Duopa Drug Information
Generic name: CARBIDOPA AND LEVODOPA
Aromatic Amino Acid [EPC]
Uses of Duopa
® is indicated for the treatment of motor fluctuations in patients with advanced Parkinson’s disease. DUOPA is a combination of carbidopa (an aromatic amino acid decarboxylation inhibitor) and levodopa (an aromatic amino acid) indicated for the treatment of motor fluctuations in patients with advanced Parkinson’s disease
Dosage & Administration of Duopa
| a. | Determine the total amount of levodopa (in milligrams) in the first dose of oral immediate-release carbidopa-levodopa that was taken by the patient on the previous day. |
|---|---|
| b. | Convert the oral levodopa dose from milligrams to milliliters by multiplying the oral dose by 0.8 and dividing by 20 mg/mL. This calculation will provide the Morning Dose of DUOPA in milliliters. |
| c. | Add 3 milliliters to the Morning Dose to fill (prime) the intestinal tube to obtain the Total Morning Dose. |
| d. | The Total Morning Dose is usually administered over 10 to 30 minutes. |
| e. | Program the pump to deliver the Total Morning Dose. |
| a. | Determine the amount of oral immediate-release levodopa that the patient received from oral immediate-release carbidopa-levodopa doses throughout the previous day (16 waking hours), in milligrams. Do not include the doses of oral immediate-release carbidopa-levodopa taken at night when calculating the levodopa amount. |
| b. | Subtract the first oral levodopa dose in milligrams taken by the patient on the previous day (determined in Step 1 (a)) from the total oral levodopa dose in milligrams taken over 16 waking hours (determined in Step 2 (a)). Divide the result by 20 mg/mL. This is the dose of DUOPA administered as a Continuous Dose (in mL) over 16 hours. |
| c. | The hourly infusion rate (mL per hour) is obtained by dividing the Continuous Dose by 16 (hours). This value will be programmed into the pump as the continuous rate. |
| d. | If persistent or numerous “Off” periods occur during the 16-hour infusion, consider increasing the Continuous Dose or using the Extra Dose function. If dyskinesia or DUOPA-related adverse reactions occur, consider decreasing the Continuous Dose or stopping the infusion until the adverse reactions subside. |
Side Effects of Duopa
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 clinical studies, 416 patients with advanced Parkinson’s disease received DUOPA. 338 patients were treated with DUOPA for more than 1 year, 233 patients were treated with DUOPA for more than 2 years, and 162 patients were treated with DUOPA for more than 3 years. 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 Preferred Term DUOPA (n = 37) % Oral immediate-release carbidopa-levodopa a (n = 34) % Complication of device insertion 57 44 Nausea 30 21 Constipation 22 21 Incision site erythema 19 12 Dyskinesia 14 12 Depression 11 3 Post procedural discharge 11 9 Peripheral edema 8 0 Hypertension 8 0 Upper respiratory tract infection 8 0 Oropharyngeal pain 8 0 Atelectasis 8 0 Confusional state 8 3 Anxiety 8 3 Dizziness 8 6 Hiatal hernia 8 6 Postoperative ileus 5 0 Sleep disorder 5 0 Pyrexia 5 0 Excessive granulation tissue 5 0 Rash 5 0 Bacteriuria 5 0 White blood cells urine positive 5 0 Hallucination 5 3 Psychotic disorder 5 3 Diarrhea 5 3 Dyspepsia 5 3 a All patients in the clinical trial regardless of treatment arm received a PEG-J. 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.
Warnings & Cautions for Duopa
Gastrointestinal and Gastrointestinal Procedure-Related Risks
Because DUOPA is administered using a PEG-J or naso-jejunal tube, gastrointestinal complications can occur. These complications include abscess, bezoar, ileus, implant site erosion/ulcer, intestinal hemorrhage, intestinal ischemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumonia (including aspiration pneumonia), pneumoperitoneum, post-operative wound infection, and sepsis. These complications may result in serious outcomes, such as the need for surgery or death.
Instruct patients to notify their healthcare provider immediately if they experience abdominal pain, prolonged constipation, nausea, vomiting, fever, or melanotic stool .
Falling Asleep During Activities of Daily Living and Somnolence Patients treated with
levodopa, a component of DUOPA, 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 (sleep attack), such as excessive drowsiness, and believed that they were alert immediately prior to the event. 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 in DUOPA-treated patients, 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 DUOPA. Before initiating treatment with DUOPA, advise patients about the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence with DUOPA such as the use of concomitant sedating medications or the presence of sleep disorders. Consider discontinuing DUOPA in patients who report significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating). If DUOPA is continued, they should be advised to avoid driving and other potentially dangerous activities that might result in harm if the patient becomes somnolent.
Orthostatic Hypotension
DUOPA-treated patients were more likely to experience a decline in orthostatic blood pressure than patients treated with oral immediate-release carbidopa-levodopa in the controlled clinical study. Orthostatic systolic hypotension (≥30 mm Hg decrease) occurred in 73% of DUOPA-treated patients compared to 68% of patients treated with oral immediate-release carbidopa-levodopa in the controlled clinical study. Orthostatic diastolic hypotension (≥20 mm Hg decrease) occurred in 70% of DUOPA-treated patients compared to 62% of patients treated with oral immediate-release carbidopa-levodopa.
Inform patients about the risk for hypotension and syncope. Monitor patients for orthostatic hypotension, especially after starting DUOPA or increasing the dose.
