Drug Interactions between Adderall and Nuedexta

GENERALLY AVOID: Coadministration with potent CYP450 2D6 inhibitors (e.g., quinidine, terbinafine) may significantly increase the plasma concentrations of dextromethorphan in patients who are extensive metabolizers of this isoenzyme (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). The proposed mechanism is inhibition of the CYP450 2D6-mediated O-demethylation of dextromethorphan. Studies in humans have shown an increase in systemic exposure of dextromethorphan of up to 43-fold when given concurrently with quinidine. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. However, this interaction has also been used clinically, with dextromethorphan in combination with quinidine indicated by some authorities for the treatment of pseudobulbar affect. Data evaluating the impact of this interaction in patients who are poor metabolizers of CYP450 2D6 are limited; most studies include extensive metabolizers of this isoenzyme. It is expected that poor metabolizers would have elevated dextromethorphan levels without concurrent quinidine

MANAGEMENT: The combination of dextromethorphan with potent CYP450 2D6 inhibitors should be generally avoided. Some manufacturers consider the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors contraindicated. If use is considered necessary, the patient should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations as well as the pharmacologic and adverse effects of amphetamines. The proposed mechanism involves the inhibition of CYP450 2D6, an isoenzyme partially responsible for the metabolic clearance of certain amphetamines. Furthermore, because CYP450 2D6 is genetically polymorphic, variations in amphetamine metabolism across populations may either increase or decrease the risk associated with this interaction. Increased exposure to amphetamines may potentiate the risk of serious adverse reactions such as serotonin syndrome, seizures, psychiatric adverse reactions (e.g., new psychotic or manic symptoms), peripheral vasculopathy (including Raynaud's Phenomenon), and cardiovascular effects (e.g., hypertension, tachycardia). However, data evaluating the interaction are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects are recommended when amphetamines are used concurrently with CYP450 2D6 inhibitors, and a reduction in the initial amphetamine dose should be considered. Patients should be more closely monitored for signs and symptoms of serotonin syndrome, particularly during the initiation of amphetamine therapy and following any dosage increases. Additional caution is advised when amphetamines are coadministered with CYP450 2D6 inhibitors that lower the seizure threshold (e.g., bupropion). Patients should be instructed to notify their healthcare provider if they experience increased amphetamine-related side effects, such as seizures, cardiovascular effects (e.g., hypertension, tachycardia), or symptoms of serotonin syndrome (e.g., mental status changes, autonomic dysfunction like tachycardia or hyperthermia, neuromuscular abnormalities such as hyperreflexia, or gastrointestinal symptoms).

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations as well as the pharmacologic and adverse effects of amphetamines. The proposed mechanism involves the inhibition of CYP450 2D6, an isoenzyme partially responsible for the metabolic clearance of certain amphetamines. Furthermore, because CYP450 2D6 is genetically polymorphic, variations in amphetamine metabolism across populations may either increase or decrease the risk associated with this interaction. Increased exposure to amphetamines may potentiate the risk of serious adverse reactions such as serotonin syndrome, seizures, psychiatric adverse reactions (e.g., new psychotic or manic symptoms), peripheral vasculopathy (including Raynaud's Phenomenon), and cardiovascular effects (e.g., hypertension, tachycardia). However, data evaluating the interaction are not available.

MANAGEMENT: Caution and closer monitoring for adverse effects are recommended when amphetamines are used concurrently with CYP450 2D6 inhibitors, and a reduction in the initial amphetamine dose should be considered. Patients should be more closely monitored for signs and symptoms of serotonin syndrome, particularly during the initiation of amphetamine therapy and following any dosage increases. Additional caution is advised when amphetamines are coadministered with CYP450 2D6 inhibitors that lower the seizure threshold (e.g., bupropion). Patients should be instructed to notify their healthcare provider if they experience increased amphetamine-related side effects, such as seizures, cardiovascular effects (e.g., hypertension, tachycardia), or symptoms of serotonin syndrome (e.g., mental status changes, autonomic dysfunction like tachycardia or hyperthermia, neuromuscular abnormalities such as hyperreflexia, or gastrointestinal symptoms).

MONITOR: Coadministration of amphetamines and amphetamine-like drugs with other agents that also increase serotonin levels or effects, may increase the risk of serotonin syndrome. The exact mechanism by which serotonin levels are increased differs depending on the specific medication(s) involved. Serotonin syndrome is believed to result from the hyperstimulation of postsynaptic 5-HT receptors and while postsynaptic 5-HT1A and 5-HT2A receptors are usually implicated, it is more likely that no single receptor is solely responsible. Clinical data are limited. Serotonin syndrome involving amphetamines has most frequently been reported with the use of MDMA, or ecstasy, an amphetamine derivative with enhanced serotonergic activity over classical amphetamines, which tend to be more dopaminergic. However, case reports of serotonin syndrome involving amphetamines and amphetamine-like drugs have been documented with concomitant use of other serotonergic substances (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors). Abuse and/or overdose may increase the risk of experiencing this adverse effect.

MANAGEMENT: Caution is recommended when amphetamines and amphetamine-like drugs are used with other agents that also increase serotonin levels or effects. Initiating patients with lower doses and ensuring close clinical monitoring for signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, tremor) is advised. Particular caution is recommended when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately, and treatment rendered as indicated.

MONITOR: Coadministration of amphetamines and amphetamine-like drugs with other agents that also increase serotonin levels or effects, may increase the risk of serotonin syndrome. The exact mechanism by which serotonin levels are increased differs depending on the specific medication(s) involved. Serotonin syndrome is believed to result from the hyperstimulation of postsynaptic 5-HT receptors and while postsynaptic 5-HT1A and 5-HT2A receptors are usually implicated, it is more likely that no single receptor is solely responsible. Clinical data are limited. Serotonin syndrome involving amphetamines has most frequently been reported with the use of MDMA, or ecstasy, an amphetamine derivative with enhanced serotonergic activity over classical amphetamines, which tend to be more dopaminergic. However, case reports of serotonin syndrome involving amphetamines and amphetamine-like drugs have been documented with concomitant use of other serotonergic substances (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors). Abuse and/or overdose may increase the risk of experiencing this adverse effect.

MANAGEMENT: Caution is recommended when amphetamines and amphetamine-like drugs are used with other agents that also increase serotonin levels or effects. Initiating patients with lower doses and ensuring close clinical monitoring for signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, tremor) is advised. Particular caution is recommended when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately, and treatment rendered as indicated.