Duopa Drug Information

DUOPA ® is indicated for the treatment of motor fluctuations in patients with advanced Parkinson’s disease.

Management of Vitamin B6 Levels

Evaluate vitamin B6 levels prior to initiating carbidopa/levodopa therapies including DUOPA, periodically during treatment, and as clinically indicated. If vitamin B6 levels are low, supplement to sufficient levels per standard of care. Patients may initiate and continue treatment with DUOPA while supplementing vitamin B6. 2. 2 DUOPA Daily Dose DUOPA is administered over a 16-hour infusion period.

The daily dose is determined by individualized patient titration and composed of: A Morning Dose A Continuous Dose Extra Doses The maximum recommended daily dose of DUOPA is 2000 mg of the levodopa component (i.e., one cassette per day) administered over 16 hours. At the end of the daily 16-hour infusion, patients will disconnect the pump from the PEG-J and take their night-time dose of oral immediate-release carbidopa-levodopa tablets. Treatment with DUOPA is initiated in 3 steps: Conversion of patients to oral immediate-release carbidopa-levodopa tablets in preparation for DUOPA treatment.

Calculation and administration of the DUOPA starting dose (Morning Dose and Continuous Dose) for Day 1. Titration of the dose as needed based on individual clinical response and tolerability. Extra Doses DUOPA has an extra dose function that can be used to manage acute “Off” symptoms that are not controlled by the Morning Dose and the Continuous Dose administered over 16 hours.

The extra dose function should be set at 1 mL (20 mg of levodopa) when starting DUOPA. If the amount of the extra dose needs to be adjusted, it is typically done in 0.2 mL increments. The extra dose frequency should be limited to one extra dose every 2 hours.

Administration of frequent extra doses may cause or worsen dyskinesias. Once no further adjustments are required to the DUOPA Morning Dose, Continuous Dose, or Extra Dose, this dosing regimen should be administered daily. Over time, additional changes may be necessary based on the patient’s clinical response and tolerability. 2. 3 Initiation and Titration Instructions Prepare for DUOPA Treatment Prior to initiating DUOPA, convert patients from all other forms of levodopa to oral immediate-release carbidopa-levodopa tablets (1:4 ratio).

Patients should remain on a stable dose of their concomitant medications taken for the treatment of Parkinson's disease before initiation of DUOPA infusion. Healthcare providers should ensure patients take their oral Parkinson's disease medications the morning of the PEG-J procedure. Determine the DUOPA Starting Dose for Day 1 The steps for determining the initial DUOPA daily dosing (Morning Dose and Continuous Dose) for Day 1 are outlined below.

Adjustments to concomitant Parkinson’s disease medications may be needed. In the controlled trial, the average number of titration days required to establish a stable Morning and Continuous Dose was 5 days. Additional dose adjustments may be necessary over time based on the patient level of activity and disease progression.

The recommendations for adjusting the DUOPA Morning and Continuous Doses are provided below. Morning Dose Adjustment If there was an inadequate clinical response within 1 hour of the Morning Dose on the preceding day, adjust the Morning Dose (excluding the 3 mL to fill the tube) as follows: If the Morning Dose on the preceding day was less than or equal to 6 mL, increase the Morning Dose by 1 mL. If the Morning Dose on the preceding day was greater than 6 mL, increase the Morning Dose by 2 mL.

If the patient experienced dyskinesias or DUOPA-related adverse reactions within 1 hour of the Morning Dose on the preceding day, decrease the Morning Dose by 1 mL. Continuous Dose Adjustment Consider increasing the Continuous Dose based on the number and volume of Extra Doses of DUOPA (i.e., total amount of levodopa component) that were needed for the previous day and the patient’s clinical response. Consider decreasing the Continuous Dose if the patient experienced troublesome dyskinesia, or other troublesome DUOPA-related adverse reactions on the preceding day: For troublesome adverse reactions lasting for a period of one hour or more, decrease the Continuous Dose by 0.3 mL per hour.

For troublesome adverse reactions lasting for two or more periods of one hour or more, decrease the Continuous Dose by 0.6 mL per hour. 2. 4 Administration Information DUOPA should be used at room temperature. Take one DUOPA cassette out of the refrigerator and out of the carton 20 minutes prior to use; failure to use the product at room temperature may result in the patient not receiving the right amount of medication. DUOPA is delivered as a 16-hour infusion through either a naso-jejunal tube for short-term administration or through a PEG-J for long-term administration.

The cassettes are for single-use only and should not be used for longer than 16 hours, even if some drug product remains. An opened cassette should not be re-used. The PEG-J should be disconnected from the pump at the end of the daily 16-hour administration period and flushed with room temperature potable water with a syringe.

Long-term administration of DUOPA requires placement of a PEG-J outer transabdominal tube and inner jejunal tube by percutaneous endoscopic gastrostomy. DUOPA is dispensed from medication cassette reservoirs that are specifically designed to be connected to the CADD ® -Legacy 1400 pump. Establishment of the transabdominal port should be performed by a gastroenterologist or other healthcare provider experienced in this procedure.

