Acute Porphyria Drug Database

L01AA09 - Bendamustine
Propably not porphyrinogenic
PNP

Important Information
Risk for gastrointestinal adverse events in the form of nausea and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.
Side effects
Infections are common in patients using bendamustine. Since infections might trigger an acute porphyric attack, vigilance regarding signs and symptoms of an infection and/ or a porphyric attack is recommended. Common adverse reactions of bendamustine that can be confused with an acute porphyric attack are nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Benamustine is a substrate of CYP1A2, but the primary biotransormation is not mediated via the CYP system. Bendamustin is not an inducer or mechanism-based inhibitor of CYP enzymes.
Chemical description
Bendamustine is a mechlorethamine derivative containing a purine-like benzimidazole ring.
Therapeutic characteristics
Bendamustine hydrochloride is an alkylating antitumour agent, used in the treatment of Chronic lymphocytic leukaemia, indolent non-Hodgkin’s Lymphomas, and multiple myeloma. It is administered as an intravenous infusion.
Metabolism and pharmacokinetics
Bendamustine is primarily biotransformed via hydrolysis. A minor portion of the drug is metabolized via CYP 1A2. In vitro studies using human liver microsomes indicate that bendamustine does not inhibit CYP1A2, 2C9/10, 2D6, 2E1, or 3A4/5 at concentrations up to 200 μM. Bendamustine did not induce metabolism of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5 enzymes in primary cultures of human hepatocytes. (Darwish 2015, FDA label Treanda) No drug-drug interactions with bendamustine as pepetrator is anticipated or observed. Bendamustine has a half-life of about 40 minutes.

References

  1. Scientific articles
  2. Darwish M, Bond M et al. Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54. #3187
  3. Government bodies
  4. U.S. Food and Drug Administration (FDA). Label information TREANDA. (Approved: 11.05. 2015). #3190
  5. Drug interaction databases
  6. Lexi-Interact, via UpToDate. #1152
  7. Micromedex® 2.0 (online). Drug Interactions). (23.05.2016). #3189
  8. The Danish medicines agency. Den nationale Interaktionsdatabase. (23.05.2016). #3188

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