rboxazid, phenelzine, tranylcypromine, linezolid, methylene blue serotonergic drugs clinical impact the concomitant use of evekeo odt 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 evekeo odt initiation or dosage increase. if serotonin syndrome occurs, discontinue evekeo odt and concomitant serotonergic drug(s) [see warnings and precautions 5.8 ] . examples selective serotonin reuptake inhibitors (ssri), serotonin norepinephrine reuptake inhibitors (snri), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, st. john's wort alkalinizing agents clinical impact may increase exposure to amphetamine and exacerbate the action of amphetamine. intervention caution should be taken when co-administering evekeo odt and gastrointestinal and urinary alkalinizing agents. examples gastrointestinal alkalinizing agents (e.g., sodium bicarbonate; proton pump inhibitors [e.g. omeprazole]) urinary alkalinizing agents (e.g. acetazolamide, some thiazides) acidifying agents clinical impact lower blood levels and efficacy of amphetamines. intervention increase dose of evekeo odt based on clinical response. examples gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid hcl, ascorbic acid) urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts) tricyclic antidepressants clinical impact may enhance the activity of tricyclic or sympathomimetic agents causing sustained increases in the concentration of d- amphetamine in the brain; cardiovascular effects can be potentiated. intervention monitor frequently and adjust evekeo odt dose or use alternative therapy based on clinical response. examples desipramine, protriptyline cyp2d6 inhibitors clinical impact the concomitant use of evekeo odt and cyp2d6 inhibitors may increase the exposure of evekeo odt 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 evekeo odt initiation and after a dosage increase. if serotonin syndrome occurs, discontinue evekeo odt and the cyp2d6 inhibitor. alternatively, consider using a drug that does not inhibit cyp2d6 [see warnings and precautions (5.8) and overdosage (10) ] . examples paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. 7.2 drug-laboratory test interactions amphetamines can cause a significant elevation in plasma corticosteroid levels. this increase is greatest in the evening. amphetamines may interfere with urinary steroid determinations.

( 5.5 ) seizures : may lower the convulsive threshold. if a seizure occurs, discontinue evekeo odt . ( 5.6 ) peripheral vasculopathy, including raynaud's phenomenon : stimulants used to treat adhd are associated with peripheral vasculopathy, including raynaud's phenomenon. careful observation for digital changes is necessary during treatment with adhd stimulants. ( 5.7 ) serotonin syndrome : increased risk when co-administered with serotonergic agents (e.g., ssris, snris, triptans), but also during overdosage situations. if it occurs, discontinue evekeo odt and initiate supportive treatment. ( 5.8 ) 5.1 potential for abuse and dependence cns stimulants, including evekeo odt, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy [see drug abuse and dependence (9.2 , 9.3) ] . 5.2 serious cardiovascular reactions sudden death, stroke, and myocardial infarction have been reported in adults with cns stimulant treatment at recommended doses. sudden death has been reported in pediatric patients with structural cardiac abnormalities and other serious heart problems taking cns stimulants at recommended doses for adhd. avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during evekeo odt treatment. 5.3 blood pressure and heart rate increases cns stimulants cause an increase in blood pressure (mean increase about 2-4 mm hg) and heart rate (mean increase about 3-6 bpm). monitor all patients for potential tachycardia and hypertension. 5.4 psychiatric adverse reactions exacerbation of pre-existing psychosis cns stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. induction of a manic episode in patients with bipolar illness cns stimulants may induce a mixed or manic episode in patients with bipolar disorder. prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or has a history of depressive symptoms or a family history of suicide, bipolar disorder, and depression). new psychotic or manic symptoms cns stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without prior history of psychotic illness or mania. if such symptoms occur, consider discontinuing evekeo odt. in a pooled analysis of multiple short-term, placebo-controlled studies of cns stimulants, psychotic or manic symptoms occurred in 0.1% of cns stimulant-treated patients compared to 0% in placebo-treated patients. 5.5 long-term suppression of growth cns stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. closely monitor growth (weight and height) in pediatric patients treated with cns stimulants, including evekeo odt. patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted [see use in specific populations (8.4) ] . 5.6 seizures there is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior eeg abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior eeg evidence of seizures. in the presence of seizures, discontinue evekeo odt. 5.7 peripheral vasculopathy, including raynaud's phenomenon stimulants, including evekeo odt, used to treat adhd are associated with peripheral vasculopathy, including raynaud's phenomenon. signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. effects of peripheral vasculopathy, including raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. signs and symptoms generally improve after reduction in dose or discontinuation of drug. careful observation for digital changes is necessary during treatment with adhd stimulants. further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. 5.8 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 such as maois, selective serotonin reuptake inhibitors (ssris), serotonin norepinephrine reuptake inhibitors (snris), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and st. john's wort [see drug interactions (7.1) ] . the co-administration with cytochrome p450 2d6 (cyp2d6) inhibitors may also increase the risk with increased exposure to evekeo odt. in these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit cyp2d6 [see drug interactions (7.1) ] . serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). concomitant use of evekeo odt with maoi drugs is contraindicated [see contraindications (4) ] . discontinue treatment with evekeo odt and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. if concomitant use of evekeo odt with other serotonergic drugs or cyp2d6 inhibitors is clinically warranted, initiate evekeo odt with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

