Drug General Information (ID: DDI16WSPEA)
Drug Name			Ranitidine		Drug Info		Ketoconazole		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiulcer Agents				Antifungal Agents
Structure

Mechanism of Ranitidine-Ketoconazole Interaction (Severity Level: Moderate)
Altered gastric pH Click to Show/Hide Mechanism Graph
Drug Name		Ranitidine				Ketoconazole
Mechanism		Gastric alkalinizer				Gastric pH sensitive
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 Ranitidine

Recommended Action
Management		Some manufacturers of ketoconazole suggest administering ketoconazole with an acidic beverage (e.g., non-diet cola, orange juice) if used concomitantly with H2 antagonists (US, GB, CA, BR). Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever H2 antagonists are added to or withdrawn from therapy with ketoconazole.

References
1	Adachi M, Hinatsu Y, et.al "Improved dissolution and absorption of ketoconazole in the presence of organic acids as pH-modifiers." Eur J Pharm Sci 76 (2015): 225-30. [PMID: 25988287]
2	Blum RA, D'Andrea DT, Florentino BM, et al "Increased gastric pH and the bioavailability of fluconazole and ketoconazole." Ann Intern Med 114 (1991): 755-7. [PMID: 2012358]
3	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]
4	Cerner Multum, Inc "ANVISA Bulario Eletrnico.".
5	Cerner Multum, Inc. "Canadian Product Information.".
6	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
7	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]
8	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]
9	Product Information. Ketoconazole (ketoconazole). Mylan Pharmaceuticals Inc, Morgantown, WV.
10	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]