Medications in the School Setting. Kristen Nichols, PharmD, BCPS-AQ ID Butler University Riley Hospital for Children

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Medications in the School Setting Kristen Nichols, PharmD, BCPS-AQ ID Butler University Riley Hospital for Children

OBJECTIVES Discuss treatment options for treatment of attention-deficit/hyperactivity disorder Identify medications used for psychiatric conditions in children and adolescents and their adverse effects Describe use of benzodiazepines for acute treatment of seizures Recognize limitations of antibiotic medications

COMMONLY PRESCRIBED MEDICATIONS 2-11 Years Amoxicillin Azithromycin Albuterol Montelukast Methylphenidate Fluticasone Prednisolone Cefdinir Cephalexin Amoxicillin/clavulanate 12-17 Years Methylphenidate Albuterol Azithromycin Amoxicillin Amphetamine/dextroamphetamine Montelukast Norgestimate-ethinyl estradiol Lisdexamfetamine Fluticasone Hydrocodone/acetaminophen Chai et al. Pediatrics. 130(1):23-31. Antibiotics, stimulants, asthma/allergy

TODAY S DISCUSSION ADHD Depression/anxiety Other behavioral medications Seizure rescue medications Rectal diazepam & intranasal midazolam Antibiotics

Attention Deficit Hyperactivity Disorder Stimulant use increased from 2002 to 2010

Evaluate individuals 4-18 years with: Academic or behavioral problems AND Symptoms of inattention, hyperactivity, or impulsivity Obtain information from Family School Child Meet DSM-V criteria Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022.

ADHD TREATMENT 4-5 years 1 st : Parent or teacher-administered behavior therapy 2 nd : Methylphenidate 6-11 years FDA-approved medications and/or Behavior therapy Preferably BOTH 12-18 years Medications WITH assent and Behavior therapy (maybe) Preferably both Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022.

4-5 YEAR OLDS: METHYLPHENIDATE Technically off-label Most data for safety & efficacy in this age group Decreased metabolism compared to older children Start low Titrate in smaller increments Methylin (+generics) Quillivant XR AGE-APPROPRIATE DOSAGE FORMS IR oral solution: 5 mg/5 ml; 10 mg/5 ml Chewable tablet: 2.5 mg, 5 mg, 10 mg XR oral solution: 25 mg/5 ml IR=immediate release XR = extended-release Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022.

START WITH A STIMULANT FROM EITHER CLASS Amphetamine compounds Methylphenidate products Mixed amphetamine salts Methylphenidate Dextroamphetamine Dexmethylphenidate Lisdexamfetamine Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022.

PRODUCT CONSIDERATIONS When is coverage needed? Time to onset Duration of effect Dosage Forms ER/XR dosage forms should not be chewed, crushed, divided Cost Convenience Abuse potential? Can be given just on school days

CARDIOVASCULAR RISK Sudden cardiac death is rare Uncertain association Baseline ECG: AAP doesn t recommend AHA says it is reasonable Evaluate cardiac history at baseline Congenital heart disease or cardiac abnormality: collaboration between family, ADHD specialist, pediatric cardiologist BP and HR s are usually mild Cortese et al. J Child Psychol Psychiatry 2013;54(3)227-46.

ADDITIONAL ADVERSE EFFECTS (STIMULANTS) appetite growth velocity Abdominal pain Headaches Insomnia Irritability Emotional lability Abuse potential Xerostomia Worsen tics Visual disturbance FDA Warning: sustained or prolonged erections Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022. Cortese et al. J Child Psychol Psychiatry 2013;54(3)227-46.

STIMULANTS WITH LESS ABUSE POTENTIAL Lisdexamfetamine (Vyvanse ): Metabolized after ingestion by erythrocyte cells to dexamphetamine Dermal methylphenidate (Daytrana ): Difficult to extract the medication; mixed into the adhesive along with silicone & acrylic OROS methylphenidate (Concerta ): Difficult to extract medication; ~20% in outer coating; remaining slowly released from small hole in core over 12H Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022

NEXT STEPS Non-response: Try other stimulant class Up to 50% of non-responders will respond Adverse effects: Try other stimulant class Partial response: ER guanfacine & clonidine approved as adjunctive therapy Refusal of stimulant or diversion potential Atomoxetine Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022.

