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Levodopa + enzymhämmare (benserazid, karbidopa, entakapon)

Klassificering: C!

Preparat: Carbidopa And Levodopa, Carbidopa/Levodopa Fair-Med, Comtess®, Dazonay, Duodopa®, Entacapone Mylan, Entacapone Orion, Entacapone Teva, Flexilev, Lecigon, Levocar, Levodopa/Benserazid 2care4, Levodopa/Benserazid Ebb, Levodopa/Benserazid Orifarm, Levodopa/Benserazid ratiopharm, Levodopa/Carbidopa Accord, Levodopa/Carbidopa ratiopharm, Levodopa/Carbidopa/Entacapone Accord, Levodopa/Carbidopa/Entacapone Orion, Levodopa/Carbidopa/Entacapone Teva, Madopar, Madopar Depot, Madopar Quick, Madopar Quick mite, Madopark®, Madopark® Depot, Madopark® Quick, Madopark® Quick mite, Pentiro, Sastravi, Sinemet, Sinemet®, Sinemet® Depot, Sinemet® Depot Mite, Stalevo®

ATC kod: N04BA02, N04BA03, N04BX02


Kvinnor behöver oftare lägre doser levodopa än män. Dyskinesier är vanligare hos kvinnor, vilket bör beaktas. Tidsförloppet till uppkomsten av dyskinesi är signifikant kortare hos kvinnor.

Levodopa + enzymhämmare används även för behandling av RLS. En studie har visat att patientens kön inte hade inverkan på den symptomökning som ofta inträffar på morgonen efter kvällsdosen.
Studier har visat att benserazid 125 mg respektive karbidopa 250 mg given i samma dos till båda könen gav en större ökning av serumprolaktinnivåer hos kvinnor än män.

Kvinnor behöver vanligen lägre doser levodopa + enzymhämmare än män.

Additional information

Pharmacokinetics and dosing

Several studies have shown that women have a higher levodopa AUC than men when receiving a standard dose of 250 mg levodopa corrected as mg/kg body weight, leading to a higher bioavailability of levodopa. This may be explained by the generally lower body weight of women [1,2,3]. Another study (67 men, 40 women) observed a greater levodopa bioavailability in women, but it was not accounted for differences in body weight. In this study, patients received a standard oral fasting dose of levodopa plus benserazide (100/25 mg). Levodopa AUC was higher in women than in men, while clearance was reduced in women. Levodopa Cmax, tmax and elimination half-life did not differ between men and women [4].

Women have shown to have a lower expression of dopamine receptor genetic polymorphism (DRD2) which seems to exert a protective role in men against dyskinesia [2]. Women with Parkinson disease have shown to have an 87% higher binding capacity of levodopa in the prefrontal cortex compared to men [5].


No studies with a clinically relevant sex analysis regarding effects of levodopa + enzyme inhibitors have been found.

Adverse effects

Women with Parkinson disease seem to be at higher risk of dyskinesia, due to pharmacokinetic factors. This is, however, not confirmed in other reports where sex has been studied as a risk factor [2]. In one study no difference in the proportion of men and women experiencing dyskinesias was observed [4]. Female sex is associated with a significantly shorter time to occurrence of levodopa-induced dyskinesia (LID). The median time to LID was 4 years for women and 6 years for men. The reason for this sex effect is unclear. It has been suggested that hormonal status may underlie this susceptibility, possibly by modifying the individual dyskinetic sensitivity to levodopa through estrogens [6,7].

Dopaminergic medication is also used as a treatment for RLS (Restless Legs Syndrome) and PLMS (Periodic Leg Movement Syndrome). For nightly treatments, a problem with morning end-of-dose rebound increases in leg movements has been reported to occur in about 25% of the patients. In one study (25 men, 21 women), patients with either RLS or PLMS were given 0,5-1 tablet levodopa/carbidopa 100/25 mg 20–30 minutes before bedtime. The dose was increased by 0.5 tablet every 3 days until satisfactory sleep occurred for the first 3 hours or the dose reached a maximum of 4 tablets. Augmentation was greater for patients with more severe RLS symptoms and for patients on higher doses (>200/50 mg) but was unrelated to sex or age [8].

