B01AE07 - Dabigatran Etexilate |
Propably not porphyrinogenic |
PNP |
Rationale
Dabigratan is not a substrate, an inhibitor or an inducer of CYP isoenzymes.
Risk for gastrointestinal adverse events in the form of nausea and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.
Therapeutic characteristics
Rivaroxoban is indicated for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery.
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 abdominal pain, diarrhoea, dyspepsia and nausea. Less common side effects are vomiting and elevated liver enzymes.
Metabolism and pharmacokinetics
Dabigatran etexilate is hydrolysed to dabigatran, which is the active form in plasma, by esterases. It is then subject to conjugation forming pharmacologically active acylglucuronides which accounts for less than 40% of the total dabigatran in plasma. Dabigatran is eliminated primarily in the unchanged form in the urine (SPC and Stangier 2008). Dabigatran etexilate is not a substrate, an inhibitor, or an inducer of CYP isoenzymes (Stangier 2008, 2009 and SPC).
A randomized, open label, three-way cross over design study showed that atorvastatin (a substrate and inhibitor of CYP3A4) had no influence on the pharmacokinetics and pharmacodynamic profile of dabigatran, and vice versa, dabigratan etexilate had no impact on the pharmacokinetics and pharmacodynamics profile of atorvastatin (Stangier 2009). This study confirms that dabigatran is not a substrate, an inhibitor or an inducer of CYP3A4.
References
- Scientific articles
- Stangier J, Rathgen K, et al. Coadministration of dabigatran etexilate and atorvastatin: assessment of potential impact on pharmacokinetics and pharmacodynamics. Am J Cardiovasc Drugs. 2009;9(1):59-68 PMID 19178132. #4371
- Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285-95. PMID 18076218. #1179
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). dabigratanetexilat. #1178
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