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Surrey and Borders NHS Foundation Trust Substance Misuse Services Community Prescribing Guidelines October 2014 Community prescribing takes place within a context in which co-existing physical, emotional, social and legal problems are addressed so far as possible. Prescribing, or pharmacotherapy, is therefore an adjunct to psychological therapy, rather than an isolated intervention. Community prescribing includes opiate substitution treatment, maintenance prescribing, opiate, benzodiazepine and alcohol detoxification from alcohol, opiates or sedatives, (either gradual or over a short period) or for relapse prevention. The decision to prescribe for individuals with substance misuse problems is only made by the prescriber after appropriate assessment at that point it time. Appointments should therefore be made for prescribing assessments, not for prescribing per se. Remaining in treatment for an adequate period of time is critical for treatment effectiveness. The appropriate duration of treatment for individuals depends on their problems and needs, but research indicates that for most people with drug dependence, the threshold of significant improvement is reached after about three months in treatment, with further gains as treatment is continued. 1 INDEX Assessment for prescribing ............................................................................................................... 4 Choice of medication of opiate dependency ..................................................................................... 5 Prescription Housekeeping ............................................................................................................... 6 Prescribing Format ........................................................................................................................... 7 Dispensing ........................................................................................................................................ 8 Issuing Prescriptions ......................................................................................................................... 8 Reviewing Treatment ....................................................................................................................... 9 Failure to attend clinic/pharmacy ...................................................................................................... 9 Failure to collect medication from pharmacy .................................................................................... 9 Lost prescriptions ........................................................................................................................... 10 Medication Diversion ...................................................................................................................... 10 Reduction Regimes ......................................................................................................................... 10 Travel away from home .................................................................................................................. 10 Travel within the UK ........................................................................................................................11 Travel out of UK ............................................................................................................................... 11 Driving motor vehicles (appendix) ................................................................................................... 12 Continued substance use .................................................................................................................13 Fertility and Contraception ............................................................................................................. 14 Discontinuation of prescriptions ..................................................................................................... 14 Discontinuation process ...................................................................................................................15 Patients leaving the area/service ......................................................................................................15 Opiate Substitution Treatment (OST) ............................................................................................. 16 Choice of OST ................................................................................................................................. 16 Methadone ...................................................................................................................................... 17 Methadone equivalent doses .......................................................................................................... 18 Buprenorphine ................................................................................................................................ 19 Opiate detoxification ...................................................................................................................... 20 Non-Opiate Detoxification Medication ........................................................................................... 20 Benzodiazepines ............................................................................................................................. 21 Indications for a reduction prescription ........................................................................................... 22 Naltrexone ...................................................................................................................................... 24 2 Acamprosate .................................................................................................................................. 