Foscarbidopa-Foslevodopa

Foscarbidopa-Foslevodopa is a prescription medication indicated for the treatment of motor fluctuations in patients with advanced  Parkinson’s disease (PD).

• Foscarbidopa-Foslevodopa is available under the following different brand names: Vyalev.

Common side effects of Foscarbidopa-Foslevodopa include:

• infusion/catheter site reactions
• infusion/catheter site infections
• hallucinations
• involuntary muscle movements (dyskinesia)

Serious side effects of Foscarbidopa-Foslevodopa include:

• hallucinations
• unusual urges such as gambling, compulsive eating, compulsive shopping, and increased sex drive
• infusion site reactions and infection symptoms include local spreading of redness, pain, swelling, warmth, and change in color when pressing on the area, fever 
• withdrawal-emergent fever (hyperpyrexia) and confusion symptoms include fever, confusion, severe muscle stiffness 
• uncontrolled sudden movements (dyskinesia)
• heart attack or other heart problems
• worsening of the increased pressure in your eye (glaucoma)

Rare side effects of Foscarbidopa-Foslevodopa include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Solution for SC injection

• (120 mg/2,400 mg)/10 mL single-dose vial

Parkinson Disease

Adult dosage

• Administered as SC infusion via Vyafuser pump
• Continuous dosage and hourly infusion rate
• Dose based on total levodopa dosage (TLD): Hourly base continuous infusion rate (mL/hr) = ([TLD x 1.3] / 240) / (number of hr patient is typically awake [e.g., 16 hours])
• Step 1
  • Calculate TLD for levodopa-containing medications that Foscarbidopa-Foslevodopa is replacing
  • All dosages should be converted to equivalent dosage of immediate-release levodopa to obtain TLD
  • Prescribers should adjust the total dose of levodopa-containing products for catechol-O-methyltransferase (COMT) inhibitor use
  • See the Prescribing Information for respective drugs for conversions or adjustments
  • Do not include rescue or as needed levodopa or any other anti-Parkinsonian medication or therapy, including medications taken outside of awake time (e.g., night-time dosing) in this calculation
• Step 2
  • Determine the total daily dosage (mg) of the foslevodopa component by multiplying TLD by 1.3
  • Conversion factor considers molecular weight and bioavailability of foslevodopa compared to levodopa
• Step 3
  • Determine the total daily volume (mL) of Foscarbidopa-Foslevodopa by dividing total daily dosage (mg) by 240
  • Each 1 mL of Foscarbidopa-Foslevodopa contains foslevodopa 240 mg
• Step 4
  • Determine hourly base continuous infusion rate of Foscarbidopa-Foslevodopa by dividing the total daily volume (mL) by the number of hours the patient is typically awake (e.g., 16 hours)
  • Foscarbidopa-Foslevodopa may be administered over waking hours or may be administered for 24 hours
  • See Administration for adjustment of an alternate infusion rate for lower overnight dosages

Maximum dosage

• Maximum recommended daily dose: 3,525 mg foslevodopa (equivalent to approximately 2,500 mg levodopa)

Optional loading dose

• If 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 before starting or re-starting the base continuous hourly infusion
• Loading doses can be administered either with Foscarbidopa-Foslevodopa or patients can continue using oral immediate-release carbidopa/levodopa tablets
• Calculate the loading dose from the first-morning dose of oral immediate-release carbidopa/levodopa taken before starting treatment with Foscarbidopa-Foslevodopa
• Calculate Foscarbidopa-Foslevodopa loading dose: First-morning dose of oral immediate-release levodopa x 1.3 and divide by 240
• Pump can deliver loading dose ranging from 0.1-3 mL, in increments of 0.1 mL

Extra dose

• The “extra dose” feature is limited to not exceeding 1 extra dose/hours
• If two and more extra doses are used during the 24-hour/day treatment period, consider revising the base continuous infusion rate

Foscarbidopa-Foslevodopa extra dose options

• 0.1 mL = approximately 17 mg levodopa
• 0.15 mL = approximately 25.5 levodopa
• 0.2 mL = approximately 34 levodopa
• 0.25 mL = approximately 42.5 levodopa
• 0.3 mL = approximately 51 levodopa

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Foscarbidopa-Foslevodopa has no noted severe interactions with any other drugs
• Foscarbidopa-Foslevodopa has no noted serious interactions with any other drugs
• Foscarbidopa-Foslevodopa has no noted moderate interactions with any other drugs
• Foscarbidopa-Foslevodopa has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Coadministration with a nonselective monoamine oxidase (MAO) inhibitor or within 2 weeks of discontinuing a nonselective MAO inhibitor

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Foscarbidopa-Foslevodopa?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Foscarbidopa-Foslevodopa?”

