Foscarbidopa and foslevodopa (foscarbidopa/foslevodopa) is a fixed combination of foscarbidopa (an aromatic amino acid decarboxylation inhibitor) and foslevodopa (an aromatic amino acid).1 Foscarbidopa is a prodrug of carbidopa and foslevodopa is a prodrug of levodopa.1
The fixed combination of foscarbidopa and foslevodopa (foscarbidopa/foslevodopa) is used for the treatment of motor fluctuations in adults with advanced Parkinson disease.1 Foscarbidopa/foslevodopa has been designated an orphan drug by FDA for treatment of late stage Parkinson disease.2
Efficacy of foscarbidopa/foslevodopa for the treatment of motor fluctuations associated with advanced Parkinson disease was established in a 12-week, phase 3, randomized, double-blind, double-dummy, active-controlled, multicenter study.1, 3 The study showed significant improvement in "On" time without troublesome dyskinesia with subcutaneous foscarbidopa/foslevodopa compared to oral immediate-release carbidopa/levodopa.1
The study enrolled patients responsive to levodopa who had motor fluctuations inadequately controlled by their current medications, which included a minimum levodopa dosage ≥400 mg daily, and at least 2.5 hours of “Off” time per day over 3 consecutive days.1, 3 Prior to the start of the study, patients entered a 3-week carbidopa/levodopa stabilization period in which all carbidopa/levodopa containing medications and catechol-O-methyltransferase (COMT) inhibitors were converted to an equivalent amount of immediate-release carbidopa/levodopa.1, 3 Non-levodopa containing medications for Parkinson disease were allowed during the trial, but dosage had to remain unchanged.3 Patients were randomized 1:1 to subcutaneous foscarbidopa/foslevodopa plus oral placebo capsules or oral immediate-release carbidopa/levodopa plus placebo subcutaneous infusion.1 During the first 4 weeks of the 12 week study period, the foscarbidopa/foslevodopa continuous infusion dosage was optimized, after which, changes were not permitted.3
A total of 141 patients were randomized in the study.1 The mean age of patients was 66.4 years and the average disease duration was 8.6 years.1, 3 The majority of the patients were male (70%) and White (93%); 74% of the foscarbidopa/foslevodopa group and 66% of the oral immediate-release carbidopa/levodopa group were receiving at least one other class of medication for Parkinson disease at baseline.1, 3
The primary outcome was the mean change in "On" time without troublesome dyskinesia from baseline to Week 12, measured through patient-recorded Parkinson disease diaries.1, 3 Foscarbidopa/foslevodopa treatment resulted in a statistically significant increase in "On" time from baseline compared to oral immediate-release carbidopa/levodopa (3.36 versus 0.85 hours, respectively).1, 3 In addition, foscarbidopa/foslevodopa showed significant efficacy in reducing "Off" time by 3.41 hours compared to 0.93 hours with immediate-release carbidopa/levodopa.1, 3
A separate phase 3, open-label, 52-week study enrolled 244 patients with levodopa-responsive Parkinson disease who experienced at least 2.5 hours of "Off" time per day for 2 consecutive days.4 Prior to study entry, patients received stable medications for at least 30 days for treatment of their Parkinson disease of which at least one medication was levodopa.4 Patients received individually optimized dosages of foscarbidopa/foslevodopa, ranging from 700-4250 mg of levodopa per 24 hours.4
The majority of patients were male (59.8%) and White (84.8%), with a mean age of 63.9 years and an average Parkinson disease duration of 10.7 years.4 By Week 52, the intent-to-treat population experienced a significant reduction in “Off” time (mean change of 3.5 hours) and a significant increase in "On" time without troublesome dyskinesia (mean change of 3.8 hours).4 Morning akinesia improved, with the percentage of affected patients decreasing significantly from 77.7% at baseline to 27.8% at Week 52.4 Sleep quality and overall quality of life also improved throughout the study.4 Only 137 (56%) of the 244 originally enrolled patients completed the study.4 Reasons for discontinuation included adverse events (23%), withdrawal of consent (12.3%), and lack of efficacy (4.5%).4
