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Veklury
Classes
Antiviral RNA-Polymerase Inhibitors
Administration
Administer remdesivir only in a setting with immediate access to medications used for the treatment of severe infusion or hypersensitivity reactions (e.g., anaphylaxis) and with the ability to activate the emergency medical system (EMS), if necessary.
The product is available in 2 dosage forms, a lyophilized powder for injection and solution for injection. There are differences in the way the 2 formulations are prepared; carefully follow the product-specific instructions. Neither dosage form contains a preservative nor bacteriostatic agent; therefore, aseptic technique must be used during the preparation of the final parenteral solution.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Discard the vial if the lyophilized powder or solution is discolored or contains particulate matter. Prior to dilution, reconstituted remdesivir for injection and remdesivir injection solution should be clear, colorless to yellow, and free of visible particles.
**For pediatric patients weighing less than 40 kg, use ONLY the lyophilized powder formulation to prepare doses.**
Remdesivir Lyophilized Powder 100 mg vials
Reconstitution
Aseptically reconstitute the lyophilized powder by adding 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial, and insert the needle in the center of the vial stopper. Sterile Water for Injection is the preferred diluent for reconstitution of the lyophilized powder. If Sterile Water for Injection is unavailable, 0.9% Sodium Chloride for Injection may be used for reconstitution; however, if 0.9% Sodium Chloride is used for reconstitution, then the subsequent dilution should ONLY be done using the 250 mL 0.9% Sodium Chloride infusion bag.
Discard the vial if a vacuum does not pull the diluent into the vial.
Immediately shake the vial for 30 seconds.
Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this process as necessary until the contents of the vial are completely dissolved. Discard the vial if the contents are not completely dissolved.
After reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.
Use the reconstituted product immediately to prepare the diluted drug product.
Dilution
Adults and Pediatric patients weighing 40 kg or more:
Withdraw and discard 20 mL (100 mg dose) or 40 mL (200 mg dose) of 0.9% Sodium Chloride from a 100 mL or 250 mL infusion bag using an appropriately sized syringe and needle. NOTE: Use the 250 mL infusion bag if the lyophilized powder was reconstituted using 0.9% Sodium Chloride for Injection.
Transfer appropriate dose of reconstituted solution (20 mL or 40 mL) to the infusion bag. Discard any unused reconstituted solution that remains in the vials.
Gently invert the bag 20 times to mix the solution in the bag. Do not shake
Storage: The prepared solution is stable for 24 hours at room temperature 20 to 25 degrees C (68 to 77 degrees F) or 48 hours under refrigeration 2 to 8 degrees C (36 to 46 degrees F).
Pediatric patients weighing less than 40 kg:
The reconstituted solution must be further diluted to a fixed concentration of 1.25 mg/mL using 0.9% Sodium Chloride Injection. Small 0.9% Sodium Chloride infusion bags (e.g., 25 mL, 50 mL, or 100 mL) or an appropriately sized syringe (for volumes less than 50 mL) should be used for pediatric dosing.
Infusion with an IV bag:
Prepare an IV bag of 0.9% Sodium Chloride with a volume equal to the total infusion volume minus the volume of reconstituted remdesivir solution that will be diluted to achieve a 1.25 mg/mL solution.
Withdraw the required volume of reconstituted solution containing remdesivir into an appropriately sized syringe.
Transfer the required volume of reconstituted remdesivir for injection to the 0.9% Sodium Chloride infusion bag.
Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
If using an empty infusion bag, transfer the required volume of reconstituted solution to the bag, followed by the volume of 0.9% Sodium Chloride sufficient to achieve a 1.25 mg/mL final volume concentration.
Storage: The prepared infusion solution is stable for 24 hours at room temperature 20 to 25 degrees C (68 to 77 degrees F) or 48 hours under refrigeration 2 to 8 degrees C (36 to 46 degrees F).
Infusion with a syringe:
Select an appropriately sized syringe equal to or larger than the calculated total volume of 1.25 mg/mL remdesivir solution needed.
