Drug Interaction Between Norethisterone and Quetiapine
There is no clinically significant pharmacokinetic interaction between norethisterone and quetiapine based on available evidence.
Metabolic Pathways and Interaction Potential
Quetiapine is primarily metabolized by CYP3A4, with minimal involvement of other cytochrome P450 enzymes 1, 2. The drug does not inhibit major CYP enzymes (1A2, 2C9, 2C19, 2D6, or 3A4) at clinically relevant concentrations 1, 2.
Norethisterone does not appear in any of the documented drug interaction studies or guidelines for quetiapine 3, 1. The comprehensive FDA labeling for quetiapine lists specific contraindicated medications and those requiring caution, but hormonal contraceptives including norethisterone are notably absent from these lists 1.
Evidence from Clinical Studies
A large therapeutic drug monitoring study of 2,111 serum samples from 1,179 patients identified 41 commonly co-administered drugs with quetiapine, and norethisterone was not among those showing significant interactions 4
Systematic reviews of quetiapine pharmacokinetics and drug interactions do not identify hormonal contraceptives as interacting agents 2, 5
Population pharmacokinetic analyses examining covariates affecting quetiapine exposure did not identify hormonal contraceptive use as a significant factor 6
Documented Quetiapine Interactions to Be Aware Of
While norethisterone is safe to use with quetiapine, clinicians should be aware of the following actual interactions:
Strong CYP3A4 Inhibitors (Contraindicated or Requiring Dose Reduction)
- Ritonavir-boosted protease inhibitors are contraindicated with quetiapine due to markedly increased quetiapine exposure 3
- Ketoconazole and other azole antifungals significantly increase quetiapine levels, requiring dose reduction to one-sixth of the original dose 1
- Fluvoxamine increases quetiapine levels by 159% 4
CYP3A4 Inducers (Requiring Dose Increase)
- Carbamazepine reduces quetiapine levels by 86%, requiring up to 5-fold dose increases 1, 4
- Phenytoin increases quetiapine clearance 5-fold 1, 2
Other Notable Interactions
- Clozapine increases quetiapine levels by 82% 4
- Central nervous system depressants and alcohol have additive sedative effects 1
Clinical Recommendations
Norethisterone and quetiapine can be safely co-administered without dose adjustments for either medication. However, monitor for:
- Quetiapine's anticholinergic effects (constipation, urinary retention) which may be relevant in patients using hormonal contraceptives 1
- Sedation and orthostatic hypotension, which are common quetiapine adverse effects regardless of co-medications 3, 1
- Weight gain and metabolic effects with quetiapine use 3, 7
Always verify all concurrent medications for the documented CYP3A4 inhibitors and inducers listed above, as these require specific dose adjustments 1.