Clinical Guideline / Formulary Document Pharmacy Department Medicines Management Services

Clinical Guideline / Formulary Document Pharmacy Department Medicines Management Services SUBSTANCE DEPENDENCY For full details of the of the medication discussed in this formulary including side effects, contraindications, drug interactions and monitoring see the Supplementary Product Characteristics available online at: http://www.medicines.org.uk/emc/ Service users should be offered information on treatments available: http://www.merseycare.nhs.uk/what_we_do/cbus/specialist_management_services/pharm acy/patient_information.aspx DUAL DEPENDENCY For persons presenting with 2 or more substances being misused the decision to carry out separate detoxification/stabilisation or concurrently should take into account the person s preference and the severity of dependence for both substances. However detoxification would usually follow the following order: 1 st Alcohol detoxification 2 nd Benzodiazepine detoxification 3 rd Opiate detoxification Specialist Advice Addiction services are available for advice: Kevin White: 0151 330 8074 Alcohol services at Windsor Clinic: 0151 525 5980 Relevant NICE Guidelines Alcohol-use disorders: diagnosis and clinical management of alcohol-related physical complications (Clinical Guideline 100 June 2010). Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence (Clinical Guideline 115 February 2011). Naltrexone for the management of opioid dependence. (Technology appraisal guidance 115 January 2007). Methadone and buprenorphine for the management of opioid dependence. (Technology appraisal guidance 114 January 2007). Drug misuse: opioid detoxification. (Clinical Guideline 52 July 2007) Substance dependency Review: Nov 2014 1

ALCOHOL DEPENDENCE Management of assisted alcohol withdrawal Benzodiazepines should not be administered when the patient is intoxicated and/or breath alcohol content is above 80mg/dl unless there is a history of seizures, in which case it can be given regardless. Benzodiazepines should not be prescribed if the patient is likely to continue drinking. Dose of benzodiazepines prescribed will depend on the assessment of severity of alcohol dependence (clinical history, number of units per drinking and severity of alcohol withdrawal symptoms). Check severity of symptoms using CIWA-AR score. Laboratory investigations may be necessary in order to correct deficiencies e.g. hypoglycaemia, hypokalaemia and hypomagnesaemia Ensure appropriate hydration. Fixed-dose regimens are recommended for routine use with symptom-triggered dosing reserved for use only with adequate monitoring. Front-loading dosing regimens are not recommended Vitamin supplementation Untreated vitamin deficiencies may result in Wernicke s encephalopathy/ that can progress to Korsakoff s psychosis, which may result in permanent cognitive damage. Alcohol withdrawal seizure Review withdrawal drug regimen Risk of alcohol withdrawal seizures may be higher with benzodiazepines with a short half-life such as oxazepam compared with longer half-life such as chlordiazepoxide Delirium Tremens Delirium tremens is a medical emergency that requires urgent treatment Review withdrawal drug regimen Maintenance Treatment Pharmacological treatment should always be adjuvant to counselling. Substance dependency Review: Nov 2014 2

Alcohol dependence Management of assisted alcohol withdrawal Chlordiazepoxide Chlordiazepoxide has a slower onset of action than diazepam or lorazepam, and has less potential for abuse. Doses of chlordiazepoxide above BNF limits should not be prescribed without prior discussion with a Consultant or Specialist Registrar. Fixed regimen. Gradually reducing over 7-14 days. Symptom-triggered regime. Service user is monitored on a regular basis and pharmacotherapy is given according to the service user s severity of withdrawal symptoms. Short term use only Other: Relative Cost Notes Diazepam It has similar efficacy to chlordiazepoxide, but has a greater potential for abuse as it has a Liquid faster onset of action. If diazepam is used in the community for acute alcohol detoxification, careful supervision is required. Short term use only Oxazepam Unlicensed use. For people with liver/pancreatic impairment after gastroenterologist advice Lorazepam Liquid Carbamazepine IR Tablets MR Tablets Not recommended: Relative Cost Notes Clomethiazole Other benzodiazepines - has been sought. Short term use only Unlicensed use. For people with liver/pancreatic impairment after gastroenterologist advice has been sought. Short term use only Unlicensed use. Adjunctive prophylactic treatment for patients with a past history of withdrawal seizures or epilepsy of any cause Alcohol combined with clomethiazole, particularly in persons with cirrhosis, can lead to fatal respiratory depression even with short-term use. Substance dependency Review: Nov 2014 3

