Dosing Frequency c. Given BID to TID (AM, noon, 4 PM if needed), 5,27 preferably 30 to 45 minutes before meals. 4

Transcription

1 PL Detail-Document # This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER March 2016 Comparison of ADHD Medications *All ADHD stimulant drugs and Strattera must be dispensed with a Medication Guide* Stimulants (methylphenidate and amphetamines) are considered first-line agents for the treatment of ADHD based on efficacy and safety. Choose a product based on dosing, duration, side effects, patient s ability to swallow pills, and cost. The chart below can be used as a guide. In about half of cases, patients not responding to one stimulant may respond to the other. 27 When switching to an alternate product, see Conversion Information below, or start with initial recommended dose and titrate. Some caregivers are uncomfortable with stimulants, and some patients respond poorly to stimulants. 27 For these patients, options include atomoxetine (Strattera), extended-release guanfacine, or extended-release clonidine. 27 Stimulants and atomoxetine are unlikely to increase stroke, heart attacks, or sudden death. 33 But avoid them in patients with serious heart problems, or if increases in blood pressure or heart rate would be a problem. 37 Regardless of chosen medication, monitor heart rate, blood pressure, height, and weight. 27 Products listed in the following chart are FDA approved for the management of ADHD. a Abbreviations: AM = morning; BID = twice daily; h = hour; IR = immediate-release; q = every QID = four times daily; TID = three times daily; yrs = years Immediate-release (IR) methylphenidate j Ritalin (Novartis) 5, 10, 20 mg tabs Generics from Actavis, CorePharma, Mallinckrodt, $56.19 (10 mg BID) Sun, Upstate (UCB), and Qualitest (Vintage) are AB rated. d Sandoz product is an authorized generic. h Given BID to TID (AM, noon, 4 PM if needed), 5,27 preferably 30 to 45 minutes before meals. 4 He 3 to 5 h 27 Initial: 5 mg BID to TID (children 6 years and older) 5,27 Adults, 5 mg BID to TID (consider QID), or 10 mg q am and q noon 5,31 5 to 10 mg mg 4 60 mg; 100 mg if over 50 kg 11

2 (PL Detail-Document #320309: Page 2 of 14) Immediate-release (IR) methylphenidate j (continued) Methylin Chewable Tabs 2.5, 5, 10 mg (Shionogi) chewable tabs Generic from Gavis (Novel) is AB rated. d $ (10 mg BID) Given BID to TID (AM, noon, 4 PM if needed), 5,6,27 preferably 30 to 45 minutes before meals. 6 3 to 5 h 27 See Ritalin See Ritalin Methylin Oral Solution (Shionogi) Generics from Breckenridge (Tris) and Gavis (Novel) are AA rated. d Mallinckrodt product is an authorized generic. h 5 mg/5 ml, 10 mg/5 ml oral solution $ (10 mg BID) Given BID to TID (AM, noon, 4 PM if needed), 5,27 preferably 30 to 45 minutes before meals. 7 3 to 5 h 27 See Ritalin See Ritalin Immediate-release (IR) dexmethylphenidate j Focalin (Novartis) 2.5, 5, 10 mg tabs Generics from Sun and Teva are AB rated. d $54.11 (5 mg BID) Given BID at least 4 hours apart without regard to meals. 8 3 to 5 h 27 Initial: 2.5 mg BID older, and adults) 8, mg with AM and/or noon dose 8,43 20 mg 8 50 mg 11 Extended-release (ER) dexmethylphenidate j Focalin XR e (Novartis) 5, 10, 15, 20, 25, 30, Generic from Actavis and 35, 40 mg caps Teva are AB rated. d Sandoz product is an authorized $ (10 mg daily) generic. h Given once daily in the morning. May be taken whole or sprinkled over applesauce. If sprinkled over applesauce, should be used immediately and not be stored for future use. Capsule and/or capsule content should not be crushed, chewed, or divided to 12 h 27 Initial: 5 mg older) or 10 mg (adults) 10 5 mg (children) or 10 mg (adults) mg children; 40 mg adults mg 11

