Composition:
Examiné médicalement par Oliinyk Elizabeth Ivanovna, Pharmacie Dernière mise à jour le 27.05.2022
Attention! Information sur la page est réservée aux professionnels de la santé! Les informations sont collectées dans des sources ouvertes et peuvent contenir des erreurs significatives! Soyez prudent et revérifiez toutes les informations de cette page!
Top 20 des médicaments avec les mêmes ingrédients:
Informations posologiques importantes
Administrer uniquement en perfusion intraveineuse .
Ne pas administrer sous forme de poussée ou de bolus intraveineux. RUXIENCE ne doit être administré que par un professionnel de la santé un soutien médical approprié pour gérer les réactions graves liées à la perfusion peut être fatal s'ils se produisent .
Prémédicat avant chaque perfusion .
Avant la première perfusion
Dépistage tous les patients pour une infection par le VHB en mesurant l'AgHB et anti-HBc avant d'initier un traitement par RUXIENCE . Obtenez une numération formule sanguine complète, y compris des plaquettes (CBC) avant à la première dose.
Pendant la thérapie RUXIENCE
Chez les patients atteints de tumeurs malignes lymphoïdes, pendant le traitement avec RUXIENCE en monothérapie, obtenir une numération formule sanguine complète (CBC) avec différentiel et le nombre de plaquettes avant chaque cours RUXIENCE. Pendant le traitement avec RUXIENCE et chimiothérapie, obtenez CBC avec un nombre différentiel et plaquettaire à intervalles hebdomadaires à mensuels et plus fréquemment chez les patients qui se développent cytopénies . Chez les patients atteints de GPA ou de MPA, obtenir CBC avec nombre différentiel et plaquettaire à intervalles de deux à quatre mois pendant Thérapie RUXIENCE. Continuez à surveiller les cytopénies après la dose finale et jusqu'à résolution.
- Première perfusion: Lancer la perfusion à raison de 50 mg / heure. En l'absence de toxicité pour la perfusion, augmenter le débit de perfusion de 50 incréments de mg / heure toutes les 30 minutes, jusqu'à un maximum de 400 mg / heure.
- Infusions ultérieures:
Infusion standard: initier la perfusion à un débit de 100 mg / heure. En l'absence de toxicité pour la perfusion, augmenter le débit par incréments de 100 mg / heure à Intervalles de 30 minutes, jusqu'à un maximum de 400 mg / heure.
Pour les patients atteints de LNH folliculaire et de DLBCL non traités auparavant :
Si les patients n'ont pas présenté d'événement indésirable lié à la perfusion de grade 3 ou 4 pendant le cycle 1, une perfusion de 90 minutes peut être administrée au cycle 2 avec a schéma de chimiothérapie contenant des glucocorticoïdes. Initier à un taux de 20% de la dose totale administrée au cours des 30 premières minutes et les 80% restants du total dose administrée au cours des 60 prochaines minutes. Si la perfusion de 90 minutes est tolérée Cycle 2, le même taux peut être utilisé lors de l'administration du reste du schéma thérapeutique (à travers les cycles 6 ou 8).
Patients atteints d'une maladie cardiovasculaire cliniquement significative ou qui en ont le nombre de lymphocytes circulants ≥5 000 / mm³ avant le cycle 2 ne doit pas l'être administré la perfusion de 90 minutes . - Interrompez la perfusion ou ralentissez le débit de perfusion réactions liées à la perfusion . Continuez la perfusion à la moitié du débit précédent amélioration des symptômes.
Dose recommandée pour le lymphome non hodgkinien (LNH)
La dose recommandée est de 375 mg / m² par voie intraveineuse perfusion selon les schémas suivants:
- Réduit ou réfractaire, de bas grade ou folliculaire , CD20-Positive, B-Cell NHL Administrer une fois par semaine pendant 4 ou 8 doses.
- Retraitement pour rechute ou réfractaire, de bas grade ou Folliculaire, CD20-Positive, B-Cell NHL Administrer une fois par semaine pendant 4 doses.
- Auparavant non traité, folliculaire, CD20-positif ,
B-Cell NHL
Administrer le jour 1 de chaque cycle de chimiothérapie, jusqu'à 8 doses. Dans patients avec réponse complète ou partielle, initiez la maintenance RUXIENCE huit semaines après l'achèvement d'un produit au rituximab en association avec chimiothérapie. Administrer RUXIENCE en tant qu'agent unique toutes les 8 semaines pour 12 doses. - Non-progressiste, de faible qualité, CD20-Positive, B-Cell NHL ,
après la chimiothérapie CVP de première ligne
Après avoir terminé 6 à 8 cycles de chimiothérapie CVP, administrer une fois hebdomadaire pour 4 doses à des intervalles de 6 mois jusqu'à un maximum de 16 doses. - Diffuse grande LNH B-Cell
Administrer le jour 1 de chaque cycle de chimiothérapie jusqu'à 8 perfusions.
