMA. The presence of HAMA may affect the accuracy of the results of in vitro and in vivo diagnostic tests and may affect the toxicity profile and efficacy of therapeutic agents that rely on murine antibody technology. Patients who are HAMA positive may be at increased risk for serious allergic reactions and other side effects if they undergo in vivo diagnostic testing or treatment with murine monoclonal antibodies.

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, radiation is a potential carcinogen and mutagen. Administration of the Bexxar therapeutic regimen results in delivery of a significant radiation dose to the testes. The radiation dose to the ovaries has not been established. There have been no studies to evaluate whether administration of the Bexxar therapeutic regimen causes hypogonadism, premature menopause, azoospermia and/or mutagenic alterations to germ cells. There is a potential risk that the Bexxar therapeutic regimen may cause toxic effects on the male and female gonads. Effective contraceptive methods should be used during treatment and for 12 months following administration of the Bexxar therapeutic regimen.

Pregnancy Category X

(See CONTRAINDICATIONS; WARNINGS.)

Nursing Mothers

Radioiodine is excreted in breast milk and may reach concentrations equal to or greater than maternal plasma concentrations. Immunoglobulins are also known to be excreted in breast milk. The absorption potential and potential for adverse effects of the monoclonal antibody component (Tositumomab) in the infant are not known. Therefore, formula feedings should be substituted for breast feedings before starting treatment. Women should be advised to discontinue nursing.

Pediatric Use

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

Geriatric Use

Clinical studies of the Bexxar therapeutic regimen did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In clinical studies, 230 patients received the Bexxar therapeutic regimen at the recommended dose. Of these, 27% (61 patients) were age 65 or older and 4% (10 patients) were age 75 or older. Across all studies, the overall response rate was lower in patients age 65 and over (41% vs. 61%) and the duration of responses was shorter (10 months vs. 16 months); however, these findings are primarily derived from 2 of the 5 studies. While the incidence of severe hematologic toxicity was lower, the duration of severe hematologic toxicity was longer in those age 65 or older as compared to patients less than 65 years of age. Due to the limited experience greater sensitivity of some older individuals cannot be ruled out.

Adverse Reactions

The most serious adverse reactions observed in the clinical trials were severe and prolonged cytopenias and the sequelae of cytopenias which included infections (sepsis) and hemorrhage in thrombocytopenic patients, allergic reactions (bronchospasm and angioedema), secondary leukemia and myelodysplasia (see BOXED WARNINGS and WARNINGS).

The most common adverse reactions occurring in the clinical trials included neutropenia, thromobocytopenia, and anemia that are both prolonged and severe. Less common but severe adverse reactions included pneumonia, pleural effusion and dehydration.

Data regarding adverse events were primarily obtained in 230 patients with non-Hodgkin’s lymphoma enrolled in five clinical trials using the recommended dose and schedule. Patients had a median follow-up of 39 months and 79% of the patients were followed at least 12 months for survival and selected adverse events. Patients had a median of 3 prior chemotherapy regimens, a median age of 55 years, 60% male, 27% had transformation to a higher grade histology, 29% were intermediate grade and 2% high grade histology (IWF) and 68% had Ann Arbor stage IV disease. Patients enrolled in these studies were not permitted to have prior hematopoietic stem cell transplantation or irradiation to more than 25% of the red marrow. In the expanded access program, which included 765 patients, data regarding clinical serious adverse events and HAMA and TSH levels were used to supplement the characterization of delayed adverse events (see ADVERSE REACTIONS, Hypothyroidism, Secondary Leukemia and Myelodysplastic Syndrome, Immunogenicity).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Hematologic Events

Hematologic toxicity was the most frequently observed adverse event in clinical trials with the Bexxar therapeutic regimen (Table 6). Sixty-three (27%) of 230 patients received one or more hematologic supportive care measures following the therapeutic dose: 12% received G-CSF; 7% received Epoetin alfa; 15% received platelet transfusions; and 16% received packed red blood cell transfusions. Twenty-eight (12%) patients experienced hemorrhagic events; the majority were mild to moderate.

Infectious Events

One hundred and four of the 230 (45%) patients experienced one or more adverse events possibly related to infection. The majority were viral (e.g., rhinitis, pharyngitis, flu symptoms, or herpes) or other minor infections. Twenty of 230 (9%) patients experienced infections that were considered serious because the patient was hospitalized to manage the infection. Documented infections included pneumonia, bacteremia, septicemia, bronchitis, and skin infections.

