Vyalev

foscarbidopa/foslevodopa · Injection · Subcutaneous

Prescription (Rx)

Uses

1 INDICATIONS AND USAGE VYALEV is indicated for the treatment of motor fluctuations in adults with advanced Parkinson’s disease (PD). VYALEV is a combination of foscarbidopa (an aromatic amino acid decarboxylation inhibitor) and foslevodopa (an aromatic amino acid) indicated for the treatment of motor fluctuations in adults with advanced Parkinson’s disease. ( 1 )

Dosage and administration

Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. ( 2.1 ) 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. ( 2.3 ) The maximum recommended daily dosage of VYALEV is 3,525 mg of foslevodopa (approximately 2,500 mg levodopa). ( 2.3 ) 2.1 Management of Vitamin B6 Levels Evaluate vitamin B6 levels prior to initiating carbidopa/levodopa therapies, including VYALEV, periodically during treatment, and as clinically indicated [see Warnings and Precautions 5.7 ] . If vitamin B6 levels are low, supplement to sufficient levels per standard of care. Patients may initiate and continue treatment with VYALEV while supplementing vitamin B6. 2. 2 Important Information For subcutaneous administration only. Patients selected for treatment with VYALEV should be capable of understanding and using the delivery system [see Healthcare Professional Instructions for Use of VYAFUSER Pump , and Patient Instructions for Use of VYAFUSER Pump ] themselves or with assistance from a caregiver. 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 ( 2.4 ), 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. All dosages should be converted to the equivalent dosage of immediate-release levodopa to obtain the TLD. Prescribers should adjust the total dose of levodopa-containing products for COMT inhibitor use. See the Prescribing Information for the 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 VYALEV foslevodopa component by multiplying the TLD by 1.3. The conversion factor takes into account the molecular weight and bioavailability of foslevodopa compared to levodopa. Step 3: Determine the total daily volume (mL) of VYALEV by dividing the total daily dosage (mg) of VYALEV by 240. 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 ( 2.4 ) 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. Loading doses can be administered either with VYALEV or patients can continue using oral immediate-release carbidopa/levodopa tablets. The loading dose should be calculated from the first morning dose of oral immediate release carbidopa/levodopa the patient took before starting treatment with VYALEV. If VYALEV is used for the loading dose, multiply the first morning dose of oral immediate release levodopa by 1.3 and divide by 240 to determine the loading dose of VYALEV. 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). Table 1. Extra Dose Option for VYALEV VYALEV extra dose volume Approximate equivalent levodopa dose * 0.1 mL 17 mg 0.15 mL 25.5 mg 0.2 mL 34 mg 0.25 mL 42.5 mg 0.3 mL 51 mg * 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 ( 2.3 ) 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 ( 3 ) ] . The infusion set (cannula) can remain in place for up to 3 days when VYALEV is infused continuously.

Dosage forms and strengths

Injection: 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL (12 mg foscarbidopa and 240 mg foslevodopa per mL). Each single-dose vial contains 10 mL of a colorless to yellow to brown (may have a purple or red tint) and clear to slightly opalescent solution. Injection: 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL (12 mg foscarbidopa and 240 mg foslevodopa per mL). ( 3 )

Contraindications

4 CONTRAINDICATIONS VYALEV is contraindicated in patients who are currently taking a non-selective monoamine oxidase (MAO) inhibitor or have recently (within 2 weeks) taken a nonselective MAO inhibitor. Hypertension can occur if these drugs are used concurrently [see Drug Interactions ( 7.1 )] . VYALEV is contraindicated in patients who are currently taking a nonselective monoamine oxidase (MAO) inhibitor or have recently (within 2 weeks) taken a nonselective MAO inhibitor. ( 4 )

