errupted, consider resuming ata slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion shouldbe discontinued and not resumed.
Some patients who experience IRRs may benefit from a slower infusion rate or additional or higher doses of one or moreof the premedications with subsequent infusions to reduce the risk of IRRs [see Dosage and Administration (2.2)].
5.2 Reduced Serum Vitamin A Levels and Recommended SupplementationONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended dailyallowance of vitamin A is advised for patients taking ONPATTRO. Higher doses than the recommended daily allowanceof vitamin A should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, asserum 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 clinically significant adverse reactions are described elsewhere in the labeling:
• Infusion-Related Reactions [see Warnings and Precautions (5.1)]
6.1 Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinicalstudies of ONPATTRO cannot be directly compared to rates in the clinical studies of another drug and may not reflect therates observed in practice.
A total of 224 patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTRamyloidosis) received ONPATTRO in the placebo-controlled and open-label clinical studies, including 186 patientsexposed for at least 1 year, 137 patients exposed for at least 2 years, and 52 patients exposed for at least 3 years. In theplacebo-controlled study, 148 patients received ONPATTRO for up to 18 months (mean exposure 17.7 months). Baselinedemographic and disease characteristics were generally similar between treatment groups. The median age of studypatients was 62 years and 74% were male. Seventy-two percent of study patients were Caucasian, 23% were Asian, 2%were Black, and 2% were reported as other. At baseline, 46% of patients were in Stage 1 of the disease and 53% were inStage 2. Forty-three percent of patients had Val30Met mutations in the transthyretin gene; the remaining patients had38 other point mutations. Sixty-two percent of ONPATTRO-treated patients had non-Val30Met mutations, compared to48% of the placebo-treated patients.
Upper respiratory tract infections and infusion-related reactions were the most common adverse reactions. One patient(0.7%) discontinued ONPATTRO because of an infusion-related reaction.
Table 1 lists the adverse reactions that occurred in at least 5% of patients in the ONPATTRO-treated group and thatoccurred at least 3% more frequently than in the placebo-treated group in the randomized controlled clinical trial.
Table 1: Adverse Reactions from the Placebo-Controlled Trial that Occurred in at Least 5% ofONPATTRO-treated Patients and at Least 3% More Frequently than in Placebo-treated Patients
Adverse Reaction
ONPATTRO
N=148
%
Placebo
N=77
%
Upper respiratory tract infections a 29 21
Infusion-related reaction b 19 9
Dyspepsia 8 4
Dyspnea c, d 8 0
Muscle spasms c 8 1
Arthralgia c 7 0
Erythema c 7 3
Bronchitis e 7 3
Vertigo 5 1
a Inc |