Hallucinations/Psychosis/Confusion
There is an increased risk for hallucinations and psychosis in patients taking DUOPA. In the controlled clinical trial, hallucinations occurred in 5% of DUOPA-treated patients compared to 3% of patients treated with oral immediate-release carbidopa-levodopa. Confusion occurred in 8% of DUOPA-treated patients compared to 3% of patients treated with oral immediate-release carbidopa-levodopa, and psychotic disorder occurred in 5% of DUOPA-treated patients compared to 3% of patients treated with oral immediate-release carbidopa-levodopa. Hallucinations associated with levodopa may present shortly after the initiation of therapy and may be responsive to dose reduction in levodopa.
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. Because of the risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with DUOPA. In addition, medications that antagonize the effects of dopamine used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effectiveness of DUOPA .
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 DUOPA, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease. 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 DUOPA. Consider reducing the dose or discontinuing DUOPA if a patient develops such urges.
Depression and Suicidality
In the controlled clinical trial, 11% of DUOPA-treated patients developed depression compared to 3% of oral immediate-release carbidopa-levodopa-treated patients. Monitor patients for the development of depression and concomitant suicidal tendencies.
Withdrawal-Emergent Hyperpyrexia and Confusion
A symptom complex that resembles neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy. Avoid sudden discontinuation or rapid dose reduction in patients taking DUOPA. If DUOPA is discontinued, the dose should be tapered to reduce the risk of hyperpyrexia and confusion .
Dyskinesia
DUOPA may cause or exacerbate dyskinesias. In the controlled clinical trial, dyskinesia occurred in 14% of DUOPA-treated patients compared to 12% of patients treated with oral immediate-release carbidopa-levodopa. The occurrence of dyskinesias may require a dosage reduction of DUOPA or other medications used to treat Parkinson’s disease.
Vitamin B6 Deficiency and Seizures Treatment with carbidopa-levodopa, including
DUOPA, may contribute to reduced vitamin B6 levels. Higher doses of carbidopa/levodopa may increase the risk of Vitamin B6 deficiency. Seizures associated with vitamin B6 deficiency have been reported in the postmarketing setting in patients taking DUOPA. In these reported cases, seizures were refractory to traditional anti-seizure medications and only resolved after vitamin B6 administration.
Other symptoms of vitamin B6 deficiency may occur, including depression, confusion, cheilosis, glossitis, dermatitis, anemia, and/or neuropathy . Evaluate vitamin B6 levels prior to initiation of DUOPA and periodically while on treatment or if symptoms associated with vitamin B6 deficiency are identified. Supplement with vitamin B6 as necessary. 5. 10 Neuropathy In clinical studies, 19 of 412 (5%) patients treated with DUOPA developed a generalized polyneuropathy. The onset of neuropathy could be determined in 13 of 19 patients.
Most cases (12/19) were classified as subacute or chronic in onset. The neuropathy was most often characterized as sensory or sensorimotor. Electrodiagnostic testing performed in 16 patients was most often (15/16) consistent with an axonal polyneuropathy, and one patient was classified as having a demyelinating neuropathy.
There was insufficient information to determine the potential role of vitamin deficiencies in the etiology of neuropathy associated with DUOPA. Patients should have clinical assessments for the signs and symptoms of peripheral neuropathy before starting DUOPA. Monitor patients periodically for signs of neuropathy after starting DUOPA, especially in patients with pre-existing neuropathy and in patients taking medications or those who have medical conditions that are also associated with neuropathy. 5.1 1 Cardiovascular Ischemic Events In clinical studies, myocardial infarction and arrhythmia were reported in patients taking carbidopa-levodopa. Ask patients about symptoms of ischemic heart disease and arrhythmia, especially those with a history of myocardial infarction or cardiac arrhythmias. 5.1 2 Laboratory Test Abnormalities DUOPA may increase the risk for elevated (above the upper limit of normal for the reference range) blood urea nitrogen (BUN) and creatine phosphokinase (CPK). In the controlled clinical trial, the shift from a low or normal value at baseline to an increased BUN value was greater for DUOPA-treated patients (13%) than for patients treated with oral immediate-release carbidopa-levodopa (4%). The shift from a low or normal value at baseline to an increased CPK value was greater for DUOPA-treated patients (17%) than for patients treated with oral immediate-release carbidopa-levodopa (7%). The incidence of patients with a markedly increased BUN (≥10 mmol/L; ≥28 mg/dL) was greater for patients treated with DUOPA (11%) than that for patients treated with oral immediate-release carbidopa-levodopa (0%). The incidence of patients with an increased CPK (>3 times the upper limit of normal) was greater for patients treated with DUOPA (9%) than that for patients treated with oral immediate-release carbidopa-levodopa (0%). Patients taking levodopa or carbidopa-levodopa may have increased levels of catecholamines and their metabolites in plasma and urine giving false positive results suggesting the diagnosis of pheochromocytoma in patients on levodopa and carbidopa-levodopa. 5.1 3 Glaucoma Carbidopa-levodopa may cause increased intraocular pressure in patients with glaucoma. Monitor intraocular pressure in patients with glaucoma after starting DUOPA.
Drug Interactions with Duopa
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 Safety for 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 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 of Duopa
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for 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 . DUOPA is contraindicated in patients taking nonselective monoamine oxidase (MAO) inhibitors
Overdosage Information for Duopa
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.
Clinical Studies of Duopa
DUOPA 8.7 4.1* LS Mean Change from Baseline based on Analysis of
Covariance (ANCOVA). *=Statistically Significant. Figure 2 shows results over time according to treatment for the efficacy variable (change from baseline in “Off” time) that served as the clinical outcome measure at the end of the trial at 12 weeks. Figure 2. Change in “Off” Time Over 12 Weeks.
Figure 2. Change in “Off” Time Over 12 Weeks.
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Duopa?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Duopa Prices