Remdesivir (Veklury)

Remdesivir (Veklury) | Some data indicated in the technical data sheet of the product: “it is in the investigational phase because it is still being studied” and “limited information is known on the safety and efficacy of using Veklury to treat people hospitalized for COVID-19”. | The possible side effects of Veklury are the following common: Cardiac disorders, Traumatic injuries, intoxications and complications of therapeutic procedures. | The official document adds that “Not many people have received Veklury. Serious and unexpected side effects may occur.” | Toxicology: Following intravenous (slow bolus) administration of remdesivir to rhesus monkeys and rats, severe renal toxicity occurred after short-term treatment (…) and unexpected death in one animal at a dose level of 20 mg/kg/ day.|

Remdesivir (Veklury ®), as indicated in its package insert, “is in the investigational phase because it is still being studied” and “limited information is known on the safety and efficacy of using Veklury to treat people hospitalized for COVID-19”. Possible side effects of Veklury include the following: allergic reactions, including serious reactions: low blood pressure, changes in heart rhythm, shortness of breath, wheezing, swelling of the lips, face, or throat, skin rash, nausea, vomiting , sweating or shakiness and increases in liver enzyme levels. The official document adds that “Not many people have received Veklury. Serious and unexpected side effects may occur.”

4.4 Special warnings and precautions for use

Hypersensitivity reactions including anaphylactic and infusion-related reactions have been observed during and after remdesivir administration. Signs and symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, pyrexia, dyspnea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, and chills.

Remdesivir treatment should not be initiated in patients with alanine aminotransferase (ALT) ≥5 times the upper limit of normal at baseline.

• Remdesivir treatment should be discontinued in patients who experience:

◦ ALT ≥5 times the upper limit of normal during treatment with remdesivir. Remdesivir can be resumed when ALT is <5 times the upper limit of normal.

◦ Elevated ALT together with signs or symptoms of hepatic inflammation or increased conjugated bilirubin, alkaline phosphatase or international normalized ratio (INR) (see sections 4.8 and 5.2).

Renal insufficiency

In animal studies, in rats and monkeys, severe renal toxicity was observed (see section 5.3). The mechanism of this renal toxicity is not fully understood. Its relevance to humans cannot be ruled out.

4.5 Interaction with other medicinal products and other forms of interaction

No clinical interaction studies have been conducted with remdesivir. The overall potential for interactions is currently unknown; patients should remain under close observation during the days of remdesivir administration.

The potential for interaction of remdesivir with inhibitors/inducers of the hydrolytic (esterase) pathway or CYP2C8, 2D6 or 3A4 has not been studied. The risk of clinically relevant interaction is unknown. Strong inhibitors may result in increased exposure to remdesivir. The use of strong inducers (eg, rifampin) may reduce plasma concentrations of remdesivir and is not recommended.

Table 2: Tabulated list of adverse reactions

Frequent and very frequent:

heart disorders
Hepatobiliary disorders
Traumatic injuries, intoxications and complications of therapeutic procedures
pediatric patients

Pharmacokinetics in pediatric patients have not been evaluated.

Renal insufficiency

The pharmacokinetics of remdesivir and GS-441524 have not been evaluated in renal impairment. Remdesivir is not significantly eliminated unchanged in the urine, but its main metabolite GS-441524 is eliminated via the kidney and plasma metabolite concentrations may theoretically be increased in patients with renal insufficiency. The excipient bedatex sulfobutyl ether sodium is eliminated via the kidneys and accumulates in patients with reduced renal function. Veklury should not be used in patients with an eGFR <30 mL/min.

Liver failure

The pharmacokinetics of remdesivir and GS-441524 have not been evaluated in hepatic impairment. The role of the liver in the metabolism of remdesivir is unknown.

Interactions

The interaction potential of remdesivir as a victim with respect to inhibition of the hydrolytic (esterase) pathway was not studied. The risk of clinically relevant interaction is unknown.

5.3 Preclinical safety data

Toxicology

Following intravenous (slow bolus) administration of remdesivir to rhesus monkeys and rats, severe renal toxicity occurred after short-term treatment. In male rhesus monkeys at dose levels of 5, 10 and 20 mg/kg/day for 7 days resulted, at all dose levels, in an increase in mean blood urea nitrogen and an increase in mean creatinine, tubular atrophy and basophilia and casts, and unexpected death in one animal at a dose level of 20 mg/kg/day