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DUOPA- levodopa and carbidopa suspension AbbVie Inc.
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 (1)
Enteral Suspension: 4.63 mg carbidopa and 20 mg levodopa per mL (3)
DUOPA is contraindicated in patients taking nonselective monoamine oxidase (MAO) inhibitors (4)
Most common adverse reactions for DUOPA (DUOPA incidence at least 7% greater than oral carbidopa-levodopa incidence) were: complication of device insertion, nausea, depression, peripheral edema, hypertension, upper respiratory tract infection, oropharyngeal pain, atelectasis, and incision site erythema. (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.
Pregnancy: Based on animal data, may cause fetal harm (8.1)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
DUOPA is indicated for the treatment of motor fluctuations in patients with advanced Parkinson’s disease.
DUOPA is administered over a 16-hour infusion period. The daily dose is determined by individualized patient titration and composed of:
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 [see Dosage and Administration (2.2)]:
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.
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.
The daily dose of DUOPA can be titrated as needed, based on the patient’s individual clinical response and tolerability after Day 1 of DUOPA treatment and until a stable daily dose is maintained. 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 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:
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.
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 [see Warnings and Precautions (5.7)].
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.
Enteral suspension: 4.63 mg carbidopa and 20 mg levodopa per mL in a single-use cassette. Each cassette contains approximately 100 mL of suspension.
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 [see Drug Interactions (7.1 and 7.2)].
Because DUOPA is administered using a PEG-J or naso-jejunal tube, gastrointestinal complications can occur.
These complications include bezoar, ileus, implant site erosion/ulcer, intestinal hemorrhage, intestinal ischemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumoperitoneum, and post-operative wound infection. 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 [see Patient Counseling Information (17)].
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.
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.
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 [see Drug Interactions (7.3)].
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.
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.
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 [see Dosage and Administration (2.4)].
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.
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.
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.
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.
Carbidopa-levodopa may cause increased intraocular pressure in patients with glaucoma. Monitor intraocular pressure in patients with glaucoma after starting DUOPA.
The following serious adverse reactions are discussed below and elsewhere in labeling:
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.
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.
The use of nonselective MAO inhibitors with DUOPA is contraindicated [see Contraindications (4)]. 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.
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 (e.g., phenothiazines, butyrophenones, risperidone, metoclopramide, papaverine) and isoniazid may reduce the effectiveness of levodopa. Monitor patients for worsening Parkinson’s symptoms.
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.
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.
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.
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.
Levodopa has been detected in human milk after administration of carbidopa-levodopa. There are no data on the presence of carbidopa in human milk, the effects of levodopa or carbidopa on the breastfed infant, or the effects on milk production. However, inhibition of lactation may occur because levodopa decreases secretion of prolactin in humans. Carbidopa is excreted in rat milk.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DUOPA and any potential adverse effects on the breastfed infant from DUOPA or from the underlying maternal condition.
Safety and effectiveness in pediatric patients have not been established.
In the controlled clinical trial, 49% of patients were 65 years and older, and 8% were 75 years and older. In patients 65 years and older, there was an increased risk for elevation of BUN and CPK (above the upper limit of the normal reference range for these laboratory analytes) during treatment with DUOPA compared to the risk for patients less than 65 years.
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.
DUOPA is a combination of carbidopa, an inhibitor of aromatic amino acid decarboxylation, and levodopa, an aromatic amino acid.
Carbidopa is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.2. It is designated chemically as (2S)-3-(3,4-dihydroxyphenyl)-2-hydrazino-2-methylpropanoic acid monohydrate. Its empirical formula is C10H14N2O4•H2O, and its structural formula is:
The content of carbidopa in DUOPA is expressed in terms of anhydrous carbidopa which has a molecular weight of 226.3. The 4.63 mg/mL of anhydrous carbidopa is equivalent to 5.0 mg/mL of carbidopa.
Levodopa is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.2. It is designated chemically as (2S)-2-Amino-3-(3,4-dihydroxyphenyl) propanoic acid. Its empirical formula is C9H11NO4, and its structural formula is:
The inactive ingredients in DUOPA are carmellose sodium and purified water.
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 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 the symptoms of Parkinson's disease.
Because its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available to the brain. The addition of carbidopa to levodopa reduces the peripheral effects (e.g., nausea and vomiting) due to decarboxylation of levodopa; however, carbidopa does not decrease the adverse reactions due to the central effects of levodopa.
The pharmacokinetics of carbidopa and levodopa with 16-hour intrajejunal infusion of DUOPA was evaluated in 18 patients with advanced Parkinson's disease who had been on DUOPA therapy for 30 days or longer. Patients remained on their individualized DUOPA doses.
The plasma concentrations versus time profile for levodopa with DUOPA 16-hour intrajejunal infusion is presented in Figure 1.
Figure 1. Plasma Concentrations (mean ± standard deviation) versus Time Profile of Levodopa with DUOPA (levodopa, 1580 ± 403 mg; carbidopa, 366 ± 92 mg) 16-Hour Infusion
Absorption and Bioavailability
Following initiation of the 16-hour intrajejunal infusion of DUOPA, peak plasma levels of levodopa is reached at 2.5 hours. The absorption of levodopa may be decreased in patients on a high-protein diet because levodopa competes with certain amino acids for transport across the gut wall. The gastric emptying rate does not influence the absorption of DUOPA since it is administered by continuous intestinal infusion. In a cross-study population pharmacokinetic analysis, DUOPA had comparable bioavailability to the oral immediate-release carbidopa-levodopa (25/100 mg) tablets (over-encapsulated tablets). The estimated bioavailability for levodopa from DUOPA relative to oral immediate-release carbidopa-levodopa tablets was 97% (95% confidence interval; 95% to 98%).
In the controlled clinical trial, the intra-subject variability in carbidopa and levodopa plasma concentrations were lower for patients treated with DUOPA (N=33, 25% and 21%, respectively) than in patients treated with oral immediate-release carbidopa-levodopa (25/100 mg) tablets (N=28, 39% and 67%, respectively).
Carbidopa is approximately 36% bound to plasma proteins. Levodopa is approximately 10-30% bound to plasma proteins.
