the burgeoning role of in therapeutics...
TRANSCRIPT
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
The Burgeoning Role of Pharmacy in Opioid Therapeutics
and Mitigating AbuseSpeaker: Jeffrey Fudin, PharmD, DAAPM, FCCP
Adjunct Associate Professor of Pharmacy
Western New England University College of Pharmacy
Adjunct Assistant Professor of Pharmacy Practice, University of Connecticut School of Pharmacy
Founder and Chair, PROMPT (Professionals for Rational Opioid Monitoring and Pharmacotherapy)
Owner and Managing Editor, PainDr.com and Pain Blog
Albany, New York
Moderator: Ernest J. Dole, PharmD, PhC, FASHP, BCPS
Clinical Pharmacist, University of New Mexico Hospitals
and
Clinical Associate Professor
University of New Mexico
Health Sciences Center, College of Pharmacy
Albuquerque, New Mexico
Disclosures
Jeffrey Fudin is on the speakers’ bureaus for Millennium Healthcare and Astra Zeneca and he is a consultant to Millennium Healthcare and Zogenix. He also serves as a section editor for Pain Medicine and on the editorial board of Practical Pain Medicine.
Ernest J. Dole is a speaker for Millennium Health
APhA’s editorial staff declares no conflicts of interests or financial interests in any products or services mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see the Education and Accreditation Information section at www.pharmacist.com/education.
Development and Support
This activity was developed by the American Pharmacists Association and supported in part by an independent educational grant from Purdue Pharma L.P.
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
4
This webinar is intended to be primer for APhA Annual Meeting – held March 27‐30, 2015 in San Diego. To register go to: aphameeting.org.
2‐hour live session held at APhA2015, “A Review of Abuse Deterrent Formulations”
Other Abuse Deterrent webinars located at pharmacist.com: (available after 12/15/14)
“An Overview of Abuse Deterrent Formulation”
Attendance Code
JF14
To obtain CPE credit for this activity, you are required to actively participate in this session. The attendance code is needed to access the evaluation and CPE form for this activity. Your CPE
must be filled by December 18, 2014 in order to receive credit.
Accreditation Information
The American Pharmacists Association is accredited by theAccreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This activity, The Burgeoning Role of Pharmacy in Opioid Therapeutics and Mitigating Abuse, is approved for 1 hours of continuing pharmacy education credit (0.1 CEUs). The ACPE Universal Activity Number assigned by the accredited provider is: 0202‐0000‐14‐179‐L04‐P. To obtain continuing pharmacy education credit for this activity, participants will be required to actively participate in the entire webinar and complete an assessment and evaluation located at www.pharmacist.com/live‐activities by December 18, 2014.
Initial Release Date: December 4, 2014Target Audience: PharmacistsACPE Activity Type: Knowledge‐basedLearning Level: 2Fee: There is no fee for this activity
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Learning Objectives
List various roles of pharmacist as part of the interdisciplinary pain team.
Discuss validated risk stratification tools to anticipate risks of abuse and misuse among patients receiving long‐term opioid therapy.
Outline unique qualifications of the pharmacists to interpret urine drugs screens and need for serum monitoring.
Describe miscalculated risks in opioid dose conversions with considerations to unique patient variability including polymorphism and pharmacogenetics.
Multiple Types of Pain
Adapted from: Woolf CJ. Ann Intern Med. 2004;140:441-451.*Chong MS, Bajwa ZH. J Pain Symptom Manage. 2003;25:S4-S11.
A. Nociceptive Pain
B. Inflammatory Pain
C. Neuropathic Pain
D. Noninflammatory/Non-neuropathic pain
Noxious peripheral
stimuli
Peripheral nerve damage
No known tissue or nerve damage
Abnormal central processing
Multiple mechanisms
Brain
Brain
Brain
Brain
Inflammation
• Patients may experience multiple pain states simultaneously*
Sustainedcurrents
PeripheralNociceptive
Fibers
Transient Activation
ACUTEPAIN
Surgicalinjury and
inflammation
Neuroplasticity and Related Counseling in the Community Setting
SustainedActivation
PeripheralNociceptive
Fibers
Sensitization
CHRONIC PAIN
CNSNeuroplasticity
Hyperactivity
Structural Remodeling
SUBACUTE PAIN
1. Woolf CJ. Ann Intern Med. 2004;140:441-51.2. Petersen-Felix S, Curatolo M. Swiss Med Weekly. 2002;132:273-8.3. Woolf CJ. Nature.1983;306:686-8.4. Woolf CJ et al. Nature. 1992;355:75-8.
