Ninavir5 mg/ml

Emergency use of Ninavir 5 mg/ml for treatment of suspected or laboratory confirmed Corona Virus Disease 2019 (COVID-19). Severe disease is defined as patients with an oxygen saturation (Sp02) <94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal ... Read moreEmergency use of Ninavir 5 mg/ml for treatment of suspected or laboratory confirmed Corona Virus Disease 2019 (COVID-19). Severe disease is defined as patients with an oxygen saturation (Sp02) <94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, Ninavir 5 mg/ml is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous agent is clinically appropriate.

Anti-viral drugs

Ninavir 5 mg/ml is a nucleoside analog that is expected to inhibit the action of RNA polymerase. By incorporating into RNA, additional nucleotides cannot be added, terminating RNA transcription. Viruses with mutations in RNA polymerase to develop partial resistance to Ninavir 5 mg/ml have been shown to be less infective.

The FDA Emergency Use Authorization suggests a loading dose of 200 mg once daily in patients ≥ 40 kg or 5 mg/kg once daily in patients 3.5 kg to less than 40 kg, followed by a maintenance dose of 100 mg once daily in patients ≥ 40 kg or 2.5 mg/kg once daily in patients 3.5 kg to less than 40 kg. Patients not needing invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) should be treated for 5 days (including the loading dose on day 1), up to 10 days if they do not show improvement. Patients requiring invasive mechanical ventilation or ECMO should be treated for 10 days.Clinical trials used a regimen of 200mg once daily on the first day, followed by 100mg once daily for another 9 days. Early data suggests that some patients may benefit from only 5 days of treatment.Ninavir 5 mg/ml was originally investigated as a treatment for Ebola virus, but has potential to treat a variety of RNA viruses. Its activity against the coronavirus (CoV) family of viruses, such as SARS-CoV and MERS-CoV, was described in 2017, and it is also being investigated as a potential treatment for SARS-CoV-2 infections.

General Information- Adult and pediatric patients (>28 days and old) must have an eGFR determined and full-term neonates (≥7 days to ≤28 days old) must have serum creatinine determined before dosing of Ninavir 5 mg/ml. Hepatic laboratory testing should be performed in all patients prior to starting Ninavir 5 mg/ml and daily while receiving Ninavir 5 mg/ml. Ninavir 5 mg/ml should be administered via intravenous infusion only. Do not administer as intramuscular injection. Adult Patients- The recommended dosage in adults requiring invasive mechanical ventilation and/or ECMO is a single loading dose of Ninavir 5 mg/ml 200 mg on day 1 followed by once daily maintenance dose of Ninavir 5 mg/ml 100 mg for 9 days. The recommended dose in adults not requiring invasive mechanical ventilation and/or ECMO is a single dose of Ninavir 5 mg/ml 200 mg on day 1 followed by once daily maintenance dose of Ninavir 5 mg/ml 100 mg for 4 days. If a patient dose not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e. up to a total of 10 days) Ninavir 5 mg/ml is to be administered via intravenous infusion in a total volume of up to 250 ml 0.9% saline over 30 to 120 minutes. Pediatric Patients- The recommended pediatric dose for pediatric patients weighing between 3.5 kg <40 kg should be calculated using the mg/kg dose according to the patient’s weight. For pediatric patients with body weight between 3.5 kg <40 kg use Ninavir 5 mg/ml for injection 100 mg lyophilized powder only. Administer a body weight-based dosing regimen of one loading dose of Ninavir 5 mg/ml 5 mg/kg IV (infused over 30 to 120 minutes) on day 1 followed by Ninavir 5 mg/ml 2.5 mg/kg IV (infused over 30 to 120 minutes) once daily for 9 days (for pediatric patients requiring invasive mechanical ventilation and/or ECMO, days 2 through 5). If a patient dose not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e. up to a total of 10 days) For pediatric patients with body weight ≥40 kg requiring invasive mechanical ventilation and/or ECMO, the adult dosage regimen of one loading dose of Ninavir 5 mg/ml 200 mg IV (infused over 30 to 120 minutes) on day 1 followed by Ninavir 5 mg/ml 100 mg IV (infused over 30 to 120 minutes) once daily for 9 days will be administered. For pediatric patients with body weight ≥40 kg requiring invasive mechanical ventilation and/or ECMO, the adult dosage regimen of one loading dose of Ninavir 5 mg/ml 200 mg IV (infused over 30 to 120 minutes) on day 1 followed by Ninavir 5 mg/ml 100 mg IV (infused 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, treatment may be extended for up to 5 additional days (i.e. up to a total of 10 days).

