Ruxience

Información importante de dosificación

Administrar solo como una infusión intravenosa .

No administrar como un empuje o bolo intravenoso. RUXIENCE solo debe ser administrado por un profesional de la salud apoyo médico apropiado para manejar reacciones graves relacionadas con la perfusión que puede ser fatal si ocurren .

Premedicar antes de cada infusión .

Antes de la primera infusión

Examine a todos los pacientes para detectar infección por VHB midiendo HBsAg y anti-HBc antes de iniciar el tratamiento con RUXIENCE . Obtenga recuentos sanguíneos completos, incluidas plaquetas (CBC) antes a la primera dosis.

Durante la terapia de RUXIENCIA

En pacientes con neoplasias linfoides, durante el tratamiento con monoterapia con RUXIENCE, obtenga recuentos sanguíneos completos (CBC) con diferencial y recuentos de plaquetas antes de cada curso RUXIENCE. Durante el tratamiento con RUXIENCIA y quimioterapia, obtenga CBC con recuentos diferenciales y plaquetarios en intervalos semanales a mensuales y con mayor frecuencia en pacientes que se desarrollan citopenias . En pacientes con GPA o MPA, obtener CBC con recuentos diferenciales y plaquetarios a intervalos de dos a cuatro meses durante Terapia de RUXIENCIA. Continúe monitoreando las citopenias después de la dosis final y hasta resolución.

• Primera infusión: Iniciar infusión a una velocidad de 50 mg / hora. En ausencia de toxicidad para la perfusión, aumente la velocidad de perfusión en 50 incrementos de mg / hora cada 30 minutos, hasta un máximo de 400 mg / hora.
• Infusiones posteriores:
  Infusión estándar: inicie la infusión a una velocidad de 100 mg / hora. En ausencia de toxicidad para la perfusión, aumente la velocidad en incrementos de 100 mg / hora a Intervalos de 30 minutos, hasta un máximo de 400 mg / hora.
  Para pacientes con NHL y DLBCL foliculares no tratados previamente:
  Si los pacientes no experimentaron un evento adverso relacionado con la perfusión de grado 3 o 4 durante el ciclo 1, se puede administrar una infusión de 90 minutos en el ciclo 2 con a régimen de quimioterapia que contiene glucocorticoides. Iniciar a una tasa del 20% de la dosis total administrada en los primeros 30 minutos y el 80% restante del total dosis administrada durante los próximos 60 minutos. Si se tolera la infusión de 90 minutos Ciclo 2, se puede usar la misma tasa al administrar el resto del régimen de tratamiento (a través del ciclo 6 u 8).
  Pacientes que tienen enfermedad cardiovascular clínicamente significativa o que tienen a recuento de linfocitos circulantes ≥5,000 / mm³ antes del ciclo 2 no debería ser administró la infusión de 90 minutos .
• Interrumpa la infusión o disminuya la velocidad de infusión reacciones relacionadas con la perfusión . Continúe la infusión a la mitad de la velocidad anterior mejora de los síntomas.

Dosis recomendada para el linfoma no Hodgkin (NHL)

La dosis recomendada es de 375 mg / m² como intravenosa infusión según los siguientes horarios:

• Recaída o refractaria, de bajo grado o folicular CD20-Positivo, B-Cell NHL Administre una vez por semana durante 4 u 8 dosis.
• Retratamiento para recaído o refractario, de bajo grado o Folicular, CD20-Positivo, B-Cell NHL Administre una vez por semana por 4 dosis.
• Anteriormente no tratado, Folicular, CD20-Positivo, B-Cell NHL
  Administre el día 1 de cada ciclo de quimioterapia, hasta 8 dosis. En pacientes con respuesta completa o parcial, inicie el mantenimiento de RUXIENCE ocho semanas después de la finalización de un producto rituximab en combinación con quimioterapia. Administre RUXIENCE como agente único cada 8 semanas durante 12 dosis.
• No progresista, de bajo grado, CD20-Positivo, B-Cell NHL, después de la quimioterapia CVP de primera línea
  Después de completar 6-8 ciclos de quimioterapia CVP, administre una vez semanalmente para 4 dosis a intervalos de 6 meses hasta un máximo de 16 dosis.
• Diffuse Large B-Cell NHL
  Administre el día 1 de cada ciclo de quimioterapia hasta 8 infusiones.