Warnings and precautions

May cause falling asleep during activities of daily living. ( 5.1 ) Hallucinations/Psychosis: May respond to dose reduction of VYALEV. ( 5.2 ) Impulse Control Behaviors: Consider dose reductions or stopping VYALEV. ( 5.3 ) Infusion Site Reactions and Infections: Monitor for infusion site infections: Following aseptic techniques while using this medication and frequent rotation of the infusion site is recommended to reduce the risk. ( 5.4 ) Avoid sudden discontinuation or rapid dose reduction to reduce the risk of withdrawal-emergent hyperpyrexia and confusion. ( 5.5 ) May cause or exacerbate dyskinesia: Consider dose reduction of VYALEV. ( 5.6 ) 5.1 Falling Asleep During Activities of Daily Living and Somnolence Patients treated with levodopa (the active metabolite of VYALEV) have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence while on levodopa, some perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event (sleep attack). Some of these events have been reported more than one year after initiation of treatment. Falling asleep while engaged in activities of daily living usually occurs in patients experiencing preexisting somnolence, although patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness while using VYALEV, especially since some of the events occur well after the start of treatment. Prescribers should be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients who have already experienced somnolence or an episode of sudden sleep onset should not participate in these activities while taking VYALEV. Before initiating treatment with VYALEV, advise patients about the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence with VYALEV such as the use of concomitant sedating medications or the presence of sleep disorders. Consider discontinuing VYALEV in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating). If VYALEV is continued, patients should be advised not to drive and to avoid other potentially dangerous activities that might result in harm if the patient becomes somnolent. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. 5.2 Hallucinations/Psychosis There is an increased risk for hallucinations and psychosis in patients taking VYALEV. In Study 1 [see Clinical Studies ( 14 )], hallucinations occurred in 12.2% of patients treated with VYALEV compared to 1.5% of patients treated with oral immediate-release carbidopa-levodopa. Psychosis occurred in 4.1% of patients treated with VYALEV compared to 1.5% of patients treated with oral immediate-release carbidopa-levodopa. Treatment with VYALEV was discontinued in 1 (1.4%) patient because of hallucinations. Hallucinations associated with levodopa may present shortly after the initiation of therapy and may be responsive to dose reduction of VYALEV or other concomitantly administered medications. 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 of treatment is recommended if these symptoms develop. Because of the risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with VYALEV. In addition, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate the symptoms of PD and may decrease the effectiveness of VYALEV [see Drug Interactions ( 7.3 ) ] . 5.3 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, and the inability to control these urges while taking one or more of the medications, including VYALEV, that increase central dopaminergic tone and that are generally used for the treatment of PD. In some cases, although not all, these urges were reported to have stopped when the dose was reduced, or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to ask patients or their caregivers specifically about the development of new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with VYALEV. Consider reducing the dose or discontinuing VYALEV if a patient develops such urges. 5.4 Infusion Site Reactions and Infections VYALEV can cause infusion site reactions and infections. In Study 1, one or more infusion site reactions were reported in 62% of patients treated with VYALEV and 8% of patients who received placebo subcutaneous infusion. Various types of reactions at the infusion site have been reported including: erythema, pain, edema, nodule, bruising, hemorrhage, induration, pruritus, extravasation, inflammation, mass, warmth, hematoma, pallor, rash, and swelling. In Study 1, 8% of patients treated with VYALEV and no patient who received placebo withdrew from treatment because of an infusion site reaction. In Study 1, infusion site infections occurred in 28% of patients treated with VYALEV compared to 3% of patients who received placebo subcutaneous infusion.

