Limbitrol has important interaction risks from both its tricyclic and benzodiazepine components, including life-threatening respiratory depression with opioids and serious serotonin or cardiovascular effects with other psychotropics.
With: Opioid agonists (for example codeine, oxycodone, morphine, methadone, hydrocodone, fentanyl)
Risk: Profound sedation, respiratory depression, coma, and death.
Action: Avoid combination when possible. If necessary, use lowest effective doses and shortest duration; monitor closely and consider prescribing an opioid overdose reversal agent.
With: Alcohol and other CNS depressants (benzodiazepines, sedative-hypnotics, barbiturates, gabapentinoids, many antihistamines)
Risk: Additive CNS and respiratory depression and impaired coordination.
Action: Avoid or minimize use; counsel patients to avoid alcohol and sedating over-the-counter products.
With: MAOIs (isocarboxazid, phenelzine, tranylcypromine, selegiline, rasagiline) and linezolid or IV methylene blue
Risk: Hypertensive crisis, serotonin syndrome, severe CNS toxicity.
Action: Contraindicated. Allow at least 14 days between discontinuing an MAOI and starting Limbitrol, and 14 days between stopping Limbitrol and starting an MAOI.
With: Serotonergic agents (SSRIs, SNRIs, other TCAs, triptans, buspirone, fentanyl, tramadol, St John’s wort, dextromethorphan, certain migraine or pain medications)
Risk: Serotonin syndrome.
Action: Use with caution; avoid high-risk combinations; monitor for serotonin syndrome symptoms.
With: CYP2D6 inhibitors (for example fluoxetine, paroxetine, duloxetine, bupropion, quinidine)
Risk: Increased amitriptyline concentrations and toxicity.
Action: Consider lower amitriptyline dose and monitor for anticholinergic and cardiac side effects.
With: CYP3A4 inhibitors (for example cimetidine, certain azole antifungals, some macrolide antibiotics)
Risk: Increased chlordiazepoxide concentrations and prolonged sedation.
Action: Monitor closely and consider dose reduction.
With: Other QT-prolonging or arrhythmogenic drugs (for example certain antiarrhythmics, antipsychotics, macrolides, fluoroquinolones)
Risk: Additive risk of QT prolongation and serious ventricular arrhythmias.
Action: Avoid when possible; if combination is necessary, monitor ECG and electrolytes.
With: Anticholinergic agents (for example many antipsychotics, antiparkinsonian agents, some antihistamines, bladder antimuscarinics)
Risk: Additive anticholinergic toxicity (constipation, urinary retention, confusion, blurred vision).
Action: Use with caution; monitor for severe anticholinergic effects.
With: Antihypertensives and alpha-agonists or alpha2-agonists
Risk: Altered blood pressure control, enhanced hypotension, or loss of antihypertensive effect.
Action: Monitor blood pressure and adjust doses as necessary.