Hypersensitivity Reactions

Fourteen patients (6%) experienced one or more of the following adverse events: allergic reaction, face edema, injection site hypersensitivity, a

Betaxon

Generic Name: levobetaxolol ophthalmic (lee voe bay TAX oh lol)

Brand Names: Betaxon

What is Betaxon (levobetaxolol ophthalmic)?

Levobetaxolol is in a class of drugs called beta-blockers. Levobetaxolol ophthalmic reduces pressure inside the eye.

Levobetaxolol ophthalmic is used to treat glaucoma or increased pressure in the eye.

Levobetaxolol ophthalmic may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Betaxon (levobetaxolol ophthalmic)?

Do not touch the dropper to any surface, including the eyes or hands. The dropper is sterile. If it becomes contaminated, it could cause an infection in the eye.

Apply light pressure to the inside corner of the eye (near the nose) after each drop to prevent the fluid from draining down the tear duct.

What should I discuss with my healthcare provider before using Betaxon (levobetaxolol ophthalmic)?

Before using levobetaxolol ophthalmic, tell your doctor if you have

• 
  

  asthma or a chronic lung disease;

  
  


• 
  

  a very slow heart rate;

  
  


• 
  

  heart disease such as high blood pressure, heart failure, or heart block;

  
  


• 
  

  a muscle weakness disease;

  
  


• 
  

  diabetes; or

  
  


• 
  

  an overactive thyroid (hyperthyroidism).

  
  

You may not be able to use levobetaxolol ophthalmic, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Levobetaxolol ophthalmic is in the FDA pregnancy category C. This means that it is not known whether levobetaxolol ophthalmic will be harmful to an unborn baby. Do not use this medication without first talking to your doctor if you are pregnant or could become pregnant during treatment. It is not known whether levobetaxolol ophthalmic passes into breast milk. Do not use levobetaxolol ophthalmic without first talking to your doctor if you are breast-feeding a baby.

How should I use Betaxon (levobetaxolol ophthalmic)?

Use levobetaxolol ophthalmic eyedrops exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Wash your hands before using the eyedrops.

If you wear contact lenses, remove them before applying levobetaxolol ophthalmic. Ask your doctor if contact lenses can be reinserted after application of the medication.

Shake the eyedrops before use.

To apply the eyedrops:

• 
  

  Tilt the head back slightly and pull down on the lower eyelid. Position the dropper above the eye. Look up and away from the dropper. Squeeze out a drop and close the eye. Apply gentle pressure to the inside corner of the eye (near the nose) for about 1 minute to prevent the liquid from draining down the tear duct. If you are using more than 1 drop in the same eye, repeat the process with about 5 minutes between drops. Repeat the process in the other eye if needed.

  
  

Do not touch the dropper to any surface, including the eyes or hands. The dropper is sterile. If it becomes contaminated, it could cause an infection in the eye. Do not use any eyedrop that is discolored or has particles in it. Store levobetaxolol ophthalmic at room temperature away from moisture and heat. Keep the bottle properly capped and protect it from light.

What happens if I miss a dose?

Apply the missed dose as soon as you remember. However, if it is almost time for the next regularly scheduled dose, skip the missed dose and apply the next one as directed. Do not use a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention if an overdose is suspected or if the drops have been ingested.

Symptoms of a levobetaxolol ophthalmic overdose may include a slow heart rate, fainting, and a heart attack.

What should I avoid while using Betaxon (levobetaxolol ophthalmic)?

Do not touch the dropper to any surface, including the eyes or hands. The dropper is sterile. If it becomes contaminated, it could cause an infection in the eye.

If you wear contact lenses, remove them before applying levobetaxolol ophthalmic. Ask your doctor if contact lenses can be reinserted after application of the medication.

Do not use other eye medications during treatment with levobetaxolol ophthalmic except under the direction of your doctor.

Betaxon (levobetaxolol ophthalmic) side effects

If you experience any of the following serious side effects, stop using levobetaxolol ophthalmic and seek emergency medical attention or contact your doctor immediately:

• 
  

  an allergic reaction (swelling of the lips, face, or tongue; difficulty breathing; closing of the throat; or hives);

  
  


• 
  

  an asthma attack (shortness of breath, wheezing); or

  
  


• 
  

  irregular, fast, or slow heartbeats or changes in blood pressure.

