Optimizing Opioid Dependence Treatment A Guideline for Pharmacists

Transcription

1 Optimizing Opioid Dependence Treatment A Guideline for Pharmacists Module 3: Optimal Use of Methadone F e b r u a r y

2 Learning Objectives To know and understand the pathophysiology of substance dependence, the principles of addiction and the harm reduction strategies that are encouraged to increase not only the safety of individuals who use, but also the safety of our communities To recognize the signs and symptoms of opioid intoxication, withdrawal and dependence To know how to use methadone and buprenorphine safely and effectively in the treatment of opioid dependence To be able to apply the NLPB Standards of Practice for the Safe and Effective Provision of Medication for the Treatment of Opioid Dependence to ensure optimal patient care delivery

3 Exemption The NLPB Standards for the Safe and Effective Provision of Medications for the Treatment of Opioid Dependence and the Methadone Maintenance Treatment Standards and Guidelines from the College of Physicians and Surgeons of Newfoundland and Labrador do not apply to the use of methadone or buprenorphine specifically for pain management.

4 Outline Module 1: Substance Use Concepts Module 2: Pharmacotherapy of Opioid Dependence Module 3: Optimal Use of Methadone Module 4: Buprenorphine and Opioid Dependence Module 5: Applying the NLPB Standards of Practice for Opioid Dependence Treatment- Methadone Module 6: Applying the NLPB Standards of Practice for Opioid Dependence Treatment- Buprenorphine Module 7: Case Studies

5 Optimal Use of Methadone Module Three

6 Module 3 - Optimal Use of Methadone 1. Formulations and dosing 2. Dispensing best practices 3. Safety a. Minimizing risk of toxicity b. QT prolongation c. Concomitant treatments and special populations 4. Duration of treatment

7 Methadone: Formulations Methadone powder Methadone tablets Intended for pain management NOT opioid dependence Not subject to the NLPB Standards for Safe and Effective Provision of Medication for the Treatment of Opioid Dependence Available commercially-prepared solutions Methadone 1 mg/ml Methadone 10 mg/ml

8 Methadone: Formulations NLPB Standards for the Safe and Effective Provision of Medication for the Treatment of Opioid Dependence Must use commercially-prepared unflavored solution in 10 mg/ml strength Health Canada Manufacturing and Compounding Drug Products Policy Recommendation from ISMP Canada to use commercial product and to stock one concentration ONLY Must have measurement capacity to ensure accuracy of at least +/- 0.1 ml Standardization of concentration dispensed intended to optimize safety Methadone is a high alert medication

9 Methadone: Compounding NLPB Standards for the Safe and Effective Provision of Medication for the Treatment of Opioid Dependence Compounding permitted in the event of drug shortage issues only If compounded it must be done to a strength of 10 mg/ml A compounding log must be kept Refer to Standards for required information

10 Methadone Storage: Commercial Product Shelf-stable Can be stored up to six months at room temperature once opened Diluted preparations prepared in advance of patient consumption must be kept in: A secure refrigerator, or In a locked container in a standard refrigerator Each dose dispensed to the patient is to be diluted qs to 100 ml with a crystalline liquid Tang or Kool-Aid type product

11 Methadone Dispensing: Best Practices and Safety Checks Methadone is a high-risk medication with potentially fatal consequences when given in error Institute of Safe Medication Practices (ISMP) recommends the development of methadone procedures that support a second independent check of all measured doses prior to dilution See for more recommendations to optimize the safety of methadone The pharmacist should verbally confirm the dose with the patient and show the patient the dose label prior to ingestion of the dose

12 Methadone: Treatment Stages Stage 1: Early stabilization (0 2 weeks) Dose is increased safely, but rapidly enough to minimize significant withdrawal symptoms Stage 2: Late stabilization ( 2-6 weeks) Period during which the stable dose is being approached Stage 3: Maintenance (6+ weeks) When stable dose has been reached

13 Methadone: Dosing Recommendations Depends upon assessment of individual patient factors If there has been recent abstinence from opioid use (low dose) If there is risk of methadone toxicity (moderate dose) Degree of opioid dependence (high = higher dose) Initial doses typically in the mg range Adjusted upwards or downwards depending upon patient variables

14 Methadone: Dosing Recommendations Maximum starting dose = 30 mg Titrated according to patient tolerability and response Treatment targets include control of cravings and opioid withdrawal symptoms Efficacy and tolerability balance often within mg range Highly individualized based on differences in absorption, metabolism, tolerability and response See next slide for CPSNL Dosing Recommendation Chart

15 Methadone: Dosing Recommendations Patient Factors Initial Dose Dosing During Early and Late Stabilization Process Recent abstinence from opioids Higher risk for methadone toxicity No risk factors or recent abstinence 10 mg or less 20 mg or less 30 mg or less Dose Increases 5 mg or less Frequency Every 5 days or more Dosing During Maintenance Stage Dose Increases Frequency 5-10 mg Every 5-7 days 5-10 mg Every 3-5 days 5-10 mg Every 5-7 days mg Every 3-5 days 5-10 mg Every 5-7 days CPSNL Methadone Maintenance Treatment Standards and Guidelines

