Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Lecigon is not recommended for the treatment of drug-induced extrapyramidal reactions.
Lecigon should be administered with caution to patients with ischaemic heart disease, 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 Lecigon 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 Lecigon with caution, provided the intra-ocular pressure is well controlled and the patient is monitored carefully for changes in intra- ocular pressure.

Lecigon may induce orthostatic hypotension. Lecigon should therefore be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension; see section 4.5.

The active substances in Lecigon have been associated with somnolence and episodes of sudden sleep onset in patients with Parkinson's disease. Caution should therefore be exercised when driving and using machines (see sections 4.7 and 4.8).

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coma) and increased serum creatine phosphokinase, has been reported when anti-Parkinsonian medicinal products were withdrawn abruptly.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 has been observed rarely in patients with Parkinson's disease. Since entacapone was introduced on the market, isolated cases of NMS have been reported, particularly after abrupt dose reduction or discontinuation of entacapone and other concomitant dopaminergic medicinal products. Patients should be carefully observed when the dose of Lecigon is reduced or treatment is discontinued abruptly, especially if the patient is also receiving anti-psychotics/neuroleptics.

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, hypersexuality, compulsive spending or buying, binge eating and compulsive eating, can occur in patients treated with dopamine agonists and/or other dopaminergic therapies containing levodopa, including Lecigon. 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.
Patients and caregivers are therefore advised to monitor for melanomas on a regular basis when using Lecigon. Ideally, periodic skin examinations should be performed by an appropriately qualified individual (e.g. dermatologist).

If general anaesthesia is required, treatment with Lecigon 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, Lecigon at the same dose as before may be restarted as soon as oral intake of fluid is allowed.

It may be necessary to adjust the dose of Lecigon downwards to avoid levodopa-induced dyskinesias.

Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with Lecigon.

Lecigon contains hydrazine, a degradation product of carbidopa that can be genotoxic and possibly carcinogenic. The average recommended daily dose of Lecigon is 46 ml (corresponding to 1.6 mg hydrazine/day) and the maximum recommended daily dose of Lecigon is 100 ml (corresponding to maximum 3.5 mg hydrazine/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 for levodopa/carbidopa in 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 non-digestible vegetable or fruit fibres) in the intestinal tract. A bezoar around the tip of the jejunal tube may serve as the starting point of intestinal obstruction or intussusception. Most bezoars are found 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 of these events may result in serious outcomes, such as surgery 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, tubes) can lead to complications. In such cases, 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 tubing system for whatever reason and must be investigated.

Weight loss has been associated with the active substances contained in Lecigon, and caregivers should therefore be aware of weight loss. Monitoring of weight is recommended to avoid severe weight loss. This applies in particular to patients with diarrhoea. For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease. Prolonged or persistent diarrhoea that appears during use of entacapone may be a sign of colitis. In the event of prolonged or persistent diarrhoea, the medicinal product should be discontinued, and appropriate medical therapy and investigations considered.

Where deemed necessary, replacement of Lecigon with either levodopa and a DDC inhibitor without entacapone or other dopaminergic therapy should be done slowly. An increase in levodopa dose may be necessary.

For patients who experience progressive anorexia, asthenia and weight loss within a relatively short period of time, a general medical evaluation including liver function assessment should be considered.

Levodopa/carbidopa may cause false positive results when a dipstick is used to test for urinary ketones, and this reaction is not altered by boiling the urine sample. The use of glucose oxidase methods may give false negative results for glycosuria.

Dopamine Dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product 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).

If abuse of the medicinal product is suspected, there is a lock function in the pump used with Lecigon (Crono LECIG).

Polyneuropathy has been reported in patients treated with Duodopa (levodopa/carbidopa intestinal gel). Before starting therapy with Lecigon evaluate patients for history or signs of polyneuropathy and known risk factors, and periodically thereafter.

This medicinal product contains 3.5 mg sodium per mL. Each cartridge contains 166 mg sodium, equivalent to 8.3% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7   Effects on ability to drive and use machines

Lecigon can have a major influence on the ability to drive and use machines. Levodopa, carbidopa and entacapone may cause orthostatic hypotension and dizziness. Therefore, caution should be exercised when driving and using machines.

Patients being treated with Lecigon 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 sections 4.4 and 4.8.