Version May 2024
| Interacting medication(s) | Effect | Approach to management |
| Mechanism: Decreased oral bioavailability of co-medication due to PPI modulation of gastric pH | ||
| Posaconazole suspension, itraconazole capsules (Sporanox brand) (NOTE: Voriconazole interaction is listed in the following section) | These specific azole formulations have decreased oral bioavailability when coadministered with medications that elevate gastric pH, particularly PPIs | Consider use of a different formulation of these azoles that do not interact with PPIs (eg, posaconazole delayed-release tablets or itraconazole oral solution). |
| Capecitabine | Inconsistent evidence of diminished capecitabine efficacy potentially due to impaired dissolution and absorption | In patients receiving a capecitabine-containing regimen, consider use of alternatives to PPIs where appropriate. |
| Mycophenolate mofetil | Impaired absorption of mycophenolate mofetil; decreased bioavailability by 25% or more | Monitor clinical effect and mycophenolic acid levels (where applicable); enteric-coated mycophenolate sodium formulation appears less likely to interact with PPIs. |
| HCV direct acting antivirals: ledipasvir- and velpatasvir-containing regimens | Impaired absorption and decreased serum concentrations of ledipasvir or velpatasvir | In general, avoid use of a PPI in patients receiving ledipasvir or velpatasvir. Refer to UpToDate topic review of direct-acting antivirals for hepatitis C infection. |
| HIV antiretrovirals: atazanavir, rilpivirine (orally administered) | Impaired dissolution and absorption; significantly decreased oral bioavailability | In general, the use of atazanavir and rilpivirine is avoided in patients requiring PPI therapy. |
| Immune checkpoint inhibitors* | Decreased clinical response | Refer to UpToDate clinical topics. |
| Tyrosine kinase inhibitors¶ | Impaired dissolution and absorption; significantly decreased oral bioavailability | Refer to UpToDate clinical topics. |
| Mechanism: Altered metabolism of co-medication due to PPI inhibition of cytochrome P450 2C19 metabolism | ||
| Cilostazol | Omeprazole increased the AUC0-24 of cilostazol and its active metabolites up to 69% | In patients receiving omeprazole or esomeprazole, consider limiting the dose of cilostazol to 50 mg twice daily; other PPIs appear less likely to interact. |
| Citalopram, escitalopram | Omeprazole increased the AUC0-24 of the active form of citalopram (ie, escitalopram) by up to 90% | In patients receiving omeprazole or esomeprazole, consider limiting the dose of citalopram to 20 mg daily or escitalopram to 10 mg daily; other PPIs appear less likely to interact. |
| Clopidogrel | Omeprazole may decrease conversion of clopidogrel to its active form and diminish antiplatelet efficacy; however, a clinically relevant effect is not well established | We advise patients requiring PPI therapy who take clopidogrel not to use omeprazole or esomeprazole and to take the PPI in the morning and clopidogrel at least four hours later, eg, at bedtime. Rabeprazole or pantoprazole appear less likely to interact. Refer to UpToDate topic review of clopidogrel resistance and treatment failure. |
| Voriconazole (NOTE: Itraconazole and posaconazole interactions are listed above) | PPIs can moderately increase serum concentrations of voriconazole | Monitor for signs/symptoms of voriconazole toxicity; refer to UpToDate topic review of pharmacology of azoles. |
| Mechanism uncertain | ||
| Methotrexate (high dose) | Delayed methotrexate elimination potentially leading to methotrexate toxicity | Consider temporarily interrupting PPI therapy in patients receiving high-dose methotrexate. Monitor for increased methotrexate toxicity and levels; adjust therapy as appropriate. Refer to UpToDate topic review of therapeutic use and toxicity of high-dose methotrexate. |
| Warfarin | Lansoprazole and omeprazole associated with a modest increase in serum concentrations of R-warfarin (ie, less active warfarin enantiomer) | Monitor for increased INR and anticoagulant effect; pantoprazole and rabeprazole appear less likely to increase INR. |
This table lists potentially significant effects of PPI use on co-medications. Although PPIs themselves are rarely the target of clinically significant interactions, UpToDate suggests avoiding their administration at the same time as anti-secretory agents (eg, H2RAs) due to decreased acid inhibitory effects. In addition, strong inducers of CYP2C19 (rifampin) may result in decreased efficacy of omeprazole, esomeprazole, and lansoprazole.
NOTE: This table does not list all possible PPI interactions. For specific interactions and approach to management, refer to UpToDate clinical topics and drug interactions program.AUC0-24: area under curve of serum concentration versus time over 24 hours; H2RA: histamine-2 receptor antagonist (eg, famotidine); PPI: proton pump inhibitor; TKI: tyrosine kinase inhibitor.
* Immune checkpoint inhibitors that can interact with PPIs include: atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, ipilimumab, nivolumab, pembrolizumab.
¶ TKIs that can interact with PPIs include: acalabrutinib capsules (acalabrutinib tablets do not interact with PPIs), bosutinib, dacomitinib, erlotinib, gefitinib, infigratinib, neratinib, nilotinib, pazopanib, and pexidartinib.آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