25 Disulfiram ....................................................................................................................................... 25 Lofexidine ....................................................................................................................................... 27 Lofexidine Schedule (one tablet = 0.2mg) ....................................................................................... 28 Pregnancy and Breastfeeding ......................................................................................................... 29 Methadone ..................................................................................................................................... 30 Buprenorphine ................................................................................................................................ 30 Depo-Provera ..................................................................................................................................31 Appendix 1 – QTc Prolongation........................................................................................................33 Appendix 2 – DVLA Guidance ......................................................................................................... 34 Drugs and Driving: blood concentration limits to be set for certain controlled drugs in a new legal offence:........................................................................................................................................... 36 Drugs included in the new offence that might be used for medicinal purposes: ............................... 37 Please discuss the implications of this new law with any person who use our services who are taking one of more of the above drugs: ...................................................................................................... 37 Appendix 3 – Opioids: Important Drug Interactions ........................................................................ 38 Appendix 4 – Benzodiazepine Withdrawal Scale ............................................................................. 40 Clinical observations ....................................................................................................................... 42 3 Assessment for prescribing There is evidence of current dependence, confirmed on urine or saliva testing. All clients should be registered with a local general practitioner, confirmed on NHS Summary Care Record. Those without a GP should be asked to register within four weeks of assessment or prescribing will not be continued. Information regarding current substance misuse, medical and psychiatric history, details of any medications currently being taken and of any known allergies should be available. Written information on prescribed drugs and harm reduction should be given. Consideration should be given to literacy and language. Ensure and record that the client is competent to consent to treatment and has an appropriate understanding of the effects side effects and hazards of any medications. DVLA guidance on drugs, drinking and driving should be given. The relevant pharmacist should be contacted and their agreement to dispense for the client obtained. Clients requiring supervised consumption should be directed to a pharmacy that provides this service and given a ‘Pharmacy Shared Care Contract’ to take to the pharmacy. 4 Choice of medication of opiate dependency All individuals should be allowed to make an informed choice about the options available to them. Consider the following factors when choosing which opiate substitute to use: Patient experience and preference. Level of current opioid use. Any drug interactions if taking other drugs or medication. According to evidence, methadone is more likely to retain patients in treatment. Blockade effect of buprenorphine may be an advantage for some. Safety, e.g. overdose risk (buprenorphine may have a lower risk of overdose). Risks to others if medication taken e.g. children. NICE recommends that, if both drugs are equally suitable, methadone should be prescribed as a first choice. Continuation of prescription from another service, including prison releases: Written evidence of prescription including form, dose, interval. Dispensing and if supervised consumption must be available. Confirmation of when any existing prescription expires and the Pharmacy which is dispensing should also be obtained. Written confirmation should be sent to the previous community service, confirming that prescribing now by SABP. For Prison Releases 5 A prescription may be continued in consultation with a prescriber, for up to seven days, while arrangements are made for the individual to see a prescriber for assessment. Prescription Housekeeping All prescription forms must be kept in a safe place, in accordance to Trust policy. (PROCEDURE REF NO SABP/EXECUTIVE BOARD/0017/PROCEDURE10 Medicines Procedure: FP10 - Prescriptions and ePACT prescribing data) 6 There should be a clear audit trail of prescription forms, including those voided, not collected and cancelled. The serial numbers of all prescriptions (whether printed, hand written and/or destroyed) must be entered on a Prescription Record Sheet (electronic or paper). The individual who prints the prescriptions should ensure they are not producing duplicate or overlapping prescriptions, and that the prescription follows the agreed care plan. Care should be taken to ensure that there is only one active prescription for each drug on the computer system. The specified pharmacy should be printed on the prescription and recorded in the notes. This is not legally binding but allows checks on compliance and welfare if necessary. The clinician who signs the prescription carries the responsibility for prescribing. Any changes to dose, collection