3 (PL Detail-Document #320309: Page 3 of 14) Extended-release (ER) methylphenidate j Ritalin LA e (Novartis) 10, 20, 30, 40, 60 mg Bead-filled capsule (½ IR LA caps and ½ enteric coated, delayed release) 12 $ (20 mg daily) Generic from Actavis is AB rated. d Given once daily in the morning. May be taken whole or sprinkled on applesauce. Applesauce should not be warm. If sprinkled over applesauce, should be used immediately and not stored for future use. Capsule and/or capsule content should not be crushed, chewed, or divided to 9 h 13,27 Initial: 10 to 20 mg older, and adults) 12,31 10 mg 12,31 See Ritalin Metadate ER (UCB) Wax matrix tab 15 Formerly a generic for Ritalin-SR (discontinued). 20 mg ER tabs $54.18 (20 mg daily) Given once daily or BID. 27 Must be swallowed whole to 8 h 14,27,L Initial: 10 mg, 11 or 20 mg q AM for children tolerating 10 mg IR AM and noon, 1 and adults 5 20 mg; 5 add 2 PM dose, 5 or add 5 or 10 mg IR tab in AM and/or at 4 PM 1 See Ritalin Metadate CD f (UCB) Bead-filled capsule (30% IR and 70% ER) 17 Kremers Urban product is an authorized generic. h Generic from Teva is AB rated. d 10, 20, 30, 40, 50, 60 mg ER caps $ (20 mg daily) Given once daily in the morning before breakfast. May be taken whole or sprinkled over about a tablespoon of applesauce and taken immediately. Capsule/capsule content should not be crushed or chewed. Avoid alcohol; alcohol may cause more rapid release to 9 h 15,27 Initial: 20 mg older and adults) 17,43 10 to 20 mg 17,43 See Ritalin

4 (PL Detail-Document #320309: Page 4 of 14) Extended-release (ER) methylphenidate j (continued) Concerta f (Janssen) 18, 27, 36, 54 mg ER OROS (osmotic system has tabs hole for drug release) with IR overcoat. 5,16 $ (36 mg daily) Generic from Actavis is authorized generic. Generics from Mallinckrodt and Kremers Urban are BX rated. d Given once daily in the morning without regard to meals. Must be swallowed whole h 16 Initial: 18 mg older) or 18 to 36 mg (adults) mg 16,27 (a 27 mg tablet is available for titration between 18 mg and 36 mg) mg children; 72 mg adolescents and adults 16 children up to 40 kg, 72 mg; 5 adolescents over 40 kg, 90 mg; 5 adults, 108 mg 5,11,m Daytrana (Noven) transdermal patch QuilliChew ER f (Pfizer) cherry chewable tablet ER mechanism: drug is released from sodium polystyrene sulfonate particles via ion exchange. (30% IR, 70% ER) 1.1 mg/hr (10 mg/9 hr) 1.6 mg/hr (15 mg/9 hr) 2.2 mg/hr (20 mg/9 hr) 3.3 mg/hr (30 mg/9 hr) $ (all strengths) 20, 30, 40 mg chewable ER tabs (20 mg and 30 mg tabs are scored) $270 (all strengths) Worn daily for 9 hours (apply 2 hours before desired effect). 18 Can be worn up to 16 hours if longer effect needed. Remove at least 3 hours before bedtime. 19 Replace patch once daily in the morning. Apply to hip area. Change application site daily h (with 9-h wear time) 19 Given once daily in the morning, 8 h 36 without regard to meals. 36 Initial: 10 mg 18 Next highest patch strength 18 Dosing based on studies in children 6 to 17 years old. 18 Initial (patients 6 yrs and older): 20 mg 36 10, 15, or 20 mg mg mg 36

5 (PL Detail-Document #320309: Page 5 of 14) Extended-release (ER) methylphenidate j (continued) Quillivant XR f (Pfizer) 5 mg/ml oral suspension oral suspension Contains approximately 20% IR and 80% ER $ (all sizes) methylphenidate. Aptensio XR (Rhodes) Capsules filled with multilayered beads. IR layer contains 40% of the dose, controlled-release layer contains 60% of the dose. 28 Peaks at two and eight hours post-dose. 28 Amphetamines j Adderall (mixed amphetamine salts) k Brand discontinued. Generics from Actavis, CorePharma, Ranbaxy (Sun), Sandoz, and Teva are AB rated. d 10, 15, 20, 30, 40, 50, 60 mg caps $195 (any strength daily) 5, 7.5, 10, 12.5, 15, 20, 30 mg tabs $<34.56 (20 mg daily) Pharmacist must reconstitute. Given once daily in the morning with or without food. Shake bottle vigorously for at least 10 seconds prior to dose. Measure dose with oral dosing dispenser provided. Store reconstituted suspension in original container at room temp for up to 4 months. 38 Given once daily in the morning, at a consistent time in regard to meals. May be taken whole or sprinkled on applesauce and taken immediately. Capsule/capsule content should not be crushed, chewed, or divided. 28 Given one to three times daily (usually once or twice daily) at four- to six-hour intervals. 11,27,35 12 h 38 Initial: 20 mg (patients 6 yrs and older) 38,43 10 to 20 mg h 28 Initial: 10 mg (patients 6 yrs and older) mg 28 6 h 27 (dosedependent) 35 Initial: 2.5 mg once daily (3 to 5 yrs of age) or 5 mg once or twice daily (6 yrs and older) 11 or 10 mg BID (adults) to 5 mg once or twice daily (children) 27 or 10 mg BID (adults) mg mg mg mg, mg if over 50 kg 11