Levodopa remains the most effective treatment for managing motor symptoms of Parkinson disease, particularly bradykinesia and rigidity, with variable effects on tremor.5, 6 Levodopa serves as the cornerstone of symptomatic therapy by replenishing dopamine levels in the nigrostriatal pathway, mitigating motor impairments.5, 6 While highly efficacious, long-term use of levodopa is associated with motor fluctuations, including "wearing-off" phenomena and dyskinesias, necessitating adjustments such as use of extended-release formulations, or adjunctive therapies such as dopamine agonists, monoamine oxidase (MAO)-B inhibitors, and catechol-O-methyltransferase (COMT) inhibitors.5, 6 Despite these limitations, levodopa remains the gold standard in Parkinson treatment due to its superior symptomatic relief of motor symptoms compared to other pharmacologic options.5, 6
There are various formulations of carbidopa/levodopa, including immediate-release, controlled-release, extended-release, and enteral suspension formulations.6 The short half-life of levodopa and inconsistent GI absorption make dosing the immediate-release and controlled-release formulations challenging.6 Switching to an extended-release formulation may reduce wearing-off episodes and motor fluctuations not controlled with other formulations.5, 6 Carbidopa/levodopa enteral suspension, delivered via an intrajejunal pump, is an option for patients with advanced disease experiencing severe motor fluctuations.5, 6 Additionally, adjunctive strategies such as combination therapy with COMT inhibitors aim to extend levodopa half-life and reduce fluctuations.5, 6
Foscarbidopa/foslevodopa is a novel prodrug formulation developed to address the limitations of traditional levodopa therapy in Parkinson disease, particularly inconsistent absorption.1, 3, 4 Unlike immediate-release levodopa, which has erratic GI uptake, foscarbidopa/foslevodopa is designed for continuous subcutaneous infusion, bypassing the GI tract and providing more stable plasma levodopa levels.1 This approach aims to reduce "Off" episodes and dyskinesias associated with fluctuating dopamine levels, offering a smoother and more sustained symptomatic benefit.1, 3, 4
The International Parkinson and Movement Disorder Society has published evidence-based recommendations for the treatment of motor symptoms of Parkinson disease.5 According to these guidelines, levodopa is recommended for the treatment of motor symptoms, including bradykinesia, rigidity, and tremor, although its effect on tremor is more variable.5 Additionally, levodopa extended-release and intestinal infusion are recommended for managing motor fluctuations, while levodopa intestinal infusion may also help reduce dyskinesia, though it requires specialized monitoring.5 Foscarbidopa/foslevodopa is not included in the guidelines as the drug was approved after publication.5
Administer foscarbidopa/foslevodopa by subcutaneous infusion using the Vyafuser pump.1
Patients should be trained on proper use of foscarbidopa/foslevodopa and the delivery system prior to initiating treatment.1
The fixed-combination preparation is available as a 10 mL single-dose vial containing 120 mg of foscarbidopa and 2400 mg of foslevodopa.1 To prepare the drug for infusion, use aseptic technique and ensure all infusion components including the syringe, infusion set, and vial adapter are sterile, single-use, and designed for the foscarbidopa/foslevodopa infusion pump.1 Do not dilute or mix with other products.1 Transfer the entire contents of each single-use foscarbidopa/foslevodopa vial into a syrin do not withdraw a partial dose.1
Administer foscarbidopa/foslevodopa subcutaneously, preferably in the abdomen, while avoiding the area within 2 inches of the navel.1 Change the infusion site and replace the infusion set and cannula at least every 3 days.1 Choose a new site at least 1 inch away from previous locations used within the past 12 days.1 Do not infuse into areas that are swollen, discolored, tender, or firm.1
