ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Remdesivir: Drug information

Remdesivir: Drug information
(For additional information see "Remdesivir: Pediatric drug information" and see "Remdesivir: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Veklury
Brand Names: Canada
  • Veklury
Pharmacologic Category
  • Antiviral Agent
Dosing: Adult
COVID-19

COVID-19:

Hospitalized patients:

Note: US guideline recommendations on the role of remdesivir for hospitalized patients vary. In general, guidelines recommend use in conjunction with dexamethasone (IDSA [Bhimraj 2021]; NIH 2022; SCCM [Alhazzani 2021]); if a corticosteroid cannot be used, may use remdesivir in combination with baricitinib (NIH 2022). However, the World Health Organization recommends against the use of remdesivir in hospitalized patients, regardless of disease severity (WHO 2020).

IV: 200 mg as a single dose on day 1, followed by 100 mg once daily. Duration is generally 5 days or until hospital discharge, whichever is first, but may extend to up to 10 days in certain patients (eg, no substantial clinical improvement by day 5, on mechanical ventilation or extracorporeal membrane oxygenation) (IDSA [Bhimraj 2021]; NIH 2022). Initiate as soon as possible after the diagnosis of symptomatic COVID-19 (manufacturer’s labeling), ideally within 72 hours of a positive SARS-CoV-2 test (SCCM [Alhazzani 2021]).

Nonhospitalized patients:

Note: Reserve use for the treatment of mild to moderate COVID-19 in nonhospitalized patients at high risk for progression to severe COVID-19, including hospitalization or death.

IV: 200 mg as a single dose on day 1, followed by 100 mg once daily on days 2 and 3. Initiate as soon as possible and within 7 days of symptom onset (Gottlieb 2021; NIH 2022).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: The remdesivir formulations contain the excipient sulfobutylether-beta-cyclodextrin (SBECD), with the injection solution containing 6 g per 100 mg remdesivir and the lyophilized powder containing 3 g per 100 mg remdesivir. SBECD accumulates in patients with kidney dysfunction, although the clinical significance of this accumulation is not certain (Luke 2010; Hoover 2018). SBECD is dialyzable (46% removed by an ~4-hour dialysis session) (Luke 2012).

eGFR ≥30 mL/minute: No dosage adjustment necessary.

eGFR <30 mL/minute: No formal safety or pharmacokinetic data are available for patients with kidney impairment or who are receiving renal replacement therapies (Barlow 2020). Manufacturer’s labeling does not recommend use; however, significant toxicity with a short duration of therapy (eg, 5 to 10 days) is unlikely (Adamsick 2020). Benefits may outweigh the risks in select patients (Adamsick 2020). In 4 small retrospective reviews of patients with chronic or acute kidney impairment (3 that included patients receiving dialysis), remdesivir, given at the recommended dose, did not routinely increase serum creatinine or cause severe hepatic toxicity (ALT >5 times the normal limit) (Ackley 2020; Estiverne 2020; Pettit 2020; Thakare 2020).

In a pharmacokinetic observation of a single patient receiving intermittent hemodialysis and a 5-day course of remdesivir, remdesivir’s predominant metabolite, GS-441524, reached high but stable concentrations, with dialysis reducing concentrations by ~50%, thus preventing accumulation (Sörgel 2020). Another observational study of 3 patients with end-stage kidney disease receiving hemodialysis who received 5-day courses of remdesivir reported similarly elevated concentrations of GS-441524; hemodialysis reduced concentrations by 45% to 49% (Davis 2021).

Dosing: Hepatic Impairment: Adult

Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturers labeling (has not been studied).

Hepatoxicity during therapy:

ALT >10 times the ULN: Consider remdesivir discontinuation.

ALT elevation AND signs or symptoms of liver inflammation: Discontinue remdesivir.

Dosing: Pediatric

(For additional information see "Remdesivir: Pediatric drug information")

COVID-19, hospitalized patients; treatment: Note: Initiate as soon as possible after diagnosis of symptomatic COVID-19. Duration is generally 5 days or until hospital discharge, whichever is first, but may be extended up to 10 days if patient does not clinically improve or requires extracorporeal membrane oxygenation or mechanical ventilation (Chiotos 2021; Goldman 2020; NIH 2022; manufacturer's labeling).

Infants ≥3 kg, Children, and Adolescents:

3 to <40 kg: Lyophilized powder only: IV: Loading dose: 5 mg/kg/dose on day 1, followed by 2.5 mg/kg/dose once daily (Chiotos 2021; manufacturer's labeling).

≥40 kg: Injection solution or lyophilized powder: IV: Loading dose: 200 mg on day 1, followed by 100 mg once daily (Chiotos 2021; manufacturer's labeling).

COVID-19, nonhospitalized patients; treatment: Note: Reserve for the treatment of mild to moderate COVID-19 in patients at high risk for progression to severe disease, including hospitalization or death; refer to the CDC for more information on patients at high risk for progression to severe disease. Initiate as soon as possible after diagnosis of symptomatic COVID-19 and within 7 days of symptom onset (FDA 2022; NIH 2022; manufacturer's labeling).