6 (PL Detail-Document #320309: Page 6 of 14) Amphetamines, j continued Adderall XR e (Shire) (mixed amphetamine salts extended-release capsule) k Generics from Actavis, Impax, and Teva are AB rated. d 5, 10, 15, 20, 25, 30 mg ER caps $ (any strength daily) Given once daily in the morning without regard to meals. May be taken whole or sprinkled on applesauce and taken immediately. Capsule/capsule content should not be crushed, chewed, or divided to 12 h 5,27 Initial: 5 to 10 mg (children 6 to 12 yrs old), 10 mg (adolescents), or 20 mg (adults) 20 5 to 10 mg 5 30 mg mg, 60 mg if over 50 kg 11 Adzenys XR-ODT (Neos) (amphetamine extendedrelease orally disintegrating tablets) k Dextrostat (dextroamphetamine) Brand discontinued; generics from Aurobindo (Aurolife), CorePharma, Mallinckrodt, Teva, and Wilshire (Mikart) are AA rated. d 3.1, 6.3, 9.4, 12.5, 15.7, 18.8 mg Tablet strengths reflect amount of amphetamine base. Pricing info N/A. 5, 10 mg tabs $< (5 mg BID) Given once daily in the morning without regard to meals. Tablet is placed on tongue and allowed to disintegrate. Tablet should not be not chewed, crushed, or swallowed whole. 44 Given BID to TID. 27 First dose upon awakening; additional doses at 4 to 6 hour intervals. 30 See Adderall XR (approval based on Adderall XR data) 44 Initial: 6.3 mg q AM (6 to 17 yrs of age), or 12.5 mg q AM (adults) to 6.3 mg 4 to 6 h 27 Initial: 2.5 mg q AM (3 to 5 yrs of age), mg q AM and noon, 5 or 5 mg q AM +/- noon dose older) 5,30 or 2.5 to 5 mg q AM and noon (adults) 5, mg/week (3 to 5 yrs of age) 30 or 2.5 to 5 mg/week older and adults) mg (ages 6 to 12 yrs) mg (ages 13 yrs and older) mg, rarely higher mg, 60 mg if over 50 kg 11

7 (PL Detail-Document #320309: Page 7 of 14) Amphetamines, j continued Dexedrine Spansule f (Amedra) (dextroamphetamine) Bead-filled capsule (50% released immediately, 50% delayed release) 39 Generics from Actavis, Mallinckrodt, and Teva are AB rated. d Lineage product is an authorized generic. h 5, 10, 15 mg SR caps $ (any strength daily) Usually once daily in the 6 to 8 h 5 morning, or BID. 21 Initial: 5 mg q AM or BID older) 21 or 10 mg q AM (adults) 5 5 mg 5,31 40 mg, rarely higher mg, 60 mg if over 50 kg 11 Dyanavel XR f (Tris Pharma) (amphetamine ER suspension) k ER suspension Drug is released from sodium polystyrene sulfonate resin via ion exchange. 2.5 mg/ml oral suspension $ (10 mg daily) Given once daily in the morning without regard to meals. Shake bottle prior to dose. 40 at least 12 h 40 Initial: 2.5 to 5 mg (children 6 years and older) to 10 mg mg 40 Evekeo (Arbor) (amphetamine [1:1 ratio of dextroamphetamine/ amphetamine]) 5, 10 mg scored tabs $ (any strength BID) Given one to three times daily. 41,42 First dose upon awakening; additional doses at 4 to 6 hour intervals. 41 at least 9.25 h 42 Initial: 2.5 mg once daily (children 3 to 5 yrs old) or 5 mg once or twice daily older), 41 or 5 to 10 mg once daily (adults) mg (children 3 to 5 yrs old), 5 mg (children 6 yrs and older), 41 or 5 to 10 mg (adults) mg, rarely higher mg (adults) 43

