G02CB03 - Cabergoline |
Propably not porphyrinogenic |
PNP |
Rationale
Cabergoline is not listed as an inhibitor or an inducer of any major CYP enzymes.
Risk for gastrointestinal adverse events in the form of nausea, obstipation, dyspepsia and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.
Chemical description
Cabergoline is a dopaminergic ergoline derivative with potent and long-lasting dopamine D2 receptor agonist properties.
Therapeutic characteristics
Cabergoline is indicated for the treatment of Parkinsons.
A very common side effect that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack is nausea. Other common side effects are obstipation, dyspepsia, vomiting, confusion, hallucinations, dizziness and dyskinesia.
Metabolism and pharmacokinetics
Cabergoline is extensively metabolised via hydrolysis in the liver. CYP450-mediated metabolism is in one study regarded to be minimal (Del Dotto 2003). The elimination half-life is between 63-109 hours (Del Dotto 2003).
When co-administrated, clarithromycin increased the plasma concentration of cabergoline about 2.7 times. The authors suggest that the concentration of cabergoline might be increased both through the inhibition of P-glycoprotein and CYP3A4 (Nakatsuka 2006).
Christensen (2002) suggests that itraconazole inhibits the metabolism of cabergoline via CYP3A4, based on two case reports where the patients got marked improvement on their Parkinson symptoms when the two drugs were co-administered.
The plasma concentration of cabergoline increased approximately 1.7 times when grapefruit jucie (a MBI of CYP3A4) was taken together with cabergoline and this indicates that CYP3A4 contributes to metabolize cabergoline (Nagai 2005).
Cabergoline is not listed as an inducer or inhibitor of any major CYP enzymes (FDA, Hisaka 2010, Isoherranen 2009 and Pelkonen 2008) and no drug-drug interaction with cabergoline as a perpetrator has been reported in the literature.
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.
References
- Scientific articles
- Christensen J, Dupont E, ØStergaard K. Cabergoline plasma concentration is increased during concomitant treatment with itraconazole. Mov Disord. 2002 Nov;17(6):1360-2. PMID 12465083. #1452
- Del Dotto P, Bonuccelli U. Clinical pharmacokinetics of cabergoline. Clin Pharmacokinet. 2003;42(7):633-45. PMID 12844325. #1453
- Hisaka A, Ohno Y, et al. Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information. Pharmacol Ther. 2010 Feb;125(2):230-48. #1138
- Isoherranen N, Hachad H, et al. Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Chem Res Toxicol. 2009 Feb;22(2):294-8. #1005
- Nagai M, Nakatsuka A, et al. Effect of grapefruit juice on cabergoline pharmacokinetics in patients with Parkinsons disease. Clin Pharmacol Ther. 2005;77(2):84 #1456
- Nakatsuka A, Nagai M, et al. Effect of clarithromycin on the pharmacokinetics of cabergoline in healthy controls and in patients with Parkinsons disease. J Pharmacol Sci. 2006 Jan;100(1):59-64. #1454
- Pelkonen O, Turpeinen M, et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol. 2008 Oct;82(10):667-715. PMID 18618097. #4347
- Government bodies
- U.S Food and Drug Administration (FDA). #1450
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Cabaser. #1455
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