Duodopa

/ AbbVie

This drug  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. This formulation   should be given initially as monotherapy. If required other medicinal products for Parkinson’s disease can be taken concurrently. For administration of this formulation  only the CADD-legacy 1400 pump (CE 0473) should be used. The total dose/day of this formulation is composed of three individually adjusted doses: the morning bolus dose, the continuous maintenance dose and extra bolus doses administered over approximately 16 hours. The drug cassettes are for single use only and should not be used for longer than 16 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 drug 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 this formulation’s 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.In exceptional cases a higher dose may be needed. See prescribing information for full details.
Example: Daily intake of levodopa in this formulation: 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 of gel 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. If medically justified this formulation may be administered during the night.
Monitoring of treatment: 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.
Paedriatric population: There is no relevant use of this drug in the paediatric population in the indication of advanced levodopa-responsive Parkinson’s disease with severe motor fluctuations and hyper-/dyskinesia.
Geriatric Population: There is 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. See prescribing information for full details.
Interruption of therapy: Patients should be carefully observed in case a sudden reduction of the dose is required or if it becomes necessary to discontinue treatment with this formulation, particularly if the patient is receiving antipsychotics. See prescribing information for full details.
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.

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

Hypersensitivity to levodopa, carbidopa or any of the excipients of the formulation. Narrow-angle glaucoma. Severe heart failure. Severe cardiac arrhythmia. Acute stroke. Non-selective MAO inhibitors and selective MAO type A inhibitors are contraindicated for use with this formulation. These inhibitors must be discontinued at least two weeks prior to initiating therapy with this drug. This drug may be administered concomitantly with the manufacturer’s recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline HCl). Conditions in which adrenergics are contraindicated: pheochromocytoma, hyperthyroidism and Cushing’s syndrome. Because levodopa may activate malignant melanoma, this drug should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.

Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk of developing melanoma than the general population. It is unclear whether the increased risk observed was due to Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease. Therefore patients and providers are advised to monitor for melanomas on a regular basis when using this drug for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g. dermatologists). Reported complications in the clinical studies include bezoar, ileus, implant site erosion/ulcer, intestinal haemorrhage, intestinal ischaemia, intestinal obstruction, intestinal perforation, pancreatitis, peritonitis, pneumoperitoneum and post-operative wound infection. Bezoars are retained concretions of undigested food material in the intestinal tract. Most bezoars reside in the stomach but bezoars may be encountered elsewhere in the intestinal tract. 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. Reported complications in the clinical studies and seen Post-marketing, include bezoar, ileus, implant site erosion/ulcer, intestinal haemorrhage, intestinal ischaemia, intestinal obstruction, intestinal perforation, intussusception, pancreatitis, peritonitis, pneumoperitoneum and post-operative wound infection. Bezoars are retained concretions of indigestible undigested food material (such as vegetable or fruit non-digestible fibers) in the intestinal tract. Most bezoars reside in the stomach but bezoars may be encountered elsewhere 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. Weight loss is seen in PD patients both before and during levodopa treatment. It appears to be a multifactorial phenomenon, with various degrees. Monitoring of body weight and nutritional status within the context of routine clinical care is considered to be a suitable measure for early identification of weight loss. Dopamine Dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some patients treated with levodopa/carbidopa. Before initiation of treatment, patients and caregivers should be warned of the potential risk of developing DDS.
See prescribing information for full details.

Hypotension, anaemia, Increased weight, Amino acid level increased (Metylmalonic acid increased), Blood homocysteine increased, Decreased appetite, Vitamin B6 deficiency, Vitamin B12 deficiency, Vitamin B6 decreased, Vitamin B12 decreased, folic acid deficiency.
See prescribing information for full details.

Antihypertensives: Symptomatic postural hypotension has occurred when combinations of levodopa and a decarboxylase inhibitor are added to the treatment of patients already receiving anti-hypertensives. Dosage adjustment of the antihypertensive agent may be required.
Antidepressants: There have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant administration of tricyclic antidepressants and carbidopa/levodopa preparations.
Anticholinergics: Anticholinergics may act synergistically with levodopa to decrease tremor. However, combined use may exacerbate abnormal involuntary movements. Anticholinergics may decrease the effects of levodopa by delaying its absorption. An adjustment of the dose of this drug  may be needed.
COMT inhibitors (tolcapone, entacapone): Concomitant use of COMT (Catechol-O-Methyl Transferase) inhibitors and this drug can increase the bioavailability of levodopa. The dose of this formulation may need adjustment.
Other medicinal products: Dopamine receptor antagonists (some antipsychotics, e.g. phenothiazines, butyrophenons and risperidone and antiemetics, e.g. metoclopramide), benzodiazepines, isoniazide, phenytoin and papaverine can reduce the therapeutic effect of levodopa. Patients taking these medicinal products together with this formulation should be observed carefully for loss of therapeutic response. This drug can be taken concomitantly with the recommended dose of an MAO inhibitor, which is selective for MAO type B (for instance selegiline-HC1). The dose of levodopa may need to be reduced when an MAO inhibitor selective for type B is added. Concomitant use of selegiline and levodopa-carbidopa has been associated with serious orthostatic hypotension. Amantadine has a synergic effect with levodopa and may increase levodopa related adverse events. An adjustment of the dose of this drug  may be needed. Sympathicomimetics may increase cardiovascular adverse events related to levodopa. Levodopa forms a chelate with iron in the gastrointestinal tract leading to reduced absorption of levodopa. As levodopa is competitive with certain amino acids, the absorption of levodopa can be disturbed in patients who are on a protein rich diet. The effect of administration of antacids and this formulations on the bioavailability of levodopa has not been studied.

Pregnancy: There are no or limited amount of data from the use of levodopa/carbidopa in pregnant women.
Lactation: Levodopa and possibly levodopa metabolites are excreted in human milk. There is evidence that lactation is suppressed during treatment with levodopa. It is unknown whether carbidopa or its metabolites are excreted in human milk.
See prescribing information for full details.

Most prominent clinical symptoms of an overdose with levodopa/ carbidopa are dystonia and dyskinesia. Blepharospasm can be an early sign of overdose. The treatment of an acute overdose of this drug 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 this formulation. 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 this drug should be taken into consideration. To date experiences with dialysis have not been reported, therefore its value in the treatment of overdose is unknown.

Effects on ability to drive and use machines: This formulation  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 this formulation 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.
See prescribing information for full details.