Dose recommandée pour la leucémie lymphoïde chronique (LLC)
La dose recommandée est de:
- 375 mg / m² la veille de l'initiation du FC chimiothérapie, puis 500 mg / m² au jour 1 des cycles 2-6 (tous les 28 jours).
Dose recommandée en tant que composant de Zevalin® pour le traitement de la LNH
- Infuser RUXIENCE 250 mg / m² dans les 4 heures précédant le administration d'Indium-111- (In-111-) Zevalin et dans les 4 heures précédant le administration d'yttrium-90- (Y-90-) Zevalin.
- Administrer RUXIENCE et In-111-Zevalin 7-9 jours avant RUXIENCE et Y-90- Zevalin.
- Reportez-vous à l'encart de paquet Zevalin pour une prescription complète informations concernant le schéma thérapeutique Zevalin.
Dose recommandée pour la granulomatose avec polyangiite (GPA) (Granulomatose de Wegener) Et Polyangiite Microscopique (MPA)
Traitement par induction des patients atteints de GPA / MPA actif
- Administrer RUXIENCE en perfusion intraveineuse de 375 mg / m² une fois par semaine pendant 4 semaines pour les patients atteints de GPA ou de MPA actifs
- Glucocorticoïdes administrés sous forme de méthylprednisolone 1 000 mg par voie intraveineuse pendant 1 à 3 jours suivi de prednisone orale 1 mg / kg / jour (ne dépassant pas 80 mg / jour et effilé par besoin clinique) sont recommandé pour traiter les symptômes graves de vascularite. Ce régime devrait commencer dans les 14 jours avant ou avec le début de RUXIENCE et peut continuer pendant et après le cours d'induction de 4 semaines du traitement RUXIENCE.
Suivi du traitement des patients atteints de GPA / MPA qui en ont Contrôle des maladies atteint avec traitement d'induction
- Administrer RUXIENCE sous forme de deux perfusions intraveineuses de 500 mg séparés par deux semaines, suivis d'une perfusion intraveineuse de 500 mg tous les 6 mois après sur la base de l'évaluation clinique.
- Les patients doivent recevoir 100 mg par voie intraveineuse méthylprednisolone à compléter 30 minutes avant chaque perfusion de RUXIENCE.
- Si le traitement d'induction d'une maladie active était avec a produit de rituximab, un traitement de suivi avec RUXIENCE doit être instauré à l'intérieur 24 semaines après la dernière perfusion d'induction avec un produit de rituximab ou sur la base de évaluation clinique, mais au plus tôt 16 semaines après la dernière induction perfusion avec un produit rituximab.
- Si le traitement d'induction d'une maladie active était avec un autre immunosuppresseurs standard, le traitement de suivi RUXIENCE doit être initié dans le délai de 4 semaines qui suit la réalisation de la lutte contre la maladie.
Dose recommandée pour la prémédication et la prophylactique Médicaments
Prémédicat à l'acétaminophène et à un antihistaminique avant chaque perfusion de RUXIENCE. Pour les patients ayant reçu RUXIENCE selon au débit de perfusion de 90 minutes, la composante glucocorticoïde de leur un schéma de chimiothérapie doit être administré avant la perfusion .
Pour les patients atteints de GPA et de MPA, les glucocorticoïdes sont administrés combinaison avec RUXIENCE (Granulomatose de Wegener) et Polyangiite Microscopique (MPA)). Fournir traitement par prophylaxie pour la pneumonie à Pneumocystis jirovecii (PCP) et l'herpès infections virales chez les patients atteints de LLC pendant le traitement et jusqu'à 12 mois après le traitement approprié .
La prophylaxie PCP est également recommandée pour les patients atteints de GPA et MPA pendant le traitement et pendant au moins 6 mois après la dernière RUXIENCE perfusion.
Administration et stockage
Utilisez une technique aseptique appropriée. Médicament parentéral les produits doivent être inspectés visuellement à la recherche de particules et de décoloration avant l'administration. RUXIENCE doit être clair à légèrement opalescent liquide incolore à jaune brunâtre pâle. N'utilisez pas de flacon si vous êtes particulaire ou la décoloration est présente.
Administration
Retirer la quantité nécessaire de RUXIENCE et diluer à a concentration finale de 1 mg / ml à 4 mg / ml dans une poche de perfusion contenant soit 0,9% de chlorure de sodium, USP ou 5% d'injection de dextrose, USP. Inversez doucement le sac mélanger la solution. Ne pas mélanger ou diluer avec d'autres médicaments. Jeter tout inutilisé portion laissée dans le flacon.
Stockage
Les solutions RUXIENCE diluées pour perfusion peuvent être stockées à 2 ° C à 8 ° C (36 ° F à 46 ° F) pendant 24 heures. Administration complète dans les 8 heures de l'élimination de la réfrigération. Aucune incompatibilité entre RUXIENCE et des sacs en polychlorure de vinyle ont été observés.
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.