intervals or supervision should only be made in consultation with the prescriber and should be brought to the attention of the prescriber prior to signature. A repeat prescription generated by nurses within Substance Misuse Teams is not deemed to be transcribing as per Standard 3 of the Nursing & Midwifery Council (NMC) Standard for Medicines Management (NMC, 2007). There are occasional circumstances where substance misuse team staff will be required to transcribe prescription information from faxed medicines charts/referral letters in order to generate a prescription. In these cases it is the responsibility of the prescriber to check the accuracy of the transcribed drug and dose details prior to signature. Prescribing Format Controlled Drug (CD) prescriptions do not have to be handwritten but they must be signed by the prescriber. The date can be computer generated. Prescriptions are only valid for 28 days. The 28 day period of validity runs from the date the prescription was signed unless the prescriber has specified a start date on the prescription. For instalment dispensing prescriptions, the first supply must be made within 28 days of the appropriate date and the remainder of the instalments must be dispensed only in accordance with the directions on the prescription. Prescriptions for Schedule 2 and 3 drugs should also state: The form (e.g. tablets) and where appropriate the strength of the preparation. The total quantity of the preparation, or the number of dose units, in words and figures. The daily dose. Blue FP10MDA forms can only be used for interval dispensing of Methadone, Buprenorphine and Diazepam. A maximum of 14 days can be prescribed on one form. The number of installments and the intervals to be observed must be specified on the prescription. Green FP10 forms are used for single collections of CD’s and all other medications. In the case of installments not being collected on the correct day the wording below enables the pharmacy to issue the remainder of the installment and prescription. “If an installment prescription covers more than one day and is not collected on the specified day, the total amount prescribed less the amount prescribed for the day(s) missed may be supplied.” 7 Dispensing Supervised consumption is recommended for three months, although this period can be shortened for those who stabilize prior to this. Do not stop supervised consumption if: A stable dose has not been reached. There is continued and unstable drug misuse, including alcohol. There is significant unstable psychiatric illness or risk of self-harm. There are concerns about the safety of storage of medication at home where children are present. There is concern that the medicine may be diverted or used inappropriately. Daily dispensing should then occur with gradual increase in the interval collection with stability and progress in treatment. Use of daily and/or supervised consumption should not be seen as a punitive measure but as an adjunct to other treatment options for those finding it difficult to stabilize on medication. Issuing Prescriptions 8 The individual person handing over the prescription must be deemed competent to undertake the role and be absolutely certain it is being handed to the right patient. It is good practice to ask for the name and date of birth if the client is not known to the individual. It is also their responsibility to assess the degree of intoxication of the client. Non-clinical staff should always defer to clinical staff if they have any concerns at all. If the client appears to be under the influence of alcohol, then the prescription should only be given if a breath alcohol is <35 µg/100mls breath. If >35 µg/100mls breath, the client should be asked to return at a later time. If the client appears to be heavily under the influence of other substances then a discussion with a senior member of staff should occur and be documented. No prescriptions should be issued to individuals if they have not been seen by a member of clinical staff for six weeks, unless a longer interval has been agreed and documented by the prescriber. Reviewing Treatment Progress should be reviewed by a clinical worker regularly, looking at response to treatment in the following areas: Drug and alcohol misuse. Physical and mental health. Social functioning. Offending and criminal justice. Broader health and well-being. Ongoing engagement in psycho-social support. Risk assessment is an ongoing process. Any risks identified should be highlighted to the patient and clearly documented in the case record. Face-to-face prescriber review should occur at least annually, with shorter intervals in complex cases, those new to treatment or where their situation has changed significantly. Failure to attend clinic/pharmacy When a patient on outpatient prescribing fails to keep clinical appointments on two or more occasions, their case should be discussed at the team meeting. This should also occur for patients regularly failing to pick up opiate medication from the pharmacy. Failure to collect medication from pharmacy Missed Day 1 No action 2 May dispense if appropriate wording 3 May dispense if appropriate wording Do not dispense, unless verified by CDAT CANCEL PRESCRIPTION 4 9 Pharmacy Action Titrating script any missed doses refer prescriber If fail to attend, inform CDAT Client to discuss with keyworker. Then may be appropriate to book prescribing re-assessment appointment. Lost prescriptions Safe custody of the prescription and any dispensed medication is the responsibility of the individual named on the prescription. The loss must be reported to the police by the service user, and a crime number issued. Lost prescriptions will only be replaced if a crime number is available and not if it is a recurring event. Medication Diversion Third party information that an individual is selling or sharing their medication should be addressed in a timely manner. The probity of the source should be noted. Discussion at the Multi-Disciplinary Team (MDT) meeting should occur at how best to address the issue and also how to manage the individual’s further treatment. The safety of the source of the information should be taken into account in these discussions. Reduction Regimes The recommended maximum rate of reduction of medication is as follows. These are guidelines and the individual should always be involved in any planning. Medication Maximum Reduction Rate Methadone 5mg/week Buprenorphine 2mg/week Diazepam 5mg/week Travel away from home A minimum of two weeks’ notice is required. 