Drug General Information (ID: DDI6L7AYHQ)
Drug Name			Ketoconazole		Drug Info		Dexlansoprazole		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antifungal Agents				Proton Pump Inhibitors
Structure

Mechanism of Ketoconazole-Dexlansoprazole Interaction (Severity Level: Moderate)
Altered gastric pH Click to Show/Hide Mechanism Graph
Drug Name		Ketoconazole				Dexlansoprazole
Mechanism		Gastric pH sensitive				Gastric alkalinizer
Key Mechanism Factor 1
		Factor Name		Gastric pH
		Factor Description		The normal pH range of gastric acid is between 1.5 and 3.5 and is highly acidic, consisting mainly of hydrochloric acid. Changes in the pH of the stomach can alter the absorption of drugs.
Mechanism Description		Decreased absorption of Ketoconazole due to altered gastric pH caused by Dexlansoprazole

Recommended Action
Management		If coadministration is necessary, an acidic pH may be produced with two capsules of glutamic acid hydrochloride administered 15 minutes before the azole dose. Administration with an acidic beverage such as Coca-Cola(R) or Pepsi(R) may also help. However, clinicians should still consider the possibility of a reduced or subtherapeutic antifungal effect. It may be appropriate to switch to an agent like fluconazole or terbinafine whose absorption is not affected by stomach pH.

References
1	Bottiger Y, Tybring G, Gotharson E, Bertilsson L "Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S-mephenytoin." Clin Pharmacol Ther 62 (1997): 384-91. [PMID: 9357389]
2	Carlson JA, Mann HJ, Canafax DM "Effect of pH on disintegration and dissolution of ketoconazole tablets." Am J Hosp Pharm 40 (1983): 1334-6. [PMID: 6310994]
3	Chin TWF, Loeb M, Fong IW "Effects of an acidic beverage (coca-cola) on absorption of ketoconazole." Antimicrob Agents Chemother 39 (1995): 1671-5. [PMID: 7486898]
4	Jaruratanasirikul S, Sriwiriyajan S "Effect of omeprazole on the pharmacokinetics of itraconazole." Eur J Clin Pharmacol 54 (1998): 159-61. [PMID: 9626921]
5	Piscitelli SC, Goss TF, Wilton JH, D'Andrea DT, Goldstein H, Schentag JJ "Effects of ranitidine and sucralfate on ketoconazole bioavailability." Antimicrob Agents Chemother 35 (1991): 1765-71. [PMID: 1952845]
6	Product Information. Aciphex (rabeprazole) Janssen Pharmaceuticals, Titusville, NJ.
7	Product Information. Kapidex (dexlansoprazole). Takeda Pharmaceuticals America, Lincolnshire, IL.
8	Product Information. Nexium (esomeprazole) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
9	Product Information. Prevacid (lansoprazole). TAP Pharmaceuticals Inc, Deerfield, IL.
10	Product Information. Prilosec (omeprazole). Merck & Co, Inc, West Point, PA.
11	Product Information. Protonix (pantoprazole) Wyeth-Ayerst Laboratories, Philadelphia, PA.
12	Van der Meer JW, Keuning JJ "The influence of gastric acidity on the bio-availability of ketoconazole." J Antimicrob Chemother 6 (1980): 552-4. [PMID: 6253434]