Esomeprazole (Nexium) Interactions
- Alendronate
- Ampicillin
Antimuscarinics
- Atazanavir
- Atovaquone; Proguanil
- Bortezomib
- Budesonide
- Carbamazepine
- Carisoprodol
- Ceftibuten
- Cilostazol
- Citalopram
- Clarithromycin
- Clomipramine
- Cyanocobalamin, Vitamin B12
- Delavirdine
- Dexmethylphenidate
- Diazepam
- Digoxin
- Efavirenz
- Escitalopram
- Felbamate
- Fluconazole
- Fluoxetine
- Fluvastatin
- Fluvoxamine
- Fosphenytoin
- Gefitinib
H2-blockers
- Imipramine
- Iron Salts
- Isoniazid, INH
- Itraconazole
- Ketoconazole
- Methylphenidate
- Misoprostol
- Naproxen
- Octreotide
- Phenytoin
- Sertraline
- Sucralfate
- Ticlopidine
- Voriconazole
- Warfarin
Esomeprazole (Nexium) Interactions
NOTE: In the hepatic oxidative system, esomeprazole is extensively metabolized, primarily by CYP2C19 and secondarily by the CYP3A4 isoenzyme. Esomeprazole inhibits the CYP2C19 isoenzyme, which may increase plasma levels of CYP2C19 substrates. With similar metabolic pathways and chemical structure, the drug interaction potential for esomeprazole is expected to be similar to omeprazole. In vitro and in vivo drug interaction studies note that esomeprazole is not likely to inhibit the CYP 3A4 isozyme, as well as 1A2, 2A6, 2C9, 2D6, and 2E1. Clinically relevant interactions with drugs metabolized by these enzymes would not be expected.
Oral contraceptives and quinidine have not clinically altered esomeprazole pharmacokinetics.
Changes in intragastric pH can potentially alter the bioavailability of other drugs with pH-dependent absorption. Esomeprazole inhibits gastric acid secretion and increases the pH of the stomach. Esomeprazole may interfere with the absorption of drugs where gastric pH is an important determinant of bioavailability (e.g., ketoconazole, itraconazole, ampicillin, iron salts, and digoxin). The bioavailability of polysaccharide-iron complex and other oral iron salts is influenced by gastric pH, and the concomitant administration of a proton pump inhibitor can completely decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. Additionally, gastric acid pump-inhibitors may increase digoxin bioavailability; however, the magnitude of the interaction is small. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when esomeprazole is coadministered with digoxin.
Agents that are potent inhibitors of the CYP2C19 isoenzyme, such as esomeprazole may increase cilostazol bioavailability. This drug interaction has been noted with omeprazole, and theoretically may occur with esomeprazole. When significant CYP2C19 inhibitors are administered with cilostazol, the cilostazol dosage should be reduced by 50%.
Fluvoxamine is a major inhibitor of the cytochrome P450 enzyme (CYP) 2C19. Several proton pump inhibitors (PPIs), including esomeprazole, are primary substrates of the CYP2C19 enzyme. Reduced metabolism and resulting elevated plasma concentrations of these PPIs may occur if combined with fluvoxamine. A single-dose pharmacokinetic study has shown that the mean AUC of omeprazole 40 mg was increased 2- to 6-fold when given after fluvoxamine 50 mg/day for 6 days. Monitor patients for PPI toxicity, such as headache or GI distress if these drugs are combined.
In the hepatic oxidative system, esomeprazole is metabolized primarily by CYP2C19 and secondarily by the CYP3A4 isoenzyme. Theoretically, esomeprazole metabolism could be inhibited if combined with drugs that inhibit CYP2C19, leading to increased plasma levels of esomeprazole. Drugs that are inhibitors of the CYP2C19 isozyme include: cimetidine, felbamate, fluconazole, fluoxetine, fluvoxamine, isoniazid, INH, and ticlopidine.
Concomitant administration of cimetidine, ranitidine, or omeprazole with fluvastatin can decrease fluvastatin clearance by 18 - 23%, and increase AUC by 24 - 33%. A similar interaction might be expected with esomeprazole.
Diazepam is a substrate for the CYP2C19 isozyme. Since esomeprazole is an inhibitor of the CYP2C19 isozyme, plasma levels of diazepam may increase. Administration of esomeprazole with diazepam resulted in a 45% reduced clearance of diazepam. According to the manufacturer, this interaction is not likely to be clinically relevant. However, it would be prudent to monitor patients more closely, particularly if other CNS depressants are prescribed. The manufacturer reports that use of diazepam does not appear to alter the pharmacokinetic profile of esomeprazole.