See Table 1 for the recommended tubing sets for PEG-J administration. For short-term, temporary administration of DUOPA prior to PEG-J tube placement, treatment may be initiated by a naso-jejunal tube with observation of the patient’s clinical response. See Table 2 for the recommended tubing sets for naso-jejunal administration.

Table 1. Recommended Tubing Sets for Long-Term PEG-J DUOPA Administration Product Name Manufacturer AbbVie PEG 15 and 20 Fr AbbVie J AbbVie Inc. AbbVie Inc.

Table 2. Recommended Tubing Sets for Short-Term Naso-Jejunal DUOPA Administration 2. 5 Discontinuation of DUOPA Avoid sudden discontinuation or rapid dose reduction in patients taking DUOPA. If patients need to discontinue DUOPA, the dose should be tapered or patients should be switched to oral immediate-release carbidopa-levodopa tablets.

When using a PEG-J tube, DUOPA can be discontinued by withdrawing the tube and letting the stoma heal. The removal of the tube should only be performed by a qualified healthcare provider.

Clinical Trials Experience

Because clinical studies are run under widely varying conditions, the incidence of adverse reactions 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 practice. In a 12-week, active-controlled clinical trial (Study 1), a total of 71 patients with advanced Parkinson’s disease were enrolled and had a PEG-J procedure. Of these, 37 patients received DUOPA and 34 received oral immediate-release carbidopa-levodopa.

The most common adverse reactions for DUOPA (incidence at least 7% greater than oral immediate-release carbidopa-levodopa) were: complication of device insertion, nausea, depression, peripheral edema, hypertension, upper respiratory tract infection, oropharyngeal pain, atelectasis, and incision site erythema. Table 3 lists the incidence of adverse reactions occurring in the DUOPA-treated group (requiring at least 2 patients in this group) in Study 1 when the incidence was numerically greater than that for oral immediate-release carbidopa-levodopa. Table 3.

Adverse Reactions in Study 1 for DUOPA in Patients with Advanced Parkinson’s disease Procedure and Device- Related Adverse Reactions The most common adverse reactions associated with complications due to naso-jejunal (NJ) insertion were: oropharyngeal pain, abdominal distention, abdominal pain, abdominal discomfort, pain, throat irritation, gastrointestinal injury, esophageal hemorrhage, anxiety, dysphagia, and vomiting. The most common adverse reactions associated with complications due to PEG-J insertion were: abdominal pain, abdominal discomfort, abdominal distension, flatulence, or pneumoperitoneum. Additional adverse reactions that were co-reported with complication of naso-jejunal and PEG-J insertion included upper abdominal pain, duodenal ulcer, duodenal ulcer hemorrhage, erosive duodenitis, erosive gastritis, gastrointestinal hemorrhage, intussusception, peritonitis, post-operative abscess, and small intestine ulcer.

Monoamine Oxidase (MAO) Inhibitors

The use of nonselective MAO inhibitors with DUOPA is contraindicated. Discontinue use of any nonselective MAO inhibitors at least two weeks prior to initiating DUOPA. The use of selective MAO-B inhibitors (e.g., rasagiline and selegiline) with DUOPA may be associated with orthostatic hypotension.

Monitor patients who are taking these drugs.

Antihypertensive Drugs

The concurrent use of DUOPA with antihypertensive medications can cause symptomatic postural hypotension. A dose reduction of the antihypertensive medication may be needed after starting or increasing the dose of DUOPA.

Dopamine D2 Receptor Antagonists and Isoniazid Dopamine

D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide, papaverine) and isoniazid may reduce the effectiveness of levodopa. Monitor patients for worsening Parkinson’s symptoms.

Iron Salts

Iron salts or multi-vitamins containing iron salts can form chelates with levodopa, carbidopa, and can cause a reduction in the bioavailability of DUOPA. If iron salts or multi-vitamins containing iron salts are co-administered with DUOPA, monitor patients for worsening Parkinson’s symptoms.

High-Protein Diet

Because levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be decreased in patients on a high-protein diet. Advise patients that a high-protein diet may reduce the effectiveness of DUOPA.

Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of DUOPA in pregnant women. 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 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 Safety and effectiveness in pediatric patients have not been established.

DUOPA is contraindicated in patients who are currently taking a nonselective monoamine oxidase (MAO) inhibitor (e.g., phenelzine and tranylcypromine) or have recently (within 2 weeks) taken a nonselective MAO inhibitor. Hypertension can occur if these drugs are used concurrently.

Management of acute overdosage with DUOPA is the same as management of acute overdosage with levodopa. Pyridoxine is not effective in reversing the actions of oral immediate-release carbidopa-levodopa. In the event of an overdosage with DUOPA, the infusion should be stopped and the pump disconnected immediately.

Administer intravenous fluids and maintain an adequate airway. Patients should receive electrocardiographic monitoring for arrhythmias and hypotension.