Dispose of the foscarbidopa/foslevodopa vial immediately after transferring the medication into a syringe.1 Dispose of the syringe and any remaining foscarbidopa/foslevodopa left in the syringe for more than 24 hours.1
Store foscarbidopa/foslevodopa vials refrigerated at 2-8°C in the outer carton to prevent breaka the drug may be kept at room temperature (≤30°C) for a single period of up to 28 days.1 Once stored at room temperature, do not return to the refrigerator, and discard if unused within 28 days.1 Do not freeze or shake.1
Dosage of foscarbidopa/foslevodopa for the treatment of motor fluctuations in adults with advanced Parkinson disease is based on total levodopa dosage (TLD).1
Calculate the hourly base continuous infusion rate (mL/hr) using the formula and instructions below.1 Treatment may be administered over the patient's awake hours or over 24 hours.1
Infusion rate (mL/hr) = ([TLD × 1.3] / 240) / (number of typical awake hours)
Step 1: To determine the base infusion rate, calculate the TLD for levodopa-containing medications that foscarbidopa/foslevodopa will replace.1 Convert all levodopa doses to their immediate-release levodopa equivalent.1 If the patient is using a COMT inhibitor, adjust the TLD accordingly, referencing the prescribing information for specific dose conversions.1 Do not include rescue doses, as-needed levodopa, or other anti-parkinsonian medication or therapy, including drugs taken outside of waking hours.1
Step 2: Determine the total daily dosage (mg) of the foslevodopa component by multiplying the TLD by a factor of 1.3 to account for differences in molecular weight and bioavailability between foslevodopa and levodopa.1
Step 3: Calculate the total daily volume (mL) of foscarbidopa/foslevodopa by dividing the total daily dosage (mg) of foslevodopa by 240, as each mL contains 240 mg of foslevodopa.1
Step 4: Determine the hourly continuous infusion rate by dividing the total daily volume (mL) of foslevodopa by the number of hours the patient is typically awake (e.g., 16 hours).1 The infusion may be administered continuously during waking hours or over a full 24 hour period.1 Adjustments may be needed for overnight dosing based on clinical needs.1
The maximum recommended daily dosage of foscarbidopa/foslevodopa is 3,525 mg of the foslevodopa component, which is equivalent to approximately 2,500 mg levodopa.1
If the patient is in an "Off" state or has not been receiving their base continuous infusion for ≥3 hours, a loading dose can be administered immediately prior to starting or resuming foscarbidopa/foslevodopa.1 The loading dose may be given using either foscarbidopa/foslevodopa or oral immediate-release carbidopa/levodopa tablets.1 Calculate the loading dose based on the patient's first morning dose of oral immediate-release carbidopa/levodopa taken before starting treatment with foscarbidopa/foslevodopa.1 If foscarbidopa/foslevodopa is used for the loading dose, multiply the first morning dose of oral immediate-release levodopa dose by 1.3 to account for differences in bioavailability and divide by 240 to determine the volume for the loading dose.1 Set the pump to deliver a loading dose between 0.1 mL and 3 mL, with available increments of 0.1 mL.1
If an extra dose is required, program the appropriate extra dose volume.1 The pump allows for only one extra dose per hour.1 If the patient uses ≥2 extra doses in a 24-hour period, reassess the base continuous infusion rate.1 The available extra dose volumes are 0.1 mL (to obtain an approximate equivalent 17 mg levodopa dose), 0.15 mL (to obtain an approximate equivalent 25.5 mg levodopa dose), 0.2 mL (to obtain an approximate equivalent 34 mg levodopa dose), 0.25 mL (to obtain an approximate equivalent 42.5 mg levodopa dose), and 0.3 mL (to obtain an approximate equivalent 51 mg levodopa dose).1
If foscarbidopa/foslevodopa infusion is interrupted, underdosing may occur.1 Avoid sudden discontinuation or rapid dosage reduction without availailability of alternative dopaminergic therapy.1 For interruptions >1 hour, use a new infusion set and rotate the infusion site.1 If the interruption exceeds 3 hours, the patient may also self-administer a loading dose, if enabled by their healthcare provider.1