and dependence while on therapy. maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically re-evaluate the need for evekeo odt use [see warnings and precautions (5.1) , and drug abuse and dependence (9) ] . 2.2 dosage information administer evekeo odt orally in the morning with or without food or liquid. the recommended starting dosage for pediatric patients 6 to 17 years of age is 5 mg once or twice daily. if necessary, administer an additional dose after 4 to 6 hours. titrate the dosage in increments of 5 mg at weekly intervals depending on response and tolerability. only in rare cases will it be necessary to exceed a total of 40 mg daily. where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy. amphetamine should be administered at the lowest effective dosage and dosage should be individually adjusted. 2.3 administration instructions instruct the patient or caregiver on the following administration instructions: do not remove the tablet from the blister pack until just prior to dosing. do not store the tablet for future use. use dry hands to open the blister. remove the tablet by pushing it through the back of the foil-lined blister pack. as soon as the blister is opened, remove the tablet and place the tablet on the patient's tongue. place the whole tablet on the tongue and allow it to disintegrate without chewing or crushing. the tablet will disintegrate in saliva so that it can be swallowed. no liquid is needed to take the tablet. the tablet can be actively moved around between the tongue and the roof of the mouth until it disintegrates. 2.4 switching from other amphetamine products switching from evekeo to evekeo odt can be done on a milligram-per-milligram basis. when switching from other amphetamine products, discontinue treatment and titrate with evekeo odt using the titration schedule above. do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine salt compositions and differing pharmacokinetic profiles [see description (11) , clinical pharmacology (12.3) ]. 2.5 dosage modifications due to drug interactions agents that alter urinary ph can impact urinary excretion and alter blood levels of amphetamine. acidifying agents (e.g., ascorbic acid) decrease blood levels, while alkalinizing agents (e.g., sodium bicarbonate) increase blood levels. adjust evekeo odt dosage accordingly [see drug interactions (7.1) ] .

