Comtan Special Precautions

Rhabdomyolysis secondary to severe dyskinesias or neuroleptic malignant syndrome (NMS) has been observed rarely in patients with Parkinson's disease. Isolated cases of rhabdomyolysis have been reported with entacapone treatment.
NMS, including rhabdomyolysis and hyperthermia, is characterized 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 (CPK) which may be a consequence of rhabdomyolysis. In individual cases, only some of these symptoms and/or findings may be evident.
Isolated cases of NMS have been reported, especially following abrupt reduction or discontinuation of entacapone and other dopaminergic medications. When considered necessary, withdrawal of entacapone and other dopaminergic treatment should proceed slowly, and if signs and/or symptoms occur despite a slow withdrawal of entacapone, an increase in levodopa dosage may be necessary.
Because of its mechanism of action, entacapone may interfere with the metabolism of medicinal products containing a catechol group and potentiate their action. Thus, entacapone should be administered cautiously to patients being treated with medicinal products metabolised by catechol-O-methyl transferase (COMT) eg, rimiterol, isoprenaline, adrenaline, noradrenaline, dopamine, dobutamine, α-methyldopa and apomorphine (see Interactions).
Entacapone is always given as an adjunct to levodopa treatment. Hence, the precautions valid for levodopa treatment should also be taken into account for entacapone treatment.
Entacapone increases the bioavailability of levodopa from standard levodopa/benserazide preparations 5-10% more than from standard levodopa/carbidopa preparations. Consequently, undesirable dopaminergic effects may be more frequent when entacapone is added to levodopa/benserazide treatment (see Adverse Reactions). To reduce levodopa-related dopaminergic adverse effects, it is often necessary to adjust levodopa dosage within the 1st days to 1st weeks after initiating entacapone treatment, according to the clinical condition of the patient (see Dosage & Administration and Adverse Reactions).
Entacapone may aggravate levodopa-induced orthostatic hypotension. Entacapone should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension.
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 medications may need to be adjusted when entacapone treatment is initiated.
Effects on the Ability to Drive or Operate Machinery: Comtan together with levodopa may cause dizziness and symptomatic orthostatism. Therefore, caution should be exercised when driving or using machines.