Alcohol dependence Vitamin supplementation Thiamine PO Vitamin Co Strong Other: Relative Cost Notes For people at high risk of developing, or with suspected, Wernicke s encephalopathy. Pabrinex IM High-risk heavy drinkers who are malnourished. Wernicke s encephalopathy suspected or diagnosed. MHRA/CHM advice. Anaphylactic shock may occasionally follow injection (IM lower risk); resuscitation facilities should be available when parenteral thiamine is administered. Alcohol dependence Alcohol withdrawal seizure Diazepam PR Emergency treatment of fits. Other: Relative Cost Notes Lorazepam Tablets Liquid IM Not Recommended: Relative Cost Notes Phenytoin Emergency treatment of fits. Unlicensed use. Adjunctive prophylactic treatment for patients with a past history of withdrawal seizures or epilepsy of any cause. Substance dependency Review: Nov 2014 4

Alcohol dependence Delirium Tremens Lorazepam Tablets Liquid IM Other: Relative Cost Notes Olanzapine PO Olanzapine IM Haloperidol PO Haloperidol IM Unlicensed use Unlicensed use. Lowers seizures threshold. Use with caution. Unlicensed use. Lowers seizures threshold. Use with caution. Alcohol dependence Maintenance Treatment Relapse Prevention Acamprosate Initiated by specialist substance misuse teams in combination with psychological interventions. Ensure continuity of prescribing in primary care. Check LFTs & U&Es Other: Relative Cost Notes Disulfiram Initiated by specialist substance misuse teams in combination with psychological interventions. Ensure continuity of prescribing in primary care. Check LFTs & U&Es Naltrexone Unlicensed use. Initiated by specialist substance misuse teams in combination with psychological interventions. Not to be prescribed to patients on opioids. Ensure continuity of prescribing in primary care. Check LFTs & U&Es Baclofen Unlicensed use. Initiated by specialist substance misuse teams in combination with psychological interventions when there is high levels of anxiety and acamprosate, naltrexone or disulfiram are not appropriate. Antidepressants - Refer to relevant section. Antidepressants should not be routinely used for the treatment of alcohol misuse alone Substance dependency Review: Nov 2014 5

Alcohol dependence Symptomatic Relief First Line: Relative Cost Notes Zopiclone Insomnia. Cautious use when co-prescribing of benzodiazepines. Short-term use Prochlorperazine Nausea and vomiting Metoclopramide Nausea and vomiting Chlorphenamine Itching. Check for signs of liver disease. Paracetamol Pain. Caution in severe liver disease Ibuprofen Pain. Caution is asthmatic patients Loperamide Severe diarrhoea Peptac Heartburn Ensure plus Nutritional Supplementation Other: Relative Cost Notes Gaviscon Heartburn Substance dependency Review: Nov 2014 6

CLINICAL INSTITUTE WITHDRAWAL ASSESSMENT OF ALCOHOL SCALE, REVISED (CIWA-AR) Patient: Date: Time: Pulse or heart rate, taken for one minute: Blood pressure: NAUSEA AND VOMITING Ask Do you feel sick to your stomach? Have you vomited? Observation: 0 No nausea and no vomiting 1 Mild nausea with no vomiting 2 3 4 Intermittent nausea with dry heaves 5 6 7 Constant nausea, frequent dry heaves and vomiting TREMOR Arms extended and fingers spread apart Observation: 0 No tremor 1 Not visible, but can be felt fingertip to fingertip 2 3 4 Moderate, with patient s arms extended 5 6 7 Severe, even with arms not extended PAROXYSMAL SWEATS Observation: 0 No sweat visible 1 Barely perceptible sweating, palms moist 2 3 4 Beads of sweat obvious on forehead 5 6 7 Drenching sweats ANXIETY Ask Do you feel nervous? Observation: 0 No anxiety, at ease 1 Mild anxious 2 3 4 Moderately anxious or guarded, so anxiety in inferred 5 6 7 Equivalent to acute panic states as seen in severe delirium or acute schizophrenic reactions TACTILE DISTURBANCES Ask Have you any itching, pins and needles sensations, any burning, any numbness, or do you feel bugs crawling on or under your skin? Observation: 0 None 1 Very mild itching, pins and needles, burning or numbness 2 Mild itching, pins and needles, burning or numbness 3 Moderate itching, pins and needles, burning or numbness 4 Moderately severe hallucinations 5 Severe hallucinations 6 Extremely severe hallucinations 7 Continuous hallucinations AUDITORY DISTURBANCES Ask Are you more aware of sounds around you? Are they harsh? Do they frighten you? Are you hearing anything that is disturbing to you? Are you hearing things you know are not there? Observation: 0 Not present 1 Very mild harshness or ability to frighten 2 Mild harshness or ability to frighten 3 Moderate harshness or ability to frighten 4 Moderately severe hallucinations 5 Severe hallucinations 6 Extremely severe hallucinations 7 Continuous hallucinations VISUAL DISTURBANCES Ask Does the light appear to be too bright? Is its colour different? Does it hurt your eyes? Are you seeing anything that is disturbing to you? Are you seeing things you know are not there? Observations: 0 Not present 1 Very mild sensitivity 2 Mild sensitivity 3 Moderate sensitivity 4 Moderately severe hallucinations 5 Severe hallucinations 6 Extremely severe hallucinations 7 Continuous hallucinations HEADACHE, FULLNESS IN HEAD Ask Does your head feel different? Does it feel like there is a band around your head? Do not rate for dizziness or light-headedness. Otherwise, rate severity: 0 Not present 1 Very mild 2 Mild 3 Moderate 4 Moderately severe 5 Severe 6 Very severe 7 Extremely severe AGITATION Observation: 0 Normal activity 1 Somewhat more than normal activity 2 3 4 Moderately fidgety and restless 5 6 7 Paces back and forth during most of the interview, or constantly thrashes about ORIENTATION AND CLOUDING OF SENSORIUM Ask What day is this? Where are you? Who am I? Observations: 0 Orientated and can do serial additions 1 Cannot do serial additions or is uncertain about date 2 Disoriented for date by no more than 2 calendar days 3 Disoriented for date by more than 2 calendar days 4 Disoriented for place / or person SCORES: <10- mild withdrawal; 10-20 moderate withdrawal; >20 severe withdrawal Substance dependency Review: Nov 2014 7