Withdraw the required volume of reconstituted solution containing remdesivir from the vial into the syringe, followed by the required volume of 0.9% Sodium Chloride needed to achieve a 1.25 mg/mL remdesivir solution.
Mix the syringe by inversion 20 times. Do not shake.
The prepared diluted solution should be used immediately.
Remdesivir Solution for Injection 100 mg/20 mL vials
Preparation
Remove the required number of single-dose vial(s) from storage.
Equilibrate the vial(s) to room temperature 20 to 25 degrees C (68 to 77 degrees F). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
Dilution
The 100 mg/20 mL remdesivir solution must be further diluted in a 250 mL 0.9% Sodium Chloride infusion bag.
Withdraw and discard 20 mL (100 mg dose) or 40 mL (200 mg dose) of 0.9% Sodium Chloride from a 250 mL infusion bag using an appropriately sized syringe and needle.
Inject approximately 10 mL of air into each remdesivir vial above the solution level before withdrawing the dose to facilitate withdrawal. Withdraw the appropriate dose of solution (20 mL or 40 mL). The last 5 mL of solution from each vial requires more force to withdraw.
Transfer the remdesivir solution to the infusion bag.
Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
Storage: The prepared solution is stable for 24 hours at room temperature 20 to 25 degrees C (68 to 77 degrees F) or 48 hours under refrigeration 2 to 8 degrees C (36 to 46 degrees F).
Intermittent IV Infusion
Do not administer by any other route.
Infuse over 30 to 120 minutes. Slowing the infusion rate to a maximum infusion time of up to 120 minutes can be considered to potentially prevent infusion-related reactions.
Do not mix with or administer simultaneously with other IV medications.
Monitor patients during the infusion and observe for at least 1 hour after the infusion is complete for signs of hypersensitivity. If a clinically significant reaction occurs, immediately discontinue the infusion and initiate appropriate treatment.
Adverse Reactions
atrial fibrillation / Early / 6.0-6.0
renal failure / Delayed / 6.0-6.0
acute respiratory distress syndrome (ARDS) / Early / 4.0-4.0
seizures / Delayed / 0-2.0
Kounis syndrome / Rapid / 0-1.0
bradycardia / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
hyperkalemia / Delayed / Incidence not known
lymphopenia / Delayed / 2.0-27.0
anemia / Delayed / 1.0-25.0
hyperglycemia / Delayed / 3.0-15.0
hypoalbuminemia / Delayed / 12.0-12.0
hyperuricemia / Delayed / 11.0-11.0
hypotension / Rapid / 8.0-8.0
elevated hepatic enzymes / Delayed / 2.0-8.0
hypernatremia / Delayed / 3.0-6.0
proteinuria / Delayed / 6.0-6.0
leukopenia / Delayed / 4.0-4.0
hypokalemia / Delayed / 4.0-4.0
hematuria / Delayed / 4.0-4.0
glycosuria / Early / 4.0-4.0
delirium / Early / 4.0-4.0
hypercalcemia / Delayed / 3.0-3.0
hyperbilirubinemia / Delayed / 0-2.0
infusion-related reactions / Rapid / Incidence not known
dyspnea / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
wheezing / Rapid / Incidence not known
hypertension / Early / Incidence not known
hypoxia / Early / Incidence not known
phlebitis / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
diarrhea / Early / 1.0-9.0
nausea / Early / 1.0-7.0
headache / Early / 4.0-5.0
rash / Early / 0-2.0
abdominal pain / Early / 1.0-1.0
diaphoresis / Early / Incidence not known
ecchymosis / Delayed / Incidence not known
shivering / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
fever / Early / Incidence not known
musculoskeletal pain / Early / Incidence not known
Common Brand Names
Veklury
Dea Class
Rx
Description
Intravenous antiviral with a broad spectrum of in vitro activity against RNA viruses
Approved to treat COVID-19 in adults and pediatric patients weighing at least 1.5 kg requiring hospitalization or mild to moderate COVID-19 in nonhospitalized patients who are at high risk for clinical progression
Associated with infusion-related reactions; monitor patients during and for at least 1 hour after infusion
Dosage And Indications
200 mg IV once on day 1, followed by 100 mg IV once daily for 9 days.