8 (PL Detail-Document #320309: Page 8 of 14) Amphetamines j (continued) ProCentra (Independence) (dextroamphetamine) Generic from Tris Pharma is AA rated. 1 mg/ml oral solution $ (5 mg BID) Given BID to TID. 27 First dose upon awakening; additional doses at 4 to 6 hour intervals to 6 h 27 Initial: 2.5 mg q AM (3 to 5 yrs of age), mg q AM and noon, 5 or 5 mg q AM +/- noon dose older) 5, mg/week (3 to 5 yrs of age) 30 or 2.5 to 5 mg/week older) 5 40 mg, rarely higher mg, 60 mg if over 50 kg 11 Vyvanse (Shire) (lisdexamfetamine Converted to active dextroamphetamine in the bloodstream , 20, 30, 40, 50, 60, 70 mg caps $ (any strength daily) Given once daily in the morning without regard to meals. May be taken whole or contents dissolved in water, yogurt, or orange juice and taken immediately to 12 h 27 (up to 14 h, adults) 22 Initial: 30 mg older and adults) to 20 mg mg 22 Nonstimulants Strattera (Eli Lilly & Co.) (atomoxetine) Response rate is lower compared to methylphenidate. 39 Continued 10, 18, 25, 40, 60, 80, 100 mg caps $ (40 mg daily) Given once daily or divided BID (i.e., morning and late afternoon/early evening) without regard to meals. 23 At least 10 to 12 h 27 Initial: 0.5 mg/kg/day (patients weighing up to 70 kg), or 40 mg/day (over 70 kg) 23 Titration, patients up to 70 kg: after 3 days, increase to children and adolescents up to 70 kg, lesser of 1.4 mg/kg or 100 mg; children and adolescents

9 (PL Detail-Document #320309: Page 9 of 14) Strattera, continued Consider atomoxetine for patients with anxiety, tics, insomnia, or substance abuse disorders. 39 Note psychiatric safety concerns. about 1.2 mg/kg/day. 23 Alternatively, after 4 days increase to 1 mg/kg/day, then increase to 1.2 mg/kg/day after 4 more days. 11 Titration, patients over 70 kg: after 3 days, increase to 80 mg/day, then up to 100 mg/day after two to four additional weeks 23 over 70 kg and adults, 100 mg 23 Lesser of 1.8 mg/kg or 100 mg 11 Kapvay (Concordia) (clonidine extended-release) Generics from Actavis and Par (Anchen) are AB-rated. d May be a good alternative for children who are intolerant to stimulants (e.g., kids with tics, insomnia, etc). 11,39 May be an add-on agent for children who do not receive enough benefit from stimulants alone (FDA approved for monotherapy or as an add-on to stimulants). 11,24,39 0.1, 0.2 mg extendedrelease tabs $ (0.1 mg BID) Tablets should not be crushed, chewed, or broken before swallowing. Do not substitute for other clonidine products on a mg-per-mg basis due to different pharmacokinetic profile. s above 0.1 mg/day should be divided twice daily with an equal or higher split dosage being given at bedtime. When discontinuing, taper the dose in decrements of no more than 0.1 mg every 3 to 7 days. 24 At least Initial: 0.1 mg 10 to 12 h 27 at bedtime mg 24 Dosing based on studies in children 6 to 17 years of age. 0.4 mg 24

10 (PL Detail-Document #320309: Page 10 of 14) Intuniv (Shire) (guanfacine) Generics from Actavis and Teva are AB-rated. d May be a good alternative for children who are intolerant to stimulants (e.g., kids with tics, insomnia, etc) 11,39 or those with anxiety or aggression. 5 Appears at least as effective as other nonstimulants. 9,26 FDA approved for monotherapy or as an add-on to stimulants. 25 1, 2, 3, 4 mg extendedrelease tabs $ (any strength daily) Given once daily; avoid high-fat meals. Tablets should not be crushed, chewed, or broken. Do not substitute for immediaterelease guanfacine tablets on a mg-per-mg basis due to different pharmacokinetic profiles. When discontinuing, taper the dose in decrements of no more than 1 mg every 3 to 7 days. 25 At least Initial: 1 mg 25 8 to 12 h 26,27 1 mg 25 Efficacy is evident at doses of 0.05 to 0.08 mg/kg once daily. s up to 0.12 mg/kg once daily may provide additional benefit. 25 Dosing based on studies in children 6 to 17 years of age. 7 mg 25 s above 4 mg have not been evaluated in children 6 to 12 years of age. 25 a. Desoxyn (methamphetamine) is also FDA approved for the management of ADHD. 2 However, its use has fallen out of favor with the availability of other long-acting stimulant products. Desoxyn is not included in current ADHD treatment guidelines. 34 b. Wholesale acquisition cost (WAC) for listed brand unless otherwise indicated. c. For stimulant products, give last dose earlier if insomnia is a problem. 39 d. AB rating: product meets necessary bioequivalence requirements. 3 AA rating: dosage form presents no actual or suspected bioequivalence problems. Has met in vitro bioequivalence standard acceptable to FDA. 3 BX rating: presumed therapeutically inequivalent due to insufficient data. 3 e. Releases some drug right away, then the rest later (mimics regular BID dosing). 10,12,20 f. Releases an immediate dose, then gradually releases the rest. 16,17,21,36,38,40 g. May differ from FDA-approved product information. h. Authorized generic: a brand-name drug sold as a generic by another manufacturer.