Infants ≥3 kg, Children, and Adolescents:

3 to <40 kg: Lyophilized powder only: IV: Loading dose: 5 mg/kg/dose on day 1, followed by 2.5 mg/kg/dose once daily on days 2 and 3 (manufacturer's labeling).

≥40 kg: Injection solution or lyophilized powder: IV: Loading dose: 200 mg on day 1, followed by 100 mg once daily on days 2 and 3 (Gottlieb 2021; manufacturer's labeling).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Note: Remdesivir contains the excipient sulfobutylether-beta-cyclodextrin (SBECD), which accumulates in patients with kidney dysfunction, although the clinical significance of this accumulation is not certain (Hoover 2018; Luke 2010). The injection solution contains 6 g of SBECD per 100 mg remdesivir; the lyophilized powder contains 3 g of SBECD per 100 mg remdesivir. SBECD is dialyzable (46% removed by an ~4-hour dialysis session) (Luke 2012).

Infants ≥3 kg, Children, and Adolescents (manufacturer's labeling):

eGFR ≥30 mL/minute: No dosage adjustment recommended.

eGFR <30 mL/minute: No formal safety or pharmacokinetic data are available for patients with kidney impairment or who are receiving renal replacement therapies (Barlow 2020; manufacturer's labeling). Use is not recommended by the manufacturer. However, significant toxicity with a short duration of therapy (eg, 5 to 10 days) is unlikely; benefits may outweigh the risks in select patients (Adamsick 2020). In retrospective studies in adult patients with acute or chronic kidney impairment, remdesivir administered at the recommended dose has not been shown to routinely increase serum creatinine or cause severe hepatic toxicity (ALT >5 times the normal limit) (Ackley 2020; Estiverne 2020; Pettit 2020; Thakare 2020).

In a pharmacokinetic observation of a single adult patient receiving intermittent hemodialysis and a 5-day course of remdesivir, remdesivir's predominant metabolite, GS-441524, reached high but stable concentrations. Dialysis reduced concentrations by ~50%, thus preventing accumulation (Sörgel 2020). Another observational study of 3 adult patients with end-stage kidney disease receiving hemodialysis who received 5-day courses of remdesivir reported similarly elevated concentrations of GS-441524; hemodialysis reduced concentrations by 45% to 49% (Davis 2021).

Dosing: Hepatic Impairment: Pediatric

Infants ≥3 kg, Children, and Adolescents (manufacturer's labeling):

Baseline hepatic impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Hepatotoxicity during therapy:

ALT >10 times the ULN and asymptomatic: Consider discontinuing remdesivir.

ALT elevation AND signs or symptoms of liver inflammation: Discontinue remdesivir.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous [preservative free]:

Veklury: 100 mg/20 mL (20 mL)

Solution Reconstituted, Intravenous:

Generic: 100 mg (1 ea [DSC]); 150 mg (1 ea [DSC])

Solution Reconstituted, Intravenous [preservative free]:

Veklury: 100 mg (1 ea)

Generic: 100 mg (1 ea)

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Veklury: 100 mg/20 mL ([DSC])

Solution Reconstituted, Intravenous:

Veklury: 100 mg (1 ea)

Prescribing and Access Restrictions

Remdesivir is available to hospitals directly from the distributor AmerisourceBergen (1-800-746-6273 or remdesivir@amerisourcebergen.com); more information is available at https://www.vekluryhcp.com/product-access/. Additionally, health care providers must track and report all medication errors and serious adverse events potentially associated with remdesivir use by either submitting a MedWatch form (https://www.fda.gov/medwatch/report.htm) or FDA Form 3500 (health professional) by fax (1-800-FDA-0178); a copy of all MedWatch forms should also be provided to Gilead (safety_fc@gilead.com).

Administration: Adult

IV: Administer as an IV infusion over 30 to 120 minutes. May be an irritant; avoid extravasation (van Merendonk 2021).

Administration: Pediatric

Parenteral: IV: Administer as an IV infusion over 30 to 120 minutes in a setting where it is possible to appropriately manage severe hypersensitivity reactions (such as anaphylaxis). Do not administer simultaneously with any other medication or IV solutions other than NS (manufacturer's labeling). May be an irritant; avoid extravasation (van Merendonk 2021).

Use: Labeled Indications

COVID-19: Treatment of laboratory-confirmed COVID-19 in adult and pediatric patients (28 days of age and older weighing at least 3 kg) who require hospitalization or nonhospitalized patients with mild to moderate COVID-19 at high risk for progression to severe COVID-19, including hospitalization or death. Remdesivir may only be administered in health care settings in which health care providers have immediate access to medications to treat a severe infusion or hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system, as necessary.

Medication Safety Issues
Other safety concerns:

Remdesivir (Veklury) is available in two formulations for IV administration, a concentrated solution and a lyophilized powder. Each product has different recommendations for storage, preparation for administration, and administration. In addition, the concentrated solution should only be used in adults and pediatric patients weighing ≥40 kg, while the lyophilized powder can be used in adults and pediatric patients weighing ≥3 kg. The Institute for Safe Medication Practices (ISMP) reports that there have been numerous medication errors related to the two formulations available; use caution with product selection and follow appropriate recommendations for the formulation (FDA 2022; ISMP 2020).

