"To address "continuing safety concerns" about severe neutropenia associated with the atypical antipsychotic clozapine (multiple brands), the US Food and Drug Administration (FDA) is making changes to requirements for monitoring, prescribing, disp"...
Hypersensitivity reactions have been reported with RIXUBIS. Anaphylaxis and other hypersensitivity reactions are possible. The risk is highest during the early phases of initial exposure in previously untreated patients (PUPs), in particular in patients with high-risk gene mutations. Early signs of allergic reactions, which can progress to anaphylaxis, include angioedema, chest tightness, hypotension, lethargy, nausea, vomiting, paresthesia, restlessness, wheezing, and dyspnea. Immediately discontinue administration and initiate appropriate treatment if allergic- or anaphylactic-type reactions occur. In case of severe allergic reactions, alternative hemostatic measures should be considered.
There have been reports in the literature showing an association between the occurrence of a factor IX inhibitor and allergic reactions. Evaluate patients experiencing allergic reactions for the presence of an inhibitor.
RIXUBIS contains trace amounts of Chinese hamster ovary (CHO) proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.
Evaluate patients regularly for the development of factor IX inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor IX inhibitor concentration if expected factor IX activity plasma levels are not attained, or if bleeding is not controlled with an expected dose. Contact a specialized hemophilia treatment center if a patient develops an inhibitor.
Patients with factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to RIXUBIS. RIXUBIS may not be effective in patients with high titer factor IX inhibitors and other therapeutic options should be considered.
Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with factor IX inhibitors. The safety and efficacy of using RIXUBIS for immune tolerance induction have not been established.
The use of factor IX containing products has been associated with the development of thromboembolic complications (e.g., pulmonary embolism, venous thrombosis, and arterial thrombosis). Due to the potential risk for thromboembolic complications, monitor patients for early signs of thromboembolic and consumptive coagulopathy, when administering RIXUBIS to patients with liver disease, with signs of fibrinolysis, peri- and post-operatively, or at risk for thromboembolic events or DIC. The benefit of treatment with RIXUBIS should be weighed against the risk of these complications in patients with DIC or those at risk for DIC or thromboembolic events.
Monitoring Laboratory Tests
- Monitor factor IX activity plasma levels by the one-stage clotting assay to confirm that adequate factor IX levels have been achieved and maintained [see DOSAGE AND ADMINISTRATION].
- Monitor for the development of inhibitors if expected factor IX activity plasma levels are not attained, or if bleeding is not controlled with the recommended dose of RIXUBIS. Assays used to determine if factor IX inhibitor is present should be titered in Bethesda Units (BUs).
Patient Counseling Information
See FDA-approved Patient Labeling (Patient Information and Instructions for Use)
- Advise patients to report any adverse reactions or problems following RIXUBIS administration to their physician or healthcare provider.
- Inform patients of the early signs of hypersensitivity reactions (including hives, generalized urticaria, chest tightness, wheezing, and hypotension) and anaphylaxis. Instruct patients to discontinue use of the product and contact their physician if these symptoms occur.
- Advise patients to contact their physician or treatment facility for further treatment and/or assessment if they experience a lack of a clinical response to factor IX replacement therapy, as in some cases this may be a manifestation of an inhibitor.
- Ask patients to follow the specific preparation and administration procedures provided by their physician.
- Inform patients to follow the recommendations in the FDA-approved patient labeling.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Nonclinical studies evaluating the carcinogenic and mutagenic potential of RIXUBIS have not been conducted.
No adverse effects on reproductive organs were observed by macroscopic and microscopic pathological investigations in repeated dose toxicity studies. No investigations on impairment of fertility have been conducted.
Use In Specific Populations
Pregnancy Category C
Animal reproduction studies have not been conducted with RIXUBIS. It is also not known whether RIXUBIS can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. RIXUBIS should be given to a pregnant woman only if clearly needed.
It is not known whether RIXUBIS is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this product is administered to a nursing woman.
Safety, efficacy and pharmacokinetics of RIXUBIS have been evaluated in 23 previously treated pediatric patients. Twelve (52.2%) were 6 to < 12 years of age and 11 subjects (47.8%) were < 6 years of age. Previously treated pediatric subjects 6 to < 12 years of age were previously treated with plasma-derived and/or recombinant factor IX concentrate(s) for a minimum of 150 exposure days (based on the subject's medical records). Subjects < 6 years of age were previously treated with plasma-derived and/or recombinant factor IX concentrate(s) for > 50 exposure days (based on the subject's medical records).
Incremental recovery was observed to be 22% lower in pediatric patients ( < 12 years) and dose adjustment is needed [see DOSAGE AND ADMINISTRATIONand CLINICAL PHARMACOLOGY]. The mean incremental recovery (in ([IU/dL]/[IU/kg]) at the initial pharmacokinetics evaluation was 0.67 (± 0.16) in subjects of both age cohorts, with lower values in the younger age cohort (0.59 ± 0.13) and higher values in the older age group (0.73 ± 0.16). Clearance was higher in the younger age cohort, with a mean clearance of 10.6 ± 1.7 mL/(kg.hr) (median: 10.5; range: 8.1-14.4) in the < 6 years age cohort compared to a mean clearance of 8.7 ± 1.2 mL/(kg.hr) (median: 8.6; range: 6.9-10.8) in the 6 to < 12 years age cohort.
In a prospective, open-label, uncontrolled multicenter trial with patients < 12 years of age, a total of 41 infusions were given for the treatment of 26 bleeding episodes (7 joint, 19 muscle and soft tissue). Bleeding was controlled in all episodes. In 23 of 26 (88.5%) of the episodes, hemostasis was achieved with one or two infusions. The mean annualized bleeding episode rate (ABR) for children < 12 years of age was 2.7 bleeds per patient per year ± 3.14 with a median of 2 ranging from 0 to 10.8. See Clinical Studies for patients 12 to < 16 years of age. The median ABR during prophylaxis was comparable among children, adolescents and adults.
Clinical studies of RIXUBIS did not include subjects aged 65 and over. It is not known whether elderly patients respond differently than younger patients. Dose selection for an elderly patient should be individualized [see DOSAGE AND ADMINISTRATION].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 2/29/2016
Additional Rixubis Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.