8:18.32 Nucleosides and Nucleotides
Generic Name
| Special Alerts:
September 20, 2024 TOPIC: One Lot of Veklury (Remdesivir) for Injection 100 mg/vial by Gilead: Recall - Due to the Presence of a Glass Particle ISSUE: Gilead Sciences is recalling of one lot of Veklury (Remdesivir) for Injection 100 mg/vial because Gilead received a customer complaint and confirmed the presence of a glass particle in the vial during the company's investigation. For more information about this recall, see the full announcement on the FDA website: www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/gilead-issues-voluntary-nationwide-recall-one-lot-veklury-remdesivir-injection-100-mgvial-due. |
Remdesivir is available as a lyophilized powder in preservative-free, single-dose vials containing remdesivir 100 mg and betadex sulfobutyl ether sodium 3 g with hydrochloric acid and/or sodium hydroxide for pH adjustment.3581 Vial contents are packaged under vacuum.3581
The contents of each vial should be reconstituted with 19 mL of sterile water for injection; vials should be discarded if the vacuum does not draw the diluent into the vial.3581 Reconstitution with isotonic diluents (e.g., dextrose 5%, sodium chloride 0.9%) results in a hypertonic solution;711 therefore, only sterile water for injection should be used for reconstitution to limit the osmolality of the solution.3581 However, if sterile water for injection is not available, the manufacturer states that sodium chloride 0.9% may be used for reconstitution.711 Immediately after adding the diluent, vials should be shaken for 30 seconds, then the contents allowed to settle for 2 to 3 minutes.3581 If the contents are not completely dissolved, the vial should be shaken again for 30 seconds and the contents allowed to settle for 2 to 3 minutes.3581 This procedure should be repeated as necessary until the contents of the vial are completely dissolved and a clear, colorless to yellow solution free of visible particles results.3581 The vial should be discarded if the contents are not completely dissolved.3581 The resulting reconstituted solution has a remdesivir concentration of 5 mg/mL.3581 The reconstituted solution must be diluted in sodium chloride 0.9% prior to administration.3581 Alternatively, the manufacturer states that dextrose 5% also may be used for dilution if water for injection was used to reconstitute the lyophilized power.711
Pediatric patients from birth to less than 18 years of age weighing at least 1.5 to less than 40 kg: Loading and maintenance doses of remdesivir, when reconstituted with sterile water for injection, must be diluted in sodium chloride 0.9% to a final concentration of 1.25 mg/mL.3581 The final diluted solution for infusion may be prepared in a prefilled 25-, 50-, or 100-mL sodium chloride 0.9% bag, or an empty infusion bag.3581 Infusion volumes less than 50 mL may be prepared in an appropriately sized syringe.3581
When preparing the diluted solution in a syringe, withdraw the volume of the appropriate dose of the reconstituted solution into an appropriately sized syringe followed by the required volume of sodium chloride 0.9% to achieve a final remdesivir concentration of 1.25 mg/mL.3581 Gently invert the syringe 20 times to mix the solution; do not shake.3581
When preparing the diluted solution in a prefilled bag of sodium chloride 0.9%, first remove a volume of fluid equal to that of the appropriate dose of the reconstituted drug plus a quantity sufficient to achieve a final remdesivir concentration of 1.25 mg/mL, then transfer the reconstituted drug to the bag using an appropriately sized syringe.3581 After adding the reconstituted solution to the infusion bag, gently invert the bag 20 times to mix the solution; do not shake.3581
When preparing the diluted solution an empty infusion bag, transfer the volume of the appropriate dose of the reconstituted solution to the bag followed by a volume of sodium chloride 0.9% sufficient to achieve a final remdesivir concentration of 1.25 mg/mL.3581
Adults and pediatric patients weighing at least 40 kg: Loading and maintenance doses of remdesivir, when reconstituted with sterile water for injection, must be diluted in either 100- or 250-mL bags of sodium chloride 0.9% after first removing and discarding a volume of infusion fluid equal to the volume of the appropriate dose of the reconstituted solution to be added.3581 After adding the reconstituted solution to the infusion bag, gently invert the bag 20 times to mix the solution; do not shake.3581 The manufacturer states that the solution reconstituted with sterile water for injection may also be diluted in 100- or 250-mL bags of dextrose 5% after first removing a proportionate amount of infusion fluid from the bag.711 If sodium chloride 0.9% was used to reconstitute remdesivir lyophilized powder, the manufacturer recommends 100- or 200-mg doses be diluted only in 250-mL bags of sodium chloride 0.9% after first removing a proportionate amount of infusion fluid from the bag.711 Dilution of a 200-mg dose of remdesivir that was reconstituted with sodium chloride 0.9% in a 100-mL bag of sodium chloride 0.9% results in a solution with osmolality greater than 400 mOsm/kg, which may affect tolerability.711
Remdesivir may also be available as a 5-mg/mL concentrate for injection in preservative-free single-dose vials containing 20 mL of the concentrate for injection.3581 Vials contain 6 g of betadex sulfobutyl ether sodium and water for injection; hydrochloric acid and/or sodium hydroxide also may be present to adjust the pH.3581 The concentrate for injection must not be used to prepare intravenous infusion solutions for pediatric patients weighing less than 40 kg.3581 The concentrate for injection must be diluted only in sodium chloride 0.9% prior to administration.3581 Prior to dilution, the vials should be allowed to come to room temperature (20 to 25°C).3581 Vials should be visually inspected to ensure that the container closure is free of defects and that the solution is free of particulate matter and discoloration.3581
