July 2015 PL CE LIVE Rachel Maynard, PharmD Associate Editor Pharmacist s Letter/Pharmacy Technician s Letter CE Information Pharmacist's Letter / Therapeutic Research Center is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. PL CE LIVE editors disclose: No financial interests related to the content No commercial support and no advertising Supported entirely by subscriptions PL CE LIVE Drug Information Consultant discloses: Dr. O Mara reports that her spouse is employed by Celgene. Pharmacist Objectives Identify emerging trends in drug therapy and their place in patient care practices. List two appropriate uses of atypical antipsychotics. Describe when non statins may be considered for dyslipidemia. Compare extended release carbidopa/levodopa (Rytary)to other formulations. Explain three strategies for safe use of fentanyl patches. Pharmacy Technician Objectives Identify emerging trends in drug therapy and their place in pharmacy practice and operations. List two appropriate uses of atypical antipsychotics. Describe when non statins may be considered for dyslipidemia. Compare extended release carbidopa/levodopa (Rytary) to other formulations. Explain three strategies for safe use of fentanyl patches. Inappropriate Use of Atypical Antipsychotics 1
Sovaldi (sofosbuvir) $7.9 billion Abilify (aripiprazole) $7.8 billion Humira (adalimumab) $7.2 billion Aripiprazole Generics Not as prone to weight gain and sedation as olanzapine or quetiapine But there are still concerns: Restlessness, risk of tardive dyskinesia, interactions, etc Generics won t provide immediate cost savings Efficacy Adverse Effects Varies by drug/condition Weight gain Metabolic effects (glucose, lipids, etc) Sedation QT prolongation Drug interactions Hyperprolactinemia Extrapyramidal side effects Tardive dyskinesia Depression Behavioral problems in children Insomnia Dementia 2
Use of Atypicals: Depression Suggest saving atypicals for patients with treatment resistant depression Those who don t respond well to: At least 2 different optimized antidepressants Combined antidepressant therapy Use of Atypicals: Depression Atypicals may be tried as augmenting agents One more patient in 9 will respond when an atypical is added to antidepressant therapy If needed, suggest a low dose of: Aripiprazole Quetiapine Olanzapine Use of Atypicals: Behavioral Problems Suggest saving atypicals for children with: Psychosis Severe aggressive or disruptive behaviors If needed, suggest aripiprazole or risperidone for severely impaired children with autism Use of Atypicals: Insomnia Discourage use of atypicals No evidence quetiapine or others improve sleep duration Recommend other options instead Sleep hygiene Treating underlying causes Zolpidem, trazodone, etc Use of Atypicals: Dementia Discourage use of atypicals One more death for every 50 100 dementia patients treated with an atypical for 8 12 weeks BOXED WARNING Increased mortality in elderly patients with dementia related psychosis: Use of Atypicals: Dementia Recommend non drug measures and evaluate underlying causes first Recommend atypicals only for dementia patients: With disabling delusions, hallucinations, agitation Who pose danger to themselves or others Elderly patients with dementia related psychosis treated with antipsychotic drugs are at an increased risk of death. 3
Use of Atypicals: Dementia If needed, suggest ¼ to ½ the usual starting dose of: Risperidone Olanzapine Aripiprazole Quetiapine Reevaluate need every 3 6 months Suggest tapering if possible Practice Pearls In most cases, help optimize other drugs with better evidence and fewer side effects first Consider drug, dose, duration Recommend monitoring weight, blood glucose, and lipids Suggest using lowest effective dose of an atypical Role of Non-Statins for Dyslipidemia 4
Bile acid sequestrants Non statins Ezetimibe Fibrates LDL Goals Specific Statin Doses Proven to Benefit Niacin Omega 3 fatty acids Adding a non statin to a statin hasn t been proven to further reduce CV mortality Adding a non statin could lead to a suboptimal statin dose being used Suggest saving non-statins for special situations... and stopping them when there s no good reason to continue. 5