5 mg/kg/dose (Max: 200 mg/dose) IV once on day 1, followed by 2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 9 days.
5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 9 days.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 9 days.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 9 days.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 4 days was successfully used in a case report of 2 ex-premature neonates. The first neonate was born at 31 weeks, weighed 2.7 kg, and presented with SARS-CoV-2 infection at 37 weeks of life. The second neonate was born at 33 weeks (birthweight 1.5 kg) and presented with SARS-CoV-2 infection at 35 weeks of life. In both cases, the SARS-CoV-2 RNA PCR became negative only after completion of treatment with remdesivir. Another case report describes 5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 10 days successfully used in an ex-premature neonate (born at 32 weeks) weighing 2.2 kg who presented with SARS-CoV-2 infection at 37 weeks of life.
200 mg IV once on day 1, followed by 100 mg IV once daily for 9 days.
200 mg IV once on day 1, followed by 100 mg IV once daily for 9 days.
NOTE: The National Institutes of Health (NIH) has issued a statement to provide guidance on treating nonhospitalized patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease. The NIH recommends using 1 of the following therapeutics :
Preferred therapies (Adults and Pediatrics, listed in order of preference)
nirmatrelvir; ritonavir
remdesivir
Alternative therapies (Adults only)
molnupiravir
200 mg IV once on day 1, followed by 100 mg IV once daily for 2 days. According to NIH, the optimal management of immunocompromised patients who have prolonged COVID-19 symptoms and evidence of ongoing viral replication despite receiving a course of antiviral therapy is unknown. Some members of the guideline panel suggest using longer or additional courses of remdesivir in these patients.
5 mg/kg/dose (Max: 200 mg/dose) IV once on day 1, followed by 2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 2 days.
5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 2 days.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 2 days.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 2 days.
200 mg IV once on day 1, followed by 100 mg IV once daily for 2 days. According to NIH, the optimal management of immunocompromised patients who have prolonged COVID-19 symptoms and evidence of ongoing viral replication despite receiving a course of antiviral therapy is unknown. Some members of the guideline panel suggest using longer or additional courses of remdesivir in these patients.
200 mg IV once on day 1, followed by 100 mg IV once daily for 2 days.
200 mg IV once on day 1, followed by 100 mg IV once daily for 4 days. May extend treatment for up to 5 additional days (i.e., 10 days total) if a patient does not demonstrate clinical improvement.
5 mg/kg/dose (Max: 200 mg/dose) IV once on day 1, followed by 2.5 mg/kg/dose (Max: 100 mg/dose) IV once daily for 4 days. May extend treatment for up to 5 additional days (i.e., 10 days total) if a patient does not demonstrate clinical improvement.
5 mg/kg/dose IV once on day 1, followed by 2.5 mg/kg/dose IV once daily for 4 days. May extend treatment for up to 5 additional days (i.e., 10 days total) if a patient does not demonstrate clinical improvement.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 4 days. May extend treatment for up to 5 additional days (i.e., 10 days total) if a patient does not demonstrate clinical improvement.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 4 days. May extend treatment for up to 5 additional days (i.e., 10 days total) if a patient does not demonstrate clinical improvement.
2.5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 4 days was successfully used in a case report of 2 ex-premature neonates. The first neonate was born at 31 weeks, weighed 2.7 kg, and presented with SARS-CoV-2 infection at 37 weeks of life. The second neonate was born at 33 weeks (birthweight 1.5 kg) and presented with SARS-CoV-2 infection at 35 weeks of life. In both cases, the SARS-CoV-2 RNA PCR became negative only after completion of treatment with remdesivir. Another case report describes 5 mg/kg/dose IV once on day 1, followed by 1.25 mg/kg/dose IV once daily for 10 days successfully used in an ex-premature neonate (born at 32 weeks) weighing 2.2 kg who presented with SARS-CoV-2 infection at 37 weeks of life.
200 mg IV once on day 1, followed by 100 mg IV once daily for 4 days. May extend treatment for up to 5 additional days (i.e., 10 days total) if a patient does not demonstrate clinical improvement.