The prepared dilution should not be administered simultaneously with any other medication. The compatibility of Ninavir 5 mg/ml injection with IV solutions and medications other than saline is not known. Please administered the diluted solution with the infusion rate described in the below table. Recommended Rate of Infusion- Diluted Ninavir 5 mg/ml for Injection Lyophilized Powder in Adults and Pediatric Patients Weighing > 40 kgInfusion bag 250 ml: Infusion Time: 30 min, Rate of Infusion: 8.33 ml/min Infusion Time: 60 min, Rate of Infusion: 4.17 ml/min Infusion Time: 120 min, Rate of Infusion: 2.08 ml/min Infusion bag 100 ml: Infusion Time: 30 min, Rate of Infusion: 3.33 ml/min Infusion Time: 60 min, Rate of Infusion: 1.67 ml/min Infusion Time: 120 min, Rate of Infusion: 0.83 ml/min

Ninavir 5 mg/ml is contraindicated in patients with known hypersensitivity to Ninavir 5 mg/ml.

An adverse reaction associated with Ninavir 5 mg/ml in clinical trials in healthy adult subjects was increased liver transaminases.

Ninavir 5 mg/ml should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.

There are limited clinical data available for Ninavir 5 mg/ml. Serious and unexpected adverse events may occur that have not been previously reported with Ninavir 5 mg/ml use.

Please do not reuse or save unused Ninavir 5 mg/ml Lyophilized powder, injection solution or diluted solution for infusion for further use. This product contains no preservatives.Lyophilized Powder: Please store Ninavir 5 mg/ml for injection, 100 mg, vials at temperature not exceeding 30°C in a dry place until required for use. Protect from light & moisture. Do not use after expiration date.After reconstitution: vials can be stored up to 4 hours at room temperature (20°C-25°C) prior to administration or 24 hours at refrigerated temperature (2°C-8°C). Please dilute within the same day as administration.Diluted Solution for Infusion: Please store diluted Ninavir 5 mg/ml solution for infusion up to 4 hours at room temperature (20°C-25°C) or 24 hours at refrigerated temperature (2°C-8°C).

The pharmacokinetics of Ninavir 5 mg/ml have not been evaluated in patients with renal impairment. The pharmacokinetics of Ninavir 5 mg/ml have not been evaluated in patients with hepatic impairment. It is not known if dosage adjustment is needed in patients with hepatic impairment and Ninavir 5 mg/ml should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk.

Anti-viral drugs

Ninavir 5 mg/ml is a preparation of Ninavir 5 mg/ml. It is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of Ninavir 5 mg/ml to Ninavir 5 mg/ml Triphosphate has been demonstrated in multiple cell types. Ninavir 5 mg/ml Triphosphate act as an analogue of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in delayed chain termination during replication of the viral RNA. Ninavir 5 mg/ml triphosphate is a weak inhibitor of mammalian DNA and RNA polymerase with low potential for mitochondrial toxicity.

No adequate and well controlled studies of Ninavir 5 mg/ml use in pregnant women have been conducted. Ninavir 5 mg/ml should be used in pregnancy only if the potential benefit justifies the potential risk for the mother fetus. There is no information regarding the presence of Ninavir 5 mg/ml in human milk, the effects on the breastfeed infants, or the effects on milk production. Because of the potential for viral transmission of SARS-CoV-2 negative infants and adverse reactions from the drug in breastfeeding infants, the development and health benefits of breastfeeding should be considered along with the mother's clinical need for Ninavir 5 mg/ml and any potential adverse effects on the breastfed child from Ninavir 5 mg/ml or from the underlying maternal condition.