unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. thioridazine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.thiothixeneMonitor Closely (1)thiothixene increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.topiramateMonitor Closely (1)topiramate increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.tramadolMonitor Closely (2)tramadol, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s). tramadol increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.tranylcypromineContraindicated (1)tranylcypromine, lisdexamfetamine. Either increases effects of the other by serotonin levels. Contraindicated. Do not use amphetamines during and within 14 days of discontinuation of monoamine oxidase inhibitors. .trazodoneMonitor Closely (1)trazodone increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trazodone, lisdexamfetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.triazolamMonitor Closely (1)triazolam increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trifluoperazineMonitor Closely (2)trifluoperazine, lisdexamfetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. trifluoperazine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.trimipramineMonitor Closely (2)trimipramine, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s). trimipramine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine, lisdexamfetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.triprolidineMonitor Closely (1)triprolidine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.venlafaxineMonitor Closely (1)venlafaxine, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).vilazodoneMonitor Closely (1)vilazodone, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).Serious - Use Alternative (1)lisdexamfetamine, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .xylometazolineMonitor Closely (2)lisdexamfetamine and xylometazoline both decrease sedation. Use Caution/Monitor. lisdexamfetamine and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.yerba mateMinor (1)yerba mate increases effects of lisdexamfetamine by pharmacodynamic synergism. Minor/Significance Unknown.yohimbeSerious - Use Alternative (1)yohimbe, lisdexamfetamine. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.yohimbineMonitor Closely (2)lisdexamfetamine and yohimbine both decrease sedation. Use Caution/Monitor. lisdexamfetamine and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.ziconotideMonitor Closely (1)ziconotide increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziprasidoneMonitor Closely (1)ziprasidone increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zolmitriptanMonitor Closely (1)zolmitriptan and lisdexamfetamine both increase serotonin levels. Use Caution/Monitor. >10% Anorexia (27%) Insomnia (27%) Xerostomia (26%) Headache (12%) Upper abdominal pain (12%) 1-10% Irritability (10%) Problem of growth and development, weight decreased (pediatric patients, 9% ) Nausea (7%) Diarrhea (7%) Seizure (4% ) Rash (pediatric patients, 3%) Hyperhidrosis (3%) Increased blood pressure (3%) Increased heart rate (2%) Dizziness (5%) Emotional lability (3%) Tremor (2%) Tics (2%) Vomiting (9%) Frequency Not Defined Serious Chest pain, sudden death (rare), myocardial infarction, palpitations, ventricular hypertrophy Cerebrovascular accident, Gilles de la Tourette syndrome Stevens-Johnson syndrome, toxic epidermal necrolysis due to drug Postmarketing Reports Ophthalmic disorders: Blurred vision, mydriasis, diplopia, difficulties with visual accommodation Cardiovascular: Palpitations, cardiomyopathy General disorders and administration site conditions: Fatigue Hepatobiliary disorders: Eosinophilic hepatitis Immune and allergy system disorders: Anaphylactic reaction, hypersensitivity, Stevens-Johnson syndrome, angioedema, urticaria Nervous system disorders: Somnolence, seizure, dyskinesia, tics, bruxism Psychiatric disorders: Psychotic episodes, mania, hallucination, depression, aggression, dysphoria, euphoria, logorrhea, dermatillomania Genitourinary: Libido changes, frequent/prolonged erections Gastrointestinal: Constipation, dysgeusia, intestinal ischemia Musculoskeletal: Rhabdomyolysis Serotonin syndrome (when coadministered with serotonergic drugs) Dermatologic: Alopecia Black Box Warnings Dextroamphetamine has a high potential for abuse; particular attention should be paid to the possibility of patients obtaining dextroamphetamine for nontherapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly Administration of dextroamphetamine for prolonged periods of time may lead to drug dependence and must be avoidedContraindications Hypersensitivity Patient taking MAOIs or within 14 days of stopping MAOIs (including linezolid or IV methylene blue) owing to increased risk of hypertensive crisis Cautions Use with caution in hyperthyroidism, glaucoma, mild to severe hypertension, advanced arteriosclerosis, symptomatic CVD, agitated states, history of psychosis or drug abuse May cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychosis; evaluate for bipolar disorder prior to stimulant use Misuse of dextroamphetamine may cause sudden death and serious cardiovascular adverse events Monitor blood pressure and pulse; consider benefits and risks before use in patients for whom blood pressure increases may be problematic Sudden death has been reported in association with CNS stimulant treatment at recommended doses in pediatric patients with structural cardiac abnormalities or other serious heart problems; in adults, sudden death, stroke, and myocardial infarction have been reported; avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, or coronary artery disease Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation Particular care should be taken in using stimulants to treat ADHD patients with comorbid bipolar disorder because of concern for possible induction of mixed/manic episode in such patients; screen for risk factors for developing a manic episode before initiating Aggressive behavior or hostility is often observed in children and adolescents with ADHD; monitor for the appearance of or worsening of aggressive behavior or hostility Monitor growth of children ages 7 to 10 years during treatment with stimulants; may need to interrupt therapy in patients not growing or gaining weight as expected Stimulants may lower convulsive threshold in patients with prior history of seizure, patients with prior EEG abnormalities in absence of seizures, and very rarely, patients without a history of seizures and no prior EEG evidence of seizures; discontinue therapy in the presence of seizures Use with caution in patients who use other sympathomimetic drugs Amphetamines may exacerbate motor and phonic tics and Tourette’s syndrome; perform clinical evaluation for tics and Tourette’s syndrome in children and their families prior to treating with stimulant medications Interrupt drug administration occasionally to assess if recurrence of behavioral symptoms sufficient to require continued treatment Associated with peripheral vasculopathy, including Raynaud phenomenon Difficulties with accommodation and blurring of vision have been reported with stimulant treatment Use of stimulants may suppress appetite, especially in children, which may cause weight loss and slows the rate of growth Rare instances of prolonged and sometimes painful erections (priapism), sometimes requiring surgical intervention, reported with methylphenidate products; typically not reported during initiation, but often subsequent to an increase in dose; seek immediate medical attention for abnormally sustained or frequent and painful erections Serotonin syndrome Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems (eg, MAOIs, SSRIs, SNRIs, triptans, TCAs, fentanyl, lithium, tramadol, tryptophan, buspirone, St John’s Wort) Coadministration with MAOI drugs is contraindicated (see Contraindications) Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by CYP2D6 and display minor CYP2D6 inhibition Discontinue therapy with any concomitant serotonergic agents immediately if symptoms of serotonin syndrome occur, and initiate supportive symptomatic treatment; concomitant use with other serotonergic drugs or CYP2D6 inhibitors should be used only if potential benefit justifies the potential risk If clinically warranted, consider initiating therapy with lower doses, monitoring patients for emergence of serotonin syndrome during drug initiation or titration, and informing patients of increased risk for serotonin syndrome Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and researchprograms/pregnancyregistry/adhd­medications/ The limited available data from published literature and postmarketing reports on use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage; adverse pregnancy outcomes, including premature delivery and low birth weight, seen in infants born to mothers dependent on amphetamines Animal data In animal reproduction studies, lisdexamfetamine dimesylate (a prodrug of d-amphetamine) had no effects on embryo-fetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis Pre- and postnatal studies were not conducted with lisdexamfetamine dimesylate; however, amphetamine (d- to l- ratio of 3:1) administration to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of amphetamine In addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with amphetamine. Long-term neurochemical and behavioral effects have also been reported in animal developmental studies using clinically relevant doses of amphetamine Amphetamines cause vasoconstriction and thereby may decrease placental perfusion; in addition, amphetamines can stimulate uterine contractions increasing risk of premature delivery; infants born to amphetamine-dependent mothers have an increased risk of premature delivery and low birth weight Monitor infants born to mothers taking amphetamines for symptoms of withdrawal such as feeding difficulties, irritability, agitation, and excessive drowsiness Lactation Lisdexamfetamine is a prodrug of dextroamphetamine; based on limited case reports in published literature, amphetamine (d-or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5; there are no reports of adverse effects on breastfed infant; Long-term neurodevelopmental effects on infants from amphetamine exposure are unknown; it is possible that large dosages of dextroamphetamine might interfere with milk production, especially in women whose lactation is not well established Because of the potential for serious adverse reactions in nursing infants, including serious cardiovascular reactions, blood pressure and heart rate increase, suppression of growth, and peripheral vasculopathy, advise patients that breastfeeding is not recommended during treatment Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Prodrug of dextroamphetamine Sympathomimetic amine that promotes release of dopamine and norepinephrine from their storage sites in the presynaptic nerve terminals; may also block reuptake of catecholamines by competitive inhibition Absorption Rapid absorption Peak plasma time: 1 hr (lisdexamfetamine); 3.5 hr (dextroamphetamine) Distribution Vd: 3.5-4.6 L/kg; distributes into CNS Elimination Half-life elimination: 10-13 hr (dextroamphetamine); < 1hr (lisdexamphetamine) Excretion: Urine (96%), feces (minimal) Oral Administration Take in AM with or without food Avoid