Metabolism and Elimination
Carbidopa is metabolized to two main metabolites (α-methyl-3-methoxy-4-hydroxyphenylpropionic acid and α-methyl-3,4-dihydroxyphenylpropionic acid). These 2 metabolites are primarily eliminated in the urine unchanged or as glucuronide conjugates. Unchanged carbidopa accounts for 30% of the total urinary excretion. The elimination half-life of carbidopa is approximately 2 hours.
Levodopa is mainly eliminated via metabolism by the aromatic amino acid decarboxylase (AAAD) and the catechol-O-methyl-transferase (COMT) enzymes. Other routes of metabolism are transamination and oxidation. The decarboxylation of levodopa to dopamine by AAAD is the major enzymatic pathway when no enzyme inhibitor is co-administered. O-methylation of levodopa by COMT forms 3-O-methyldopa. When administered with carbidopa, the elimination half-life of levodopa is approximately 1.5 hours (see Figure 1).
Drug Interaction Studies
Systemic exposure of levodopa is expected to increase in the presence of entacapone.
In rat, oral administration of carbidopa-levodopa for two years resulted in no evidence of carcinogenicity. DUOPA contains hydrazine, a degradation product of carbidopa. In published studies, hydrazine has been demonstrated to be carcinogenic in multiple animal species. Increases in liver (adenoma, carcinoma) and lung (adenoma, adenocarcinoma) tumors have been reported with oral administration of hydrazine in mouse, rat, and hamster.
Carbidopa was positive in the in vitro Ames test, in the presence and absence of metabolic activation, and the in vitro mouse lymphoma tk assay in the absence of metabolic activation but was negative in the in vivo mouse micronucleus assay.
In published studies, hydrazine was reported to be positive in in vitro genotoxicity (Ames, chromosomal aberration in mammalian cells, and mouse lymphoma tk) assays and in the in vivo mouse micronucleus assay.
Impairment of Fertility
In reproduction studies, no effects on fertility were observed in rats receiving carbidopa -levodopa.
The efficacy of DUOPA was established in a randomized, double-blind, double-dummy, active-controlled, parallel group, 12-week study (Study 1) in patients with advanced Parkinson's disease who were levodopa-responsive and had persistent motor fluctuations while on treatment with oral immediate-release carbidopa-levodopa and other Parkinson's disease medications.
Patients were eligible for participation in the studies if they were experiencing 3 hours or more of “Off” time on their current Parkinson's disease drug treatment and they demonstrated a clear responsiveness to treatment with levodopa. Seventy-one (71) patients enrolled in the study and 66 patients completed the treatment (3 patients discontinued treatment because of adverse reactions, 1 patient for lack of effect, and 1 patient for non-compliance).
Patients enrolled in this study had a mean age of 64 years and disease duration of 11 years. Most patients (89%) were taking at least one concomitant medication for Parkinson’s disease (e.g., dopaminergic agonist, COMT-inhibitor, MAO-B inhibitor) in addition to oral immediate-release carbidopa-levodopa. Thirty nine percent of patients were taking two or more of such concomitant medications.
Patients were randomized to either DUOPA and placebo capsules or placebo suspension and oral immediate-release carbidopa-levodopa 25/100 mg capsules. Patients in both treatment arms had a PEG-J device placement. DUOPA or placebo-suspension was infused over 16 hours daily through a PEG-J tube via the CADD®-Legacy 1400 model ambulatory infusion pump. The mean daily levodopa dose was 1117 mg/day in the DUOPA group and 1351 mg/day in the oral immediate-release carbidopa-levodopa group.
The clinical outcome measure in Study 1 was the mean change from baseline to Week 12 in the total daily mean “Off” time, based on a Parkinson's disease diary. The "Off" time was normalized to a 16-hour awake period, based on a typical person's waking day and the daily infusion duration of 16 hours. The mean score decrease (i.e., improvement) in “Off” time from baseline to Week 12 for DUOPA was significantly greater (p=0.0015) than for oral immediate-release carbidopa-levodopa. Additionally, the mean score increase (i.e., improvement) in “On” time without troublesome dyskinesia from baseline to Week 12 was significantly greater (p=0.0059) for DUOPA than for oral immediate-release carbidopa-levodopa. The treatment difference (DUOPA – oral immediate release carbidopa-levodopa) for decrease in “Off” time was approximately 1.9 hours and the treatment difference for the increase in “On” time without troublesome dyskinesia was approximately 1.9 hours. Results of Study 1 are shown in Table 4.
LS Mean Change from Baseline based on Analysis of Covariance (ANCOVA).
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.
Single-use cassettes containing 4.63 mg carbidopa (as 5 mg of the monohydrate) and 20 mg levodopa per mL of enteral suspension. Each cassette contains approximately 100 mL of suspension.
Carton of 7 DUOPA cassettes: NDC 0074-3012-07
Store in freezer at -20oC (-4oF). Thaw in refrigerator at 2oC to 8oC (36oF to 46oF) prior to dispensing. Cassettes should be protected from light and kept in the carton prior to use.
Thawing instructions for pharmacies
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Ask patients if they have had any previous surgery in the upper part of their abdomen that may lead to difficulty in performing the gastrostomy or jejunostomy [see Dosage and Administration (2.3)].
Advise patients that foods that are high in protein may reduce the effectiveness of DUOPA [see Drug Interactions (7.5) and Clinical Pharmacology (12.3)].
Interruption of DUOPA Infusion
If the patient anticipates disconnecting the pump for a short period of time (less than 2 hours such as to swim, shower, or short medical procedure), no supplemental oral medication is needed, but the patient may be advised to take an extra-dose of DUOPA before disconnecting. Instruct the patient to stop the continuous rate, turn off the pump, clamp the cassette tube, disconnect the tubing, and replace the red cap on the cassette tube. The DUOPA cassette can remain attached to the pump until the tubing is reconnected. Refer the patient to the Patient Instructions for Use for additional information (i.e., changing the DUOPA Cassette: disconnecting Steps 1-5 and reconnecting Steps 10-16).
Advise the patient to contact their healthcare provider and to take oral carbidopa-levodopa until the patient is able to resume DUOPA infusion, if the patient will have prolonged interruption of therapy lasting more than 2 hours [see Dosage and Administration (2.4)].