10 Travel within the UK For those who are dispensed daily +/- supervised consumption, collection can be arranged at another pharmacy. For those on less frequent collections, it may be possible to allow collection of medication for the whole of the away period. These decisions will be made by the keyworker and prescriber on an individual basis. Travel out of UK 11 Prescriptions for travel abroad can only be issued for a total of four weeks. Proof of travel must be provided prior to the issuing of prescriptions. Travel for less than three months does not require a personal licence to enter or leave the United Kingdom. A letter should be provided, to confirm client’s name, travel itinerary, names of medication, dosages and total amounts to be carried. The letter should be signed by the prescriber or keyworker. Other countries may have their own regulations for controlled drugs and prescription medicines. This can be checked with the UK-based representatives of each country. Driving motor vehicles (appendix) It is the duty of the licence holder to notify the DVLA of any condition which may affect safe driving; the DVLA is then legally responsible for deciding if a person is medically unfit to drive. Prescribers should be familiar with the following publications: For Medical Practitioners – at a glance guide to the current medical standards of fitness to drive (DVLA, May 2014). Confidentiality: Reporting concerns about patients to the DVLA or the DVA (GMC, 2009). The person must have it made clear to them that: Individuals must be informed that their driving may be impaired and that they have a legal duty to inform the DVLA. If they refuse to accept this advice they may wish to seek a second opinion. Appropriate arrangements should be made to enable them to do so. They should be advised not to drive until the second opinion has been obtained. If the person continues to drive every reasonable effort should be made to persuade them to stop. This may include telling their next of kin. If it becomes clear that the person is continuing to drive, contrary to advice, relevant clinical information should be passed immediately, in confidence to the medical advisor at DVLA. 12 Before giving information to the DVLA the person should be informed of the decision to do so. Once the DVLA has been informed the person should have confirmation, in writing that disclosure has been made. The provision of advice in relation to alcohol, drugs and the responsibility to inform DVLA of any impairment is provided in standard form to all clients. Staff should discuss the effect of any drugs prescribed on driving and a note made of this discussion. Mileage expenses should not paid to people known to be unsafe who continue to drive. Continued substance use Alcohol use 20-50% of clients prescribed methadone also use alcohol. Evidence suggests that continued prescribing in the face of alcohol misuse should follow a careful appraisal of risks versus benefits together with interventions targeted at alcohol. Those who regularly attend having consumed alcohol, or are judged to be dependent on alcohol should be informed of the additional risks this poses in terms of general health and overdose. They should then be managed according to the appropriate alcohol treatment pathway. Alcohol detoxification should be offered as appropriate. Clients who refuse to address their alcohol use should have their Opiate Substitution Treatment (OST) reviewed in line with the guidance on discontinuing OST on safety grounds. Opiate use 13 Ascertain whether use is in addition to taking prescribed medication properly or prescribed medication being taken intermittently with illicit use. Is prescribed medication being stored or diverted? Reconsider reduced interval prescribing and the use of supervised consumption. If collections are missed for logistic reasons, solutions should be explored and may include a trial of less frequent collections. Where medication is consumed daily but on top use continues then increase in dose should be considered in the first instance. If on top use is clearly hedonistic then the potential benefits of higher dose must be traded against additional risk. Consideration of changing to an alternative OST should preclude any discussions about discontinuation if this is deemed safer. Fertility and Contraception Contraception is an important subject to discuss with women commencing treatment. Many women cease ovulation during periods of uncontrolled drug use and resume ovulation as they stabilise on opiate substitution treatment. If this change is unexpected it can easily result in unplanned pregnancy. All females should therefore be given advice about the risk of conception and suitable contraception. It is desirable for the health and welfare of mother and baby that pregnancies should be planned or at least delayed until the mother is healthier and life less chaotic. Discontinuation of prescriptions Involuntary withdrawal should be a last resort, and decisions relating to termination of treatment should be initiated only after careful consideration and input from