4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens that may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically significant for ADD/ADHD medications are summarized in Table 7. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level* |
|---|---|---|---|---|
| amphetamines, amphetamine-related compounds, dexmethylphenidate, methylphenidate, serdexmethylphenidate | antihypertensive agents | combined administration decreases hypotensive effect of antihypertensive agents | closely monitor blood pressure and adjust antihypertensive therapy doses as necessary | 2- major (CP) |
| amphetamines, amphetamine-related compounds | CYP2D6 Inhibitors | co-administration results in increased exposure to amphetamine and amphetamine related compounds | initiate at lower doses and monitor for signs and symptoms of serotonin syndrome, particularly after initiation and after dose increases. If serotonin syndrome occurs discontinue amphetamine or amphetamine related compound and CYP2D6 inhibitor | 3- moderate (CP) major-(Micromedex) |
| amphetamines, amphetamine-related compounds, dexmethylphenidate, methylphenidate, serdexmethylphenidate | monoamine oxidase inhibitors (MAOIs) and drugs with MAOI-like actions (e.g., procarbazine) | combined administration increases risk of enhanced vasopressor effects and hypertensive crisis due to increased norepinephrine availability; amphetamines, dexmethyl-phenidate, and methylphenidate potentiate catecholamine neurotransmitter effects, while MAOIS block catecholamine degradation and increase norepinephrine levels at nerve receptor sites | concurrent administration as well as amphetamine, dexmethyl-phenidate, methylphenidate, or serdexmethylphenidate administration within 14 days of MAOI use is contraindicated | contraindicated (DrugReax) 1-severe (CP) |
| amphetamines, amphetamine-related compounds | phenothiazines | co-administration results in decreased effectiveness of both drug classes | avoid combination, if possible | 2-major (CP) major (DrugReax) |
| amphetamines, amphetamine-related compounds | SSRIs, SNRIs | combined administration may produce additive pharmacologic effects and increase risk of serotonin syndrome as amphetamines may stimulate serotonin release in central nervous system (CNS) | administer cautiously together and observe for signs/ symptoms of serotonin syndrome; discontinue therapy and treat as necessary if serotonin syndrome develops | major (DrugReax) 2-major (CP) |
| amphetamines, amphetamine-related compounds | TCAs | adjunctive administration may potentiate amphetamine pharmacologic/ adverse effects including hypertension, other cardiac effects, and CNS stimulation due to additive effects on norepinephrine release/activity | administer combination cautiously; observe for increased adverse effects | moderate (DrugReax) 2-major (CP) |
| amphetamines, amphetamine-related compounds | urinary alkalinizers | combination results in increased renal tubular absorption of amphetamines and amphetamine-related compounds, decreased urinary excretion and the potential for enhanced amphetamine therapeutic/ adverse effects | combination should be avoided | 2-major (CP) moderate (DrugReax) |
| atomoxetine | albuterol | combined administration may produce increased heart rate, blood pressure due to unknown mechanism | administer combination cautiously; monitor blood pressure and heart rate | major (DrugReax) 3-moderate (CP) |
| atomoxetine | MAOIs | co-administration may result in additive serotonergic effects/ increased risk of serotonin syndrome as atomoxetine inhibits serotonin reuptake and MAOIs inhibit catecholamine breakdown | concomitant administration as well as atomoxetine administration within 14 days of MAOI use contraindicated | contraindicated (DrugReax) 1-severe (CP) |
| clonidine | mirtazapine | co-administration may result in hypertension | monitor for signs of intense sweating, facial flushing, frequent headaches, racing, or pounding heartbeat | major (DrugReax) |
| clonidine | beta blockers | co-administration may result in sinus bradycardia & exaggerated clonidine withdrawal response | monitor heart rate when combined with beta blocker therapy. Gradual withdrawal of beta blocker recommended before discontinuing clonidine | major (DrugReax) |