Gastrointestinal and Gastrointestinal Procedure-Related Risks
Inform patients of the gastrointestinal procedure-related risks including bezoar, ileus, implant site erosion/ulcer, intestinal hemorrhage, intestinal ischemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumoperitoneum, post-operative wound infection and sepsis. Advise patients of the symptoms of the above listed complications and instruct them to contact their healthcare provider if they experience any of these symptoms [see Warnings and Precautions (5.1)].
Falling Asleep during Activities of Daily Living and Somnolence
Alert patients to the potential sedating effects caused by DUOPA, 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 DUOPA to gauge whether or not 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 physician.
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 DUOPA or when taking a concomitant medication that increases plasma levels of levodopa [see Warnings and Precautions (5.2)].
Advise patients that they may experience syncope and may develop hypotension with or without symptoms such as dizziness, nausea, syncope, and sometimes sweating while taking DUOPA. Accordingly, caution patients against standing rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially at the initiation of treatment with DUOPA [see Warnings and Precautions (5.3)].
Inform patients that they may experience hallucinations (unreal visions, sounds, or sensations) and other symptoms of psychosis can occur while taking DUOPA. Tell patients to report hallucinations, abnormal thinking, psychotic behavior or confusion to their healthcare provider promptly should they develop [see Warnings and Precautions (5.4)].
Impulse Control/Compulsive Behaviors
Advise patients that they may experience impulse control and/or compulsive behaviors while taking DUOPA. Advise patients to inform their physician or healthcare provider if they develop new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with DUOPA [see Warnings and Precautions (5.5)].
Depression and Suicidality
Inform patients that they may develop depression or experience worsening of depression while taking DUOPA. Instruct patients to contact their healthcare provider if they experience depression, worsening of depression, or suicidal thoughts [see Warnings and Precautions (5.6)].
Withdrawal-Emergent Hyperpyrexia and Confusion
Advise patients to contact their healthcare provider before stopping DUOPA. Tell patients to inform their healthcare provider if they develop withdrawal symptoms such as fever, confusion, or severe muscle stiffness [see Warnings and Precautions (5.7)].
Inform patients that DUOPA may cause or exacerbate pre-existing dyskinesias [see Warnings and Precautions (5.8)].
Inform patients that neuropathy may develop or they may experience worsening neuropathy on DUOPA, and to contact their healthcare provider if they develop any symptoms or features suggesting neuropathy [see Warnings and Precautions (5.9)].
Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant during therapy [see Use in Specific Populations (8.1)].
Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2)].
Manufactured by AbbVie Inc., North Chicago, IL 60064, USAor by Fresenius Kabi Norge AS, 1788 Halden, NorwayFor AbbVie Inc.North Chicago, IL 60064, USA
03-C094 December 2019
(carbidopa and levodopa) enteral suspension
Read this Medication Guide before you start using DUOPA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.
What is the most important information I should know about DUOPA?
DUOPA can cause serious side effects, including:
Some of these problems may require surgery and may lead to death.
You will need to have a procedure to make a small hole (called a “stoma”) in your stomach wall to place a gastro-jejunostomy tube (called a PEG-J tube) in an area of your small intestine called the jejunum. DUOPA is delivered directly to your small intestine through this tube. Your healthcare provider will talk to you about the stoma procedure. Before the stoma procedure, tell your healthcare provider if you have ever had a surgery or problems with your stomach.
Talk to your healthcare provider about what you need to do to care for your stoma. After the procedure, you and your healthcare provider will need to regularly check the stoma for any signs of infection.
If your PEG-J tube becomes kinked, knotted, or blocked this may cause you to have worsening of your Parkinson’s symptoms or recurring movement problems (motor fluctuations). Call your healthcare provider if your Parkinson’s symptoms get worse or you have slow movement while you are treated with DUOPA.
What is DUOPA?
DUOPA is a prescription medicine used for treatment of advanced Parkinson's disease. DUOPA contains 2 medicines, carbidopa and levodopa.
DUOPA should not be given to children (younger than 18 years).
Who should not use DUOPA?
Do not use DUOPA if you:
What should I tell my healthcare provider before using DUOPA?
Before you use DUOPA, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, herbal supplements.
Using DUOPA with certain other medicines may affect each other and cause serious side effects.
Especially tell your healthcare provider if you take:
Eating high protein foods may affect how DUOPA works. Tell your healthcare provider if you change your diet.
Ask your healthcare provider or pharmacist for a list of these medicines or foods if you are not sure.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I use DUOPA?
What should I avoid while using DUOPA?
What are the possible side effects of DUOPA?
DUOPA may cause serious side effects, including:
Call your healthcare provider or get medical care right away if you have any of the above symptoms. Your healthcare provider will tell you if you should stop treatment with DUOPA and if needed, tell you how to discontinue DUOPA.
Tell your healthcare provider if you have any side effect that bothers you or does not go away.
These are not all of the possible side effects of DUOPA. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store DUOPA?
Keep DUOPA and all medicines out of the reach of children.
General information about the safe and effective use of DUOPA.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use DUOPA for a condition for which it was not prescribed. Do not give DUOPA to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about DUOPA. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about DUOPA that was written for healthcare professionals.
For more information go to www.DUOPA.com or call 1-844-386-4968.
What are the ingredients in DUOPA?
Active ingredients: carbidopa and levodopa
Inactive ingredients: carmellose sodium and purified water
This Medication Guide has been approved by the U.S. Food and Drug Administration.
03-C094 Revised: December 2019
INSTRUCTIONS FOR USE
Note: The original design of the Y-Connector is represented in the Figures throughout this Instructions for Use.This Instructions for Use provides information for the CADD-Legacy® model 1400 pump only. There are other CADD-Legacy® pump models available. Read the label on the back of the pump to make sure it is a model 1400 pump.Your healthcare provider prescribed DUOPA for you. Your healthcare provider programs your prescription into the CADD-Legacy® 1400 pump. The CADD-Legacy® 1400 pump is approved for use with DUOPA. DUOPA is provided as medication inside cassettes that connect to the CADD-Legacy® 1400 pump.