  
  

Other, less serious side effects may be more likely to occur. Continue to use levobetaxolol ophthalmic and talk to your doctor if you experience

• 
  

  eye burning or stinging;

  
  


• 
  

  blurred vision;

  
  


• 
  

  anxiety;

  
  


• 
  

  dizziness; or

  
  


• 
  

  upset stomach.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Betaxon (levobetaxolol ophthalmic)?

Do not use other eye medications during treatment with levobetaxolol ophthalmic except under the direction of your doctor.

Before using levobetaxolol ophthalmic, tell your doctor if you are taking any of the following drugs:

• 
  

  another beta-blocker by mouth, such as propranolol (Inderal), atenolol (Tenormin), or metoprolol (Lopressor);

  
  


• 
  

  reserpine, prazosin (Minipress), doxazosin (Cardura), tamsulosin (Flomax), or terazosin (Hytrin); or

  
  


• 
  

  a stimulant drug, such as amphetamine, amphetamine-dextroamphetamine (Adderall); dextroamphetamine (Dexedrine, Dextrostat), diethylpropion (Tenuate, Tenuate Dospan), methylphenidate (Ritalin); pemoline (Cylert); phentermine (Adipex-P, Fastin, Ionamin); and others.

  
  

You may not be able to use levobetaxolol ophthalmic, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with levobetaxolol ophthalmic. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

More Betaxon resources

• Betaxon Side Effects (in more detail)
• Betaxon Use in Pregnancy & Breastfeeding
• Betaxon Drug Interactions
• Betaxon Support Group
• 0 Reviews for Betaxon - Add your own review/rating

Compare Betaxon with other medications

• Glaucoma, Open Angle

Where can I get more information?

• Your pharmacist has additional information about levobetaxolol ophthalmic written for health professionals that you may read.

What does my medication look like?

Levobetaxolol ophthalmic is available with a prescription under the brand name Betaxon in a 0.5% suspension. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about levobetaxolol ophthalmic, especially if this medication is new to you.

See also: Betaxon side effects (in more detail)

Betamethasone Valerate Lotion

Pronunciation: bay-ta-METH-a-sone VAL-eh-rate
Generic Name: Betamethasone Valerate
Brand Name: Beta-Val

Betamethasone Valerate Lotion is used for:

Reducing itching, redness, and swelling associated with many skin conditions.

Betamethasone Valerate Lotion is a topical corticosteroid. It works by depressing the formation, release, and activity of different cells and chemicals that cause swelling, redness, and itching.

Do NOT use Betamethasone Valerate Lotion if:

• you are allergic to any ingredient in Betamethasone Valerate Lotion

Contact your doctor or health care provider right away if any of these apply to you.

Before using Betamethasone Valerate Lotion:

Some medical conditions may interact with Betamethasone Valerate Lotion. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have thinning of the skin, a skin infection, tuberculosis (TB), chickenpox, shingles, measles, or a positive TB skin test, or have recently been vaccinated

Some MEDICINES MAY INTERACT with Betamethasone Valerate Lotion. Because little, if any, of Betamethasone Valerate Lotion is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Betamethasone Valerate Lotion may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Betamethasone Valerate Lotion:

Use Betamethasone Valerate Lotion as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Do not mix Betamethasone Valerate Lotion with other medications.


• Shake well before each use.


• Apply a small amount of medicine to the affected area. Gently rub the medicine in until it is evenly distributed. Wash your hands after applying Betamethasone Valerate Lotion, unless your hands are part of the treated area.


• Do not cover the areas being treated with bandages or other dressings unless advised to do so by your doctor.


• If you miss a dose of Betamethasone Valerate Lotion, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Betamethasone Valerate Lotion.

Important safety information:

• Avoid long-term use, especially near the eyes, on the face, on the genital and rectal areas, and in skin folds.


• Betamethasone Valerate Lotion is for external use only. Avoid contact with eyes or eyelids. If you get Betamethasone Valerate Lotion in your eyes, immediately flush with cool tap water.


• Do not use Betamethasone Valerate Lotion for other skin conditions at a later time.


• If Betamethasone Valerate Lotion was prescribed to treat the diaper area of a child, avoid using tight-fitting diapers or plastic pants.


