Ramdivir5 mg/ml

Ramdivir is a broad-spectrum antiviral (nucleotide analog prodrug) indicated for:

• Established/approved use: Treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult and pediatric patients.
• Established/approved use: Treatment of COVID-19 in non-hospitalized adult and pediatric patients with mild-to-moderate disease who are at high risk for progression to severe disease, including hospitalization or death.

Ramdivir is not indicated for the treatment of conditions other than COVID-19; it has no established role against other respiratory viruses.

Ramdivir is a nucleotide analog prodrug that is metabolized intracellularly to its active nucleoside triphosphate form, which acts as an inhibitor of viral RNA-dependent RNA polymerase (RdRp). It was developed as a broad-spectrum antiviral agent and gained clinical importance during the COVID-19 pandemic as one of the first antivirals shown to shorten time to recovery in hospitalized patients with SARS-CoV-2 infection.

Ramdivir is administered exclusively by intravenous infusion under medical supervision; it is not available as an oral formulation.

Antiviral agent - Nucleotide analog RNA polymerase inhibitor

Remdesivir is a prodrug that is metabolized within cells to its pharmacologically active nucleoside triphosphate metabolite (GS-443902). This active metabolite acts as an analog of adenosine triphosphate and competes for incorporation into nascent viral RNA chains by the viral RNA-dependent RNA polymerase (RdRp). Once incorporated, it causes delayed chain termination during viral RNA synthesis, thereby inhibiting replication of susceptible RNA viruses, including SARS-CoV-2.

Pharmacokinetics: Remdesivir is rapidly distributed intracellularly following intravenous infusion and is extensively metabolized via hydrolase and esterase pathways to form the active triphosphate metabolite. It is primarily eliminated renally, largely as an inactive metabolite (GS-441524), with a plasma elimination half-life of approximately 1 hour for the parent drug.

For intravenous infusion only, administered by a healthcare professional. Reconstituted/diluted solution is infused over 30 to 120 minutes. Not for intramuscular or oral use. Compatible diluent and infusion rate must follow the manufacturer's instructions and hospital protocol.

Clinically significant interactions with Ramdivir include:

• Chloroquine or hydroxychloroquine: Coadministration is not recommended, as it may reduce the antiviral activity of Ramdivir based on cell culture data.
• Strong CYP inducers/inhibitors and drugs affecting OATP1B1/OATP1B3 transporters: May theoretically alter formation or exposure of the active metabolite of Ramdivir; clinical significance is not fully established but caution is advised with concomitant strong enzyme-modulating drugs.
• Nephrotoxic or hepatotoxic drugs: Concomitant use may increase the risk of renal or hepatic adverse effects associated with Ramdivir; monitor renal and liver function closely.

Adverse effects reported with Ramdivir include:

• Common: Nausea, increased liver transaminases (ALT/AST elevation), infusion-site reactions.
• Less common but clinically important: Hypersensitivity and infusion-related reactions (hypotension, sweating, shivering, nausea, flushing), which may occur during or shortly after infusion and can be severe or rarely anaphylactic.
• Other reported effects: Headache, rash, elevated prothrombin time, and rarely, bradycardia (particularly noted in some hospitalized patients) and seizures.

Patients should be monitored during infusion for hypersensitivity reactions; if a severe reaction occurs, the infusion should be stopped immediately and appropriate treatment given (see Contraindications and Precautions).

Pregnancy: No formal pregnancy category has been assigned to Ramdivir. Available data from clinical use in the second and third trimester have not identified a clear drug-associated risk of major birth defects, though data on first-trimester exposure remain limited. Ramdivir should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus, and only under the guidance of a physician.

Lactation: It is not known whether Ramdivir or its metabolites are present in human breast milk. A decision on whether to continue or discontinue breastfeeding during treatment with Ramdivir should be made in consultation with a physician, weighing the benefits of breastfeeding against the mother's need for treatment.

The following precautions apply to the use of Ramdivir:

• Hepatic effects: Liver function tests should be performed in all patients before starting and during treatment with Ramdivir as clinically appropriate. Discontinuation should be considered if ALT levels rise significantly along with signs of liver inflammation or injury.
• Renal function: Use in patients with reduced kidney function requires caution, as the formulation vehicle (SBECD) is renally cleared and may accumulate; renal function should be assessed before and during treatment.
• Hypersensitivity/infusion-related reactions: Monitor patients during infusion and for at least 1 hour afterward; slower infusion rates may reduce the risk of these reactions (see Side Effects).
• Use only under medical supervision: Ramdivir must be administered exactly as prescribed, in a healthcare setting equipped to manage acute hypersensitivity reactions; it should never be self-administered or obtained without a prescription.

There is limited clinical experience with overdosage of Ramdivir. In the event of a suspected overdose, treatment should be supportive, with close monitoring for adverse effects, particularly signs of hepatic or renal impairment and hypersensitivity reactions. There is no specific antidote for Ramdivir overdose. Seek immediate medical attention or contact a poison control center/emergency services if an overdose is suspected.

Store lyophilized powder vials at room temperature (below 30°C); store solution vials in a refrigerator (2°C to 8°C), protected from light, unless otherwise directed on the product label. Do not freeze. Reconstituted and diluted solutions have specific, limited storage times as directed by the manufacturer and hospital pharmacy. Keep out of reach of children. Administration is performed by healthcare professionals only.

Renal impairment: Use with caution in patients with reduced kidney function; the cyclodextrin excipient may accumulate at lower estimated glomerular filtration rates, so renal function should be assessed before and during treatment with Ramdivir, per institutional protocol.

Hepatic impairment: Use with caution; liver function should be monitored before and during treatment (see Precautions and Warnings).

Elderly: No overall differences in safety or efficacy have been observed based on age; no dose adjustment is required solely for elderly patients, though age-related organ function should be considered.

Pediatric patients: Approved for use from birth (weighing at least 1.5 kg or 3 kg depending on formulation/dosing table) through 18 years of age, using weight-based dosing for patients under 40 kg (see Dosage and Administration and Pediatric Uses).

Treatment duration with Ramdivir depends on clinical setting: 3 days for non-hospitalized high-risk outpatients, 5 days for most hospitalized patients (extendable to a total of 10 days if adequate clinical improvement is not observed, particularly in patients requiring mechanical ventilation or ECMO).

Lyophilized powder vials of Ramdivir must be reconstituted with the appropriate diluent (typically Sterile Water for Injection) to form a concentrate, which is then further diluted in an appropriate IV fluid (e.g., 0.9% sodium chloride) before infusion, strictly following the manufacturer's instructions for reconstitution volume, gentle mixing technique, and use of a compatible in-line filter. This must be performed by trained healthcare/pharmacy personnel under aseptic conditions.

Antiviral agents; Nucleotide analogs; RNA-dependent RNA polymerase (RdRp) inhibitors

Remdesivir is a prodrug converted intracellularly to its active nucleoside triphosphate metabolite, which is incorporated by the viral RNA-dependent RNA polymerase into nascent viral RNA, causing delayed chain termination and thereby suppressing replication of susceptible RNA viruses such as SARS-CoV-2.

Ramdivir is approved for use in pediatric patients from birth (neonates weighing at least 1.5 kg to 3 kg, depending on the approved dosing table) through 18 years of age for the treatment of COVID-19, using weight-based dosing regimens for children weighing less than 40 kg and adult dosing for those weighing 40 kg or more. Use in pediatric patients should be guided by a pediatrician or physician experienced in managing COVID-19 in children, with close monitoring of liver and kidney function and observation for infusion-related reactions, consistent with the precautions described for adults.