MAVER (REDMESIVIR)
MAVER
(REMDESIVIR)
1.AUTHORIZES USE
Maver (Remdesivir) is authorized for use under an EUA for Vestment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with oxygen saturation (Sp021594% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECM()) Specifically Mover (Remdesivir) is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous agent is clinically appropriate.
2. DOSAGE AND
ADMINISTRATION
2.1- General Information
The optimal dosing and duration of treatment is unknown. The suggested dose and duration may be updated as data from clinical trials becomes available
· Adult and pediatnc patients (>28 days old) must have an eGFR determined and full-term neonates (27 days to 528 days old) must have serum creatinine determined before dosing of Maver (Remdesivir).
· Hepatic laboratory testing should be performed in all patients prior to starting Maver (Remdesivir) and dairy while receiving Maver (Remdesivir).
· Maver (Remdesivir) should be administered via intravenous (IV) infusion only Do not administer as an intramuscular (PA) injection.
2.2 Adult Patients
The recommended dosage in adults requiring invasive mechanical ventilation and/or ECMO 200 mg on Day 1 followed by once-daily maintenance doses of Maver (Remdesivir) 100 mg for 9
· The recommended dosage in adults not requiring invasive mechanical ventilation and/or ECMO is a single dose of Maver (Remdesivir) 200 ngtenance doses of Maver (Remdesivir) 100 mg for 4 days If a pabent does not demonstrate clinical mg on Day 1 followed tv improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).
· Maver (Remdesivir) is to be administered via intravenous infusion in a total volume of up to Dosane and administration (2.7)].
All adult patients must have creatinine clearance determined before dosing [see Dosage and Administration (2.5)].
Hepatic laboratory testing should be performed in all patients prior to starting Maver (Remdesivir) and daily while receiving Maver (Remdesivir) dosing [see Dosage and Administration (2.6)].
2.3 Pediatric Patients
Dosing in pediatric patients is based upon physiologically based (P8PIC) modeling and simulation
subjects
The recommended pediatric dose for pediatric patients weighing according o the patients weight [see Dosage and Administration (2.8)1
· For pediatric patients with body weight 240 kg requiring invasive mechanical ventilation and/or ECMO, the adult dosage regimen of one loading dose of Maver (Remdesivir) 200 mg IV (infused over 30 to 120 minutes) on Day 1 followed by Maver (Remdesivir) 100 mg IV (infused
· For pediatric patients with body weight 240 kg not requiring invasive mechanical ventilation and/or ECMO. the adult dosage regimen of one loadmg dose of Maver iRerndestvirl 200 mg Yi infused over 30 to 120 minutes) on Day I followed by Maver (Remdemvir) 100 mg IV (infused treatment may be extended for up to 5 additional days (i.e.. up to a total of 10 days). Use of the adult dose in these pediatric patients is expected to maintain exposures of [toga Maver (Remdesivir) and the nucleoside analog GS-441524 generally within the expected adult steady-state exposure range following administration of the adult. therapeutic dosage regimen in healthy volunteers (N=20 Study over 30 to 120 minutes) once daily for 4 days (days 2 through 5) will be administered. If a patient does not demonstrate clinical improvement, GS-US-399 5505).
· For pediatric patients with body weight between 3.5 kg and <40 kg. use Maver (Remdesivir) for injection. 100 mg, Lyophilized only. Administer a body weight-based dosing regimen of one loading dose of Maver (Remdesivir) 5 mg/kg IV (infused over 30 to 120 min) on Day i followed by Maver (Remdesivir) 2.5 mg/kg IV (infused over 30 to 120 min) once daily for 9 days (for pediatric patients requiring invasive mechanical ventilation and/or ECMO, days 2 through 10) or for 4 days (for pediatric patients not requiring invasive mechanical ventilation and/or ECMO, days 2 through 5). If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (ie, upic a total of 10 days) Use of this weight-based dosing regimen is expected to maintain Maver (Remdesivir) exposure that is comparable to that observed in adults while limiting the exposure of the nucleoside analog GS441524 in very young children Pediatric patents (>28 days old) must have an eGFR determined and full-term neonates (7 dayS to 028 days old) must have serum creatinine determined before dosing (see Dosage and Administration (2.5)). Hepatic laboratory testing should be performed in all patients prior to starting Maver (Remdesivir) and day when rooming Mere, (Remdesivir) dosing [sce Dosage and Administration (2.6)).