The pump delivers DUOPA in 3 ways:
You will need the following items to complete these steps:
The display shows programming information and messages. The main screen, which the pump displays most of the time, shows the following:
WARNINGS and CAUTIONS
Failure to follow the Warnings and Cautions below could cause return of your symptoms, damage to the pump, serious injury, or may lead to death in rare cases.
WARNING: Use only DUOPA cassettes to make sure the pump works correctly.
For instructions on changing a DUOPA cassette, see Changing the Cassette.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
03-B884 Revised: March 2019
Legacy 1400 Operator's Manual
CADD-Legacy® 1400 PumpModel 1400
This online version differs from the printed version. Certain information that is not intended for patients has been removed.
This operator’s manual is for clinician use only. Read the entire operator’s manual before operating the pump.
This manual pertains only to the CADD-Legacy® 1400 pump. There are other CADD-Legacy® pump models available; review the rear label of the pump to ensure it is a CADD-Legacy® 1400 pump before programming. This pump is designed for enteral delivery of medication and can be programmed to deliver a continuous rate, a morning dose, and extra doses.
This manual is intended for clinician use only. Do not permit patients to have access to this manual. The pump has 3 security levels designed to limit patient access. Do not disclose the pump’s security codes or any other information that would allow inappropriate access to programming and operating functions.
The issue date of this operator’s manual is included on the back cover for the clinician’s information. In the event one year has elapsed between the issue date and product use, the clinician should contact Smiths Medical to see if a later revision of this manual is available.
If you have comments or questions concerning the operation of the CADD-Legacy® 1400 pump, please call the number given below. When calling, please specify the pump’s software revision. This information is located on the pump’s display during power up.
Our staff at Smiths Medical is available to help clinicians 24 hours a day with the programming and operation of the CADD-Legacy® 1400 pump.
Smiths Medical ASD, Inc.1265 Grey Fox RoadSt. Paul, MN 55112 USATel: 1 800 258 5361 (USA)Tel: +1 614 210 7300www.smiths-medical.com
Read this entire operator’s manual before operating the CADD-Legacy® 1400 pump.
Failure to follow the warnings and cautions below could result in return of symptoms, damage to the pump, serious injury, or death in extreme cases.
Please refer to the full prescribing information for DUOPA (carbidopa and levodopa) enteral suspension for indications and usage, contraindications, warnings, precautions, and adverse reactions.
1.0 General Description
The CADD-Legacy® 1400 pump provides enteral delivery of medication to patients in hospital or outpatient settings. Therapy should always be overseen by a physician or a certified, licensed healthcare professional. As appropriate to the situation, the patient should be instructed in using and troubleshooting the pump.
The CADD-Legacy® 1400 pump is indicated solely for the enteral delivery of medication contained in a medication cassette reservoir supplied by AbbVie. The medication cassette reservoir attaches to the bottom of the pump.
Refer to AbbVie’s full prescribing information for DUOPA (carbidopa and levodopa) enteral suspension for indications and usage, contraindications, warnings, precautions, and adverse reactions.
Description of the Keys, Display, and Features
AC Indicator Light
The green indicator light is on when you are using the AC adapter to power the pump.
The liquid crystal display (LCD) shows programming information and messages. In this manual, the term “display” is synonymous with display panel or LCD.
The keys on the keypad are described below. A key beeps when pressed if it is operable in the current lock level.
You may plug an AC adapter into the power jack as an alternate source of power. The indicator light on the front of the pump will illuminate when the AC adapter is in use.
The accessory jack is used for attaching accessory cables. See the instructions for use supplied with those accessories.
Medication Cassette Reservoir
The medication cassette reservoir is the single-use reservoir designed for use with the CADD-Legacy® 1400 pump. In this manual and on the pump’s display, the word “disposable” refers to the medication cassette reservoir. In AbbVie’s patient instructions for use, medication cassette reservoir is referred to as DUOPA cassette.
Two AA batteries fit into the battery compartment. The AA batteries serve as the primary source of power, or as backup power when an AC adapter is in use.
The cassette latch attaches the cassette to the pump. The term “cassette” refers to the part of the medication cassette reservoir that attaches to the bottom of the pump. If the cassette becomes unlatched while the pump is running, delivery will stop and an alarm will occur. If the cassette becomes unlatched while the pump is stopped, an alarm will occur.
Other Features Not Shown
Upstream Occlusion Sensor: The pump contains an upstream occlusion sensor. This feature may be turned on or off (see Section 4, Biomed Functions). When the sensor is turned on, and an occlusion in the reservoir is detected, an alarm will sound, delivery will stop, and the display will show Upstream Occlusion.
Downstream Occlusion Sensor: The pump contains a downstream occlusion sensor. When a downstream occlusion (between the pump and the patient) is detected, an alarm will sound, delivery will stop, and the display will show High Pressure.
Reservoir Volume Alarm: The reservoir volume alarm indicates when the volume of medication in the medication cassette reservoir is low or depleted. Each time you change the medication cassette reservoir, you may reset the reservoir volume to the originally programmed value. Then, as medication is delivered, the reservoir volume automatically decreases. When the pump calculates that 5 ml remain in the medication cassette reservoir, beeps sound and ResVol Low appears on the main screen. This alarm recurs at every subsequent decrease of 1 ml until the reservoir volume reaches 0 ml, at which point the pump stops and the reservoir volume empty alarm sounds.
NOTE: The default setting for Reservoir Volume is Not in Use. The reservoir volume alarm is activated only when a value is programmed into the Reservoir Volume screen. Programming a reservoir volume value is not required for general use, but is available at provider discretion.
The Main Screen
The main screen is the starting point for programming or viewing the pump’s settings.
If no keys are pressed for 2 minutes, the display reverts to the main screen. When the two AA batteries are low, LowBat appears on the main screen.
*Does not appear on the main screen if reservoir volume is programmed to Not In Use.
Lock levels are used to limit patient access to certain programming and operating functions. The table on the next page lists the functions that are accessible in lock level 0 (LL0), lock level 1 (LL1), and lock level 2 (LL2). When a function is accessible, the key associated with the function beeps when pressed. If a function is not accessible, the pump ignores the key press and a beep does not sound. Section 2, Pump Setup and Programming, describes how to change the lock level.
