From the Guidelines
Taking methylene blue with oxycodone and amitriptyline is potentially dangerous and should be avoided due to the risk of serotonin syndrome, a potentially life-threatening condition. Methylene blue is a monoamine oxidase inhibitor (MAOI) that can interact with both amitriptyline (a tricyclic antidepressant) and oxycodone (an opioid that has some serotonergic effects) [ 1 ]. This combination can cause excessive serotonin levels in the brain, leading to symptoms such as agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremors, excessive sweating, diarrhea, and in severe cases, seizures or even death.
Some key points to consider when taking these medications together include:
- Methylene blue should be used with caution in patients with certain medical conditions, such as G6PD deficiency, renal failure, and pregnancy [ 1 ].
- The risk of serotonin syndrome is higher when methylene blue is combined with other serotonergic medications, such as amitriptyline [ 1 ].
- If you are currently taking amitriptyline and oxycodone, you should wait at least 14 days after stopping these medications before using methylene blue.
- Similarly, if you have received methylene blue, you should wait at least 2 weeks before starting amitriptyline or oxycodone [ 1 ].
- Always consult with your healthcare provider before combining these medications, as they may need to adjust dosages, recommend alternatives, or monitor you closely for signs of serotonin syndrome if the combination cannot be avoided.
It is essential to prioritize caution when combining methylene blue with oxycodone and amitriptyline, as the risk of serotonin syndrome can have severe consequences on morbidity, mortality, and quality of life [ 1 ].
From the FDA Drug Label
Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact:MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5. 3)]. Intervention:The use of oxycodone hydrochloride tablets is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Serotonergic Drugs Clinical Impact:The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Adverse Reactions (6. 2)]. Intervention:If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue oxycodone hydrochloride tablets if serotonin syndrome is suspected Examples:Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). MAOI Interaction Inform patients to avoid taking oxycodone hydrochloride tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking oxycodone hydrochloride tablets [see Drug Interactions (7)]
The concomitant use of oxycodone and methylene blue (a monoamine oxidase inhibitor) may increase the risk of serotonin syndrome or opioid toxicity. The concomitant use of oxycodone and amitriptyline (a tricyclic antidepressant that affects the serotonergic neurotransmitter system) may increase the risk of serotonin syndrome. Key interactions to consider:
- Methylene blue: avoid concomitant use due to increased risk of serotonin syndrome or opioid toxicity 2
- Amitriptyline: use with caution and monitor for signs of serotonin syndrome 2
From the Research
Methylene Blue Interactions
- Methylene blue can interact with serotonergic medications, such as selective serotonin reuptake inhibitors, to lead to serotonin excess syndrome 3, 4, 5.
- This interaction is potentially lethal and should be considered when administering methylene blue to patients undergoing cardiopulmonary bypass or taking serotonergic medications 3, 4.
Oxycodone and Amitriptyline Interactions
- There is no direct evidence of interactions between methylene blue and oxycodone or amitriptyline in the provided studies.
- However, it is known that drug-drug interactions can occur when multiple drugs are administered together, and can lead to adverse effects such as increased risk of seizures, prolonged QT interval, increased central nervous system depression, and increased risk of serotonin syndrome 6.
General Drug Interaction Considerations
- Drug-drug interactions can occur through various mechanisms, including pharmacodynamic and pharmacokinetic interactions 6.
- Strategies to prevent drug incompatibility during simultaneous multi-drug infusion include filtration, use of multi-lumen devices, purging of infusion lines, incompatibility tables and databases, and standard operating procedures 7.
- It is essential to consider the potential risks and benefits of drug interactions on a patient-specific basis and to use clinical judgment when interpreting drug interaction alerts 6.