• Betamethasone Valerate Lotion should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Betamethasone Valerate Lotion while you are pregnant. It is not known if Betamethasone Valerate Lotion is found in breast milk. If you are or will be breast-feeding while you use Betamethasone Valerate Lotion, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Betamethasone Valerate Lotion:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Acne; cracking and stinging of the skin; dryness; excessive hair growth; inflamed hair follicles; itching; skin irritation.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); itching, burning, redness, or swelling not present before the use of Betamethasone Valerate Lotion; secondary infection; skin thinning and discoloration.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center ( http://www.aapcc.org), or emergency room immediately. Betamethasone Valerate Lotion may be harmful if swallowed.

Proper storage of Betamethasone Valerate Lotion:

Store Betamethasone Valerate Lotion at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Betamethasone Valerate Lotion out of the reach of children and away from pets.

General information:

• If you have any questions about Betamethasone Valerate Lotion, please talk with your doctor, pharmacist, or other health care provider.


• Betamethasone Valerate Lotion is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Betamethasone Valerate Lotion. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Betamethasone Valerate resources

• Betamethasone Valerate Use in Pregnancy & Breastfeeding
• Betamethasone Valerate Drug Interactions
• Betamethasone Valerate Support Group
• 13 Reviews for Betamethasone Valerate - Add your own review/rating

Compare Betamethasone Valerate with other medications

• Atopic Dermatitis
• Dermatitis
• Dermatological Disorders
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• Lichen Sclerosus

Beyaz

Pronunciation: droe-SPYE-re-none/ETH-i-nil ES-tra-DYE-ol/LEE-voe-me-FOE-late
Generic Name: Drospirenone/Ethinyl Estradiol/Levomefolate
Brand Name: Beyaz

Cigarette smoking increases the risk of serious heart problems associated with use of Beyaz. This risk increases with age and with heavy smoking. Women who are over 35 years old have a greater risk. Women who are over 35 years old and smoke should not use Beyaz.

Beyaz is used for:

Preventing pregnancy. It is also used to treat premenstrual dysphoric disorder (PMDD) or certain types of acne in women who are using Beyaz for birth control. It is also used to increase folate levels in order to decrease the risk of certain birth defects in women who become pregnant while taking Beyaz or shortly after stopping Beyaz. It may also be used for other conditions as determined by your doctor.

Beyaz is a progesterone and estrogen combination birth control pill. It also contains a folate. It works by preventing ovulation. It may also change cervical mucus to prevent the sperm from reaching the egg, and change the lining of the uterus to prevent a fertilized egg from implanting in the uterus.

Do NOT use Beyaz if:

• you are allergic to any ingredient in Beyaz


• you are pregnant or think you may be pregnant


• you have a history of blood clotting problems, severe blood clots (eg, in the lungs, legs, eyes), certain blood vessel problems (eg, in the brain or heart, bleeding in the brain, a heart attack, a stroke), or breast cancer


• you have certain heart problems (eg, heart valve problems, certain types of irregular heartbeat); chest pain caused by angina; certain types of headaches or migraines; uncontrolled high blood pressure; endometrial, cervical, or vaginal cancer; estrogen-dependent growths; or undiagnosed abnormal vaginal bleeding


• you have kidney disease; adrenal disease; diabetes that affects circulation, nerves, eyes, or kidney; liver disease or liver tumors; or a history of yellowing of the eyes or skin caused by pregnancy or prior birth control use


• you have had surgery and are or will be confined to a bed or a chair for an extended period of time


• you are over 35 years old and you smoke


• you have been through menopause

Contact your doctor or health care provider right away if any of these apply to you.

Before using Beyaz:

Some medical conditions may interact with Beyaz. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of endometriosis, growths in the uterus, an abnormal mammogram, irregular menstrual periods, abnormal vaginal bleeding, a lump in the breast, or fibrocystic breast disease, or if a family member has had breast cancer


• if you have a history of diabetes or high blood sugar, gallbladder problems, migraines or severe or persistent headaches, heart problems, high blood pressure, high blood cholesterol or lipid levels, kidney or liver problems, blood or bleeding problems, mental or mood problems (eg, depression), lupus, high blood calcium or potassium levels, chorea (jerky, involuntary movements of the face, arms, or legs), varicose veins, yellowing of the eyes or skin, pancreas problems, seizures, or a condition called hereditary angioedema


• if you smoke, are very overweight, have not yet had your first menstrual period, have certain types of anemia (eg, pernicious anemia), have certain blood problems (eg, porphyria), or have fluid retention or swelling problems