Dosis recomendada para la leucemia linfocítica crónica (CLL)

La dosis recomendada es:

• 375 mg / m² el día anterior al inicio del FC quimioterapia, luego 500 mg / m² en el día 1 de los ciclos 2-6 (cada 28 días).

Dosis recomendada como componente de Zevalin® para el tratamiento de NHL

• Infundir RUXIENCE 250 mg / m² dentro de las 4 horas previas a la administración de Indium-111- (In-111-) Zevalin y dentro de las 4 horas previas a la administración de itrio-90- (Y-90-) Zevalin.
• Administre RUXIENCE e In-111-Zevalin 7-9 días antes RUXIENCIA e Y-90- Zevalin.
• Consulte el inserto del paquete Zevalin para obtener la prescripción completa información sobre el régimen terapéutico de Zevalin.

Dosis recomendada para granulomatosis con poliangiitis (GPA) (Granulomatosis de Wegener) y Poliangiitis microscópica (MPA)

Tratamiento de inducción de pacientes con GPA / MPA activo

• Administre RUXIENCE como una infusión intravenosa de 375 mg / m² una vez a la semana durante 4 semanas para pacientes con GPA o MPA activo
• Glucocorticoides administrados como metilprednisolona 1,000 mg por vía intravenosa por día durante 1 a 3 días seguido de prednisona oral 1 mg / kg / día (que no exceda los 80 mg / día y cónico por necesidad clínica) son recomendado para tratar síntomas de vasculitis severa. Este régimen debería comenzar dentro de los 14 días anteriores o con el inicio de RUXIENCE y puede continuar durante y después del curso de inducción de 4 semanas de tratamiento con RUXIENCE.

Tratamiento de seguimiento de pacientes con GPA / MPA que lo han hecho Control de enfermedades logrado con tratamiento de inducción

• Administre RUXIENCE como dos infusiones intravenosas de 500 mg separado por dos semanas, seguido de una infusión intravenosa de 500 mg cada 6 meses después basados en la evaluación clínica.
• Los pacientes deben recibir 100 mg por vía intravenosa metilprednisolona se completará 30 minutos antes de cada infusión de RUXIENCE.
• Si el tratamiento de inducción de la enfermedad activa fue con a producto rituximab, el tratamiento de seguimiento con RUXIENCE debe iniciarse dentro 24 semanas después de la última infusión de inducción con un producto de rituximab o basado en evaluación clínica, pero no antes de las 16 semanas posteriores a la última inducción infusión con un producto rituximab.
• Si el tratamiento por inducción de la enfermedad activa fue con otro inmunosupresores estándar de atención, el tratamiento de seguimiento de RUXIENCE debe ser iniciado dentro del período de 4 semanas que sigue al logro del control de la enfermedad.

Dosis recomendada para premedicación y profiláctico Medicamentos

Premedicar con acetaminofén y un antihistamínico antes de cada infusión de RUXIENCE. Para pacientes a los que se les administró RUXIENCE de acuerdo a la velocidad de infusión de 90 minutos, el componente glucocorticoide de sus El régimen de quimioterapia debe administrarse antes de la perfusión .

Para pacientes con GPA y MPA, se administran glucocorticoides combinación con RUXIENCE (Granulomatosis de Wegener) y Poliangiitis microscópica (MPA)). Proporcionar tratamiento de profilaxis para neumonía por Pneumocystis jirovecii (PCP) y herpes infecciones de virus para pacientes con CLL durante el tratamiento y hasta por 12 meses después del tratamiento según corresponda .

La profilaxis con PCP también se recomienda para pacientes con GPA y MPA durante el tratamiento y durante al menos 6 meses después de la última RUXIENCIA infusión.

Administración y almacenamiento

Utilice la técnica aséptica adecuada. Droga parenteral los productos deben inspeccionarse visualmente para detectar partículas y decoloración antes de la administración. RUXIENCE debe ser claro a ligeramente opalescente líquido incoloro a amarillo parduzco pálido. No use vial si hay partículas o la decoloración está presente.

Administración

Retirar la cantidad necesaria de RUXIENCIA y diluir a a concentración final de 1 mg / ml a 4 mg / ml en una bolsa de infusión que contenga cualquiera de ellos 0.9% de cloruro de sodio, USP o 5% de inyección de dextrosa, USP. Invierta suavemente la bolsa para mezclar la solución. No mezclar ni diluir con otras drogas. Deseche cualquier no utilizado porción dejada en el vial.

