Safety profile evaluated in the largest clinical study of hATTR amyloidosis1,a
The safety profile of ONPATTRO was generally consistent across all subgroups.2,3,b
Adverse reactions- The majority of adverse reactions in the APOLLO study were mild or moderate in severity3
- The most common adverse reactions were upper respiratory tract infections (29%) and infusion-related reactions (IRRs) (19%)4
- The frequency of adverse events leading to discontinuation was lower in the ONPATTRO group (5%) compared to the placebo group (14%)3
- In ONPATTRO-treated patients, all IRRs were either mild (95%) or moderate (5%) in severity5
- —Severe hypotension and syncope have been reported as symptoms of IRRs in the expanded access program and postmarketing setting4
- Among ONPATTRO-treated patients who experienced an IRR, 79% experienced the first IRR within the first 2 infusions and the frequency of IRRs decreased over time4
- IRRs led to treatment discontinuation in <1% of patients4
aAPOLLO was a global, randomized, double-blind, multicenter, placebo-controlled study of 225 patients.1,3,4
bSubgroups included age, sex, V30M variant status, previous tetramer stabilizer use, and disease stage.4
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ONPATTRO during pregnancy. Physicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the program by calling 1-877-256-9526 or by contacting alnylampregnancyprogram@iqvia.com.
Adverse reactions that occurred in at least 5% of patients treated with ONPATTRO and at least 3% more frequently than in patients treated with placebo4
| Adverse Reactiona | ONPATTRO N=148 % |
Placebo N=77 % |
| Upper respiratory tract infections |
29 | 21 |
| Infusion-related reaction | 19 | 9 |
| Dyspepsia | 8 | 4 |
| Dyspnea | 8 | 0 |
| Muscle spasms | 8 | 1 |
| Arthralgia | 7 | 0 |
| Erythema | 7 | 3 |
| Bronchitis | 7 | 3 |
| Vertigo | 5 | 1 |
There are no contraindications for ONPATTRO.4
Important Safety Information and Indication
Important Safety Information
Infusion-Related Reactions
Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO® (patisiran). In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.
To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.
Reduced Serum Vitamin A Levels and Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum 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).
Adverse Reactions
The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).
Indication
ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
For additional information about ONPATTRO, please see the full Prescribing Information.
References:
1. Adams D, Suhr OB, Dyck PJ, et al. BMC Neurol. 2017;17(1):181.
2. Data on file: Clinical Study Report. Alnylam Pharmaceuticals, Inc; 2020.
3. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.
4. ONPATTRO Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.
5. Polydefkis M, Adams D, Kristen A, et al. Poster presented at: Peripheral Nerve Society (PNS) Annual Meeting; July 22-25, 2018; Baltimore, MD.
