Drug Interaction:
Drug Interactions- summary Inform patients that VEKLURY may interact with other drugs.
Advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including chloroquine phosphate or hydroxychloroquine sulfate.
DRUG INTERACTIONS- details
Due to antagonism observed in cell culture, concomitant use of VEKLURY with chloroquine phosphate or hydroxychloroquine sulfate is not recommended.
Drug-drug interaction trials of VEKLURY and other concomitant medications have not been conducted in humans
. Remdesivir and its metabolites are in vitro substrates and/or inhibitors of certain drug metabolizing enzymes and transporters.
The clinical relevance of these in vitro assessments has not been established
Indication:
U.S. FDA APPROVED DRUGS DURING 2020
Sr.No- 42
Name of the Drug- VENKLURY
Active Ingredient - Remdesvir
Pharmacological Classification-
To treat Covid-19
Date of Approval- 10/22/2020
(Ref- FDA approved List 2020)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
VEKLURY safely and effectively.
See full prescribing information for VEKLURY. VEKLURY® (remdesivir) for injection, for intravenous use VEKLURY® (remdesivir) injection, for intravenous use
Initial U.S. Approval: 2020
INDICATIONS AND USAGE
VEKLURY is a SARS-CoV-2 nucleotide analog RNA polymerase inh bitor indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization.
VEKLURY should only be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care.
Adverse Reaction:
ADVERSE REACTIONS-
The most common adverse reactions (incidence greater than or equal to 5%, all grades) observed with treatment with VEKLURY are nausea, ALT increased, and AST increased.
Contra-Indications:
CONTRAINDICATIONS-
VEKLURY is contraindicated in patients with a history of clinically significant hypersensitivity reactions to VEKLURY or any components of the product.
WARNINGS AND PRECAUTIONS-
• Hypersensitivity including infusion-related and anaphylactic reactions: Hypersensitivity reactions have been observed during and following administration of VEKLURY.
Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent signs and symptoms of hypersensitivity.
If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue administration of VEKLURY and initiate appropriate treatment.
• Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and have also been reported in patients with COVID-19 who received VEKLURY. Perform hepatic laboratory testing in all patients before starting VEKLURY and while receiving VEKLURY as clinically appropriate. Consider discontinuing VEKLURY if ALT levels increase to greater than 10 times the upper limit of normal. Discontinue VEKLURY if ALT elevation is accompanied by signs or symptoms of liver inflammation.
• Risk of reduced antiviral activity when coadministered with chloroquine phosphate or hydroxychloroquine sulfate: Coadministration of VEKLURY and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on cell culture data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of VEKLURY.
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Dosages/ Overdosage Etc:
DOSAGE AND ADMINISTRATION-
• Testing: In all patients, before initiating VEKLURY and during treatment as clinically appropriate, perform renal and hepatic laboratory testing and assess prothrombin time.
• Recommended dosage in adults and pediatric patients 12 years of age and older and weighing at least 40 kg: a single loading dose of VEKLURY 200 mg on Day 1 followed by once-daily maintenance doses of VEKLURY 100 mg from Day 2 infused over 30 to 120 minutes.
• For patients not requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days for a total treatment duration of up to 10 days.
• For patients requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.
• Administer VEKLURY via intravenous (IV) infusion over 30 to 120 minutes.
• Renal impairment: VEKLURY is not recommended in patients with eGFR less than 30 mL/min.
• Dose preparation and administration: Refer to the full prescribing information for further details for both formulations.
• Storage of prepared dosages: VEKLURY contains no preservative.
DOSAGE FORMS AND STRENGTHS -
• For injection: 100 mg of remdesivir as a lyophilized powder, in a single-dose vial.
• Injection: 100 mg/20 mL (5 mg/mL) remdesivir, in a single-dose vial.
Patient Information:
PATIENT COUNSELING INFORMATION-
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity Reactions- Inform patients that hypersensitivity reactions have been seen in patients receiving VEKLURY during and after infusion.
