Acute Porphyria Drug Database

C09XA02 - Aliskiren
Propably not porphyrinogenic
PNP

Rationale
Aliskiren does not inhibit or induce CYP3A4 and it is not listed as an inhibitor or an inducer of any major CYP enzymes. Risk for gastrointestinal adverse events in the form of diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.
Therapeutic characteristics
Aliskiren is indicated for the treatment of hypertension. A 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 diarrhoea. Another common side effect is arthralgia.
Metabolism and pharmakokinetics
Alsikiren is metabolised minimally by CYP450 enzymes. 1.4 % of an oral dose is metabolised by CYP3A4. 78 % is eliminated unchanged via faeces (SPC and Vaidyanathan 2008). Half-life elimination is 40 hours. Aliskiren does not inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A. It does not induce CYP3A4 (SPC). Drug-drug interaction studies have shown that aliskiren does not significantly affect drugs that are primarily metabolised by CYP isoenzymes (amlodipine, atorvastatin, lovastatin, fenofibrate, warfarin, acenocoumarol, pioglitazone, celecoxib) (Vaidyanathan 2008). The drugs listed are substrates of CYP isoenzymes which include CYP3A4, CYP2C9 and CYP2C8. This indicates that aliskiren is not an inhibitor or an inducer of those CYP enzymes in vivo.

References

  1. Scientific articles
  2. Vaidyanathan S, Jarugula V, et al. Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47(8):515-31. #1320
  3. Summary of Product Characteristics
  4. Norwegian medicines agency. Summary of Product Characteristics (SPC). Alisikiren. #1319

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