Acute Porphyria Drug Database

H05BX01 - Cinacalcet
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
Common adverse reactions of cinacalcet 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
Cinacalcet is a not an inducer or a mechanism-based inhibitor of CYP enzymes and is therefore probably not porphyrinogenic.
Chemical description
Cinacalcet is a trifluorometyl phenyl propyl naphthalene methanamine.
Therapeutic characteristics
Cinacalcet is a calcimimetic drug indicated for patients with secondary hyperparathyroidism (HPT) in advanced renal insufficiency under treatment in chronic dialysis, parathyroid carcinoma or primary HPT where operation is unsuitable or contraindicated. It is administered orally and has a terminal elimination half-life of 30 to 40 hours.
Metabolism and pharmacokinetics
Cinacalet is metabolized by multiple CYP enzymes, primarily CYP3A4, CYP1A2 and CYP2D6. The major routes of metabolism are N-dealkylation, leading to carboxylic acid derivatives, and oxidation of the naphthalene ring system to form dihydrodiols. The oxidative metabolites are conjugated before elimination (Pandhi 2009). Strong, competitive inhibition of CYP 2D6 is shown in vitro and in vivo (Harris 2007, Nakashima 2007, SPC). Based on in vitro data cinacalcet does not inhibit other CYP enzymes at concentrations achieved clinically, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 and it does not induce CYP1A2, CYP2C19 and CYP3A4 (SPC). In vivo data indicates that cinacalcet does not affect the metabolism of substrates of CYP3A4, CYP1A2 or CYP2C9 (pandhi 2009, SPC).

References

  1. Scientific articles
  2. Harris RZ, Salfi M et al. Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. Eur J Clin Pharmacol. 2007 Feb;63(2):159-63. PMID 16680561. #1596
  3. Nakashima D, Takama H et al. Effect of cinacalcet hydrochloride, a new calcimimetic agent, on the pharmacokinetics of dextromethorphan: in vitro and clinical studies. J Clin Pharmacol. 2007 Oct;47(10):1311-9. PMID 17652181. #1597
  4. Padhi D, Harris R. Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clin Pharmacokinet. 2009;48(5):303-11. Review. PMID 19566113. #1598
  5. Summary of Product Characteristics
  6. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Mimpara. (Last edition: July.2014). #1595

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