2.4 Pregnancy
Maver (Remdesivir) should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus
2.5 Renal Impairment
The pharmacokinetics of Maver (Remdesivir) have not been evaluated in patients with renal impairment Adult and pediatric patients (>28 old) most have an eGFR determined and full-term neonates (27 days to 528 days old) must have serum creatinine determined before dosing. Because the excipient sulfobutylether-(B-cyclodexthn sodium salt (SBECD) is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as Maver (Remdesivir)) is not recommended in adults and pediatric patients days (>28 days old) with eGFR less than 30 mL per minute or in full-term neonates (27 days and 528 days old) with serum creatinine clearance 21 mg/dt unless the potential benefit outweighs the potential risk
2.6-Hepatic Impairment
The pharmacokinebcs of Maven (Remdesivir) have not been evaluated in patients with hepatic impairment. It is not known if dosage adjustment is needed in patients with hepatic impairment and Maver (Remdesivir) should only be used in patients with hepatic impairment if the potential Hepatic laboratory testing should be performed in all patients peon to staging Maver (Remdesivir) and daily while receiving Maver (Remdesivir).benefit outweighs the potential risk (seeWarnings and Precautions 15.2)].
2.7-Adult Dose Preparation and Administration
Maver (Remdesivir) for Injection, 100 mg, Lyophilized Reconstitution Instructions Remove the required number of single-dose vial(s) from storage. For each vial,
· Aseptically reconstitute Maver (Remdesivir) Lyophilized by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial • Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial
· Immediately Shake the vial for 30 seconds.
· Alloe 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 procedure as necessary until the contents of the vial are completely dissolved.
· Following reconstitution, each vial contains 100 mg/20 of Maver (Remdesivir) solution.
· Parenteral drug products should be inspected visually for particulate matter and discoloration prior to artninistration. whenever solution and container permit.
· After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C )36°F to 46°9).
Dilution Instructions
Care should be taken during admixture to preyed Inadvertent microbiecontamination. As there is no preservative or bactenostatic agent present in this product aseptic technique must be used in preparation of the final parenteral sotubon It is always recommended to administer IV inedmabon immediately afterpreparation when possible. from the infusion bag. Using Table 1. determine the volume of 0.9% saline to withdraw
• Withdraw the required volume of saline from the bag using an appropriately sized syringe and needle. Discard the seine that was withdrawn from the bag
• Withdraw the required volume of reconstituted Maver (Remdesivir) for injection from the Maver (Rerndesivir) vial using an appropriately syringe per Table 1 Discard any unused portion remaining in the Maver (Remdesivir) vial.
• Transfer the required volume of reconstituted Maver (Remdesivir) for injection to the selected Mullion bag.
• Gently invert the bag 20 times to mix the solution in the bag. Do not shake.aced
• The prepared diluted solution is stable for d hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of Maver (Remdesivir) injection with IV solutions and medications other than saline is not known. Administer the diluted solution with the infusion rate described in Table 2.
2.8- Pediatric Dose Preparation and Administration
Maver (Remdesivir) for Injection, 100 mg, Lyophilized
For pediatric patients with body weight between 3.5 kg and <40 kg, use Maver (Remdesivir) for injection, 100 mg. Lyophilized anu Reconstitution Instructions
Remove the required number of single-dose vial(s) from storage. For each vial:
• Aseptically reconstitute Maver (Remdesivir) Lyophilized by addition of 19 mL of Sterile and needle per vial.
• Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.
• Immediately shake the via for 30 seconds.
• Allow the contents of the vial to settle for 2 to 3 minutes. A clear solulion 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 procedure as necessary until the contents of the vial are completely dissolved.
• Parenteral drug products should be inspected visually for particulate metier and discoloration prior to administration, whenever solution and container permit.
• After reconstitution. the total storage time before administration should not exceed 4 hours at room temperature or 24 hours refrigerated temperature (2°C to 8°C [36°F to 46°F]).
Dilution Instructons
Care should be taken during mambas to prevent inadvertent microbe( contamination. As there is no preservative or bacteriostalic present in this product. aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparabon when possible.
