Source: Health Products Regulatory Authority (IE) Revision Year: 2023 Publisher: AbbVie Limited, Citywest Business Campus, Dublin 24, Ireland
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.
Duodopa is a gel for continuous intestinal administration. For long-term administration, the gel should be administered with a portable pump directly into the duodenum or upper jejunum by a permanent tube via percutaneous endoscopic gastrostomy with an outer transabdominal tube and an inner intestinal tube. Alternatively, a radiological gastrojejunostomy may be considered if percutaneous endoscopic gastrostomy is not suitable for any reason. Establishment of the transabdominal port and dose adjustments should be carried out in association with a neurological clinic.
A temporary nasoduodenal/nasojejunal tube should be considered to determine if the patient responds favourably to this method of treatment before a permanent percutaneous endoscopic gastrostomy with jejunal tube (PEG-J) is placed. In cases where the physician considers this assessment is not necessary, the nasojejunal test phase may be waived and treatment initiated directly with placement of the PEG-J. The dose should be adjusted to an optimal clinical response for the individual patient, which means maximizing the functional ON-time during the day by minimizing the number and duration of OFF episodes (bradykinesia) and minimizing ON-time with disabling dyskinesia. See recommendations under Dosage.
Duodopa should be given initially as monotherapy. If required other medicinal products for Parkinson's disease can be taken concurrently. For administration of Duodopa only the CADD-legacy 1400 pump (CE Marked) should be used. A manual with instructions for using the portable pump is delivered together with the pump.
Treatment with Duodopa using a permanent tube can be discontinued at any time by withdrawing the tube and letting the wound heal. Treatment should then continue with oral medicinal products including levodopa/carbidopa.
The total dose/day of Duodopa is composed of three individually adjusted doses: the morning bolus dose, the continuous maintenance dose and extra bolus doses administered over approximately 16 hours. Treatment is usually administered during the patient's awake period. If medically justified, Duodopa may be administered for up to 24 hours.
The medicine cassettes are for single use only and should not be used for longer than 24 hours, even if some medicinal product remains. Do not reuse an opened cassette.
By the end of the storage time the gel might become slightly yellow. This does not influence the concentration of the medicine or the treatment.
Morning dose: The morning bolus dose is administered by the pump to rapidly achieve the therapeutic dose level (within 10-30 minutes). The dose should be based on the patient's previous morning intake of levodopa + the volume to fill the tubing. The total morning dose is usually 5-10 ml, corresponding to 100-200 mg levodopa. The total morning dose should not exceed 15 ml (300 mg levodopa).
Continuous maintenance dose: The maintenance dose is adjustable in steps of 2 mg/hour (0.1 ml/hour). The dose should be calculated according to the patient's previous daily intake of levodopa. When supplementary medicines are discontinued the Duodopa dose should be adjusted. The continuous maintenance dose is adjusted individually. It should be kept within a range of 1-10 ml/hour (20-200 mg levodopa/hour) and is usually 2-6 ml/hour (40-120 mg levodopa/hour). The maximum recommended daily dose is 200 ml (see section 4.4). In exceptional cases a higher dose may be needed.
Example:
Daily intake of levodopa as Duodopa: 1640 mg/day
Morning bolus dose: 140 mg = 7 ml (excluding the volume to fill the intestinal tube)
Continuous maintenance dose: 1500 mg/day
1500 mg/day: 20 mg/ml = 75 ml Duodopa per day
The intake is calculated over 16 hours: 75 ml/16 hours = 4.7 ml/hour.
Extra bolus doses: To be given as required if the patient becomes hypokinetic during the day. The extra dose should be adjusted individually, normally 0.5-2.0 ml. 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.
After the initial dose setting, fine adjustments of the morning bolus dose, the maintenance dose and extra bolus doses should be carried out over a few weeks.
A sudden deterioration in treatment response with recurring motor fluctuations should lead to the suspicion that the distal part of the tube has become displaced from the duodenum/jejunum into the stomach. The location of the tube should be determined by X-ray and the end of the tube repositioned to the duodenum/jejunum.
There is no relevant use of Duodopa in the paediatric population in the indication of advanced levodopa-responsive Parkinson's disease with severe motor fluctuations and hyper-/dyskinesia.
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.
There are no studies on the pharmacokinetics of carbidopa and levodopa in patients with hepatic or renal impairment. Dosing with Duodopa is individualized by titration to optimal effect (which corresponds to individually optimized levodopa and carbidopa plasma exposures); 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 (see section 4.4).
Patients should be carefully observed in case a sudden reduction of the dose is required or if it becomes necessary to discontinue treatment with Duodopa, particularly if the patient is receiving antipsychotics, see section 4.4.
In the case of suspected or diagnosed dementia with a decreased confusion threshold, the pump of the patient should be handled only by the nursing staff or a caregiver.
When a cassette is about to be used, it should be attached to the portable pump and the system connected to the nasoduodenal tube or duodenal/jejunal tube for administration, according to the instructions given.
Most prominent clinical symptoms of an overdose with levodopa/carbidopa are dystonia and dyskinesia. Blepharospasms can be an early sign of overdose.
The treatment of an acute overdose of Duodopa is in general the same as that of an acute overdose of levodopa: However, pyridoxine has no effect on the reversal of the action of Duodopa. Electrocardiographic monitoring should be used and the patient observed carefully for the development of cardiac arrhythmias; if necessary an appropriate antiarrhythmic therapy should be given. The possibility that the patient took other medicinal products together with Duodopa should be taken into consideration. To date experiences with dialysis have not been reported, therefore its value in the treatment of overdose is unknown.
Unopened: 15 weeks.
Once opened: Use immediately. The product is to be used for up to 24 hours once it is out of the refrigerator. Discard any unused portion.
Store and transport refrigerated (2°C-8°C).
Keep the cassette in the outer carton in order to protect from light.
For storage conditions after first opening of the medicinal product, see section 6.3.
Total amount of 100 ml in PVC bag inside a hard plastic cassette for protection, carton with 7 cassettes.
Cassettes are for single use only.
Do not re-use an opened cassette.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Empty/used cassettes should be returned to the pharmacy for destruction.
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