THE NALTREXONE CHALLENGE

Transcription

1 THE NALTREXONE CHALLENGE

2 DISCLOSURE Natasha Rodney-Cail, Pharmacist, Drug Evaluation Unit Has no conflicts of interest Maureen Allen Has no conflicts of interest

3 DONNA 68 years old Currently treated with naltrexone 50 mg daily for a history of alcohol and opioid use disorder She is scheduled for a total abdominal hysterectomy for uterine cancer What are the appropriate preoperative recommendations for this patient regarding her oral naltrexone regimen?

4 NALTREXONE Oral opioid receptor antagonist Analog of naloxone Indications Maintenance of opioid free state in detoxified, formerly opioid dependent individuals Component of alcohol dependence treatment to support abstinence and reduce risk of relapse

5 NALTREXONE Competitive binding at opioid receptors Blocks euphoric effects of opioids Not associated with tolerance or dependence Not associate with disulfiram-like reaction Dosed 50 mg OD Must only be started in opioid free state Flexible approach may be used in cases of supervised administration

6 Does it have a place in clinical practice?

7 13.1% of Canadian adults used opioids in % for nonmedical purposes One of the most challenging forms of addiction 3987 deaths in 2017 OUD Repeated occurrence of 2 clinically significant impairments in a 12 month period DSM-V OUD = opioid abuse + opioid dependence

8 GUIDELINES/RECOMMENDATIONS

9

10 Alcohol abuse AUD Alcohol dependence

11 2011 CCSA released Canada s low-risk Alcohol Drinking Guideline Excessive consumption is a leading cause of preventable death and disability DSM-V AUD Alcohol use causing clinically significant impairment or distress Alcohol most common drug used by Canadians 3 medication treatments available in Canada Abstinence is often primary goal Harm reduction strategy considered acceptable

12 Abstinence is the primary goal.if not attainable a harmreduction strategy is a desirable goal Pharmacotherapy with medical counselling Evidence supporting use of oral naltrexone revision 2016 The optimal dose and duration remain to be adequately addressed along with appropriate population and optimal treatment goal Medical counseling is effective without additional behavioral treatment by a specialist allowing for treatment of many patients with alcohol dependence in the primary care setting

13 POTENTIAL BENEFITS OF NALTREXONE Discourages the use of some of the most commonly abused substances: opioids & alcohol Offers an approach that differs from other therapies Utilizes a purely antagonistic approach eliminates the side effects of chronic opioid agonism (i.e. potential for withdrawal, constipation, tolerance etc.) But does it work?

14 EVIDENCE FOR OPIOID USE DEPENDENCE CADTH Evidence Bundles.informing Canada s response to the opioid crisis A 2017 review concluded oral naltrexone does not improve the duration of abstinence in OUD

15 NALTREXONE IN OUD Does not improve the duration of abstinence compared to placebo Subgroups of patients forced to abstinence Higher rates of retention and abstinence with naltrexone compared to placebo Less effective at maintaining abstinence compared to buprenorphine Studies conducted to date do not allow an adequate evaluation of oral naltrexone in OUD.. Maintenance therapy with naltrexone cannot be considered a treatment which has been scientifically proved to be superior to other kinds of treatment!

16 ADDITIONAL RCTs in OUD No difference in maintaining abstinence compared to placebo and behavioral therapy Patients taking the drug had fewer positive urine tests and longer duration of abstinence Less effective at maintaining abstinence compared to buprenorphine/naloxone Patients taking the drug had fewer positive urine tests

17 EVIDENCE FOR RETURN TO HEAVY DRINKING Naltrexone Acamprosate NNT = No significant difference NNT = Direct comparisons found no difference

18 EVIDENCE FOR RETURN TO ANY DRINKING Naltrexone Acamprosate NNT= NNT= No effect NNT= Direct comparisons found no difference

19 COMBINED PHARMACOTHERAPIES AND BEHAVIORAL INTERVENTIONS COMBINE Evaluated the efficacy of naltrexone, acamprosate and specialized behavioral counselling individually and in combination MM 16 week, DB, MC, RCT, M=1383 MM+ CBI All groups had increase in % days abstinent 23%-27% pre-study to 73%-80% during treatment Naltrexone/placebo Acamprosate/placebo Placebo/placebo Acamprosate/naltrexone Naltrexone/placebo Acamprosate/placebo Placebo/placebo Acamprosate/naltrexone Evaluated % days abstinent & risk of heavy drinking Patients receiving MM showed better outcomes when also receiving either CBI or naltrexone CBI+naltrexone did not further improve outcomes Naltrexone+acamprosate did not increase efficacy Acamprosate no greater efficacy than placebo Alcohol dependent patients may benefit from being treated by a health care professional who adopts medical management and utilizes either naltrexone and/or refers to a specialized alcohol counselor using CBI techniques

20 PHARMACOLOGICALLY CONTROLLED DRINKING Drinking alcohol while using an opioid antagonist blocks the reinforcing effects of alcohol Extinguishes craving.leading to reduced consumption Either daily naltrexone in non-abstinent patients OR Targeted use of medication (Sinclair method).administer 1-2 hours before alcohol consumption There is very little evidence to support this theory!

21 Can precipitate withdrawal if not completely free of opioids Risk of hepatocellular injury Blockade is surmountable Reduce tolerance can lead to overdose

22 CLINICALLY RELEVANT HARMS Potent opioid antagonist BUT blockade is surmountable Patients treated with naltrexone will respond to lower doses to opioids.reduced tolerance can lead to overdose

23 ARE WE USING NALTREXONE? A little bit..the number of patients in the Nova Scotia Provincial Drug Plan is going up.from 30 patients to >70 patients in the last 3 years Generally, using it for AUD or other indications..not for OUD

24 If I put my patient on naltrexone and they require surgery, how can I prepare them?

25 WHAT TO CONSIDER Oral naltrexone ½ life = 14 hours. Current recommendations are to discontinue naltrexone use 72 hours before elective surgery Discontinuation of naltrexone results in a vulnerable time for relapse (and potential overdose) for a previously opiate dependent patient, so, close observation and care is required

26 DONNA 68 years old Currently treated with naltrexone 50 mg daily for a history of alcohol and opioid use disorder She is scheduled for a total abdominal hysterectomy for uterine cancer