ludes nasopharyngitis, upper respiratory tract infection, respiratory tract infection, pharyngitis, rhinitis, sinusitis, viralupper respiratory tract infection, upper respiratory tract congestion. b Infusion-related reaction symptoms include, but are not limited to: arthralgia or pain (including back, neck, or
musculoskeletal pain), flushing (including erythema of face or skin warm), nausea, abdominal pain, dyspnea or cough,chest discomfort or chest pain, headache, rash, chills, dizziness, fatigue, increased heart rate or palpitations, hypotension,hypertension, facial edema. c Not part of an infusion-related reaction. d Includes dyspnea and exertional dyspnea.
e Includes bronchitis, bronchiolitis, bronchitis viral, lower respiratory tract infection, lung infection.
Four serious adverse reactions of atrioventricular (AV) heart block (2.7%) occurred in ONPATTRO-treated patients,
including 3 cases of complete AV block. No serious adverse reactions of AV block were reported in placebo-treated
patients.
Ocular adverse reactions that occurred in 5% or less of ONPATTRO-treated patients in the controlled clinical trial, but in
at least 2% of ONPATTRO-treated patients, and more frequently than on placebo, include dry eye (5% vs. 3%), blurred
vision (3% vs. 1%), and vitreous floaters (2% vs. 1%).
Extravasation was observed in less than 0.5% of infusions in clinical studies, including cases that were reported as serious.
Signs and symptoms included phlebitis or thrombophlebitis, infusion or injection site swelling, dermatitis (subcutaneous
inflammation), cellulitis, erythema or injection site redness, burning sensation, or injection site pain.
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 ONPATTRO in the studies described
below with the incidence of antibodies in other studies or to other products may be misleading.
Anti-drug antibodies to ONPATTRO were eva luated by measuring antibodies specific to PEG2000-C-DMG, a lipid
component exposed on the surface of ONPATTRO. In the placebo-controlled and open-label clinical studies, 7 of
194 (3.6%) patients with hATTR amyloidosis developed anti-drug antibodies during treatment with ONPATTRO. One
additional patient had pre-existing anti-drug antibodies. There was no evidence of an effect of anti-drug antibodies on
clinical efficacy, safety, or the pharmacokinetic or pharmacodynamic profiles of ONPATTRO. Although these data do not
demonstrate an impact of anti-drug antibody development on the efficacy or safety of ONPATTRO in these patients, the
available data are too limited to make definitive conclusions.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
There are no available data on ONPATTRO use in pregnant women to inform a drug-associated risk of adversedevelopmental outcomes. ONPATTRO treatment leads to a decrease in serum vitamin A levels, and vitamin Asupplementation is advised for patients taking ONPATTRO. Vitamin A is essential for normal embryofetal development;
howeve |