Side effects

The following serious adverse reactions are discussed below and elsewhere in labeling: Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions ( 5.1 ) ] Hallucinations/Psychosis [see Warnings and Precautions ( 5.2 ) ] Impulse Control/Compulsive Behaviors [see Warnings and Precautions ( 5.3 ) ] Infusion Site Reactions and Infections [see Warnings and Precautions ( 5.4 )] Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions ( 5.5 ) ] Dyskinesia [see Warnings and Precautions ( 5.6 ) ] Vitamin B6 Deficiency and Seizures [see Warnings and Precautions ( 5.7 ) ] Cardiovascular Ischemic Events [see Warnings and Precautions ( 5.8 ) ] Glaucoma [see Warnings and Precautions ( 5.9 )] Most common adverse reactions for VYALEV (VYALEV incidence at least 10% and greater than oral carbidopa-levodopa incidence) were infusion/catheter site reactions, infusion/catheter site infections, hallucinations, and dyskinesia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In Study 1, a 12-week, active-controlled clinical trial, a total of 141 patients with advanced PD were enrolled [see Clinical Studies ( 14 )]. Of these, 74 patients received VYALEV and 67 received oral immediate-release carbidopa-levodopa with placebo subcutaneous infusion. Adverse reactions led to discontinuation of VYALEV in 22% of patients, which included hallucinations, infusion site reactions, and infusion site infections [see Warnings and Precautions ( 5.2 , 5.5 )]. Table 2 presents the adverse reactions that occurred in ≥3% of patients who received VYALEV and with a difference of >2% between the VYALEV and the oral immediate release carbidopa-levodopa groups in Study 1. Table 2. Adverse Reactions in Study 1 that Occurred in ≥3% of Patients with Advanced PD who Received VYALEV and 2% Difference from Active Control Adverse Reaction VYALEV (n = 74 ) % Oral immediate-release carbidopa-levodopa (n = 67 ) % Infusion/catheter site reaction a 62 8 Infusion/catheter site infection b 28 3 Hallucination 12 2 Dyskinesia 11 6 On and off phenomenon 8 0 Balance disorder 5 0 Constipation 5 0 Peripheral swelling 5 0 Agitation 4 2 Insomnia 4 2 Psychotic disorder c 4 2 Dyspnea 4 0 Infusion/catheter site reaction includes multiple related terms. Infusion site/catheter site infections includes multiple related terms. Psychotic disorder includes psychotic disorder, delusion, and paranoia.

Drug interactions

Selective MAO-B inhibitors: May cause orthostatic hypotension. ( 7.1 ) Antihypertensive drugs: May cause symptomatic postural hypotension. Dosage adjustment of the antihypertensive drug may be needed. ( 7.2 ) Dopamine D2 receptor antagonists and isoniazid may reduce the effectiveness of VYALEV. ( 7.3 ) 7.1 Monoamine Oxidase (MAO) Inhibitors Nonselective MAO Inhibitors The use of nonselective MAO inhibitors (e.g., phenelzine and tranylcypromine) with VYALEV is contraindicated [see Contraindications ( 4 ) ] . Discontinue use of any nonselective MAO inhibitors at least two weeks prior to initiating VYALEV. Selective MAO Inhibitors The use of selective MAO-B inhibitors (e.g., rasagiline and selegiline) with VYALEV may be associated with orthostatic hypotension. Monitor patients who are taking these drugs. 7.2 Antihypertensive Drugs The concurrent use of VYALEV with antihypertensive medications can cause symptomatic postural hypotension. A dose reduction of the antihypertensive medication may be needed after starting or increasing the dosage of VYALEV. 7.3 Dopamine D2 Receptor Antagonists and Isoniazid Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide, papaverine) and isoniazid may reduce the effectiveness of foslevodopa. Monitor patients for worsening Parkinson’s symptoms when patients are taking these medications with VYALEV.