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Rational Polypharmacy
Advantages
• Reduction in pain intensity
• Reduction in Rx toxicity & SEs
• Improved efficacy
• Possible improvement in surgical outcome & decreased LOS?
Disadvantages
• Requires knowledge of drugs, PK data, & pharmacodynamics
• Every analgesic has its own unique adverse event profile
• May increase drug‐drug interactions
1. Sinatra RS. Ann Meeting Cleveland Soc of Anesthesiology. Nov 2010.2. Kehlet H, Wilmore DW. Am J Surg. 2002;183:630‐41.
Managing Opioid Side Effects
Side Effect Treatment
• Constipation
• Nausea and vomiting
• Sedation
• Itching
• Edema and sweating
• Dizziness
• Confusion
• Endocrine dysfunction
• Urinary retention
• Increase fluid intake; use of cathartics, stoolsofteners, enemas, and nonopioid analgesics
• Switch opioid; use antiemetic
• Lower dose; add stimulants?
• Switch opioid; antihistamines
• Switch opioids
• Anti vertiginous agents
• Titrate dose; switch opioid; add neuroleptic
• Endocrine monitoring; testosterone replacement
• Switch opioids
• Risk of falling for the elderly • Lower dose; use nonopioid analgesics
Therapeutic Strategies in Pain Management
• Lifestyle changes
• Rehabilitative
• Psychological
• Complementary and integrative medicine
• Educational
• Pharmacotherapy
• Injection, surgical, neuromodulation
Fine PG, Portenoy RK. A Clinical Guide to Opioid Analgesia. Minneapolis, MN: McGraw-Hill; 2004.
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Types of Screening Tools
• Risk Assessment Tools
• SOAPP
• SOAPP‐R
• ORT
• DIRE
• Opioid Misuse Tools
• PADT
• COMM
• ABC
Risk Assessment Tools
Question Formats Indications Advantages Disadvantages Scoring Validated
SOAPP1 5, 14, 24 1° Care, Assess for high abuse risk, suitability for long‐term opioid tx, preferable to ORT in high‐risk populations
Best psychometrics, less susceptible to deception, 5‐10 minutes
Dependent on patient reporting, Copyrighted
Numeric, simple to interpret
Yes, 14 quest ion studied in 396 pts
SOAPP‐R2 24 Primary Care 5 minutes, Cross‐validated, Less susceptible to overt deception c/t SOAPP
Less sensitive and less specific than SOAPP
Numeric, simple to interpret
Yes, 283 pts
ORT3 5 Categorizes patients as low risk, moderate risk, and high risk
Less than 1 minute, simple scoring, high sensitivity & specificity when stratifying patients
1 question in the ORT is limited by patient’s knowledge of family history of substance abuse
Numeric, simple to interpret
Yes, (male and female), Preliminary Validation in 185 patients at 1 pain clinic, high degree of sensitivity and specificity
DIRE4 7, by ptinterview
Risk of opioid abuse and suitability of candidates for long‐term opioid therapy
2 minutes, score correlates well with patient’s compliance & efficacy of long‐term opioid therapy
Prospective validation needed
Numeric, simple to interpret
?, Retrospective validation only of 61 pts over 38 months
1. J Pain Symptom Manage. 2006;32:287–93. 2. J Pain. 2008; 9(4):360‐372.3. Pain Med 2005;6:432–42.4. J Pain 2006;7:671–81.
Opioid Abuse Tools
Opioid Misuse Tools
Question Formats Indications Advantages Disadvantages Scoring Validated
PADT5N/A To streamline the
assessment of outcomes in patients with chronic pain, 2‐sided chart note based on 4‐A’s*
5 minutes, Documents progress over time, Complements a comprehensive clinical evaluation
Not intended to be predictive of drug‐seeking behavior or predict positive or negative outcomes to opioid therapy
N/A Further studies needed to confirm the reliability and validity, Studied in 388 patients by 27 clinicians
COMM6
17 To assess aberrant medication‐related behaviors of chronic pain patients
10 minutes, Useful in assessing & reassessing adherence to opioid Rx(s)
Long‐term reliability is unknown
Numeric 222 pts, Long‐term reliability is unknown, Validated in small study, needs to be replicated
ABC720 questions Ongoing clinical
assessment of chronic pain patients on opioid therapies
Concise and easy to scoreStudied in the VA setting
Needs validation in non‐VA setting.