The following security codes are preset by the manufacturer for the clinician’s use:
Lock Level 0 (LL0) Table
This table lists the operations that are accessible in lock level 0 (LL0) while the pump is stopped and running. LL0 permits complete access to all programming and operating functions.
Lock Levels 1 and 2 (LL1, LL2) Table
This table lists the operations that are accessible in lock level 1 (LL1) and lock level 2 (LL2) while the pump is stopped and running. LL1 permits limited control of pump programming and operations. LL2 permits only minimal control of pump operations.
*When in LL1, you can program up to the LL0 value. No programming is allowed in LL2.
2.0 Pump Setup and Programming
Installing or Replacing the Batteries
Use new, AA alkaline batteries such as DURACELL® or EVEREADY® ENERGIZER® batteries to power the pump. The pump retains all programmed values while the batteries are removed.
Dispose of used batteries in an environmentally safe manner, and according to any regulations which may apply.
In order to install or replace the batteries, be sure the pump is Stopped. Then, follow these steps:
1. Push down and hold the arrow button while sliding the door off.
2. Remove the used batteries. Pulling on the end of the battery strap will make battery removal easier.
3. Install the new batteries in the compartment, making sure the battery strap is positioned correctly under the batteries.
4. Place the battery door over the battery compartment and slide the door closed.
5. Ensure that the door is latched by trying to remove the door without pressing the arrow button.
NOTE: The power-up sequence will start, the pump will go through an electronic self-test, and the pump will beep 6 times at the end of the power-up sequence. All of the display indicators, the software revision, and each parameter will appear briefly.
6. Resume operation of the current program by pressing and holding to start the pump or proceed to program the pump.
Watching Power Up
When you install the batteries, the pump will start its power up sequence during which it performs self-tests and displays programmed values. Watch for the following:
NOTE: To move quickly through the power-up screens, press repeatedly. To skip the automatic review entirely, pressIf you attempt to skip screens before the pump is powered up, it will not respond.
Changing to Lock Level 0 (LL0)
Before programming the pump, make sure the pump is set to LL0. LL0 allows the clinician to access all programming and operating functions.
Programming the Pump: General Instructions
The procedure for changing a programmed setting is similar for most programming screens.
The CADD-Legacy® 1400 pump offers 3 methods of delivery:
The following graph illustrates the combined delivery methods. The continuous rate, extra dose, and morning dose are programmed as described in this section. Ranges and programming increments are listed in the Specifications in Section 5.
These are the programming screens for the CADD-Legacy® 1400 pump. Descriptions of the screens follow.
NOTE: The default setting for Reservoir Volume is Not in Use. Programming a reservoir volume value is not required for general use, but is available at provider discretion.
If you wish to use the reservoir volume feature, enter the volume of medication contained in the filled medication cassette reservoir. The reservoir volume value decreases as the pump delivers medication or as you prime the tubing. When you change the medication cassette reservoir, reset the reservoir volume value on this screen. If you do not wish to use the reservoir volume feature, scroll down to Not In Use (located before 1 and after 9999 in the range of values).
The reservoir volume value could be set higher than the capacity of the medication cassette reservoir. Be sure to program the reservoir volume to reflect the actual volume in the reservoir.
Enter the continuous rate of medication delivery in ml/hr. The maximum rate is 20 ml/hr. If the prescription does not call for a continuous rate, enter zero.
NOTE: If you intend to run the pump in lock level 1 so the continuous rate can be varied, you should enter the maximum allowable rate while programming in lock level 0. After programming, you may then change to lock level 1 and decrease the rate to its starting value. See Programming with Upper Limits, Adjusting Doses in LL1 at the end of Section 2.
Enter the amount of medication to be delivered when the patient presses If the prescription does not call for an extra dose, enter zero.
NOTE: If you intend to run the pump in lock level 1 so the extra dose can be varied, you should enter the maximum allowable dose while programming in lock level 0. After programming, you may then change to lock level 1 and decrease the dose to its starting value. See Programming with Upper Limits, Adjusting Doses in LL1 at the end of Section 2.
This screen shows the total amount of medication delivered since the last time this value was cleared. The amount shown is rounded to the nearest 0.05 ml. If this value reaches 99999.95, it automatically returns to 0 and continues counting. When using the pump’s key, the amount of medication used is not included in the Given amount.
Other Programming Information
The morning dose should be programmed separately following programming of the above. Information on programming the morning dose can be found later in this section.
To program the pump, enter the prescribed values.
1. Begin at the main screen.
2. Enter the reservoir volume (optional – not required for general use).
3. Enter the continuous rate.
4. Enter the extra dose amount.
NOTE: If required, program the extra dose lockout time, as instructed in Section 4, Biomed Functions.
5. Clear the amount given.
6. Review the program.
Press repeatedly to review the programming screens. If you need to reprogram a setting, press until the appropriate screen appears and change the setting as described in this section.
Programming a Morning Dose
To program a morning dose the pump must be running and a medication cassette reservoir must be attached.
To program a morning dose
Once entered, the morning dose amount is retained in the pump’s memory. The patient can then press twice to display and deliver the morning dose.
NOTE: If required, program the morning dose lockout time, as instructed in Section 4, Biomed Functions.
Removing a Medication Cassette Reservoir
To remove the medication cassette reservoir from the pump
Attaching a Medication Cassette Reservoir
Obtain a new, filled medication cassette reservoir.
After attaching the medication cassette reservoir, proceed to the reservoir volume screen to reset the value for the volume, and then prime the tubing.
Priming the Tubing and Connecting to the Patient
The pump must be stopped and in LL0 or LL1 in order to prime the fluid path. If the pump is in LL2, you cannot prime the fluid path.
NOTE: If you are not changing the medication cassette reservoir but wish to prime the fluid path, you may follow the same procedure.
NOTE: Medication delivered during priming is subtracted from the reservoir volume, but is not added to the given screen since this amount is not delivered to the patient.
NOTE: Each time you press and hold you pump a maximum of 1 ml of medication into the tubing. The pumping action will stop automatically when 1 ml has been delivered. Releaseif you finish priming the fluid path sooner. If the fluid path is not fully primed, repeat the above priming procedure.
Setting the Lock Level for the Patient
The lock level must be changed to LL1 or LL2 to prevent the patient from having complete access to all programming and operating functions.