Evaluate Statin Use Emphasize adherence to lifestyle changes and evidence based statin dose first Assess statin tolerance Encourage patients to take stock of any muscle symptoms before starting the statin Look for potential interactions Especially with simvastatin, lovastatin, atorvastatin Consider a lower dose, different statin, etc Role of Non-Statins Add on therapy Monotherapy Bile acid sequestrants Advise saving nonstatin add ons for patients with a prior cardiovascular event Who can t tolerate a highintensity statin (atorvastatin 80 mg, etc) Who don t get expected % LDL lowering from a statin Non statins Ezetimibe Fibrates Niacin Omega 3 fatty acids Which Non-Statins to Consider as Add- On Therapy? No good evidence of improved CV outcomes when adding on: Bile acid sequestrants, fibrates, niacin, omega 3s Suggest ezetimibe if a non statin add on is needed Only non statin shown to improve CV outcomes when added to a statin Which Non-Statins to Consider as Add- On Therapy? Role of ezetimibe IMPROVE IT trial Modest benefit in specific high risk patients One less CV event for every 50 ACS patients on ezetimibe + simvastatin 40 mg x 7 years compared to simvastatin alone Did not reduce mortality No evidence of improved CV outcomes when Added to a statin in lower risk patients Used alone 6
Role of Non-Statins Add on therapy Monotherapy Suggest saving nonstatin monotherapy for certain patients High CV risk and can t use a statin Very high triglycerides Which Non-Statins to Consider as Monotherapy? For high cardiovascular risk, suggest meds that seem to reduce CV events when used alone: Bile acid sequestrant Gemfibrozil Niacin Which Non-Statins to Consider as Monotherapy? Bile acid sequestrants (cholestyramine, etc) For high LDL Gemfibrozil High triglycerides and low HDL Niacin Caution about hyperglycemia, muscle pain, liver toxicity, flushing, etc Which Non-Statins to Consider as Monotherapy? For very high triglycerides: Emphasize lifestyle changes Help optimize blood glucose control Recommend a statin first in most patients Suggest saving omega 3 fatty acids or fibrates if triglycerides 500 mg/dl or approaching 1000 mg/dl No proof using these meds to triglycerides improves CV outcomes 7
Parkinson s Disease Background: Parkinson s Disease Progressive neurologic disease affecting movement Occurs due to: Lack of dopamine due to loss of nerve cells in certain areas of the brain Characterized by: Tremor, rigidity, bradykinesia, postural instability Carbidopa/ levodopa Dopamine agonists Other options Immediate release (Sinemet, etc) Sustained release (Sinemet CR, etc) Extended release (Rytary) Pramipexole (Mirapex, Mirapex ER, etc) Ropinirole (Requip, Requip XL, etc) Rotigotine (Neupro) MAO B inhibitors (selegiline, rasagiline, etc) Anticholinergics (benztropine, trihexyphenidyl, etc) Amantadine COMT inhibitors (entacapone, tolcapone, etc) Disease progression Drug efficacy Control of Parkinson s symptoms Dopaminerelated side effects 8
Carbidopa/Levodopa Most effective drug for Parkinson s symptoms First line, especially in elderly patients Long term use associated with: Dyskinesias Motor fluctuations on off, wearing off Side effects Nausea, orthostatic hypotension, confusion, etc Carbidopa/Levodopa Immediate or controlled release can be used Start low, go slow with dosing Suggest titrating to lowest effective dose After the honeymoon is over... After the Honeymoon To reduce off time : Suggest levodopa dosing interval by 30 60 minutes Point out sustained release (Sinemet CR, etc) does not reduce off time better than immediate release Probably because it takes ~2 hours for CR to kick in Some patients may take both IR + CR Other options: Adding a dopamine agonist, COMT inhibitor, or MAO B inhibitor Carbidopa/Levodopa Extended-Release (Rytary) Similar onset to immediate release Starts to work within an hour, faster than CR Similar duration to sustained release Lasts about 6 hours, longer than IR Reduces off time by ~70 minutes/day compared to IR Too soon to say how it compares to CR 9
Carbidopa/Levodopa Extended-Release (Rytary) Suggest saving Rytary for advanced Parkinson s Consider it an alternative for patients: Taking both the IR + CR forms Who still have off time despite taking other carbidopa/levodopa forms 4 times daily Costs ~$700/month Compared to ~$200/month for generics Carbidopa/Levodopa Extended-Release (Rytary) Explain a higher dose will be needed Rytary has lower bioavailability than IR or CR Dyskinesiasmay worsen during a switch Ensure patients can handle high pill burden Usual dosage: 3 4 caps TID Check that other carbidopa/levodopa forms are stopped when Rytary is started Carbidopa/Levodopa Extended-Release (Rytary) Advise swallowing capsule whole May also be sprinkled onto applesauce Watch for product mix ups Rytary is available in 4 carbidopa/levodopa strengths 23.75 mg/95 mg 36.25 mg/145 mg 48.75 mg/195 mg 61.25 mg/245 mg Safe Use of Fentanyl Patches 10
