From the Guidelines
Adding low-dose naltrexone (LDN) and pitolisant to the patient's current medication regimen requires caution due to potential interactions, and it is recommended to start with the lowest effective doses and gradually titrate while monitoring for side effects. The patient's current regimen includes multiple CNS-active medications (fluoxetine, trazodone, Adderall) that could interact with the proposed additions. Pitolisant (Wakix) may interact with fluoxetine since both affect histamine and serotonin pathways, potentially altering the metabolism of either medication, as noted in the context of serotonergic drug interactions 1. Additionally, combining pitolisant with Adderall could theoretically enhance stimulant effects and increase the risk of cardiovascular side effects. LDN generally has fewer interactions but could potentially affect the efficacy of opioid-containing medications if they're needed for breakthrough migraines.
Before adding these medications, it is essential to check for QT interval prolongation risk, as several of her current medications (fluoxetine, famotidine) can affect cardiac conduction 1. The patient should be closely monitored for side effects like insomnia, anxiety, or changes in blood pressure. Given her perimenopausal status, hormone fluctuations may also influence how she responds to these medications, so close follow-up is essential. A medication reconciliation with her pharmacist would be beneficial to identify any additional potential interactions specific to her complete regimen.
Key considerations include:
- Starting with low doses and gradual titration to minimize risks
- Monitoring for serotonin syndrome, given the combination of serotonergic agents
- Regular assessment of QT interval prolongation risk
- Close follow-up for side effects and adjustment of the medication regimen as needed
- Consideration of the patient's perimenopausal status and potential impact on medication response
- Collaboration with a pharmacist for medication reconciliation to identify potential interactions.
From the FDA Drug Label
The safety and efficacy of concomitant use of naltrexone hydrochloride and other drugs have not been evaluated, and caution is advised if the concomitant administration of naltrexone hydrochloride and other drugs is required. WAKIX may reduce the effectiveness of hormonal contraceptives. Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with WAKIX and for at least 21 days after discontinuing treatment.
The proposed medication regimen, which includes adding LDN (Naltrexone) and Pitolisant to the patient's current medications, may pose potential interactions and risks.
- Hormonal Contraception: The patient is taking Opill birth control, which may be less effective when used with Pitolisant.
- Concomitant Use: There is limited information available on the concomitant use of Naltrexone and Pitolisant with the patient's current medications, including fluoxetine, trazodone, Adderall, and others. Given the potential risks and lack of information on concomitant use, it is recommended to exercise caution and consider alternative treatment options or closely monitor the patient for potential interactions and adverse effects 2 3.
From the Research
Medication Regimen Safety
To assess the safety of the proposed medication regimen, it is essential to examine all medications being taken, whether prescription or not, and review each drug regimen in a systematic manner, noting history of adverse effects, need for the drug, duplication in therapy, inappropriate dose, route, or schedule, current adverse effects, drug-drug interactions, and drug-disease interactions 4.
Potential Interactions and Considerations
The patient is currently taking fluoxetine, trazodone, adderall, Ubrelvy, Opill birth control, proair inhaler, vitamin C, calcium, magnesium, iron, psyllium fiber, colostrum, hyaluronic acid, MSM, magnesium citrate, xyzal, flonase, and famotidine. Adding LDN and pitolisant to this regimen requires careful consideration of potential interactions.
- LDN has shown promise in reducing symptoms related to chronic pain conditions, and its mechanism appears to be modulation of neuro-inflammation 5.
- However, there is limited information available on the potential interactions between LDN and the patient's current medications.
- Pitolisant is a histamine H3 receptor inverse agonist used for the treatment of excessive daytime sleepiness in adults with narcolepsy. Its potential interactions with the patient's current medications, particularly those affecting the central nervous system, should be carefully evaluated.
Strategies for Simplifying the Medication Regimen
Given the complexity of the patient's medication regimen, strategies to simplify it should be considered, such as consolidating dosing times, standardizing routes of administration, using long-acting rather than shorter-acting formulations, and switching to combination products in place of single-ingredient products 6.
- Obtaining a best possible medication history, ensuring appropriateness of current therapy, and deprescribing are important steps prior to implementing regimen simplification.
- The patient's pharmacist can be an excellent resource for determining appropriate dosages, potential for interaction, and overlapping drugs 4.
Selective Serotonin Reuptake Inhibitors (SSRIs)
The patient is currently taking fluoxetine, an SSRI.
- A meta-analysis of 20 short-term comparative studies of 5 SSRIs has shown no difference in efficacy between individual compounds but a slower onset of action of fluoxetine 7.
- Fluoxetine may not be the drug of first choice for patients in whom a rapid antidepressant effect is important or for those who are agitated, but it may have advantages over other SSRIs in patients who are poorly compliant with treatment and those who have previously had troublesome discontinuation symptoms 7.
- Drug interactions mediated by cytochrome P450 enzymes are theoretically less likely to occur during treatment with citalopram and sertraline, but there is a sparsity of clinical data to support this 7.