Lansoprazole (Prevacid) Interactions
- Ampicillin
Antimuscarinics
- Atazanavir
- Delavirdine
- Dexmethylphenidate
- Digoxin
- Fluvoxamine
- food
- Gefitinib
H2-blockers
- Iron Salts
- Itraconazole
- Ketoconazole
- Methylphenidate
- Misoprostol
- Octreotide
- Sucralfate
- Theophylline, Aminophylline
- Voriconazole
- Warfarin
Lansoprazole (Prevacid) Interactions
NOTE: Lansoprazole is a substrate of the cytochrome P-450 system via the CYP2C19 and CYP3A4 isoenzymes.
Sucralfate has been shown to delay the absorption and reduce the bioavailability of oral lansoprazole by about 17%. Lansoprazole should be taken no less than 30 minutes before sucralfate if these drugs are to be used concomitantly. Concurrent administration of oral lansoprazole and antacids may reduce the bioavailability of lansoprazole; except when the antacids are given at least one hour before lansoprazole administration. The manufacturer states that antacids were given with lansoprazole in clinical trials, with the interpretation that concurrent antacids did not interfere with lansoprazole’s effects.
Lansoprazole is metabolized by the hepatic cytochrome P450 system, specifically through the CYP3A and CYP2C19 isozymes. However, no interactions have been reported between lansoprazole and antipyrine, clarithromycin, diazepam, ibuprofen, indomethacin, oral contraceptives, phenytoin, prednisone, propranolol, or terfenadine in healthy subjects.
In a study of healthy subjects neither the pharmacokinetics of warfarin enantiomers nor prothrombin time were affected following single or multiple 60 mg doses of lansoprazole. However, there have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including lansoprazole, and warfarin concomitantly. It is prudent to monitor the INR more closely if a proton pump inhibitor is combined with warfarin.
Concomitant use of theophylline (CYP1A2 and CYP3A substrate) and lansoprazole has led to a small increase (10%) in theophylline clearance. Theophylline may require dosage adjustment when therapy with lansoprazole is initiated or discontinued.
Lansoprazole has a long-lasting effect on the secretion of gastric acid. For drugs whose bioavailability is influenced by gastric pH, the concomitant administration of lansoprazole can exert a significant effect on their absorption. Drugs that could be affected by lansoprazole in this way include ampicillin, digoxin, iron salts, itraconazole, and ketoconazole. 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. Lansoprazole has been shown to lack a clinically significant interaction with amoxicillin. Gastric acid pump-inhibitors may increase digoxin bioavailability, however, the magnitude of the interaction is small. The potential interaction between lansoprazole and digoxin has not been specifically studied. Omeprazole increases the AUC of digoxin by about 10%. When rabeprazole is co-administered with digoxin, the AUC and Cmax for digoxin increases approximately 19% and 29%, respectively. 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 a gastric acid pump-inhibitor is coadministered with digoxin.
Lansoprazole is metabolized by the hepatic cytochrome P450 system, specifically via the CYP3A and CYP2C19 isozymes; voriconazole is a known inhibitor of these isozymes. The manufacturer for voriconazole has recommended that higher dosages of a related proton pump inhibitor, omeprazole, be reduced by one-half when initiating voriconazole therapy, due to increased omeprazole serum concentrations produced by this interaction. Although data are not available, theoretically a similar interaction may occur between lansoprazole and voriconazole. Higher daily doses of lansoprazole may need to be reduced when initiating voriconazole therapy.
Long-term treatment with lansoprazole in conjunction with diazepam therapy has been studied. Plasma elimination half-life, clearance, and volume of distribution of diazepam were not affected by concurrent use of lansoprazole.
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.
Fluvoxamine is a major inhibitor of the cytochrome P450 enzyme (CYP) 2C19. Several proton pump inhibitors (PPIs), including lansoprazole, 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.
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.
Administer a lansoprazole oral dosage 30 minutes prior to food whenever possible. The presence of a meal (food) in the stomach decreases the bioavailability by about 50%.
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.
[ Last revised: 6/30/2005 4:19:00 PM ]
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