• if you will be having surgery or will be confined to a bed or a chair for a long period of time


• if a family member has a history of high blood triglyceride levels


• if you are taking a folate (folic acid) supplement

Some MEDICINES MAY INTERACT with Beyaz. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Aldosterone blockers (eg, eplerenone), angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril), angiotensin-receptor blockers (eg, losartan), heparin, nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, naproxen), potassium-sparing diuretics (eg, spironolactone), or potassium supplements because the risk of high blood potassium levels may be increased


• Acetaminophen, ascorbic acid (vitamin C), atorvastatin, or tranexamic acid because they may increase the risk of Beyaz's side effects


• Azole antifungals (eg, ketoconazole) or HIV protease inhibitors (eg, ritonavir) because they may decrease Beyaz's effectiveness, resulting in pregnancy or breakthrough bleeding, or they may increase the risk of Beyaz's side effects


• Aprepitant, armodafinil, barbiturates (eg, phenobarbital), bosentan, carbamazepine, felbamate, griseofulvin, hydantoins (eg, phenytoin), modafinil, nevirapine, oxcarbazepine, penicillins (eg, ampicillin), phenylbutazone, rifamycins (eg, rifampin), rufinamide, St. John's wort, tetracyclines (eg, doxycycline), topiramate, or troglitazone because they may decrease Beyaz's effectiveness, resulting in breakthrough bleeding or pregnancy


• Certain antiseizure medicines, cholestyramine, methotrexate, or sulfasalazine because they may decrease the effectiveness of the folate in Beyaz


• Beta-blockers (eg, propranolol), corticosteroids (eg, prednisolone), cyclosporine, theophylline, tizanidine, or troleandomycin because the risk of their side effects may be increased by Beyaz


• Anticoagulants (eg, warfarin) because their effectiveness may be decreased or the risk of their side effects may be increased by Beyaz


• Certain antiseizure medicines (eg, phenytoin, valproic acid), clofibric acid (clofibrate), lamotrigine, methotrexate, morphine, pyrimethamine, salicylic acid, temazepam, or thyroid hormones (eg, levothyroxine) because their effectiveness may be decreased by Beyaz

This may not be a complete list of all interactions that may occur. Ask your health care provider if Beyaz may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Beyaz:

Use Beyaz as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Beyaz. Talk to your pharmacist if you have questions about this information.


• Take Beyaz by mouth with or without food. It is preferable to take Beyaz after the evening meal or at bedtime with liquid.


• Talk with your doctor about how you should start to take your first pack of Beyaz. If you begin to take Beyaz during the first 24 hours of your period, you do not need to use an extra form of birth control. If you begin to take Beyaz on the Sunday after your period starts, you will need to use an extra form of birth control for 7 days after you start taking Beyaz.


• If you are switching from another birth control pill to Beyaz, start Beyaz on the same day that you would have started a new pack of your previous birth control pills. If you are switching to Beyaz from another type of hormonal birth control (eg, patch, vaginal ring), ask your doctor or pharmacist about when to start taking Beyaz.


• Take Beyaz at the same time each day. After taking the last pill in the pack, start taking the first pill from the new pack the very next day.


• Severe vomiting or diarrhea may decrease Beyaz's effectiveness. Talk with your doctor about what to do if severe vomiting or diarrhea occurs while you take Beyaz. If you vomit within 3 to 4 hours after you take Beyaz, this should be considered a missed dose.


• For Beyaz to be effective, it must be taken every day. Do not skip doses even if you do not have sex very often. Do not skip pills if you are spotting, bleeding, or nauseated. If you have these side effects and they do not go away, check with your doctor.


• If you miss 1 dose of Beyaz, take it as soon as possible. Take your next dose at the regular time. This means you may take 2 doses on the same day. You do not need to use a backup form of birth control if you only miss 1 pill. If you miss more than 1 dose, read the extra patient leaflet that comes with Beyaz or contact your doctor for instructions. You must use a backup form of birth control (eg, condom, spermicide) if you miss more than 1 dose. If you are not sure how to handle missed doses, use an extra form of birth control (eg, condoms) and talk with your doctor.

Ask your health care provider any questions you may have about how to use Beyaz.

Important safety information:

• Beyaz may increase the risk of a stroke, a heart attack, blood clots, high blood pressure, or similar problems. The risk is greater if you smoke. Do not smoke or use other tobacco products while taking Beyaz.