11 (PL Detail-Document #320309: Page 11 of 14) i. Stimulants are commonly used in preschoolers (i.e., four- or five-year-olds) with inadequate response to behavior therapy, but there are limited controlled studies. 11,27 conservatively and titrate slowly; methylphenidate is metabolized slowly in this age group. 27 In children less than 16 kg, short-acting agents are typically used initially. 11 j. Plateau effect after first week is not tolerance. 5 Stimulant dose based on weight, disease severity, and target symptoms (e.g., hyperactivity may require higher doses than inattentiveness). 39 Long-acting medications just as effective as shorter-acting agents. 11 Long-acting agents usually preferred for convenience and to minimize breakthrough symptoms, irritability, and headache. 11,39 The most common side effects of stimulants are anorexia, abdominal pain, insomnia, and headache. 34 For help with management, see our PL Detail-Document, Managing ADHD Stimulant Side Effects. Rarely, stimulants may cause psychotic symptoms such as hallucinations. 11,34 Final adult height might be decreased by less than an inch. 34 k. Approximately 75% dextroamphetamine and 25% l-amphetamine. 20,40,44 L. Slow onset, variable release/efficacy. 5,15 m. AACAP guidelines give a max Concerta daily dose of 108 mg regardless of weight. 11 Please continue to the next section for Conversion Information

12 (PL Detail-Document #320309: Page 12 of 14) Conversion Information n Note: Product labeling for QuilliChew ER and Dyanavel XR (and Adzenys XR-ODT if switching from any product other than Adderall XR) recommends starting with the initial dose and titrating when switching to these products due to differences among products in salt forms and pharmacokinetics. 36,40,44 Previous Methylphenidate Daily : Recommended Concerta starting dose 16 5 mg BID or TID: 18 mg Concerta every morning 10 mg BID or TID: 36 mg Concerta every morning 15 mg BID or TID: 54 mg Concerta every morning 20 mg BID or TID: 72 mg Concerta every morning Previous Methylphenidate Daily : Recommended Daytrana starting dose (9-h wear time) 19,o 5 mg TID or Concerta 18 mg daily: Daytrana 10 mg 7.5 mg TID or Concerta 27 mg daily: Daytrana 15 mg 10 mg TID or Concerta 36 mg daily: Daytrana 20 mg 15 mg TID or Concerta 54 mg daily: Daytrana 30 mg Recommended dexmethylphenidate starting dose Start with half the total daily dose of methylphenidate. 8,10 For IR dexmethylphenidate, divide BID with at least four hours between doses. 8 Give Focalin XR once daily in AM. 10 If converting from IR dexmethylphenidate to Focalin XR, use same total daily dose. 10 Recommended Metadate ER or Ritalin LA starting dose Dosage conversion from methylphenidate IR (BID dosing) or Metadate ER to Ritalin LA: use same total daily dose. Give once daily. 12 Metadate ER 20 mg: may use in place of IR methylphenidate when the 8-h dose is 20 mg 14 (e.g., convert IR methylphenidate 10 mg q AM and noon to Metadate ER 20 mg q AM) Methylphenidate/ dextroamphetamine/mixed amphetamine salts conversion No specific guidance in literature. Amphetamines are dosed at about half the methylphenidate dose. 5,39 So consider switching from methylphenidate to amphetamines at half the dose, or from amphetamines to methylphenidate at the same dose and titrating up. Or, start with recommended initial dose and titrate up. 5 Previous Adderall XR Daily : Recommended Adzenys XR-ODT Daily 44 Adderall XR 5 mg: Adzenys XR-ODT 3.1 mg Adderall XR 10 mg: Adzenys XR-ODT 6.3 mg Adderall XR 15 mg: Adzenys XR-ODT 9.4 mg Adderall XR 20 mg: Adzenys XR-ODT 12.5 mg Adderall XR 25 mg: Adzenys XR-ODT 15.7 mg Adderall XR 30 mg: Adzenys XR-ODT 18.8 mg n. May differ from product labeling. Use chart only as a guide. When converting patients from one agent to another, use clinical judgment and monitor the patient closely for clinical and adverse effects. o. FDA-approved labeling recommends patients converting from other methylphenidate formulations start with 10 mg due to differences in bioavailability among products. 18

