Lisdexamfetamine Interactions

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust lisdexamfetamine dimesylate capsules dosage accordingly ( 2.6 , 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 5 Drugs having clinically important interactions with amphetamines. MAO Inhibitors (MAOI) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Intervention Do not administer lisdexamfetamine dimesylate capsules during or within 14 days following the administration of MAOI [see Contraindications (4) ] . Serotonergic Drugs Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during lisdexamfetamine dimesylate capsules initiation or dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the concomitant serotonergic drug(s) [see Warnings and Precautions (5.7) ] . CYP2D6 Inhibitors Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate capsules compared to the use of the drug alone and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during lisdexamfetamine dimesylate capsules initiation and after a dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10) ] . Alkalinizing Agents Clinical Impact Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of lisdexamfetamine dimesylate capsules and urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. 7.2 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate Capsules From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate capsules is necessary when lisdexamfetamine dimesylate capsules is co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when lisdexamfetamine dimesylate capsules is co-administered [see Clinical Pharmacology (12.3) ] . From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when VYVANSE is co-administered [see Clinical Pharmacology (12.3) ] .

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust lisdexamfetamine dimesylate capsules dosage accordingly. ( 2.6 , 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 5 Drugs having clinically important interactions with amphetamines. MAO Inhibitors (MAOI) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Intervention Do not administer lisdexamfetamine dimesylate capsules during or within 14 days following the administration of MAOI [see Contraindications (4) ] . Serotonergic Drugs Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during lisdexamfetamine dimesylate capsules initiation or dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the concomitant serotonergic drug(s) [see Warnings and Precautions (5.7) ] . CYP2D6 Inhibitors Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate capsules, compared to the use of the drug alone and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during lisdexamfetamine dimesylate capsules initiation and after a dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10) ] . Alkalinizing Agents Clinical Impact Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of lisdexamfetamine dimesylate capsules and urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. 7.2 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate Capsules From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate capsules is necessary when lisdexamfetamine dimesylate capsules are co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when lisdexamfetamine dimesylate capsules are co-administered [see Clinical Pharmacology (12.3) ] . From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate capsules are co-administered [see Clinical Pharmacology (12.3) ] .

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust lisdexamfetamine dimesylate capsules dosage accordingly. ( 2.6 , 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 5 Drugs having clinically important interactions with amphetamines. MAO Inhibitors (MAOI) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Intervention Do not administer lisdexamfetamine dimesylate capsules during or within 14 days following the administration of MAOI [see Contraindications (4) ] . Serotonergic Drugs Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during lisdexamfetamine dimesylate capsules initiation or dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the concomitant serotonergic drug(s) [see Warnings and Precautions (5.7) ] . CYP2D6 Inhibitors Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate capsules, compared to the use of the drug alone and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during lisdexamfetamine dimesylate capsules initiation and after a dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10) ] . Alkalinizing Agents Clinical Impact Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of lisdexamfetamine dimesylate capsules and urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. 7.2 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate Capsules From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate capsules is necessary when lisdexamfetamine dimesylate capsules are co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when lisdexamfetamine dimesylate capsules are co-administered [see Clinical Pharmacology (12.3) ] . From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate capsules are co-administered [see Clinical Pharmacology (12.3) ] .