a number of other sources and after all attempts have been made to solve any presenting issues, where appropriate. Before any decision to withdraw OST is made, the key worker, prescriber or other relevant clinical staff member must discuss the matter with the client and, wherever possible, written warnings should be provided before the decision is made to withdraw treatment. Situations that may lead to consideration of treatment discontinuation: 14 Failure to adhere to the safety requirements of the OST programme OST is not considered an effective treatment (that is, the harm minimisation benefits of OST are outweighed by the negative outcomes and elements of risk of continued prescribing. The individual takes regular overdoses or is frequently, significantly intoxicated from psychoactive substance use, with concerns that prescribing may be increasing risk. The client is threatening or violent towards staff, other clients, the prescriber or pharmacist. Repeated failure to keep to the safety requirements of the OST provider. Discontinuation process All clients should be made aware of the situations that might lead to discontinuation of prescribing at the outset of treatment. Keyworker and/or prescriber should discuss the team view with the client and attempt to reformulate the care plan. Prescriptions should not be continued for more than six weeks without a face to face review by a member of clinical staff. Every effort should be made to see the client with flexibility of time and venue and the client should be issued with a warning letter prior to discontinuation if this has not been possible. In patients for whom discontinuation may be needed, the reasons for this and specific expected behaviours they can take to avoid discontinuation should be carefully discussed and documented. It is often helpful to ask the client to sign that they have understood what is written in the notes in this regard. The reasons for discontinuation should be clearly documented including the parties involved in the decisions. The decision and rationale should be communicated in writing to the client, their GP and any other agencies involved in their care and risk assessment updated. Patients leaving the area/service 15 Where a patient attending the service and on medication wishes to leave the area the care coordinator should facilitate both the transfer of care and prescribing if this is felt to be appropriate. The drug treatment service local to the patient’s new address should be contacted, details of their referral processes obtained and a full report sent outlining the current treatment plan as well as relevant past history. Any prescribing arrangements required to cover the transition period should be agreed at a team meeting. Patients should not normally continue to receive prescriptions for a period in excess of two weeks unless there is evidence that arrangements for transfer of care and prescribing responsibility are still being made. Opiate Substitution Treatment (OST) The aims of an opioid treatment program are to: Reduce or eliminate heroin and other illicit drug use by those in treatment. Improve the health, psychological functioning and wellbeing of individuals and families. Facilitate the social rehabilitation of those in treatment. Reduce the spread of blood borne viruses (BBV) associated with injecting opioid use. Reduce the risk of overdoses and deaths associated with opioid use. Reduce the level of involvement in crime associated with opioid use. Choice of OST NICE, 2010 examined all the evidence pertaining to treatment of opiate dependence with either Methadone or Buprenorphine. They concluded that: ‘Both methadone and buprenorphine in flexible dosing regimens are clinically effective and cost effective, compared with no treatment, for maintenance therapy in the management of opioid dependence.’ However, if both drugs are equally suitable for a person, then Methadone should be prescribed as it is the cheaper drug. (NICE 2010) Prescribing should form one element within a wider care plan, agreed with the client and addressing physical, psychological and social needs. Good evidence exists for the effect of motivational enhancement therapies, and a range of other psychosocial interventions (Drug misuse and dependence – UK guidelines on clinical management DH, 2007). 16 Methadone and Buprenorphine should be administered daily, under supervision, for at least the first three months. Supervision should be relaxed only when the patient’s compliance is assured. Both drugs should be given as part of a programme of supportive care. Methadone Pharmacology Methadone mixture sugar-free 1mg/1ml commonest. Administered once daily. Onset of effect ½ to 1 hour. Peak 2-4hours. Duration 24-36hours. With regular dosing, duration may be up to 47hours. Agonist at opiate µ receptors. Methadone is a strong inhibitor of serotonin uptake. Mainly metabolized by liver enzymes CYP3A4 and CYP2D6 meaning extensive first pass metabolism. Acidification of urine can increase clearance x3, and so reduce duration of effectiveness. Metabolism – fast and slow. Indications Opiate detoxification, stabilization and maintenance. Investigations Annual ECG. Dose > 100mg/day. Cardiac risk factors. Other QTc prolonging medications. Precautions Hepatitis C infection may induce CYP enzymes so require increase in dose. Reduced does of methadone will need to be considered for patients with prolonged QTc intervals ( >440ms for men, >470ms for women) See appendix. It is advisable to caution pregnant women taking methadone that the use of heroin and cocaine has been shown to increase transfer of methadone to the fetus (Malek A 2009). Dose Initial dose of methadone should not exceed 40mg daily. Experienced and competent clinicians with patients who are tolerant and heavily dependent may use up to 40mg