200 mg IV once on day 1, followed by 100 mg IV once daily for 4 days. May extend treatment for up to 5 additional days (i.e., 10 days total) if a patient does not demonstrate clinical improvement.
Dosing Considerations
No dosage adjustments are recommended for patients with mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C).
No dosage adjustments are needed for patients with any degree of renal impairment, including patients on dialysis. Remdesivir is not efficiently removed through hemodialysis and may be administered without regard to the timing of dialysis.
Drug Interactions
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Consider a reduced dose of dihydrocodeine with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, consider increasing the dihydrocodeine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Concomitant use of dihydrocodeine with remdesivir may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Dihydrocodeine is partially metabolized via CYP3A and remdesivir is a weak CYP3A inhibitor.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Acetaminophen; HYDROcodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like remdesivir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If remdesivir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; oxyCODONE: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like remdesivir can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If remdesivir is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
ALFentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a CYP3A substrate, and coadministration with CYP3A inhibitors like remdesivir can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If remdesivir is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
ALPRAZolam: (Major) Avoid coadministration of alprazolam and remdesivir due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with remdesivir, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
ARIPiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of remdesivir. Patients receiving both a CYP2D6 inhibitor plus remdesivir may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; remdesivir is a weak CYP3A inhibitor.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Aspirin, ASA; oxyCODONE: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like remdesivir can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If remdesivir is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Benzhydrocodone; Acetaminophen: (Moderate) Consider a reduced dose of benzhydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like remdesivir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of benzhydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If remdesivir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to benzhydrocodone.
Buprenorphine: (Moderate) Concomitant use of buprenorphine and remdesivir can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when remdesivir is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping remdesivir, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If remdesivir is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and remdesivir is a CYP3A inhibitor.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine and remdesivir can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when remdesivir is added after a stable buprenorphine dose is achieved. If concurrent use is necessary, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping remdesivir, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If remdesivir is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A and remdesivir is a CYP3A inhibitor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
carBAMazepine: (Moderate) Monitor carbamazepine concentrations closely during coadministration of remdesivir; carbamazepine dose adjustments may be needed. Concomitant use may increase carbamazepine concentrations. Carbamazepine is a CYP3A substrate and remdesivir is a CYP3A inhibitor.
Celecoxib; Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with remdesivir is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of remdesivir, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Chloroquine: (Major) Coadministration of remdesivir and chloroquine is not recommended. Based on data from cell culture experiments, the intracellular metabolic activation and antiviral activity of remdesivir may be antagonized by chloroquine phosphate in a dose-dependent manner.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Chlorpheniramine; HYDROcodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like remdesivir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If remdesivir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Cisapride: (Major) Avoid concomitant use of cisapride and remdesivir; use increases cisapride exposure and the risk for adverse effects such as QT/QTc prolongation and torsade de pointes (TdP). Cisapride is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor. Concomitant use of cisapride with CYP3A inhibitors is disallowed under the Propulsid Limited Access Program.
cloZAPine: (Moderate) Consider a clozapine dose reduction if coadministered with remdesivir and monitor for adverse reactions. If remdesivir is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A; remdesivir is a weak CYP3A inhibitor.
Codeine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Codeine; guaiFENesin: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Codeine; guaiFENesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with remdesivir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of remdesivir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If remdesivir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine and by CYP3A to norcodeine( norcodeine does not have analgesic properties); remdesivir is a weak inhibitor of CYP3A.
cycloSPORINE: (Moderate) Closely monitor cyclosporine whole blood trough concentrations as appropriate and watch for cyclosporine-related adverse reactions if coadministration with remdesivir is necessary. The dose of cyclosporine may need to be adjusted. Concurrent use may increase cyclosporine exposure causing an increased risk for cyclosporine-related adverse events. Cyclosporine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
diazePAM: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with remdesivir is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP3A substrate and remdesivir is a CYP3A inhibitor.
Disopyramide: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with remdesivir is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A inhibitors.
