When omeprazole is used in combination with drugs, pay attention to the interaction.👀

Omeprazole is a proton pump inhibitor (PPI) that can be converted into sulfenamide compounds by protonation in an acidic environment. This compound can specifically bind to the α subunit of H+/K+-ATPase and inhibit its acid secretion activity. It is currently one of the most commonly used drugs for the treatment of acid-related diseases in clinical practice.

Omeprazole

The sulfinyl group in the chemical structure of omeprazole can be decomposed in acidic solution to cause polymerization and discoloration. Its stability may be affected by various factors such as the pH value of the solution, light, and temperature. This leads to contraindications between omeprazole and a variety of drugs.

1. The influence of pH.

Omeprazole is a benzimidazole compound and a weakly alkaline substance. The effect of pH change on its stability is particularly obvious, which can lead to its discoloration and precipitation. The main reasons are:

• Causes chemical structure changes: Omeprazole is relatively stable when the pH is around 9.0. It is easy to decompose in acidic environment to produce sulfone compounds and sulfide compounds, which cause discoloration of the solution.
• Causes solubility changes: Omeprazole is insoluble in water. After it is made into sodium salt, the solubility is improved. The maximum concentration commonly used in clinic is 40mg omeprazole sodium dissolved in 100ml normal saline (concentration is 0.4mg/ml). When the pH value of the omeprazole sodium solution decreases, free omeprazole is formed, causing turbidity or precipitation.

Acidic drugs: 

Omeprazole sodium is weakly alkaline. It will react with acidic drugs to produce new compounds. Reactions such as precipitation and discoloration will occur, and at the same time will lead to a reduction of active ingredients. Such acidic drugs include sulfacetamide, penicillin sodium, cefotaxime, piperacillin, fructose diphosphate sodium, vitamin C, vitamin B6, aminophylline, cimetidine, gentamicin and so on.

Drugs that depend on the pH of the stomach for absorption: 

Iron agents are mainly absorbed in the form of ferrous ions, which depend on the presence of gastric acid. The non-absorbed ferric iron can be converted into the divalent iron that can be absorbed under the action of gastric acid. Omeprazole can inhibit gastric acid, affect the absorption of iron, and reduce the efficacy. When the pH in the stomach rises, the tetracycline drug easily becomes insoluble free tetracycline, the absorption is reduced, and the curative effect is reduced. The absorption of ketoconazole also depends on sufficient gastric acid secretion. The acid suppression effect of omeprazole can reduce the absorption of ketoconazole and the blood concentration. The low acid environment can also reduce the absorption of itraconazole, so if necessary, acidic beverages can be used to take its capsule preparation.

2. Drugs related to metabolic enzymes.

Omeprazole is mainly metabolized to 5-OH-omeprazole by CYP2C19, or metabolized to omeprazole sulfone by CYP3A4, the former being the main metabolic pathway. Omeprazole can delay the elimination of drugs metabolized by the liver cytochrome P450 system in the body. Therefore, when omeprazole is combined with drugs related to CYP2C19 metabolizing enzymes, interactions are likely to occur.

Clopidogrel (CYP2C19 substrate):

Clopidogrel is a prodrug. It can only exert its antiplatelet effect after it enters the body and is metabolized by CYP2C19. Omeprazole is also metabolized in the liver by CYP2C19. The simultaneous use of the two may produce competitive inhibition. Clopidogdar does not have the effect of anti-platelet aggregation, which increases the risk of patients with ischemic stroke, compound stroke and myocardial infarction.

Diazepam (CYP2C19 substrate):

Omeprazole can weaken the metabolism of diazepam and increase its efficacy by inhibiting liver cytochrome P450 enzymes. Therefore, when used in combination, it should be monitored for enhanced sedation. If necessary, reduce the dose of diazepam.

Warfarin:

Omeprazole delays the clearance of warfarin by acting on the CYP450 enzyme system. The increase in warfarin exposure increases the international normalized ratio (INR) and prolongs the prothrombin time, which may lead to abnormal bleeding and even death. INR and prothrombin time should be monitored when used in combination. If necessary, adjust the warfarin dose to ensure that the INR is within the target range.

CYP2C19 or CYP3A4 inhibitors (such as voriconazole) and inducers (such as rifampicin):

Voriconazole can increase the exposure of omeprazole, except that patients with Zollinger-Eye syndrome may need to adjust the dose of omeprazole, and other generally do not need to be adjusted. Rifampicin can reduce the blood concentration of omeprazole. The combination of the two should be avoided.

Cilostazol (CYP2C19 substrate):

Omeprazole can increase the exposure of the active metabolite of cilostazol (3,4-dihydro-cilostazol). The dosage of cilostazol should be reduced to 50 mg once, twice a day.

Citalopram (CYP2C19 substrate):

Omeprazole can increase the exposure of citalopram and increase the risk of Q-T interval prolongation. The maximum dose of citalopram when used in combination should be 20 mg per day.

3. Other.

Methotrexate:

Omeprazole can inhibit the H+/K+-ATPase of the kidney. This will inhibit the active secretion of methotrexate and increase its blood concentration and toxicity.

Bismuth agent, montmorillonite powder, hydrotalcite, etc.:

They have a certain adsorption effect on omeprazole and can reduce the efficacy of omeprazole. In addition, the bismuth agent can better form a film in an acidic environment, and play the best role in protecting the gastric mucosa. If it is in a low-acid environment, its efficacy is reduced.