Adults and pediatric patients weighing at least 40 kg: Loading and maintenance doses of remdesivir prepared from the concentrate for injection must be diluted in 250-mL bags of sodium chloride 0.9% after first removing and discarding a volume of infusion fluid equal to the volume of the appropriate dose of the concentrate for injection to be added.3581 To withdraw the concentrate for injection from the vial, the plunger rod of an appropriately sized syringe should be pulled back to fill the syringe with approximately 10 mL of air.3581 The air should be injected into the vial above the level of the solution.3581 The vial should then be inverted in order to withdraw the appropriate dose of the concentrate for injection; withdrawal of the final 5 mL of solution remaining in the vial requires more force.3581 After adding the concentrate for injection to the infusion bag, the bag should be gently inverted 20 times to mix the solution; the bag should not be shaken.3581
pH
Remdesivir lyophilized powder has a pH from 3.4 to 3.6 before reconstitution and dilution.1685 Following reconstitution of the lyophilized powder with sterile water for injection and dilution in sodium chloride 0.9% to a volume of 100 or 250 mL, the final diluted solution for infusion has a pH from 3.9 to 4.1.1685
Osmolality
Remdesivir lyophilized powder reconstituted as recommended with sterile water for injection has an osmolality of 483 mOsm/kg.711 Following reconstitution of the lyophilized powder with sterile water for injection, a 100-mg dose further diluted in sodium chloride 0.9% to a volume of 100 or 250 mL has an osmolality of 318 or 299 mOsm/kg, respectively, and a 200-mg dose diluted in sodium chloride 0.9% to a volume of 100 or 250 mL has an osmolality of 352 or 314 mOsm/kg, respectively.711 Dilution of remdesivir reconstituted with sterile water for injection in dextrose 5% produced solutions with osmolalities similar to those using sodium chloride 0.9% as a diluent.711
When reconstituted with sodium chloride 0.9%, remdesivir solution has an osmolality of 780 mOsm/kg.711 Following reconstitution of the lyophilized powder with sodium chloride 0.9%, a 100-mg dose further diluted in sodium chloride 0.9% to a volume of 100 or 250 mL has an osmolality of 378 or 327 mOsm/kg, respectively, and a 200-mg dose diluted in sodium chloride 0.9% to a volume of 100 or 250 mL has an osmolality of 468 or 361 mOsm/kg, respectively.711
Trade Name(s)
Veklury
Remdesivir is administered by intravenous infusion only; the drug should not be administered by any other route.3581 Remdesivir solutions prepared as directed in sodium chloride 0.9% should be infused over 30 to 120 minutes.3581 Following infusion of remdesivir, the line should be flushed with a sufficient volume (i.e., a volume at least greater than the priming volume of the infusion tubing) of sodium chloride 0.9%, to be administered at the same infusion rate as the remdesivir infusion, to ensure complete administration of the remdesivir dose.2019
The lyophilized formulation of remdesivir is a white to off-white to yellow powder that forms a clear solution upon reconstitution.3581 Intact vials of remdesivir lyophilized powder should be stored at temperatures less than 30°C.3581 The manufacturer states that the lyophilized powder has been stored in the original vial at 40°C with 75% relative humidity, 60°C, and -20 to 14°C for acceptable durations of 6 months, 1 month, and 1 month, respectively.1689 The reconstituted solution should be used immediately to prepare the diluted solution for infusion.3581
Remdesivir concentrate for injection is a clear, colorless to yellow solution free of visible particulates.3581 Intact vials of remdesivir concentrate for injection should be stored at 2 to 8°C; however, intact vials may be stored at room temperature (20 to 25°C) for up to 12 hours prior to dilution.3581
Because no preservatives are present in either formulation, any unused solution remaining in a vial after preparation of the diluted solution for infusion should be discarded.3581 The diluted solution for infusion should be visually inspected for particulate matter and discoloration prior to administration; if particulate matter is present or discoloration occurs, the diluted solution for infusion should be discarded.3581 Diluted solutions in infusion bags may be stored for up to 24 hours at room temperature (20 to 25°C) or 48 hours at 2 to 8°C;3581; 3779 however, the manufacturer recommends administering the diluted solution for infusion immediately after preparation when possible.3581 The manufacturer also recommends that diluted solutions for infusion prepared with either formulation should be administered within the same day as dilution.3581 Diluted solutions prepared in syringes should be used immediately after preparation.3581
The manufacturer states that remdesivir should not be administered simultaneously with any other drugs.3581
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Infusion Solutions
In a simulated Y-site administration study, remdesivir (Gilead) 1 mg/mL in sodium chloride 0.9% was physically compatible with Ringer's injection, acetated for up to 4 hours.2736
For a list of references cited in the text of this monograph, search the monograph titled References.