16 Methadone: Dosing Recommendations Evidence suggests maintenance doses in the range of 60 mg to 100 mg or more are associated with lower drop out rates and less illicit drug use Faggiano F, Vigna-Taglianti F, Versino E, Lemma P: Methadone maintenance at different doses for opioid dependence. Cochrane Database Systematic Reviews 2003 Continued co-use over prolonged periods of time requires re-evaluation MAY indicate a need to further titrate dose Optimal dose is one which Relieves withdrawal symptoms Blocks drug cravings Does not produce significant adverse effects Is individualized

17 Opioid Dependence Treatment: Duration Research is lacking as to when, in whom or how to withdraw opioid dependence treatment Studies comparing short and longer term use show better results with longer treatment durations RCT data beyond 12 months of treatment is lacking Available RCT data comparing weeks of treatment to treatment durations up to 12 months show better results with the longer treatment period No RCT data to inform treatment periods greater than one year Observational studies demonstrate A mortality benefit for those who remain on treatment Cessation of treatment poses a risk of relapse into opioid use

18 Opioid Dependence Treatment: Duration Should be viewed as open-ended and continue as long as clinically indicated Highly individualized Both risk of relapse and the consequences of relapse must be considered Should involve informed patient input Use should be periodically re-evaluated Addictions are complex and widely viewed as a chronic disease state Prolonged treatment periods should not be viewed as treatment failure

19 The Bad: Methadone and Safety Associated with an increased risk of mortality early in treatment Recent prospective population studies demonstrate an increased risk of mortality within the first two weeks of beginning MMT Respiratory depression Crude mortality rate of 17 per 1000 patient years Mortality > 6 x heroin users not on treatment and 98 x that of patients on MMT for longer periods Low therapeutic margin of safety especially in methadone naïve individuals Death has resulted with ingestion of a single 40 mg dose No ceiling effect to respiratory depression Prolonged half life and slow bio-accumulation also contributed

20 Opioid Toxicity Important for all health care providers in circle of care to know how to assess and identify Early signs include: Ataxia Slurred speech Nodding off Emotional lability Opioid toxicity leading to overdose characterized by: Decreased level of consciousness Respiratory depression Pinpoint pupils

21 Minimizing Risk of Toxicity Patient education Signs and symptoms Educate family members where appropriate Close follow-up during dose titration Efficacy Tolerability Concomitant substance use Minimize use of sedating drugs where clinically feasible Assess for drug-drug interactions Effective two-way communication between prescriber and pharmacist

22 The Bad: Methadone and Safety Concurrent use of benzodiazepines, alcohol and sedating medications increases the risk of death due to methadone toxicity Patient-specific factors may increase risk for toxicity Recent benzodiazepine use Use of other sedating drugs Concomitant drugs that inhibit methadone metabolism Decompensated hepatic disease Alcohol dependence Over 60 years of age Respiratory illnesses Lower opioid tolerance Recent incarceration Recent discharge from an inpatient rehab facility

23 Methadone & Benzodiazepines Benzodiazepine use in MMT patients associated with increased psychological distress, risk for overdose, higher risk of suicidal behavior, violence, impaired attention and memory, impaired driving and risk for continuing poly-drug use Bleich et al 2002, Brands et al 2008, Caplehorn & Drummer 2002, Darke et al 2010, Darke et al 2009, DeMaria et al 2000, Man Lan-Ho et al 2004 WHO Guidelines (2009) suggest that gradual withdrawal from benzodiazepines may be necessary for benzodiazepine users in MMT programs Use should be reviewed prior to MMT initiation and tapered and discontinued where clinically indicated

24 Methadone Take-Home Doses & Benzodiazepines Caution advised when considering initiation or continuation of take-home doses in patients on benzodiazepines or opioids unless: Patient is clinically stable, and Exceptional circumstances regarding the prescribing of these agents are met: Benzodiazepine is prescribed or recommended by a treating psychiatrist or neurologist, Opioids are prescribed or recommended by a treating physician for the short term treatment of acute pain, or Opioids are prescribed or recommended by a pain management specialist for chronic pain

25 Methadone Take-Home Doses & Benzodiazepines MMT physician should consult with the prescriber and controlled dispensing of both should occur to optimize safety Periodic re-evaluation of the continued indication of benzodiazepine or opioid is encouraged (CPSNL Standards) Pharmacist should document concerns in patient s record and take necessary action to address the concern in the interest of patient safety

26 Methadone & QT Prolongation Case reports of QT prolongation and Torsades de Pointe Higher doses used: > 150 mg per day There is drug accumulation Pre-existing cardiac disease Concomitant medications with QT prolongation risk Concomitant medications that inhibit methadone breakdown through CYP450 3A4 pathway Patients should be screened for risk factors for Torsades de Pointe

27 Risk Factors for Torsades de Pointe Use of cocaine and other substances Heavy alcohol consumption Family history of congenital long QT syndrome Electrolyte disturbances Medications that are associated with QT prolongation Structural heart disease: previous MI, cardiomyopathy or valve disease HIV infection Hepatic dysfunction Medications that affect methadone levels

