fluenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to INCRELEX® with the incidence of antibodies to other products may be misleading.
Anti-IGF-1 antibodies were present at one or more of the periodic assessments in 14 of 23 children with Primary IGFD treated for 2 years. However, no clinical consequences of these antibodies were observed (e.g., attenuation of growth).
6.3 Post-Marketing ExperienceThe following adverse reactions have been identified during post approval use of INCRELEX®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Systemic hypersensitivity: anaphylaxis, generalized urticaria, angioedema, dyspnea
In the post-marketing setting, the frequency of cases indicative of anaphylaxis was estimated to be 0.3%. Symptoms included hives, angioedema, and dyspnea, and some patients required hospitalization. Upon re-administration, symptoms did not re-occur in all patients.
Local allergic reactions at the injection site: pruritus, urticaria
Skin and Subcutaneous Tissue Disorders: alopecia, hair texture abnormal
General Disorders and Administrative Site Conditions: injection site reactions (e.g. erythema, pain, haematoma, haemorrhage, induration, rash, swelling)
Musculoskeletal and Connective Tissue Disorders: osteonecrosis/avascular necrosis (occasionally associated with slipped capital femoral epiphysis)
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C. Studies to assess embryo-fetal toxicity eva luated the effects of INCRELEX® during organogenesis in Sprague Dawley rats given 1, 4, and 16 mg/kg/day and in New Zealand White rabbits given 0.125, 0.5, and 2 mg/kg/day, administered intravenously. There were no observed embryo-fetal developmental abnormalities in rats given up to 16 mg/kg/day (20 times the maximum recommended human dose [MRHD] based on body surface area [BSA] comparison). In the rabbit study, the NOAEL for fetal toxicity was 0.5 mg/kg (2 times the MRHD based on BSA) due to an increase in fetal death at 2 mg/kg. INCRELEX® displayed no teratogenicity or maternal toxicity in rabbits given up to 2 mg/kg (8 times the MRHD based on BSA).
The effects of INCRELEX® on an unborn child have not been studied. Therefore, there is insufficient medical information to determine whether there are significant risks to a fetus.
8.3 Nursing MothersExcretion of INCRELEX® in human milk has not been studied. Caution should be exercised when INCRELEX® is administered to a nursing woman.
8.4 Pediatric UseSafety and effectiveness in pediatric patients below the age of 2 years of age have not been established.
8.5 Geriatric UseThe safety and effectiveness of INCRELEX® in patients aged 65 and over has not been established.
8.6 Renal ImpairmentNo Studies have been conducted in Primary IGFD children or adult subjects with renal impairment [see Clinical Pharmacology (12.3)].
8.7 Hepatic ImpairmentNo studies have been conducted in Primary IGFD children or adult subjects with hepatic impairment [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
Treatment of acute overdose should be directed at reversing hypoglycemia. O |
