Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIETGIAZJ)
  Drug Name Lidocaine Drug Info Cimetidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anesthetics Antiulcer Agents
  Structure

 Mechanism of Lidocaine-Cimetidine Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Lidocaine Cimetidine
      Mechanism CYP450 substrate CYP450 inhibitor
      Key Mechanism Factor 1
Factor Name Cytochrome P450 Structure Sequence
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:20702771, PubMed:19965576, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:2732228, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:21576599, PubMed:21490593). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:14559847, PubMed:12865317). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:2732228, PubMed:15373842, PubMed:15764715, PubMed:22773874). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:2732228, PubMed:15373842, PubMed:15764715). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Lidocaine caused by Cimetidine mediated inhibition of CYP450 enzyme

Recommended Action
      Management Patients receiving concomitant therapy should be monitored for clinical (tremor, nystagmus, lightheadedness) and laboratory evidence of lidocaine toxicity. A reduction in the lidocaine infusion rate may be necessary. Nizatidine and famotidine are not expected to interact and may be considered as alternatives.

References
1 Berk SI, Gal P, Bauman JL, et al "The effect of oral cimetidine on total and unbound serum lidocaine concentrations in patients with suspected myocardial infarction." Int J Cardiol 14 (1987): 91-4. [PMID: 3804509]
2 Feely J, Wilkinson GR, McAllister CB, Wood AJ "Increased toxicity and reduced clearance of lidocaine by cimetidine." Ann Intern Med 96 (1982): 592-4. [PMID: 7073151]
3 Jackson JE, Bentley JB, Glass SJ, et al "Effects of histamine-2 receptor blockade on lidocaine kinetics." Clin Pharmacol Ther 37 (1985): 544-8. [PMID: 3987178]
4 Knapp AB, Maguire W, Keren G, et al. "The cimetidine-lidocaine interaction." Ann Intern Med 98 (1983): 174-7. [PMID: 6824249]
5 Powell JR, Foster J, Patterson JH, Cross R, Wargin W "Effect of duration of lidocaine infusion and route of cimetidine administration on lidocaine pharmacokinetics." Clin Pharm 5 (1986): 993-8. [PMID: 3802729]
6 Robson RA, Wing LMH, Miners JO, Lillywhite KJ, Birkett DJ "The effect of ranitidine on the disposition of lignocaine." Br J Clin Pharmacol 20 (1985): 170-3. [PMID: 4041336]
7 Wing LM, Miners JO, Birkett DJ, et al "Lidocaine disposition: sex differences and effects of cimetidine." Clin Pharmacol Ther 35 (1984): 695-701. [PMID: 6713782]