Pediatric Attention Deficit Hyperactivity Disorder (ADHD) Medication

Updated: Apr 24, 2017
  • Author: Maggie A Wilkes, MD; Chief Editor: Caroly Pataki, MD  more...
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Medication

Medication SummaryPediatric dosing of stimulant medicationsDose conversionsCategories of medications

The 2 major components in the medical care of children with attention deficit hyperactivity disorder (ADHD), previously termed attention deficit disorder (ADD), are behavioral and pharmaceutical therapies. The behavioral component is covered in the Treatment section.

Dosing of stimulant medications vary among ADHD (ADD) centers throughout the medical community in the United States. The table below is derived from the stimulant trial protocol of The Affinity Center, Inc, a center for the evaluation and treatment of ADHD (ADD) and mood disorders in Cincinnati, Ohio.

Table 1. Pediatric Dosing of Stimulant Medications (Open Table in a new window)

Medication Initial Pediatric Dose Pediatric Dosage Range and Maximum Dose* Common Pediatric Dose* Preparations
Methylphenidate immediate release (IR) (Ritalin, Methylin, generic) 2.5-5 mg 0.1-0.8 mg/kg/dose PO qd to 5 times/d; not to exceed 60 mg/d 0.3-0.5 mg/kg/dose PO tid/qid All preparations available as 5-mg, 10-mg, or 20-mg scored tabs; Methylin also available as 2.5-mg, 5-mg, or 10-mg chewable tab and PO solution (5 mg/5 mL and 10 mg/mL)
Methylphenidate sustained-release (SR) (Ritalin LA, Metadate CD) Convert from IR or use 10 mg. 0.2-1.4 mg/kg/dose PO qd/tid; not to exceed 60 mg/d 0.6-1 mg/kg/dose PO qd/bid 10-mg, 20-mg, 30-mg, or 40-mg tabs (Metadate also has 50-mg and 60-mg tabs.); can be sprinkled into soft food (Do not cut, crush, or chew.)
Methylphenidate extended release (ER)‡ (Ritalin SR, Methylin ER, Metadate ER, Quillivant XR, generic SR) Convert from IR



May initiate treatment with Quillivant XR



0.2-1.4 mg/kg/dose PO qd/tid; not to exceed 60 mg/d



Quillivant XR: Once daily dosing



0.6-1 mg/kg/dose PO qd/bid 20-mg Spansules (Do not cut, crush, or chew)



Quillivant XR 5 mg/mL suspension



Methylphenidate OROS tablets (Concerta) Convert from IR or use 18 mg. 0.3-2 mg/kg PO qd; not to exceed 54 mg/d 0.8-1.6 mg/kg PO qd 18-mg, 27-mg, 36-mg, and 54-mg tabs (Do not cut, crush, or chew.)
Methylphenidate transdermal patch (Daytrana) Convert from IR or use 10 mg (12.5 cm2 patch) released over 9 h and titrate up prn. 0.3-2 mg/kg released over 9 h; not to exceed one 30-mg patch 10-30 mg released over 9 h 10-mg, 15-mg, 20-mg, 30-mg patches, applied to the hip
Dexmethylphenidate IR (Focalin) 2.5-5-mg 0.1-0.5 mg/kg/dose PO qd to qid; not to exceed 20 mg/d 0.2-0.3 mg/kg/dose PO bid/tid 2.5-mg, 5-mg, or 10-mg scored tabs (Do not cut, crush, or chew.)
Dexmethylphenidate extended release (Focalin-XR) 5-10-mg 0.2-1 mg/kg/dose PO qd to bid; not to exceed 20 mg/d 0.4-0.6 mg/kg/dose PO qd/bid 5-mg, 10-mg, or 20-mg scored tabs; can be sprinkled into soft food (Do not cut, crush, or chew.)
Dextroamphetamine (Dexedrine, Dextrostat) 2.5-5 mg 0.1-0.7 mg/kg/dose PO qd/qid; not to exceed 60 mg/d 0.3-0.5 mg/kg/dose PO qd/tid Dexedrine: 5-mg scored tabs; Dextrostat: 5-mg and 10-mg scored tabs
Dextroamphetamine Spansules (Dexedrine CR) 5 mg 0.1-0.75 mg/kg/dose PO qd/bid; not to exceed 60 mg/d 0.3-0.6 mg/kg/dose PO qd/bid 5-mg, 10-mg, or 15-mg Spansules; can be sprinkled into soft food (Do not cut, crush, or chew.)
Mixed amphetamine salts IR (Adderall, generic) 2.5-5 mg 0.1-0.7 mg/kg/dose PO qd/qid; not to exceed 40 mg/d 0.3-0.5 mg/kg/dose PO tid/qid 5-mg, 7.5-mg, 10-mg, 12.5-mg, 15-mg, 20-mg, or 30-mg scored tabs
Mixed amphetamine salt XR (Adderall-XR) Convert from IR or use 5-10 mg 0.2-1.4 mg/kg/dose PO qd/tid



Not to exceed 30 mg/d



0.6-1 mg/kg/dose PO qd/bid 5-mg, 10-mg, 15-mg, 20-mg, 25-mg, or 30-mg Spansules; can be sprinkled into soft food (Do not cut, crush, or chew.)
Lisdexamfetamine (Vyvanse) 30 mg PO qam 30-70 mg PO qam Data limited 20-mg, 30-mg, 40-mg, 50-mg, 60-mg, or 70-mg caps (Swallow cap whole, sprinkle into soft food, or dissolve contents in glass of water and drink immediately.)Risk of apnea in patients with chronic pulmonary disease; closely monitor these patients, when initiating and titrating therapy; alternatively, consider the use of alternative non-opioid analgesics in these patients (see Black Box Warnings and Contraindications)
Amphetamine (Evekeo, Dyanavel XR), Adzenys XR-ODT Evekeo: 2.5 mg PO BID/TID



 



Dyanavel XR: 2.5-5 mg PO once daily



 



Adzenys XR-ODT: 6.3 mg PO qAM



Evekeo: 2.5 mg BID/TID; only in rare cases is it necessary to exceed 40 mg/day



 



Dyanavel XR: 2.5-5 mg/day; not to exceed 20 mg/day



 



Adzenys XR-ODT: Not to exceed 18.8 mg/day (aged 6-12 y) or 12.5 mg/day (aged 13-17 y)



Data limited Evekeo: 5-mg, 10-mg tablets



 



Dyanavel XR: 2.5-mg/mL extended-release oral suspension (do not substitute oral suspension for other amphetamine products on a milligram-per-milligram basis)



 



Adzenys XR-ODT: 3.1-mg, 6.3-mg, 9.4-mg, 12.5-mg, 15.7-mg, 18.8-mg extended-release oral disintegrating tablets



Note. In general, when the terms methylphenidate, Dexedrine, and Ritalin are used without abbreviations for extended-release preparations (eg, continuous release [CR], SR, osmotic-release oral system [OROS]), a short-acting, IR preparation is implied.



* Maximum pediatric dose suggested by the US Food and Drug Administration (FDA). Although some children benefit greatly from doses greater than these, benefit from use of either the lowest and highest ends of the dose range is uncommon.



†The methylphenidate patch contains a different total methylphenidate dose than the name implies because it is designed to last 12 hours (eg, 10-mg patch [patch size 12.5 cm2] delivers about 10 mg over 9 h [estimated delivery rate is 1.1 mg/h for this particular patch]). Delivery rate varies depending on patch size.



‡Many patients describe their experience with methylphenidate SR preparations as erratic and uncomfortable.



Conversions for psychostimulants are always approximations, especially when one is converting between stimulants, such as methylphenidate and dextroamphetamine. Different forms of the same drug have slightly different pharmacokinetics, and patients often have different responses to them. FDA-recommended conversions between short-acting and long-acting (LA) preparations of the same drug are based on attempts to match serum-concentration curves and not clinical-performance curves.

In clinical practice, ratios for converting among medications vary by ADHD (ADD) manifestations, adverse effects, comorbidities, and the patients' metabolism. Common approximations are described below. Individual patients vary; therefore, close follow-up, and possibly titration, is initially necessary.

For methylphenidate LA, CD, or ER preparations, convert by using a ratio of 2:1 with immediate-release methylphenidate. For example, Ritalin 10 mg q4h is converted to Ritalin LA 20 mg q8h. For a few patients, effects last only 5-6 hours with the LA preparations, although effects last 3.5-4 hours with the IR form. However, a short effect from one 8-hour preparation does not always mean another 8-hour preparation has the same problem.

For XR mixed amphetamine salts (MAS), convert using a ratio of 2:1 with IR MAS. The half-life of MAS widely varies among individuals. Some patients do better with a lower second dose and, thus, may benefit from an IR and XR morning combination.

Dexedrine Spansule seems to have the greatest interpatient variance when converting the IR form to the CR form. The IR-to-CR ratio for equivalent clinical effects appears to vary from 1:1 to about 1:1.5; however, this conversion has not been well studied. For example, Dextrostat 10 mg q4h is converted to Dexedrine CR 10-15 mg q8h.

Methylphenidate OROS tablets are converted in an 18:5 ratio with methylphenidate. For example, Ritalin 10 mg q4h is converted to Concerta 36 mg. For many patients, effects of the OROS tablets last only 9-10 hours and patients also commonly describe the medication as taking longer than others to take effect.

Methylphenidate OROS tablets are converted in an 18:10 ratio with methylphenidate LA, CD, or ER. For example, Ritalin LA 10 mg q8h is converted to Concerta 18 mg.

Methylphenidate transdermal patch is converted in a 1:1 ratio with methylphenidate IR and a 1:2 ratio with the LA preparations, although the FDA suggests starting with the lowest dose patch and working up.

Lisdexamfetamine dosing conversion may be compared with dextroamphetamine immediate-release (Dexedrine IR). The prescribing information describes a dose of lisdexamfetamine dimesylate 100 mg as equivalent to d-amphetamine sulfate immediate-release 40 mg.

Psychostimulants are effective in patients with ADHD (ADD). In addition, they have been available for many decades, allowing for a strong appreciation of their lack of major adverse effects when used at therapeutic doses. However, a study published in 2014 suggests that psychostimulants may be associated with increased risk of CV events. [10, 11]

In a longitudinal, prospective cohort study of all children born in Denmark between 1990 and 1999 (mean follow-up 9.5 years), researchers found that use of psychostimulants was associated with nearly two-fold increased risk for a CV event compared with nonuse of the drugs (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.10 - 3.04), and the risk among stimulant users with ADHD was even higher (HR, 2.34; 95% CI, 1.15 - 4.75). [10, 11] The actual cardiovascular event rate was low (84 events per 100,000 person-years), the study included a broad definition of cardiovascular events, and the use of other medications was not controlled for, making the clinical significance of the study’s findings uncertain. [10, 11]

In December 2013, the US Food and Drug Administration (FDA) issued a warning that methylphenidate has been linked to rare cases of priapism, with the drug's labeling updated accordingly. [12]

In December 2015, the FDA approved a chewable tablet form of extended-release methylphenidate, to be sold as QuilliChew ER, for treatment of ADHD in patients aged 6 years or older. The tablet comes in strengths of 20, 30, and 40 mg and are scored so they can be split easily. The product is to be taken once daily in the morning. [13]

In May 2013, the FDA approved the stimulant lisdexamfetamine dimesylate (Vyvanse, Shire Plsc) as a maintenance treatment in children and adolescents (aged 6 years and older) with ADHD. The drug was previously approved as a maintenance treatment only in adults. [14]

In June 2017, the FDA approved 2 new ADHD medications, Contempla XR-ODT and Mydayis. Contempla XR-ODT is approved for the treatment of ADHD in children and adolescents between 6 and 17 years of age. It is an oral disintegrating tablet form of extended-release methylphenidate, given once every morning, and is available as a 8.6 mg, 17.3 mg, and 25.9 mg tablet. [43]  Mydayis is also approved for the treatment of ADHD in adolescents and adults aged 13 years or older. It is an extended-release capsule of mixed amphetamine salts administered each morning. It is available as a 12.5 mg, 25 mg, 37.5mg, and 50 mg capsule. [44]

Approval for lisdexamfetamine dimesylate was based on a 32-week trial designed to evaluate efficacy of the drug in 276 children and adolescents aged 6-17 years. Patients received dosages of 30 mg/day, 50 mg/day, or 70mg/day. Treatment failures at the end point of the 6-week withdrawal period occurred at a significantly lower rate in the drug group (15.8%) than in the placebo group (67.5%). This evidence strongly suggested that patients treated with the drug maintain greater ADHD symptom control.

Blader et al (2009) evaluated the ability of divalproex to reduce aggressive behavior in children with ADHD and a disruptive disorder. Children with persistent aggressive behavior that was underresponsive to psychostimulant therapy were randomly assigned to receive divalproex or placebo in addition to stimulant therapy for 8 weeks. A higher proportion of improved behavior was observed in the divalproex group (8 of 14 [57%]) compared with placebo (2 of 13 [15%]). A larger trial is needed to further study the use of divalproex to ameliorate aggressive behavior in patients with ADHD. [15]

Atomoxetine (Strattera), a nonstimulant selective norepinephrine reuptake inhibitor (SNRI), has been effective in many people with ADHD (ADD). This relatively new medication has the advantages of qd-to-bid dosing and unscheduled status with the Drug Enforcement Agency (DEA). However, cases of reversible hepatic failure have been directly attributed to atomoxetine, and an evaluation of other long-term adverse effects has been limited to data from a few years.

Patients may significantly benefit more from stimulants than from atomoxetine, but some may have untenable adverse effects with any stimulant product or dose. In the experience of numerous subspecialists, these patients may benefit from a combination of atomoxetine and a stimulant. For many patients, atomoxetine appears to augment the clinical effects of the stimulant, allowing for clinical efficacy with a low dose and decreasing the likelihood of adverse effects.

Antidepressants and alpha-agonists have an important role in some individuals with ADHD (ADD). Most have well-known adverse-effect profiles. Antidepressants and alpha-agonists can cause cardiac adverse effects, and this possibly must be kept in mind.

A cohort study published in the Journal of the American Medical Association in 2011 showed that current or new use of ADHD medications in young and middle-aged adults was not associated with an increased risk of serious cardiovascular events. The limitations of this study included lack of complete information on some potentially important risk factors. [16]

Clonidine extended-release (Kapvay) was approved for children with ADHD in September 2010. The immediate-release clonidine has been used off-label for ADHD; however, sedation was a drawback. The extended-release product provides less fluctuation of serum levels and may be better tolerated.

Modafinil (Provigil), a medication used to treat excessive daytime sleepiness, improves core symptoms in many children with ADHD (ADD). In early studies in children, common adverse affects occurring at rates higher than those of placebo were insomnia (24%) and anorexia (14%).

In August 2006, Cephalon, the manufacturer of modafinil (Sparlon), received a nonapprovable letter from the FDA for the treatment of ADHD (ADD). Cephalon has decided that it will not pursue further development of Sparlon for ADHD (ADD). Modafinil is still available as Provigil, which does have FDA approval to improve wakefulness for adults with narcolepsy, sleep apnea, or shift-work sleep disorders. Many ADHD (ADD) specialists continue to use modafinil in selected patients without problems. To view information from a media briefing describing the FDA decision, see Cephalon Media Briefing.

Transcripts of the FDA Psychopharmacologic Drugs Advisory Committee minutes that describe the rashes observed in clinical trials with modafinil are available. For more information see FDA Psychopharmacologic Drugs Advisory Committee minutes from March 23, 2006 that discuss modafinil for ADHD.

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Alpha2-adrenergic Agonists

Class Summary

Alpha2-adrenergic agonists can be helpful in treating hyperactivity, tics, or delayed sleep onset. They have a long history of pediatric use for this indication. Rare cases of sudden death had been reported several years ago in a few children who were given clonidine with concurrent methylphenidate. Reports also described fatal ventricular fibrillation in patients in whom treatment with clonidine was abruptly stopped rather than slowly tapered, as is appropriate. Details of these cases do not substantiate a cause-and-effect association, only concurrence.

The FDA has not stated that these drugs should not be simultaneously used. Nevertheless, a prudent approach is to avoid using these drugs together in any patient with a first-degree relative who died from a sudden cardiac cause without first getting an ECG. Obtaining an ECG in any patient who may benefit from this combination but who has a history of arrhythmia is also prudent. Most experts continue to use clonidine with any of the stimulants when clinically indicated.

The data from one study suggest that morning or evening guanfacine extended release (GXR; ≤4 mg/d) adjunctive to a long-acting psychostimulant resulted in improvement in ADHD symptoms over psychostimulants used alone. [17]

An extended-release clonidine (Kapvay) was approved by the FDA in September 2010 as adjunctive therapy to stimulants for ADHD or as monotherapy.

Guanfacine (Intuniv)

Selectively stimulates alpha2a-adrenoreceptors in brainstem, activating an inhibitory neuron, which reduces sympathetic outflow. This action results in decreased vasomotor tone and HR. The mechanism of action of guanfacine in ADHD is not known. Indicated for ADHD. Effectiveness for long-term use (ie, >9 wk) has not been studied in controlled trials

Clonidine (Kapvay)

Stimulates alpha2-adrenoreceptors in brainstem, activating an inhibitory neuron, which reduces sympathetic outflow. Result is decreased vasomotor tone and HR. Mechanism for ADHD unknown. Extended-release form indicated for ADHD as adjunctive therapy to stimulants or as monotherapy.

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Selective norepinephrine reuptake inhibitors (SNRIs)

Class Summary

These are nonstimulant ADHD (ADD) medications generally used as adjuncts to stimulants.

Atomoxetine (Strattera)

SNRI that inhibits presynaptic norepinephrine transporter. Also appears to indirectly stimulant dopamine activity in frontal lobes. Many anecdotal reports state that, when stimulants are not well-tolerated at a dose necessary for efficacy (eg, because of anxiety) and atomoxetine is not efficacious enough alone, the combination of atomoxetine and low dose (tolerable) stimulants is often very effective.

About 5-10% of patients are poor metabolizers of the drug and have increased drug exposure, peak serum levels, and half-lives. If intolerable but benign adverse effects are present at FDA-recommended doses, but not at lower dose, efficacy may be observed at the lower dose; therefore consider a low-dose trial. Usually clinically effective qd despite 5-h half-life (24 h in poor metabolizers); unknown if serum levels are correlated with efficacy.

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Antidepressants

Class Summary

Many patients have reported clinically significant improvement with the use of some antidepressants. Although antidepressants are beneficial when added to a stimulant or SNRI in certain clinical situations, a psychostimulant or SNRI is still the medication of choice for most persons with ADHD (ADD) because of its safety profile and superior efficacy.

Imipramine (Tofranil)

Inhibits reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at presynaptic neuron.

Bupropion (Wellbutrin)

Inhibits neuronal dopamine reuptake. Weak blocker of serotonin and norepinephrine reuptake.

Desipramine (Norpramin)

May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase and downregulation of beta-adrenergic and serotonin receptors. Adjust dose to response and serum level.

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Stimulants

Class Summary

Psychostimulants stimulate the areas of decreased activation to a higher state of arousal. The spectrums of therapeutic efficacy and adverse effects of all the FDA-scheduled category II psychostimulants for ADHD (ADD) are similar. For any individual, therapeutic efficacy may vary greatly among drugs, preparations, or formulations (generic vs brand name).

The most common adverse effects include anorexia, sleep disturbances, mild anxiety, and rebound (eg, post-therapeutic agitation, anger, lethargy). Most individuals who take psychostimulants for ADHD (ADD) develop tolerance for the adverse effects within a few weeks. Although adverse-effect profiles, akin to therapeutic profiles, are similar for all psychostimulants, patients have their own positive and negative responses, which vary among the drugs.

Individuals with certain current or latent coexistent psychiatric disorders (eg, psychosis, bipolar disorder, some disorders of anxiety or depression) are particularly vulnerable to the adverse effects of stimulants if they do not receive concurrent medication, psychological counseling, or both for the coexistent condition.

The following contains FDA-approved dosing information and FDA-stated contraindications. Of note, many experts question the FDA's maximums for most stimulant medications (see the Table above for ranges). Experts also question several comorbidities thought to be contraindications because evidence suggests that tics may be as likely to improve with stimulants as worsen with them. Furthermore, blood pressure improves in some individuals with hypertension receiving stimulants, whereas others simply need a slight increase in their dose of antihypertensive. Finally, although the FDA lists glaucoma as a contraindication, the specific concern is only narrow-angle glaucoma.

Dextroamphetamine (Dexedrine, Dexedrine Spansules, Dextrostat)

Increases amount of circulating dopamine and norepinephrine in cerebral cortex by blocking reuptake of norepinephrine or dopamine from synapse. Short-acting brands fairly similar in cost; generic is 50-60% less expensive. Dexedrine available as 5-mg scored tab. Dextrostat available as 5-mg or 10-mg scored tab. Dexedrine Spansules (CR) available as 5-mg, 10-mg, or 15-mg Spansules

Methylphenidate (Aptensio XR, Concerta, Cotempla XR-ODT)

Stimulates cerebral cortex and subcortical structures. Generic and branded-generic (Methylin and Metadate regular or ER) formulations 50-60% less expensive than Ritalin. LA preparations more expensive than short-acting preparations. Concerta (LA) tends to be more expensive than other preparations; 1 cap of Concerta, similar to other stimulants, costs the same whatever dose.

Although clinical difference between generic drug and branded-generics or Ritalin has not been verified, many patients have enough variability among preparations that they are willing to pay the price difference. Many experts observed enough variability that they do not prescribe plain generic products unless patient (or insurance) insists. FDA allows for 20% variability in certain parameters between generics and brands and determines equivalence solely by pharmacokinetics and not data from clinical studies.

Dextroamphetamine and amphetamine mixture (Adderall, Mydayis)

Produce CNS and respiratory stimulation. CNS effect may occur in cerebral cortex and reticular activating system. May have direct effect on alpha-receptor and beta-receptor sites in peripheral system and release stores of norepinephrine in adrenergic nerve terminals. Mixture contains various salts of amphetamine and dextroamphetamine. Adderall is available as 5-mg, 7.5-mg, 10-mg, 12.5-mg, 15-mg, 20-mg, or 30-mg scored IR tabs and 10-mg, 20-mg, and 30-mg XR caps. Mydayis is also available as 12.5 mg, 25 mg, 37.5 mg, 50 mg extended release caps.

Dexmethylphenidate (Focalin, Focalin XR)

Contains pharmacologically active d-enantiomer of racemic methylphenidate. Blocks norepinephrine and dopamine reuptake into presynaptic neuron and increases release of these monamines into extraneuronal space.

Methylphenidate transdermal patch (Daytrana)

CNS stimulant. Therapeutic action for ADHD (ADD) not known but thought to block norepinephrine and dopamine reuptake into presynaptic neuron and to increase release of these monoamines into extraneuronal space. Racemic mixture composed of the d-enantiomer and l-enantiomer. The d-enantiomer is more pharmacologically active than the l-enantiomer. Transdermal administration exhibits minimal first-pass effect compared with PO administration; consequently, lower dose of transdermal methylphenidate (on mg/kg basis) compared with PO dose of methylphenidate may still produce higher d-methylphenidate level.

Available in 4 dosage strengths. Different-sized patches contain different amounts of methylphenidate and deliver different amounts over 9-h dose period. Respective patch sizes, methylphenidate content per patch, and dose delivered over 9 h are 12.5, 18.75, 25, and 37.5 cm2; 27.5, 41.3, 55, and 82.5 mg; and 10, 15, 20, and 30 mg. Onset of desired effect occurs approximately 2 h after application and persists 3-4 h after removal.

Lisdexamfetamine (Vyvanse)

Inactive prodrug of dextroamphetamine. Elicits CNS stimulant activity. Blocks norepinephrine and dopamine reuptake in presynaptic neurons and increases release of these monoamines in extraneuronal space. It is indicated for initial and maintenance treatment of ADHD in children aged 6-17 years and adults.

Amphetamine (Dyanavel XR, Evekeo)

Noncatecholamine, sympathomimetic amine that elicits CNS stimulant activity. The precise mechanism by which amphetamines produce mental and behavioral effects are unclear. Available as short-acting tablets (Evekeo) that need 2-3 doses/day in children aged 3 y or older. It is also available as a long-acting, once daily oral suspension (Dyanavel XR) or extended release oral disintegrating tablets (Adzenys XR-ODT) for patients aged 6 y or older.

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