In one study, multiple dose administration of omeprazole increased the Cmax, AUC, and elimination half-life of carbamazepine when given as an extended-release formulation in healthy male volunteers. Based on these results, it would be prudent to monitor carbamazepine serum concentrations when omeprazole or esomeprazole is added to the drug regimen.
Phenytoin is both a substrate as well as an inducer for the CYP2C19 isoenzyme. Esomeprazole, which is a strong inhibitor of CYP2C19, may lead to increased levels of phenytoin (or fosphenytoin which is metabolized to phenytoin), a substrate of CYP2C19. The manufacturer reports that esomeprazole does not significantly change the pharmacokinetics of phenytoin. In addition, the manufacturer states that phenytoin does not appear to alter the pharmacokinetic profile or esomeprazole (CYP2C19 substrate).
Esomeprazole, a strong inhibitor of the CYP2C19 isozyme, theoretically may lead to increased levels of warfarin, a substrate for this enzyme. The manufacturer reports that clinically significant drug interactions have not been detected between esomeprazole and warfarin during drug interaction studies. However, post-marketing reports of the combination of esomeprazole or omeprazole and warfarin have indicated elevations in prothrombin time (PT). It is prudent to monitor the INR more closely if esomeprazole is combined with warfarin.
Omeprazole can impair absorption of cyanocobalamin, vitamin B12. It is thought that omeprazole interferes with secretion of gastric acid and pepsin which are necessary for the release of B12 from its protein binding sites in food. Theoretically this interaction is possible with esomeprazole, although data are lacking.
Sucralfate has been shown to delay absorption and reduce the bioavailability of another PPI, lansoprazole by about 17%. Lansoprazole should be taken no less than 30 minutes before sucralfate. No information is available to determine if a similar interaction occurs with esomeprazole.
Drug interactions have not been detected between esomeprazole and amoxicillin. However, triple therapy with esomeprazole, clarithromycin and amoxicillin resulted in increased plasma levels of esomeprazole and 14-hydroxyclarithromycin, but did not result in a need to alter dosing of clarithromycin. This drug combination is approved to eradicate duodenal H. pylori; the drugs may be used together. The co-administration of clarithromycin with pimozide is contraindicated; therefore, triple therapy with esomeprazole, clarithromycin and amoxicillin is also contraindicated.
Proton pump inhibitors (PPIs), which increase gastric pH, may reduce the absorption of delavirdine. However, since these agents affect gastric pH for an extended period, separation of doses may not eliminate the interaction. Chronic use of proton pump inhibitors (PPIs) with delavirdine is not recommended.
Drugs that cause a significant sustained elevation in gastric pH [e.g., proton pump inhibitors (PPIs)] may reduce plasma concentrations of gefitinib and thus potentially may reduce gefitinib efficacy.
The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be decreased if given with other antisecretory agents (e.g., antimuscarinics, octreotide, H2-blockers, or misoprostol). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
In the hepatic oxidative system, esomeprazole is metabolized primarily by CYP2C19 and secondarily by the CYP3A4 isoenzyme. Theoretically, esomeprazole may inhibit the CYP2C19 isoenzyme, leading to increased plasma levels of drugs that are substrates for the CYP2C19 isoenzyme, such as: carisoprodol, citalopram, clomipramine, escitalopram, imipramine, mephenytoin, phenytoin, proguanil (atovaquone; proguanil), sertraline, voriconazole, R-warfarin, and other proton pump inhibitors (PPI’s). This list is not inclusive of all CYP2C19 substrates.
A randomized, open-label, multiple-dose drug interaction study of atazanavir (300 mg) with ritonavir (100 mg) coadministered with omeprazole 40 mg, found a reduction in atazanavir AUC and Cmin of 76% and 78%, respectively. Based on these study results, atazanavir, with or without ritonavir, should not be coadministered with omeprazole due to the reduction in atazanavir exposure levels. It is not known whether the over-the-counter dose of omeprazole (20 mg once daily) would produce similar results; therefore, coadministration is not recommended. Increasing the atazanavir and ritonavir doses to 400 and 100 mg, respectively, with omeprazole did not result in atazanavir exposures comparable to those observed with a regimen of atazanavir 300 mg with ritonavir 100 mg without omeprazole. Due to similar mechanisms, other proton pump inhibitors (PPIs) (e.g., esomeprazole, pantoprazole, rabeprazole, and lansoprazole) should not be used with atazanavir. When such substantial reductions in atazanavir serum concentrations are seen, therapeutic failure and resistance development may be expected.