The manufacturer makes no dosage recommendations for hepatic impairment.1
The manufacturer makes no dosage recommendations for renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Falling Asleep During Activities of Daily Living and Somnolence
Patients taking levodopa, the active metabolite of foscarbidopa/foslevodopa, have reported falling asleep during daily activities, including driving; such events have sometimes resulted in accidents.1 These events can occur even after long-term use.1 Although many patients reported somnolence while receiving the drug, some patients did not perceive warning signs, such as excessive drowsiness, and believed they were alert prior to sudden sleep onset.1
Before initiating foscarbidopa/foslevodopa therapy, advise patients of the potential to develop drowsiness and specifically ask about any factors that may increase the risk of somnolence (e.g., concomitant use of sedating drugs or presence of sleep disorders).1 Patients with a history of somnolence or sudden sleep onset should avoid activities requiring alertness.1 Consider discontinuing treatment if significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating) occur.1 If continued, advise patients to avoid driving and other potentially dangerous activities that may be harmful if patient becomes somnolent.1 There is insufficient information to establish whether dosage reduction will eliminate this adverse event.1
An increased risk of hallucinations and psychosis has been reported in patients receiving foscarbidopa/foslevodopa.1 In the principal efficacy study of the fixed-combination drug in patients with Parkinson disease, hallucinations occurred in 12.2% of patients receiving foscarbidopa/foslevodopa compared with 1.5% of patients receiving oral immediate-release carbidopa/levodopa; psychosis occurred in 4.1% versus 1.5% of these patients, respectively.1 One patient (1.4%) receiving foscarbidopa/foslevodopa discontinued treatment due to hallucinations.1
Hallucinations may appear early in therapy after initiation and may respond to dosage reduction of foscarbidopa/foslevodopa or adjustment of other concomitant medications.1 Symptoms such as confusion, insomnia, excessive dreaming, paranoia, delusions, agitation, or delirium may also occur.1 Reevaluate treatment if these symptoms develop.1
Avoid use of foscarbidopa/foslevodopa in patients with major psychotic disorders, as the drug may worsen psychosis.1 Dopamine antagonists used for psychosis may exacerbate symptoms of Parkinson disease and reduce foscarbidopa/foslevodopa effectiveness.1
Impulse Control/Compulsive Behaviors
Patients taking foscarbidopa/foslevodopa or other dopaminergic medications for Parkinson disease may experience intense urges and compulsive behaviors (e.g., urge to gamble, increased sexual urges, binge eating, uncontrolled spending, other intense urges) and the inability to control these urges.1 These urges resolved with dosage reduction or discontinuation in some cases.1
Since patients may not recognize these behaviors as abnormal, prescribers should ask patients and caregivers about new or increased compulsive urges during foscarbidopa/foslevodopa therapy.1 If these behaviors develop, consider dosage reduction or discontinuation of foscarbidopa/foslevodopa.1
Infusion Site Reactions and Infections
Foscarbidopa/foslevodopa may cause infusion site reactions and infections.1 In the principal efficacy study, 62% of patients receiving foscarbidopa/foslevodopa experienced infusion site reactions compared to 8% with placebo.1 Treatment led to discontinuation in 8% of patients receiving the fixed-combination drug.1 Reported reactions included erythema, pain, edema, nodules, bruising, and inflammation.1
Infusion site infections occurred in 28% of patients receiving foscarbidopa/foslevodopa versus 3% with placebo, with cellulitis being the most common.1 Treatment was discontinued in 5% of patients because of an infusion site infection.1 If an infection is suspected at the infusion site, remove the cannula.1 If the cannula is removed due to an infection, insert a new cannula at a different site or if an extended interruption occurs, transition the patient to oral carbidopa/levodopa until foscarbidopa/foslevodopa can be resumed.1
