DUODOPA 20mg/ml + 5mg/ml intestinal gel:
The Summary of Product Characteristics (SPC)
should be read thoroughly for full prescribing information.
PRESENTATION: Intestinal gel containing 20mg/ml levodopa and 5mg/ml carbidopa monohydrate.
INDICATION: 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: Adults/Elderly: Administration by portable pump directly into the duodenum or upper jejeunum 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. Total dose/day is composed of three individually adjusted doses: morning bolus, continuous maintenance and extra bolus doses. 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) 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. 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. 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 16 hours). In addition to daytime, if medically justified Duodopa may be administered during the night. Opened cassettes should not be reused. Children: There is no relevant indication for use in children and adolescents.
CONTRAINDICATIONS, WARNINGS, PRECAUTIONS: Contraindications: Hypersensitivity to ingredients, 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 Non-selective MAO-inhibitors and selective MAO type A inhibitors are contraindicated and should be withdrawn at least two weeks before starting Duodopa.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. Warnings/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 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 bezoar, ileus, implant site erosion/ulcer, intestinal haemorrhage, intestinal ischaemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumoperitoneum and post-operative wound infection. Drug Interactions: 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.
PREGNANCY AND LACTATION: Potential risk in pregnancy is not known. Women should not breast feed.
ABILITY TO DRIVE AND OPERATE MACHINERY: Caution; Duodopa has a major influence on the ability to drive and use machines. Refrain if somnolence or sudden sleep onset occur.
SIDE EFFECTS: Very Common & Common: Anaemia, weight change (increase or decrease), amino acid level increased, decreased appetite, Vitamin B6 & B12 deficiency, anxiety, depression, insomnia, abnormal dreams, agitation, confusional state, hallucination, impulsive behaviour, psychotic disorder, sleep attacks, sleep disorder, dyskinesia, Parkinson’s disease, dizziness, dystonia, headache, hypoaesthesia, on and off phenomenon, paraesthesia, polyneuropathy, somnolence, syncope, tremor, irregular heartbeat, orthostatic hypotension, hypertension, hypotension, dyspnoea, oropharyngeal pain, pneumonia, aspiration, nausea, constipation, abdominal distension, diarrhoea, dry mouth, dysgeusia, dyspepsia, dysphagia, flatulence, vomiting, contact dermatitis, hyperhidrosis, peripheral oedema, pruritus, rash, muscle spasms, neck pain, urinary incontinence or retention, fatigue, pain, asthenia and fall. Serious side effects include: Anaphylactic reaction, leucopenia, thrombocytopenia, agranulocytosis, neuroleptic malignant syndrome, eye disorders, gastrointestinal bleeding and duodenal ulceration, malignant melanoma. Laboratory values: May change. Other less common and rarely reported side effects are listed in the SPC. Complications of the device & surgery: Very common & common: postoperative wound infection, incision site cellulitis, post-procedural infection, abdominal pain, abdominal discomfort, upper abdominal pain, peritonitis, pneumo-peritoneum, excessive granulation tissue, complications of device insertion, device dislocation, device occlusion, incision site erythema, post procedural discharge, procedural pain, procedural site reaction, gastrointestinal stoma complication, incision site pain, postoperative ileus, post-procedural complication, discomfort or haemorrhage. Occlusions, kinks or knots in tube occur. See SPC for complete listing of side effects.
MARKETING AUTHORISATION NUMBER: PL 41042/0001
BASIC NHS PRICE: 7 x 100ml cassettes: £539
LEGAL CATEGORY: POM
FURTHER INFORMATION AVAILABLE FROM THE MARKETING AUTHORISATION
HOLDER: AbbVie Ltd, Maidenhead, SL6 4UB
DATE OF REVISION OF PI: September 2017