Veklury Special Precautions

Precautions Concerning Indication: Given the majority of VEKLURY use in clinical trials, VEKLURY should be used for the following patients. Also, refer the latest guideline on the treatment target of VEKLURY [See Pharmacology: Clinical Studies for Efficacy and Safety: Global Phase III study and Other Phase III study under Actions].
Patients who do not require oxygen support and are considered to need treatment with VEKLURY because of their risk factors for disease progression of SARS-CoV-2 infection etc.
Patients with pneumonia who are infected with SARS-CoV-2.
Precautions Concerning Dosage and Administration: VEKLURY should be added to saline and infused intravenously over 30 to 120 minutes. [See Important Precautions as follows and Precautions Concerning the Preparation of the drug under Cautions for Usage.]
The treatment course of VEKLURY should be initiated as soon as possible after symptom of SARS CoV-2 infection has developed, VEKLURY is administered until Day 3. As a guide, VEKLURY is administered until Day 5 for patients with pneumonia who are infected with SARS-CoV-2, VEKLURY is administered until Day10 if patients do not obtain improvement.
The pharmacokinetics in pediatric patients are unknown. It should be noted that the approved dosage and administration for pediatrics is determined based on a simulation using a physiologically-based pharmacokinetic model. [See Use in Children as follows and Pharmacology: Pharmacokinetics: Patients with Specific Backgrounds: Pediatric Patients under Actions.]
Important Precautions: Since hepatic impairment may occur, patients should be closely monitored by performing liver function tests, before and periodically after initiating administration of remdesivir [See Patients with ALT ≥5 times the Upper Limit of Normal Range as follows and Clinically Significant Adverse Reactions: Hepatic Impairment under Adverse Reactions].
Since hypersensitivity including infusion reactions and anaphylactic reactions may occur, patient's condition should be carefully monitored, and if any abnormalities are observed, administration of this drug should be discontinued immediately, and appropriate measures should be taken. Slower infusion rates can be considered to potentially prevent these events. [See Precautions Concerning Dosage and Administration as mentioned previously and Hypersensitivity (Including infusion reactions and anaphylactic reactions) under Adverse Reactions]
Patients should be closely monitored by performing renal function tests before and periodically after initiating administration of remdesivir because Sulfobutylether β-cyclodextrin sodium of excipient may cause renal impairment. [See Patients with Renal Impairment as follows]
Other Precautions: Information Based on Clinical Use: In a clinical study (NIAID ACTT-1) of patients with SARS-CoV-2 infection, the incidence of increased prothrombin time or INR was higher in subjects who received VEKLURY compared to placebo. In addition, there was no difference observed in the incidence of bleeding events between the two groups.
Information Based on Nonclinical Studies: In the 7-day intravenous administration study in rhesus monkeys, deaths associated with renal toxicity occurred in the 20 mg/kg/day dose group, and increases in blood urea nitrogen and creatinine, and renal tubular tissue damage were observed in the ≥5 mg/kg/day dose groups. In the 14 or 28-day intravenous administration study in rats, abnormalities of blood renal function markers, increases of urea nitrogen and creatine, urine electrolyte and protein abnormalities, and renal tubular tissue damage were observed at below the clinical exposure level (≥10 mg/kg/day). In the 28-day intravenous administration study in cynomolgus monkeys, no nephrotoxicity was observed at the highest dose (10 mg/kg).
Precautions Concerning Patients with Specific Backgrounds: Patients with Renal Impairment: Since the excipient sulfobutylether-β-cyclodextrin sodium accumulates in the renal tubules, renal impairment may be exacerbated. In nonclinical study, effects on renal tubular have been observed by remdesivir. No clinical studies have been completed in patients with renal impairment [See Important Precautions, Other Precautions: Information Based on Clinical Use as previously mentioned and Pharmacology: Pharmacokinetics: Patients with Specific Backgrounds: Renal Impairment under Actions].
Patients with Severe Renal Impairment (eGFR<30 mL/min/1.73 m² for Adults, Infants, Children and Older Children; Serum Creatinine ≥1 mg/dL for Newborn [7 days to 28 days]): Not recommended to administer. Remdesivir should be considered to only administer if the therapeutic benefits outweigh the risks [See Use in Children as follows and Pharmacology: Clinical Studies: Clinical Studies for Efficacy and Safety: Global Phase III study and Other Phase III study under Actions].
Patients with Hepatic Impairment: Patients with ALT ≥5 times the Upper Limit of Normal Range: Preferable not to administer. Hepatic impairment may be exacerbated. No clinical studies have been completed in patients with hepatic impairment [See Important Precautions as previously mentioned, Clinically Significant adverse reactions under Adverse Reactions: Hepatic Impairment under Adverse Reactions, Pharmacology: Clinical Results: Efficacy and Safety Studies under Actions, and Pharmacology: Pharmacokinetics: Patients with Specific Backgrounds: Hepatic Impairment under Actions].
Use in Children: Remdesivir should be administered only if the therapeutic benefits outweigh the risks. No clinical studies in children have been completed. The excipient sulfobutylether-β-cyclodextrin sodium shows toxicity to the renal tubules and its effect on children aged <2 years (whose kidneys are still developing) is unknown. [See Patients with Renal Impairment as previously mentioned.]
The pharmacokinetics in pediatric patients are unknown. The dosage and administration approved for pediatric patients were determined using simulations based on physiological pharmacokinetic models. [See Precautions Concerning Dosage and Administration as previously mentioned and Pharmacology: Pharmacokinetics: Patients with Specific Backgrounds: Pediatric Patients under Actions.]
Use in Elderly: Remdesivir should be carefully administered while monitoring the patient's condition. In general, elderly patients may have decreased physiological functions, higher frequencies of co-morbid conditions or previous history of diseases.