Dofetilide: (Moderate) Monitor for an increase in dofetilide-related adverse reactions, including QT prolongation, if coadministration with remdesivir is necessary as concurrent use may increase dofetilide exposure. Dofetilide is a minor CYP3A substrate and remdesivir is a weak CYP3A inhibitor; however, because there is a linear relationship between dofetilide plasma concentration and QTc, concomitant administration of CYP3A inhibitors may increase the risk of arrhythmia (torsade de pointes).
Eliglustat: (Major) Coadministration of eliglustat and remdesivir is not recommended in poor CYP2D6 metabolizers (PMs). In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. Eliglustat is a CYP3A and CYP2D6 substrate; remdesivir is a weak CYP3A inhibitor. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Felodipine: (Moderate) Concurrent use of felodipine and remdesivir should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor. Concurrent use of another weak CYP3A inhibitor increased felodipine AUC and Cmax by approximately 50%.
fentaNYL: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A substrate, and coadministration with CYP3A inhibitors like remdesivir can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If remdesivir is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or remdesivir; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A inhibitors, including remdesivir, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A inhibitors and flibanserin should be discussed with the patient.
Homatropine; HYDROcodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like remdesivir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If remdesivir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
HYDROcodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like remdesivir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If remdesivir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
HYDROcodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A substrate, and coadministration with CYP3A inhibitors like remdesivir can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If remdesivir is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydroxychloroquine: (Major) Coadministration of remdesivir and hydroxychloroquine is not recommended. Based on data from cell culture experiments, the intracellular metabolic activation and antiviral activity of remdesivir may be antagonized by chloroquine phosphate in a dose-dependent manner.
Isradipine: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with remdesivir is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of remdesivir is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Lemborexant: (Major) Limit the dose of lemborexant to 5 mg PO once daily if coadministered with remdesivir as concomitant use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A substrate; remdesivir is a weak CYP3A inhibitor. Coadministration with a weak CYP3A inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with remdesivir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Lidocaine; EPINEPHrine: (Moderate) Monitor for lidocaine toxicity if coadministration with remdesivir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with remdesivir is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Lomitapide: (Major) Decrease the dose of lomitapide by one-half not to exceed 30 mg/day PO if coadministration with remdesivir is necessary. Concomitant use may significantly increase the serum concentration of lomitapide. Lomitapide is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A inhibitors.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and remdesivir; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, reduce to or continue lonafarnib at a dosage of 115 mg/m2 and closely monitor patients for lonafarnib-related adverse reactions. Resume previous lonafarnib dosage 14 days after discontinuing remdesivir. Lonafarnib is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with remdesivir is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and remdesivir is a weak CYP3A inhibitor.
Meperidine: (Moderate) Consider a reduced dose of meperidine with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, meperidine plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to meperidine. Meperidine is a substrate of CYP3A and remdesivir is a weak CYP3A inhibitor. Concomitant use with remdesivir can increase meperidine exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of meperidine.
Methadone: (Moderate) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; remdesivir is a weak CYP3A inhibitor. Concomitant use with remdesivir can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone.
Methylergonovine: (Moderate) Monitor for an increase in the incidence and severity of vasospastic adverse reactions, including cerebral and peripheral ischemia, during concomitant use of methylergonovine and remdesivir. Concomitant use may increase methylergonovine exposure. Methylergonovine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Midazolam: (Moderate) Use caution when midazolam is coadministered with remdesivir. Concurrent use may increase midazolam exposure leading to prolonged sedation. Midazolam is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of remdesivir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
niMODipine: (Moderate) Monitor blood pressure and reduce the dose of nimodipine as clinically appropriate if coadministration with remdesivir is necessary. Concurrent use may increase nimodipine exposure. Nimodipine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with remdesivir due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A substrate and remdesivir is a CYP3A inhibitor. Coadministration with another CYP3A inhibitor increased the AUC of nisoldipine by 30% to 45%.