Withdrawal-Emergent Hyperpyrexia and Confusion
A symptom complex resembling neuroleptic malignant syndrome (NMS; characterized by elevated temperature, muscular rigidity, altered consciousness, autonomic instability) has been reported in association with rapid dosage reduction of, withdrawal of, or changes in dopaminergic therapy.1 To minimize risk, avoid abrupt withdrawal or rapid dosage reduction of foscarbidopa/foslevodopa.1 If discontinuation is necessary, taper the dosage gradually.1
Foscarbidopa/foslevodopa may cause or worsen dyskinesias.1 In the principal efficacy study, dyskinesia occurred in 11% of patients receiving foscarbidopa/foslevodopa compared with 6% of patients receiving oral immediate-release carbidopa/levodopa.1 Dosage reduction of foscarbidopa/foslevodopa or other parkinson medications may be necessary if dyskinesias develop.1
Cardiovascular Ischemic Events
Myocardial infarction and arrhythmias have been reported in patients taking carbidopa/levodopa, the active metabolites of foscarbidopa/foslevodopa.1 Assess patients for symptoms of ischemic heart disease and arrhythmias, especially those with a history of cardiac disease.1
Carbidopa/levodopa, the active metabolites of foscarbidopa/foslevodopa, may increase intraocular pressure in patients with glaucoma.1 Monitor intraocular pressure after initiating treatment.1
There are no data on the potential developmental risks of foscarbidopa/foslevodopa in pregnant women.1 In animal studies, carbidopa/levodopa, the active metabolites, caused developmental toxicity, including teratogenic effects, at clinically relevant dosages.1
There are no data on the presence of foscarbidopa or foslevodopa in human milk or their effects on milk production or the breastfed infant.1 Carbidopa has not been studied in human milk but is excreted in rat milk.1 Levodopa has been detected in human milk and may inhibit lactation by reducing prolactin secretion.1 The benefits of breastfeeding should be weighed against the mother's need for foscarbidopa/foslevodopa and potential risks to the infant.1
Safety and effectiveness of foscarbidopa/foslevodopa in pediatric patients have not been established.1
Clinical studies of foscarbidopa/foslevodopa lacked sufficient numbers of geriatric patients ≥65 years of age to assess age-related differences in response.1 Select dosage cautiously in geriatric patients, considering their higher likelihood of reduced organ function, comorbidities, and use of concomitant medications.1
The most common adverse reactions reported with foscarbidopa/foslevodopa in clinical studies, occurring in ≥10% of patients and more frequently than oral carbidopa/levodopa, were infusion/catheter site reactions, infusion/catheter site infections, hallucinations, and dyskinesia.1
Nonselective monoamine oxidase (MAO) inhibitors (e.g., phenelzine, tranylcypromine) are contraindicated in patients receiving foscarbidopa/foslevodopa; discontinue MAO inhibitors at least 2 weeks before starting treatment with foscarbidopa/foslevodopa.1
Concomitant use of selective MAO inhibitors (e.g., rasagiline, selegiline) with foscarbidopa/foslevodopa may cause orthostatic hypotension, requiring patient monitoring.1
Concomitant use of foscarbidopa/foslevodopa with antihypertensive agents may cause symptomatic postural hypotension, requiring a potential dosage reduction of the antihypertensive drug.1
Dopamine Receptor Antagonists and Isoniazid
Dopamine D2 receptor blockers such as phenothiazines, butyrophenones, risperidone, metoclopramide, and papaverine, as well as isoniazid, may decrease the effectiveness of foslevodopa.1 Monitor patients receiving these drugs with foscarbidopa/foslevodopa for any decline in parkinsonian symptoms.1