| clonidine | calcium channel blockers | co-administration may result in sinus bradycardia | monitor heart rate when combined with calcium channel blocker therapy | major (DrugReax) |
| dexmethylphenidate, methylphenidate, serdexmethylphenidate | risperidone | concomitant administration may increase risk of extrapyramidal symptoms during doses changes of either medication | monitor for signs of extrapyramidal symptoms | major (Micromedex) |
| dexmethylphenidate, methylphenidate, serdexmethylphenidate | halogenated anesthetics | Concomitant use may increase risk of sudden blood pressure and heart rate increases during surgery | Avoid use in patients being treated with anesthetics on the day of surgery | major (Micromedex) |
| dexmethylphenidate, methylphenidate, serdexmethylphenidate | select anticonvulsants [e.g., phenobarbital, hydantoins (e.g., phenytoin) and primidone] | adjunctive administration may increase serum anticonvulsant levels of select anticonvulsants due to unknown mechanism; dexmethylphenidate, methylphenidate may also lower seizure threshold | monitor serum anticonvulsant levels closely and monitor patients for increased adverse effects; adjust anticonvulsant doses as needed; also monitor seizure frequency | moderate (DrugReax) 2-major, 3-moderate (CP) |
| dexmethylphenidate, methylphenidate, serdexmethylphenidate | warfarin | co-administration may increase warfarin serum levels and enhance pharmacologic/adverse effects, including bleeding | closely monitor INR with combined therapy and adjust warfarin doses as necessary | moderate (DrugReax) 3-moderate (CP) |
| guanfacine | antihypertensive agents | combined administration may result in additive hypotensive effects | closely monitor blood pressure and adjust doses as necessary | 3-moderate (CP) |
| guanfacine | CNS depressants | combined administration may result in additive pharmacologic (sedative) effects | administer cautiously together | 3-moderate (CP) |
| guanfacine | strong CYP3A4 inhibitors (e.g., ketoconazole) | adjunctive administration may result in increased guanfacine concentrations and the potential for enhanced pharmacologic/ adverse effects as guanfacine is metabolized by CYP3A4 | administer cautiously together and monitor for increased pharmacologic effects (e.g., hypotension, bradycardia, sedation) | unknown |
| guanfacine | CYP3A4 inducers (e.g., rifampin, phenytoin) | concurrent administration reduces guanfacine AUC by 70% and may result in decreased guanfacine serum levels and reduced pharmacologic/clinical effects (guanfacine metabolized by CYP3A4) | monitor for loss of guanfacine clinical effects; increased guanfacine doses may be necessary | 3-moderate (CP) |
| guanfacine | valproic acid (VA) | combined administration may result in increased VA serum levels, potentially due to competition for glucuronidation metabolic pathway | monitor for additive CNS effects; VA dosage adjustments may be required | unknown |
| methylphenidate | bupropion | concurrent use may result in increased seizure risk | if combination is necessary, closely monitor patient | major (DrugReax) 2-major (CP) |
| methylphenidate | carbamazepine | co-administration may result in reduced methylphenidate serum levels and decreased pharmacologic effects due to unknown mechanism; methylphenidate may also lower seizure threshold | closely monitor patient response to methylphenidate therapy, monitor seizure frequency, and adjust methylphenidate doses as necessary with this drug combination | moderate (DrugReax) 2-major (CP) |
| viloxazine | CYP1A2 substrates, sensitive or narrow therapeutic range | viloxazine is a strong CYP1A2 inhibitor, increasing total exposure to sensitive CYP1A2 substrates | concurrent use is contraindicated | contraindicated (Micromedex) |
| viloxazine | CYP1A2 substrates, moderate sensitive | viloxazine is a strong CYP1A2 inhibitor, increasing total exposure to sensitive CYP1A2 substrates | concurrent administration is not recommended. Dose reduction may be warranted if coadministered | major (Micromedex) |
| viloxazine | MAOI | increased risk of potentially life-threatening hypertensive crisis | concurrent administration is contraindicated | contraindicated (Micromedex) |
Legend:
- * CP = Clinical Pharmacology, Micromedex, product labeling