What are the potential drug interactions with quetiapine?

Potential Drug Interactions with Quetiapine

Quetiapine should be used with extreme caution when combined with CYP3A4 inhibitors, requiring a dose reduction to one-sixth of the original dose, while doses may need to be increased up to 5-fold when combined with CYP3A4 inducers. 1

Pharmacokinetic Interactions

CYP3A4 Inhibitors

• Strong CYP3A4 inhibitors significantly increase quetiapine exposure 1:
  • Ketoconazole, itraconazole, indinavir, ritonavir, nefazodone
  • HIV protease inhibitors (particularly ritonavir-boosted regimens)
  • Dose adjustment: Reduce quetiapine dose to one-sixth of original dose 1, 2
  • Clinical consequences: Excessive sedation, mental confusion, and severe weight gain have been reported 3

CYP3A4 Inducers

• Strong CYP3A4 inducers significantly decrease quetiapine exposure 1:
  • Phenytoin, carbamazepine, rifampin, avasimibe, St. John's wort
  • Dose adjustment: Increase quetiapine dose up to 5-fold to maintain therapeutic effect 1
  • When inducer is discontinued: Reduce quetiapine dose to original level within 7-14 days 1

Pharmacodynamic Interactions

CNS Depressants

• Alcohol: Quetiapine potentiates cognitive and motor effects of alcohol; limit alcoholic beverages 1
• Other CNS depressants: Use with caution due to additive CNS depression 1

Cardiovascular Effects

• Antihypertensive agents: Quetiapine may enhance hypotensive effects 1
• QT-prolonging medications: Caution with concurrent use of other QT-prolonging drugs
  • Combination of quetiapine with ziprasidone has been reported to cause QTc prolongation (482 ms) 4

Dopaminergic Agents

• Levodopa and dopamine agonists: Quetiapine may antagonize their effects 1, 5

Specific Drug Class Interactions

HIV Protease Inhibitors

• Ritonavir-boosted regimens: Strong interaction potential 3, 2
  • Case reports of coma and severe sedation exist 2
  • Approximately 0.4% of quetiapine patients receive concurrent ritonavir 2
  • In 90% of cases, quetiapine dose was not appropriately reduced 2
  • Recommendation: Follow the 6-fold dose reduction guideline strictly 2

Contraindicated Combinations

• Specific medications: Pimozide, terfenadine, astemizole, cisapride 6
• Atazanavir-ritonavir: Case reports of severe adverse effects including weight gain, sedation, and mental confusion 3

Monitoring Recommendations

1. Before initiating quetiapine:

   • Obtain complete medication history including prescription, OTC, and illicit drugs 6
   • Screen for potential CYP3A4 inhibitors or inducers 1

2. During treatment:

   • Monitor for excessive sedation when combined with CYP3A4 inhibitors 3, 2
   • Monitor for reduced efficacy when combined with CYP3A4 inducers 1
   • Monitor cardiovascular parameters (blood pressure, heart rate, ECG) with relevant combinations 4

3. When adding or removing interacting medications:

   • Adjust quetiapine dose according to recommendations 1
   • Monitor closely during transition periods

Special Populations

• Hepatic impairment: Increased risk of drug interactions due to reduced metabolic capacity 7
• Elderly: Use lower doses and monitor more closely for adverse effects 7
• HIV patients: Extreme caution with antiretroviral therapy, especially protease inhibitors 3, 2

Clinical Implications

The most clinically significant interactions with quetiapine involve medications that affect CYP3A4 metabolism. Failure to adjust dosing appropriately can lead to serious adverse events including excessive sedation, mental confusion, and potentially coma with CYP3A4 inhibitors 3, 2, or treatment failure with CYP3A4 inducers 1.

When prescribing quetiapine, always check for potential drug interactions and make appropriate dose adjustments to ensure both safety and efficacy.