Cautions

• Falling asleep/somnolence during daily activities
  • Falling asleep while engaged in activities of daily living (e.g., motor vehicle operation) resulting in accidents has been reported
  • Pre-existing somnolence may increase the risk, although patients may not give such a history
  • Somnolence while on levodopa may have no warning signs (e.g., excessive drowsiness); some patients believed that they were alert immediately before the event (sleep attack)
  • Some events have been reported for more than 1 year after treatment initiation; reassess for drowsiness or sleepiness since some events may occur later
  • Patients may not acknowledge drowsiness or sleepiness until directly questioned
  • Patients who have already experienced somnolence or an episode of sudden sleep onset should not participate in these activities
  • Before initiating, advise patients regarding the potential to develop drowsiness and specifically ask about factors that may increase risk (e.g., use of concomitant sedating medications, presence of sleep disorders)
  • Consider discontinuing the drug if significant daytime sleepiness or episodes of falling asleep during activities reported
  • If a decision is made to continue therapy, advise patients not to drive and to avoid other potentially dangerous activities that might result in harm if they become somnolent
  • Information is insufficient to establish that dose reduction will eliminate episodes of falling asleep
• Hallucinations/psychosis
  • Increased risk for hallucinations and psychosis
  • Confusion, insomnia, and excessive dreaming may accompany hallucinations
  • Abnormal thinking and behavior may present with one or more symptoms, including paranoid ideation, delusions, hallucinations, confusion, psychosis, disorientation, aggressive behavior, agitation, and delirium
  • Review treatment if these symptoms develop; hallucinations may be responsive to dose reduction or other concomitantly administered medications
  • Owing to the risk of exacerbating psychosis, do not prescribe Foscarbidopa-Foslevodopa in patients with a major psychotic disorder
  • Additionally, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate symptoms of PD and may decrease Foscarbidopa-Foslevodopa efficacy
• Impulse control/compulsive behaviors
  • Patients may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges, including the inability to control these urges while taking medications that increase central dopaminergic tone
  • In some cases, these urges stopped when dosage was reduced, or medication discontinued
  • Because patients may not recognize these behaviors as abnormal, ask patients or their caregivers specifically about the development of new or increased urges during treatment
  • Consider reducing the dose or discontinuing if urges develop
• Infusion site reactions and infections
  • Can cause infusion site reactions and infections
  • Reactions include erythema, pain, edema, nodule, bruising, hemorrhage, induration, pruritus, extravasation, inflammation, mass, warmth, hematoma, pallor, rash, and swelling
  • The most frequent infusion site infection reported was cellulitis
  • If infection is suspected, remove the cannula from the infusion site
  • If the cannula is removed, replace it with a new cannula or, if prolonged interruption, prescribe oral carbidopa/levodopa until Foscarbidopa-Foslevodopa resumed
• Withdrawal-emergent hyperpyrexia and confusion
  • A symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability) reported with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy
  • Avoid sudden discontinuation or rapid dose reduction
  • If discontinued, taper dose to reduce risk
• Dyskinesia
  • May cause or exacerbate dyskinesias
  • If dyskinesias occur, consider dosage reduction of foscarbidopa/levodopa or other medications used to treat PD
• Cardiovascular ischemic events
  • Myocardial infarction (MI) and arrhythmia reported in patients taking carbidopa-levodopa
  • Ask patients about symptoms of ischemic heart disease and arrhythmia, especially those with a history of MI or arrhythmias
• Glaucoma
  • May increase intraocular pressure (IOP) in patients with glaucoma
  • Monitor IOP in patients with glaucoma after initiating
• Drug interaction overview
  • Nonselective MAO inhibitors
    • Contraindicated
    • Coadministration of nonselective MAO inhibitors (e.g., phenelzine, tranylcypromine) may cause hypertension (including hypertensive crisis)
    • Discontinue nonselective MAO inhibitors at least 2 weeks before initiating Foscarbidopa-Foslevodopa
  • Selective MAO inhibitors
    • Monitor
      • Coadministration of selective MAO-B inhibitors (e.g., rasagiline, selegiline) may be associated with orthostatic hypotension
• Antihypertensive drugs
  • Modify dose/monitor
    • Coadministration with antihypertensive medications can cause symptomatic postural hypotension
    • Dose reduction of the antihypertensive may be needed after starting or increasing the Foscarbidopa-Foslevodopa dose
• Dopamine D2 receptor antagonists and isoniazid
  • Monitor
    • Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide, papaverine) and isoniazid may reduce the efficacy of foslevodopa
    • If coadministered, monitor for worsening Parkinson symptoms

Pregnancy and Lactation

• Data are unavailable regarding developmental risks associated with use during pregnancy
• Lactation
  • Carbidopa
    • There is no adequate data regarding the presence of drug in human milk, its effects on breastfed infants, or milk production
    • Carbidopa is excreted in rat milk
  • Levodopa
    • Levodopa has been detected in human milk after administration of carbidopa/levodopa
    • Levodopa decreases secretion of prolactin in humans, which may inhibit lactation
• There are no adequate data on the effects on breastfed infants