USE IN SPECIAL POPULATION

Pregnancy

Risk Summary

No adequate and well-controlled studies of remdesivir use in pregnant women have been conducted. Remdesivir should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus. In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse effect on embryofetal development when administered to pregnant animals at systemic exposures (AUC) of the predominant circulating metabolite of remdesivir (GS-441524) that were 4 times (rats and rabbits) the exposure in humans at the recommended human dose (RHD).

Animal Data

Remdesivir was administered via intravenous injection to pregnant rats and rabbits (up to 20 mg/kg/day) on Gestation Days 6 through 17, and 7 through 20, respectively, and also to rats from Gestation Day 6 to Lactation/Post-partum Day 20. No adverse effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed in rats and rabbits at nontoxic doses in pregnant animals. During organogenesis, exposures to the predominant circulating metabolite (GS-441524) were 4 (rats and rabbits) times higher than the exposure in humans at the RHD. In a pre/postnatal development study, exposures to the predominant circulating metabolite of remdesivir (GS-441524) were similar to the human exposures at the RHD.

Nursing Mothers

Risk Summary

There is no information regarding the presence of remdesivir in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, remdesivir and metabolites have been detected in the nursing pups of mothers given remdesivir, likely due to the presence of remdesivir in milk. Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for remdesivir and any potential adverse effects on the breastfed child from remdesivir or from the underlying maternal condition.

Animal Data

Remdesivir and its metabolites were detected in the plasma of nursing rat pups, likely due to the presence of remdesivir and/or its metabolites in milk, following daily intravenous administration of remdesivir to pregnant mothers from Gestation Day 6 to Lactation Day 20. Exposures in nursing pups were approximately 1% that of maternal exposure on lactation day 10.

Pediatric Use

The safety and effectiveness of remdesivir for treatment of COVID-19 have not been assessed in pediatric patients. Dosing instructions for pediatric patients were derived based on pharmacokinetic data from adult healthy volunteers and in vitro data for remdesivir and other similar compounds, as part of the PBPK modeling and simulation approach which accounts for age-dependent changes in metabolism, distribution, and elimination of remdesivir.

For pediatric patients with body weight between 3.5 kg to <40 kg, use remdesivir for injection, 100 mg, lyophilized powder only [For further information see Dosage and Administration].

Pediatric patients (>28 days) must have creatinine clearance determined and fullterm neonates (≥7 days to ≤28 days) must have serum creatinine determined before dosing. Pediatric patients should be monitored for renal function and consideration given for stopping therapy in the setting of substantial decline. The use of remdesivir is not recommended in pediatric patients (>28 days old) with eGFR <30 mL/min and in full-term neonates (≥7 days and ≤28 days old) with serum creatinine clearance ≥1 mg/dL unless the potential benefit outweighs the potential risk.

Because the excipient sulfobutylether-β-cyclodextrin sodium salt (SBECD) is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as remdesivir) is not recommended in adults and pediatric patients (>28 days old) with eGFR less than 30 mL per minute or in full-term neonates (≥7 days and ≤28 days old) with serum creatinine clearance ≥1 mg/dL unless the potential benefit outweighs the potential risk.

Geriatric Use

The pharmacokinetics of remdesivir have not been evaluated in patients >65 years of age. In general, appropriate caution should be exercised in the administration of remdesivir and monitoring of elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Impairment

Use in patients with renal impairment are based on potential risk and potential benefit considerations. Patients with eGFR greater than or equal to 30 mL/min are reported to have received remdesivir for treatment of COVID-19 with no dose adjustment of remdesivir. All patients must have an eGFR determined before dosing.

Hepatic Impairment

The pharmacokinetics of remdesivir have not been evaluated in patients with hepatic impairment. It is not known if dosage adjustment is needed in patients with hepatic impairment and remdesivir should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk [For further information see Warnings and Precautions].

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

DESREM™, Remdesivir Prescribing Information. Mylan Laboratories Limited. 2020.