13 (PL Detail-Document #320309: Page 13 of 14) Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. Project Leader in preparation of this PL Detail- Document: Melanie Cupp, Pharm.D., BCPS References 1. Institute for Clinical Systems Improvement (ICSI). Health care guideline: Diagnosis and management of attention deficit hyperactivity disorder in primary care for school-age children and adolescents. 8 th Ed. Bloomington, MN: Institute for Clinical Systems Improvement (ICSI). March ww.icsi.org/adhd/adhd_2300.html. (Accessed January 5, 2016). 2. Product information for Desoxyn. Recordati Rare Disease Inc. Lebanon, NJ February FDA. Orange book preface. Therapeutic equivalence-related terms. 34th edition. ess/ucm htm. (Accessed January 8, 2016). 4. Product information for Ritalin and Ritalin-SR. Novartis Pharmaceuticals. East Hanover, NJ April Canadian Attention Deficit Hyperactivity Disorder Resource Alliance. Canadian ADHD Practice Guidelines. Third edition. Chapter 7 update. November apter07.pdf.. (Accessed January 5, 2015). 6. Product information for Methylin Chewable Tablets. Shionogi Pharma, Inc. Atlanta, GA December Product information for Methylin Oral Solution. Shionogi Pharma, Inc. Atlanta, GA December Product information for Focalin. Novartis Pharmaceuticals. East Hanover, NJ April Hervas A, Huss M, Johnson M, et al. Efficacy and safety of an extended-release guanfacine hydrochloride in children and adolescents with attention-deficit/hyperactivity disorder: a randomized, controlled, phase III trial. Eur Neuropsychopharmacol 2014;24: Product information for Focalin XR. Novartis Pharmaceuticals. East Hanover, NJ June Pliszka S, AACAP Work Group on Quality Issues. Practice parameter for assessment and treatment of children and adolescents with attentiondeficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007;46: Product information for Ritalin LA. Novartis Pharmaceuticals. East Hanover, NJ July Biederman J, Quinn D, Weiss M, et al. Efficacy and safety of Ritalin LA, a new, once daily, extendedrelease dosage form of methylphenidate, in children with attention deficit hyperactivity disorder. Paediatr Drugs 2003;5: Product information for Metadate ER. UCB Inc. Smyrna, GA January Elia J. Attention deficit/hyperactivity disorder: pharmacotherapy. Psychiatry (Edgmont) 2005;2: Product information for Concerta. Janssen Pharmaceuticals, Inc. Titusville, NJ September Product information for Metadate CD. UCB Inc. Smyrna, GA February Product information for Daytrana. Noven Therapeutics, LLC. Miami, FL August Arnold LE, Lindsay RL, Lopez FA, et al. Treating attention-deficit/hyperactivity disorder with a stimulant transdermal patch: the clinical art. Pediatrics 2007;120: Product information for Adderall XR. Shire US Inc. Wayne, PA December Product information for Dexedrine Spansules. Amedra Pharmaceuticals, LLC. Middlesex, NJ October Product information for Vyvanse. Shire US Inc. Wayne, PA December Product information for Strattera. Eli Lilly and Company. Indianapolis, IN June Product information for Kapvay. Concordia Pharmaceuticals Inc. Bridgetown, Barbados BB January Product information for Intuniv. Shire US Inc. Wayne, PA December Sallee F, McGough J, Wigal T, et al. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebocontrolled trial. J Am Acad Child Adolesc Psychiatry 2009;48: American Academy of Pediatrics. Supplemental Information. Implementing the key action statements: an algorithm and explanation for process of care for the evaluation, diagnosis, treatment, and monitoring of ADHD in children and adolescents. 11/10/11/peds DC1/zpe p.pdf. (Accessed January 5, 2016). 28. Product information for Aptensio XR. Rhodes Pharmaceuticals L.P. Coventry, RI May Product information for ProCentra. Independence Pharmaceuticals LLC. Newport, KY September 2015.

14 (PL Detail-Document #320309: Page 14 of 14) 30. Product information for dextroamphetamine tablets. Teva Pharmaceuticals USA, Inc. North Wales, PA September Kolar D, Keller A, Golfinopoulos M, et al. Treatment of adults with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat 2008;4: Spencer T, Biederman J, Wilens T, et al. Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2001;58: Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med 2011;365: Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee on Quality Improvement and Management. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 2011;128: Product information for dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate and amphetamine sulfate tablet. CorePharma LLC. Middlesex, NJ April Product information for Quillichew ER. Pfizer Inc. New York, NY December FDA. FDA drug safety communication: safety review update of medications used to treat attentiondeficit/hyperactivity disorder (ADHD) in children and young adults. November 1, 2011 (last updated January 7, 2016). m. (Accessed January 8, 2016). 38. Product information for Quillivant XR. Pfizer Inc. New York, NY February Institute for Clinical Systems Improvement (ICSI). Health care guideline: diagnosis and management of attention deficit hyperactivity disorder in primary care for school-age children and adolescents. 9 th Ed. Bloomington, MN: Institute for Clinical Systems Improvement (ICSI). March Interactive0312.pdf. (Accessed January 6, 2016). 40. Product information for Dyanavel XR. Tris Pharma, Inc. Monmouth Junction, NJ November Product information for Evekeo. Arbor Pharmaceuticals, LLC. Atlanta, GA November Childress AC, Brams M, Cutler AJ, et al. The efficacy and safety of Evekeo, racemic amphetamine sulfate, for treatment of attention-deficit/hyperactivity disorder symptoms: a multicenter, dose-optimized, double-blind, randomized, placebo-controlled crossover laboratory classroom study. J Child Adolesc Psychopharmacol 2015;25: Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; (Accessed January 10, 2016). 44. Product information for Adzenys XR-ODT. Neos Therapeutics, L.P. Grand Prairie, TX January Cite this document as follows: PL Detail-Document, Comparison of ADHD Medications. Pharmacist s Letter/Prescriber s Letter. March Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2016 by Therapeutic Research Center Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to or

15 (Page 1 of 3) PL Technician Tutorial: Dispensing ADHD Medications About one out of every ten school-aged children has ADHD, or attention deficit hyperactivity disorder. Boys are about twice as likely as girls to be diagnosed with ADHD, and older children are more likely to be diagnosed than younger children. The rates of diagnosis of ADHD appear to increase with each passing year. Considering these statistics, it s no surprise that pharmacies are filling a lot of prescriptions for ADHD meds. This PL Technician Tutorial reviews medications that are used for ADHD. Information about dispensing ADHD drugs and preventing errors is also included. George Fidgette brings in an Rx for his 7-year-old son Henry for methylphenidate immediaterelease tabs, 5 mg BID, take before breakfast and lunch, #28, no refills. This is a new Rx for Henry, who has only received a course of antibiotics one time from your pharmacy. Henry s dad tells you that Henry has been diagnosed with ADHD. You double check with Henry s dad to make sure Henry s info is correct in the computer. You note his date of birth, add in a new allergy for him (strawberries) and update his weight to 40 lbs. What types of meds are used to treat ADHD? There are two classes of drugs used to treat ADHD: stimulants and nonstimulants. Stimulants include methylphenidate, dexmethylphenidate (U.S. only), dextroamphetamine, dextroamphetamine/amphetamine, and lisdexamfetamine. These meds increase levels of certain chemicals in the brain. Stimulant drugs for ADHD work by reducing symptoms, such as fidgeting and interrupting, and they help improve attention span. Nonstimulants include atomoxetine (Strattera), clonidine, and guanfacine. These also affect levels of chemicals in the brain, and increase attention span and reduce hyperactivity. It s not unusual for an individual to take more than one ADHD med at a time. For example, clonidine or another nonstimulant may be used together with a stimulant for improved drug effects. Or an immediaterelease stimulant may be used with an extended-release stimulant to provide better effects. What s the buzz about stimulant ADHD meds? There has been a lot of controversy surrounding the treatment of ADHD with stimulants. But the medical community is now agreeing that stimulant meds may be the best. However, there have been periodic shortages of stimulant meds over the past few years. This is partially due to a shortage of raw materials for producing stimulant meds. The government allows a quarterly release of these raw materials based on estimates of what will be needed. Unfortunately, the actual need has been more than the estimated need at Phone: ~ Fax: ~

