Understanding the concentration of VIGIV for mpox
A prescriber ordered Vaccinia Immune Globulin Intravenous (Human) (VIGIV) (National Drug Code 60492-0173-1) 6,000 units/kg for a hospitalized 3.49 kg neonate (total dose of 20,940 units) with mpox-like signs and symptoms. VIGIV is a solvent/detergent-treated, filtered sterile solution of purified immunoglobulin G (IgG) fraction of human plasma containing antibodies to vaccinia virus. A single-dose vial arrived from the national stockpile in an unlabeled carton without a package insert. The immediate vial label read, "greater than or equal to 50,000 units per vial," without listing a corresponding volume or concentration (see Vaccinia Immune Globulin Intravenous [Human] CNJ-016 vial label).
When trying to determine how to prepare this product, a pharmacist found the package insert on DailyMed (http://www.ismp.org/ext/997), which states that VIGIV is provided in a 20 mL single-dose vial containing antibodies to vaccinia virus at greater than or equal to 50,000 units per vial. The package insert states to remove the entire contents of the vial to obtain the labeled dosage of VIGIV. With this information, practitioners might assume the vial contains a total volume of 20 mL equaling 50,000 units. However, 20 mL refers to the size of the glass vial. The actual volume in each vial is variable.
The pharmacist at the above hospital consulted with the CDC and was instructed to withdraw the total volume in the vial, then divide 50,000 units by the volume to determine the final concentration. The total volume was determined to be 11.5 mL and resulted in a concentration of 4,348 units/mL. Therefore, the patient-specific dose (20,940 units) was calculated to be 4.82 mL. If the CDC specialist had not been available, the pharmacist might have incorrectly determined the concentration to be 50,000 units/20 mL (2,500 units/mL), which would have resulted in a final dose of 36,436 units/8.38 mL (almost double the intended dose).
Also, before the pharmacist could verify the order in the electronic health record and generate a patient-specific label, which requires the volume and concentration, the technician had to first draw up the volume of the vial to determine the concentration. Specifically, the technician had to manipulate the VIGIV before the label was printed. This leaves room for error because the technician will not have a printed label for the syringe.
The CDC explained that the vials are filled from pooled plasma with a minimum of 50,000 units per vial; thus, the volume and concentration vary per vial. When this medication is requested and approved to treat mpox, the CDC emails an investigational new drug (IND) protocol to the prescriber in advance, which should be distributed to pharmacy staff to refer to for dose preparation and titration instructions (http://www.ismp.org/ext/1030).
In addition to the container label issue, the "administration" section of the package insert states that VIGIV should be given I.V. at an infusion rate no greater than 2 mL/min. For patients weighing less than 50 kg, it should be administered at a rate no greater than 0.04 mL/kg/min (133.3 units per kg/min). However, when the pharmacist consulted with CDC, they learned about the IND protocol which indicated that for certain patients, VIGIV administration should be initiated at an infusion rate of 0.01-0.02 mL/kg/min for the first 30 minutes and then it can be increased by 0.01-0.02 mL/kg/min from the initial infusion rate for the next 30 minutes. After that time, the remaining infusion may be administered at a rate of 2 mL/min.
If a patient requires the use of VIGIV, healthcare professionals must obtain the current IND protocol from the prescriber or CDC, consider creating a worksheet to calculate the concentration of the vial in hand, and include a label to use when drawing up the vial contents. Complete titration instructions for nurses must also be included so that VIGIV is administered at the correct rate.