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Drug Interactions between Deprizine and Noxafil

This report displays the potential drug interactions for the following 2 drugs:

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Moderate

raNITIdine posaconazole

Applies to: Deprizine (ranitidine) and Noxafil (posaconazole)

GENERALLY AVOID: Coadministration with H2-receptor antagonists may decrease the systemic bioavailability of posaconazole from the oral suspension. The proposed mechanism is reduced solubility and absorption of posaconazole due to an increase in gastric pH induced by these agents. In healthy volunteers, posaconazole mean peak plasma concentration (Cmax) and systemic exposure (AUC) were each reduced by 39% during coadministration of posaconazole 200 mg once a day with cimetidine 400 mg twice a day for 10 days. Based on this and other data reported in the literature, particularly with proton pump inhibitors, it appears likely that posaconazole oral bioavailability from non-delayed release formulations is at least partially dependent on gastric pH. However, the product labeling states that no clinically relevant effects on posaconazole bioavailability, efficacy, or safety were observed when the oral suspension is administered with an H2 antagonist other than cimetidine, and no particular precaution is recommended during concomitant use except with cimetidine. Several published studies investigating the factors affecting posaconazole plasma concentrations in various patient cohorts found no association with ranitidine exposure, and a pharmacokinetic subanalysis conducted in a pivotal phase 3 clinical trial also reported no effect of H2 antagonists on posaconazole concentration, while a study from Australia identified ranitidine use as a significant factor in reduced posaconazole concentrations in a multiple linear regression analysis. The reason for this discrepancy has not been established.

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. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  2. "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation (2006):
  3. 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
  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
  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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
View all 11 references

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Drug and food interactions

Moderate

posaconazole food

Applies to: Noxafil (posaconazole)

ADJUST DOSING INTERVAL: Food significantly increases the absorption of posaconazole from the oral suspension but only modestly from the delayed-release tablet. Following single-dose administration, posaconazole mean peak plasma concentration (Cmax) and systemic exposure (AUC) are approximately 2.5 to 3 times higher when the oral suspension is given with a nonfat meal or a nutritional supplement (14 grams of fat) than when given under fasting conditions, and approximately 3.5 to 4 times higher when given during or 20 minutes after a high-fat meal (50 grams of fat) than under fasting conditions. Acidic beverages may also increase posaconazole absorption. In 12 healthy volunteers, administration of a single 400 mg dose of posaconazole suspension with 12 ounces of ginger ale increased posaconazole Cmax by 92% and AUC by 70% compared to administration after fasting. In contrast, the Cmax and AUC of posaconazole increased by just 16% and 51%, respectively, when posaconazole tablets were given as a single 300 mg dose to healthy volunteers after a high-fat meal relative to a fasted state.

GENERALLY AVOID Concomitant use of alcohol and posaconazole administered in the form of delayed-release oral suspension may lead to a faster release of posaconazole. An in vitro dissolution study determined a potential for alcohol-induced dose-dumping with the delayed-release oral suspension of posaconazole.

MONITOR: In 5 study subjects, posaconazole Cmax decreased by 27% to 53% and AUC decreased by 33% to 51% when the oral suspension was administered via a nasogastric tube as opposed to orally.

MANAGEMENT: Posaconazole tablets should be taken with food, whereas posaconazole oral suspension should be administered during or immediately (i.e., within 20 minutes) following a full meal to enhance bioavailability. Patients who cannot eat a full meal should take the suspension with a liquid nutritional supplement or an acidic carbonated beverage such as ginger ale. In patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage and who do not have the option of taking another formulation of posaconazole, alternative antifungal therapy should be considered; otherwise, monitor patients closely for breakthrough fungal infections. Patients receiving posaconazole via a nasogastric tube should also be closely monitored due to increased risk of treatment failure associated with lower plasma exposure. Administration of alcohol with posaconazole from the delayed-release oral suspension formulation is not recommended.

References

  1. "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation (2006):
  2. Sansone-Parsons A, Krishna G, Calzetta A, et al. "Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers." Antimicrob Agents Chemother 50 (2006): 1881-3
  3. 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
  4. 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
View all 4 references

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Minor

raNITIdine food

Applies to: Deprizine (ranitidine)

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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