Adverse Reactions (Significant): Considerations
Cardiac effects

Postmarketing reports of bradycardia, including severe bradycardia (some fatal) and sinus bradycardia, have been reported in patients receiving remdesivir for COVID-19. An observational study using data from the WHO pharmacovigilance database found that bradycardia was more likely to be reported with remdesivir treatment than with hydroxychloroquine, lopinavir/ritonavir, tocilizumab, or glucocorticoid treatment, and reports included mostly males in the United States over a wide spectrum of ages (43 to 79 years of age). Most of these patients were not receiving concurrent cardiovascular medications. Other cardiac effects were observed, most notably hypotension (Ref).

Mechanism: Unknown; it has been suggested that the active metabolite of remdesivir, a nucleotide triphosphate derivative, may slow sinoatrial node automaticity due to its similarity with adenosine triphosphate (Ref).

Onset: Bradycardia: Varied; a median onset of 2.4 days (range: 1 to 6 days) was observed in an observational study (Ref). Other reports have noted onset of bradycardia within 24 hours of administration of first dose (Ref).

Hepatic effects

Mild to moderate (grades 1 to 2), reversible transaminase elevations, including increased serum alanine aminotransferase and increased serum aspartate aminotransferase, have been observed in healthy volunteers and adult and pediatric patients with COVID-19. It is unclear if these effects are drug-related or related to COVID-19. Most aminotransferase elevations during treatment for COVID-19 were reversible and not associated with jaundice; cases with jaundice rarely occurred, typically in patients with other risk factors for liver toxicity (Ref).

Hypersensitivity and infusion related reactions

Hypersensitivity reactions, including anaphylaxis and infusion related reactions, have been reported during and following remdesivir administration. Patients may experience angioedema, bradycardia, diaphoresis, dyspnea, fever, hypertension, hypotension, hypoxia, nausea, shivering, skin rash, tachycardia, and wheezing. Slower infusion rates (maximum infusion time of up to 120 minutes) may be considered in patients to potentially prevent hypersensitivity or infusion related reactions.

Onset: Rapid; most commonly occurs within 1 hour.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adolescents and adults.

>10%:

Endocrine & metabolic: Increased serum glucose (grades 3/4: 3% to 11%)

Renal: Decreased creatinine clearance (grades 3/4: 2% to 19%), increased serum creatinine (grades 3/4: 3% to 15%)

1% to 10%:

Dermatologic: Skin rash (<2%)

Gastrointestinal: Nausea (3% to 7%)

Hematologic & oncologic: Decreased hemoglobin (grades 3/4: 1% to 8%), lymphocytopenia (grades 3/4: 2%), prolonged prothrombin time (grades 3/4: 9%) (table 1)

Remdesivir: Adverse Reaction: Prolonged Prothrombin Time

Drug (Remdesivir)

Placebo

Dose

Indication

Number of Patients (Remdesivir)

Number of Patients (Placebo)

Grades 3/4: 9%

4%

200 mg on Day 1 and 100 mg once daily on subsequent days, for 10 days of treatment

SARS-CoV-2 infection

532

516

Hepatic: Increased serum alanine aminotransferase (2% to 7%), increased serum aspartate aminotransferase (3% to 6%)

Hypersensitivity: Hypersensitivity reaction (<2%)

Nervous system: Seizure (<2%)

Frequency not defined:

Hepatic: Increased serum alkaline phosphatase

Hypersensitivity: Angioedema, infusion-related reaction

Local: Erythema at injection site

Postmarketing:

Cardiovascular: Bradycardia (including severe bradycardia and sinus bradycardia) (Gubitosa 2020, Jacinto 2021, Touafchia 2021), heart failure (Wang 2020), hypotension (Touafchia 2021)

Hepatic: Acute hepatic failure (Carothers 2020)

Hypersensitivity: Anaphylaxis (Hopkins 2021)

Contraindications

Hypersensitivity to remdesivir or any component of the formulation.

Warnings/Precautions

Disease-related concerns:

Renal impairment: Use caution in patients with eGFR <30 mL/minute and assess risk versus benefit based upon dosing information in renal impairment.

Dosage form specific issues:

• Injection: Contains the excipient cyclodextrin (sulfobutylether-beta-cyclodextrin [SBECD]; 6 g per 100 mg remdesivir [injection solution] or 3 g per 100 mg remdesivir [lyophilized powder]), which may accumulate in patients with renal impairment.

Warnings: Additional Pediatric Considerations

Sulfobutylether-beta-cyclodextrin sodium salt (SBECD) is an excipient in remdesivir; SBECD is renally cleared and accumulates in patients with decreased renal function. The lyophilized powder formulation contains 3 g of SBECD per 100 mg remdesivir, while the injection solution 5 mg/mL contains 6 g of SBECD per 100 mg remdesivir. In pediatric patients weighing <40 kg, the manufacturer recommends use of the lyophilized powder only.