oxyCODONE: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A substrate, and coadministration with weak CYP3A inhibitors like remdesivir can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If remdesivir is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Pimozide: (Major) Avoid concomitant use of pimozide and remdesivir. Concomitant use may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is CYP3A substrate, and remdesivir is a weak CYP3A inhibitor.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with remdesivir; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid simultaneous use of propafenone and remdesivir with a CYP2D6 inhibitor or in patients with CYP2D6 deficiency. Propafenone is a CYP3A and CYP2D6 substrate; remdesivir is a weak CYP3A inhibitor.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of remdesivir. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
SUFentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if remdesivir must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of remdesivir is necessary. If remdesivir is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A substrate, and coadministration with a weak CYP3A inhibitor like remdesivir can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If remdesivir is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with remdesivir is necessary. The dose of tacrolimus may need to be reduced. Tacrolimus is a CYP3A substrate with a narrow therapeutic range; remdesivir is a weak CYP3A inhibitor.
traMADol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with remdesivir is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of remdesivir, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Tramadol; Acetaminophen: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with remdesivir is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of remdesivir, a weak CYP3A inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with remdesivir. Coadministration may increase the exposure of triazolam. Triazolam is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with remdesivir. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A substrate; remdesivir is a weak CYP3A inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with remdesivir is necessary. Vinorelbine is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with remdesivir is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. The R-enantiomer of warfarin is a CYP3A substrate and remdesivir is a weak CYP3A inhibitor. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
How Supplied
Veklury Intravenous Inj Pwd: 100mg
Veklury Intravenous Inj Sol Conc: 1mL, 5mg
Maximum Dosage
200 mg IV on day 1, followed by 100 mg/day IV.
200 mg IV on day 1, followed by 100 mg/day IV.
5 mg/kg/dose (Max: 200 mg/dose) IV on day 1, followed by 2.5 mg/kg/day (Max: 100 mg/day) IV.
5 mg/kg/dose (Max: 200 mg/dose) IV on day 1, followed by 2.5 mg/kg/day (Max: 100 mg/day) IV.
weighing 3 kg or more: 5 mg/kg/dose IV on day 1, followed by 2.5 mg/kg/day IV.
weighing less than 3 kg: 2.5 mg/kg/dose IV on day 1, followed by 1.25 mg/kg/day IV.
Term Neonates weighing 1.5 kg or more: 2.5 mg/kg/dose IV on day 1, followed by 1.25 mg/kg/day IV.
Term Neonates weighing less than 1.5 kg: Safety and efficacy have not been established.
Premature Neonates: Safety and efficacy have not been established; however, doses of 2.5 mg/kg/dose IV on day 1, followed by 1.25 mg/kg/day IV have been used off-label.
Mechanism Of Action
Remdesivir is a monophosphoramidate prodrug of remdesivir triphosphate (RDV-TP), an adenosine analog that acts as an inhibitor of RNA-dependent RNA polymerases (RdRps). Remdesivir triphosphate competes with adenosine-triphosphate (ATP) for incorporation into nascent viral RNA chains. Once incorporated at position (i), RDV-TP terminates RNA synthesis at position (i+3). Because it does not cause immediate chain termination and allows for the incorporation of 3 additional nucleotides, RDV-TP appears to evade proofreading by viral exoribonuclease (an enzyme thought to excise nucleotide analog inhibitors). This delayed chain termination disrupts viral replication.
Remdesivir displays a broad spectrum of in vitro antiviral activity against RNA viruses, including those from the Filoviridae, Paramyxoviridae, Pneumoviridae, and Orthocoronavirinae families. The 50% effective concentration (EC50) against a clinical isolate of SARS-CoV-2 in primary human airway epithelial (HAE) cells is 9.9 nM after 48 hours of treatment. The EC50 against SARS-CoV-2 in the continuous human lung epithelial cell lines Calu-3 and A549-hACE2 is 280 nM after 72 hours and 115 nM after 48 hours of treatment, respectively. Against clinical isolates of the following SARS-CoV-2 variants [Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Epsilon (B.1.429), Gamma (P.1), Iota (B.1.526), Kappa (B.1.617.1), Lambda (C.37), Zeta (P.2), and Omicron variants (B.1.1.529/BA.1, BA.2, BA.2.12.1, BA.2.75, BA.2.86, BA.4, BA.4.6, BA.5, BF.5, BF.7, BQ.1, BQ.1.1, CH.1.1, EG.1.2, EG.5.1, EG.5.1.4, FL.22, HK.3, HV.1, JN.1, XBB, XBB.1.5, XBB.1.5.72, XBB.1.16, XBB.2.3.2, XBC.1.6, and XBF)], remdesivir retains antiviral activity that is similar (i.e., 0.2- to 2.3-fold change in EC50 value) to an earlier lineage SARS-CoV-2 isolate (lineage A). Using the SARS-CoV-2 replicon system, remdesivir also retains similar antiviral activity against Omicron subvariants JN.1.7, JN.1.18, KP.2, KP.3, LB.1, and XBB.1.9.2 compared to the wildtype reference replicon (lineage B).
