From the Guidelines
Quetiapine (Seroquel) side effects can be increased by drug-drug interactions, especially those arising from using drugs affecting the same metabolic pathways, such as cytochrome P450 (CYP) enzymes, particularly CYP2D6 1.
Factors that Increase Side Effects
- Antipsychotic polypharmacy: combining quetiapine with other antipsychotics can lead to a wider variety of side effects, unless the side effects are contrary to each other 1.
- Metabolic status: slow metabolizers may experience side effects at lower doses, while fast metabolizers may not achieve optimal treatment effects even with high doses 1.
- Other pharmaceuticals or over-the-counter products: substances that affect CYP enzymes, such as smoking status, caffeine consumption, and recreational drug use, can impact blood drug concentrations and increase side effects 1.
- Substance abuse: can worsen compliance and adherence, leading to increased side effects 1.
Specific Interactions
- CYP2D6 inhibitors: can increase quetiapine plasma concentrations and worsen side effects 1.
- CYP3A4 inhibitors: can also increase quetiapine plasma concentrations and worsen side effects, although this is less well-studied than CYP2D6 interactions. It is essential to consider these factors and interactions when prescribing quetiapine to minimize the risk of increased side effects. Regular monitoring of side effects and adjustment of treatment as needed can help mitigate these risks 1.
From the FDA Drug Label
DRUG INTERACTIONS SECTION 7. 1 Effect of Other Drugs on Quetiapine The risks of using quetiapine in combination with other drugs have not been extensively evaluated in systematic studies. Given the primary CNS effects of quetiapine, caution should be used when it is taken in combination with other centrally acting drugs Quetiapine potentiated the cognitive and motor effects of alcohol in a clinical trial in subjects with selected psychotic disorders, and alcoholic beverages should be limited while taking quetiapine. Quetiapine exposure is increased by the prototype CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). CYP3A4 inhibitors: Coadministration of ketoconazole, a potent inhibitor of cytochrome CYP3A4, resulted in significant increase in quetiapine exposure
The following can increase the side effects of Quetiapine (Seroquel):
- Centrally acting drugs: Quetiapine should be used with caution when taken in combination with other centrally acting drugs due to its primary CNS effects.
- Alcohol: Quetiapine potentiated the cognitive and motor effects of alcohol, and alcoholic beverages should be limited while taking quetiapine.
- CYP3A4 inhibitors: Drugs such as ketoconazole, itraconazole, indinavir, ritonavir, and nefazodone can increase quetiapine exposure, potentially increasing the risk of side effects 2.
From the Research
Factors that Increase Side Effects of Quetiapine
- Increasing the dose of quetiapine can increase the risk of side effects, such as serotonin syndrome 3
- Combining quetiapine with serotonergic agents, such as selective serotonin reuptake inhibitors, can increase the risk of serotonin syndrome 3
- High doses of quetiapine (approximately 600 mg per day) may be more likely to cause side effects, such as weight gain and increased triglycerides, compared to low doses (approximately 150-300 mg per day) 4
- Quetiapine-induced elevations in low-density lipoprotein and total cholesterol may be more common in patients with schizophrenia compared to other psychiatric disorders 4
- The risk of extrapyramidal symptoms, such as tremors and akathisia, may be increased with high doses of quetiapine, although this is less common compared to typical antipsychotics 5, 6, 7
Specific Side Effects
- Serotonin syndrome: a potentially life-threatening condition caused by excessive levels of serotonin in the body, which can occur with increasing doses of quetiapine or combining quetiapine with serotonergic agents 3
- Weight gain: a common side effect of quetiapine, particularly at high doses 5, 4
- Increased triglycerides: a potential side effect of quetiapine, particularly at high doses 4
- Extrapyramidal symptoms: a potential side effect of quetiapine, although less common compared to typical antipsychotics 5, 6, 7