• Bleeding or spotting may occur while you are taking Beyaz, especially during the first 3 months. Do not stop taking Beyaz if this occurs. If bleeding or spotting is persistent or if it occurs after menstrual cycles that were previously regular, contact your doctor.


• If you miss more than 2 periods in a row or if you miss 1 period when you have not taken your pills correctly, contact your doctor. Also, if you have morning sickness or unusual breast tenderness, contact your doctor. You may be pregnant if any of these occur.


• Certain antibiotics, anticonvulsants, and other medicines may decrease the effectiveness of Beyaz. Ask your pharmacist if you have questions about which medicines may decrease Beyaz's effectiveness. To prevent pregnancy while taking these medicines, use an extra form of birth control (eg, condoms). You may also need to use an extra form of birth control for a period of time after you stop taking these medicines. Check with your doctor for more information.


• Tell your doctor or dentist that you take Beyaz before you receive any medical or dental care, emergency care, or surgery. If possible, Beyaz should be stopped at least 4 weeks before surgery or any time you might be confined to a bed or chair for a long period of time (eg, long plane flight, bedrest, lengthy illness).


• You should usually not take Beyaz within 4 weeks after giving birth or after a second-trimester abortion. Talk with your doctor about how to start taking Beyaz in these instances.


• Beyaz may cause dark skin patches on your face. Exposure to the sun may make these patches darker. If patches develop, use a sunscreen or wear protective clothing when exposed to the sun, sunlamps, or tanning booths.


• If you wear contact lenses and you develop problems with them or other vision changes, contact your doctor.


• You may experience a delay in being able to become pregnant after stopping Beyaz. This effect may be greater in patients who had irregular periods before starting Beyaz. Discuss any concerns with your doctor or pharmacist.


• Beyaz does not stop the spread of HIV and other sexually transmitted diseases (STDs) to others through blood or sexual contact. Use barrier methods of birth control (eg, condoms) if you have HIV infection or an STD.


• When your medicine supply is low, get more from your doctor or pharmacist as soon as you can. Do not run out of medicine. Your chance of becoming pregnant may be increased if you do not take Beyaz every day as directed.


• Diabetes patients - Beyaz may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Examine your breasts monthly as directed by your doctor. Report any lumps right away.


• Beyaz has folic acid in it. Before you start any new medicine, check the label to see if it has folic acid in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Beyaz may interfere with certain lab tests, such as cholesterol or diabetes. Be sure your doctor and lab personnel know you are taking Beyaz.


• Lab tests, including breast exams, Pap, physicals, and blood pressure, may be performed while you use Beyaz. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Beyaz should not be used in CHILDREN who have not yet had their first menstrual period; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Do not take Beyaz if you are pregnant. If you think you may become pregnant, contact your doctor right away. Beyaz is found in breast milk. Do not breast-feed while you are taking Beyaz.

Possible side effects of Beyaz:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Breast tenderness; bleeding or spotting between menstrual periods; headache; nausea; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); breast pain, lump, or discharge; calf or leg pain, swelling, or tenderness; change in the amount of urine produced; chest pain or heaviness; confusion; coughing of blood; fainting; irregular heartbeat; left-sided jaw, neck, shoulder, or arm pain; mental or mood changes (eg, depression); migraines; missed menstrual period; muscle cramps or weakness; numbness of an arm or leg; one-sided weakness; persistent, severe, or recurring headache or dizziness; persistent vaginal spotting; severe or persistent trouble sleeping; severe stomach pain or tenderness; shortness of breath; slurred speech; sudden, severe vomiting; swelling of the fingers, hands, legs, or ankles; symptoms of liver problems (eg, yellowing of the skin or eyes, fever, dark urine, pale stools, loss of appetite); unusual or severe vaginal bleeding; unusual tiredness or weakness; vaginal irritation or discharge; vision changes (eg, sudden vision loss, double vision).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Beyaz side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include severe nausea; unexplained vaginal bleeding.

Proper storage of Beyaz:

Store Beyaz at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Beyaz out of the reach of children and away from pets.

General information:

• If you have any questions about Beyaz, please talk with your doctor, pharmacist, or other health care provider.