NOTE: You may change the lock level at any time by stopping the pump and following the procedure below.
To change the lock level
Programming with Upper Limits, Adjusting Doses in Lock Level 1
If a prescription allows for the continuous rate, extra dose, or morning dose to be adjusted during the course of therapy, you may wish to operate the pump in LL1. Then, when necessary, you can adjust values up to the maximum value that was programmed in LL0.
Programming the pump to use this feature
Adjusting the rate or dose while the pump is in use
To change the morning dose, press
NOTE: You will not be able to adjust the continuous rate, extra dose, or morning dose beyond the value originally programmed in LL0.
3.0 Operating the Pump
Starting the Pump
When you start the pump, programmed values will be automatically reviewed. Then medication delivery will begin as programmed, and RUN will appear on the main screen. If the pump will not start, a message will appear on the display. Refer to the Messages and Alarms Table in Section 5.
To start the pump
Starting and 3 sets of dashes appear on the display; then the dashes disappear one-by-one, each accompanied by a single beep.
Stopping the Pump
Stopping the pump stops delivery. When the pump is stopped, STOPPED will appear on the main screen, and you will hear 3 beeps every 5 minutes.
To stop the pump
Stopping and 3 sets of dashes appear one-by-one on the pump’s display, each accompanied by a single beep.
Turning the Pump On/Off
When the pump is stopped, you may put the pump into a low power state by turning it off. The pump may be turned off when it is disconnected from the patient and it is going to be stored for short periods of time.
To turn the pump off
To turn the pump on
Starting a Morning Dose
A morning dose may be delivered in any lock level while the pump is running. It allows you to deliver a specified amount of medication, as a loading dose for example.
If the patient attempts to deliver a morning dose during the lockout time, the pump will not deliver the dose. The lockout time is determined by the value entered in Morning Dose Lockout, in biomed functions. The extra dose lockout setting has no effect on morning dose frequency. A morning dose may be stopped in progress.
NOTE: A morning dose cannot be started while an extra dose or another morning dose is in progress.
To start a morning dose
To program a morning dose, the pump must be running and a medication cassette reservoir must be attached.
NOTE: Thekey must be pressed twice for morning dose delivery to start.
The current morning dose value (or the default value of 0 ml) will appear UNLESS the morning dose is currently locked out (in which case the screen will not appear). If the desired morning dose amount appears in the display, pressagain to begin delivery.
NOTE: If the desired morning dose amount does not appear in the display, program the desired morning dose amount as instructed in Section 2, Pump Setup and Programming.
The screen will show the value decreasing as the morning dose is delivered.
Starting an Extra Dose
If an extra dose has been programmed, the patient may start an extra dose while the pump is running. The amount delivered is added to the amount provided by the continuous rate.
If the patient attempts to deliver an extra dose during the lockout time, the pump will not deliver the dose. The lockout time is determined by the value entered in Extra Dose Lockout, in biomed functions.
NOTE: An extra dose cannot be started while another extra dose or a morning dose is in progress.
To start an extra dose
Stopping an Extra Dose or Morning Dose
An extra dose or morning dose can be stopped in progress. The pump may be in any lock level.
To stop an extra dose or morning dose in progress
Resetting the Reservoir Volume
To reset the reservoir volume to the value programmed in LL0, the pump may be in any lock level.
4.0 Biomed Functions
Overview: Accessing the Biomed Functions and Programming the Lockouts
The biomed functions are pump configurations that are less frequently changed. The biomed functions are accessible only when the pump is stopped and in lock level 0 (LL0).
To access the Biomed Functions
4. Pressto select the setting you wish to view or change, then follow the instructions in this section for the appropriate screen.
NOTE: To leave a biomed function setting unchanged, press
5. To exit the biomed functions, pressuntil you get to the screen that reads, NEXT for Biomed, ENTER for Main.
6. Pressto return to the main screen.
Extra Dose Lockout
The extra dose lockout time determines how often a patient can receive an extra dose of medication. The lockout time is the minimum amount of time which must elapse between the start of one dose and the start of the next.
Morning Dose Lockout
The morning dose lockout time determines how often a patient can receive a morning dose. The lockout time is the minimum amount of time which must elapse between the start of one dose and the start of the next.
Upstream Occlusion Sensor On/Off
The upstream occlusion sensor can be set to On or Off. If this screen is set to On, and an occlusion in the medication cassette reservoir is detected, an alarm will sound, delivery will stop, and the display will show Upstream Occlusion.
Messages and Alarms, Alphabetical List
If the medication cassette reservoir or the battery door is loose or damaged, do not use the pump. Immediately stop the pump, close the tubing clamp, and contact Smiths Medical.
Cleaning the Pump and Accessories
NOTE: Refer to the Instructions for Use for each accessory before proceeding with cleaning.
The following solutions may be used to clean the pump and accessories, unless otherwise specified:
Cleaning the Battery Contacts
Routinely clean the battery contacts, possibly as part of the preventative maintenance cycle, to remove buildup of foreign material on the contacts.
Use the following to clean the battery contacts:
Exposure to Radiation, Ultrasound, Magnetic Resonance Imaging (MRI), or Use near ECG Equipment
Continuous Rate Scroll Ranges
Extra Dose, Morning Dose Scroll Ranges
Accuracy Test Results
The following graphs are designed to show flow accuracy of the infusion system plotted against given time periods. The medication cassette reservoir used for flow accuracy tests was supplied by AbbVie.
Electromagnetic Emissions and Immunity Declarations
Electrostatic discharge (ESD)
±8 kV contact
±15 kV air
Electrical fast transient/burst
Voltage dips, short interruptions and voltage variations on power supply input lines
<5 % UT (>95 % dip in UT) for 0,5 cycle
40 % UT (60 % dip in UT) for 5 cycles
70 % UT (30 % dip in UT) for 25 cycles
<5 % UT (>95 % dip in UT) for 5 sec
Recommended separation distance
d=0.27*P1/2 80MHz to 800 MHz
d=0.54*P1/2 800MHz to 2,5 GHz
Where P is the maximum output power rating of the transmitter in watts (W) according to the transmitter manufacturer and d is the recommended separation distance in meters (m).