Metabolism/Transport Effects

Substrate of CYP2C8 (minor), CYP2D6 (minor), CYP3A4 (minor), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Chloroquine: May diminish the therapeutic effect of Remdesivir. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Remdesivir. Risk C: Monitor therapy

Hydroxychloroquine: May diminish the therapeutic effect of Remdesivir. Risk X: Avoid combination

Pregnancy Considerations

Information related to use of remdesivir in pregnant patients is available from small studies and case reports (Budi 2022; Burwick 2021; Eid 2022; Jorgensen 2021; Nasrallah 2021). Based on available data, use is well tolerated (NIH 2022) and early administration improves clinical outcomes in pregnant patients (Eid 2022).

• Outcome data are available from pregnant (n = 67) and postpartum (n = 19) patients who received remdesivir through the compassionate use program:

- COVID-19 was confirmed in all cases, and all patients had an oxygen saturation ≤94% on room air or required oxygen support. Dosing was the same as nonpregnant adults. Exposure occurred <24 weeks' gestation (n = 12), 24 to 32 weeks' gestation (n = 44), >32 weeks' gestation (n = 11), or within 3 days postpartum (delivery between 24 and 32 weeks' gestation [n = 13]; delivery >32 weeks' gestation [n = 5]). Sixty-four percent of women had a comorbid medical condition that classified their pregnancy as high risk (obesity 17%, asthma 12%, gestational diabetes 10%, chronic hypertension 8%, diabetes mellitus 8%).

- In patients given remdesivir, 93% treated during pregnancy and 89% treated postpartum recovered within 28 days. Recovery was defined as discharge from hospital if on room air at baseline, return to room air or discharge if oxygen previously needed, or extubation if previously ventilated. Women not requiring ventilation had a median time to recovery of 5 days.

- Adverse effects were similar to those in nonpregnant patients; remdesivir was discontinued in 7 pregnant patients (10%) due to adverse events, most commonly due to an increase in liver enzymes (n = 5). Based on this preliminary data, maternal treatment with remdesivir during pregnancy had a high rate of recovery (Burwick 2021).

• A smaller study demonstrated the benefits of remdesivir treatment for pregnant patients hospitalized with moderate COVID-19:

- The study included 35 women (median gestation age 29.2 weeks) with moderate infection, defined as lower respiratory disease diagnosed by imaging or clinical assessment (abnormal blood gas, dyspnea, fever ≥39.0°C (102.2°F) not relieved with acetaminophen, pneumonia) and oxygen saturation on ambient air ≥94%. All patients in the study were managed with oral or IV corticosteroids and antibiotics when appropriate.

- Clinical recovery was defined as breathing on ambient air and/or hospital discharge on hospital day 7. A 5-day course of remdesivir led to clinical recovery in all patients (n = 17) when treatment was started within 48 hours of admission and in no patients when remdesivir was initiated >48 hours from admission (n = 7). Eleven pregnant patients were not treated with remdesivir; 3 progressed to severe disease and 8 required supplemental oxygen on hospital day 7.

- Oligohydramnios was diagnosed in 3 women within 5 days of their last remdesivir dose and in none of the women who did not receive remdesivir. Patients diagnosed with oligohydramnios did not have known risk factors and it is unclear if this finding was related to treatment, COVID-19 infection, or idiopathic. Amniotic fluid monitoring is recommended (Nasrallah 2021).

• A retrospective cohort study evaluated use of remdesivir to prevent ICU admission in hospitalized pregnant patients diagnosed with COVID-19 infection. Patients who received remdesivir within 7 days of symptoms (n = 24) were compared to those who received treatment ≥7 days from symptom onset (n = 17). None of the patients in this study had previously received a COVID-19 vaccine. Patients who received early remdesivir treatment were less likely to be admitted to the ICU, progress to critical disease, and had shorter hospital stays (Eid 2022).

The risk of severe illness from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID-19. Pregnant patients with symptoms may require ICU admission, mechanical ventilation, or ventilatory support (ECMO) compared to symptomatic nonpregnant patients. Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG 2022; NIH 2022).

In general, the treatment of COVID-19 infection during pregnancy is the same as in nonpregnant patients. Use of remdesivir should not be withheld if otherwise needed (NIH 2022). Information related to the treatment of COVID-19 during pregnancy continues to emerge; refer to current guidelines for the treatment of pregnant patients.

Data collection to monitor maternal and infant outcomes following exposure to remdesivir during pregnancy is ongoing.

- Pregnant and recently pregnant patients exposed to remdesivir are encouraged to enroll in the registry (800-616-3791 or http://covidpr.pregistry.com)

- Health care providers are encouraged to enroll patients exposed to COVID-19 during pregnancy in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (877-311-8972; https://mothertobaby.org/join-study/).

Breastfeeding Considerations

Remdesivir and the GS-441524 metabolite have been detected in breast milk.

Breast milk concentrations of remdesivir were evaluated in a patient diagnosed with COVID-19 infection 2 days following delivery at 38 weeks' gestation. Remdesivir 200 mg IV was administered on the first day, followed by 100 mg daily for 4 days. The mother had initiated breastfeeding prior to diagnosis and pumped to maintain the milk supply during remdesivir treatment. Breast milk was sampled on treatment day 5 prior to and 1, 3, 6, and 24 hours after remdesivir administration. Concentrations of remdesivir were measurable only in the sample obtained 1 hour prior to administration (1.29 ng/mL; corresponding maternal serum concentration 14.4 ng/mL). Concentrations of the GS-441524 metabolite in breast milk prior to and 24 hours after dosing were 13.5 ng/mL and 64.34 ng/mL; corresponding maternal serum concentrations were 389.9 ng/mL and 201.1 ng/mL, respectively. Metabolite concentrations in breast milk ranged from 13.5 ng/mL to 284.9 ng/mL. The half-life of GS-441524 in breast milk was 9.3 hours. Authors of the study calculated the relative infant dose (RID) of remdesivir to be <1% and the RID of GS-441524 to be 1.55%, concentrations considered acceptable for breastfeeding (Wada 2022).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Breast milk has not been found to contain infectious materials from SARS-CoV-2 and maternal infection is not a contraindication to breastfeeding. However, lactating patients with COVID-19 infection should take all precautions to avoid spreading the virus to the infant (eg, hand hygiene, mask wearing, etc) and the infant should be isolated with the mother; alternately, breast milk can be expressed and fed to the infant by someone without confirmed or suspected COVID-19 (ACOG 2022).

Interim guidance is available from the Centers for Disease Control and Prevention for the care of lactating patients who are diagnosed with coronavirus disease 2019 (COVID-19) (https://www.cdc.gov/coronavirus/2019-ncov/hcp/care-for-breastfeeding-women.html). Information related to COVID-19 and breastfeeding is also available from the World Health Organization (https://www.who.int/news/item/28-04-2020-new-faqs-address-healthcare-workers-questions-on-breastfeeding-and-covid-19).

Monitoring Parameters

Baseline and during remdesivir administration when clinically appropriate: Heart rate (Touafchia 2021); hepatic function tests (ALT, AST, bilirubin, alkaline phosphatase, prothrombin time); renal function tests (serum creatinine, CrCl); signs/symptoms of infusion reaction.

Monitor patients during infusion and observe patients for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate.

Mechanism of Action

Remdesivir is an inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which is essential for viral replication. Remdesivir is an adenosine nucleotide prodrug that is metabolized to the pharmacologically active nucleoside triphosphate metabolite after being distributed into cells. Remdesivir triphosphate (GS-443902) acts as an adenosine triphosphate analog and competes for incorporation into RNA chains by the SARS-CoV-2 RdRp, resulting in delayed chain termination during viral RNA replication. Remdesivir triphosphate can also inhibit viral RNA synthesis due to incorporation into the viral RNA template.

Pharmacokinetics

Protein binding: Remdesivir: 88% to 93.6%; GS-441524: 2%; GS-704277: 1%.

Half-life elimination: Remdesivir: ~1 hour; GS-441524: 27 hours; GS-704277: 1.3 hours.

Excretion:

Urine: Remdesivir: 10%; GS-441524: 49%; GS-704277: 2.9%

Feces: Remdesivir: Not detected; GS-441524: 0.5%; GS-704277: Not detected.

Pharmacokinetics: Additional Considerations

Expected drug exposure in adults with normal renal function:

Cmax (peak): IV: 100 mg once daily, steady state: Remdesivir: 2,229 ng/mL; GS-441524: 145 ng/mL; GS-704277: 246 ng/mL.

Cmin (trough): IV: 100 mg once daily, steady state: Remdesivir: Not detected; GS-441524: 69.2 ng/mL; GS-704277: Not detected.

AUC: IV: 100 mg once daily, steady state: Remdesivir: 1,585 ng • hour/mL; GS-441524: 2,229 ng • hour/mL; GS-704277: 462 ng • hour/mL.

Pediatric: In a pharmacokinetic modeling study, exposure to remdesivir and metabolites (Cmax, AUC) was higher in pediatric patients ≥28 days of age weighing ≥3 kg receiving recommended dosing regimens as compared to adults. The difference in exposure is not expected to be clinically significant.

Pricing: US

Solution (Veklury Intravenous)

100 mg/20 mL (per mL): $31.20

Solution (reconstituted) (Remdesivir Intravenous)

100 mg (per each): $624.00

Solution (reconstituted) (Veklury Intravenous)

100 mg (per each): $624.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Veklury (AU, DK, EE, FR, GB, HR, LT, LV, NL, NZ, PT, SK)


