Limitations: This safety classification applies only to preparations containing a combination of the three drugs levodopa, carbidopa and entacapone (ATC code: N04B X02). The same ATC-code (N04B A03) can in some countries be used for different combinations of levodopa and other drugs, which in theory may be porphyrinogenic. Combination products which contain the three substances levodopa, carbidopa and entacapone are safety classified as Probably not porphyrinogenic (PNP). If the combination contains a substance which is not classified (NC) or has been classified as porphyrinogenic (PSP, PRP or P), the safety classification of such a combination as PNP is no longer valid. Levodopa is not a CYP substrate. Carbidopa is most probably not an inhibitor or inducer of CYP enzymes in vivo. For more details on entacapone please refer to the monograph of entacapone (ATC code: N04B X02). Risk for gastrointestinal adverse events in the form of nausea, diarrhoea, vomiting and reduced appetite motivates vigilance against insufficient intake of food, especially of carbohydrate.

This combination product is indicated for the treatment of Parkinsons disease. Levodopa is a prodrug for dopamine and is also an amino acid. Carbidopa is a decarboxylase inhibitor. Very common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are nausea and diarrhoea. Other very common side effects are discolouration of urine, muscle, musculoskeletal and connective tissue pain. Common side effects are weight loss, reduced appetite, vomiting, arthralgia and urinary tract infections.

Levodopa is metabolised to dopamine and catecholamines (SPC) by decarboxylase, monoamine oxidase, β-hydroxylase, catechol O-methyltransferase and N-methyltransferase (Patrick 2005). Elimination half-life is 15 hours. Carbidopa is metabolised to catecholamine. It is metabolised to two main metabolites which are excreted in the urine as glucuronides and conjugated compounds. 30% of the total urinary excretion is unchanged carbidopa (SPC). No drug-drug interactions with levodopa or carbidopa as perpetrators regarding CYP enzymes are observed (Interaksjoner and Interaktionsdatabasen), which indicate that none of them are inhibitors or inducers of CYP enzymes.

A patient with acute porphyria used the combination levodopa and benserazide with no adverse effects on the porphyria. Levodopa is therefore listed as potentially safe (Gorchein 1995).