Score of ≥3 indicates possible inappropriate opioid based on Y/N answers
Studied 136 veterans in a multidisciplinary VA Chronic Pain Clinic
5. Clin Ther. 2004;26:552–61.6. Pain. 2007; 130(1‐2):144‐156.7. J Pain Symptom Manage. 2006;32:342‐351.
Opioid Misuse Tools
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
16
The Opioid Pendulum
Opiophobia
Balance of Addiction Medicine and Pain
Management Principles1
Opiophillia
1Gourlay DL et al. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Medicine, 2005;6(2):107‐112.
Alliance of States with Prescription Monitoring Programs. http://www.namsdl.org/library/6D4C4D9F-65BE-F4BB-A428B392538E0663/Last accessed 11/7/2014
Which of the following CYP450 enzymes is associated with methadone cardiotoxicity?
A. 2C19
B. 2D6
C. 2B6
D. 3A4
18
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
What is a pitfall of UDTs?
A. False negatives
B. False positives
C. Adulterated sample
D. All of the above
19
The last state to enact a PDMP was:
A. Tennessee
B. Idaho
C. Missouri
D. Florida
20
Which of the following dehydroxylated phenanthrenes has a similar mechanism of action to methadone without the metabolic problems associated with Phase I metabolism?
A. Dextromethorphan
B. Levorphanol
C. Buprenorphine
D. Nalbuphine
21
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Pain Management CompetenciesRoles of the Pharmacy Pain Specialist
• Chronic pain syndromes
• Pain pharmacotherapy
• Interventional therapies
• Risk assessment and management
• Toxicology and urine drug screening evaluation
• Behavioral interventionso Motivational interviewing
• Addiction medicine
• Inter‐professional communication and collaboration
• Responsible opioid prescribing/universal precautions
• Referrals
Herndon CM et al. J Pain Symptom Manage. 2012;43(5):925-944.
Pharmacists: Natural Experts for UDT Interpretation
23
ImmunoassayQualitative Testing
Laboratory‐based Quantitative Testing
“Urine Drug Screen” “Urine Drug Test”
Qualitative testing Quantitative Testing
In‐clinic or hospital immunoassay
Laboratory‐based GC‐MS (gas chromatography‐mass spectrometry) or LC‐MS/MS (liquid chromatography tandem mass spectrometry)
Identifies primarily drug classes, present/absent
Identifies specific drugs, medications,and metabolites
URINE control or YOU’RE in control
Available at http://paindr.com/?s=urine+control. Last accessed 11/10/2014
ImmunoassayQualitative Testing
Laboratory‐based Quantitative Testing
“Urine Drug Screen” “Urine Drug Test”
Qualitative testing Quantitative Testing
In‐office immunoassay or laboratory‐based immunoassay
Laboratory‐based GC‐MS (gas chromatography‐mass spectrometry) or LC‐MS/MS (liquid chromatography tandem mass spectrometry)
Identifies primarily drug classes, present/absent
Identifies specific drugs, medications,and metabolites
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
The Clean Whiz Kit http://www.youtube.com/watch?v=91knqnsu_hU
Chemical Classes of Opioids
PHENANTHRENES BENZOMORPHANS PHENYLPIPERIDINES DIPHENYLHEPTANES
MORPHINE PENTAZOCINE MEPERIDINE METHADONERx EXAMPLES > morphine pentazocine meperidine methadone
codeine diphenoxylate fentanyl propoxyphenehydrocodone* loperamide sufentanilhydromorphone* alfentanillevorphanol* remifentaniloxycodone*oxymorphone*buprenorphine*nalbuphinebutorphanol*naloxone*heroin (diacetyl morphine)
X-SENSITIVITY > PROBABLE POSSIBLE LOW RISK LOW RISK
*These agents lack the 6-OH group of morphine, possibly decreasing cross-sensitivity within the phenanthrene group. Reisine T, Pasternak G. Opioid analgesics and antagonists. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill Companies; 1996:521-555.Willette RE. Analgesic agents. In: Delgado JN, Remers WA, eds. Wilson and Gisvold’s Textbook of Organic Medicinal Chemistry. 9th ed. JB Lippincott Company, Philadelphia, Pa. 1991:629-654.Courtesy of Dr. J. Fudin 2003
tapentadol & tramadol athttp://paindr.com/wp‐content/uploads/2012/05/Opioid‐Chemistry‐09‐2011.pdf. Last accessed 11/10/2014.