For country abbreviations used in Lexicomp (show table)
  1. Ackley TW, Mcmanus D, Topal JE, Cicali B, Shah S. A valid warning or clinical lore: an evaluation of safety outcomes of remdesivir in patients with impaired renal function from a multicenter matched cohort. Antimicrob Agents Chemother. Published online November 23, 2020. doi:10.1128/AAC.02290-20 [PubMed 33229428]
  2. Adamsick ML, Gandhi RG, Bidell MR, et al. Remdesivir in patients with acute or chronic kidney disease and COVID-19. J Am Soc Nephrol. 2020;31(7):1384-1386. doi:10.1681/ASN.2020050589 [PubMed 32513665]
  3. Agostini ML, Andres EL, Sims AC, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio. 2018;9(2):e00221-18. doi:10.1128/mBio.00221-18 [PubMed 29511076]
  4. Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. Published online January 28, 2021. doi:10.1097/CCM.0000000000004899 [PubMed 33555780]
  5. American College of Obstetricians and Gynecologists (ACOG). COVID-19 FAQs for obstetricians-gynecologists, obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed February 22, 2022.
  6. Barlow A, Landolf KM, Barlow B, et al. Review of emerging pharmacotherapy for the treatment of coronavirus disease 2019. Pharmacotherapy. Published online April 7, 2020. doi:10.1002/phar.2398 [PubMed 32259313]
  7. Beigel JH, Tomashek KM, Dodd LE, et al; ACTT-1 Study Group Members. Remdesivir for the treatment of covid-19 - final report. N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764 [PubMed 32445440]
  8. Bhimraj A, Morgan RL, Shumaker AH, et al. Infectious Diseases Society of America (IDSA) guidelines on the treatment and management of patients with COVID-19. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/. Updated April 14, 2021. Accessed April 22, 2021.
  9. Budi DS, Pratama NR, Wafa IA, Putra M, Wardhana MP, Wungu CDK. Remdesivir for pregnancy: a systematic review of antiviral therapy for COVID-19. Heliyon. 2022;8(1):e08835. doi:10.1016/j.heliyon.2022.e08835 [PubMed 35128114]
  10. Burwick RM, Yawetz S, Stephenson KE, et al. Compassionate use of remdesivir in pregnant women with severe coronavirus disease 2019. Clin Infect Dis. 2021;73(11):e3996-e4004. doi:10.1093/cid/ciaa1466 [PubMed 33031500]
  11. Carothers C, Birrer K, Vo M. Acetylcysteine for the treatment of suspected remdesivir-associated acute liver failure in COVID-19: a case series. Pharmacotherapy. Published online October 2, 2020. doi:10.1002/phar.2464 [PubMed 33006138]
  12. Chiotos K, Hayes M, Kimberlin DW, et al. Multicenter interim guidance on use of antivirals for children with coronavirus disease 2019/severe acute respiratory syndrome coronavirus 2. J Pediatric Infect Dis Soc. 2021;10(1):34-48. doi:10.1093/jpids/piaa115 [PubMed 32918548]
  13. Chow EJ, Maust B, Kazmier KM, Stokes C. Sinus bradycardia in a pediatric patient treated with remdesivir for acute coronavirus disease 2019: a case report and a review of the literature. J Pediatric Infect Dis Soc. 2021;10(9):926-929. doi:10.1093/jpids/piab029 [PubMed 34173663]
  14. Davis MR, Pham CU, Cies JJ. Remdesivir and GS-441524 plasma concentrations in patients with end-stage renal disease on haemodialysis. J AntimicrobChemother. 2021;76(3):822-825. doi:10.1093/jac/dkaa472 [PubMed 33152758]
  15. Eid J, Abdelwahab M, Colburn N, et al. Early administration of remdesivir and intensive care unit admission in hospitalized pregnant individuals with Coronavirus disease 2019 (COVID-19). Obstet Gynecol. Published online February 8, 2022. doi: 10.1097/AOG.0000000000004734 [PubMed 35134032]
  16. Estiverne C, Strohbehn IA, Mithani Z, et al. Remdesivir in patients with estimated glomerular filtration rate < 30 mL/min/1.73 m2 or on renal replacement therapy. Kidney Int Rep. Published online November 27, 2020. doi:10.1016/j.ekir.2020.11.025 [PubMed 33263094]
  17. Frauenfelder C, Brierley J, Whittaker E, Perucca G, Bamford A. Infant with SARS-CoV-2 infection causing severe lung disease treated with remdesivir. Pediatrics. 2020;146(3):e20201701. doi:10.1542/peds.2020-1701 [PubMed 32554811]
  18. Gilead Sciences Inc. Pediatrics and remdesivir [written communication]. Foster City, CA: Gilead Sciences Inc; May 8, 2020a.
  19. Gilead Sciences Inc. Questions re: remdesivir [written communication]. Foster City, CA: Gilead Sciences Inc; May 19, 2020b.
  20. Gilead Sciences Inc. Update on the company's ongoing response to COVID-19. https://www.gilead.com/purpose/advancing-global-health/covid-19. Accessed September 2, 2020c.
