Usage
- Remdesivir is indicated for the treatment of coronavirus disease 2019 (COVID-19) in adult and pediatric patients (birth to less than 18 years of age weighing at least 1.5 kg) who are:
- Hospitalized, or
- Not hospitalized and have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.
- Pharmacological Classification: Antiviral Agent; Nucleoside analogue RNA polymerase inhibitor.
- Mechanism of Action: Remdesivir acts as a prodrug of the active nucleoside triphosphate metabolite (GS-441524). GS-441524 inhibits viral RNA polymerase, thereby disrupting viral replication.
Alternate Names
- GS-5734
- Veklury (brand name)
How It Works
- Pharmacodynamics: Remdesivir’s active metabolite (GS-441524) incorporates into nascent viral RNA chains, causing premature termination. This inhibits viral RNA polymerase, which ultimately disrupts viral replication.
- Pharmacokinetics:
- Absorption: Following intravenous administration, remdesivir is rapidly converted to its active metabolite.
- Metabolism: Remdesivir is metabolized to the pharmacologically active nucleoside triphosphate, GS-441524, intracellularly.
- Elimination: Remdesivir and its metabolites are primarily eliminated by the kidneys (approximately 74%), with a smaller portion eliminated through the feces.
- Mode of Action: Remdesivir acts as a delayed chain terminator of viral RNA synthesis. The active metabolite competes with adenosine triphosphate for incorporation into RNA chains by viral RNA polymerase.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Inhibits viral RNA polymerase.
- Elimination Pathways: Predominantly renal excretion (approximately 74%), with some fecal elimination.
Dosage
Standard Dosage
Adults (and Pediatric Patients ≥40 kg):
- Loading dose: 200 mg IV on Day 1.
- Maintenance dose: 100 mg IV daily from Day 2.
- Treatment Duration:
- Hospitalized patients not requiring invasive mechanical ventilation and/or ECMO: 5 days; may be extended to 10 days if no clinical improvement is observed.
- Hospitalized patients requiring invasive mechanical ventilation and/or ECMO: 10 days.
- Non-hospitalized patients: 3 days
Children (<40 kg):
- Refer to Table 1 for detailed pediatric dosing recommendations based on weight. Use the lyophilized powder formulation for pediatric patients 1.5kg to <40kg. Use the concentrated solution for children ≥40kg.
- Neonates (<28 days old, ≥1.5 kg): Loading dose: 2.5 mg/kg IV on Day 1; Maintenance dose: 1.25 mg/kg IV daily from Day 2.
- Infants/Children (≥28 days old, <40 kg):
- 1.5kg to <3kg: Loading dose: 2.5 mg/kg IV on Day 1; Maintenance dose: 1.25 mg/kg IV daily.
- 3 kg to <40 kg: Loading dose: 5 mg/kg IV on Day 1; Maintenance dose: 2.5 mg/kg IV daily.
Special Cases:
- Elderly Patients: No dosage adjustment necessary.
- Patients with Renal Impairment: No dosage adjustment necessary.
- Patients with Hepatic Dysfunction: No dosage adjustment necessary. (Although not extensively studied, available data suggest no adjustment necessary).
- Patients with Comorbid Conditions: Consider comorbidities when assessing the risk-benefit of Remdesivir therapy. Monitor closely for adverse events.
Clinical Use Cases
The dosage guidelines remain the same for clinical scenarios including intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations.
Dosage Adjustments
Generally, no dose adjustments are required based on renal or hepatic impairment. However, close monitoring for adverse events is advised.
Side Effects
Common Side Effects:
- Nausea
- Elevated liver enzymes (ALT, AST)
- Increased Prothrombin Time
Rare but Serious Side Effects:
- Hypotension (potentially leading to cardiac arrest)
- Hepatic dysfunction
- Hypersensitivity reactions
Long-Term Effects:
Limited data are available on long-term effects. Monitor patients for potential renal or hepatic complications following treatment.
Adverse Drug Reactions (ADR):
- Anaphylaxis
- Acute kidney injury
- Hepatotoxicity
Contraindications
- Hypersensitivity to remdesivir or any of its components.
Drug Interactions
- Potential interactions with drugs metabolized by CYP450 enzymes (CYP2C8, CYP2D6, CYP3A4) exist, though clinical significance is uncertain.
- Concomitant use with chloroquine or hydroxychloroquine is not recommended due to in vitro antagonism.
- Strong CYP inducers (e.g., rifampicin, lopinavir/ritonavir) may reduce remdesivir plasma concentrations and are not recommended.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Limited data available. Weigh the potential benefits against potential risks.
- Fetal Risks/Teratogenicity: Animal data show potential adverse developmental effects. Insufficient human data to assess the risk.
- Drug Excretion in Breast Milk: Unknown. Avoid breastfeeding during treatment and for a reasonable period after the last dose.
Drug Profile Summary
- Mechanism of Action: Inhibits viral RNA polymerase.
- Side Effects: Nausea, elevated liver enzymes, increased prothrombin time, hypotension (rarely).
- Contraindications: Hypersensitivity to remdesivir.
- Drug Interactions: Potential interactions with CYP450 substrates and inhibitors; avoid concomitant use with chloroquine/hydroxychloroquine and strong CYP inducers.
- Pregnancy & Breastfeeding: Limited data; weigh risks and benefits.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Liver function tests (ALT, AST), prothrombin time, renal function, serum creatinine (in neonates), vital signs.
Popular Combinations
- The use of remdesivir with dexamethasone may be considered for hospitalized patients with severe COVID-19 requiring supplemental oxygen.
Precautions
- General Precautions: Assess renal and hepatic function prior to and during treatment, and monitor for adverse events.
- Specific Populations:
- Pregnant Women: Use with caution; consider potential risks to the fetus.
- Breastfeeding Mothers: Avoid breastfeeding.
- Children & Elderly: Refer to specific dosage recommendations.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Remdesivir?
A: See detailed dosage guidelines above.
Q2: What is the mechanism of action of Remdesivir?
A: Remdesivir inhibits viral RNA polymerase, blocking viral replication.
Q3: What are the common side effects of Remdesivir?
A: Common side effects include nausea, elevated liver enzymes, and increased prothrombin time.
Q4: Is Remdesivir safe for patients with renal impairment?
A: No dosage adjustment is necessary for patients with renal impairment, including those on dialysis. However, safety data are limited, particularly for patients with severe renal impairment and end-stage renal disease.
Q5: Can Remdesivir be used in pregnant women?
A: Limited data are available. Weigh the potential benefits against potential risks to the fetus. Animal studies suggest potential adverse developmental effects.
Q6: What are the contraindications for Remdesivir?
A: The main contraindication is a known hypersensitivity to remdesivir or any of its components.
Q7: What is the role of Remdesivir in the treatment of COVID-19?
A: Remdesivir is indicated for the treatment of COVID-19 in hospitalized and certain non-hospitalized patients at high risk of disease progression.
Q8: What monitoring parameters are important when administering Remdesivir?
A: Monitor liver function tests (ALT, AST), prothrombin time, renal function (including serum creatinine in neonates), and vital signs during treatment.
Q9: How is Remdesivir administered?
A: Remdesivir is administered intravenously. It should be reconstituted and diluted before use, then infused over 30 to 120 minutes.
Q10: Are there any specific drug interactions I should be aware of with Remdesivir?
A: Avoid co-administration with chloroquine or hydroxychloroquine. Be cautious with concomitant use of drugs metabolized by CYP450 enzymes and avoid co-administration with strong CYP inducers.
