Omeprazole and antibiotic drug interactions

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Omeprazole and Antibiotic Drug Interactions: Mechanisms and Clinical Implications

Omeprazole and Macrolide Antibiotics: Clarithromycin, Erythromycin, and Others

Omeprazole is often combined with macrolide antibiotics like clarithromycin and erythromycin for Helicobacter pylori eradication. When omeprazole is taken with clarithromycin, the blood levels of omeprazole nearly double, while its breakdown product (5-OH-omeprazole) decreases significantly. This happens because clarithromycin inhibits the enzyme CYP3A4, which is involved in omeprazole metabolism, leading to higher omeprazole exposure in the body. This interaction does not significantly affect clarithromycin levels, but it can enhance omeprazole’s therapeutic effect and may influence the metabolism of other drugs processed by CYP3A4 34.

Similarly, omeprazole interacts with erythromycin at the level of CYP3A4. Omeprazole reduces the rate at which CYP3A4 metabolizes erythromycin, but erythromycin does not significantly affect omeprazole metabolism. This is likely due to omeprazole having a stronger binding affinity to CYP3A4 than erythromycin .

Electrochemical studies also show that omeprazole forms complexes with macrolide antibiotics (azithromycin, clarithromycin, roxithromycin) through electrostatic interactions, with varying binding strengths. These interactions may influence the drugs’ behavior in the body, but the clinical significance is mainly seen with clarithromycin .

Omeprazole and Other Antibiotics: Amoxicillin, Metronidazole, Doxycycline

Omeprazole is also used with amoxicillin and metronidazole in H. pylori treatment. Omeprazole increases the stability of amoxicillin and clarithromycin in the stomach by raising gastric pH, which slows their degradation and helps maintain effective antibiotic concentrations. Metronidazole is already stable in acidic conditions, so omeprazole’s effect is less pronounced for this drug .

Omeprazole can also change the concentration of antibiotics in gastric juice. It increases amoxicillin levels in the stomach, decreases metronidazole levels, and does not significantly affect clarithromycin levels. These changes are due to omeprazole’s acid-suppressing action, which alters the volume and composition of gastric juice .

With doxycycline, omeprazole forms a strong complex, but the clinical impact of this interaction is less clear compared to the macrolides and amoxicillin .

Omeprazole and Fluoroquinolones or Aminoglycosides

Studies show that omeprazole does not have direct antibacterial activity and does not significantly enhance the effect of antibiotics like gentamicin or ciprofloxacin against resistant bacteria. However, combining omeprazole with these antibiotics does not appear to cause harmful interactions .

Clinical Relevance and Therapeutic Implications

The most important drug-drug interactions between omeprazole and antibiotics occur with clarithromycin and, to a lesser extent, erythromycin. These interactions can increase omeprazole levels, potentially improving treatment outcomes for H. pylori infection. Omeprazole also helps stabilize certain antibiotics in the stomach, making them more effective. However, these interactions can also affect the metabolism of other drugs that rely on the same liver enzymes, so caution is needed when combining omeprazole, macrolide antibiotics, and other medications metabolized by CYP3A4 347.

Conclusion

Omeprazole interacts with several antibiotics, especially macrolides like clarithromycin and erythromycin, mainly by affecting drug metabolism and stability in the stomach. These interactions can enhance the effectiveness of H. pylori eradication regimens but may also influence the metabolism of other drugs. Understanding these interactions is important for optimizing therapy and avoiding potential side effects.

Sources and full results

Most relevant research papers on this topic

ELECTROCHEMICAL BEHAVIOUR OF OMEPRAZOLE INTERACTING WITH MYCIN DERIVATIVES AND DOXYCYCLINE

Omeprazole's binding affinity increases with antibiotics, with roxithromycin being the most effective, followed by clarithromycin, azithromycin, and doxycycline.

2014·

2citations

·M. Ghandour et al.

[Modeling of drug-drug interactions between omeprazole and erythromycin with cytochrome P450 3A4 in vitro assay].

Omeprazole and erythromycin show drug-drug interactions during CYP3A4-mediated metabolism, potentially impacting Helicobacter pylori eradication therapy.

In Vitro Study

2020·

2citations

·P. I. Koroleva et al.

Pharmacokinetic interactions between omeprazole/pantoprazole and clarithromycin in health volunteers.

Clarithromycin can significantly increase omeprazole levels, potentially improving therapeutic response but potentially affecting CYP3A4 metabolism or interfering with drug absorption.

RCT

2004·

23citations

·L. Calabresi et al.

[Drug-drug interaction in pharmacogenetics and pharmacogenomics].

Drug-drug interactions can cause severe gastrointestinal and bone marrow toxicities, or result in beneficial interactions, such as when omeprazole, amoxicillin, and clarithromycin are co-administered for Helicobacter pylori eradication.

2002·

5citations

·S. Ozawa

Effect of omeprazole on the distribution of metronidazole, amoxicillin, and clarithromycin in human gastric juice.

Omeprazole reduces metronidazole concentrations in gastric juice by reducing acid secretion and increases amoxicillin concentrations partly by reducing gastric juice volume, enhancing antimicrobial therapy against Helicobacter pylori.

RCTHighly Cited

1996·

231citations

·AF Goddard et al.