Alcohol detoxification regime Please use CLINICAL INSTITUTE WITHDRAWAL ASSESSMENT OF ALCOHOL SCALE REVISED (CIWA-AR) to establish the severity of alcohol dependence and document full history and CIWA score in clinical records. Chlordiazepoxide regime Not to be administered if the patient is intoxicated and/or breath alcohol content is above 80mg/dl unless there is a history of seizures Not recommended in older adults and people with liver impairment. They may need shorter acting benzodiazepines (e.g. oxazepam). Seek advice. Check severity of symptoms using CIWA-Ar score. Mild(< 10 CIWA-AR Score) Chlordiazepoxide 5 mg PRN TDS if necessary Moderate (10 20 CIWA-AR score) DAY 1 DAY 2 DAY 3 DAY 4 DAY 5 10-20 mg QDS 10-15 mg QDS 5-10 mg QDS 5 mg QDS 5 mg BD Severe (>20 CIWA-AR score) (seek specialist advice) Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day 10 30-40 mg QDS 30-40 mg QDS 20-30 mg QDS 20-25 mg QDS 20 mg QDS 15 mg QDS 10 mg QDS 10 mg TDS 10 mg bd 10 mg nocte Adjuvant medication Thiamine 100mg PO BD/TDS Vitamin B complex Co-strong two tablets PO BD/TDS Chlordiazepoxide 5 mg TDS PRN maximum 15 mg Diazepam 5 mg PR PRN (for seizures) Considering prescribing Pabrinex for: High risk heavy drinker who are malnourished Wernicke s encephalopathy Please ensure that flumazenil and resuscitation facilities are available when following this protocol. Substance dependency Review: Nov 2014 8

DRUG MISUSE Opioid dependence Drugs in this section identified by the symbol for Controlled Drugs are subject to prescription requirements, must be indelible, and must be signed by the prescriber, be dated, and specify the prescriber s address. The prescription must always state: o the name and address of the patient; in the case of a preparation, the form (e.g. tablets) and where appropriate the strength of the preparation; o either the total quantity (in both words and figures) of the preparation, or the number (in both words and figures) of dosage units, as appropriate, to be supplied; in any other case, the total quantity (in both words and figures) of the Controlled Drug to be supplied; o the dose. Substitution treatments Opioid substitution treatments should not start until use has been confirmed by positive drug test, the dose has been confirmed by GP or drug clinic, collection has been confirmed by community chemist and opioid withdrawal symptoms are evident. Selection of methadone or buprenorphine should be made on a case-by-case basis taking into consideration patient s preference, but methadone should be prescribed if both drugs are equally suitable. CAUTION: Methadone, even in low doses is a special hazard for children; nondependent adults are also at risk of toxicity; dependent adults are at risk if tolerance is incorrectly assessed during induction. Methadone and Buprenorphine should be prescribed for daily administration, under supervision, for at least the first 3 months. Symptomatic relief Lofexidine is a α2-adrenergic agonist that acts to reduce the noradrenergic hyperactivity seen in opioid withdrawal (e.g. piloerection, sweating, runny nose). Maintenance treatment When prescribing Naltrexone patients should be warned that an attempt to overcome the blockade of opioid receptors by overdosing could result in acute opioid intoxication. Opioid overdoses Opioids in overdose cause coma, respiratory depression and pinpoint pupils. Call an ambulance and start routine emergency lifesaving procedures Other considerations Ultra-rapid detoxification is not recommended Substance dependency Review: Nov 2014 9

Opioid dependence Opioid Substitution treatments Methadone Oral 1mg Solution 1mg in 1ml Buprenorphine S/L Tablets Other: Relative Cost Notes Buprenorphine with naloxone S/L Tablets [Suboxone ] Dihydrocodeine Tablets Monitor QT interval in patients with heart or liver disease, electrolyte abnormalities, concomitant treatment with drugs that can prolong QT interval and patients requiring more than 100 mg daily. Dose should take into consideration drug interactions. Sugar Free (SF) should be considered for diabetics and to avoid tooth decay in long-term users Administer the first dose when the patient is exhibiting signs of withdrawal or at least 6 12 hours after the last use of heroin (or other short-acting opioid), or 24 48 hours after the last dose of methadone. In patients receiving methadone, dose of methadone should be reduced to max. 30 mg daily before starting buprenorphine. Only by specialist substance misuse teams. See Buprenorphine advice. Prevents/Reduces the liability for abuse, if crushed and intravenously injected, withdrawal effects occur. Unlicensed use. Only by specialist substance misuse teams. Methadone Tablets Unlicensed use. Only by specialist substance misuse teams. They can be crushed and inappropriately injected, and should only be prescribed under specialist supervision Methadone Conc mixture Only by specialist substance misuse teams. High risk of overdose and inappropriate injection Methadone injection Under specialist supervision for a person with a long history of injecting heroin who has gained no benefit from using oral methadone Diamorphine Injection - Only medical practitioners who hold a special license issued by the Home Secretary may prescribe, administer, or supply diamorphine Substance dependency Review: Nov 2014 10

Opioid dependence Symptomatic relief Lofexidine Monitor pulse and blood pressure. Withdraw gradually over 2-4 days (or longer) to minimise risk of rebound hypertension and associated symptoms. It may be use in place of opioid substitution treatments Zopiclone Insomnia.. Cautious use when co-prescribing of benzodiazepines. Short-tem use Prochlorperazine Nausea and vomiting Metoclopramide Nausea and vomiting Chlorphenamine Itching. Check for signs of liver disease. Paracetamol Pain. Caution in severe liver disease Ibuprofen Pain. Caution in asthmatic patients Loperamide Severe diarrhoea Peptac Heartburn Ensure plus Nutritional Supplementation Other: Relative Cost Notes Gaviscon Heartburn Nefopam Pain Antipsychotics - Refer to relevant section. Unlicensed. Antidepressants - Refer to relevant section. Unlicensed. Substance dependency Review: Nov 2014 11

Opioid dependence Abstinence Maintenance Treatment Naltrexone Only by specialist substance misuse teams in combination with counselling. Avoid concomitant use of opioids. Administer first dose 7-10 days after last opioids consumption Opioid dependence Opioid overdose Naloxone Contact Emergency Services. Short duration, repeated administration may be needed. Substance dependency Review: Nov 2014 12

METHADONE PRESCRIBING FOR OPIOID DEPENDENCE Before prescribing methadone, opioid use must be confirmed by positive urine results for opioids and objective signs of withdrawal (see table). GP, community pharmacy, keyworker or prison medical officer should be contacted when relevant and documented in clinical notes. Opioid withdrawal symptoms Objective opioid withdrawal scales Symptoms Absent/normal Mild-Moderate Severe Lacrimation Absent Eyes watery Eyes streaming/wiping eyes Rhinorrhoea Absent Sniffing Profuse secretion (wiping nose) Agitation Absent Fidgeting Can t remain seated Perspiration Absent Clammy skin Beads of sweat Piloerection Absent Barely palpable Readily palpable, visible hairs standing up Pulse rate (BPM) <80 >80 but <100 >100 Vomiting Absent Absent Present Shivering Absent Absent Present Yawning/10 min <3 3-5 6 or more Dilated pupils Normal <4mm Dilated 4-6 mm Widely dilated >6mm Subjective opioid withdrawal symptoms can include: nausea; stomach cramps, muscular tension; muscle spasms/twitching; aches and paints; insomnia. Opioid withdrawal is not a life-threatening condition, opioid toxicity is. Do not administer methadone if the patient is drowsy or asleep Methadone prescribing If methadone dose is confirmed and clinically appropriate it is recommended that the total daily dose is prescribed as two split doses for 3 days. Dose can be prescribed as a single dose thereafter. Doses above 40mg should be agreed with the consultant. It is important to remember that several missed doses may mean a loss of tolerance to opioids. Three more days missed consecutively should lead to a dose review. If methadone dose is not confirmed Prescribe a single dose of methadone 10mg on the "once only" part of the prescription chart. A second dose of methadone 10mg may be prescribed and given no sooner than four hours after the first dose. The patient should not receive more than 20mg of methadone in the first 12 hours and no more than 40mg in 24hours Where doses need to be increased during the first seven days, the increment should be no more than 5 mg to 10mg on one day. In any event, a total weekly increase should not usually exceed 30mg above the starting day s dose. Substance dependency Review: Nov 2014 13