daily as a first dose. Titrate up at a rate of 5-10mg/24hours. Maximum dose increase of 20mg/week. Aim to stabilize on dose that eliminates withdrawal symptoms and craving to use illicit drugs without causing undue sedation. Adverse Effects Respiratory depression, nausea, vomiting, dizziness, mental clouding, dysphoria, pruritus, impaired sexual function, constipation, urinary retention and hypotension. Pregnancy Stability for mother and fetus is the primary aim. Increased doses or split doses may be required in the third trimester (29-40weeks) due to increased metabolism of methadone at this stage. Breastfeeding should be encouraged, even if the mother continues to use drugs, except where she uses crack cocaine or a very high level of benzodiazepines. Depressant effects enhanced by other CNS depressants. Increasing risk of respiratory depression and hypotension. Drug interactions 17 Effects may potentially by Cytochrome P450 inhibitors such as anti-HIV agents, macrolide antibiotics, ciprofloxacin and azole antifungals. Effects may be reduced by enzyme inducing drugs such as rifampicin, some HIV treatments, phenytoin and quetiapine. Contra-indicated with citalopram and escitalopram. Grapefruit juice can increase the blood levels and effects of methadone. For full list see Appendix Form Methadone tablets may be prescribed in place of liquid methadone for a temporary period for patients travelling (e.g. holidays). However, it should be borne in mind that methadone tablets are not licensed for the treatment of opiate addiction and they are associated with additional risks. Methadone equivalent doses Dose equivalent of different opiates shown below. Derived through practical experience they are rough approximations. Calculations are based on the equivalent Methadone dose that would prevent withdrawal symptoms. Name and Dose of Short Acting Opiate Methadone Dose Equivalence Pharmaceutical diamorphine 10mg 20mg Morphine 10mg 10mg Pethidine 50mg 5mg DF118 (dihydrocodeine) 30mg 2-3mg Codeine or codeine phosphate 30mg 2mg Diconal (dipipanone) 10mg 4mg Palfium (dextromoramide) 5mg 5-10mg Fortral (pentazocine) 25mg 2mg Codeine linctus, Gee’ s linctus, Collis Brown 100ml 10mg Approximately £10 worth of heroin = 10mg Methadone as a rough rule of thumb. 18 Buprenorphine Pharmacology Semi-synthetic opiate. Partial agonist at µ receptors. Antagonist at κ receptors. Sub-lingual tablets, poorly absorbed if swallowed. Full blockage achieved at dose of 16mg. Peak effect after 1-4hours. Duration action 48-72hours at 16mg+ (less with lower doses). Metabolized by CYP3A4. Suboxone contains Naloxone – this is inactive if taken sublingually, however can induce opiate withdrawals if taken IV or snorted. Precipitate withdrawal Buprenorphine has a stronger affinity for opioid receptors than other opiates and so will displace existing opiates causing withdrawal symptoms. Commence in the first 30-90 minutes. Peak within three hours. Treat with symptomatic medications and Lofexidine. Indications Opiate detoxification, stabilization and maintenance. Investigations Dose LFTs in those with history of liver disease. Prior to first dose, withdrawal symptoms should be present. First dose at least 24 hours after methadone. 12-16 hours after short-acting opioids (oxycodone, heroin, morphine). Less for codeine, dihydrocodeine. Up to 8mg can be taken in the first 24 hours, in divided doses to allow full dissociation of other opiates from receptors. Dose can be increased up to 16mg on the following day if needed. Maximum dosage 32mg Buprenorphine, 24mg Suboxone. Suboxone should be used if there is concern the patient is diverting or misusing prescribed Buprenorphine. Community Detoxification Buprenorphine doses should be initially reduced by increments of 2mg. From 4mg reductions may be in increments of 400-800 micrograms. For those who persistently fail to start Buprenorphine in the community, a short admission may be necessary to allow initiation and titration in those who wish. Adverse Effects Common side effects include insomnia, dizziness, drowsiness, headache and constipation. Drug Interactions Depressant effects enhanced by other CNS depressants. May also cause respiratory depression and hypotension. Effects may be potentiated by Cytochrome P450 inhibitors. 19 Cautions Severe breathing problems including asthma. Opiate Detoxification Providing information, advice and support Detoxification should be a readily available treatment option for people who are opioid dependent and have expressed an informed choice to become abstinent. In order to obtain informed consent, staff should give detailed information to service users about detoxification and the associated risks, including: Physical and psychological aspects of opioid withdrawal, including the duration and intensity of symptoms, and how these may be managed. Use of non-pharmacological approaches to manage or cope with opioid withdrawal symptoms. Loss of opioid tolerance following detoxification, and the ensuing increased risk of overdose and death from illicit drug use that may be potentiated by the use of alcohol or benzodiazepines. Importance of continued support, as well as psychosocial and appropriate pharmacological interventions, to maintain abstinence, treat comorbid mental health problems and reduce the risk of adverse outcomes (including death). Non-Opiate Detoxification Medication Medication LOPERAMIDE Dose 2mg Indication Schedule oral Diarrhoea 4mg stat then 2mg after each loose stool – Max16mg/24hrs oral Stomach Cramps Max qds HYOSCINE HYDROBROMIDE (BUSCOPAN) 20mg IBUPROFEN 400mg oral Aches & Pains Max qds ZOPICLONE 7.5mg oral Insomnia nocte DIAZEPAM 5-10mg oral Agitation Up to 30mg daily for 3 days only 20 Benzodiazepines Benzodiazepine dependence occurs in two distinct populations Therapeutic – Prescribed medication