  21. Gilead Sciences Inc. Veklury (remdesivir) compatibility with alternative diluents. https://www.askgileadmedical.com/api/rendition.php?doc=17818. Updated January 10, 2022. Accessed January 12, 2022.
  22. Gilead Sciences Inc. Veklury (remdesivir) overfill during dose preparation. https://www.askgileadmedical.com. Updated October 23, 2020d.
  23. Goldman DL, Aldrich ML, Hagmann SHF, et al. Compassionate use of remdesivir in children with severe COVID-19. Pediatrics. 2021;147(5):e2020047803. doi:10.1542/peds.2020-047803 [PubMed 33883243]
  24. Goldman JD, Lye DCB, Hui SH, et al. Remdesivir for 5 or 10 days in patients with severe covid-19. N Engl J Med. Published online May 27, 2020. doi:10.1056/NEJMoa2015301 [PubMed 32459919]
  25. Gottlieb RL, Vaca CE, Paredes R, et al; GS-US-540-9012 (PINETREE) Investigators. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. Published online December 22, 2021. doi:10.1056/NEJMoa2116846 [PubMed 34937145]
  26. Gubitosa JC, Kakar P, Gerula C, et al. Marked sinus bradycardia associated with remdesivir in COVID-19: a case and literature review. JACC Case Rep. 2020;2(14):2260-2264. doi:10.1016/j.jaccas.2020.08.025 [PubMed 33163977]
  27. Holshue ML, DeBolt C, Lindquist S, et al; Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929-936. doi: 10.1056/NEJMoa2001191 [PubMed 32004427]
  28. Hoover RK, Alcorn H Jr, Lawrence L, et al. Clinical pharmacokinetics of sulfobutylether-β-cyclodextrin in patients with varying degrees of renal impairment. J Clin Pharmacol. 2018;58(6):814-822. doi:10.1002/jcph.1077 [PubMed 29578585]
  29. Hopkins BJ, Prokesch BC. Anaphylaxis due to remdesivir. Antimicrob Agents Chemother. 2021;65(5):e00233-21. doi:10.1128/AAC.00233-21 [PubMed 33593840]
  30. Institute for Safe Medication Practices (ISMP). Reported medication errors with Veklury (remdesivir) Emergency Use Authorization. ISMP Medication Safety Alert! Acute Care Edition. 2020;25(18):1-2.
  31. Jacinto JP, Patel M, Goh J, Yamamura K. Remdesivir-induced symptomatic bradycardia in the treatment of COVID-19 disease. HeartRhythm Case Rep. 2021;7(8):514-517. doi:10.1016/j.hrcr.2021.05.004 [PubMed 34026493]
  32. Jorgensen SCJ, Davis MR, Lapinsky SE. A review of remdesivir for COVID-19 in pregnancy and lactation. J Antimicrob Chemother. 2021;77(1):24-30. doi:10.1093/jac/dkab311 [PubMed 34427297]
  33. Jorgensen SCJ, Kebriaei R, Dresser LD. Remdesivir: review of pharmacology, pre-clinical data, and emerging clinical experience for COVID-19. Pharmacotherapy. 2020;40(7):659-671. doi:10.1002/phar.2429 [PubMed 32446287]
  34. Kalani-Moghaddam F, Pouralizadeh N, Pourdowlat G, Sarfarazi-Moghaddam S, Gharib MH, Pakdel M. The youngest surviving COVID-19 patient: A case report. Int J Surg Case Rep. 2022;94:107065. doi:10.1016/j.ijscr.2022.107065 [PubMed 35433235]
  35. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Updated 2022 Feb 3. https://www.ncbi.nlm.nih.gov/books/NBK564049/ [PubMed LiverTox.1]
  36. Luke DR, Tomaszewski K, Damle B, Schlamm HT. Review of the basic and clinical pharmacology of sulfobutylether-beta-cyclodextrin (SBECD). J Pharm Sci. 2010;99(8):3291-3301. doi:10.1002/jps.22109 [PubMed 20213839]
  37. Luke DR, Wood ND, Tomaszewski KE, Damle B. Pharmacokinetics of sulfobutylether-β-cyclodextrin (SBECD) in subjects on hemodialysis. Nephrol Dial Transplant. 2012;27(3):1207-1212. doi:10.1093/ndt/gfr472 [PubMed 21868395]
  38. Nasrallah S, Nguyen AQ, Hitchings L, et al. Pharmacological treatment in pregnant women with moderate symptoms of coronavirus disease 2019 (COVID-19) pneumonia. J Matern Fetal Neonatal Med. 2021:1-8. doi:10.1080/14767058.2021.1903426 [PubMed 33771091]
  39. National Institute of Allergy and Infectious Diseases (NIAID). NIH clinical trial shows remdesivir accelerates recovery from advanced COVID-19. https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19National. Accessed May 1, 2020.
  40. National Institutes of Health. COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. https://www.covid19treatmentguidelines.nih.gov/. Updated January 19, 2022. Accessed January 27, 2022.
  41. Parsons S, Tran VL. The trilogy of SARS-CoV-2 in pediatrics (part 1): acute COVID-19 in special populations. J Pediatr Pharmacol Ther. 2021;26(3):220-239. doi:10.5863/1551-6776-26.3.220 [PubMed 33833623]
  42. Pettit NN, Pisano J, Nguyen CT, et al. Remdesivir use in the setting of severe renal impairment: a theoretical concern or real risk? Clin Infect Dis. 2020:ciaa1851. doi:10.1093/cid/ciaa1851 [PubMed 33315065]