Chemical Classes of Opioids (continued)Dimethylamino hydrochlorides
Tapentadol Tramadol
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
UDT Unexpected Results‐1
o N = 470 patients; 8 prescribing physicians
o Abnormal or unexpected UDT if…
• Absence of prescribed opioid
• Presence of non‐prescribed controlled substance
• Presence of illicit substance
• Adulterated sample
28
Michna E, Jamison RN, Pham LD, et al. Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings. Clin J Pain. 2007;23:173‐179.
UDT Unexpected Results‐2
55% Normal (expected)
17.6% Illicit Substances
14.5% Unprescribed Drug
10.2% Prescribed Drug Absent
2.6% Adulterated
29
Michna E, Jamison RN, Pham LD, et al. Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings. Clin J Pain. 2007;23:173‐179.
Serum versus Urine (Partial Chart)
30
Available at http://paindr.com/wp‐content/uploads/2012/05/Opioid‐Chemistry‐09‐2011.pdf. Last accessed 11/10/2014
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Available Online OpioidConversion Calculators
WA State Agency
Med Calc
Pain Research
Pain Physicians
Hopkins
Palliative Care
Global RPh
Practical Pain Management (PPM)
Shaw K, Fudin J. Evaluation and comparison of online equianalgesicopioid dose conversion calculators. Practical Pain Management. 2013;13(7):61‐66.
(+/‐) % Variation (Compared to Manual Calculation)
‐33%
‐55%
+100%
+242%
VARIOUSOPIOIDS
FENTANYL
METH
ADONE
0%
RISKS:Underdose &Withdrawal
RISKS:Overdose & Death
Shaw K, Fudin J. Evaluation and comparison of online equianalgesicopioid dose conversion calculators. Practical Pain Management. 2013;13(7):61-66.
Variability in Opioid Equivalence Survey
Sept 13 through Nov 4, 2013, 362 Respondents
RPhs, MD/DOs, NPs, PAs
Convert to Daily MEQ:
– Hydrocodone 80 mg; Fentanyl 75 mcg/hr; Methadone 40 mg; Oxycodone 120 mg; Hydromorphone 48 mg
Rennick A, Atkinson T, Cimino N, McPherson ML, Fudin J. Variability in Opioid Equivalence. (Poster: 9‐236). American Society of Health‐System Pharmacists (ASHP) 2013 Midyear Clinical Meeting and Exhibition; Orlando, FL.
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Rennick A, Atkinson T, Cimino N, McPherson ML, Fudin J. Variability in Opioid Equivalence. (Poster: 9‐236). American Society of Health‐System Pharmacists (ASHP) 2013 Midyear Clinical Meeting and Exhibition; Orlando, FL.
What do you think were the most outrageous conversions?
Serum Fentanyl Concentrations Following Multiple Applications of Duragesic 100 mcg/h (n=10)
Duragesic (Fentanyl Transdermal System) Prescribing Information. Available at http://www.duragesic.com/duragesic/shared/pi/duragesic.pdf#zoom=100. Accessed July 27, 2008.
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Methadone Statistics(CDC 2012)
• 2% of prescriptions for opioid analgesics are for methadone
• Methadone accounts for nearly 1 in 3 prescription opioid overdose deaths in the U.S., 6X times the number in 2009
http://www.cdc.gov/features/vitalsigns/methadoneoverdoses/
Fudin J, Marcoux MD, Fudin JA. Mathematical model for methadone conversion examined. Practical Pain Management. 2012;12(8):46-51.
Fudin J, Marcoux MD, Fudin JA. Mathematical model for methadone conversion examined. Practical Pain Management. 2012;12(8):46-51.