Foscarbidopa/foslevodopa is a fixed combination preparation consisting of foscarbidopa (carbidopa-4´-monophosphate), an aromatic amino acid decarboxylation inhibitor, and foslevodopa (levodopa-4´-monophosphate), an aromatic amino acid; both are prodrugs that undergo enzymatic conversion by alkaline phosphatase to carbidopa and levodopa, respectively.1 Following subcutaneous administration, foscarbidopa/foslevodopa is rapidly converted to the pharmacologically active carbidopa and levodopa forms.1, 3 Symptoms of Parkinson syndrome are related to depletion of striatal dopamine, and levodopa is believed to act principally by increasing dopamine concentrations in the brain.1, 3
When levodopa is administered orally, it is rapidly decarboxylated to dopamine in peripheral tissues, reducing the amount that reaches the brain.1 Carbidopa inhibits this peripheral conversion by blocking aromatic amino acid decarboxylase, allowing more levodopa to cross the blood-brain barrier and be converted to dopamine in the CNS.1, 6 This helps replenish dopamine in depleted areas and improves motor symptoms of Parkinson disease.1, 3, 4
Foscarbidopa/foslevodopa is rapidly converted to carbidopa/levodopa, with plasma levels detectable within 30 minutes and steady-state levodopa levels achieved within 2 hours.1 Pharmacokinetic analysis showed comparable drug exposure across different subcutaneous administration sites, including the abdomen, arm, and thigh.1
Because foscarbidopa/foslevodopa bypasses the GI tract, food intake does not affect its absorption or systemic exposure.1
Foscarbidopa/foslevodopa exhibit plasma protein binding of 24-26%.1 Levodopa distributes between erythrocytes and plasma in a 1:1 ratio, with <10% bound to plasma proteins.1 Levodopa is transported into the brain via the large neutral amino acid carrier mechanism.1 Carbidopa, which binds approximately 36% to plasma proteins, does not cross the blood-brain barrier.1
Levodopa is primarily metabolized via aromatic amino acid decarboxylase (AAAD) and COMT.1 Other metabolic pathways include transamination and oxidation.1 Without an enzyme inhibitor (e.g., carbidopa), AAAD-mediated conversion of levodopa to dopamine is the dominant pathway, whereas COMT converts levodopa to 3-O-methyldopa.1 When co-administered with carbidopa, the elimination half-life of levodopa is approximately 1.5 hours.1
Carbidopa undergoes metabolism to 2 primary metabolites, which are primarily excreted in the urine unchanged or as glucuronide conjugates.1 Unchanged carbidopa accounts for approximately 30% of total urinary excretion, with an elimination half-life of about 2 hours.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Foscarbidopa/foslevodopa is available through designated specialty pharmacies. Contact manufacturer or consult the foscarbidopa/foslevodopa website ([Web]) for specific information.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for subcutaneous use | Foscarbidopa 12 mg/mL and foslevodopa 240 mg/mL | Vyalev® | AbbVie |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions April 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. AbbVie Inc. Vyalev® (foscarbidopa/foslevodopa) SUBCUTANEOUS prescribing information. 2024 Oct. [Web]
2. Food and Drug Administration. Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website. Accessed 2025 Jan 19. [Web]
3. Soileau MJ, Aldred J, Budur K, et al. Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced parkinson disease: a randomised, double-blind, active-controlled, phase 3 trial [published correction appears in Lancet Neurol. 2023 Mar;22(3):e5. doi: 10.1016/S1474-4422(23)00048-0.]. Lancet Neurol. 2022;21(12):1099-1109. doi:10.1016/S1474-4422(22)00400-8
4. Aldred J, Freire-Alvarez E, Amelin AV, et al. Continuous subcutaneous foslevodopa/foscarbidopa in parkinson disease: Safety and efficacy results from a 12-month, single-arm, open-label, phase 3 study [published correction appears in Neurol Ther. 2023 Dec;12(6):1959-1960. doi: 10.1007/s40120-023-00554-w.]. Neurol Ther. 2023;12(6):1937-1958. doi:10.1007/s40120-023-00533-1
5. Fox SH, Katzenschlager R, Lim SY, et al. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of parkinson disease [published correction appears in Mov Disord. 2018 Dec;33(12):1992. doi: 10.1002/mds.27548.]. Mov Disord. 2018;33(8):1248-1266. doi:10.1002/mds.27372
6. Tanner CM, Ostrem JL. Parkinson's disease. N Engl J Med. 2024;391(5):442-452. doi:10.1056/NEJMra2401857