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Interactions between Omesec and Posaconazole

1 drug interaction and 13 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

omeprazole posaconazole

Applies to: Omesec (omeprazole) and posaconazole
Generally avoid

Coadministration with proton pump inhibitors (PPIs) 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. When a single 400 mg dose of posaconazole was given to 12 healthy subjects following pretreatment with esomeprazole 40 mg once a day for 3 days, mean posaconazole peak plasma concentration (Cmax) and systemic exposure (AUC) were reduced by 46% and 32%, respectively, compared to posaconazole administered alone under fasting conditions. In the same study, coadministration of posaconazole with 12 ounces of ginger ale, an acidic beverage, increased posaconazole Cmax by 92% and AUC by 70%. When given with both esomeprazole and ginger rale together, posaconazole Cmax and AUC decreased by 33% and 21%, respectively. These data suggest that posaconazole oral bioavailability from non-delayed release formulations is at least partially dependent on gastric pH. Clinical studies in various patient cohorts receiving prophylaxis or treatment for invasive fungal infection have found PPI use to be associated with significantly reduced posaconazole plasma concentrations. The interaction was also suspected in a 58-year-old patient receiving posaconazole for invasive aspergillosis. Posaconazole serum trough level decreased significantly during coadministration with omeprazole for 3 days, but returned to baseline following discontinuation of omeprazole.

Management

Concomitant use of posaconazole oral suspension with proton pump inhibitors should generally be avoided. If possible, prescribers may consider suspending the PPI 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 PPIs, as no pharmacokinetic interaction has been demonstrated with esomeprazole.

References (10)
  1. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation
  2. Krishna G, Moton A, Ma L, Malavade D, Medlock M, McLeod J (2008) "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, p. 20
  3. Krishna G, Abutarif M, Xuan F, Martinho M, Angulo D, Cornely OA (2008) "Pharmacokinetics of oral posaconazole in neutropenic patients receiving chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome." Pharmacotherapy, 28, p. 1223-32
  4. Krishna G, Moton A, Ma L, Medlock MM, McLeod J (2009) "The pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers." Antimicrob Agents Chemother, 53, p. 958-66
  5. Alffenaar JW, van Assen S, van der Werf TS, Kosterink JG, Uges DR (2009) "Omeprazole significantly reduces posaconazole serum trough level." Clin Infect Dis, 48, p. 839
  6. Neubauer WC, Engelhardt M, Konig A, et al. (2010) "Therapeutic drug monitoring of posaconazole in hematology patients: experience with a new high-performance liquid chromatography-based method." Antimicrob Agents Chemother, 54, p. 4029-32
  7. Walravens J, Brouwers J, Spriet I, Tack J, Annaert P, Augustijns P (2011) "Effect of pH and Comedication on Gastrointestinal Absorption of Posaconazole: Monitoring of Intraluminal and Plasma Drug Concentrations." Clin Pharmacokinet, 50, p. 725-34
  8. Dolton MJ, Ray JE, Chen SC, Ng K, Pont L, McLachlan AJ (2012) "Multicenter study of posaconazole therapeutic drug monitoring: exposure-response and factors affecting concentration." Antimicrob Agents Chemother, 56, p. 5503-10
  9. Vaes M, Hites M, Cotton F, et al. (2012) "Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplasic syndrome." Antimicrob Agents Chemother, 56, p. 6298-303
  10. Shields RK, Clancy CJ, Vadnerkar A, et al. (2011) "Posaconzaole serum concentrations among cardiothoracic transplant recipients: factors impacting trough levels and correlation with clinical response to therapy." Antimicrob Agents Chemother, 55, p. 1308-11

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

posaconazole Food/Lifestyle

Applies to: 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 (4)
  1. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation
  2. Sansone-Parsons A, Krishna G, Calzetta A, et al. (2006) "Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers." Antimicrob Agents Chemother, 50, p. 1881-3
  3. Krishna G, Moton A, Ma L, Malavade D, Medlock M, McLeod J (2008) "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, p. 20
  4. Walravens J, Brouwers J, Spriet I, Tack J, Annaert P, Augustijns P (2011) "Effect of pH and Comedication on Gastrointestinal Absorption of Posaconazole: Monitoring of Intraluminal and Plasma Drug Concentrations." Clin Pharmacokinet, 50, p. 725-34

Disease interactions

12 potential interactions Applies to: 11 conditions, including Osteoporosis, Diarrhea, Arrhythmia, Liver Disease, and Renal Dysfunction.

Arrhythmia

Moderate:

posaconazole

Posaconazole has a moderate potential interaction with Arrhythmia.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Diarrhea

Major:

Omesec

The omeprazole in Omesec has a major potential interaction with Diarrhea.

Published observational studies suggest that proton pump inhibitor (PPI) use may be associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD), especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. It is recommended that patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Close monitoring is recommended in patients with diarrhea and in those taking antibacterial agents as CDAD has been reported with the use of nearly all these agents. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Moderate:

posaconazole

Posaconazole has a moderate potential interaction with Diarrhea.

Patients with severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections when using posaconazole delayed-release tablets, oral suspension, or powder for delayed-release oral suspension.