�4% and at a rate at least twice placebo) in pediatric patients are: decreased appetite and insomnia. ( 6 ) to report suspected adverse reactions, contact arbor pharmaceuticals, llc at 1-800-461-7449 or fda at 1-800-fda-1088 or www.fda.gov/medwatch . 6.1 clinical trials experience because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. study 1 was conducted with evekeo tablets (i.e., not the odt formulation) in children ages 6 to 12 years who met diagnostic and statistical manual of mental disorders, 4 th edition, text revision (dsm-iv-tr) criteria for adhd. this study began with an 8-week, open-label, dose-optimization phase followed by a 2-week double-blind, placebo-controlled, randomized, crossover phase. adverse reactions reported in > 5% of patients (n=105; doses of 10 to 40 mg/day) during the open-label phase included: decreased appetite (28%), infections (22%), abdominal pain (15%), irritability (14%), headache (13%), nausea (6%), vomiting (6%), affect lability (includes mood swings; 9%), tachycardia (9%), insomnia (10%), fatigue (10%),and dry mouth (6%). during the open-label phase, six patients discontinued due to adverse reactions: irritability (n=3), affect lability (n=1), initial insomnia (n=1), and rash (n=1). table 1 lists the adverse reactions reported during the double-blind, cross-over phase. no patient discontinued the study for an adverse reaction during the double-blind crossover phase. because of the trial design (an initial 8-week, open-label, active treatment phase), the adverse reaction rates described in the double-blind phase are lower than expected in clinical practice. table 1: adverse reactions reported in ≥ 2%, and > placebo, of evekeo-treated pediatric patients (6 to 12 years) during the double-blind cross-over weeks. drug exposures and placebo exposures from cross-over were combined for analysis. system organ class preferred term evekeo (n= 97) placebo (n= 97) subjects with at least one adverse event 22% 14% metabolism and nutrition disorders decreased appetite 4% 0% gastrointestinal disorders abdominal pain 3% 0% psychiatric disorders affect lability includes mood swings. 3% 0% insomnia 4% 0% injury, poisoning and procedural complications injury 3% 2% 6.2 postmarketing experience the following adverse reactions have been associated during post approval use of amphetamines. because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. cardiovascular: palpitations, tachycardia, elevation of blood pressure, sudden death, myocardial infarction. there have been isolated reports of cardiomyopathy associated with chronic amphetamine use. central nervous system: psychotic episodes at recommended doses, overstimulation, irritability, restlessness, dizziness, insomnia, euphoria, mood swings, aggression, anger, logorrhea, dermatillomania, dyskinesia, dysphoria, tremor, fatigue, headache, exacerbation of motor and phonic tics and tourette's syndrome gastrointestinal: dry mouth, unpleasant taste, constipation, nausea, intestinal ischemia, other gastrointestinal disturbances, anorexia, and weight loss. allergic: urticaria, rash, hypersensitivity reactions, including angioedema and anaphylaxis. serious skin rashes, including stevens-johnson syndrome and toxic epidermal necrolysis have been reported. endocrine: impotence, changes in libido, and frequent or prolonged erections. skin : alopecia. vascular disorders : raynaud's phenomenon. musculoskeletal: rhabdomyolysis.

rboxazid, phenelzine, tranylcypromine, linezolid, methylene blue serotonergic drugs clinical impact the concomitant use of evekeo odt 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 evekeo odt initiation or dosage increase. if serotonin syndrome occurs, discontinue evekeo odt and concomitant serotonergic drug(s) [see warnings and precautions 5.8 ] . examples selective serotonin reuptake inhibitors (ssri), serotonin norepinephrine reuptake inhibitors (snri), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, st. john's wort alkalinizing agents clinical impact may increase exposure to amphetamine and exacerbate the action of amphetamine. intervention caution should be taken when co-administering evekeo odt and gastrointestinal and urinary alkalinizing agents. examples gastrointestinal alkalinizing agents (e.g., sodium bicarbonate; proton pump inhibitors [e.g. omeprazole]) urinary alkalinizing agents (e.g. acetazolamide, some thiazides) acidifying agents clinical impact lower blood levels and efficacy of amphetamines. intervention increase dose of evekeo odt based on clinical response. examples gastrointestinal acidifying agents (e.g., guanethidine, reserpine, glutamic acid hcl, ascorbic acid) urinary acidifying agents (e.g., ammonium chloride, sodium acid phosphate, methenamine salts) tricyclic antidepressants clinical impact may enhance the activity of tricyclic or sympathomimetic agents causing sustained increases in the concentration of d- amphetamine in the brain; cardiovascular effects can be potentiated. intervention monitor frequently and adjust evekeo odt dose or use alternative therapy based on clinical response. examples desipramine, protriptyline cyp2d6 inhibitors clinical impact the concomitant use of evekeo odt and cyp2d6 inhibitors may increase the exposure of evekeo odt 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 evekeo odt initiation and after a dosage increase. if serotonin syndrome occurs, discontinue evekeo odt and the cyp2d6 inhibitor. alternatively, consider using a drug that does not inhibit cyp2d6 [see warnings and precautions (5.8) and overdosage (10) ] . examples paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir. 7.2 drug-laboratory test interactions amphetamines can cause a significant elevation in plasma corticosteroid levels. this increase is greatest in the evening. amphetamines may interfere with urinary steroid determinations.

hetamine sulfate has been shown to have embryotoxic effects when administered to a/jax mice and c57bl mice in doses approximately 6 times the maximum human dose. embryotoxic effects were not seen in new zealand white rabbits. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions amphetamines, such as evekeo odt, cause vasoconstriction and thereby decrease placental perfusion. in addition, amphetamines can stimulate uterine contractions, increasing the risk of premature delivery. infants born to mothers taking amphetamines during pregnancy 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. 8.2 lactation risk summary based on limited case reports in published literature, amphetamine ( d- or dl ) 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 the breastfed infant. long-term neurodevelopmental effects on infants from amphetamine exposure are unknown. it is possible that large dosages of amphetamine 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, advise patients that breast feeding is not recommended during treatment with evekeo odt. 8.4 pediatric use the safety and effectiveness of evekeo odt have been established in pediatric patients 6 years and older. use of evekeo odt is based on one adequate and well-controlled study with another immediate-release amphetamine sulfate product (evekeo) in pediatric patients 6 to 12 years [see clinical studies (14) ], along with dosing and safety information for other amphetamine products. safety and efficacy in pediatric patients below the age of 6 years have not been established. long-term growth suppression growth should be monitored during treatment with stimulants, including evekeo odt. pediatric patients aged 6 to 17 years who are not growing or gaining weight as expected may need to have their treatment interrupted [see warnings and precautions (5.5) , adverse reactions (6.1) ] . 8.5 geriatric use evekeo odt has not been studied in patients over the age of 65 years.

ximately 6 times the maximum human dose. embryotoxic effects were not seen in new zealand white rabbits. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations fetal/neonatal adverse reactions amphetamines, such as evekeo odt, cause vasoconstriction and thereby decrease placental perfusion. in addition, amphetamines can stimulate uterine contractions, increasing the risk of premature delivery. infants born to mothers taking amphetamines during pregnancy 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.

of immediate-release amphetamine sulfate tablets (evekeo) tablets swallowed intact with water. median (range) t max of d- and l- amphetamine was reached at approximately 3.5 (2-8) hours and 3.0 (1 -6) hours after administration without water and with water, respectively. effect of food administration of food (a high fat meal) does not affect the observed auc and c max of d- and l- amphetamine after single-dose oral administration of evekeo odt (20 mg) in healthy adults who allowed the tablet to be disintegrated/dissolved in their oral cavity prior to swallowing without water. median (range) t max increased from 2.5 (1.5 – 6) hours to 4.5 (2.5 – 8.0) hours when administration without compared to with food. elimination amphetamine undergoes both hepatic and renal elimination. the plasma elimination half-life of d- and l- amphetamine averaged 10.0 and about 11.7 hours in healthy adult volunteers. metabolism amphetamine d- and l- enantiomers are highly metabolized largely by two primary oxidative pathways, one via cyp2d6 to produce active metabolite 4-hydroxyamphetamine, and the other by oxidative deamination. cyp2d6 is one of several enzymes involved in the biotransformation of amphetamine. excretion amphetamine is renally eliminated in a ph-dependent manner. the renal excretion rate of unchanged amphetamine at a urine ph of 6.6 averages 70% versus 17% - 43% at urine ph of >6.7.

.5 – 6) hours to 4.5 (2.5 – 8.0) hours when administration without compared to with food. elimination amphetamine undergoes both hepatic and renal elimination. the plasma elimination half-life of d- and l- amphetamine averaged 10.0 and about 11.7 hours in healthy adult volunteers. metabolism amphetamine d- and l- enantiomers are highly metabolized largely by two primary oxidative pathways, one via cyp2d6 to produce active metabolite 4-hydroxyamphetamine, and the other by oxidative deamination. cyp2d6 is one of several enzymes involved in the biotransformation of amphetamine. excretion amphetamine is renally eliminated in a ph-dependent manner. the renal excretion rate of unchanged amphetamine at a urine ph of 6.6 averages 70% versus 17% - 43% at urine ph of >6.7.

, in rodents. the significance of these findings to humans is unknown.

. the primary efficacy outcome assessed by the skamp-combined score at 2 hours postdose was statistically significantly better in evekeo treatment compared to placebo (table 3). key secondary efficacy endpoints were the time-to-onset and duration-of-effect of evekeo using skamp-combined scores. skamp-combined scores were statistically significantly better for patients in the evekeo treatment group compared to patients in the placebo treatment group beginning at 0.75 hours post-dose and at each assessment through 10 hours post-dose. (figure 1). table 3: summary of primary efficacy results in pediatric patients (6 to 12 years) with adhd (study 1) study number treatment group primary efficacy measure: skamp-combined score at 2 hours post-dose mean pre-dose score (sd) ls mean (se) at 2 hours post-dose placebo-subtracted difference difference (drug minus placebo) in least-squares mean. (95% ci) sd: standard deviation; se: standard error; ls mean: least-squares mean; ci: confidence interval. study 1 evekeo 18.1 (11.6) 10.3 (1.09) -7.9 (-10.1, -5.6) placebo 15.3 (11.4) 18.1 (1.09) -- figure 1: ls mean skamp-combined scores by treatment and timepoint for pediatric patients (6 to 12 years) with adhd after 1 week of double blind treatment (study 1) the values at pre-dose hour (zero) are observed means. figure 1

the other ndc 24338-037-15: one blister card of 15-count 20 mg strength tablets within a plastic sleeve ndc 24338-037-02: carton containing two 15-count plastic sleeves store at 20°c to 25°c (68°f to 77°f); excursions permitted to 15°c -30°c (59°f to 86°f) [see usp controlled room temperature]. store evekeo odt blister packages in the provided plastic sleeve. disposal comply with local laws and regulations on drug disposal of cns stimulants. dispose of remaining, unused, or expired evekeo odt at authorized collection sites such as retail pharmacies, hospital or clinic pharmacies, and law enforcement locations. if no take-back program or authorized collector is available, mix evekeo odt with an undesirable, nontoxic substance to make it less appealing to children and pets. place the mixture in a container such as a sealed plastic bag and discard evekeo odt in the household trash.

d blister packaging. as soon as the blister is opened, place the tablet on the patient's tongue. the whole tablet should be placed on the tongue and allowed to disintegrate without chewing or crushing. the tablet will disintegrate in saliva so that it can be swallowed. serious cardiovascular risks advise patients, caregivers, and family members that there is a potential serious cardiovascular risk (including sudden death, myocardial infarction, stroke, and hypertension) with evekeo odt. instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see warnings and precautions (5.2) ] . blood pressure and heart rate increases instruct patients and their caregivers that evekeo odt can cause elevations of their blood pressure and pulse rate and that patients should be monitored for such effects [see warnings and precautions (5.3) ] . psychiatric risks advise patients and their caregivers that evekeo odt, at recommended doses, may cause psychotic symptoms or mania even in patients without prior history of psychotic symptoms or mania [see warnings and precautions (5.4) ] . long-term suppression of growth advise patients, family members, and caregivers that evekeo odt may cause slowing of growth including weight loss [see warnings and precautions (5.5) ] . circulation problems in fingers and toes [peripheral vasculopathy, including raynaud's phenomenon] instruct patients and their caregivers beginning treatment with evekeo odt about the risk of peripheral vasculopathy, including raynaud's phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change from pale, to blue, to red. instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking evekeo odt. further clinical evaluation (e.g. rheumatology referral) may be appropriate for certain patients [see warnings and precautions (5.7) ] . serotonin syndrome caution patients and their caregivers about the risk of serotonin syndrome with concomitant use of evekeo odt and other serotonergic drugs including ssris, snris, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, st. john's wort, and with drugs that impair metabolism of serotonin (in particular maois, both those intended to treat psychiatric disorders and also others such as linezolid [see contraindications (4) , warnings and precautions (5.8) and drug interactions (7.1) ]. advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome. concomitant medications advise patients and their caregivers to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions [see drug interactions (7.1) ] . pregnancy registry advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to evekeo odt during pregnancy [see use in specific populations (8.1) ]. pregnancy advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with evekeo odt [see use in specific populations (8.1) ] . advise patients of the potential fetal effects from the use of evekeo odt during pregnancy [see use in specific populations (8.1) ]. lactation advise patients not to breastfeed if they are taking evekeo odt [see use in specific populations (8.2) ] .