Use in specific populations

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) 8.1 Pregnancy Risk Summary There are no data on the developmental risk associated with the use of VYALEV (foscarbidopa and foslevodopa) in pregnant women. Foscarbidopa is a prodrug of carbidopa, and foslevodopa is a prodrug of levodopa. In animal studies, carbidopa-levodopa has been shown to be developmentally toxic (including teratogenic effects) at clinically relevant doses (see Data). The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data When administered to pregnant rabbits throughout organogenesis, carbidopa-levodopa caused both visceral and skeletal malformations in fetuses at all doses and ratios of carbidopa-levodopa tested. No teratogenic effects were observed when carbidopa-levodopa was administered to pregnant mice throughout organogenesis. There was a decrease in the number of live pups delivered by rats receiving carbidopa-levodopa during organogenesis. 8.2 Lactation Risk Summary Foscarbidopa and Foslevodopa There are no adequate data on the presence of foscarbidopa or foslevodopa in human milk, the effects of foscarbidopa or foslevodopa on milk production or on the breastfed infant. Foscarbidopa is a prodrug of carbidopa, and foslevodopa is a prodrug of levodopa. Carbidopa There are no adequate data on the presence of carbidopa in human milk, the effects on the breastfed infant, or the effects on 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 of levodopa on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VYALEV and any potential adverse effects on the breastfed infant from VYALEV or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of VYALEV did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Pregnancy

8.1 Pregnancy Risk Summary There are no data on the developmental risk associated with the use of VYALEV (foscarbidopa and foslevodopa) in pregnant women. Foscarbidopa is a prodrug of carbidopa, and foslevodopa is a prodrug of levodopa. In animal studies, carbidopa-levodopa has been shown to be developmentally toxic (including teratogenic effects) at clinically relevant doses (see Data). The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data When administered to pregnant rabbits throughout organogenesis, carbidopa-levodopa caused both visceral and skeletal malformations in fetuses at all doses and ratios of carbidopa-levodopa tested. No teratogenic effects were observed when carbidopa-levodopa was administered to pregnant mice throughout organogenesis. There was a decrease in the number of live pups delivered by rats receiving carbidopa-levodopa during organogenesis.

Pediatric use

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Clinical studies of VYALEV did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Overdosage

In the event of an overdosage with VYALEV, the infusion should be stopped immediately. Administer intravenous fluids and maintain an adequate airway. Electrocardiographic monitoring should be used, and the patient observed carefully for the development of cardiac arrhythmias; if necessary, an appropriate antiarrhythmic therapy should be given. Patients must also be monitored for hypotension.

Description

11 DESCRIPTION VYALEV injection is a solution that is a combination of foscarbidopa (carbidopa-4´-monophosphate) and foslevodopa (levodopa-4´-monophosphate). Foscarbidopa and foslevodopa are prodrugs that undergo enzymatic bioconversion via intrinsic alkaline phosphatase to carbidopa and levodopa, respectively, in vivo . Foscarbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white to light yellow powder, freely soluble in aqueous media, with a molecular weight of 306.21 g/mol anhydrous. It is designated chemically as (2 S )-2-hydrazinyl-3-[3-hydroxy-4-(phosphonooxy)phenyl]-2-methylpropanoic acid trihydrate. Its empirical formula is C 10 H 15 N 2 O 7 P (anhydrous basis), and its structural formula is: Foslevodopa, an aromatic amino acid, is a white to off-white powder, freely soluble in aqueous media, with a molecular weight of 277.17 g/mol. It is designated chemically as (2 S )-2-amino-3-[3-hydroxy-4-(phosphonooxy)phenyl] propanoic acid. Its empirical formula is C 9 H 12 NO 7 P, and its structural formula is: VYALEV (foscarbidopa and foslevodopa) injection is a sterile, preservative-free solution for subcutaneous infusion. VYALEV is supplied in a 10 mL single-dose glass vial that contains 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL (12 mg foscarbidopa and 240 mg foslevodopa per mL). VYALEV may contain sodium hydroxide and/or hydrochloric acid to adjust the pH to approximately 7.4. Foscarbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white to light yellow powder, freely soluble in aqueous media, with a molecular weight of 306.21 g/mol anhydrous. It is designated chemically as (2S)-2-hydrazinyl-3-[3-hydroxy-4-(phosphonooxy)phenyl]-2-methylpropanoic acid trihydrate. Its empirical formula is C10H15N2O7P (anhydrous basis), and its structural formula is: Foslevodopa, an aromatic amino acid, is a white to off-white powder, freely soluble in aqueous media, with a molecular weight of 277.17 g/mol. It is designated chemically as (2S)-2-amino-3-[3-hydroxy-4-(phosphonooxy)phenyl] propanoic acid. Its empirical formula is C9H12NO7P, and its structural formula is:

