Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

The most common adverse reaction in healthy volunteers is increased transaminases (14%). The most common adverse reaction in patients with COVID-19 is nausea (4%).

Tabulated summary of adverse reactions

The adverse reactions in Table 6 are listed below by system organ class and frequency. Frequencies are defined as follows: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); not known (cannot be estimated from the available data).

Table 6:       Tabulated list of adverse reactions
Frequency                      Adverse reaction
Immune system disorders
Rare                           hypersensitivity
Not known                      anaphylactic reaction, anaphylactic shock Nervous system disorders
Common                         headache
Cardiac disorders
Not known                      sinus bradycardia*
Gastrointestinal disorders
Common                         nausea
Hepatobiliary disorders
Very common                    transaminases increased
Skin and subcutaneous tissue disorders
Common                         rash
Investigations
Very common                    prothrombin time prolonged
Injury, poisoning and procedural complications
Rare                           infusion-related reaction
*Reported in post-marketing, usually normalised within 4 days following last remdesivir administration without additional intervention

Description of selected adverse reactions

Transaminases Increased
In healthy volunteer studies, increases in ALT, aspartate aminotransferase (AST) or both in subjects who received remdesivir were grade 1 (10%) or grade 2 (4%). In a randomised, double-blind, placebo-controlled clinical study of patients with COVID-19 (NIAID ACTT-1), any grade (≥ 1.25 × upper limit of normal (ULN)) laboratory abnormalities of increased AST and increased ALT occurred in 33% and 32% of patients, respectively, receiving remdesivir compared with 44% and 43% of patients, respectively, receiving placebo.
Grade ≥ 3 (≥ 5.0 × ULN) laboratory abnormalities of increased AST and increased ALT occurred in 6% and 3% of patients, respectively, receiving remdesivir compared with 8% and 6% of patients, respectively, receiving placebo. In a randomised, open-label multi-centre clinical trial (Study GS-US-540-5773) in hospitalised patients with severe COVID-19 receiving remdesivir for 5 (n=200) or 10 days (n=197), any grade laboratory abnormalities of increased AST and increased ALT occurred in 40% and 42% of patients, respectively, receiving remdesivir. Grade ≥ 3 laboratory abnormalities of increased AST and increased ALT both occurred in 7% of patients receiving remdesivir. In a randomised, open-label multi-centre clinical trial (Study GS-US-540-5774) in hospitalised patients with moderate COVID-19 receiving remdesivir for 5 (n=191) or 10 days (n=193) compared to standard of care (n=200), any grade laboratory abnormalities of increased AST and increased ALT occurred in 32% and 33% of patients, respectively, receiving remdesivir, and 33% and 39% of patients, respectively, receiving standard of care. Grade ≥ 3 laboratory abnormalities of increased AST and increased ALT occurred in 2% and 3% of patients, respectively, receiving remdesivir and 6% and 8%, respectively, receiving standard of care.

Prothrombin time prolonged
In a clinical study (NIAID ACTT-1) of patients with COVID-19, the incidence of prolonged prothrombin time or INR (predominantly Grades 1-2) was higher in subjects who received remdesivir compared to placebo, with no difference observed in the incidence of bleeding events between the two groups. Prothrombin time should be monitored while receiving remdesivir as clinically appropriate.
In Study GS-US-540-9012, the incidence of increased prothrombin time or INR was similar in patients treated with remdesivir compared to placebo.

Paediatric population
The safety assessment of remdesivir in children 4 weeks of age and older and weighing at least 3 kg with COVID-19 is based on data from a Phase 2/3, open-label clinical trial (Study GS-US-540-5823) that enrolled 53 patients who were treated with remdesivir (see Section 5.1). The adverse reactions observed were consistent with those observed in clinical trials of remdesivir in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il