Fentanyl Patches Fentanyl Patches 12.5 25 50 75 100 12.5 25 37.5 50 62.5 75 87.5 100 *Note: products designated as 12 deliver dose of 12.5 *Note: products designated as 12 deliver dose of 12.5 Ensuring Safe Use of Fentanyl Patches Ensure fentanyl patches are used only in opioid tolerant patients with chronic pain In general, patients on oral morphine 60 mg/day or equivalent for 1 week Watch for use in acute, post op, or mild pain Ensuring Safe Use of Fentanyl Patches Be alert for patients with respiratory problems Watch for drug interactions with CYP3A4 CYP3A4 inhibitors may increase or prolong effects of fentanyl and could lead to respiratory depression Ketoconazole, clarithromycin, diltiazem, grapefruit juice, nefazodone, etc Ensuring Safe Use of Fentanyl Patches Continue to recommend starting with usual standard doses Recommend individualizing based on patient factors and clinical judgment Age, renal/liver function, interactions, etc Daily Dose of Oral Morphine Starting Fentanyl Patch Dose 60 134 mg 25 135 224 mg 50 225 314 mg 75 315 404 mg 100 Ensuring Safe Use of Fentanyl Patches When switching from fentanyl patch another opioid Do not use same conversion May overestimate new opioid dose 11
Intermediate Strength Fentanyl Patches Fentanyl Patches Suggest saving the intermediate strengths Consider if smaller steps needed during dose adjustments Consider to avoid using multiple patches 12.5 25 37.5 50 62.5 75 87.5 100 *Note: products designated as 12 deliver dose of 12.5 Intermediate Strength Fentanyl Patches Intermediate strength patches may be more expensive than standard doses 25 $100/month 37.5 $450/month 50 $150/month Point out that using one patch is preferred to multiple patches to reduce risk of errors Ensuring Safe Use of Fentanyl Patches Avoid dispensing mishaps Select strengths carefully and closely look at Rxs 87.5 patch could be confused with 37.5 Watch decimal points What do you tell patients? Practice Pearls Remind patients to remove the old patch before applying a new one Fentanyl can still be absorbed from old patch Help patients set up a dosing calendar Advise avoiding heating pads, electric blankets, hot tubs, etc Heat can fentanyl absorp on Tell patients never to cut fentanyl patches 12
Practice Pearls Proper storage Keep out of reach of children auxiliary label Advise storing unused patches in a secure location away from children or pets Proper disposal Fold sticky sides of patch together and flush down toilet Remind patients not to dispose of fentanyl patches in household trash http://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/ensuringsafeuseofmedicine/safedisposalofmedicines/ucm186187.htm Practice Pearls Caution about use with other CNS depressants Educate patients and caregivers of signs of fentanyl overdose Shallow/slow breathing, extreme sleepiness, unresponsive, etc Dispense with a MedGuide Flozins and Ketoacidosis 13
SGLT2 Inhibitors and Ketoacidosis Risk of ketoacidosis seems to be a class effect Canagliflozin (Invokana, etc) Dapagliflozin (Farxiga, etc) Empagliflozin (Jardiance, etc) SGLT2 Inhibitors and Ketoacidosis Diabetic ketoacidosis usually occurs: When insulin levels are too low During prolonged fasting In patients with type 1 diabetes With very high blood glucose levels Ketoacidosis with SGLT2 inhibitors is different Seen in type 1 or 2 diabetes Glucose levels near normal or only slightly elevated SGLT2 Inhibitors and Ketoacidosis Watch for high risk patients Recent in insulin dose, acute illness, dehydration, renal impairment, reduced food/fluid intake Symptoms often occur within 2 weeks after starting the flozin But can happen at any time Bottom Line Tell patients to stop the flozin and seek medical help for symptoms of ketoacidosis: Difficulty breathing, nausea, vomiting, abdominal pain, confusion, unusual fatigue, etc Be aware ketoacidosis may occur even if blood glucose is not very high Continue to warn about other flozin side effects Yeast infections, UTIs, hypotension, etc Practice Pearls Continue to weigh pros and cons of flozins as a metformin add on for type 2 diabetes Caution about using flozins in renal impairment Moderate renal impairment: avoid dapagliflozin Severe renal impairment: avoid all flozins Report adverse effects of SGLT2 inhibitors to the FDA MedWatch program Polls/Questions 14