WARNINGS
As with any intravenous protein product, allergic type hypersensitivity reactions are possible. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis. Patients should be advised to discontinue use of the product and contact their physicians if these symptoms occur.
PRECAUTIONS
GENERAL
Activity-neutralizing antibodies (inhibitors) have been detected in patients receiving factor VIII-containing products. Low titer inhibitors are common in previously untreated patients and in previously treated patients on factor VIII products, as are high titer inhibitors in previously untreated patients. High titer inhibitors, which are generally rare in previously treated patients, have been reported in previously treated patients on ReFacto. As with all coagulation factor VIII products, patients should be monitored for the development of inhibitors that should be titrated in Bethesda Units using appropriate biological testing.
Reports of lack of effect, mainly in prophylaxis patients, have been received in the clinical trials and in the post-marketing setting. The reported lack of effect has been described as bleeding into target joints, bleeding into new joints or a subjective feeling by the patient of new onset bleeding. When switching to ReFacto it is important to individually titrate and monitor each patient's dose in order to ensure an adequate therapeutic response (see DOSAGE AND ADMINISTRATION).
FORMATION OF ANTIBODIES TO MOUSE AND HAMSTER PROTEIN
As Antihemophilic Factor (Recombinant), ReFacto contains trace amounts of mouse protein (maximum of 5 ng/1000 IU) and hamster protein (maximum of 30 ng/1000 IU), the remote possibility exists that patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.
CARCINOGENICITY, MUTAGENICITY, IMPAIRMENT OF FERTILITY
ReFacto® Antihemophilic Factor (Recombinant) has been shown to be nonmutagenic in the mouse micronucleus assay. No other mutagenicity studies and no investigations on carcinogenesis or impairment of fertility have been conducted.
PREGNANCY CATEGORY C
Animal reproduction and lactation studies have not been conducted with ReFacto® Antihemophilic Factor (Recombinant). It is not known whether ReFacto can affect reproductive capacity or cause fetal harm when given to pregnant women. ReFacto should be administered to pregnant and lactating women only if clearly indicated.
PEDIATRIC USE
ReFacto® Antihemophilic Factor (Recombinant) is appropriate for use in children of all ages, including newborns. Safety and efficacy studies have been performed both in previously treated children and adolescents (N=22, ages 8-15 years) and in previously untreated neonates, infants, and children (N=101, ages 0-52 months) (see CLINICAL PHARMACOLOGY and PRECAUTIONS).
GERIATRIC USE
Clinical studies of ReFacto did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. As with any patient receiving ReFacto, dose selection for an elderly patient should be individualized.
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