• Beyaz is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Beyaz. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Beyaz resources

• Beyaz Side Effects (in more detail)
• Beyaz Use in Pregnancy & Breastfeeding
• Beyaz Drug Interactions
• Beyaz Support Group
• 58 Reviews for Beyaz - Add your own review/rating

• Beyaz Prescribing Information (FDA)


• Beyaz Consumer Overview


• Beyaz Advanced Consumer (Micromedex) - Includes Dosage Information


• Safyral Prescribing Information (FDA)


• Safyral Consumer Overview

Compare Beyaz with other medications

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Betaseron

Generic Name: interferon beta-1b (Subcutaneous route)

in-ter-FEER-on BAY-ta-1b

Commonly used brand name(s)

In the U.S.

• Betaseron


• Extavia

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Immunological Agent

Pharmacologic Class: Interferon, Beta (class)

Uses For Betaseron

Interferon beta-1b is used to treat the relapsing-remitting form of multiple sclerosis (MS). This medicine will not cure MS, but may decrease the number of relapses of the disease.

This medicine is available only with your doctor's prescription.

Before Using Betaseron

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of interferon beta-1b in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of interferon beta-1b in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rotavirus Vaccine, Live

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Mental depression or thoughts of suicide—This medicine may make the condition worse

Proper Use of interferon beta-1b

This section provides information on the proper use of a number of products that contain interferon beta-1b. It may not be specific to Betaseron. Please read with care.

Use this medicine exactly as directed by your doctor in order to help your condition as much as possible.

Taking interferon beta-1b at bedtime may help lessen the flu-like symptoms.

Special patient directions come with interferon beta-1b. Read the directions carefully before using this medicine.

It is important to follow several steps to prepare your interferon beta-1b injection correctly. Before injecting the medication, you need to:

• Collect the items you will need before you begin.


• Wash your hands thoroughly with soap and water. Do not touch your hair or skin afterwards.


• Make sure the needle guards are on the needles tightly.


• Remove the plastic cap from the interferon beta-1b and the diluent vial. Use an alcohol wipe to clean the tops of the vials. Move the alcohol wipe in one direction and use one wipe per vial. Leave the alcohol wipe on top of each vial until you are ready to use it.

In order to keep everything sterile, it is important that you do not touch the tops of the vials or the needles. If you do touch a stopper, clean it with a fresh alcohol wipe. If you touch a needle, or if the needle touches any surface, throw away the entire syringe and start over with a new syringe. Also, use only the diluent (sodium chloride 0.54%) provided with the interferon beta-1b to dilute the medicine for injection.

To mix the contents of one vial:

• Resting your hands on a stable surface, remove the needle cover on the 3-mL syringe by pulling the cover straight off the needle. Do not touch the needle itself.


• Pull back the plunger of the syringe back to the 1.2-mL mark.


• Holding the vial of diluent for interferon beta-1b on a stable surface, slowly insert the needle straight through the stopper into the top of the vial.


• Push in the plunger all the way to gently inject 1.2 mL of air into the vial. Leave the needle in the vial of diluent.


• Turn the vial upside down using one hand and make sure the tip of the needle is covered by solution. With your other hand, slowly pull back the plunger of the syringe to withdraw 1.2 mL of diluent into the syringe.


• Keeping the vial upside down, gently tap the syringe until any air bubbles that formed rise to the top of the barrel of the syringe.


• Carefully push in the plunger to eject only the air through the needle. Remove the needle/syringe from the vial of diluent.


• Holding the interferon beta-1b vial on a stable surface, slowly insert the needle of the syringe (containing 1.2 mL of diluent) all the way through the stopper of the vial.


• Push the plunger down slowly, directing the needle toward the side of the vial to allow the diluent to run down the inside wall. Injecting the diluent directly onto the white cake of medicine will cause excess foaming.


• Remove the needle/syringe from the vial of interferon beta-1b.


• Roll the vial between your hands gently to completely dissolve the white cake of medicine.


• Check the solution to make sure it is clear. If you can see anything solid in the solution or if the solution is discolored, discard it and start again.

To prepare the injection syringe:

• Remove the needle guard from the 1-mL syringe and pull back the plunger to the 1-mL mark.


• Insert the needle of the 1-mL syringe through the stopper of the vial of interferon beta-1b solution.


• Gently push the plunger all the way down to inject air into the vial.


• Turn the vial of interferon beta-1b solution upside down, keeping the needle tip in the liquid.


• Pull back the plunger of the syringe to withdraw 1 mL of liquid into the syringe.


• Hold the syringe with the needle pointing upward. Tap the syringe gently until any air bubbles that formed rise to the top of the barrel of the syringe.