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust lisdexamfetamine dimesylate capsules dosage accordingly. ( 2.6 , 7.1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 5: Drugs having clinically important interactions with amphetamines. MAO Inhibitors (MAOI) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Intervention Do not administer lisdexamfetamine dimesylate capsules during or within 14 days following the administration of MAOI [see Contraindications ( 4 )] . Serotonergic Drugs Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during lisdexamfetamine dimesylate capsules initiation or dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the concomitant serotonergic drug(s) [see Warnings and Precautions ( 5.7 )] . CYP2D6 Inhibitors Clinical Impact The concomitant use of lisdexamfetamine dimesylate capsules and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate capsules compared to the use of the drug alone and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during lisdexamfetamine dimesylate capsules initiation and after a dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate capsules and the CYP2D6 inhibitor [see Warnings and Precautions ( 5.7 ) and Overdosage ( 10 )] . Alkalinizing Agents Clinical Impact Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of lisdexamfetamine dimesylate capsules and urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. 7.2 Interference with Laboratory Test Allow for an adequate washout period between administration of lisdexamfetamine dimesylate capsules and radioactive diagnostic agents used for dopamine transporter (DAT) visualization. Lisdexamfetamine dimesylate capsules can interfere with the test results of a radioactive diagnostic agent (ioflupane I-123) that is used for DAT visualization by binding and internalization of the DAT, which may result in lower DAT in the striatum. This may lead to false-positive diagnostic results.

7 DRUG INTERACTIONS Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of amphetamine. Acidifying agents decrease amphetamine blood levels, while alkalinizing agents increase amphetamine blood levels. Adjust lisdexamfetamine dimesylate dosage accordingly. ( 2.6 , 7 .1 ) 7.1 Drugs Having Clinically Important Interactions with Amphetamines Table 5: Drugs having clinically important interactions with amphetamines. MAO Inhibitors (MAOI) Clinical Impact MAOI antidepressants slow amphetamine metabolism, increasing amphetamines effect on the release of norepinephrine and other monoamines from adrenergic nerve endings causing headaches and other signs of hypertensive crisis. Toxic neurological effects and malignant hyperpyrexia can occur, sometimes with fatal results. Intervention Do not administer lisdexamfetamine dimesylate during or within 14 days following the administration of MAOI [see Contraindications (4) ] . Serotonergic Drugs Clinical Impact The concomitant use of lisdexamfetamine dimesylate and serotonergic drugs increases the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during lisdexamfetamine dimesylate initiation or dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate and the concomitant serotonergic drug(s) [see Warnings and Precautions (5.7) ] . CYP2D6 Inhibitors Clinical Impact The concomitant use of lisdexamfetamine dimesylate and CYP2D6 inhibitors may increase the exposure of dextroamphetamine, the active metabolite of lisdexamfetamine dimesylate compared to the use of the drug alone and increase the risk of serotonin syndrome. Intervention Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during lisdexamfetamine dimesylate initiation and after a dosage increase. If serotonin syndrome occurs, discontinue lisdexamfetamine dimesylate and the CYP2D6 inhibitor [see Warnings and Precautions (5.7) and Overdosage (10 )] . Alkalinizing Agents Clinical Impact Urinary alkalinizing agents can increase blood levels and potentiate the action of amphetamine. Intervention Co-administration of lisdexamfetamine dimesylate and urinary alkalinizing agents should be avoided. Acidifying Agents Clinical Impact Urinary acidifying agents can lower blood levels and efficacy of amphetamines. Intervention Increase dose based on clinical response. Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. Intervention Monitor frequently and adjust or use alternative therapy based on clinical response. 7.2 Drugs Having No Clinically Important Interactions with Lisdexamfetamine Dimesylate From a pharmacokinetic perspective, no dose adjustment of lisdexamfetamine dimesylate is necessary when lisdexamfetamine dimesylate is co-administered with guanfacine, venlafaxine, or omeprazole. In addition, no dose adjustment of guanfacine or venlafaxine is needed when lisdexamfetamine dimesylate is co-administered [see Clinical Pharmacology (12.3) ] . From a pharmacokinetic perspective, no dose adjustment for drugs that are substrates of CYP1A2 (e.g., theophylline, duloxetine, melatonin), CYP2D6 (e.g., atomoxetine, desipramine, venlafaxine), CYP2C19 (e.g., omeprazole, lansoprazole, clobazam), and CYP3A4 (e.g., midazolam, pimozide, simvastatin) is necessary when lisdexamfetamine dimesylate is co-administered [see Clinical Pharmacology (12.3) ] .