Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Special warnings and precautions for Produodopa
Several warnings and precautions below are generic for levodopa and, therefore, also for Produodopa.

•     Produodopa is not recommended for the treatment of drug-induced extrapyramidal reactions.
•     Produodopa 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 Produodopa 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. Higher frequency of hallucinations can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including Produodopa. Review of treatment is recommended if such symptoms develop.
•     Concomitant administration of antipsychotics with dopamine receptor-blocking properties, particularly D2 receptor antagonists, should be carried out with caution, and the patient should be 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 Produodopa with caution, provided the intra-ocular pressure is well controlled and the patient is monitored carefully for changes in intra-ocular pressure during therapy.
•     Produodopa may induce orthostatic hypotension. Therefore, Produodopa 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 NMS 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 antipsychotics. Neither NMS nor rhabdomyolysis has been reported in association with Produodopa.
•     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 Produodopa. 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 Produodopa for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).


•     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.
•     The dose of Produodopa 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 Produodopa.
•     Produodopa contains hydrazine, a degradation product of foscarbidopa, that can be genotoxic and probably carcinogenic. The median daily dose of Produodopa is approximately 2541 mg/day of foslevodopa and 127 mg/day of foscarbidopa. The maximum recommended daily dose is 6000 mg foslevodopa and 300 mg foscarbidopa. This includes hydrazine at up to a median exposure of 0.2 mg/day, with a maximum of 0.5 mg/day. The clinical significance of this hydrazine exposure is not known.
•     Reduced ability to handle the delivery system can lead to complications. In such patients a caregiver (e.g., 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.
•     Polyneuropathy has been reported in patients treated with levodopa/carbidopa-containing products. Before starting therapy evaluate patients for history or signs of polyneuropathy and known risk factors, and periodically thereafter.
•     Infusion site events (see section 4.8) have been reported in patients receiving Produodopa.
Following aseptic techniques while using this medication and frequent rotation of the infusion site are recommended to reduce the risk. In clinical studies, few patients who reported infusion site reactions also experienced infusion site infections. Therefore, careful monitoring of serious infusion site reactions and infusion site infections is recommended.

Produodopa contains sodium

Produodopa contains 42.4 mg (approximately 1.84 mmol) of sodium per ml, equivalent to 2.1% of the WHO recommended maximum daily dietary intake of sodium. The maximum daily dose of this medicine contains 54% of the WHO recommended maximum daily intake of sodium.

Produodopa is high in sodium. This should be considered especially in patients on a low salt diet.

Effects on Driving

4.7   Effects on ability to drive and use machines

Produodopa 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 Produodopa 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).