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
40
Met
had
on
e (m
g)
Morphine (mg)
Equianalgesic Dose of Morphine to Methadone
300 mg Morphine = 60 mg Methadone
302.5 mg Morphine = 30 mg Methadone
Case #1: Rifampin & Morphine
• 51 YOWM with hx of heroin abuse
• Admitted to hospital with endocarditis
• RX on admission:
– Oxacillin 2 g, infuse over 30 min q4h IV
– Hydromorphone 2 mg/1 mL q4h PRN IV
– Nystatin 500,000 units/5 mL PO TID
– Gentamicin 100 mg, infuse over 30 min q8h
– Warfarin 7.5 mg PO daily
– Lactobaccillus 1 tab PO BID
– Omeprazole 40 mg PO BID
– Enoxaparin 80 mg/0.8 mL BID SQ
– Rifampin 600 mg PO daily
Fudin J, Fontenelle DV, Payne A. Rifampin reduces oral morphine absorption; a case of transdermal buprenorphine selection based on morphine pharmacokinetics. Journal of Pain and Palliative Care Pharmacotherapy. 2012;26:362–367.
Case #1: Rifampin and MorphineDATE PLAN PATIENT RESPONSE
7/19 Discontinue hydromorphone Initiate morphine SA 75 mg PO q8hNo IV opioids under any circumstances, Clonidine 0.2 mg POQAM and 0.1 mg PO QPM36.9 (±15.1) ng/mL of serum free morphine for every 100 mg of morphine SR
3/10SERUM LEVEL ORDERED
EXPECTED = 83 ng/mLACTUAL= 19 ng/mL
7/24 Morphine SA 60 mg PO q8hMorphine sulfate 15 mg IRPO q8h PRN
3/10, No BT Rx requested
7/30 Morphine SA 45 mg 6 AM and2 PM Morphine SA 60 mg q10 PM IR coverage provided
3/10, No BT Rx requested
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Why is the serum morphine so low?
A. Rifampin is a potent CYP450 inducer that will lower serum morphine levels
B. Rifampin is a potent CYP450 inhibitor that will lower serum morphine levels
C. Rifampin does not affect CYP450
D. Morphine levels are diminished for another reason
The Answer
Rifampin induces the gastric P‐glycoprotein efflux pump
Case #1: Rifampin and Morphine
A. Buprenorphine transdermal is okay based on the prescribed dose
B. Based on FDA labeling, buprenorphine transdermal is contraindicated
C. Based on serum morphine of 19 ng/mL, buprenorphine transdermal is plausible
D. B and C above
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Pharmacokinetics of Methadone Methadone half‐life is 15‐60 hours
CYP450 Enzyme Metabolism1
– Substrate: 3A4, 2B6, 2C8, 2C9, 2C19, & 2D6 • Auto‐inducer 2D6 effected by genetic
pGP Substrate2
Membrane Transport2,3
– OATP, ABCB1 Excretion (15% fecal)
– EDDP (2‐ethyl‐1,5‐dimethyl‐3,‐3‐diphenylpyrrolinium)
– EMDP (2‐ethyl‐5‐methyl‐3,3‐diphenylpyraline)
46
1. Fudin J, Fontenelle DV, Fudin HR, Carlyn C, Ashley CC, Hinden DA. Potential P-glycoprotein Pharmacokinetic Interaction of Telaprevir with Morphine or Methadone. Journal of Pain and Palliative Care Pharmacotherapy. August 2013, Vol. 27, No. 3, Pages 261-267.
2. Miemi Pasanen MK, Neuvonen PJ. Organic anion transporter polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011;63:157–181.
3. Fonseca F, de la Torre R, D´ıaz L, et al. Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response. PLoS ONE 2011;6:e19527. doi: 10.1371/journal.pone.0019527.
Other Underappreciated Risks
Pharmacogenetic differences
– Metabolizer types
• Poor
• Intermediate
• Extensive
• Ultra‐rapid
Methadone enantiomers and 2B6
47
Pharmacology of Methadone Methadone is a racemic mixture
– R‐enantiomer is a highly affinity full agonist at the mu opioidreceptor
– Both R‐ and S‐enantiomers are N‐methyl‐D‐aspartate (NMDA) receptor antagonists
Produces pain relief in both acute and chronic pain conditions
Affinity and/or efficacy at other receptors (delta, kappa) are sufficiently low to rule out clinical significance
48
Bart G, Walsh SL. In: Cruciani RA, Knotkova H. Handbook of Methadone Prescribing and Buprenorphine Therapy. Spring. 2013; p. 62.