BENZODIAZEPINE DEPENDENCE Management of assisted benzodiazepine withdrawal Withdrawal of a benzodiazepine should be gradual because abrupt discontinuation may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Benzodiazepine withdrawal may be undertaken with or without switching to diazepam but the switch is recommended for people: o with previous difficult withdrawal attempts o on short-acting potent benzodiazepines such as alprazolam and lorazepam o on preparations that do not easily allow for small reductions in dose (that is alprazolam, flurazepam, loprazolam and lormetazepam) Approximate equivalent doses of diazepam 5mg o Chlordiazepoxide 15mg o Loprazolam 0.5-1mg o Lorazepam 0.5mg-1mg o Lormetazepam 0.5-1mg o Nitrazepam 5 mg o Oxazepam 15mg o Temazepam 10mg Steps may be adjusted according to initial dose and duration of treatment and can range from diazepam 500micrograms (one quarter of a 2mg tablet) to 2.5mg. Emergency treatment of overdoses Benzodiazepine overdose cause drowsiness, ataxia, dysarthria, nystagmus, and occasionally respiratory depression and coma. Substance dependency Review: Nov 2014 14

Benzodiazepine dependence Substitution treatments First Line: Price Band Notes Diazepam Diazepam is preferred because it possesses a long half-life and is available in a variety of Tablets strengths and formulations. Liquid Second Line: Price Band Notes Nitrazepam For nitrazepam dependent patients. Temazepam For temazepam dependent patients. Benzodiazepine dependence Symptomatic relief Other: Price Band Notes Propranonol IR Tablets Less suitable for prescribing. For severe, physical symptoms of anxiety (such as palpitations, tremor and sweating) only if other measures fail. MR Tablets Liquid Antidepressants When depression or panic disorder coexist or emerge during drug withdrawal. See relevant section. Benzodiazepine dependence Emergency treatment of overdoses First Line Price Band Notes Flumazenil Contact Emergency Services. In in-patients services may be administered IV by doctors only. Other Substance dependency Review: Nov 2014 15

REFERENCES 1. BAP updated evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity (2012) 2. BNF 63 (2012) British National Formulary. 62nd edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain. 3. CHM (2006) Risk of QT interval prolongation with methadone. Current Problems in Pharmacovigilance 31 4. DH (2007). Drug misuse and dependence: UK guidelines on clinical management. (September 2007) 5. Maudsley (2009). Taylor D, Paton C and Kapur S. The South London and Maudsley NHS Trust 2009 Prescribing Guidelines 10th Edition. 6. NICE (2010). Alcohol-use disorders: diagnosis and clinical management of alcoholrelated physical complications (Clinical Guideline 100 June 2010). 7. NICE (2011) Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence (Clinical Guideline 115 February 2011). 8. NICE (2007a) Naltrexone for the management of opioid dependence. (Technology appraisal guidance 115 January 2007). 9. NICE (2007b) Methadone and buprenorphine for the management of opioid dependence. (Technology appraisal guidance 114 January 2007). 10. NICE (2007d) Drug misuse: opioid detoxification. (Clinical Guideline 52 July 2007) 11. NTA (2006). National Treatment Agency for Substance Misuse. Review of the effectiveness of treatment for alcohol problems (November 2006) 12. NTA (2006a) Treating drug misuse problems: evidence of effectiveness. 13. RCGP (2011) Guidance for the use of substitute prescribing in the treatment of opioid dependence in primary care. 14. SIGN (2003). Scottish Intercollegiate Guidelines Network. The management of harmful drinking and alcohol dependence in primary care (September 2003) 15. Sweetman, S.C. (Ed.) (2005) Martindale: the complete drug reference. 34th edn. London: Pharmaceutical Press. Substance dependency Review: Nov 2014 16