Foscarbidopa/Foslevodopa

FDA Drug Information • Also known as: Vyalev

Brand Names: Vyalev
Dosage Form: INJECTION
Product Type: DRUG FOR FURTHER PROCESSING

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...

What Is Foscarbidopa/Foslevodopa Used For?

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

2 DOSAGE AND ADMINISTRATION For subcutaneous administration only, preferably in the abdomen, via the VYAFUSER pump. ( 2.1 , 2.2 , 2.3 ) See the Full Prescribing Information for calculation of the base continuous dosage, hourly infusion rate, optional loading dose, and extra dose. ( 2.2 ) The maximum recommended daily dosage of VYALEV is 3,525 mg of foslevodopa (approximately 2,500 mg levodopa). ( 2.2 ) 2.1 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. 2.2 Recommended Dosage VYALEV (foscarbidopa and foslevodopa) is administered as a subcutaneous infusion with the VYAFUSER pump [ see Dosage and Administration ( 2.3 ), 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 ( 2.3 ) 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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 ) ] Cardiovascular Ischemic Events [see Warnings and Precautions ( 5.7 ) ] Glaucoma [see Warnings and Precautions ( 5.8 )] 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

7 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.

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 )

Pregnancy and Breastfeeding

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.

Overdosage

10 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.