WARNINGS AND PRECAUTIONS

There are limited clinical data available for remdesivir. Serious and unexpected adverse events may occur that have not been previously reported with remdesivir use.

Infusion-Related Reactions

Infusion-related reactions have been observed during, and/or been temporally associated with, administration of remdesivir. Signs and symptoms may include hypotension, nausea, vomiting, diaphoresis, and shivering. If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. The use of remdesivir is contraindicated in patients with known hypersensitivity to remdesivir.

Increased Risk of Transaminase Elevations

Transaminase elevations have been observed in the remdesivir clinical development program, including in healthy volunteers and patients with COVID19. In healthy volunteers who received up to 150 mg daily for 14 days, alanine aminotransferase (ALT) elevations were observed in the majority of patients, including elevations to up to 10 times baseline values in one subject without evidence of clinical hepatitis; no ≥ Grade 3 adverse events were observed. Transaminase elevations have also been reported in patients with COVID-19 who received remdesivir, including one patient with ALT elevation up to 20 times the upper limit of normal. As transaminase elevations have been reported as a component of COVID-19 in some patients, discerning the contribution of remdesivir to transaminase elevations in this patient population is challenging.

Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.

• Remdesivir should not be initiated in patients with 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. Remdesivir 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 INR
• Risk of Reduced Antiviral Activity When Coadministered with Chloroquine or Hydroxychloroquine Coadministration of Remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of Remdesivir