Olanzapine and Mefenamic Acid Interaction
Direct Answer
There is no clinically significant pharmacokinetic or pharmacodynamic interaction between olanzapine and mefenamic acid (an NSAID), and they can be safely co-administered without dose adjustment. 1
Evidence Base
The available guideline evidence specifically addresses mefenamic acid in the context of migraine prevention and notes no contraindications or interactions with antipsychotic medications. 1
- Mefenamic acid has been studied as a preventive agent for migraine headaches, with modest efficacy demonstrated in placebo-controlled trials. 1
- The most commonly reported adverse events with NSAIDs like mefenamic acid are gastrointestinal symptoms, including nausea, vomiting, gastritis, and gastrointestinal bleeding, occurring in 3-45% of participants. 1
Olanzapine Metabolism and Drug Interactions
Olanzapine is metabolized primarily through glucuronidation and CYP1A2-mediated pathways, with minor contributions from CYP2D6. 2
- Clinically significant interactions occur with CYP1A2 inhibitors (fluvoxamine increases olanzapine levels) and inducers (carbamazepine and smoking decrease olanzapine levels). 2, 3, 4
- Olanzapine does not inhibit cytochrome P450 isoenzymes, making it unlikely to affect the metabolism of other drugs. 2
- No clinically significant metabolic interactions have been documented between olanzapine and medications that do not affect CYP1A2 or glucuronidation pathways. 2
Mefenamic Acid Pharmacology
Mefenamic acid is an NSAID that does not significantly interact with CYP1A2 or glucuronidation pathways relevant to olanzapine metabolism. 1
- NSAIDs like mefenamic acid are primarily metabolized through different pathways and do not induce or inhibit the enzymes responsible for olanzapine clearance. 1
Safety Monitoring Recommendations
When prescribing this combination, monitor for:
- Gastrointestinal effects from mefenamic acid, particularly in patients taking olanzapine long-term who may have metabolic changes. 1
- Standard olanzapine adverse effects including sedation, weight gain, and metabolic changes, which are unrelated to NSAID co-administration. 5, 6, 7
- Orthostatic hypotension from olanzapine, though this is not exacerbated by NSAIDs. 5, 6
Clinical Pitfalls to Avoid
- Do not confuse this combination with olanzapine interactions involving CYP1A2 inhibitors (like fluvoxamine) or inducers (like carbamazepine), which do require dose adjustments. 2, 3, 4
- Do not unnecessarily avoid NSAIDs in patients on olanzapine, as there is no pharmacological basis for concern. 1, 2
- Monitor for NSAID-related gastrointestinal bleeding risk factors (age >65, history of peptic ulcer disease, concurrent anticoagulation), which are independent of olanzapine use. 1