SARS-CoV-2 isolates with reduced susceptibility to remdesivir have been selected in cell culture. Viral pools expressing amino acid substitutions at V166A, N198S, S759A, V792I, C799F, and C799R in the viral RdRp (nsp12) emerged when selected with GS-441524, the parent nucleoside of remdesivir. When these substitutions were individually introduced into a wild-type recombinant virus, the susceptibility to remdesivir decreased by 1.7- to 3.5-fold. In a cell culture resistance selection experiment, the nsp12 amino acid substitution E802D emerged and resulted in a 1.4- to 2.5-fold reduction in susceptibility to remdesivir. This nsp12 E802D substitution has emerged in 1 remdesivir treated patient and resulted in a 1.4- to 2.5-fold increase in the remdesivir EC50 value. In another section study using a SARS-CoV-2 isolate containing the P323L substitution in viral polymerase, a single amino acid substitution at V166L emerged. In recombinant SARS-CoV-2 with substitutions at P323L alone and P323L + V166L in combination, the reductions in remdesivir susceptibility were 1.3- and 1.5-fold, respectively. In clinical trials, the rate of emerging nsp12 substitutions in patients treated with remdesivir was similar to those who received placebo.
Note: SARS-CoV-2 RNA shedding results from clinical trials indicate that remdesivir does not significantly reduce the amount of detectable SARS-CoV-2 RNA in oropharyngeal or nasopharyngeal swabs or in plasma samples as compared to placebo.
Pharmacokinetics
Remdesivir is administered via intravenous infusion. It is extensively metabolized. The rapid decline in remdesivir plasma concentrations is accompanied by the sequential appearance of the intermediate metabolite GS-704277 and the nucleoside metabolite GS-441524. Within cells, the GS-441524 monophosphate undergoes rapid conversion to the pharmacologically active analog of adenosine triphosphate, GS-443902. The pharmacokinetic parameters of remdesivir and its metabolites (GS-441524 and GS-704277) were evaluated in a multiple dose study involving healthy adults. In this study, the percent bound to human plasma proteins and the blood-to-plasma ratio were 88% to 93.6% and 0.68 to 1 for remdesivir, 2% and 1.19 for GS-441524, and 1% and 0.56 for GS-704277, respectively. Remdesivir is predominately metabolized by carboxylesterase 1 (CES1, 80%), with minor contributions from cathepsin A (CatA, 10%) and CYP3A (10%). The metabolite GS-704277 is further metabolized by histidine triad nucleotide-binding protein 1 (HINT1), while GS-441524 is not significantly metabolized. The elimination half-lives for remdesivir, GS-441524, and GS-704277 are 1 hour, 27 hours, and 1.3 hours, respectively. The major route of elimination for remdesivir and GS-704277 is via metabolism, with only 10% of remdesivir and 2.9% of GS-704277 being excreted in the urine. GS-441524 is primarily eliminated via glomerular filtration and active tubular secretion (49% in urine and 0.5% in feces).