Advise patients to inform their healthcare provider if they experience any of the following: changes in heart rate; fever; shortness of breath, wheezing; swelling of the lips, face, or throat; rash; nausea; sweating; or shivering(Increased
Risk of Transaminase Elevations- Inform patients that VEKLURY may increase the risk of hepatic laboratory abnormalities. Advise patients to alert their healthcare provider immediately if they experience any symptoms of liver inflammation
Drug Interactions- Inform patients that VEKLURY may interact with other drugs.
Advise patients to report to their healthcare provider the use of any other prescription or nonprescription medication or herbal products, including chloroquine phosphate or hydroxychloroquine sulfate.
Pregnancy - Inform patients to notify their healthcare provider immediately in the event of a pregnancy
Lactation- Inform mothers that it is not known whether VEKLURY can pass into their breast milk.
VEKLURY is a trademark of Gilead Sciences, Inc., or its related companies.
All other trademarks referenced herein are the property of their respective owners. © 2020 Gilead Sciences, Inc. All rights reserved
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action- Remdesivir is an antiviral drug with activity against severe acute respiratory syndrome coronavirus 2
2. Pharmacodynamics- Remdesivir and metabolites exposure-response relationships and the time course of pharmacodynamics response are unknown.
3.. Pharmacokinetics- The pharmacokinetic (PK) properties of remdesivir and metabolites are provided below-
Absorption Tmax (h)a 0.67-0.68 1.51-2.00 0.75-0.75
Distribution % bound to human plasma proteins 88-93.6b 2 1
Blood-to-plasma ratio 0.68-1.0 1.19 0.56
Elimination t1/2 (h)c 1 27 1.3
Metabolism Metabolic pathway(s) CES1 (80%) Cathepsin A (10%) CYP3A (10%)
Excretion Major route of elimination
Metabolism- Glomerular filtration and active tubular secretion
Metabolism % of dose excreted in urined 10 49 2.9 % of dose excreted in fecesd ND 0.5 ND ND=not detected
Specific Populations- Pharmacokinetic differences based on sex, race, age, renal function, and hepatic function on the exposures of remdesivir have not been evaluated.
Pediatric Patients - The pharmacokinetics of VEKLURY in pediatric patients have not been evaluated.
Using modeling and simulation, the recommended dosing regimen is expected to result in comparable steady-state plasma exposures of remdesivir and metabolites in patients 12 years of age and older and weighing at least 40 kg as observed in healthy adults .
Drug Interaction Studies- Clinical drug-drug interaction studies have not been performed with VEKLURY. In vitro, remdesivir is a substrate for drug metabolizing enzyme CYP3A4, and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OATP1B1) and P-glycoprotein (P-gp) transporters.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary - Available data from published case reports and compassionate use of remdesivir in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
2. Lactation Risk Summary- There are no available data on the presence of remdesivir in human milk, the effects on the breastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VEKLURY and any potential adverse effects on the breastfed child from VEKLURY or from the underlying maternal condition.
Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.
3.Pediatric use - The safety and effectiveness of VEKLURY for the treatment of COVID-19 have been established in pediatric patients 12 years and older and weighing at least 40 kg. Use in this age group is based on extrapolation of pediatric efficacy from adequate and well-controlled studies in adults
The safety and effectiveness of VEKLURY have not been established in pediatric patients younger than 12 years of age or weighing less than 40 kg.
4.Geriatric Use Reported clinical experience has not identified differences in responses between the elderly and younger patients.. No dosage adjustment is required in patients over the age of 65 years.
5. Renal Impairment The pharmacokinetics of VEKLURY have not been evaluated in patients with renal impairment. Patients with eGFR greater than or equal to 30 mL per minute have received VEKLURY for treatment of COVID-19 with no dose adjustment of VEKLURY
6.Hepatic Impairment The pharmacokinetics of VEKLURY have not been evaluated in patients with hepatic impairment. Perform hepatic laboratory testing in all patients before starting VEKLURY and while receiving VEKLURY as clinically appropriate.
OVERDOSAGE-
There is no human experience of acute overdosage with VEKLURY. Treatment of overdose with VEKLURY should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with VEKLURY.
Manufacturer Details