Interaction between
Amlodipine
and
Carbamazepine
Major
Metabolism
Basic Information
| ID | DDInter79 and DDInter293 |
| Interaction | Coadministration with carbamazepine may significantly decrease the plasma concentrations and pharmacologic effects of calcium channel blockers (CCBs), especially the dihydropyridines (e.g., amlodipine, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine). The proposed mechanism is carbamazepine induction of CYP450-mediated metabolism. |
| Management | Concomitant use of calcium channel blockers with potent CYP450 3A4 inducers such as carbamazepine should generally be avoided. If coadministration is necessary, pharmacologic response should be monitored more closely following the initiation, discontinuation or change of dosage of carbamazepine, and the CCB dosage adjusted accordingly. |
| References | [1] Yasui-Furukori N, Tateishi T "Carbamazepine decreases antihypertensive effect of nilvadipine." J Clin Pharmacol 42 (2002): 100-3 [2] Capewell S, Critchley JA, Freestone S, et al "Reduced felodipine bioavailability in patients taking anticonvulsants." Lancet Aug (1988): 480-2 [3] Bahls FH, Ozuna J, Ritchie DE "Interactions between calcium channel blockers and the anticonvulsants carbamazepine and phenytoin." Neurology 41 (1991): 740-2 [4] Patsalos PN, Perucca E "Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs." Lancet Neurol 2 (2003): 473-81 [5] Tartara A, Galimberti CA, Manni R, et al "Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients." Br J Clin Pharmacol 32 (1991): 335-40 [6] Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8 [7] "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals, East Hanover, NJ. [8] Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77 [9] Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther 64 (1998): 248-56 [10] Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10 [11] Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8 [12] Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77 [13] Bailey DG, Arnold JM, Munoz C, Spence JD "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther 53 (1993): 637-42 [14] "Product Information. Procardia (nifedipine)." Pfizer US Pharmaceuticals, New York, NY. [15] Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84 [16] Edgar B, Bailey D, Bergstrand R, Johnsson G, Regardh CG "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance." Eur J Clin Pharmacol 42 (1992): 313-7 [17] Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93 [18] "Product Information. Plendil (felodipine)." Merck & Co, Inc, West Point, PA. [19] Fuhr U, Muller-Peltzer H, Kern R, et al. "Effects of grapefruit juice and smoking on verapamil concentrations in steady state." Eur J Clin Pharmacol 58 (2002): 45-53 [20] Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41 [21] Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32 [22] "Product Information. Sular (nisoldipine)." Zeneca Pharmaceuticals, Wilmington, DE. [23] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [24] "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4 [25] Takanaga H, Ohnishi A, Maatsuo H, et al. "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol 49 (2000): 49-58 [26] Ho PC, Ghose K, Saville D, Wanwimolruk S "Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers." Eur J Clin Pharmacol 56 (2000): 693-8 [27] Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther 54 (1993): 589-94 |
| Alternative for Amlodipine |
C09X
C10B C09B C07F C09D |
| Alternative for Carbamazepine |
N03A
|
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.