Mechanism of action

12.1 Mechanism of Action VYALEV is a prodrug combination of foscarbidopa (carbidopa-4´-monophosphate) and foslevodopa (levodopa-4´-monophosphate). Foscarbidopa and foslevodopa are converted in vivo to carbidopa and levodopa. Carbidopa When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain. Levodopa Levodopa is the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa treats symptoms of Parkinson's disease.

How supplied

16.1 How Supplied VYALEV injection contains 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL (12 mg foscarbidopa and 240 mg foslevodopa per mL) and is a colorless to yellow to brown (may have a purple or red tint), and clear to slightly opalescent solution. Each single-dose glass vial is filled with approximately 10 mL of solution and is fitted with a grey rubber stopper, aluminum crimp cap, and turquoise plastic flip-off cap. The rubber stopper on the vial does not contain natural rubber latex. Carton of 7 VYALEV vials: NDC 0074-0501-01 The VYAFUSER pump used to administer VYALEV (foscarbidopa and foslevodopa) is provided separately. 16.2 Storage and Handling Keep the medication vials in the outer carton to protect the vials from breaking. Store VYALEV refrigerated at 2°C to 8°C (36°F to 46°F). VYALEV may be stored at room temperature up to a maximum of 30°C (86°F) for a single period of up to 28 days. Once VYALEV has been stored at room temperature, do not return the product to the refrigerator. If stored at room temperature, discard VYALEV if not used within 28 days. Do not freeze. Do not shake. 16.1 How Supplied VYALEV injection contains 120 mg foscarbidopa and 2,400 mg foslevodopa per 10 mL (12 mg foscarbidopa and 240 mg foslevodopa per mL) and is a colorless to yellow to brown (may have a purple or red tint), and clear to slightly opalescent solution. Each single-dose glass vial is filled with approximately 10 mL of solution and is fitted with a grey rubber stopper, aluminum crimp cap, and turquoise plastic flip-off cap. The rubber stopper on the vial does not contain natural rubber latex. Carton of 7 VYALEV vials: NDC 0074-0501-01 The VYAFUSER pump used to administer VYALEV (foscarbidopa and foslevodopa) is provided separately.

Storage

16.2 Storage and Handling Keep the medication vials in the outer carton to protect the vials from breaking. Store VYALEV refrigerated at 2°C to 8°C (36°F to 46°F). VYALEV may be stored at room temperature up to a maximum of 30°C (86°F) for a single period of up to 28 days. Once VYALEV has been stored at room temperature, do not return the product to the refrigerator. If stored at room temperature, discard VYALEV if not used within 28 days. Do not freeze. Do not shake.

