mal serum vitamin A levels during treatment with TEGSEDI, as serum vitamin A levels do not reflect the total vitamin A in the body.
Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
Thrombocytopenia [see Warnings and Precautions (5.1)]
Glomerulonephritis and Renal Toxicity [see Warnings and Precautions (5.2)]
Stroke and Cervicocephalic Arterial Dissection [see Warnings and Precautions (5.4)]
Inflammatory and Immune Effects [see Warnings and Precautions (5.5)]
Liver Effects [see Warnings and Precautions (5.6)]
Hypersensitivity [see Warnings and Precautions (5.7)]
Reducted Serum Vitamin A Levels and Recommended Supplementation [see Warnings and Precautions (5.9)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of TEGSEDI cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice.
A total of 112 adult patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR) received TEGSEDI in Study 1 and 60 patients received placebo. The, mean age of the study patients was 59 years (27 to 78 years of age). Of the TEGSEDI-treated patients, 69% were male and 94% were Caucasian, with a mean exposure of 385 days, and median exposure of 449 days. Baseline disease characteristics were largely similar in TEGSEDI-treated patients and patients in the placebo control group. Sixty-seven percent of patients were in Stage 1 of the disease at baseline, and 33% in Stage 2. Fifty-two percent of patients had Val30Met mutations in the TTR gene, with the remaining 48% comprised of 26 different other point mutations.
TABLE 2 presents common adverse reactions that occurred in at least 5% of TEGSEDI-treated patients and that occurred at least 5% more frequently or two times more frequently than on placebo.
The most common adverse reactions that occurred in at least 20% of TEGSEDI-treated patients and more frequently than on placebo were injection site reactions, nausea, headache, fatigue, thrombocytopenia, and fever. Serious adverse reactions were more frequent in TEGSEDI-treated patients (32%) than in patients on placebo (21%). The most common adverse reactions leading to discontinuation were thrombocytopenia and cachexia.
Table 2: Adverse Reactions Reported in At Least 5% TEGSEDI-Treated Patients and that Occurred At Least 5% More Frequently or At Least Two Times More Frequently than Placebo Patients (Study 1)
a Includes bruising, erythema, hematoma, hemorrhage, induration, inflammation, mass, edema, pain, pruritus, rash, swelling, and urticaria.
b Includes arrhythmia, atrial fibrillation, atrial flutter, bradyarrhythmia, bradycardia, extrasystoles, sinus arrhythmia, sinus bradycardia, supraventricular extrasystoles, tachycardia, and ventricular extrasystoles.
c Includes bacteremia, cellulitis staphylococcal, clostridium difficile infection, conjunctivitis bacterial, cystitis Escherichia, Helicobacter gastritis, Helicobacter infection, Staphylococcal infection.
TEGSEDI
(N=112)
% Placebo
(N=60)
%
Injection site reactionsa 49 10
Nausea 31 12
Headache& |