  43. Rau C, Apostolidou S, Singer D, Avataneo V, Kobbe R. Remdesivir, sinus bradycardia and therapeutic drug monitoring in children with severe COVID-19. Pediatr Infect Dis J. 2021;40(12):e528-e529. doi:10.1097/INF.0000000000003309 [PubMed 34591799]
  44. Saikia B, Bandi S. RE: Remdesivir use in premature neonates with SARS-CoV-2 infection. https://pediatrics.aappublications.org/content/re-remdesivir-use-premature-neonates-sars-cov-2-infection. Published April 29, 2021a. Accessed September 10, 2021.
  45. Saikia B, Tang J, Robinson S, et al. Neonates with SARS-CoV-2 infection and pulmonary disease safely treated with remdesivir. Pediatr Infect Dis J. 2021b;40(5):e194-e196. doi:10.1097/INF.0000000000003081 [PubMed 33847299]
  46. Sarhan MA, Casalino M, Paopongsawan P, et al. SARS-CoV-2 associated respiratory failure in a preterm infant and the outcome after remdesivir treatment. Pediatr Infect Dis J. 2022;41(5):e233-e234. doi:10.1097/INF.0000000000003504 [PubMed 35213865]
  47. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396):eaal3653. doi:10.1126/scitranslmed.aal3653 [PubMed 28659436]
  48. Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020;11(1):222. doi:10.1038/s41467-019-13940-6 [PubMed 31924756]
  49. Sörgel F, Malin JJ, Hagmann H, et al. Pharmacokinetics of remdesivir in a COVID-19 patient with end-stage renal disease on intermittent haemodialysis. J Antimicrob Chemother. Published online November 30, 2020. doi:10.1093/jac/dkaa500 [PubMed 33251541]
  50. Thakare S, Gandhi C, Modi T, et al. Safety of remdesivir in patients with acute or chronic kidney disease. Kidney Int Rep. Published online October 10, 2020. doi:10.1016/j.ekir.2020 [PubMed 33073066]
  51. Touafchia A, Bagheri H, Carrié D, Durrieu G, Sommet A, Montastruc F. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19): a new safety concerns. Clin Microbiol Infect. Published online February 26, 2021. doi:10.1016/j.cmi.2021.02.013 [PubMed 33647441]
  52. US Department of Health and Human Services (HHS). HHS announces shipments of donated remdesivir for hospitalized patients with COVID-19. https://www.hhs.gov/about/news/2020/05/09/hhs-ships-first-doses-of-donated-remdesivir-for-hospitalized-patients-with-covid-19.html. Accessed May 12, 2020a.
  53. US Food and Drug Administration (FDA). Fact sheet for health care providers Emergency Use Authorization (EUA) of Veklury® (remdesivir). https://www.fda.gov/media/137566/download. Updated January 2022. Accessed January 27, 2022.
  54. US Food and Drug Administration (FDA). Frequently asked questions on the Emergency Use Authorization for Veklury® (remdesivir) for hospitalized COVID-19 patients. https://www.fda.gov/media/137574/download. Updated October 22, 2020. Accessed October 27, 2020b.
  55. van Merendonk LN, Leeuwerik AF, den Brok MWJ, et al. Peripheral infiltration of remdesivir in 3 patients with COVID-19: case series and discussion. Am J Health Syst Pharm. 2021;78(21):1944-1951. doi:10.1093/ajhp/zxab197 [PubMed 33950198]
  56. Veklury (remdesivir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; April 2022.
  57. Veklury (remdesivir) [product monograph]. Mississauga, Ontario, Canada: Gilead Sciences Canada Inc; April 2022.
  58. Wada YS, Saito J, Hashii Y, et al. Remdesivir and human milk: a case study. J Hum Lact. Published online February 21, 2022. doi:10.1177/08903344221076539 [PubMed 35189734]
  59. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial [published correction appears in Lancet. 2020 May 30;395(10238):1694]. Lancet. 2020;395(10236):1569-1578. doi:10.1016/S0140-6736(20)31022-9 [PubMed 32423584]
  60. Wardell H, Campbell JI, VanderPluym C, Dixit A. Severe acute respiratory syndrome coronavirus 2 infection in febrile neonates. J Pediatric Infect Dis Soc. 2020;9(5):630-635. doi:10.1093/jpids/piaa084 [PubMed 32645175]
  61. World Health Organization (WHO). WHO R&D Blueprint – Ad-hoc expert consultation on clinical trials for Ebola Therapeutics: Appendix 4. Summaries of evidence from selected experimental therapeutics, as of October 2018. https://www.who.int/ebola/drc-2018/summaries-of-evidence-experimental-therapeutics.pdf?ua=1. Published October 11, 2018. Accessed March 24, 2020.
  62. World Health Organization (WHO). Therapeutics and COVID-19: living guideline. https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline. Updated November 20, 2020. Accessed December 7, 2020.
Topic 127259 Version 141.0