TX CHILDREN S MED ALGORITHM PROJECT After trying both stimulant classes: Atomoxetine Bupropion or tricyclic antidepressant Bupropion or tricyclic antidepressant (opposite) Alpha agonists (clonidine & guanfacine) Pliszka SR et al. J Am Acad Child Adolesc Psychiatry. 2006;45(6):64-657

AAP ADHD GUIDELINES No specific algorithm after stimulants Strength of data: Atomoxetine ER guanfacine ER clonidine Subcommittee on ADHD. Pediatrics. 2011;128:1007-1022.

ATOMOXETINE Selective norepinephrine-reuptake inhibitor Improves comorbid tics Maximum effect in 4-6 weeks Potential drug interactions Capsules only Adverse effects: Risk of suicidal ideation during initiation in BP & HR; cardiovascular events? Somnolence Appetite & growth suppression Pediatric and Neonatal Lexi-Drugs Online

BUPROPION Not FDA approved or in AAP guidelines Weak inhibitor of norepinephrine & dopamine IR & SR/XL tablets (start with IR & titrate) Don t crush or chew SR/XL dosage forms Adverse effects Risk of suicidal ideation during initiation Anxiety/insomnia/activation BP Lower seizure threshold Pediatric and Neonatal Lexi-Drugs Online

ALPHA 2 ADRENERGIC AGONISTS FDA approvals: extended-release formulations Maximum response in 2-4 weeks No breaks, taper when discontinuing BP upon discontinuation, HR GUANFACINE Intuniv & generic Typically better tolerated Longer half-life Sedation Exfoliative rash CLONIDINE Kapvay /Nexiclon XR Available as a liquid Hypotension, bradycardia Sedation Adjunct to stimulants if insomnia Pediatric and Neonatal Lexi-Drugs Online

Psychiatry Medications Depression & Anxiety Medications for Autism Spectrum Disorder

DEPRESSION Prevalence: 0.5 3.5% More common in females More common in 12-17 years Risk factors Family history Early exposure to adversity Psychosocial stressors Traumatic brain injury Gender dysphoria/homosexuality Chronic illness Kreys TM. Pediatric Depression. Pediatric Pharmacotherapy. ACCP

DEPRESSION TREATMENT Consider patient-specific factors Psychotherapy/CBT Pharmacotherapy Selective serotonin-reuptake inhibitors (SSRIs) Serotonin-norepinephrine-reuptake inhibitors (SNRIs) Bupropion (dopamine/norepi reuptake inhibitor) Mirtazipine Venlafaxine TCAs/MAOIs not typically recommended Acute, continuation, & maintenance phases Hughes CW et al. J Am Acad Child Adolesc Psychiatry. 2007;46:667-86. Birmaher B et al. J Am Acad Child Adolesc Psychiatry. 2007;46:1503-26

SELECTIVE SEROTONIN-REUPTAKE INHIBITORS First-line Fluoxetine (FDA labeled for 8-18 yrs) Escitalopram (FDA labeled for 12-17 yrs) Sertraline Citalopram Hughes CW et al. J Am Acad Child Adolesc Psychiatry. 2007;46:667-86. Birmaher B et al. J Am Acad Child Adolesc Psychiatry. 2007;46:1503-26

SSRI Pearls Also useful for anxiety Elimination may be faster in children Usually initiate at lower dose & titrate based on efficacy & tolerability Some may have drug interactions Fluoxetine in AM Sertraline GI effects Do not stop abruptly withdrawal Flu-like symptoms, hyperarousal, insomnia, imbalance Less likely with fluoxetine

SUICIDALITY BOXED WARNING Boxed warning following a meta-analysis Applies to all antidepressants for individuals through 24 years of age Discuss risks & benefits prior to initiation Monitor patients on any antidepressants for worsening, suicidality, unusual behavior Weekly meetings with clinician during first month recommended Pediatric and Neonatal Lexi-Drugs Online

MEDICATIONS IN AUTISM No medications will address underlying disorder Medications may be used to target specific behaviors or comorbid conditions Should be used in combination with behavioral and educational therapies Ji NY et al. Curr Opin Psychiatry. 2015;28:91-101.

MEDICATIONS USED IN AUTISM Atypical Antipsychotics SSRIs Depression + CNS Stimulants α 2 agonists Hyperactivity Inattention Repetitive behavior + + + + + Irritability Aggression Self Injury + + Ji NY et al. Curr Opin Psychiatry. 2015;28:91-101.

