PL CE LIVE February 2011 Forum

Transcription

1 February 2011 PL CE LIVE Kristin W. Weitzel, Pharm.D., CDE, FAPhA Associate Editor and Director of Editorial Projects Pharmacist s Letter/Prescriber s Letter Atypical Antipsychotics Atypical Antipsychotics Drug Brand Name Generic available? Aripiprazole No Asenapine No Clozaril Yes Iloperidone No Lurasidone No Olanzapine, IM No (exp late 2011) Paliperidone, Sustenna No (exp 2012) Quetiapine, XR No (exp 2012) Risperdal, Risperdal Consta Yes Ziprasidone No (exp 2012) Clinical Use Schizophrenia best efficacy; limited by agranulocytosis Similar therapeutic properties; diverse adverse effect profiles Bipolar disorder,,, risperidone,, Treatment resistant depression Lower dose than used for schizophrenia,, Clinical Use Pediatrics In some geographic areas, 25% of atypical antispychotic Rxs are for kids Autism, irritability, bipolar disorder, schizophrenia (most evidence in kids),, Dementia Increased risk of mortality in older patients Use declined by 50% from 2004 to 2008 Adverse Effect Profiles Metabolic effects Weight gain Diabetes Dyslipidemia Sedation Low to none Moderate High 1

2 Adverse Effect Profiles Metabolic effects Weight gain Diabetes Dyslipidemia Sedation Low to none Moderate High QT Prolongation * CYP 3A4 Metabolism Yes Minor No Take-Home Messages Choice based on adverse event profile, cost, drug interactions Help prioritize based on most important factor Watch for inappropriate indications or use Ongoing adverse effects or major drug interaction Other safer or more effective therapeutic options exist Risk outweighs the benefits Acetaminophen Toxicity Acetaminophen Toxicity Most common cause of acute liver failure Half of acute liver failure cases are due to unintentional overdoses As little as 6 g/day for 2 days can cause toxicity About 100 deaths and 56,000 people to ER per year Rx products are more likely to be linked to toxicity/overdose than OTCs Toxicity/overdose is often unknown due to nonspecific, flu like symptoms Mechanism of Toxicity Nontoxic conjugates Excreted in Urine glutathione Acetaminophen NAPQI Liver toxicity 90% Sulfate and glucuronide conjugates Excreted in Urine 2

3 What dose is toxic? Patients 6 years and older Acute: at least 10 g or 200 mg/kg (whichever is less) Chronic: at least 10 g or 200 mg/kg (whichever is less) over a 24 hour period or at least 6 g or 150 mg/kg (whichever is less) per 24 hour period for the preceding 48 hours or longer Contact poison control or refer patient to the emergency dept at these doses 2009 FDA Panel Recommendations Limit OTC liquid forms to only one concentration Lower max OTC strength of single ingredient products to 650 mg (from 1,000 mg) 1,000 mg available as Rx only Lower max daily dil dose from current 4 g/day Ban Rx opioid acetaminophen combo products Panel recommended against pulling acetaminophencontaining combo products off the market Black box warning on Rx acetaminophen meds, new warnings on OTC products Current Changes to Acetaminophen Products Combination analgesics will be limited to 325 mg acetaminophen per tab or cap High dose formulations phased out by 2014 New boxed warning about liver toxicity in patients who take more than 4000 mg/day or drink alcohol with acetaminophen Changes to Rx meds only Attention Deficit Hyperactivity Disorder Treatment - Stimulants Generally used first line At least 80% of patients will respond May be limited by side effects (insomnia, weight loss, etc) Multiple formulations, dosage forms Treatment - Stimulants Methylphenidate Immediate release (Ritalin, etc) Extended release (Ritalin LA, Concerta, Daytrana, Metadate CD, etc) Dexmethylphenidate Immediate release (Focalin) Extended release (Focalin XR) Extended release dextroamphetamine and amphetamine salts mixture (Adderall XR) Sustained release dextroamphetamine (Dexedrine) Lisdexamfetamine (Vyvanse) 3

4 Treatment Atomoxetine (Strattera) Selective norepinephrine reuptake inhibitor Alternative to stimulants Not usually as effective as stimulants May take several weeks to work Some children may respond to atomoxetine that don t respond to stimulants Useful in those with prior stimulant misuse or abuse or those experiencing adverse effects from stimulants (insomnia, etc) Alpha-Adrenergic Adrenergic Agonists Alternative or add on to stimulants Usually less effective than stimulants Kids that don t tolerate stimulants or for more severe ADHD symptoms or ADHD with aggression Extended release guanfacine (Intuniv) Seems to work at least as well as Strattera Increased drowsiness or fatigue Extended release clonidine (Kapvay) Dosed once or twice daily Lower peak blood levels than IR clonidine may lead to better tolerability Treatment Considerations Most kids will start with stimulants Choose based on dosing preference, cost, schedule (e.g., school dosing), etc Alpha agonists Add on therapy for tics, severe symptoms, aggression, etc Other alternatives Bupropion Tricyclic antidepressants Bupropion Forms Bupropion Use Depression (Wellbutrin, etc) Second line or add on therapy Less sexual dysfunction and weight gain than SSRIs or SNRIs Common ADRs: headache, insomnia (35 40%), dry mouth Smoking Cessation (Zyban, etc) Doubles chance of quitting smoking compared to placebo Alone or add on to nicotine replacement therapy Useful in smokers who are depressed or concerned about weight gain Available Forms Brands Bupropion hydrochloride Wellbutrin, Wellbutrin SR, Wellbutrin XL Zyban Bupropion hydrobromide Aplenzin Generics Bupropion IR, SR, XL Budeprion Buproban 4

5 Bottom Line Budeprion Use Budeprion SR for Wellbutrin SR Use Budeprion XL for Wellbutrin XL Buproban Use Buproban for Zyban Aplenzin No generic forms Use appropriate dose conversion if switching to/from Wellbutrin forms Bottom Line Bupropion generics OK in most cases to use for Zyban or Wellbutrin forms; check AB rating if you re unsure AB = Wellbutrin AB1 = Wellbutrin SR AB2 = Zyban AB3 = Wellbutrin XL Look for SR or XL or ONCE DAILY or TWICE DAILY on the label 5

6 New Drugs/Developments New Drugs Cycloset (bromocriptine) Dopamine agonist usually used for Parkinson s or to lower prolactin levels Lowers A1C about 0.5%; costs $120 to $360/month Butrans (buprenorphine) Once weekly patch for persistent moderate to severe pain Most likely used as a step up from non opioids Don t exceed Butrans 20 mcg/hour due to QT prolongation Polls/Questions 6