Almacenamiento

Las soluciones diluidas de RUXIENCE para perfusión pueden almacenarse en 2 ° C a 8 ° C (36 ° F a 46 ° F) durante 24 horas. Administración completa dentro de las 8 horas de eliminación de refrigeración. No hay incompatibilidades entre RUXIENCE y Se han observado bolsas de cloruro de polivinilo.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Infusion-Related Reactions

Rituximab products can cause severe, including fatal, infusion-related reactions. Severe reactions typically occurred during the first infusion with time to onset of 30 to 120 minutes. Rituximab product-induced infusion-related reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death.

Premedicate patients with an antihistamine and acetaminophen prior to dosing. Institute medical management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion-related reactions as needed. Depending on the severity of the infusion-related reaction and the required interventions, temporarily or permanently discontinue RUXIENCE. Resume infusion at a minimum 50% reduction in rate after symptoms have resolved. Closely monitor the following patients: those with pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm³ ) .

Severe Mucocutaneous Reactions

Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with rituximab products. These reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has been variable and includes reports with onset on the first day of rituximab exposure. Discontinue RUXIENCE in patients who experience a severe mucocutaneous reaction. The safety of re-administration of rituximab products to patients with severe mucocutaneous reactions has not been determined.

Hepatitis B Virus (HBV) Reactivation

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies, including rituximab products. Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti-HBc) positive. Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive and hepatitis B surface antibody (anti-HBs) positive).

HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA levels or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, i.e., increase in transaminase levels. In severe cases increase in bilirubin levels, liver failure, and death can occur.

Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with RUXIENCE. For patients who show evidence of prior hepatitis B infection (HBsAg positive (regardless of antibody status) or HBsAg negative but anti-HBc positive), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and/or during RUXIENCE treatment.

Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following RUXIENCE therapy. HBV reactivation has been reported up to 24 months following completion of rituximab therapy.

In patients who develop reactivation of HBV while on RUXIENCE, immediately discontinue RUXIENCE and any concomitant chemotherapy, and institute appropriate treatment. Insufficient data exist regarding the safety of resuming RUXIENCE treatment in patients who develop HBV reactivation. Resumption of RUXIENCE treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV.

Progressive Multifocal Leukoencephalopathy (PML)

JC virus infection resulting in PML and death can occur in rituximab product-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received rituximab in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of rituximab.

Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture.

Discontinue RUXIENCE and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML.

Tumor Lysis Syndrome (TLS)

Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, sometimes fatal, can occur within 12-24 hours after the first infusion of rituximab products in patients with NHL. A high number of circulating malignant cells (≥25,000/mm³ ) or high tumor burden, confers a greater risk of TLS.

Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated .

Infections

Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of rituximab product-based therapy. Infections have been reported in some patients with prolonged hypogammaglobulinemia (defined as hypogammaglobulinemia >11 months after rituximab exposure). New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue RUXIENCE for serious infections and institute appropriate anti-infective therapy . RUXIENCE is not recommended for use in patients with severe, active infections.

Cardiovascular Adverse Reactions

Cardiac adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock may occur in patients receiving rituximab products. Discontinue infusions for serious or life-threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RUXIENCE for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina .

Renal Toxicity

Severe, including fatal, renal toxicity can occur after rituximab product administration in patients with NHL. Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and RUXIENCE is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue RUXIENCE in patients with a rising serum creatinine or oliguria ).

Bowel Obstruction And Perforation

Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving rituximab products in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1-77) days in patients with NHL. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur.

Immunization

The safety of immunization with live viral vaccines following rituximab product therapy has not been studied and vaccination with live virus vaccines is not recommended before or during treatment.

Embryo-Fetal Toxicity

Based on human data, rituximab products can cause fetal harm due to B-cell lymphocytopenia in infants exposed in-utero. Advise pregnant women of the risk to a fetus. Females of childbearing potential should use effective contraception while receiving RUXIENCE and for 12 months following the last dose of RUXIENCE.

