nbsp;26 12
Fatigue 25 20
Thrombocytopenia 24 2
Fever 20 8
Peripheral edema 19 10
Chills 18 3
Anemia 17 3
Vomiting 15 5
Myalgia 15 10
Decreased renal function 14 5
Arrhythmiab 13 5
Arthralgia 13 8
Pre-syncope or syncope 13 5
Decreased appetite 10 0
Paresthesia 10 3
Dyspnea 9 3
Elevated liver function test 9 3
Orthostasis 8 2
Influenza like illness 8 3
Contusion 7 2
Bacterial infectionc 7 3
Eosinophilia 5 0
Dry mouth 5 2
6.2 Immunogenicity
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. In addition, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced 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 TEGSEDI in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
In Study 1, 30% of TEGSEDI-treated patients tested positive for anti-drug antibodies (ADA) following 65 weeks of treatment [see Warnings and Precautions (5.7, 5.8)]. However, the assay measured only IgG isotypes and the existence of other isotypes may be possible. In many cases adverse reactions occurred in patients with ADA, although the available data are too limited to make definitive conclusions about the relationship.
7 DRUG INTERACTIONS
7.1 Antiplatelet Drugs or Anticoagulant Medications
Because of the risk of thrombocytopenia, caution should be used when using antiplatelet drugs (e.g., adenosine, clopidogrel, prasugrel, ticagrelor, or ticlopidine), including non-prescription products that affect platelets (e.g., aspirin, nonsteroidal anti-inflammatory drugs), or anticoagulants (e.g., heparin, warfarin), concomitantly with TEGSEDI [see Warnings and Precautions (5.1)].
7.2 Nephrotoxic Drugs
Because of the risk of glomerulonephritis and renal toxicity, caution should be used when using nephrotoxic drugs and other drugs that may impair renal function concomitantly with TEGSEDI [see Warnings and Precautions (5.2)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no data on the developmental risk associated with the use of TEGSEDI use in pregnant women. TEGSEDI treatment leads to a decrease in serum vitamin A levels, and vitamin A supplementation is advised for patients taking TEGSEDI. Vitamin A is essential for normal embryofetal development; however, excessive levels of Vitamin A are associated with adverse developmental effects. The effects on the fetus of a reduction in maternal serum TTR caused by TEGSEDI and of vitamin A supplementation are unknown [see Clinical Pharmacology (12.2), Warnings and Precautions (5.9)].
In animal studies, subcutaneous administration of inotersen to pregnant rabbits resulted in premature delivery and reduced fetal body weight at the highest dose tested, which was associated with maternal toxicity. No adverse developmental effects were observed when inotersen or a pharmacologically-active surrogate was administered to pregnan |