Esomeprazole should be taken at least 1 hour before a meal. The presence of a meal (food) in the stomach decreases the AUC of esomeprazole 43 - 53%.
The effects of gastrointestinal pH alterations on the absorption of methylphenidate extended release capsules (Ritalin® LA) and dexmethylphenidate extended-release tablets (Focalin™ XR) have not been studied. Although the SODAS® system (drug delivery system utilized in Ritalin® LA and Focalin™ XR) is thought to be minimally affected by changes in pH, per the manufacturer, the modified release characteristics of both extended-release formulations are pH-dependent. It is possible that the administration of proton pump inhibitors (PPIs) or other acid suppressants could alter the release of dexmethylphenidate or methylphenidate. Patients receiving these extended-release products (Focalin™ XR or Ritalin® LA) with acid suppressants should be monitored for adverse effects and therapeutic efficacy.
Bortezomib may inhibit CYP2C19 activity at therapeutic concentrations and increase exposure to drugs that are substrates for this enzyme. However, no drug interaction data are available and potential metabolic interactions remain theoretical. Drugs that are primary or significant substrates for CYP2C19 include the proton pump inhibitors (PPIs) lansoprazole, omeprazole, esomeprazole, pantoprazole, and rabeprazole. The clinical significance of these potential interactions has not been determined.
The effect of increased gastric pH on the bioavailability of ceftibuten was evaluated in 18 healthy adult volunteers. Each volunteer was administered one 400-mg ceftibuten capsule. A single dose of liquid antacid did not affect the Cmax or AUC of ceftibuten; however, 150 mg of ranitidine every 12 hours for 3 days increased the ceftibuten Cmax by 23% and ceftibuten AUC by 16%. The clinical relevance of these increases is not known. Although no specific studies were performed, other H2-blockers, proton pump inhibitors (PPIs), and didanosine, ddI (contains buffering agents) may possibly affect the kinetics of ceftibuten.
The enteric-coated, delayed-release naproxen tablets (EC Naprosyn®) are designed to dissolve at a pH of 6 or greater. Concomitant use of this particular naproxen product with antacids, sucralfate, H2-blockers, or proton pump inhibitors (PPIs) is not recommended due to the gastric pH alteration. Increased gastric pH will affect the dissolution site and thus, absorption characteristics of the enteric-coated, delayed-release naproxen tablets. Periodic antacid use should not be problematic as long as the antacid and enteric-coated naproxen administration are separated by at least 2 hours.
In vitro studies have shown that efavirenz inhibits CYP2C9 and CYP2C19 in the range of observed efavirenz plasma concentrations. Although drug interaction studies have not been conducted, efavirenz may inhibit the metabolism of substrates for CYP2C9 or CYP2C19 such as esomeprazole.
Although the clinical significance has not been determined, the bioavailability of oral alendronate is doubled by concomitant administration of intravenous ranitidine. Investigations have not been undertaken to determine if other H2-antagonists have a similar effect on bioavailability. Patients should be closely monitored when antiulcer medications, such as proton pump inhibitors (PPIs), gastric mucosal agents, and H2-blockers, or other medications for GI disorders, are coadministered as they may affect the bioavailability of alendronate, leading to a higher likelihood of developing GI adverse effects while taking alendronate.
Enteric-coated budesonide granules dissolve at a pH > 5.5. Concomitant use of budesonide oral capsules and antacids, milk, or other drugs that increase gastric pH levels can cause the coating of the granules to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When 1 gram/day PO of cimetidine is administered with an uncoated formulation of oral budesonide, a slight increase in absorption as well as peak plasma concentrations occurs, resulting in significant cortisol suppression. In general, it may be prudent to avoid drugs such as H2-blockers or antacids in combination with enteric-coated budesonide. Omeprazole slightly inhibits CYP3A4, but has not been shown to affect the absorption or pharmacokinetics of oral budesonide; data on other proton pump inhibitors (PPIs) are not available, be alert for theoretical interactions based on changes in gastric pH that may occur as a result of acid suppression by the PPI.
[ Last revised: 3/30/2006 8:41:00 PM ]
References
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