After the approvement of a new drug application (NDA) for Veklury (remdesivir), a drug indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization on October 22, 2020, FDA (The U.S. Food and Drug Administration) understand that some compounders might be interested in compounding remdesivir drug products.
However, the Administration cautions against compounding remdesivir products and recommends that health care providers utilize the FDA-approved drug for patients who are prescribed remdesivir.
The Veklury approval includes two presentations: remdesivir for injection, 100 milligrams (mg), a sterile, preservative-free lyophilized powder and remdesivir injection, 100 mg/20 milliliters (mL) (5 mg/mL), a sterile, preservative-free solution.
” Veklury is an injectable drug and should only be administered in a hospital or in a health care setting capable of providing acute care comparable to inpatient hospital care. Important information about using Veklury to treat COVID-19 for its approved use is available in the prescribing information which includes dosing instructions, potential side effects and drug interactions,” – The FDA said.
The most common side effects include increased levels of liver enzymes, which may be a sign of liver injury; and allergic reactions, which may include changes in blood pressure and heart rate, low blood oxygen level, fever, shortness of breath, wheezing, swelling (e.g., lips, around eyes, under the skin), rash, nausea, sweating or shivering.
Remdesivir Drug And API
Remdesivir API is complex and neither a United States Pharmacopeia (USP) monograph nor other public quality standard for the API used in FDA-approved remdesivir is available. Remdesivir API has six stereocenters and has multiple polymorphic forms.2,3 Using API forms that differ from the API in the FDA-approved drug may affect the compounded drug’s quality, including the solubility of the API in the compounded drug.
Because it is challenging to formulate remdesivir as a stable drug, the agency is concerned that compounded remdesivir drug products could be of low quality potentially resulting in patient harm.
“FDA is aware of various entities (separate from the suppliers named in the approved remdesivir NDA) selling what they claim to be remdesivir API. FDA often lacks detailed information about the composition and quality of the API that suppliers sell to compounders,” – Administration report.
In addition to complexities and risks related to the API, remdesivir drug products are complex to produce. It may be challenging for compounders to formulate remdesivir drug products that will remain stable over time and have an appropriate pH. FDA-approved remdesivir is administered intravenously as an aqueous solution and remdesivir has limited aqueous solubility. FDA is concerned that compounders may have difficulty identifying an appropriate solubilizing agent and sourcing one of sufficient quality.
The use of remdesivir API to compound drugs may potentially pose significant risks. The FDA urges compounders not to compound drug products using remdesivir API and recommends that providers utilize the FDA-approved drug for patients who are prescribed remdesivir. Compounded drugs are not FDA-approved, which means FDA has not evaluated the safety, effectiveness or quality of compounded drugs. Compounded drugs should only be used in patients whose medical needs cannot be met by an FDA-approved drug.