• Carefully push in the plunger to eject only the air through the needle.


• Remove the needle/syringe from the vial. Replace the needle guard on the syringe.


• Throw away the unused portion of the solution remaining in the vial.

The injection should be administered immediately after mixing. If the injection is delayed, refrigerate the solution and inject it within 3 hours.

To give yourself the injection:

Before you self-inject the interferon beta-1b dose, decide where you will inject yourself. There are eight areas for injection, and each area has an upper, a middle, and a lower injection site. To help prevent injection site reactions, select a site in an area different from the area where you last injected yourself. You should not choose the same area for two injections in a row. Keeping a record of your injections will help make sure you rotate areas.

Do not self-inject into any area in which you feel lumps, bumps, firm knots, or pain. Do not use any area in which the skin is discolored, depressed, red, scabbed, tender, or has broken open. Talk to your doctor or other health care professional about these or any other unusual conditions that you find. If you experience a break in the skin or drainage of fluid from the injection site, contact your doctor before continuing injections with interferon beta-1b.

• Clean the injection site with a fresh alcohol wipe, and let it air dry.


• Pick up the 1-mL syringe you already filled with interferon beta-1b. Hold the syringe as you would a pencil or dart. Remove the needle guard from the needle, but do not touch the needle itself.


• Gently pinch the skin together around the site, to lift it up a bit.


• Resting your wrist on the skin near the site, stick the needle straight into the skin at a 90° angle with a quick, firm motion.


• Using a slow steady push, inject the medicine by pushing the plunger all the way in until the syringe is empty.


• Hold a swab on the injection site. Remove the needle by pulling straight out.


• Gently massage the injection site with a dry cotton ball or gauze.

To dispose of needles and syringes:

Needles, syringes, and vials should be used for only one injection. Place all used syringes, needles, and vials in a syringe disposal unit or in a hard-walled plastic container, such as a liquid laundry detergent container. Keep the cover closed tightly, and keep the container out of the reach of children. When the container is full, check with your physician or nurse about proper disposal, as laws vary from state to state.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form:
  
  • For multiple sclerosis (MS):
    
    • Adults—0.25 milligrams (mg) every other day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

The next injection should be scheduled about 48 hours later.

Storage

Store in the refrigerator. Do not freeze.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

If refrigeration is not available, vials may be kept for up to 7 days at room temperature, as long as the temperature does not go above 86 °F.

Betaseron Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

More common

• Abdominal pain


• break in the skin at place of injection, with blue-black discoloration, swelling, or drainage of fluid


• flu-like symptoms including chills, fever, generalized feeling of discomfort or illness, increased sweating, and muscle pain


• headache or migraine


• hives, itching, or swelling at place of injection


• hypertension (high blood pressure)


• irregular or pounding heartbeat


• pain at place of injection


• redness or feeling of heat at place of injection


• stuffy nose

Less common

• Breast pain


• bloody or cloudy urine


• changes in vision


• cold hands and feet


• difficult, burning, or painful urination


• fast or racing heartbeat


• frequent urge to urinate


• pain


• pelvic pain


• swollen glands


• troubled breathing


• unusual weight gain

Rare

• Abnormal growth in breast


• benign lumps in breast


• bleeding problems


• bloating or swelling


• changes in menstrual periods


• confusion


• convulsions (seizures)


• cyst (abnormal growth filled with fluid or semisolid material)


• decreased sexual ability in males


• dry, puffy skin


• feeling cold


• hyperactivity


• increased muscle tone


• increased urge to urinate


• loss of memory


• mental depression with thoughts of suicide


• problems in speaking


• red, itching, or swollen eyes


• swelling of front part of neck


• unusual weight loss

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Constipation


• diarrhea


• dizziness


• laryngitis (loss of voice)


• menstrual pain or other changes


• unusual tiredness or weakness

Less common

• Anxiety


• drowsiness


• hair loss


• nervousness


• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Betaseron side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Betaseron resources

• Betaseron Side Effects (in more detail)
• Betaseron Use in Pregnancy & Breastfeeding
• Betaseron Drug Interactions
• Betaseron Support Group
• 2 Reviews for Betaseron - Add your own review/rating

• Betaseron Prescribing Information (FDA)


• Betaseron Consumer Overview


• Betaseron Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• Interferon Beta-1b Professional Patient Advice (Wolters Kluwer)


• Extavia Prescribing Information (FDA)


• Extavia Consumer Overview

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