There are no data on the use of elosulfase alfa in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy or embryo-foetal development. These studies however, are of limited relevance. As a precautionary measure, it is preferable to avoid the use of elosulfase alfa during pregnancy, unless clearly necessary.
Available reproductive data in animals have shown excretion of elosulfase alfa in milk. It is not known whether elosulfase alfa is excreted in human breast milk, but systemic exposure via breast milk is not expected. Due to lack of human data, elosulfase alfa should only be administered to breast-feeding woman if the potential benefit is considered to outweigh the potential risk to the infant.
No impairment of fertility has been observed in nonclinical studies with elosulfase alfa.
Elosulfase alfa has minor influence on the ability to drive and use machines. Dizziness was reported during elosulfase alfa infusions; if dizziness occurs after the infusion, the ability to drive and use machines may be affected.
The assessment of adverse reactions is based on the exposure of 176 patients with MPS IVA, ages 5 to 57 years old to 2 mg/kg elosulfase alfa once a week (n=58), 2 mg/kg elosulfase alfa once every other week (n=59), or placebo (n=59) in a randomised, double-blind, placebo-controlled study.
The majority of adverse reactions in clinical studies were IRs, which are defined as reactions occurring after initiation of infusion until the end of the day following the infusion. Serious IRs were observed in clinical studies and included anaphylaxis, hypersensitivity and vomiting. The most common symptoms of IRs (occurring in ≥10% of patients treated with elosulfase alfa and ≥5% more when compared to placebo) were headache, nausea, vomiting, pyrexia, chills and abdominal pain. IRs were generally mild or moderate, and the frequency was higher during the first 12 weeks of treatment and tended to occur less frequently with time.
The data in the table below describes adverse reactions from clinical studies in patients treated with elosulfase alfa.
Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions in patients treated with elosulfase alfa:
| MedDRA System organ class | MedDRA Preferred term | Frequency |
|---|---|---|
| Immune system disorders | Anaphylaxis | Uncommon |
| Hypersensitivity | Common | |
| Nervous system disorders | Headache | Very common |
| Dizziness | Very common | |
| Respiratory, thoracic, and mediastinal disorders | Dyspnoea | Very common |
| Gastrointestinal disorders | Diarrhoea, vomiting, oropharyngeal pain, upper abdominal pain, abdominal pain, nausea | Very common |
| Musculoskeletal and connective tissue disorders | Myalgia | Common |
| Chills | Very common | |
| General disorders and administration site conditions | Pyrexia | Very common |
All patients developed antibodies to elosulfase alfa in clinical studies. Approximately 80% of patients developed neutralizing antibodies capable of inhibiting the elosulfase alfa from binding to the cation- independent mannose-6-phosphate receptor. Sustained improvements in efficacy measures and reductions in urine keratan sulphate (KS) over time were observed across studies, despite the presence of anti elosulfase alfa antibodies. No correlations were found between higher antibody titres or neutralizing antibody positivity and reductions in efficacy measurements or occurrence of anaphylaxis or other hypersensitivity reactions. IgE antibodies against elosulfase alfa were detected in ≤10% of treated patients and have not consistently been related to anaphylaxis or other hypersensitivity reactions and/or treatment withdrawal.
In patients <5 years of age, the overall safety profile of elosulfase alfa at 2 mg/kg/week was consistent with the safety profile of elosulfase alfa observed in older children.
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