Summary

Ketoconazole significantly increases prednisone blood levels by inhibiting its metabolism, potentially leading to enhanced corticosteroid effects and increased risk of side effects. This interaction requires careful monitoring and possible dose adjustments when these medications are used together.

Introduction

Prednisone is a synthetic corticosteroid medication commonly prescribed to treat inflammatory conditions, autoimmune disorders, and allergic reactions. It works by suppressing the immune system and reducing inflammation throughout the body. Ketoconazole is an antifungal medication belonging to the azole class, primarily used to treat serious fungal infections. It works by inhibiting fungal cell membrane synthesis and is also known for its ability to inhibit certain liver enzymes involved in drug metabolism.

Mechanism of Interaction

The interaction between prednisone and ketoconazole occurs through inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme system. Ketoconazole is a potent CYP3A4 inhibitor, which significantly reduces the metabolism of prednisone and its active metabolite prednisolone. This inhibition leads to increased plasma concentrations of corticosteroids, prolonged half-life, and enhanced pharmacological effects. The interaction can result in up to a 4-fold increase in corticosteroid exposure, making patients more susceptible to both therapeutic and adverse effects of prednisone.

Risks and Symptoms

The primary clinical risks of this interaction include increased susceptibility to corticosteroid-related adverse effects such as immunosuppression, increased infection risk, hyperglycemia, hypertension, fluid retention, mood changes, and adrenal suppression. Patients may experience enhanced anti-inflammatory effects but also face a higher likelihood of developing Cushing's syndrome-like symptoms, osteoporosis, muscle weakness, and delayed wound healing. The interaction is considered clinically significant and may require immediate medical attention if signs of corticosteroid toxicity develop.

Management and Precautions

When concurrent use is necessary, prednisone doses should be reduced by 50-75% and patients should be closely monitored for signs of corticosteroid excess. Regular monitoring should include blood glucose levels, blood pressure, electrolytes, and assessment for signs of infection or mood changes. Healthcare providers should consider alternative antifungal agents with less CYP3A4 inhibition potential when possible. If ketoconazole must be used, the lowest effective dose should be employed for the shortest duration necessary. Patients should be educated about potential symptoms of corticosteroid toxicity and advised to report any concerning symptoms immediately.

Prednisone interactions with food and lifestyle

Prednisone should be taken with food or milk to reduce stomach irritation and gastrointestinal upset. Alcohol consumption should be limited or avoided while taking prednisone, as both can increase the risk of stomach ulcers and gastrointestinal bleeding. Patients should also limit sodium intake and increase calcium and vitamin D consumption, as prednisone can cause sodium retention and bone loss. Grapefruit and grapefruit juice should be avoided as they may increase prednisone levels in the blood. Live vaccines should be avoided during prednisone treatment due to immunosuppression.

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.