Patient information

Advise the patient to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use ). Administration Information Refer patients to the Instructions for Use for complete administration instructions. Inform patients of aseptic technique and of subcutaneous administration site selection and rotation [see Dosage and Administration ( 2.4 )] . Instruct the patient to record the date when VYALEV is first removed from the refrigerator in the space provided on the carton [see Storage and Handling ( 16.2 )] . Interruption of VYALEV Infusion Inform patients that if they disconnect the pump for less than 1 hour (e.g., to shower or for a short medical procedure), a new infusion set (tubing and cannula) or rotation of the infusion site is not needed before resuming infusion, unless medically indicated. Instruct the patient to stop the pump and disconnect the tubing. The syringe can remain attached to the pump until the tubing is reconnected. Refer the patient to the Patient Instructions for Use for additional information. Inform patients that if they have a prolonged interruption of therapy lasting more than 1 hour, a new infusion set (tubing and cannula) should be used, and rotation to a different infusion site is required before resuming infusion. In addition, if VYALEV is interrupted for more than 3 hours, advise patients to administer a loading dose with either VYALEV or oral immediate-release carbidopa and levodopa [see Dosage and Administration ( 2.3 )] . Instruct patients to have oral carbidopa and levodopa available in case treatment with VYALEV is interrupted for 1 hour or longer. Falling Asleep during Activities of Daily Living and Somnolence Alert patients to the potential sedating effects caused by VYALEV, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Because somnolence is a common adverse reaction with potentially serious consequences, patients should not drive a car, operate machinery, or engage in other potentially dangerous activities until they have gained sufficient experience with VYALEV to gauge whether it affects their mental and/or motor performance adversely. Advise patients that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., conversations, eating, driving a motor vehicle, etc.) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities until they have contacted their healthcare professional. Advise patients of possible additive effects when patients are taking other sedating medications, alcohol, or other central nervous system depressants (e.g., benzodiazepines, antipsychotics, antidepressants, etc.) in combination with VYALEV or when taking a concomitant medication that increases plasma levels of levodopa [see Warnings and Precautions ( 5.1 ) ] . Hallucinations/Psychosis/Confusion Inform patients that they may experience hallucinations (unreal visions, sounds, or sensations) and other symptoms of psychosis while taking VYALEV. Tell patients to report hallucinations, abnormal thinking, psychotic behavior, or confusion to their healthcare professional promptly should they develop [see Warnings and Precautions ( 5.2 ) ] . Impulse Control/Compulsive Behaviors Advise patients that they may experience impulse control and/or compulsive behaviors while taking VYALEV. Advise patients to inform their healthcare professional if they develop new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with VYALEV [see Warnings and Precautions ( 5.3 ) ] . Infusion Site Reactions and Infections Advise patients to contact their healthcare professional if they notice signs of inflammation or infection at the infusion site, such as local spreading of redness, swelling, warmth, pain, discoloration when they apply pressure to the area, and/or fever. Tell patients to follow aseptic techniques while using VYALEV and to regularly change the infusion site (at least every third day), using a new infusion set. Advise patients to make sure the new infusion site is at least 1 inch (2.5 cm) from a site used in the last 12 days. Instruct patients to remove the cannula if an infection at the infusion site occurs and to contact their healthcare provider. Inform patients that they may need to change the infusion site more often than every third day if they notice any of the above-mentioned signs of infection [see Warnings and Precautions ( 5.4 )]. Withdrawal-Emergent Hyperpyrexia and Confusion Advise patients to contact their healthcare professional before stopping VYALEV. Tell patients to inform their healthcare professional if they develop withdrawal symptoms such as fever, confusion, or severe muscle stiffness [see Warnings and Precautions ( 5.5 ) ] . Dyskinesia Inform patients that VYALEV may cause or exacerbate pre-existing dyskinesias [see Warnings and Precautions ( 5.6 ) ] . Vitamin B6 Deficiency and Seizures Inform patients that vitamin B6 deficiency may develop during treatment with carbidopa/levodopa therapies, including VYALEV. Tell patients to inform their healthcare provider if they develop symptoms such as depression, confusion, cheilosis, glossitis, dermatitis, anemia, neuropathy, and/or seizures [see Warnings and Precautions ( 5.7 )]. Pregnancy Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant during treatment [ see Use in Specific Populations ( 8.1 ) ] . Lactation Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations ( 8.2 ) ] . Manufactured for: AbbVie Inc. North Chicago, IL 60064 U.S.A VYALEV and its design are trademarks of AbbVie AB. VYAFUSER™ is a trademark of AbbVie AB. ©2026 AbbVie. All rights reserved. 20098507 R1 03-2026

Label text from the FDA structured product label by AbbVie Inc. (revised Mar 19, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Foscarbidopa in 1 product
Foslevodopa in 1 product

Vyalev NDC products (1)

NDC	Strength & form	Labeler	Type
0074-0501	Foscarbidopa 12 mg/mL; Foslevodopa 240 mg/mL Injection	AbbVie Inc.	NDA