Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Hypersensitivity including infusion-related and anaphylactic reactions 
Hypersensitivity reactions including infusion-related and anaphylactic reactions have been observed during and following administration of remdesivir. Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnoea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, and shivering. Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent these signs and symptoms. Monitor patients for hypersensitivity reactions during and following administration of remdesivir as clinically appropriate. Patients receiving remdesivir in an outpatient setting should be monitored after administration according to local medical practice. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment.

Transaminase elevations

Transaminase elevations have been observed in the remdesivir clinical trials, including in healthy volunteers and patients with COVID-19. Liver function should be determined in all patients prior to starting remdesivir and should be monitored while receiving it as clinically appropriate. No clinical studies with remdesivir have been conducted in patients with hepatic impairment. Remdesivir should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk.
•     Remdesivir should not be initiated in patients with alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal at baseline
•     Remdesivir should be discontinued in patients who develop: ◦      ALT ≥ 5 times the upper limit of normal during treatment with remdesivir. It may be restarted when ALT is < 5 times the upper limit of normal.
OR

◦      ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalised ratio (INR) (see sections 4.8 and 5.2).

Renal impairment

In animal studies on rats and monkeys, severe renal toxicity was observed (see section 5.3). The mechanism of this renal toxicity is not fully understood. A relevance for humans cannot be excluded.

All patients should have eGFR determined prior to starting remdesivir and while receiving it as clinically appropriate. Remdesivir should not be used in patients with eGFR < 30 mL/min.

Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine 
Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulphate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir (see sections 4.5 and 5.1) 
Immunocompromised patients:

It is unclear if the treatment duration of three days is sufficient to clear the virus in immunocompromised patients, in whom prolonged viral shedding occurs. There is a potential risk of resistance development. Only limited data are available.

Excipients

Veklury contains betadex sulfobutyl ether sodium, which is renally cleared and accumulates in patients with decreased renal function, which may potentially adversely affect renal function. Therefore Veklury should not be used in patients with eGFR < 30 mL/min (see sections 4.2 and 5.2).

Effects on Driving

4.7    Effects on ability to drive and use machines

Remdesivir is predicted to have no or negligible influence on these abilities.