PRESCRIBING INFORMATION (PI)

DUODOPA (levodopa and carbidopa) 20 mg/ml + 5 mg/ml intestinal gel

Refer to the Summary of Product Characteristics (SmPC) before prescribing.

PRESENTATION: 1 ml contains 20 mg levodopa and 5 mg carbidopa monohydrate. 100 ml contain 2000 mg levodopa and 500 mg carbidopa monohydrate.

INDICATION: Treatment of advanced levodopa-responsive Parkinson’s disease with severe motor fluctuations and hyperkinesia or dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results.

DOSAGE AND ADMINISTRATION: Posology: Administration by portable pump directly into the duodenum or upper jejunum by a permanent tube via a percutaneous endoscopic gastrostomy (PEG) or radiological gastrojejunostomy tube. Duodopa is given initially as monotherapy and dose adjusted to optimal response for the individual patient. Dosage: Total dose/day is composed of three individually adjusted doses: morning bolus, continuous maintenance and extra bolus doses administered over approximately 16 hours. Total morning dose is usually 5-10ml (100-200mg levodopa) but not exceeding 15ml (300mg levodopa). Continuous maintenance dose should be between 1-10ml/hour (20-200mg levodopa/hour) but usually 2-6ml/hour (40-120mg levodopa/hour). Extra bolus doses (if patient becomes hypokinetic during the day) are normally 0.5-2.0ml. In rare cases a higher dose may be needed. If the need for extra bolus doses exceeds 5 per day the maintenance dose should be increased. The maximum recommended daily dose is 200 ml. Fine adjustments to the morning bolus, maintenance and extra bolus doses should be made over a few weeks after the initial dose setting. Interruption of therapy: Sudden deterioration in response with recurring motor fluctuations indicates the tube may have moved from the duodenum into the stomach and needs repositioning. The medicine cassettes are for single use only and should not be used for longer than one day (up to 24 hours). Treatment is usually administered during the patient’s awake period. If medically justified, Duodopa may be administered for up to 24 hours. Opened cassettes should not be reused. Cardiac function should be monitored with particular care during the period of initial dosage adjustments.

Special populations: Paediatric Population: There is no relevant indication for use in children and adolescents. Geriatric Population: There is a considerable experience in the use of levodopa/carbidopa in elderly patients. Doses for all patients including geriatric population are individually adjusted by titration.

Renal/hepatic impairment: There are no studies on the pharmacokinetics of carbidopa and levodopa in patients with hepatic or renal impairment. Dosing is individually optimised therefore potential effects of hepatic or renal impairment on levodopa and carbidopa exposure are indirectly accounted for in dose titration. Dose titration should be conducted with caution in patients with severe renal and hepatic impairment.

CONTRAINDICATIONS: Hypersensitivity to the active substance or any of the excipients, narrow-angle glaucoma, severe heart failure or cardiac arrhythmia, acute stroke. Conditions where adrenergics are contraindicated. Non-selective MAO-inhibitors and selective MAO type A inhibitors are contraindicated and should be withdrawn at least two weeks before starting Duodopa. Duodopa should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.

SPECIAL WARNINGS AND PRECAUTIONS: Not recommended for drug-induced extrapyramidal reactions. Caution in severe pulmonary or cardiovascular disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions, past or current psychosis, chronic wide-angle glaucoma, co-administration with antipsychotics with dopamine receptor blocking properties, particularly D₂ receptor antagonists or with medicines which may cause orthostatic hypotension. In patients with a history of myocardial infarction who have residual nodal or ventricular arrhythmias, cardiac function should be monitored with care during initial dose adjustments. Monitor all patients for mental changes, depression with suicidal tendencies and other serious mental changes. Neuroleptic malignant like syndrome with secondary rhabdomyolysis has not been reported with Duodopa but may occur on abrupt dose reduction/withdrawal. Periodically evaluate hepatic, haematopoietic, cardiovascular and renal function during extended therapy. Increases in impulse control disorders have been reported and patients should be monitored and reviewed. Patients and providers are advised to monitor for melanomas on a regular basis when using Duodopa. Dose may need to be adjusted downwards to avoid levodopa induced dyskinesia. Sudden or gradual worsening of bradykinesia may indicate an obstruction in the device and should be investigated. Duodopa contains hydrazine, a degradation product of carbidopa that can be genotoxic and possibly carcinogenic. Reported complications in the clinical studies include abscess, bezoar, ileus, implant site erosion/ulcer, intestinal haemorrhage, intestinal ischaemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumonia (including aspiration pneumonia), pneumoperitoneum, post-operative wound infection and sepsis. Bezoars are retained concretions of indigestible material in the intestinal tract. A bezoar around the tip of the jejunal tube may function as a lead point for intestinal obstruction or the formation of intussusception. Abdominal pain may be a symptom of the above listed complications. Some events may result in serious outcomes, such as surgery and/or death. Patients should be advised to notify their physician if they experience any of the symptoms associated with the above events. Polyneuropathy has been reported in patients treated with levodopa/carbidopa intestinal gel. Before starting therapy evaluate patients for history or signs of polyneuropathy and known risk factors, and periodically thereafter. Levodopa has been associated with somnolence and episodes of sudden sleep onset in patients with Parkinson’s disease and caution should therefore be exercised when driving and operating machines. If general anaesthesia is required, treatment with Duodopa may be continued for as long as the patient is permitted to take fluids and medicinal products by mouth. If therapy has to be stopped temporarily, Duodopa at the same dose as before may be restarted as soon as oral intake of fluid is allowed. Previous surgery in the upper part of the abdomen may lead to difficulty in performing gastrostomy or jejunostomy. Reduced ability to handle the system (pump, tube connections) can lead to complications. In such patients a caregiver (e.g., nurse, assistant nurse, or close relative) should assist the patient. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing Dopamine Dysregulation Syndrome (DDS).

INTERACTIONS: No interaction studies have been performed with Duodopa. The following interactions are known from the generic combination of levodopa/carbidopa. Caution is needed in concomitant administration of Duodopa with the following medicinal products: antihypertensives, tricyclic antidepressants, anticholinergics, dopamine receptor antagonists, benzodiazepines, isoniazid, phenytoin, papaverine, sympathicomimetics, iron, protein-rich diet, COMT inhibitors (e.g., tolcapone, entacapone) and amantadine may increase levodopa related adverse events. Duodopa dose adjustment may be needed when used with these medicines. Duodopa can be taken with MAO type B inhibitors (e.g., selegiline) although serious orthostatic hypotension may occur and the dose of levodopa may need to be reduced.

FERTILITY, PREGNANCY AND LACTATION: Pregnancy: There are no or limited amount of data from the use of levodopa/carbidopa in pregnant women. Studies in animals have shown reproduction toxicity. Duodopa is not recommended during pregnancy and in women of childbearing potential not using contraception unless the benefits for the mother outweigh the risks to the foetus. Breast-feeding: Breast-feeding should be discontinued during treatment with Duodopa. Fertility: No adverse reactions on fertility have been observed in preclinical studies with carbidopa or levodopa alone. Fertility studies in animals have not been conducted with the combination of levodopa and carbidopa.

ABILITY TO DRIVE AND USE MACHINES: Caution; Duodopa has a major influence on the ability to drive and use machines. Levodopa and carbidopa may cause dizziness and orthostatic hypotension. Therefore, caution should be exercised when driving or using machines. Patients being treated with Duodopa and presenting with somnolence and/or sudden sleep episodes must be advised to refrain from driving or engaging in activities where impaired alertness may put them, or others, at risk of serious injury or death (e.g., operating machines) until such recurrent episodes and somnolence have resolved.

UNDESIRABLE EFFECTS: See SmPC for full list of adverse reactions.

Very Common (≥1/10): urinary tract infections, weight decreased, anxiety, depression, insomnia, dyskinesia, Parkinson’s disease, orthostatic hypotension, nausea, constipation, and fall.

