Summary

Ketoconazole significantly increases quetiapine blood levels by inhibiting the CYP3A4 enzyme responsible for quetiapine metabolism. This interaction can lead to enhanced quetiapine side effects and requires careful dose adjustment and monitoring.

Introduction

Quetiapine (brand name Seroquel) is an atypical antipsychotic medication primarily used to treat schizophrenia, bipolar disorder, and major depressive disorder as an adjunct therapy. It belongs to the dibenzothiazepine class of antipsychotics and works by blocking dopamine and serotonin receptors. Ketoconazole is a potent antifungal medication from the azole class, used to treat serious fungal infections. It is a strong inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system, which metabolizes many medications including quetiapine.

Mechanism of Interaction

The interaction between quetiapine and ketoconazole occurs through inhibition of the CYP3A4 enzyme pathway. Quetiapine is extensively metabolized by CYP3A4 in the liver, with this pathway accounting for the majority of its clearance from the body. Ketoconazole is a potent CYP3A4 inhibitor that significantly reduces the enzyme's activity. When administered concurrently, ketoconazole blocks the metabolism of quetiapine, leading to increased plasma concentrations and prolonged elimination half-life of quetiapine. This results in enhanced and prolonged pharmacological effects of the antipsychotic medication.

Risks and Symptoms

The primary clinical risk of this interaction is significantly increased quetiapine exposure, which can lead to enhanced adverse effects. Patients may experience increased sedation, dizziness, orthostatic hypotension, and extrapyramidal symptoms. More serious risks include prolonged QT interval, which can lead to potentially fatal cardiac arrhythmias, particularly torsades de pointes. Other concerning effects may include severe hypotension, respiratory depression, and increased risk of metabolic side effects such as hyperglycemia and weight gain. Elderly patients and those with pre-existing cardiac conditions are at particularly high risk for serious complications from this interaction.

Management and Precautions

When concurrent use of quetiapine and ketoconazole is necessary, significant dose reduction of quetiapine is required. The quetiapine dose should typically be reduced to one-sixth of the original dose when used with ketoconazole. Close monitoring is essential, including regular assessment of vital signs, cardiac monitoring with ECGs to evaluate QT interval, and monitoring for signs of quetiapine toxicity such as excessive sedation or movement disorders. Blood glucose levels should be monitored due to increased risk of hyperglycemia. If possible, alternative antifungal agents with less CYP3A4 inhibition should be considered. Healthcare providers should educate patients about potential side effects and advise them to report any unusual symptoms immediately.

Quetiapine interactions with food and lifestyle

Quetiapine should not be taken with alcohol as it can increase the risk of drowsiness, dizziness, and impaired coordination. Grapefruit juice may increase quetiapine levels in the blood and should be avoided. Patients should be cautious when driving or operating machinery due to potential sedation effects. Smoking may decrease quetiapine effectiveness, and patients should discuss smoking cessation with their healthcare provider.

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.