OTHER MEDICATIONS WITH EFFICACY DATA Atomoxetine Oxytocin Valproic acid Melatonin Ji NY et al. Curr Opin Psychiatry. 2015;28:91-101.

ATYPICAL ANTIPSYCHOTICS FDA approval for indications in ASD: Aripiprazole Risperidone Weigh risks & benefits Adverse effects appetite/weight gain blood glucose lipids Sedation Parkinsonism Tardive dyskinesia Hyperprolactinemia Ji NY et al. Curr Opin Psychiatry. 2015;28:91-101. Pediatric and Neonatal Lexi-Drugs Online.

OTHER ATYPICAL ANTIPSYCHOTICS Less toxic than typical (1 st generation) antipsychotics Also used for other psychiatric disorders Schizophrenia Bipolar disorder Mood disorders Other agents used Quetiapine (QT prolongation, anticholinergic) Olanzapine (weight gain) Others being studied

Seizure Rescue Therapy

STATUS EPILEPTICUS Many children continue to experience seizures while on therapy Definition Seizure lasting > 5 min OR 2 discrete episodes without regaining consciousness Support for early intervention: time seizing, difficulty in control Seizures > 5 minutes are less likely to resolve without intervention Harm Cerebral injury Neurologic sequelae in 20% Eiland LS. Seizure Disorders. ACCP Pediatric Pharmacotherapy

RESCUE THERAPY Community rescue therapy: Breakthrough seizures Increased seizure activity in patients already receiving anti-epileptic drugs Has been shown to ER visits and improve family QOL Benzodiazepines Quick onset of action Enhance inhibitory effect of GABA Diazepam & midazolam

DIASTAT ACUDIAL Prefilled, unit dose, rectal delivery system 2 per pack + 2 packets of lubricating jelly Presentation Doses Rectal Tip Size 2.5 mg 2.5 mg 4.4 cm 10 mg 5, 7.5, 10 mg 4.4 cm 20 mg 12.5, 15, 17.5, 20 mg 6 cm 2-5 yrs: 0.5 mg/kg 6-11 yrs: 0.3 mg/kg 12 yrs: 0.2 mg/kg Diastat Prescribing Information

GREEN READY BAND AcuDial is locked in to the correct dose by the pharmacist upon dispensing Verify dose in dose display window Look for green ready band www.diastat.com

DIASTAT ADMINISTRATION Helpful website: www.diastat.com Lay person on side Push up with thumb & pull to remove cap (including seal pin) Lubricate rectal tip with provided jelly Bend upper leg forward to expose rectum Separate buttocks Gently insert tip into rectum (snug rim) www.diastat.com

DIASTAT ADMINISTRATION Slowly count to 3 for each: Pushing in plunger until it stops Remove syringe from rectum Hold buttocks together to prevent leakage Keep person on side & observe, noting time Disposal: 2.5 mg: discard in a garbage can away from children AcuDial: completely remove plunger, point tip over sink or toilet, replace plunger, push until it stops; THEN discard in a garbage can

INTRANASAL MIDAZOLAM Rectal Diazepam Intranasal Midazolam Cost $$$ $ Social Concerns Social concerns/ need for privacy More convenient Abuse potential? Time to Peak 1.5 hours 5 10 minutes Elimination t 1/2 15-50 hours 3 5 hours Disease Interference Constipation Bowel movement URTI Nasal Congestion Dose prep Remove cap Draw up in syringe Onset 3-4 minutes; data mixed regarding which is faster Holsti et al. Ped Emerg Care. 2007;23:148-153.

INTRANASAL MIDAZOLAM ~0.2 mg/kg (max 10 mg) Use 5 mg/ml solution for inject Store at room temp Can give ½ in each nare Ideal to use an atomizer Pediatric and Neonatal Lexi-Drugs Online

IN MIDAZOLAM ADMINISTRATION Remove vial cap & swab with alcohol Using syringe & needle withdraw desired amount of medication from vial Re-cap & remove needle Twist atomizer onto syringe With child (typically) on back/side, put tip of atomizer into one nostril Press plunger to given ½ Repeat on other side

EMERGENCY SEIZURE TREATMENT

MONITORING When to activate EMS Adverse effects: Sedation, somnolence Respiratory depression (RR, O 2 sat depression) Dizziness, lack of coordination Typically max q5 days or 5 times/month

Antibiotics They don t treat viruses #SavAbx

Medications in the School Setting Kristen Nichols, PharmD, BCPS-AQ ID Butler University Riley Hospital for Children