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Sub‐pops, Pharmacogenetics
Gerber JG et al. Stereoselective metabolism of methadone N‐demethylation by cytochrome P4502B6 and 2C19. Chirality. 2004;16:36‐44.
CYP3A4R‐methadoneParent Drug
EDDP inactive metabolite
S: Sorrowing outcome. (Cardiotoxic effects, QT prolongation with potential of Torsade de pointes
CYP2B6
S‐methadoneParent Drug
EDDP inactive metabolite
R: Responsible for analgesia
49
CYP2B6 demonstrates selectively metabalizes S‐enantiomerPotential risk?
Methadone Compared With Levorphanol
50
Levorphanol Methadone
Pharmacology:
Opioid agonist activity μ, κ1, κ3 >>κ2 μ
NE reuptake blockade NMDA inhibition
Pharmacokinetics:
Half‐life 11‐16 hours 15‐60 hours
Duration of action 6‐15 hours 4‐8 hours
Metabolic pathwayPhase II glucuronidation to levorphanol‐3‐glucuronide
3A4, 2B6, 2C19 mediated N‐demethylation to 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidene (EDDP)
Opioid chemistry Dehydroxylated phenanthrene Diphenylheptane
Dosing:
PO equivalent dose to 30 mg/day of PO morphine
4 mg 7.5 mg
Suggested starting dose in opioid naïve patients
1 mg (1/2 x 2mg tablet) PO TID to QID (Maximum daily starting dose = 4 mg)Titrate upward by up to 25% weekly, i.e. if starting at 1 mg PO QID first week, increase to 1 mg PO 5x daily at second week.
2.5 mg (1/2 x 5 mg tablet) PO TID (Maximum daily starting dose = 7.5 mg)Titrate upward by up to 25% weekly, i.e. if starting at 2.5 mg PO TID first week, increase to 2.5 mg PO 4 or 5x daily at second week.(Note: As the dose increases, percentage of upward titration decreases due to complex pharmacokinetics)
Atkinson TJ, Fudin J, Pandula A, Mirza M. Medication management in the elderly: unique and underutilized treatment options. Clinical Therapeutics. 2013;34:1669-1689.
Which of the following CYP450 enzymes is associated with methadone cardiotoxicity?
A. 2C19
B. 2D6
C. 2B6
D. 3A4
51
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
What is a pitfall of UDTs?
A. False negatives
B. False positives
C. Adulterated sample
D. All of the above
52
The last state to enact a PDMP was:
A. Tennessee
B. Idaho
C. Missouri
D. Florida
53
Which of the following dehydroxylated phenanthrenes has a similar mechanism of action to methadone without the metabolic problems associated with Phase I metabolism?
A. Dextromethorphan
B. Levorphanol
C. Buprenorphine
D. Nalbuphine
54
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Conclusions Rational polypharmacy is only rational if benefits outweigh risks
Have a healthy respect for drug interactions
Consider therapeutic challenges unique to varying populations and age groups
Don’t be shy about calling and communicating with colleagues
Conclusions
Healthy respect for CYP450 drug interactions
All that glitters is not gold…
– Remember P‐glycoprotein and titrate slowly
Use care in titrating opioids
Use RATIONAL polypharmacy…
– But consider the pharmacokinetic risks
Don’t be shy about calling a pharmacist
57
This webinar is intended to be primer for APhA Annual Meeting – held March 27‐30, 2015 in San Diego. To register go to aphameeting.org.
2‐hour live session held at APhA2015, “A Review of Abuse Deterrent Formulations”
Other Abuse Deterrent webinars located at pharmacist.com: (available after 12/15/14)
“An Overview of Abuse Deterrent Formulation”
© 2014 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Attendance Code
JF14
To obtain CPE credit for this activity, by 12/18 go to:
pharmacist.com/live‐activities login click “claim credit” enroll in the activity complete the assessment and evaluation