Field strengths from fixed RF transmitters, as determined by an electromagnetic site survey,a should be less than the compliance level in each frequency range.b
Interference may occur in the vicinity of equipment marked with the following symbol:
Rated maximum output power of transmitter
Separation distance according to frequency of transmitter
150 kHz to 80 MHz
80 MHz to 800 MHz
800 MHz to 2,5 GHz
Safety Features and Fault Detection
Hardware Safety Features
Key hardware safety features include a watchdog timer circuit, motor driver and motor watchdog circuits, and a voltage detector circuit. Each safety circuit performs a unique function to insure the overall safety of the device.
Watchdog Timer Circuit
The microprocessor must send an appropriate signal to the watchdog circuit at least once per second. If the microprocessor does not, the watchdog circuit will time out and shut down the pump controller.
Watchdog timer circuitry is provided to monitor the status of the microprocessor and disable the motor and enable the audible alarm if the microprocessor fails to function properly. The microprocessor must strobe the watchdog circuit at least once every second in order to prevent the watchdog from performing its reset function. The reset output from the watchdog circuit is a pulse output. This acts to “jump startˮ the microprocessor. This unique feature allows the microprocessor to test the watchdog circuit on every power-up.
By setting a flag in the memory and not strobing the watchdog, the microprocessor can force a watchdog time-out. After being reset, the microprocessor checks the status flag to see if this was a time-out test. If so, the microprocessor continues normal power-up activities. If the reset occurred when the microprocessor was not expecting it, the microprocessor traps the event, sounds the audible alarm and displays an error message on the LCD.
Motor Driver/Motor Watchdog Circuit
Motor drive circuitry is composed of a series of power FET transistors, passive components, and 2 voltage comparators. Built into the motor drive circuitry is an RC timer which times how long the motor runs each time it is turned on. If the motor runs for more than an average of 3 seconds, the circuit will time out and disable the motor. A unique feature of this circuit is that control lines to and from the microprocessor circuit allow the microprocessor to perform a complete functional test of the motor drive circuit without running the motor. The microprocessor performs this test function every several minutes to assure its continued functionality. An input from the watchdog circuit prevents motor operation if the watchdog timer expires. The software verifies this function during the watchdog test described above.
Voltage Detector Circuit
Low voltage detection is performed by part of the watchdog circuit and by the microprocessor via software. Three low voltage levels are detected. The first 2 levels are detected by software and the third by hardware. The first level to be reached is the low battery warning threshold which occurs when the battery voltage decays to a nominal value of 2.4 volts when the motor is off or 1.8 volts when the motor is active. An analog to digital converter (ADC) built into the microprocessor allows the microprocessor, via software, to monitor the battery voltage. At the low battery warning threshold, the microprocessor enables a periodic series of beeps and displays a low battery warning message on the LCD. As the voltage operating the motor reaches a nominal value of 4.75 volts, the software disables delivery, places a battery depleted message on the LCD, and enables a constant two tone audible alarm. When the battery voltage decays to a nominal value of 1.0 volts, a hardware reset circuit is triggered which places the microprocessor in reset. This prevents ambiguous microprocessor operation when the battery voltage continues to decay. The hardware reset continues until the battery is completely discharged or until it is removed. Once the pump controller goes into low battery shutdown, only replacing the depleted batteries with new ones will clear the condition.
Software Safety Features
Hardware-related Software Safety Features
Program Memory Check
At power up and at regular intervals thereafter, the program memory is tested by calculating a cyclic redundancy code (CRC) on the program and then comparing it with the CRC stored with the program.
If the stored and calculated CRCs do not match, the software will display a system fault screen, turn on a continuous two-tone audible alarm, and stop all medication delivery.
RAM Memory Check
At power up, the random access memory is checked. A series of bit patterns is written to and read from each address in the RAM. If the read data is different from the written data, the software will display a system fault screen, turn on a continuous two-tone audible alarm, and stop all medication delivery.
Motor Circuit Check
At power up and at regular intervals thereafter, the motor circuit is checked to ensure that no power is being applied to the motor unless the motor is actually on. If the software detects power being applied to the motor at any other time, it will sound a continuous two-tone audible alarm and will no longer attempt to deliver medication. During every pump activation, the software checks to see whether the motor completes one activation. If the motor fails to turn, or fails to complete a cycle, the software will display a system fault screen, turn on a continuous two-tone audible alarm, and stop all medication delivery.
Keyboard Encoder Check
Every time the software receives data from the keyboard encoder, it is checked. If the data is not a valid key press, the software will disregard the key press. The keyboard is designed with redundant switches for , , and . The software must detect that both switches are activated before taking any action.
Data Handling Software Safety Features
Data Stored in RAM
Before use, data associated with delivery and stored in RAM is tested by calculating a CRC on the data and then comparing it with the CRC stored with the data. If the stored and calculated CRCs do not match, the software will display a system fault screen, turn on a continuous two-tone audible alarm, and stop all medication delivery.
Data Stored in EEPROM
Before use, data associated with delivery and stored in EEPROM is tested by calculating a CRC on the data and then comparing it with the CRC stored with the data. If the stored and calculated CRCs do not match, the software will display a system fault screen, turn on a continuous two-tone audible alarm, and stop all medication delivery.
Data Stored in NOVRAM
Before use, data associated with delivery and stored in NOVRAM is tested by calculating a CRC on the data and then comparing it with the CRC stored with the data. If the stored and calculated CRCs do not match, the software will display a system fault screen, turn on a continuous two-tone audible alarm, and stop all medication delivery.
Data Used in Calculations
Calculations on data used in some way to control the delivery of medication are performed redundantly.
The two calculated values are then compared. If the two values do not match, the software will display a system fault screen, turn on a continuous two-tone audible alarm, and stop all medication delivery.
Timer Data Registers
The data in the real time clock is checked at regular intervals. If the data is not reasonable, the software will turn on a continuous two-tone audible alarm and stop all medication delivery.
Annual Functional Inspection
Smiths Medical recommends annual functional inspections and tests on the CADD-Legacy® 1400 pump. Contact Smiths Medical to coordinate return and inspection of the pump.
This product contains electronic and other components (such as batteries) that may contain materials which, if disposed of with general household waste, could be damaging to the environment.