28 Methadone: Drug Interactions Pharmacodynamic CNS depressant effects Pose greater risk for toxicity on treatment initiation Carry risk of CNS depression throughout treatment Alcohol, benzodiazepines and other CNS depressants QT prolongation Classifies based on 3 categories: at risk (eg; citalopram, erythromycin), possible risk and conditional risk For further information: barbara.thomas@easternhealth.ca Anticholinergic effects Urinary retention Constipation

29 Methadone: Drug Interactions Pharmacokinetic Metabolized through CYP450 3A4 (primary) and 2D6 pathways Inducers of CYP450 3A4 Decrease concentration of methadone May precipitate withdrawal or increased cravings due to loss of effect Moderate and strong inducers include carbamazepine, phenytoin, St. John s Wort, several antiretrovirals, others

30 Methadone: Drug Interactions Pharmacokinetic Inhibitors of CYP450 3A4 Increase concentration of methadone Risk for opioid toxicities including respiratory depression, QT prolongation Moderate and strong inhibitors include clarithromycin, erythromycin, grapefruit juice, several antiretrovirals, antifungals (such as ketoconazole) Consult drug interaction references to assess safety of specific agents

31 Methadone: Contraindications Absolute Hypersensitivity to methadone Significant respiratory compromise Paralytic ileus Relative Cardiac conduction abnormalities Chronic conditions accompanied by hypoxia, hypercapnia or decreased respiratory reserve

32 The Good: Methadone & Safety Once dose is stabilized, methadone has a demonstrated mortality benefit that continues for as long as methadone is given.

33 Special Populations Adolescents Pregnancy and lactation Opioid use and MMT Psychiatric illness

34 Special Populations: Adolescents Assess risk versus benefit Agonist therapies can be given However, alternate approaches should also be considered if: Duration of opioid use is relatively brief Highly motivated individual with a strong support system in place Opioid withdrawal and psychosocial supports may suffice

35 Methadone: Pregnancy & Lactation Opioid dependence treatment encouraged where indicated to restrict harms to the developing fetus and to enhance the ability to care for a young infant or small children Considered a priority referral for MMT Encourage contact with Opioid Treatment Centre or other referral source Close monitoring of mother and baby is needed throughout pregnancy and delivery Methadone is associated with neonatal abstinence syndrome

36 Methadone Pregnancy & Lactation Methadone considered standard of care based on long term exposure data Emerging safety data with buprenorphine suggest that it should also be considered (ACOG 2012) Dose increases or potentially split doses may be needed in second and third trimester Methadone and buprenorphine are considered to be breast-feeding compatible

37 Methadone: Pain Management Non-opioid analgesics recommended first-line for mild to moderate pain May need higher or more frequent dosing of methadone if opioids are clinically indicated Short term acute pain requiring opioids Split methadone dose with an additional mg added to the evening dose Give an additional opioid along with methadone Recommend to select one that has not been misused in the past Codeine or tramadol preferred followed by morphine if needed Recommended in small amounts for the shortest duration possible

38 Methadone: Mental Illness Concurrent disorders are common Stability of one disorder affects the other Must be treated in an integrative way To optimize benefit To manage risk On-going use of benzodiazepines and other sedating agents warrants assessment (CPSNL Standards) Indication Alternative therapies if clinically feasible Goal to stabilize illness and minimize risk

39 Methadone: Summary MMT is well established Efficacy is evidence-based Cost effective treatment MMT reduces drug use MMT decreases transmission of HIV, Hepatitis C and other communicable diseases MMT saves lives

40 References Standards for the Safe and Effective Provision for the Treatment of Opioid Dependence. Newfoundland and Labrador Pharmacy Board 2015 Methadone Maintenance Treatment. Standards and Guidelines. College of Physician s and Surgeons of Newfoundland and Labrador 2013 Addiction Treatment Standards. Clinical Guidelines and Standards of Practice in Newfoundland and Labrador. Department of Health and Community Services 2013 Trebault J, Fiellin. Current and Potential Pharmacological Treatment Options for Maintenance Therapy in Opioid-Dependent Individuals. Drugs 2012; 72(2): Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence. WHO 2009 Mattick RP, Kimber J, Breen C, Davioli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews 2008 Faggiano F, Vigna-Taglianti F, Versino E, Lemma P. Methadone maintenance at different dosages for opioid dependence. Cochrane Database of Systematic Reviews 2008 ACOG Committee Opinion No. 524: Opioid abuse, dependence and addiction in pregnancy. Obstet Gynecol 2012 May; 119(5): Jones H, Finnegan L, Kaltenback K. Methadone and Buprenorphine for the Management of Opioid Dependence in Pregnancy. Drugs April 2012, Vol 72, Issue 6 pp Farrell M, WodakA, Gowing L. Maintenance drugs to treat opioid dependence. BMJ 2012;344:e2823 doi: 10;1136/bmj.e2823 (published May 2012) Orser S, Elkader A. An Update on the Treatment of Opioid Dependence. Pharmacy Practice June 2011 Safe Methadone Practices ISMP Canada

41 Questions? Contact NLPB: Contact Program Developer: