ABBREVIATED PRESCRIBING INFORMATION:
Duodopa 20 mg/ml + 5 mg/ml intestinal gel (levodopa/carbidopa)
Please refer to the Summary of Product Characteristics (SmPC) before prescribing.
PRESENTATION: 100 ml contains 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: Administration by portable pump directly into the duodenum or upper jejeunum by a permanent tube via 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/hr (20-200mg levodopa/hr) but usually 2-6ml/hr (40-120mg levodopa/hr). Maximum recommended daily dose is 200ml. Extra bolus doses (if patient becomes hypokinetic during the day) are normally 0.5-2.0ml. Increase maintenance dose if more than 5 extra bolus doses/day are needed. Fine adjustments to the morning bolus, maintenance and extra bolus doses should be made over a few weeks after the initial dose setting. Sudden deterioration in response with recurring motor fluctuations indicates tube may have moved from duodenum/jejunum into stomach and needs repositioning. Medicine cassettes are for single use only and should not be used for longer than 24 hours, even if some medicinal product remains. 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.
Special populations: Paediatric population: There is no relevant indication for use in the paediatric population. Geriatric population: 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. Dose titration should be conducted with caution in patients with severe renal and hepatic impairment.
CONTRAINDICATIONS: Hypersensitivity to the active substances or any of the excipients, narrow-angle glaucoma, severe heart failure or cardiac arrhythmia, acute stroke. Conditions where adrenergics are contraindicated (e.g. pheochromocytoma, hyperthyroidism, Cushing’s syndrome). 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. A symptom complex resembling Neuroleptic Malignant Syndrome (NMS), and rhabdomyolysis secondary to NMS or severe dyskinesias, has not been reported with Duodopa but may occur on abrupt dose reduction/withdrawal especially if the patient is receiving anti-psychotics. 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. Ideally, periodic skin examinations should be performed by dermatologists. 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, clinical significance of exposure unknown. Reported complications in 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. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing Dopamine Dysregulation Syndrome (DDS). 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. 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.
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, isoniazide, 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: There is limited data relating to 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 should be discontinued during treatment with Duodopa. No adverse reactions on fertility have been observed in preclinical studies with carbidopa or levodopa alone.
ABILITY TO DRIVE AND OPERATE MACHINERY: Caution; Duodopa can have a major influence on the ability to drive and use machines. May cause dizziness and orthostatic hypotension, therefore exercise caution. Refrain from driving/operating machinery if somnolence and/or sudden sleep episodes occur, until such recurrent episodes and somnolence have resolved.
UNDESIRABLE EFFECTS: Very common (≥1/10): urinary tract infections,weight decreased, anxiety, depression, insomnia, dyskinesia, parkinson’s disease, orthostatic hypotension, nausea, constipation, fall. Common (≥ 1/100 to <1/10): anaemia, increased weight, amino acid level increased (metylmalonic acid increased), blood homocysteine increased, decreased appetite, vitamin B6 & 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, urinary retention, fatigue, pain, asthenia. Device and Procedure Related Adverse Reactions: Very common: postoperative wound infection, abdominal pain, excessive granulation tissue, complications of device insertion, incision site erythema, post procedural discharge, procedural pain, procedural site reaction. Common: incision site cellulitis, post procedural infection, abdominal discomfort, abdominal pain upper, peritonitis, pneumoperitoneum, pneumonia/aspiration pneumonia, device dislocation, device occlusion, gastrointestinal stoma complication, incision site pain, postoperative Ileus, post procedural complication, post procedural discomfort, post procedural haemorrhage. Laboratory values: May change. Refer to Section 4.8 of the SmPC for details of other side effects, and for further information.
Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, website: www.hpra.ie.
LEGAL CATEGORY: POM (S1B)
MARKETING AUTHORISATION NUMBER: PA 1824/2/1
Further information is available on request from: AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24 .
DATE OF REVISION: January 2024.
Pl/2/006
IE-DUOD-240006. Date of preparation: March 2024.