Concomitant Use With Other Biologic Agents And DMARDS In GPA And MPA

Limited data are available on the safety of the use of biologic agents or disease modifying antirheumatic drugs (DMARDs). Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly. Use of concomitant immunosuppressants other than corticosteroids has not been studied in GPA or MPA patients exhibiting peripheral B-cell depletion following treatment with rituximab products.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Infusion-Related Reactions

Inform patients about the signs and symptoms of infusion-related reactions. Advise patients to contact their healthcare provider immediately to report symptoms of infusion-related reactions including urticaria, hypotension, angioedema, sudden cough, breathing problems, weakness, dizziness, palpitations, or chest pain .

Severe Mucocutaneous Reactions

Advise patients to contact their healthcare provider immediately for symptoms of severe mucocutaneous reactions, including painful sores or ulcers on the mouth, blisters, peeling skin, rash, and pustules .

Hepatitis B Virus Reactivation

Advise patients to contact their healthcare provider immediately for symptoms of hepatitis including worsening fatigue or yellow discoloration of skin or eyes .

Progressive Multifocal Leukoencephalopathy (PML)

Advise patients to contact their healthcare provider immediately for signs and symptoms of PML, including new or changes in neurological symptoms such as confusion, dizziness or loss of balance, difficulty talking or walking, decreased strength or weakness on one side of the body, or vision problems .

Tumor Lysis Syndrome (TLS)

Advise patients to contact their healthcare provider immediately for signs and symptoms of tumor lysis syndrome such as nausea, vomiting, diarrhea, and lethargy .

Infections

Advise patients to contact their healthcare provider immediately for signs and symptoms of infections including fever, cold symptoms (e.g., rhinorrhea or laryngitis), flu symptoms (e.g., cough, fatigue, body aches), earache or headache, dysuria, oral herpes simplex infection, and painful wounds with erythema and advise patients of the increased risk of infections during and after treatment with RUXIENCE .

Cardiovascular Adverse Reactions

Advise patients of the risk of cardiovascular adverse reactions, including ventricular fibrillation, myocardial infarction, and cardiogenic shock. Advise patients to contact their healthcare provider immediately to report chest pain and irregular heartbeats .

Renal Toxicity

Advise patients of the risk of renal toxicity. Inform patients of the need for healthcare providers to monitor kidney function .

Bowel Obstruction And Perforation

Advise patients to contact their healthcare provider immediately for signs and symptoms of bowel obstruction and perforation, including severe abdominal pain or repeated vomiting .

Embryo-Fetal Toxicity

Advise a pregnant woman of the potential risk to a fetus. Advise female patients that rituximab products can cause fetal harm if taken during pregnancy and to use effective contraception during treatment with RUXIENCE and for at least 12 months after the last dose of RUXIENCE. Advise patients to inform their healthcare provider of a known or suspected pregnancy .

Lactation

Advise women not to breastfeed during treatment with RUXIENCE and for 6 months after the last dose .

This product"s label may have been updated. For current full prescribing information, please visit www.pfizer.com.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of rituximab products or to determine potential effects on fertility in males or females.

Use In Specific Populations

Pregnancy

Risk Summary

Based on human data, rituximab products can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed in-utero . In animal reproduction studies, intravenous administration of rituximab to pregnant cynomolgus monkeys during the period of organogenesis caused lymphoid B-cell depletion in the newborn offspring at doses resulting in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Advise pregnant women of the risk to a fetus.

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk of major birth defects and miscarriage for the indicated populations is unknown. The estimated background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Observe newborns and infants for signs of infection and manage accordingly.

Data

Human Data

Postmarketing data indicate that B-cell lymphocytopenia generally lasting less than six months can occur in infants exposed to rituximab in-utero. Rituximab was detected postnatally in the serum of infants exposed in-utero.

Animal Data

An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received rituximab via the intravenous route during early gestation (organogenesis period; post coitum Days 20 through 50). Rituximab was administered as loading doses on post coitum (PC) Days 20, 21, and 22, at 15, 37.5, or 75 mg/kg/day, and then weekly on PC Days 29, 36, 43, and 50, at 20, 50, or 100 mg/kg/week. The 100 mg/kg/week dose resulted in 80% of the exposure (based on AUC) of those achieved following a dose of 2 grams in humans. Rituximab crosses the monkey placenta. Exposed offspring did not exhibit any teratogenic effects but did have decreased lymphoid tissue B cells.