Electrolyte Abnormalities

Moderate:

posaconazole

Posaconazole has a moderate potential interaction with Electrolyte Abnormalities.

Electrolyte disturbances (especially those involving potassium, magnesium, or calcium levels) should be monitored and corrected as needed before and during posaconazole therapy.

Fructose Intolerance

Major:

posaconazole

Posaconazole has a major potential interaction with Fructose Intolerance.

Posaconazole powder for delayed-release oral suspension is contraindicated in patients with known/suspected hereditary fructose intolerance (HFI). This formulation contains sorbitol (inactive ingredient) and may precipitate a metabolic crisis that may include (but is not limited to) life-threatening hypoglycemia, hypophosphatemia, lactic acidosis, and hepatic failure in patients with HFI. Careful history of HFI symptoms (nausea, vomiting, abdominal pain) with sorbitol/fructose/sucrose exposure should be obtained before administration of posaconazole powder for delayed-release oral suspension because a diagnosis of HFI may not yet be established in pediatric patients.

Liver Disease

Moderate:

posaconazole

Posaconazole has a moderate potential interaction with Liver Disease.

Posaconazole has been associated with hepatic reactions (e.g., mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis); cases of more severe hepatic reactions (including cholestasis or hepatic failure including deaths) have been reported during therapy in patients with serious underlying medical conditions (e.g., hematologic malignancy), primarily in patients receiving 800 mg/day. Liver tests should be assessed at the start of and during posaconazole therapy. No dose adjustment of posaconazole is necessary in patients with mild to severe liver dysfunction (Child-Pugh A, B, or C). However, posaconazole delayed-release tablets, powder for delayed-release oral suspension, and injection have not been specifically studied; caution is recommended.

Magnesium Imbalance

Moderate:

Omesec

The omeprazole in Omesec has a moderate potential interaction with Magnesium Imbalance.

Symptomatic and asymptomatic hypomagnesemia has been reported rarely in patients treated with PPIs for at least 3 months, in most cases after a year of therapy. Serious adverse events can include tetany, seizures, and arrhythmias. Caution should be used in patients prone to magnesium imbalances such as patients taking other medications that can cause hypomagnesemia (e.g., diuretics). Regular monitoring is recommended.

Myeloproliferative Disorders

Moderate:

posaconazole

Posaconazole has a moderate potential interaction with Myeloproliferative Disorders.

Posaconazole has been associated with hepatic reactions (e.g., mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin, and/or clinical hepatitis); cases of more severe hepatic reactions (including cholestasis or hepatic failure including deaths) have been reported during therapy in patients with serious underlying medical conditions (e.g., hematologic malignancy), primarily in patients receiving 800 mg/day. Liver tests should be assessed at the start of and during posaconazole therapy. No dose adjustment of posaconazole is necessary in patients with mild to severe liver dysfunction (Child-Pugh A, B, or C). However, posaconazole delayed-release tablets, powder for delayed-release oral suspension, and injection have not been specifically studied; caution is recommended.

Osteoporosis

Moderate:

Omesec

The omeprazole in Omesec has a moderate potential interaction with Osteoporosis.

Various published observational studies have reported that PPI therapy may be associated with an increased risk for osteoporosis related fractures of the hip, wrist or spine. The risk was increased in patients who received high doses (multiple daily doses), and long term treatment (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Caution should be used in patients at risk for osteoporosis related fractures and should be managed according to established treatment guidelines.

Pseudomembranous Colitis

Major:

Omesec

The omeprazole in Omesec has a major potential interaction with Pseudomembranous Colitis.

Published observational studies suggest that proton pump inhibitor (PPI) use may be associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD), especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. It is recommended that patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Close monitoring is recommended in patients with diarrhea and in those taking antibacterial agents as CDAD has been reported with the use of nearly all these agents. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile. C. difficile produces toxins A and B, which contribute to the development of CDAD. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Renal Dysfunction

Moderate:

posaconazole

Posaconazole has a moderate potential interaction with Renal Dysfunction.

Posaconazole injection should be avoided in patients with moderate or severe renal dysfunction (estimated glomerular filtration rate [eGFR] less than 50 mL/min) unless an assessment of the risks and benefits justifies its use. Since the IV vehicle, betadex sulfobutyl ether sodium (SBECD), is expected to accumulate in patients with moderate or severe renal dysfunction using the injection, serum creatinine levels should be closely monitored in these patients, and if increases occur, switching to oral posaconazole therapy should be considered. No dose adjustment is needed for oral dosing in patients with mild to severe renal dysfunction; however, patients with severe renal dysfunction (eGFR less than 20 mL/min/1.73 m2) should be closely monitored for breakthrough fungal infections due to variability in exposure with posaconazole delayed-release tablets, oral suspension, and powder for delayed-release oral suspension.

Vomiting

Moderate:

posaconazole

Posaconazole has a moderate potential interaction with Vomiting.

Patients with severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections when using posaconazole delayed-release tablets, oral suspension, or powder for delayed-release oral suspension.

More resources

Omesec

A total of 269 drugs are known to interact with Omesec.

posaconazole

A total of 650 drugs are known to interact with posaconazole.

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.