Studies have shown that the increase in serum prolactin after receiving carbidopa or benserazide is larger in women than in men. In one study, healthy young men and women were given a single 125 mg oral dose benserazide. Women had a larger percent increase of serum prolactin than men. In the general population, prolactin secretion is more affected by various stimuli in women [9]. In another similar study, benserazide was given in doses ranging between 10–125 mg and carbidopa was given in doses ranging between 10–250 mg to different groups of women. Two different groups of men were given 125 mg of benserazide and 250 mg of carbidopa, respectively. Significant prolactin rises were observed in both men and women for all doses tested. Secretion areas were lager in women than in men and peak values were higher in women than in men. This sex related finding is not unexpected considering the well-known sex related differences in both spontaneous levels in blood and responses to various stimuli. Serotonergic regulation of prolactin secretion may also be affected by sex differences [10]. Regarding entacapone, pre-marketing clinical trials did not note any differences in the rate of adverse events attributable to entacapone by sex [11].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

In a Swedish study, women were found to use lower doses of levodopa compared to men [12]. A similar trend was noted in a study from the USA [13]. A reason for this could be the metabolic differences and the risk of side effects such as dyskinesia (see the Pharmacokinetics and dosing).

Försäljning på recept

Fler män än kvinnor hämtade ut läkemedel innehållande kombination av levodopa och dekarboxylashämmare (ATC-kod N04BA02) på recept i Sverige år 2015, totalt 15 406 män och 14 567 kvinnor. Det motsvarar 3,2 respektive 3,0 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 75 år och äldre hos båda könen. I genomsnitt var läkemedel innehållande kombination av levodopa och dekarboxylashämmare 1,4 gånger vanligare hos män [14].

Fler män än kvinnor hämtade ut tabletter innehållande kombination av levodopa, dekarboxylashämmare och COMT-hämmare (ATC-kod N04BA03) på recept i Sverige år 2015, totalt 1 972 män och 1 058 kvinnor. Det motsvarar 0,4 respektive 0,2 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-84 år hos båda könen. I genomsnitt var tabletter innehållande kombination av levodopa, dekarboxylashämmare och COMT-hämmare 2,1 gånger vanligare hos män [14].

Fler män än kvinnor hämtade ut tabletter innehållande entakapon (ATC-kod N04BX02) på recept i Sverige år 2015, totalt 751 män och 519 kvinnor [14].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2013-03-22


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  2. Sharma JC, Bachmann CG, Linazasoro G. Classifying risk factors for dyskinesia in Parkinson's disease. Parkinsonism Relat Disord. 2010;16:490-7. PubMed
  3. Zappia M, Crescibene L, Arabia G, Nicoletti G, Bagalà A, Bastone L et al. Body weight influences pharmacokinetics of levodopa in Parkinson's disease. Clin Neuropharmacol. 2002;25:79-82. PubMed
  4. Martinelli P, Contin M, Scaglione C, Riva R, Albani F, Baruzzi A. Levodopa pharmacokinetics and dyskinesias: are there sex-related differences?. Neurol Sci. 2003;24:192-3. PubMed
  5. Kaasinen V, Nurmi E, Brück A, Eskola O, Bergman J, Solin O et al. Increased frontal [(18)F]fluorodopa uptake in early Parkinson's disease: sex differences in the prefrontal cortex. Brain. 2001;124:1125-30. PubMed
  6. Hassin-Baer S, Molchadski I, Cohen OS, Nitzan Z, Efrati L, Tunkel O et al. Gender effect on time to levodopa-induced dyskinesias. J Neurol. 2011;258:2048-53. PubMed
  7. Zappia M, Annesi G, Nicoletti G, Arabia G, Annesi F, Messina D et al. Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Arch Neurol. 2005;62:601-5. PubMed
  8. Allen RP, Earley CJ. Augmentation of the restless legs syndrome with carbidopa/levodopa. Sleep. 1996;19:205-13. PubMed
  9. Murialdo G, Masturzo P, Carolei A, Polleri A. Dose and sex related effects of benserazide on prolactin secretion. Boll Soc Ital Biol Sper. 1979;55:373-7. PubMed
  10. Polleri A, Masturzo P, Murialdo G, Carolei A. Dose and sex related effects of aromatic aminoacids decarboxylase inhibitors on serum prolactin in humans. Acta Endocrinol (Copenh). 1980;93:7-12. PubMed
  11. Comtan (entacapone). DailyMed [www]. US National Library of Medicine. [updated 2011-04-01, cited 2013-09-16]. länk
  12. Nyholm D, Karlsson E, Lundberg M, Askmark H. Large differences in levodopa dose requirement in Parkinson's disease: men use higher doses than women. Eur J Neurol. 2010;17:260-6. PubMed
  13. Baba Y, Putzke JD, Whaley NR, Wszolek ZK, Uitti RJ. Gender and the Parkinson's disease phenotype. J Neurol. 2005;252:1201-5. PubMed
  14. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-29] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Expertrådet för neurologiska sjukdomar

Godkänt av: Mia von Euler