Limitations: This safety classification applies only to preparations containing a combination of the drugs levodopa and benserazid OR levodopa and carbidopa. The same ATC-code (N04B A02) can in some countries be used for different combinations of levodopa and other drugs, which in theory may be porphyrinogenic. Combination products which contains the two substances levodopa and benserazid OR levodopa and karbidopa are safety classified as Probably not porphyrinogenic (PNP). Levodopa is not a CYP substrate. Benserazid and carbidopa are most probably not inhibitors or inducers of CYP enzymes in vivo. Risk for gastrointestinal adverse events in the form of loss of appetite, nausea, vomiting and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.

The combinations of the drugs are indicated for the treatment of Parkinsons disease. Levodopa is a prodrug for dopamine and is also an amino acid. Benserazid and carbidopa are decarboxylase inhibitors. Levodopa in combination with benserazide: 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 vomiting. Another common side effect is anorexia. Levdopa in combination with carbidopa: 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 vomiting. Another common side effect is loss of appetite. Less common side effects are abdominal pain, obstipation, diarrhoea and discolouration of urine.

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. Benserazid is hydroxylated to trihydroxybenzylhydrazin, a potent inhibitor of decarboxylase (SPC). Carbidopa is metabolised to catecholamines. 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, benserazid 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.

Andersson; patient inquiry: used without ill effects (n=1). Thunell; patient inquiry: tolerated (n=1).

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

Uneventful use reported in 7 patients with acute porphyria. In 2 of the reports it is reported a combination of levodopa with benserazid. For the last 5 reports it is unknown whether levodopa is in combination with benserazid or carbidopa.