Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Infusion-related reactions
IRRs have been observed in patients treated with Onpattro. In patients experiencing an IRR, the majority experienced the first IRR within the first 2 infusions (see section 4.8). Across clinical studies, the most common symptoms (reported in ≥ 2% of patients) of IRRs were flushing, back pain, nausea, abdominal pain, dyspnoea, and headache. IRRs may also include hypotension and syncope.


To reduce the risk of IRRs, patients should receive premedications on the day of Onpattro infusion, at least 60 minutes prior to the start of infusion (see section 4.2). If an IRR occurs, slowing or interrupting the infusion and institution of medical management (e.g., corticosteroids or other symptomatic treatment) should be considered, as clinically indicated. If the infusion is interrupted, resumption of the infusion at a slower infusion rate may be considered after symptoms have resolved.
The infusion should be discontinued in the case of a serious or life-threatening IRR.

Some patients who experience IRRs may benefit from a slower infusion rate or additional or higher doses of one or more of the premedications with subsequent infusions to reduce the risk of IRRs.

Vitamin A deficiency

By reducing serum TTR protein, Onpattro treatment leads to a decrease in serum vitamin A (retinol) levels (see section 5.1). Serum vitamin A levels below the lower limit of normal should be corrected and any ocular symptoms or signs due to vitamin A deficiency should be evaluated prior to initiation of treatment.

Patients receiving Onpattro should take oral supplementation of approximately 2 500 IU vitamin A per day to reduce the potential risk of ocular toxicity due to vitamin A deficiency. Referral for ophthalmological assessment is recommended if patients develop ocular symptoms suggestive of 
vitamin A deficiency, including reduced night vision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration, corneal thickening or corneal perforation.

Serum vitamin A levels should not be used to guide vitamin A supplementation during treatment with Onpattro (see section 4.5).

During the first 60 days of pregnancy, both too high or too low vitamin A levels may be associated with an increased risk of foetal malformation. Therefore, pregnancy should be excluded before initiating Onpattro and women of childbearing potential should practise effective contraception. If a woman intends to become pregnant, Onpattro and vitamin A supplementation should be discontinued, and serum vitamin A levels should be monitored and have returned to normal before conception is attempted.

In the event of an unplanned pregnancy, Onpattro should be discontinued (see section 4.6). Vitamin A supplementation should be discontinued during the first trimester, unless the pregnant woman has clinical signs of vitamin A deficiency. If such signs are present, vitamin A supplementation should not exceed 2 500 IU per day. Thereafter, vitamin A supplementation of 2 500 IU per day should be resumed in the second and third trimesters if serum vitamin A levels have not returned to normal, because of the increased risk of vitamin A deficiency in the third trimester.

Excipients with known effect

This medicinal product contains 3.99 mg sodium per mL, equivalent to 0.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7    Effects on ability to drive and use machines

On the basis of the pharmacodynamic and pharmacokinetic profiles, Onpattro is considered to have no or negligible influence on the ability to drive or use machines.