Common (≥1/100 to <1/10): Anaemia, increased weight ), amino acid level increased (Metylmalonic acid increased), blood homocysteine increased, decreased appetite, Vitamin B6 & Vitamin B12 deficiency, abnormal dreams, agitation, confusional state, hallucination, impulsive behaviour, psychotic disorder, sleep attacks, sleep disorder, dizziness, dystonia, headache, hypoaesthesia, on and off phenomenon, paraesthesia, polyneuropathy, somnolence, syncope, tremor, heart rate irregular, hypertension, hypotension, dyspnoea, oropharyngeal pain, abdominal distension, diarrhoea, dry mouth, dysgeusia, dyspepsia, dysphagia, flatulence, vomiting, dermatitis contact, hyperhidrosis, oedema peripheral, pruritus, rash, muscle spasms, neck pain, urinary incontinence or retention, fatigue, pain and asthenia.

Serious side effects include: Anaphylactic reaction, leukopenia, thrombocytopenia, agranulocytosis, neuroleptic malignant syndrome, eye disorders, gastrointestinal bleeding and duodenal ulceration, malignant melanoma, completed suicide, suicide attempt, depression, phlebitis, rash, sepsis, convulsion, optic ischaemic neuropathy, erythema; haemolytic anaemia – observed with oral levodopa/carbidopa.

Laboratory values: The following laboratory abnormalities have been reported with levodopa/carbidopa treatment and should, therefore, be acknowledged when treating patients with Duodopa: elevated urea nitrogen, alkaline phosphatases, S-AST, S-ALT, LDH, bilirubin, blood sugar, creatinine, uric acid and positive Coomb's test, and lowered values of haemoglobin and haematocrit. Leucocytes, bacteria and blood in the urine have been reported.

Complications of the device & surgery:

Very common (≥1/10): postoperative wound infection, abdominal pain, excessive granulation tissue, complications of device insertion, incision site erythema, post procedural discharge, procedural pain, procedural site reaction. Complication of device insertion was a commonly reported adverse reaction for both the nasojejunal tube and the PEG-J. This adverse reaction was co-reported with 1 or more of the following adverse reactions for the nasojejunal tube: oropharyngeal pain, abdominal distention, abdominal pain, abdominal discomfort, pain, throat irritation, gastrointestinal injury, esophageal haemorrhage, anxiety, dysphagia, and vomiting. For the PEG-J, this adverse reaction was co-reported with 1 or more of the following adverse reactions: abdominal pain, abdominal discomfort, abdominal distension, flatulence, or pneumoperitoneum. Other non-serious adverse reactions that were co-reported with complication of device insertion included abdominal discomfort, abdominal pain upper, duodenal ulcer, duodenal ulcer haemorrhage, erosive duodenitis, gastritis erosive, gastrointestinal haemorrhage, peritonitis, pneumoperitoneum, small intestine ulcer. Occlusions, kinks or knots in tube occur.

Common (≥1/100 to <1/10): incision site cellulitis, post-procedural infection, abdominal discomfort, abdominal pain upper, peritonitis, pneumo-peritoneum, pneumonia, aspiration pneumonia, device dislocation, device occlusion, gastrointestinal stoma complication, incision site pain, postoperative ileus, post-procedural complication, discomfort or haemorrhage.

Device and procedure related serious adverse reactions: sepsis, peritonitis, colitis ischaemic, gastrointestinal ischaemia, gastrointestinal obstruction, pancreatitis, small intestinal haemorrhage, large intestinal perforation, gastric perforation, gastrointestinal perforation, pneumonia, aspiration pneumonia, post procedural haemorrhage, incision site erythema, bezoar, small intestinal perforation.

MARKETING AUTHORISATION NUMBER / PRESENTATION / NHS LIST PRICE:

PL 41042/0001, 7 x 100 ml cassettes: £539

LEGAL CLASSIFICATION: POM

MA HOLDER: Further information available from AbbVie Ltd, Maidenhead, SL6 4UB.

DATE OF REVISION: November 2023

DOCUMENT NUMBER: DUOD-UK-00001-C

UK-DUOD-230134. Date of preparation: December 2023.