with dosage in therapeutic range. Non-therapeutic – As part of poly-drug use, often with excessive doses. In all the conditions in which they are used, benzodiazepines tend to produce dependence and withdrawal reactions therefore benzodiazepines should only be used for periods of up to four weeks in non-dependent individuals. There is no consensus evidence base for the management of benzodiazepine abuse and/or dependence. Benzodiazepine Equivalent to 5mg diazepam Alprazolam Xanax 0.25mg-0.5mg Chlordiazepoxide Librium 15mg Clobazam Frisium 10mg Clonazepam Rivotril 0.5mg-1mg Flunitrazepam Rohypnol 0.5mg Loprazolam Dormonoct 0.5mg-1mg Lorazepam Ativan 0.5mg Nitrazepam Mogadon 5mg Oxazepam 15mg Temazepam 10mg Triazolam 21 Trade Name Halcion 0.25mg When negotiating a structured reduction programme with a client it is often useful to calculate the total quantity of Benzodiazepines used as an equivalent dose of diazepam so an agreed baseline level of use can be determined from which to commence reduction. Extra caution should occur in clients with hepatic dysfunction. Indications for a reduction prescription Individuals on long-term prescription on assessment although if possible, prescribing should remain in primary care with guidance from CDAT. Individuals stabilized on OST with a history if moderate to severe benzodiazepine dependence syndrome. Use must be confirmed by at least two consecutive urine screens positive for Benzodiazepines. There is some evidence that reduction to 30-40mg diazepam can occur quite rapidly, and some clinicians will only prescribe a maximum of 40mg. Pharmacology Enhances action of GABA. Hepatically metabolized. Active metabolites. Long half-life. Accumulates in liver disease. Reversed by flumazenil. Indications for CDAT prescribing Benzodiazepine detoxification where there is a co-morbid, clear (chronic and regular) dependency with opioids of at six months duration. Patients must have explored alternative ways of addressing their benzodiazepine use. 2-3x urine samples positive for benzodiazepines, over the last few months. Evidence of withdrawal symptoms (see CIWA_B) Relatively low dose brief detoxification is adequate for most. Persistent use despite abstinence from other substances may indicate the need for longer, slower withdrawal regime. In a very small proportion, maintenance benzodiazepine prescribing may be appropriate. This decision should be taken at MDT and senior prescriber level. Dose All benzodiazepines should be converted to diazepam. The initial daily prescribed dose should not exceed 30mg diazepam. Reduction should begin after a limited period of stabilization. Adverse Effects Short term drowsiness, sedation and ataxia. Long term cognitive damage. Be aware of the potential for paradoxical benzodiazepine disinhibition. Although this is thought to be an infrequent problem in most cases (1%) groups at greater risk include those on high potency drugs and those with pre-existing CNS damage or a history of aggression or impulsivity (Paton, 2002). Drug Interactions CNS depressants effects may be enhanced if diazepam is used with other centrally acting drugs. 22 23 Effects may be potentiated by cyto-chrome P450 inhibitors. Effects may be reduced by cyto-chrome P450 enzyme inducing drugs. Medical review for decision to prescribe benzodiazepines. Clear guidance to client regarding rationale for detoxification and discussion of regime. Use CIWA-B to monitor reduction, every four weeks and decide further reduction. APPENDIX CIWA_B. Naltrexone Pharmacology/ Information Fully opioid antagonist. Rapidly absorbed. Displaces opioids from receptors precipitating withdrawals. Blocks the effects of opioids. Metabolized by liver. Indications Maintaining abstinence after opiate detoxification. Maintaining abstinence after alcohol detoxification. Investigations Baseline LFTs the three monthly. U&Es. Dose Initiate after patient has been opiate-free for 5-10days (confirm by urinalysis). Challenge – 25mg Naltrexone. If tolerated, then maintenance dose 50mg daily. Can be taken three times a week (Mon – 100mg, Wed – 100mg, Fri – 150mg). Naltrexone is recommended for the prevention of relapse in formerly opioid-dependent patients who are motivated to remain in a supportive care abstinence programme. (NICE January 2007). Prescribed for up to one year with concomitant psycho-social intervention. Opiate Antagonist Challenge Adverse Effects Drug Interactions Further Information 24 Administer Naltrexone 25mg orally. Monitor for opiate withdrawal for 2-3 hours. Signs and symptoms may develop within five minutes and last up to 48hours. Check BP and pulse. Request medical advice if BP 90/50 or 160/100 or if pulse 50 or 140. Alternatively Naloxone (400 micrograms) intramuscularly or subcutaneously can be used. Side effects are common but tend to be transient and mild. GI symptoms, anxiety, insomnia, poor appetite, headache and increased sweating. Patients should be made aware that Naltrexone can interfere with pain relief and that they should let healthcare professionals know they are taking it. These are cards available from the manufacturers stating this fact. Patients should be warned about taking opioid-containing medicines such as in cough mixtures, some cold remedies and some anti-diarrhoeals. Significantly increases Acamprosate levels. Avoid in hepatic and renal impairment. Can cause constriction of the pupils (mechanism unknown). Overdose can occur if individual takes enough opiate to overcome blockade. Acamprosate Pharmacology/ Information Reduces alcohol cravings. Exact mechanism of action unknown but thought to antagonize excitatory amino acids such as glutamate. With counselling and social support. Indications Abstinence maintenance in alcohol dependence and harmful alcohol use. Investigations None. Dose Ideally initiate at start