Mechanisms of Voquezna's Drug Interactions
Voquezna's potential for drug interactions stems from two primary mechanisms: its powerful ability to suppress stomach acid and its metabolism through Cytochrome P450 (CYP) enzymes in the liver. By profoundly reducing gastric acidity, Voquezna can affect the absorption of other orally administered medications that depend on an acidic environment. Furthermore, Voquezna can act as a weak inhibitor of the CYP3A enzyme and an inhibitor of the CYP2C19 enzyme, which can alter the metabolic clearance and blood levels of other drugs.
Drugs That Interact Due to Changes in Gastric pH
Voquezna dramatically decreases stomach acid, which can significantly alter the absorption of drugs that require acidity to dissolve properly. If absorption is decreased, the drug's effectiveness can be reduced, leading to treatment failure.
Contraindicated HIV Medications
Concomitant use of Voquezna is contraindicated with HIV medications that contain rilpivirine (e.g., Edurant, Complera, Juluca). Rilpivirine's effectiveness is significantly reduced when taken with Voquezna, which can lead to HIV drug resistance. Avoid co-administration with atazanavir and nelfinavir as well, as Voquezna can decrease their absorption and efficacy.
Certain Antifungals
Antifungal medications like ketoconazole and itraconazole depend on stomach acid for proper absorption. Taking Voquezna with these drugs can lower their blood levels, making them less effective at treating fungal infections.
Select Cancer Therapies
Some tyrosine kinase inhibitors (TKIs) used to treat certain cancers also require an acidic environment for absorption. Voquezna can render them less effective. Examples include dasatinib, erlotinib, and nilotinib.
Other Affected Medications and Supplements
- Mycophenolate mofetil: An immunosuppressant used to prevent organ rejection. Voquezna can reduce its absorption.
- Iron Supplements: The absorption of iron from oral supplements can be reduced when taking Voquezna.
Drugs That Interact Due to CYP Enzyme Modulation
Vonoprazan is primarily metabolized by the CYP3A4 enzyme, with lesser involvement from other CYP enzymes. This makes Voquezna susceptible to interactions with drugs that either induce or inhibit these enzymes. Furthermore, vonoprazan inhibits CYP2C19, affecting drugs metabolized by that pathway.
Drugs that Decrease Voquezna's Effectiveness (CYP Inducers)
Medications that speed up the activity of the CYP3A4 enzyme can cause Voquezna to be cleared from the body too quickly, lowering its effectiveness. Avoid or use an alternative for the following:
- Certain antiepileptic drugs: Carbamazepine, phenytoin, phenobarbital.
- The herbal supplement St. John's wort: Speeds up CYP3A4 metabolism.
- Antibiotics: Rifampin.
Drugs with Increased Side Effect Risk (CYP2C19 Substrates)
Voquezna inhibits the CYP2C19 enzyme, which can cause increased exposure and side effects for drugs metabolized by that enzyme.
- Cilostazol: Used to treat peripheral artery disease. Voquezna can increase its exposure.
- Citalopram: An antidepressant. Vonoprazan can raise citalopram levels, increasing the risk of side effects.
The Clopidogrel Interaction
Voquezna can decrease the antiplatelet effect of clopidogrel, a medication used to prevent blood clots. This occurs because clopidogrel relies on CYP2C19 to be converted into its active form, and Voquezna's inhibition of this enzyme can lower the concentration of the active metabolite. Careful monitoring is recommended when co-administering these medications.
Potential for Increased Side Effects (CYP3A Substrates)
As a weak CYP3A inhibitor, vonoprazan may increase the exposure of certain drugs that are sensitive CYP3A substrates and have a narrow therapeutic index. Monitoring drug levels and observing for adverse reactions is important.
- Tacrolimus: An immunosuppressant. Voquezna can increase the risk of side effects from tacrolimus.
Other Important Considerations
Hypomagnesemia and Mineral Metabolism
Voquezna can cause hypomagnesemia (low magnesium), especially during long-term use. This can be exacerbated by other drugs that lower magnesium, such as certain diuretics. Patients taking digoxin are also at a higher risk of toxicity if their magnesium levels are low.
Interactions with Diagnostic Tests
Voquezna can interfere with certain diagnostic tests by altering gastric chemistry.
- Chromogranin A (CgA) Test: Used to diagnose neuroendocrine tumors. Voquezna can cause false-positive results by increasing CgA levels. Discontinue Voquezna at least 14 days before this test.
- Secretin Stimulation Test: Used to assess pancreatic function. Voquezna can cause a hyper-response in gastrin secretion, suggesting a gastrinoma falsely. Discontinue Voquezna at least 4 weeks prior to the test.
Comparison of Voquezna vs. PPI Interactions
While both Voquezna (a PCAB) and Proton Pump Inhibitors (PPIs) suppress stomach acid, their drug interaction profiles differ significantly. A key difference is the interaction with clopidogrel, where the clinical significance of Voquezna's interaction is less certain, whereas PPIs are known to cause a significant effect.
| Feature | Voquezna (Vonoprazan) | Proton Pump Inhibitors (PPIs) | Comment |
|---|---|---|---|
| Mechanism | Potassium-competitive acid blocker (PCAB). | Irreversible proton pump inhibitor. | Fundamentally different binding mechanisms. |
| Gastric pH Interaction | Reduces gastric acidity, affecting absorption of pH-dependent drugs (e.g., HIV drugs, antifungals). | Reduces gastric acidity, affecting absorption of pH-dependent drugs (e.g., HIV drugs, antifungals). | Similar effect on gastric pH, so interactions with pH-dependent drugs overlap. |
| CYP2C19 Inhibition | Inhibits CYP2C19, raising levels of substrates like citalopram and affecting clopidogrel's activation. | Inhibits CYP2C19 to varying degrees (e.g., omeprazole), impacting substrates like citalopram and clopidogrel activation. | Both can inhibit CYP2C19, but the clinical significance and specific impact differ. |
| CYP3A4 Metabolism | Metabolized mainly by CYP3A4, susceptible to induction by drugs like rifampin and St. John's Wort. | Primarily metabolized by CYP2C19 and CYP3A4; susceptible to induction. | Both are affected by CYP3A4 inducers, potentially reducing their effectiveness. |
| Clopidogrel Interaction | Reduces the active metabolite of clopidogrel by inhibiting CYP2C19, though clinical relevance is debated. | Can reduce the antiplatelet effect of clopidogrel by inhibiting CYP2C19. | Both have potential to interact, but the clinical guidance can differ. |
| Rilpivirine Contraindication | Contraindicated with rilpivirine-containing products. | No direct contraindication based on rilpivirine interaction. | Specific to Voquezna's interaction profile. |
Conclusion
Voquezna is a powerful new treatment for acid-related disorders, but its unique mechanism of action means it is associated with a distinct set of potential drug interactions. These interactions, driven by changes in gastric pH and its effect on CYP enzymes, can impact the efficacy of other medications or increase the risk of side effects. Notably, drugs requiring an acidic environment for absorption and those metabolized by CYP2C19 and CYP3A4 can be significantly affected. The contraindication with rilpivirine-containing HIV drugs is a critical safety consideration. Patients should always provide a complete list of their medications and supplements to their healthcare provider to allow for a thorough review of potential interactions before starting or modifying Voquezna treatment. This proactive approach ensures both safety and the best possible therapeutic outcome.