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CES1, CatA, OATP1B1, OATP1B3, MATE1, P-gp, UGT1A1
In vitro, remdesivir is a substrate for the enzymes CYP3A4, CES1, and CatA and the drug transporters organic anion transporting polypeptide 1B1 (OATP1B1) and P-glycoprotein (P-gp); the metabolite GS-704277 is a substrate for OATP1B1 and OATP1B3. Remdesivir is an in vitro inhibitor of CYP3A4, UDP glucuronosyltransferase 1A1 (UGT1A1), OATP1B1, OATP1B3, and the multidrug and toxin extrusion protein 1 (MATE1). However, no clinically significant effects on substrates of UGT1A1 or MATE1 are expected and in an in vivo study of healthy volunteers, remdesivir did not inhibit OATP1B1/1B3 and was a weak inhibitor for CYP3A. No inhibitory effects have been identified for GS-704277 or GS-441524. Based on a drug interaction study, no clinically significant drug interactions are expected with inducers of CYP3A4 or inhibitors of OATP1B1/1B3 and P-gp.
Remdesivir is not suitable for oral delivery due to significant first-pass clearance.
After multiple remdesivir doses to healthy adults, the maximum plasma concentrations (Cmax) and systemic exposures (AUC) were 2,700 ng/mL and 1,710 ng x hour/mL for remdesivir, 143 ng/mL and 2,410 ng x hour/mL for GS-441524, and 198 ng/mL and 392 ng x hour/mL for GS-704277, respectively. The times to reach peak concentration were 0.67 to 0.68 hours for remdesivir, 1.51 to 2 hours for GS-441524, and 0.75 hours for GS-704277.
Pregnancy And Lactation
The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend that remdesivir be offered to pregnant patients if indicated. When evaluating the risk and benefits of remdesivir, consider that COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. Data from a clinical trial, published reports, the COVID-PR pregnancy exposure registry, and compassionate use of remdesivir in pregnant patients have not identified a drug-associated risk of major birth defects, miscarriages, or adverse maternal or fetal outcomes following exposure in the second and third trimester. However, there are insufficient pregnancy data available to evaluate the risk of remdesivir exposure during the first trimester. A non-randomized, open-label clinical study (IMPAACT 2032) evaluated the safety of up to 10 days of treatment with remdesivir in 25 hospitalized pregnant and 28 hospitalized non-pregnant patients of childbearing potential. Of the 25 pregnant patients, median gestational age was 28 weeks at baseline (range: 22 to 33 weeks) and approximately half of the patients were in each of the second and third trimesters of pregnancy. The adverse reactions observed were consistent with those observed in clinical trials of remdesivir in adults. A systemic review of 13 observational studies that included 113 pregnant patients found few adverse effects from the use of remdesivir during pregnancy. The most common adverse event was mild elevations in transaminase concentrations. Among 95 pregnant patients with moderate, severe, or critical COVID-19 who were included in a secondary analysis of data from a COVID-19 pregnancy registry in Texas, the composite maternal and neonatal outcomes were similar between those who received remdesivir (n = 39) and those who did not. Remdesivir was discontinued in 16.7% of patients due to elevated transaminase concentrations; however, it was not possible to determine if the elevated concentrations were due to the drug, COVID-19, or pregnancy-related conditions. In another report, remdesivir was well tolerated among 67 pregnant and 19 postpartum patients (median postpartum day = 1; range 0 to 3 days) who were hospitalized with severe COVID-19 and received remdesivir through a compassionate use program. In this study, 45 deliveries were observed. No neonatal deaths occurred during the 28-day observation period; however, 1 spontaneous miscarriage occurred at 17 weeks gestation in a mother with concurrent S. aureus bacteremia, endocarditis, and septic arthritis. In animal studies involving rats and rabbits, no adverse effects on embryo-fetal development were observed after exposure to the predominant circulating metabolite (GS-441524) that were 4-times the exposure at the recommended human dose.
A published case report describes the presence of remdesivir and active metabolite GS-441524 in human milk. Available data (n=11) from pharmacovigilance reports do not indicate adverse effects on breast-fed infants from exposure to remdesivir and its metabolites through breast milk. There are no available data on the effects of remdesivir on milk production. The National Institutes of Health (NIH) states that concentrations of remdesivir that would reach a breast-fed infant are estimated to be low; thus, if indicated, treatment should be offered to a lactating patient and breast-feeding can continue without interruption. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.