Foscarbidopa and foslevodopa

2 DOSAGE AND ADMINISTRATION Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. For subcutaneous administration only, preferably in the abdomen, via the VYAFUSER pump. ( 2.2 , 2.3 , 2.4 ) See the Full Prescribing Information for calculation of the base continuous dosage, hourly infusion rate, optional loading dose, and extra dose.

Patients should be trained on the proper use of VYALEV and the delivery system prior to initiating. 2. 3 Recommended Dosage VYALEV (foscarbidopa and foslevodopa) is administered as a subcutaneous infusion with the VYAFUSER pump [ see Dosage and Administration, Healthcare Professional Instructions for Use of VYAFUSER Pump , and Patient Instructions for Use of VYAFUSER Pump ] .

VYALEV Base Continuous Dosage and Hourly Infusion Rate The continuous infusion rate is based on total levodopa dosage (TLD). The hourly base continuous infusion rate (mL/hr) = [(TLD x 1.3) / 240] / [number of hours the patient is typically awake (e.g., 16 hours)], as shown in the steps below. Step 1: Calculate the TLD for the levodopa-containing medications that VYALEV is replacing.

Each 1 mL of VYALEV contains 240 mg of foslevodopa. Step 4: Determine the hourly base continuous infusion rate of VYALEV by dividing the total daily volume (mL) of VYALEV by the number of hours the patient is typically awake (e.g., 16 hours). VYALEV may be administered over the patient’s waking hours or may be administered for 24 hours.

See Dosage and Administration for adjustment of and alternate infusion rates for lower overnight dosages. Maximum Dosage The maximum recommended daily dosage of VYALEV is 3,525 mg of the foslevodopa component (equivalent to approximately 2,500 mg levodopa). Optional Loading Dose If VYALEV therapy is being initiated in an “Off” state or the patient has not been receiving their base continuous infusion for more than 3 hours, a loading dose can be administered immediately prior to starting or re-starting the base continuous hourly infusion.

The pump is capable of delivering a loading dose ranging from 0.1 mL to a maximum of 3 mL, in increments of 0.1 mL. Extra Dose An extra dose volume can be programmed to 1 of 5 options (see Table 1). The “extra dose” feature is limited to no more than 1 extra dose per hour. If 2 or more extra doses are used by the patient during the 24-hour/day treatment period, a revision of the base continuous infusion rate should be considered (refer to the Healthcare Professional Instructions for Use of VYAFUSER Pump details). [See table below.] * See Step 1 2. 4 Preparation and Administration Instructions Patients should be trained on the proper use of VYALEV and the delivery system prior to initiating treatment with VYALEV and, as necessary, thereafter [see Dosage and Administration and the Patient Instructions for Use of VYAFUSER Pump ] .

Preparation Use aseptic technique. Use sterile, single-patient-use infusion components (syringe, infusion set, and vial adapter) qualified for use with the pump to infuse VYALEV. Do not dilute. Do not mix VYALEV with other products. The medication vials are for single dose only. The entire contents of a VYALEV vial should be transferred into a syringe for administration.

Do not withdraw a partial portion of the vial contents. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit [see Dosage Forms and Strengths ] . The infusion set (cannula) can remain in place for up to 3 days when VYALEV is infused continuously.

Administration Site Selection Administer VYALEV subcutaneously, preferably in the abdomen, avoiding the area with a 2-inch radius from the navel. Rotate the infusion site and use a new infusion set at least every 3 days. Select new infusion sites at least 1 inch from sites used within the previous 12 days. Do not infuse VYALEV into areas where the site is tender, bruised, red, or hard to the touch.

Infusion Flow Rates Adjustment: Infusion rates may be adjusted in increments of 0.01 mL/hr (which is equivalent to approximately 1.7 mg of levodopa/hour). Alternative Flow Rates: The healthcare professional has the option to enable and pre-program the pump with 2 alternative continuous infusion rates (Low/High) that the patient may select to account for changes in functional demand (e.g., lowering the dosage at night or increasing the dose for prolonged intense activity) (see the Healthcare Professional Instructions for Use of VYAFUSER Pump ) .

Sudden discontinuation or rapid dose reduction of VYALEV, without administration of alternative dopaminergic therapy, should be generally avoided [see Warnings and Precautions]. Following interruptions of more than 1 hour, a new infusion set (tubing and cannula) should be used and rotated to a different infusion site. If the infusion has been interrupted for longer than 3 hours, the patient may also self-administer a loading dose, if enabled by their healthcare professional [see Dosage and Administration] .