In accordance with Directive 2002/96/EC Waste Electrical and Electronic Equipment, Smiths Medical requires that residents of the European Union return this product for proper disposal at the end of its useful life.
If you are unsure of the proper disposal method, contact your local distributor for specific disposal instructions.
Smiths Medical ASD, Inc. (the “Manufacturer”) warrants to the Original Purchaser that the infusion pump (the “Pump”), not including accessories, shall be free from defects in materials and workmanship under normal use, if used in accordance with this Operator’s Manual, for a period of one year from the actual date of sale to the Original Purchaser. THERE ARE NO OTHER WARRANTIES.
This warranty does not cover normal wear and tear and maintenance items, and specifically excludes batteries, administration sets, extension sets or any other accessory items or equipment used with the Pump.
Subject to the conditions of and upon compliance with this Limited Warranty, the Manufacturer will repair or replace at its option without charge (except for a minimal charge for postage and handling) any Pump (not including accessories) which is defective if a claim is made during such one-year period.
The following conditions, procedures, and limitations apply to the Manufacturer’s obligation under this warranty:
A. Parties Covered by this Warranty: This warranty extends only to the Original Purchaser of the Pump. This warranty does not extend to subsequent purchasers. The Original Purchaser may be a patient, medical personnel, a hospital, or institution which purchases the Pump for treatment of patients. The Original Purchaser should retain the invoice or sales receipt as proof as to the actual date of purchase.
B. Warranty Performance Procedure: Notice of the claimed defect must be made in writing or by telephone to the Manufacturer as follows: Smiths Medical ASD, Inc. 1265 Grey Fox Road, St. Paul MN 55112 USA, 1 800.258.5361 (USA). Notice to the Manufacturer must include date of purchase, model and serial number, and a description of the claimed defect in sufficient detail to allow the Manufacturer to determine and facilitate any repairs which may be necessary. AUTHORIZATION MUST BE OBTAINED PRIOR TO RETURNING THE PUMP. If authorized, the Pump must be properly and carefully packaged and returned to the Manufacturer, postage prepaid. Any loss or damage during shipment is at the risk of the sender.
C. Conditions of Warranty: The warranty is void if the Pump has been 1) repaired by someone other than the Manufacturer or its authorized agent; 2) altered so that its stability or reliability is affected; 3) misused; or, 4) damaged by negligence or accident. Misuse includes, but is not limited to, use not in compliance with the Operator’s Manual or use with nonapproved accessories. The Pump is a sealed unit, and the fact that the seal has been broken will be considered conclusive evidence that the Pump has been altered or misused. Removal or damage to the Pump’s serial number will invalidate this warranty.
D. Limitations and Exclusions: Repair or replacement of the Pump or any component part thereof is the EXCLUSIVE remedy offered by the Manufacturer. The following exclusions and limitations shall apply:
E. Computer Program License:
The Manufacturer disclaims responsibility for the suitability of the Pump for any particular medical treatment or for any medical complications resulting from the use of the Pump. The Manufacturer shall not be responsible for any incidental damages or consequential damages to property, loss of profits, or loss of use caused by any defect or malfunction of the Pump.
This warranty gives the Original Purchaser specific legal rights, and the Original Purchaser may have other legal rights which may vary from state to state.
Appendix A – Pump Programming Quick Reference for Healthcare Providers
This quick reference provides for step-by-step directions for several of the common pump programming tasks performed with the CADD-Legacy® 1400 pump. Additional pump information including warnings, cautions and more information on pump operations is located in the referenced sections of the pump Operator’s Manual. Please refer to the full prescribing information for DUOPA (carbidopa and levodopa) enteral suspension for indications and usage, contraindications, warnings, precautions, and adverse reactions.
Begin programming the pump by:
For instruction on attaching a medication cassette reservoir, see Section 2, Pump Setup and Programming.
Changing to Lock Level 0 (LL0)
Lock level 0 (LL0) allows the health care provider to adjust settings so they are appropriate for the patient. For more information on lock levels descriptions, see Section 1, General Description. For more information on changing the lock level, see Section 2, Pump Setup and Programming.
Pump Programming Settings
Program the pump settings to customize the medication delivery inputs for the patient. For more information see Section 2, Pump Setup and Programming.
NOTE: Ensure that the pump is in lock level 0 (LL0) and appears on the screen.
NOTE: Not in Use is the default setting for the reservoir volume. The reservoir volume feature is not required for use, but is available at provider discretion.
Pump Status: The continuous rate is now set.
Pump Status: The extra dose amount is now set.
NOTE: To change a setting again, press NEXT until the appropriate screen appears. Press or to adjust the setting, then press to confirm.
Changing Lockout Times
Program the dose lockout times to customize medication delivery inputs for each patient. Lockout times will determine how often a patient can deliver a morning dose and an extra dose. These values should be determined during titration. For more information on DUOPA titration, refer to the full prescribing information for DUOPA (carbidopa and levodopa) enteral suspension.
The biomed functions allow the health care provider access to the extra dose lockout and morning dose lockout settings. For more information about biomed functions, see Section 4, Biomed Functions.
Programming the Morning Dose
Program the morning dose to customize medication delivery for the patient. For more information, see Section 2, Pump Setup and Programming.
NOTE: In LL0, programming in the full range is possible. In LL1, you can program up to the LL0 value.
Setting the Lock Level
For patient use, the pump must be set to lock level 2 (LL2) or lock level 1 (LL1). For more information on lock levels descriptions, see Section 1, General Description. For more information on changing the lock level, see Section 2, Pump Setup and Programming.
Manufacturer:Smiths Medical ASD, Inc.1265 Grey Fox RoadSt. Paul, MN 55112 USATel: 1 800 258 5361 (USA), +1 614 210 7300www.smiths-medical.com
CADD, CADD-Legacy, and Smiths Medical design mark are trademarks of Smiths Medical. The symbol ® indicates the trademark is registered in the U.S. Patent and Trademark Office and certain other countries. All other names and marks mentioned are the trade names, trademarks or service marks of their respective owners.
© 2015 Smiths Medical. All rights reserved.
NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.
The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected over dosage, the drug's identity should be verified by chemical analysis.