16 (Page 2 of 3) some points. It is important to note that shortages can result in a need to switch between meds. Alert the pharmacist if you get a prescription for a med that is unavailable so that he or she can contact the prescriber to suggest an appropriate alternative. What information should I get for ADHD Rxs at patient drop-off? ADHD is often thought of as a condition that affects school-age children. However, some ADHD meds can be prescribed for kids as young as three years old. ADHD meds can also be prescribed for adults. In fact, one out of every 20 adults might have symptoms of ADHD. Be sure to ask for date of birth, not only for identification of the patient, but also so the pharmacist can double check that the ADHD med is age appropriate. In addition, get the patient s current weight so the pharmacist can double check that the dose of the med is appropriate. What s important to remember with order entry of ADHD meds? While there are under ten drugs total used to treat ADHD, the fact that there are multiple brand names and different dosage forms for some of these meds can be very confusing. This is especially true for the stimulants. For example, in the U.S., methylphenidate comes as Ritalin tabs, Methylin chewable tabs, Methylin oral solution, Ritalin LA caps, Metadate ER tabs, Concerta tabs, Metadate CD caps, Quillivant XR powder for suspension, and Daytrana patches. Plus, the newest methylphenidate formulations are Aptensio XR, a sprinkle cap, and QuilliChew ER, another chewable. There are generics of some methylphenidate products and some of the brands are interchangeable. We have a very helpful chart, Comparison of Drugs for ADHD, that lists all of the drugs for ADHD available in the U.S. along with available doses and generic substitutions. We have a similar chart for Canadian ADHD products. All of the different suffixes can also be confusing. Some of these are immediate-release dosage forms, such as Ritalin tabs, Methylin chewable tabs (U.S. only), and Methylin oral solution (U.S. only). You may see the suffix IR written on prescriptions for immediate-release forms, even though IR isn t actually part of the drug name. Others are extended-release dosage forms, such as Ritalin LA caps (U.S. only), Metadate ER tabs (U.S. only), Concerta tabs, Metadate CD caps (U.S. only), and Daytrana patches (U.S. only). The directions for taking the med can be a clue to the correct dosage form. Immediate-release forms will be given two or three times daily, while extended-release forms are usually given only once or twice daily. However, remember it s never safe to guess if a prescription is unclear. You should always check with the pharmacist for clarification. There are three nonstimulant meds used for ADHD: atomoxetine (Strattera), clonidine (Kapvay; U.S. only), and guanfacine (Intuniv-U.S., Intuniv XR-Canada). Clonidine (Catapres, etc) and guanfacine have actually been on the market for years, for the treatment of high blood pressure. However, the formulations for ADHD and the formulations for hypertension are not interchangeable. Catapres (and its generics) and Kapvay come in the same strengths, but Kapvay is extended-release whereas Catapres and its generics are immediate-release. As a result, these drugs are not equivalent and cannot be substituted. Generic guanfacine and Intuniv come in similar strengths, but Intuniv is extended-release whereas generic guanfacine is immediate-release. Once again, these drugs are not equivalent and cannot be substituted. You might see prescribers write for generic clonidine or guanfacine for ADHD. This isn t wrong. You just can t substitute these generics for an Rx that is written specifically for Kapvay or Intuniv. ADHD meds often have the dose increased gradually, so be sure to cancel any refills on older prescriptions when a patient presents a new one. Phone: ~ Fax: ~

17 (Page 3 of 3) Don t be surprised to see prescriptions written with directions to take stimulant meds early in the day, or for doses needed later in the day to be immediate-release formulations. These meds can cause insomnia, and taking them as early in the day as possible is a strategy that can help reduce this risk. What s important to remember when filling prescriptions for ADHD? In the U.S., all of the stimulant ADHD meds are Schedule II controlled substances. (Stimulant ADHD meds are Schedule I [amphetamine derivatives] or III [methylphenidate] controlled drugs in Canada.) You ll need to follow all the rules for C-IIs, such as not accepting refills for these meds, following your pharmacy s policy for who can count out C-IIs, etc. In the U.S., you ll need to dispense a MedGuide with every Rx for stimulant ADHD meds, as well as for atomoxetine. You go ahead and fill Henry s Rx with generic immediate-release methylphenidate tabs. The Rx is clearly written and there is no question in your mind as to the drug, directions, etc. You print a MedGuide to be dispensed with the drug as well. You let George Fidgette know that the pharmacist can provide counseling and any answers to his questions. Mr. Fidgette answers with absolutely. He has several questions for the pharmacist. Is there anything special I should do at patient pick-up for ADHD meds? Of course the offer for pharmacist counseling should be made at or before patient pick-up. You can do this if your state allows. Pharmacist counseling may be especially important for ADHD meds since they are most often used in children. Parents or caregivers might have questions or concerns that the pharmacist can help with. In addition, teens can get into trouble when managing their own ADHD meds, leading to problems such as unintentional overdoses. Pharmacist counseling can help them learn how to take their meds correctly. Mr. Fidgette is concerned that his son is too young to start meds for ADHD, and also about the risks associated with ADHD meds. The pharmacist explains that ADHD meds are in fact approved for kids as young as Henry. He also goes over the risks associated with ADHD meds, including the ones associated with heart problems. After about ten minutes, Mr. Fidgette seems satisfied that his questions have been answered. He thanks the pharmacist and heads out the door. Project Leader in preparation of this PL Technician Tutorial: Stacy A. Hester, R.Ph., BCPS, Assistant Editor Cite this document as follows: PL Technician Tutorial, Dispensing ADHD Medications. Pharmacist s Letter/Pharmacy Technician s Letter. February Phone: ~ Fax: ~