Does Pantoprazole (PPI) interfere with other medications?

From the Guidelines

Pantoprazole can interfere with certain medications, particularly clopidogrel, by reducing its effectiveness in preventing blood clots, although the evidence suggests that pantoprazole may be a safer option compared to other proton pump inhibitors like omeprazole, lansoprazole, or rabeprazole, which inhibit CYP450 2C19 1. When considering the use of pantoprazole with other medications, it is essential to evaluate the potential interactions and their impact on patient outcomes. Some key points to consider include:

• The reduction of clopidogrel's effectiveness in preventing blood clots when combined with pantoprazole, although the evidence is not as strong as with other proton pump inhibitors 1
• The potential for pantoprazole to increase blood levels of certain medications, such as diazepam, warfarin, and phenytoin, by affecting liver enzymes that metabolize these drugs
• The importance of informing healthcare providers about all medications, including over-the-counter drugs and supplements, before starting pantoprazole to minimize potential interactions Some studies have suggested that the adverse cardiovascular outcomes associated with the combination of clopidogrel and a proton pump inhibitor may be explained by the individual proton pump inhibitor used, with omeprazole, lansoprazole, and rabeprazole being more likely to cause these adverse outcomes due to their inhibition of CYP450 2C19 1. In contrast, pantoprazole has been reported to not be associated with recurrent MI among patients receiving clopidogrel, possibly due to its lack of inhibition of CYP450 2C19 1. Therefore, when a proton pump inhibitor is necessary for patients taking clopidogrel, pantoprazole may be a safer option compared to other proton pump inhibitors, although the decision should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history 1.

From the FDA Drug Label

Table 4: Clinically Relevant Interactions Affecting Drugs Co-Administered with Pantoprazole Sodium and Interactions with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. ... Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. ... Clopidogrel Clinical Impact: Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition ... Methotrexate Clinical Impact: Concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities ... Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole) Clinical Impact: Pantoprazole can reduce the absorption of other drugs due to its effect on reducing intragastric acidity

Pantoprazole Interference with Medications:

• Antiretrovirals: may reduce antiviral effect and promote the development of drug resistance
• Warfarin: increased INR and prothrombin time, may lead to abnormal bleeding and even death
• Clopidogrel: no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition
• Methotrexate: may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities
• Drugs Dependent on Gastric pH for Absorption: may reduce the absorption of other drugs due to its effect on reducing intragastric acidity 2

From the Research

Pantoprazole Interference with Medications

• Pantoprazole has a lower affinity for hepatic cytochrome P450 and shows no clinically relevant pharmacokinetic or pharmacodynamic interactions at therapeutic doses with a wide range of drug substrates for this isoenzyme system 3.
• However, vitamin K antagonist interactions, although rare, were the most common suspected drug interactions recorded, with a frequency of 0.09 per million packages for omeprazole and 0.11 per million packages for lansoprazole and pantoprazole 4.
• Proton pump inhibitors (PPIs), including pantoprazole, have been reported to interact with warfarin, with some studies suggesting a reduced time in therapeutic range (TTR) and increased incidence of minor bleeds 5, 6.
• One study found that patients taking PPIs with warfarin had significantly lower TTRs and higher incidence of minor bleeds, suggesting that this combination warrants additional caution and monitoring 6.
• Another study found that PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin, but the certainty of evidence was low to moderate 5.

Specific Interactions

• Warfarin: Pantoprazole may interact with warfarin, reducing TTR and increasing the incidence of minor bleeds 5, 6.
• Vitamin K antagonists: Pantoprazole may interact with vitamin K antagonists, although the frequency of these interactions is rare 4.
• Other medications: Pantoprazole has been shown to have minimal risk of drug interaction with a wide range of medications, including benzodiazepines, phenytoin, and others 3, 4.