Special Warning : אזהרת שימוש

4.4      Special warnings and precautions for use
Several warnings and precautions below are generic for levodopa and, therefore, also for Duodopa.
• Duodopa is not recommended for the treatment of drug-induced extrapyramidal reactions.
• Duodopa therapy should be administered with caution to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions.
• In patients with a history of myocardial infarction who have residual atrial nodal or ventricular arrhythmias, cardiac function should be monitored with particular care during the period of initial dosage adjustments.
• All patients treated with Duodopa should be monitored carefully for the development of mental changes, depression with suicidal tendencies, and other serious mental changes.
Patients with past or current psychosis should be treated with caution.
• Concomitant administration of antipsychotics with dopamine receptor blocking properties, particularly D2 receptor antagonists should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect or worsening of parkinsonian symptoms, see section 4.5.
•   Patients with chronic wide-angle glaucoma may be treated with Duodopa with caution, provided the intra-ocular pressure is well controlled and the patient is monitored carefully for changes in intra-ocular pressure.
•   Duodopa may induce orthostatic hypotension. Therefore, Duodopa should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension, see section 4.5.
•   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 (see section 4.7).
•   A symptom complex resembling Neuroleptic Malignant Syndrome (NMS), including muscular rigidity, increased body temperature, mental changes (e.g. agitation, confusion, coma) and increased serum creatine phosphokinase, has been reported when anti- Parkinsonian medicinal products were withdrawn abruptly. Rhabdomyolysis secondary to Neuroleptic Malignant Syndrome or severe dyskinesias have been observed rarely in patients with Parkinson’s disease. Therefore, patients should be carefully observed when the dose of levodopa/carbidopa combinations are abruptly reduced or discontinued, especially if the patient is receiving anti-psychotics. Neither NMS nor rhabdomyolysis has been reported in association with Duodopa.
•   Patients should be regularly monitored for the development of impulse control disorders.
Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathologic gambling, increased libido and hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including Duodopa. Review of treatment is recommended if such symptoms develop.
•   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 medicines used to treat Parkinson’s disease. Therefore, patients and providers are advised to monitor for melanomas on a regular basis when using Duodopa for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g.
dermatologists).
•   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.
•   The dose of Duodopa may need to be adjusted downwards in order to avoid levodopa induced dyskinesias.
•   Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with Duodopa.
•   Duodopa contains hydrazine, a degradation product of carbidopa that can be genotoxic and possibly carcinogenic. The average recommended daily dose of Duodopa is 100 ml, containing 2 g levodopa and 0.5 g carbidopa. The maximum recommended daily dose is 200 ml. This includes hydrazine at up to an average exposure of 4 mg/day, with a maximum of 8 mg/day. The clinical significance of this hydrazine exposure is not known.
•   Previous surgery in the upper part of the abdomen may lead to difficulty in performing gastrostomy or jejunostomy.
•   Reported complications in the clinical studies, and seen post-marketing, 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 (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.
•   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.
•   A sudden or gradual worsening of bradykinesia may indicate an obstruction in the device for whatever reason and needs to be explored.
•   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 also section 4.8).
•   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.
•   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.

Effects on Driving

4.7   Effects on ability to drive and use machines
Duodopa can have 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, see also section 4.4.