Effects of Omeprazole and Caffeine Alone and in Combination with Gentamicin and Ciprofloxacin Against Antibiotic Resistant Staphylococcus Aureus and Escherichia Coli Strains

Caffeine and omeprazole combined with antibiotics effectively remove antibiotic-resistant Staphylococcus aureus and Escherichia coli infections, with no significant drug efflux mechanism of resistance.

In Vitro Study

2019·

20citations

·Bibi Sedigheh Fazli Bazzaz et al.

The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment of Helicobacter pylori infection.

Co-administration of omeprazole with amoxycillin and clarithromycin increases their chemical stability in gastric juice, potentially enhancing their antibacterial action against Helicobacter pylori.

In Vitro StudyHighly Cited

1997·

263citations

·Patrick O. Erah et al.

Omeprazole Induces CYP3A4 mRNA Expression but Not CYP3A4 Protein Expression in HepaRG Cells.

Omeprazole increases CYP3A4 mRNA expression in HepaRG cells, but does not increase CYP3A4 protein expression, suggesting the need for broader drug-drug interaction examination beyond transcriptional induction and enzyme-activity inhibition tests.

In Vitro Study

2024·

2citations

·Yuto Fujita et al.

Notable drug-drug interaction between omeprazole and voriconazole in CYP2C19 1 and 2 (rs4244285, 681G>A) alleles in vitro

Omeprazole can inhibit voriconazole metabolism in both CYP2C191 and CYP2C192 (681G>A) alleles, potentially increasing blood concentrations in patients with CYP2C19*2 allele.

In Vitro Study

2024·

1citation

·Xue Li

Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management

Omeprazole can cause adverse drug interactions with various medications, requiring enhanced clinical risk management to avoid adverse consequences.

Systematic ReviewRigorous JournalHighly Cited

2013·

71citations

·Wei Li et al.

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Omeprazole and antibiotic drug interactions

Pro Research Analysisby

Omeprazole and Antibiotic Drug Interactions: Mechanisms and Clinical Implications

Omeprazole and Macrolide Antibiotics: Clarithromycin, Erythromycin, and Others

Omeprazole and Other Antibiotics: Amoxicillin, Metronidazole, Doxycycline

Omeprazole and Fluoroquinolones or Aminoglycosides

Clinical Relevance and Therapeutic Implications

Conclusion

Sources and full results

ELECTROCHEMICAL BEHAVIOUR OF OMEPRAZOLE INTERACTING WITH MYCIN DERIVATIVES AND DOXYCYCLINE

Omeprazole's binding affinity increases with antibiotics, with roxithromycin being the most effective, followed by clarithromycin, azithromycin, and doxycycline.

[Modeling of drug-drug interactions between omeprazole and erythromycin with cytochrome P450 3A4 in vitro assay].

Omeprazole and erythromycin show drug-drug interactions during CYP3A4-mediated metabolism, potentially impacting Helicobacter pylori eradication therapy.

Pharmacokinetic interactions between omeprazole/pantoprazole and clarithromycin in health volunteers.

Clarithromycin can significantly increase omeprazole levels, potentially improving therapeutic response but potentially affecting CYP3A4 metabolism or interfering with drug absorption.

[Drug-drug interaction in pharmacogenetics and pharmacogenomics].

Drug-drug interactions can cause severe gastrointestinal and bone marrow toxicities, or result in beneficial interactions, such as when omeprazole, amoxicillin, and clarithromycin are co-administered for Helicobacter pylori eradication.

Effect of omeprazole on the distribution of metronidazole, amoxicillin, and clarithromycin in human gastric juice.

Omeprazole reduces metronidazole concentrations in gastric juice by reducing acid secretion and increases amoxicillin concentrations partly by reducing gastric juice volume, enhancing antimicrobial therapy against Helicobacter pylori.

Effects of Omeprazole and Caffeine Alone and in Combination with Gentamicin and Ciprofloxacin Against Antibiotic Resistant Staphylococcus Aureus and Escherichia Coli Strains

Caffeine and omeprazole combined with antibiotics effectively remove antibiotic-resistant Staphylococcus aureus and Escherichia coli infections, with no significant drug efflux mechanism of resistance.

The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment of Helicobacter pylori infection.

Co-administration of omeprazole with amoxycillin and clarithromycin increases their chemical stability in gastric juice, potentially enhancing their antibacterial action against Helicobacter pylori.

Omeprazole Induces CYP3A4 mRNA Expression but Not CYP3A4 Protein Expression in HepaRG Cells.

Omeprazole increases CYP3A4 mRNA expression in HepaRG cells, but does not increase CYP3A4 protein expression, suggesting the need for broader drug-drug interaction examination beyond transcriptional induction and enzyme-activity inhibition tests.

Notable drug-drug interaction between omeprazole and voriconazole in CYP2C19 *1 and *2 (rs4244285, 681G>A) alleles in vitro

Omeprazole can inhibit voriconazole metabolism in both CYP2C19*1 and CYP2C19*2 (681G>A) alleles, potentially increasing blood concentrations in patients with CYP2C19*2 allele.

Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management

Omeprazole can cause adverse drug interactions with various medications, requiring enhanced clinical risk management to avoid adverse consequences.

Try another search

Notable drug-drug interaction between omeprazole and voriconazole in CYP2C19 1 and 2 (rs4244285, 681G>A) alleles in vitro

Omeprazole can inhibit voriconazole metabolism in both CYP2C191 and CYP2C192 (681G>A) alleles, potentially increasing blood concentrations in patients with CYP2C19*2 allele.