A subsequent pre- and postnatal reproductive toxicity study in cynomolgus monkeys was completed to assess developmental effects including the recovery of B cells and immune function in infants exposed to rituximab in-utero. Animals were treated with a loading dose of 0, 15, or 75 mg/kg every day for 3 days, followed by weekly dosing with 0, 20, or 100 mg/kg dose. Subsets of pregnant females were treated from PC Day 20 through postpartum Day 78, PC Day 76 through PC Day 134, and from PC Day 132 through delivery and postpartum Day 28. Regardless of the timing of treatment, decreased B cells and immunosuppression were noted in the offspring of rituximab-treated pregnant animals. The B-cell counts returned to normal levels, and immunologic function was restored within 6 months postpartum.

Lactation

Risk Summary

There are no data on the presence of rituximab products in human milk, the effect on the breastfed child, or the effect on milk production. However, rituximab is detected in the milk of lactating cynomolgus monkeys, and IgG is present in human milk. Since many drugs including antibodies are present in human milk, advise a lactating woman not to breastfeed during treatment and for at least 6 months after the last dose of RUXIENCE due to the potential for serious adverse reactions in breastfed infants.

Females And Males Of Reproductive Potential

Rituximab products can cause fetal harm .

Contraception

Females

Females of childbearing potential should use effective contraception while receiving RUXIENCE and for 12 months following treatment.

Pediatric Use

The safety and effectiveness of rituximab products in pediatric patients have not been established.

Hypogammaglobulinemia has been observed in pediatric patients treated with rituximab.

Geriatric Use

Diffuse Large B-Cell NHL

Among patients with DLBCL evaluated in three randomized, active-controlled trials, 927 patients received rituximab in combination with chemotherapy. Of these, 396 (43%) were age 65 or greater and 123 (13%) were age 75 or greater. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse reactions, mostly supraventricular arrhythmias, occurred more frequently among elderly patients. Serious pulmonary adverse reactions were also more common among the elderly, including pneumonia and pneumonitis.

Low-Grade Or Follicular Non-Hodgkin"s Lymphoma

Patients with previously untreated follicular NHL evaluated in NHL Study 5 were randomized to rituximab as single-agent maintenance therapy (n=505) or observation (n=513) after achieving a response to rituximab in combination with chemotherapy. Of these, 123 (24%) patients in the rituximab arm were age 65 or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other clinical studies of rituximab in low-grade or follicular, CD20-positive, B-cell NHL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

Chronic Lymphocytic Leukemia

Among patients with CLL evaluated in two randomized active-controlled trials, 243 of 676 rituximab-treated patients (36%) were 65 years of age or older; of these, 100 rituximab-treated patients (15%) were 70 years of age or older.

In exploratory analyses defined by age, there was no observed benefit from the addition of rituximab to fludarabine and cyclophosphamide among patients 70 years of age or older in CLL Study 11 or in CLL Study 12; there was also no observed benefit from the addition of rituximab to fludarabine and cyclophosphamide among patients 65 years of age or older in CLL Study 12 . Patients 70 years or older received lower dose intensity of fludarabine and cyclophosphamide compared to younger patients, regardless of the addition of rituximab. In CLL Study 11, the dose intensity of rituximab was similar in older and younger patients, however in CLL Study 12 older patients received a lower dose intensity of rituximab.

The incidence of Grade 3 and 4 adverse reactions was higher among patients receiving R-FC who were 70 years or older compared to younger patients for neutropenia (44% vs. 31% (CLL Study 11); 56% vs. 39% (CLL Study 12)), febrile neutropenia (16% vs. 6% (CLL Study 10 (NCT00719472)), anemia (5% vs. 2% (CLL Study 11); 21% vs. 10% (CLL Study 12)), thrombocytopenia (19% vs. 8% (CLL Study 12)), pancytopenia (7% vs. 2% (CLL Study 11); 7% vs. 2% (CLL Study 12)), and infections (30% vs. 14% (CLL Study 12)).

Granulomatosis With Polyangiitis (GPA) (Wegener"s Granulomatosis) And Microscopic Polyangiitis

Of the 99 rituximab-treated GPA and MPA patients in GPA/MPA Study 1, 36 (36%) were 65 years old and over, while 8 (8%) were 75 years and over. No overall differences in efficacy were observed between patients that were 65 years old and over and younger patients. The overall incidence and rate of all serious adverse events was higher in patients 65 years old and over. The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.

In GPA/MPA Study 2, 30 (26%) of the enrolled patients were at least 65 years old, of which 12 patients were exposed to non-U.S.-licensed rituximab and 18 were exposed to azathioprine. The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects.