Stimulants

Attention Deficit Hyperactivity Disorder:  Not recommended for children under 3 years of age. In children from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In children 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Narcolepsy: Usual dose 5 mg to 60 mg per day in divided doses, depending on the individual patient response.
Narcolepsy seldom occurs in children under 12 years of age; however, when it does, dextroamphetamine sulfate may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

====================ADDERAL XL CAPSULES====================

Dosing Considerations for all Patients

Individualize the dosage according to the therapeutic needs and response of the patient. Administer ADDERALL XR at the lowest effective dosage.

Based on bioequivalence data, patients taking divided doses of immediate-release ADDERALL, (for example, twice daily), may be switched to ADDERALL XR at the same total daily dose taken once daily. Titrate at weekly intervals to appropriate efficacy and tolerability as indicated.

ADDERALL XR capsules may be taken whole, or the capsule may be opened and the entire contents sprinkled on applesauce. If the patient is using the sprinkle administration method, the sprinkled applesauce should be consumed immediately; it should not be stored. Patients should take the applesauce with sprinkled beads in its entirety without chewing. The dose of a single capsule should not be divided. The contents of the entire capsule should be taken, and patients should not take anything less than one capsule per day.

ADDERALL XR may be taken with or without food.

ADDERALL XR should be given upon awakening. Afternoon doses should be avoided because of the potential for insomnia.

Where possible, ADDERALL XR therapy should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Children: In children with ADHD who are 6-12 years of age and are either starting treatment for the first time or switching from another medication, start with 10 mg once daily in the morning; daily dosage may be adjusted in increments of 5 mg or 10 mg at weekly intervals. When in the judgment of the clinician a lower initial dose is appropriate, patients may begin treatment with 5 mg once daily in the morning. The maximum recommended dose for children is 30 mg/day; doses greater than 30 mg/day of ADDERALL XR have not been studied in children. ADDERALL XR has not been studied in children under 6 years of age.

Adolescents: The recommended starting dose for adolescents with ADHD who are 13-17 years of age and are either starting treatment for the first time or switching from another medication is 10 mg/day. The dose may be increased to 20 mg/day after one week if ADHD symptoms are not adequately controlled.

Adults: In adults with ADHD who are either starting treatment for the first time or switching from another medication, the recommended dose is 20 mg/day.

HOW SUPPLIED
5 mg, 7.5 mg, 10mg, 15mg, 20mg, 30 mg tablets.

ADDERALL XL:
5 mg, 10mg, 15mg, 20mg, 25MG, 30 mg CAPSULES.

U.S. Approval:  2015 [Initial U.S. Approval: 1960]

Mechanism of Action: Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in ADHD is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

INDICATIONS AND USAGE:  DYANAVEL XR is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD)

HOW SUPPLIED: Extended-release oral suspension contains 2.5 mg amphetamine base per mL.

Review boxed WARNING: ABUSE AND DEPENDENCE
CNS stimulants, including ADZENYS XR-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

Initial U.S. Approval:  1960

Mechanism of Action: Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in ADHD is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

INDICATIONS AND USAGE:  ADZENYS XR-ODT is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older.

DOSAGE AND ADMINISTRATION:
May be taken with or without food. Allow tablet to disintegrate in saliva then swallow. (2.2)
Pediatric patients (ages 6 to 17 years): Starting dose is 6.3 mg once daily in the morning. Maximum dose is 18.8 mg once daily for patients 6 to 12 years, and 12.5 mg once daily for patients 13 to 17 years. (2.3)
Adults: 12.5 mg once daily in the morning. (2.4)
To avoid substitution errors and overdosage, do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and differing pharmacokinetic profiles. (2.5, 5.7)

HOW SUPPLIED:
Extended-release orally disintegrating tablets: 3.1 mg, 6.3 mg, 9.4 mg, 12.5 mg, 15.7 mg, 18.8 mg

Shift Work Sleep Disorder (SWD) :
The recommended dose of NUVIGIL for patients with SWD is 150 mg given daily approximately 1 hour prior to the start of their work shift.

Dosage adjustment should be considered for concomitant medications that are substrates for CYP3A4/5, such as steroidal contraceptives, triazolam, and cyclosporine.

Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, and phenytoin may have prolonged elimination upon coadministration with NUVIGIL and may require dosage reduction and monitoring for toxicity.

In patients with severe hepatic impairment, NUVIGIL should be administered at a reduced dose.

There is inadequate information to determine safety and efficacy of dosing in patients with severe renal impairment.  In elderly patients, elimination of armodafinil and its metabolites may be reduced as a consequence of aging. Therefore, consideration should be given to the use of lower doses in this population
HOW SUPPLIED
NUVIGIL® (armodafinil) Tablets [C-IV]
50 mg, 150mg, 250 mg tablets

Dosing (usual): Treatment of ADHD in children and adolescents up to 70 kg body weight. Optimal doses appear to be 1.2 mg/kg daily, given once daily or in two divided doses. For children/adolescents over 70 kg body wt and adult patients, dose titration to 80 mg daily is recommended (single dose or two divided doses).

Dosing (Adults): Treatment of ADHD: Oral: Initial: 40 mg/day, increased after minimum of 3 days to ~80 mg/day; may administer as either a single daily dose or 2 evenly divided doses in morning and late afternoon/early evening. May increase to 100 mg in 2-4 additional weeks to achieve optimal response. Dosage adjustment in patients receiving strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine, quinidine): Do not exceed  80 mg/day; dose adjustments should occur only after 4 weeks.

Note: Atomoxetine may be discontinued without the need for tapering dose.

Supplied:  Capsule: 10 mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg, 100 mg

[Supplied: 50 mg tablet]

In general, dosage adjustments may proceed at approximately weekly intervals. Patients currently using methylphenidate: recommended starting dose is half the dose of methylphenidate.
The maximum recommended dose is 20 mg/day (10 mg twice daily).

A diagnosis of ADHD implies the presence of hyperactive-impulsive and/or inattentive symptoms that cause impairment and were present before the age of 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; "on the go"; excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.

Special Diagnostic Considerations
Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV® characteristics.

Need for Comprehensive Treatment Program
INTUNIV® is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, and social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. INTUNIV® is not intended for use in patients who exhibit symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational/vocational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe INTUNIV® will depend upon the physician's assessment of the chronicity and severity of the patient's symptoms and on the level of functional impairment.

DOSAGE AND ADMINISTRATION
2.1 General Dosing Information
INTUNIV® is an extended-release tablet and should be dosed once daily. Tablets should not be crushed, chewed or broken before swallowing because this will increase the rate of guanfacine release. Do not administer with high fat meals, due to increased exposure.

Do not substitute for immediate-release guanfacine tablets on a mg-per-mg basis, because of differing pharmacokinetic profiles. INTUNIV® has a delayed Tmax, reduced Cmax and lower bioavailability compared to those of the same dose of immediate-release guanfacine.

2.2 Dose Selection
If switching from immediate-release guanfacine, discontinue that treatment, and titrate with INTUNIV® according to the following recommended schedule.

Begin at a dose of 1 mg/day, and adjust in increments of no more than 1 mg/week, for both monotherapy and adjunctive therapy to a psychostimulant.

Maintain the dose within the range of 1 mg to 4 mg once daily, depending on clinical response and tolerability, for both monotherapy and adjunctive therapy to a psychostimulant. In clinical trials, patients were randomized or dose optomized to doses of 1 mg, 2 mg, 3 mg or 4 mg and received INTUNIV® once daily in the morning in monotherapy trials and once daily in the morning or the evening in the adjunctive therapy trial.

In monotherapy trials, clinically relevant improvements were observed beginning at doses in the range 0.05-0.08 mg/kg once daily. Efficacy increased with increasing weight-adjusted dose (mg/kg). If well tolerated, doses up to 0.12 mg/kg once daily may provide additional benefit. Doses above 4 mg/day have not been systematically studied in controlled clinical trials.

In the adjunctive trial, the majority of subjects reached optimal doses in the 0.05-0.12 mg/kg/day range.

In clinical trials, there were dose-related and exposure-related risks for several clinically significant adverse reactions (hypotension, bradycardia, sedative events). Thus, consideration should be given to dosing INTUNIV® on a mg/kg basis, in order to balance the exposure-related potential benefits and risks of treatment.

2.3 Maintenance Treatment
The effectiveness of INTUNIV® for longer-term use (more than 9 weeks) has not been systematically evaluated in controlled trials. Therefore the physician electing to use INTUNIV® for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

2.4 Discontinuation
In a pharmacodynamic study in healthy young adult volunteers receiving INTUNIV® (4 mg once daily) or placebo, the effects of abrupt discontinuation were compared to tapering. There were greater mean increases in systolic and diastolic blood pressure and heart rate after abrupt discontinuation of INTUNIV®, but these changes generally reflected a return to original baseline and were not meaningfully different for the two discontinuation strategies. However, infrequent, transient elevations in blood pressure above original baseline (i.e., rebound) have been reported to occur upon abrupt discontinuation of guanfacine. To minimize these effects, the dose should generally be tapered in decrements of no more than 1 mg every 3 to 7 days.

2.5 Missed Doses
When reinitiating patients to the previous maintenance dose after two or more missed consecutive doses, physicians should consider titration based on patient tolerability.

DOSAGE FORMS AND STRENGTHS
1 mg, 2 mg, 3 mg and 4 mg extended-release tablets

The efficacy of Vyvanse in the treatment of ADHD was established on the basis of two controlled trials in children aged 6 to 12, one controlled trial in adolescents aged 13 to 17, and two controlled trials in adults who met DSM-IV-TR® criteria for ADHD.

A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV®) implies the presence of hyperactive-impulsive and/or inattentive symptoms that cause impairment and were present before the age of 7 years. The symptoms must cause clinically significant impairment, e.g. in social, academic, or occupational functioning, and be present in two or more settings, e.g. school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least 6 of the following symptoms (or adult equivalent symptoms) must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; "on the go"; excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.

Special Diagnostic Considerations
Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but also of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the patient and not solely on the presence of the required number of DSM-IV characteristics.

Need for Comprehensive Treatment Program
Vyvanse is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Stimulants are not intended for use in patients who exhibit symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational/vocational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the patient's symptoms and on the level of functional impairment.

Long-Term Use
The effectiveness of Vyvanse for long-term use, i.e., for more than 4 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Vyvanse for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

DOSAGE AND ADMINISTRATION
Dosage should be individualized according to the therapeutic needs and response of the patient. Vyvanse should be administered at the lowest effective dosage.

In patients who are either starting treatment for the first time or switching from another medication, 30 mg once daily in the morning is the recommended dose. If the decision is made in the judgment of the clinician to increase the dose beyond 30 mg/day, daily dosage may be adjusted in increments of 10 mg or 20 mg at approximately weekly intervals. The maximum recommended dose is 70 mg/day; doses greater than 70 mg/day of Vyvanse have not been studied. Vyvanse has not been studied in children under 6 years of age.

Vyvanse should be taken in the morning. Afternoon doses should be avoided because of the potential for insomnia.

Vyvanse may be taken with or without food.

Vyvanse capsules may be taken whole, or the capsule may be opened and the entire contents dissolved in a glass of water. The solution should be consumed immediately and should not be stored. The dose of a single capsule should not be divided. The contents of the entire capsule should be taken, and patients should not take anything less than one capsule per day.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued treatment.

DOSAGE FORM AND STRENGTHS
20 mg, 30mg, 40mg, 50mg, 60mg, 70mg capsules

Dosing (Adults):
Narcolepsy: Oral: 10 mg 2-3 times/day, up to 60 mg/day.
Depression: Oral: Initial: 2.5 mg every morning before 9 AM; dosage may be increased by 2.5-5 mg every 2-3 days as tolerated to a maximum of 20 mg/day. May be divided (eg, 7 AM and 12 noon), but should not be given after noon. Do not use sustained release product. ADHD: Oral: Refer to pediatric dosing.

Pediatric:
ADHD: Oral: Children >/= 6 years: Initial: 0.3 mg/kg/dose or 2.5-5 mg/dose given before breakfast and lunch; increase by 0.1 mg/kg/dose or by 5-10 mg/day at weekly intervals; usual dose: 0.5-1 mg/kg/day; maximum dose: 2 mg/kg/day or 90 mg/day

Extended release products:
Metadate® ER, Methylin® ER, Ritalin® SR: Duration of action is 8 hours. May be given in place of regular tablets, once the daily dose is titrated using the regular tablets and the titrated 8-hour dosage corresponds to sustained release tablet size.
Metadate® CD, Ritalin® LA: Initial: 20 mg once daily; may be adjusted in 10-20 mg increments at weekly intervals; maximum: 60 mg/day

Concerta®: Initial dose: Children not currently taking methylphenidate: 18 mg once daily in the morning.  Children currently taking methylphenidate: Note: Dosing based on current regimen and clinical judgment; suggested dosing listed below:
Patients taking methylphenidate 5 mg 2-3 times/day or 20 mg/day sustained release formulation: 18 mg once every morning.  Patients taking methylphenidate 10 mg 2-3 times/day or 40 mg/day sustained release formulation: 36 mg once every morning.
Patients taking methylphenidate 15 mg 2-3 times/day or 60 mg/day sustained release formulation: 54 mg once every morning.
Dose adjustment: May increase dose in increments of 18 mg; dose may be adjusted at weekly intervals. A dosage strength of 27 mg is available for situations in which a dosage between 18-36 mg is desired. Maximum dose should not exceed 2 mg/kg/day or 54 mg/day in children 6-12 years or 72 mg/day in children 13-17 years.

Supplied:
Capsule, extended release:  Metadate® CD: 10 mg, 20 mg, 30 mg.  Ritalin® LA: 10 mg, 20 mg, 30 mg, 40 mg.
Solution, oral:   Methylin®: 5 mg/5 mL (500 mL); 10 mg/5 mL (500 mL)]
Tablet: 5 mg, 10 mg, 20 mg  (Methylin®, Ritalin®: 5 mg, 10 mg, 20 mg)
Tablet, chewable: Methylin®: 2.5 mg; 5 mg; 10 mg.
Tablet, extended release: 20 mg.  Concerta®: 18 mg, 27 mg, 36 mg, 54 mg [osmotic controlled release].  Metadate® ER, Methylin® ER: 10 mg, 20 mg.
Tablet, sustained release (Ritalin-SR®): 20 mg

Adult (usual):  Start 37.5 mg orally once daily in the morning. Usual effective dose: 56.25 to 75 mg/day. Max: 112.5 mg/day. Follow LFT's.

[Supplied: 105 mg SR, 35 mg tablet]

Supplied: 8, 15, 18.75, 30. 37.5 mg

[Supplied: 5, 10, 15 mg capsule]