Drug General Information (ID: DDI2RQXZ3F)
Drug Name			Ranitidine		Drug Info		Posaconazole		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiulcer Agents				Antifungal Agents
Structure

Mechanism of Ranitidine-Posaconazole Interaction (Severity Level: Moderate)
Altered gastric pH Click to Show/Hide Mechanism Graph
Drug Name		Ranitidine				Posaconazole
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 Posaconazole due to altered gastric pH caused by Ranitidine

Recommended Action
Management		Concomitant use of posaconazole oral suspension with cimetidine should generally be avoided. Until more information is available, this precaution should also be considered for other H2-receptor antagonists, although the manufacturer suggests otherwise. If possible, prescribers may consider suspending the H2 antagonist until completion of posaconazole therapy, or substituting an antifungal agent like fluconazole or voriconazole whose absorption is not affected by stomach pH. Delayed-release tablets of posaconazole may be used with H2 antagonists, as no pharmacokinetic interaction has been demonstrated with ranitidine or other agents affecting gastric pH such as proton pump inhibitors or antacids.

References
1	Alffenaar JW, van Assen S, van der Werf TS, Kosterink JG, Uges DR "Omeprazole significantly reduces posaconazole serum trough level." Clin Infect Dis 48 (2009): 839. [PMID: 19220151]
2	Canadian Pharmacists Association.
3	Dolton MJ, Ray JE, Chen SC, Ng K, Pont L, McLachlan AJ "Multicenter study of posaconazole therapeutic drug monitoring: exposure-response and factors affecting concentration." Antimicrob Agents Chemother 56 (2012): 5503-10. [PMID: 22890761]
4	Krishna G, Abutarif M, Xuan F, Martinho M, Angulo D, Cornely OA "Pharmacokinetics of oral posaconazole in neutropenic patients receiving chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome." Pharmacotherapy 28 (2008): 1223-32. [PMID: 18823218]
5	Krishna G, Moton A, Ma L, Medlock MM, McLeod J "The pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers." Antimicrob Agents Chemother 53 (2009): 958-66. [PMID: 19075045]
6	Neubauer WC, Engelhardt M, Konig A, et al. "Therapeutic drug monitoring of posaconazole in hematology patients: experience with a new high-performance liquid chromatography-based method." Antimicrob Agents Chemother 54 (2010): 4029-32. [PMID: 20547790]
7	Product Information. Noxafil (posaconazole). Schering-Plough Corporation, Kenilworth, NJ.
8	Shields RK, Clancy CJ, Vadnerkar A, et al "Posaconzaole serum concentrations among cardiothoracic transplant recipients: factors impacting trough levels and correlation with clinical response to therapy." Antimicrob Agents Chemother 55 (2011): 1308-11. [PMID: 21189337]
9	Vaes M, Hites M, Cotton F, et al. "Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplasic syndrome." Antimicrob Agents Chemother 56 (2012): 6298-303. [PMID: 23027198]
10	Walravens J, Brouwers J, Spriet I, Tack J, Annaert P, Augustijns P "Effect of pH and Comedication on Gastrointestinal Absorption of Posaconazole: Monitoring of Intraluminal and Plasma Drug Concentrations." Clin Pharmacokinet 50 (2011): 725-34. [PMID: 21973269]
11	Krishna G, Moton A, Ma L, Malavade D, Medlock M, McLeod J "Effect of gastric pH, dosing regimen and prandial state, food and meal timing relative to dose, and gastro-intestinal motility on absorption and pharmacokinetics of the antifungal posaconazole." 18th European Congress of Clinical Microbiology and Infectious Diseases April (2008): 20.