Drug Interactions between omeprazole and Pylera

CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption. The calcium content in some foods can form nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals. Because oral tetracycline has caused rare cases of esophagitis and esophageal ulceration, patients should be advised to take tetracycline with a large glass of water while standing or sitting upright and to avoid laying down immediately afterwards.

ADJUST DOSING INTERVAL: Food may impair the gastrointestinal absorption and decrease the bioavailability of bismuth from the administration of bismuth subcitrate potassium (also known as colloidal bismuth subcitrate or tripotassium dicitratobismuthate). The clinical significance of this effect is unknown, as the relative importance of systemic versus local bismuth concentrations for antimicrobial activity against Helicobacter pylori has not been established. Investigators have suggested that the increased gastric retention time of bismuth in the presence of food may be beneficial by prolonging the local exposure of Helicobacter pylori to high concentrations of bismuth, although the amount of bismuth absorbed systemically and secreted back into the gastric fluid may also contribute to its therapeutic effect. When Pylera (a treatment preparation for Helicobacter pylori infection that contains bismuth subcitrate potassium 420 mg, metronidazole 375 mg, and tetracycline 375 mg per recommended dose) was administered after a standardized high-fat breakfast in 23 healthy volunteers, mean systemic exposure (AUC) for bismuth decreased by 60% compared to administration in the fasting state. Metronidazole and tetracycline AUC values were also reduced by 6% and 34%, respectively. However, these changes are not deemed clinically relevant, as eradication rates of Helicobacter pylori near 90% have been reported in trial patients administered Pylera routinely after meals.

MANAGEMENT: Pylera and generic equivalents should be administered after meals (breakfast, lunch, and dinner) and at bedtime (preferably with a snack). The manufacturers for some of the other bismuth subcitrate potassium products have recommended avoiding the ingestion of food, beverages, or other medications within one-half hour before and after each dose. The prescribing information or package labeling should be consulted for dosing and administration instructions that are appropriate for each product.

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.