Stalevo Special Precautions

Stalevo is not recommended for the treatment of drug-induced extrapyramidal reactions.
Stalevo 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 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 Stalevo should be monitored carefully for the development of mental changes (eg, hallucinoses and psychoses), depression with suicidal tendencies and serious antisocial behaviour. 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.
Patients with chronic wide-angle glaucoma may be treated with Stalevo with caution, provided the intraocular pressure is well controlled and the patient is monitored carefully for changes in intraocular pressure.
Stalevo may induce orthostatic hypotension. Therefore, caution is necessary when giving Stalevo to patients who are taking other medicinal products which may cause orthostatic hypotension.
Entacapone in combination with 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 or operating machines (see also Effects on the Ability to Drive or Operate Machinery as follows).
In clinical studies, undesirable dopaminergic effects eg, dyskinesia, were more common in patients who received entacapone and dopamine agonists (eg, bromocriptine), selegiline or amantadine compared to those who received placebo with this combination. The doses of other antiparkinsonian medicinal products may need to be adjusted when Stalevo is introduced in a patient not previously treated with entacapone.
Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson's disease. Close monitoring is therefore necessary in an event of abrupt dosage reductions or withdrawal of levodopa, particularly in patients who are also receiving neuroleptics. NMS, including rhabdomyolysis and hyperthermia, is characterised by motor symptoms (rigidity, myoclonus, tremor), mental status changes (eg, agitation, confusion, coma), hyperthermia, autonomic dysfunction (tachycardia, labile blood pressure) and elevated serum creatine phosphokinase. In individual cases, only some of these symptoms and/or findings may be evident. Early diagnosis is important for the appropriate management of NMS. A syndrome resembling NMS including muscular rigidity, elevated body temperature, mental changes and increased serum creatine phosphokinase has been reported with the abrupt withdrawal of antiparkinsonian agents. Neither NMS nor rhabdomyolysis was reported in association with entacapone treatment in controlled trials in which entacapone was discontinued abruptly. Since the introduction of entacapone into the market, cases with some similar signs and symptoms have been rarely reported. Prescribers should exercise caution when switching patients from Stalevo to levodopa/DDC inhibitor therapy without entacapone. When considered necessary, the replacement of Stalevo with levodopa and DDC inhibitor without entacapone should proceed slowly and an increase in levodopa dosage may be necessary.
If general anaesthesia is required, therapy with Stalevo may be continued for as long as the patient is permitted to take fluids and medication by mouth. If therapy has to be stopped temporarily, Stalevo may be restarted as soon as oral medication can be taken at the same daily dosage as before.
Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with Stalevo.
For patients experiencing diarrhoea, a follow-up of weight is recommended in order to avoid potential excessive weight decrease.
Effects on the Ability to Drive or Operate Machinery: Levodopa, carbidopa and entacapone together may cause dizziness and symptomatic orthostatism. Therefore, caution should be exercised when driving or using machines.
Patients being treated with Stalevo and presenting with somnolence and/or sudden sleep onset episodes must be instructed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (eg, operating machines) until such recurrent episodes have resolved (see also Precautions).
Use in Pregnancy: There are no adequate data from the use of the combination of levodopa/carbidopa/entacapone in pregnant women. Studies in animals have shown reproductive toxicity of the separate compounds (see Toxicology: Preclinical Safety Data under Actions). The potential risk for humans is unknown. Stalevo should not be used during pregnancy.
Use in Lactation: Levodopa is excreted in human breast milk. There is evidence that lactation is suppressed during treatment with levodopa. Carbidopa and entacapone were excreted in milk in animals but it is not known whether they are excreted in human breast milk. The safety of levodopa, carbidopa or entacapone in the infant is not known. Women should not breastfeed during treatment with Stalevo.