Koffex-DM (Dextromethorphan) Medication Interactions
Koffex-DM (dextromethorphan) has several significant drug interactions, with monoamine oxidase inhibitors (MAOIs) being the most dangerous contraindicated combination due to risk of potentially fatal serotonin syndrome.
Major Contraindicated Interactions
MAOIs (Monoamine Oxidase Inhibitors): Absolutely contraindicated with dextromethorphan due to risk of potentially life-threatening serotonin syndrome. This includes phenelzine, tranylcypromine, isocarboxazid, selegiline, and linezolid 1, 2
SSRIs (Selective Serotonin Reuptake Inhibitors): Combining dextromethorphan with SSRIs like sertraline, fluoxetine, or paroxetine significantly increases the risk of serotonin syndrome, characterized by mental status changes, neuromuscular hyperactivity, and autonomic instability 3, 4
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors): Similar to SSRIs, these medications can increase serotonin levels and lead to serotonin syndrome when combined with dextromethorphan 1
Moderate Interactions Requiring Caution
Tricyclic Antidepressants (TCAs): Concomitant use with dextromethorphan may increase serotonergic effects and risk of serotonin syndrome 1
Opioids: Combining dextromethorphan with opioids increases CNS depression and risk of serotonin syndrome, particularly with tramadol, meperidine, methadone, and fentanyl 1, 3
Quinidine: While sometimes intentionally combined therapeutically (as in Nuedexta), quinidine inhibits CYP2D6 metabolism of dextromethorphan, significantly increasing dextromethorphan plasma concentrations 5, 6
Stimulants: Amphetamine-class medications and possibly methylphenidate may increase risk of serotonin syndrome when combined with dextromethorphan 3
Other Notable Interactions
Over-the-counter medications: Products containing chlorpheniramine or other antihistamines may have additive CNS depressant effects 3
Herbal supplements: St. John's Wort and L-tryptophan supplements can increase serotonin levels and should be avoided with dextromethorphan 3
Illicit drugs: MDMA (ecstasy), methamphetamine, cocaine, and LSD can significantly increase the risk of serotonin syndrome when combined with dextromethorphan 3, 2
Signs of Serotonin Syndrome to Monitor
Early symptoms develop rapidly (within 24-48 hours) and include agitation, confusion, tremor, hyperreflexia, and clonus 4
Advanced symptoms include hyperthermia, tachycardia, fever, seizures, arrhythmias, and potentially death 4, 3
Risk Mitigation Strategies
Always check for potential drug interactions before prescribing or recommending dextromethorphan-containing products 2
Educate patients about avoiding over-the-counter medications without consulting a healthcare provider 1
When switching from MAOIs to other medications (or vice versa), ensure adequate washout periods (typically 2 weeks, 5 weeks for fluoxetine) 1
Be particularly cautious with elderly patients or those with multiple medications, as they may be at higher risk for adverse interactions 3
Common Pitfalls to Avoid
Failing to recognize that many over-the-counter cold and cough medications contain dextromethorphan 2, 7
Not considering the recreational abuse potential of dextromethorphan ("robotripping"), which can lead to intoxication delirium at high doses 8
Overlooking the fact that patients may not report all supplements or over-the-counter medications they are taking 3