• Using Table 3 and Table 4. determine the volume of 0.9% saline to withdraw from the infusion bag. Table 3 and Table 4 include the volume requirements for preparing pediatric weight-based dosing regimens at 5mg/kg and 2.5 mg/kg, respectively
• Withdraw the required volume of saline from the bag using an appropriately sized syringe and needle. Discard the saline withdrawn from the bag.
• Withdraw the required volume of reconstituted Maver (Remdesivir) for injection from the Maver (Remdesivir) vial using an appropriate sized syringe per Table 3 or 4. Discard any unused portion remaining in are Maver (Remdesivir) vial.
• Transfer the required volume of reconstituted Maver (Remdesivir) for injection to the selected infusion bag.
• Gently invert the bag 20 limes to mix the solution in the bag. Do notshake
• The prepared diluted solution is stable for 4 hours at room temperature '20°C to 25°C [68°F to 77°F)) or 24 hours in the refrigerator 2°C to 8°C (36°F to 46°F) (including any time before dilution into intravenous infusion fluids).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility (Remdesivir) injection with IV solutions and medications other than saline a not known.
Administer the diluted solution with the infusion rate described in Table 5
a. Note Rate of infusion may be adjusted based on total volume to be Infused.
2.9-Storage of Prepared Dosages
Lyophilized
After reconstitution, vials can be stored up to 4 hours at room temperature below 30°C (86 °F)prior to administration or 24 hours at refrigerated emperature (2°C to 8°C [36°F to 46°F) Dilute within the some day as administration. Diluted Infusion Solution
Store diluted Maver (Remdesivir) solution for infusion up to 4 hours at room temperature (20°C to 25°C (68°F to 77°F]) or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]). This product contains no preservative. Any unused portion of a single-dose Maver (Remdesivir) vial should be discarded after a diluted solution
IMPORTANT:
is prepared. Maintain adequate records showing receipt, use. and disposition of Maver (Remdesivir). For unused intact vials, maintain adequate records showing disposition of Maver (Remdesivir); do not discard unused intact vials.
3. DOSAGE FORMS AND
STRENGTHS
• Maver (Remdesivir) for injection. 100 mg Each single-dose vial of Maver (Remdesivir) for injection, 100 mg. contains a sterile, preservative-free white to off-white to yellow Lyophilized that is to be reconstituted with 19 mL of Sterile Water for Injection and diluted into 0.9% saline prior to administration by intravenous infusion.
4. CONTRAINDICATIONS
Maver (Remdesivir) is contraindicated in patients with known hypersensitivity to any ingredient of Maver (Remdesivir) [see Product Description (13)).
5. WARNINGS AND
PRECAUTIONS
There are limited clinical data available for Maver (Remdesivir). Sepous and unexpected adverse events may occur that have not been previously reported with Maver (Remdesivir) use.
5.1 Infusion-Reiated Reactions
Infusion-related reactions have been observed during. been temporally associated with. administration of Maver (Remdesivir). Signs and symptoms may include hypotension. nau sea. vomiting. diaphoresis, and shivering. If signs and symptoms of a clinically significant infusion reaction occur, immediately discontinue administrabon of Maver (Remdesivir) and initiate appropriate treatment. The use of Maver (Remdesivir) is contraindicated in patients with known hypersensitivity to Maven (Remdesivir).
5.2- Increased Risk of Transaminase Elevations
Transaminase elevations have been observed in the Maver (Remdesivir) clinical development program. including in healthy volunteers and patients with COVID-1 in healthy volunteers who received up to 150 mg daily for 14 days. alanine aminotransferase (ALT) elevations were observed in the majority of patients, including elevations to up to 10 times baseline values in one subject without evidence of clinical hepatitis: no > Grade 3 adverse events were observed
Transaminase elevations have also been reported in patients with COVID-19 who received Maver (Remdesivir), including one patient with ALT elevation up to 20 times the upper limit of normal. As transaminase elevations have been reported as a component of COVID-19 in some patients discerning the contribution of Maver (Remdesivir) to transaminase elevations in this patient population is challenging. Hepatic laboratory testing should be performed in all patients prior to starting Maver (Remdesivir) and daily while receiving Maver (Remdesivir)
• Maver (Remdesivir) should not be initialed in patients with ALT 5 times the upper limit of normal at baseline
• Maver (Remdesivir) should be discontinued in patients who develop: o ALT 5 times the upper time of normal during treatment with Maver (Remdesivir). Maver the upper limit of normal
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