Summary

Lansoprazole significantly reduces ketoconazole absorption by increasing gastric pH, potentially leading to treatment failure of fungal infections. This interaction is considered clinically significant and requires careful management or alternative treatment options.

Introduction

Lansoprazole is a proton pump inhibitor (PPI) commonly prescribed to treat gastroesophageal reflux disease (GERD), peptic ulcers, and other acid-related disorders by reducing stomach acid production. Ketoconazole is an antifungal medication belonging to the azole class, used to treat serious systemic fungal infections and certain skin conditions caused by fungi.

Mechanism of Interaction

The interaction occurs because ketoconazole requires an acidic environment for optimal absorption in the gastrointestinal tract. Lansoprazole works by irreversibly blocking the hydrogen-potassium ATPase enzyme system (proton pump) in gastric parietal cells, significantly raising gastric pH above 3-4. This elevated pH dramatically reduces ketoconazole's dissolution and absorption, potentially decreasing its bioavailability by up to 95% when gastric pH exceeds 6.

Risks and Symptoms

The primary risk is therapeutic failure of antifungal treatment due to subtherapeutic ketoconazole levels. This can lead to persistent or worsening fungal infections, development of antifungal resistance, prolonged treatment duration, and potential complications from untreated systemic mycoses. Patients with serious fungal infections may experience treatment failure, which could be life-threatening in immunocompromised individuals.

Management and Precautions

Avoid concurrent use when possible by selecting alternative antifungal agents (such as fluconazole or voriconazole) that are less pH-dependent for absorption. If ketoconazole must be used, consider temporarily discontinuing lansoprazole or switching to H2 receptor antagonists with careful timing. When co-administration is unavoidable, administer ketoconazole with acidic beverages (cola) and separate dosing by at least 2 hours. Monitor antifungal therapeutic response closely and consider therapeutic drug monitoring if available. Consult with clinical pharmacists or infectious disease specialists for complex cases.

Lansoprazole interactions with food and lifestyle

Lansoprazole should be taken on an empty stomach, preferably 30-60 minutes before meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be limited or avoided while taking lansoprazole, as alcohol can increase stomach acid production and counteract the medication's acid-reducing effects. Additionally, alcohol may worsen gastroesophageal reflux disease (GERD) symptoms that lansoprazole is intended to treat.

Ketoconazole interactions with food and lifestyle

Ketoconazole requires an acidic environment for optimal absorption. Take ketoconazole with food or an acidic beverage to enhance absorption. Avoid taking ketoconazole with antacids, H2 blockers, or proton pump inhibitors as these medications reduce stomach acid and significantly decrease ketoconazole absorption. If antacids must be used, take them at least 2 hours after ketoconazole. Alcohol should be avoided during ketoconazole treatment as both ketoconazole and alcohol can cause liver toxicity, and concurrent use may increase the risk of hepatotoxicity. Grapefruit juice may increase ketoconazole blood levels and should be avoided to prevent increased risk of side effects.