of alcohol detoxification. Two tablets (666mg) TDS in patients weighing 60kg or more. Four tablets divided into three daily doses in patients <60kg. (two tablets morning, one noon and one at night). Adverse Effects Diarrhea and stomach pain, headache, skin rash and sexual problems. Drug Interactions Acamprosate levels may be slightly increased by Naltrexone. Pharmacology/ Information Blocks Acetaldehyde Dehydrogenase resulting in accumulation of Acetaldehyde of alcohol taken. Indications Desire to maintain abstinence from alcohol. Second line treatment. Relatively stable personalities. Investigations None. Flushing, nausea and vomiting, tachycardia, palpitations, hypertension, headache if alcohol taken. Have been fatalities. Disulfiram Dose Adverse Effects Drug Interactions 25 26 Lofexidine Pharmacology/ Information Alpha-2 adrenergic agonist. Opiate withdrawal symptoms are from noradrenergic over activity. Indications Management of opiate withdrawal symptoms in a planned opiate detoxification, clients with mild or uncertain dependence (NICE 2007) and those who have made in an informed and clinically appropriate decision not to use OST. They should live in a safe, stable environment and have a responsible supporter. A suitably trained staff member should monitor treatment and to see the patient daily for at least the first three days. Dose Adverse Effects The dose should be gradually increased from 0.2mgs qds to a maximum of 0.6mg qds. Blood pressure monitoring should occur after each increase in dose. Similarly, the dose should be tapered off over 2-3days to prevent the occurrence of rebound hypertension. Side effects include drowsiness (6.6%), dry mouth (.3%), hypotension (7.5%), bradycardia and rebound hypertension. Falls in blood pressure and/or pulse rate are the most usual reasons for intolerance. May have a sedative effect thus advise not to drive or operate machinery. Caution Caution in those with sever coronary insufficiency , recent myocardial infarction, renal impairment and in people with marked bradycardia (55 beats per minute). There have been reports of asymptomatic QT prolongation during treatment with Lofexidine or if taking other drugs known to cause QT prolongation. Drug Interactions Enhances sedative effects of alcohol, anxiolytics and hypnotics. May enhance the effects of anti-hypertensive therapy. Concomitant use of tricyclic antidepressants may reduce the efficacy of Lofexidine. Further Information Safety in pregnancy and breast feeding is not established. 27 Lofexidine Schedule (one tablet = 0.2mg) Day Number Breakfast Lunch Dinner 1 0.2mg 0.2mg 2 0.2mg 0.2mg 0.2mg 0.2mg 3 0.4mg 0.2mg 0.2mg 0.4mg 4 0.4mg 0.4mg 0.4mg 0.4mg 5 0.6mg 0.4mg 0.4mg 0.6mg 6 0.6mg 0.6mg 0.6mg 0.6mg 7* 0.6mg 0.6mg 0.6mg 0.6mg 8* 0.6mg 0.4mg 0.4mg 0.6mg 9* 0.4mg 0.4mg 0.4mg 0.4mg 10 0.4mg 0.2mg 0.2mg 0.4mg 11 0.2mg 0.2mg 0.2mg 0.2mg 12 0.2mg 13 28 Bed 0.2mg 0.2mg Note: Days 7,8 and 9 may need to be repeated for clients withdrawing from methadone. Omit Days 6-8 if withdrawal is not severe. A maximum does of 0.4mg qds may be sufficient for some individuals. Pregnancy and Breastfeeding 29 Women who misuse substances and become pregnant have particular difficulties, so attracting these patients into drug treatment services is vital. Evidence demonstrate that the long-term outcome in women who enter methadone treatment programmes during pregnancy is better in terms of their pregnancy, childbirth and infant development, irrespective of continuing illicit drug misuse. A medical review should be undertaken to assess physical and mental health, and discuss treatment options. If a partner is also using illicit opiates they too should be offered drug treatment. Substitute prescribing can occur at any time in pregnancy and is lower risk than continuing illicit use. Methadone and Buprenorphine can be safely prescribed in pregnancy and will almost always outweigh the risk of harm of heroin use. Methadone Pregnancy Not a known teratogen and can reduce illicit drug use in pregnancy. Stability in pregnancy, with no illicit drug use in the first aim. Maintain pregnant women on a dose sufficient to get benefit. Methadone metabolism may increase in the third trimester causing reduced levels and withdrawal symptoms, so dose may need to be increased. Is a risk of Neonatal Abstinence Syndrome, particularly in higher doses. Reduction in Pregnancy: Breastfeeding Rapid reduction should be avoided in pregnancy. Slow reduction is preferable at a rate of 5mg or less/week. Reductions should be led by the mother. Methadone is excreted in the breast milk but this is not a contraindication to breastfeeding. Methadone doses should be kept as low as possible whilst breastfeeding. Abrupt cessation of breastfeeding can result in Neonatal Abstinence Syndrome, so mothers should be advised to slowly wean from the breast. Buprenorphine Pregnancy Breastfeeding 30 Buprenorphine is not licensed for use in pregnancy. However, there is a consensus view that for women on Buprenorphine who become pregnant, then it is safe and appropriate to continue prescribing. There is also a growing body of evidence of the safety of Buprenorphine in pregnancy. Neonatal Abstinence Syndrome can occur; however appears to be lower incidence than with methadone. Buprenorphine should not be used during breastfeeding. There is currently limited data but research has demonstrated no adverse effects in breastfeeding. Low levels of Buprenorphine are found in breast milk however it has poor oral bioavailability. Depo-Provera Indications Long-acting reversible contraception. Investigations Pregnancy Test. Contraindications Pregnancy. Current DVT or pulmonary embolus. Unexplained vaginal bleeding, suspicious for a serious underlying condition. Diabetes with nephropathy, retinopathy, neuropathy, or vascular complications. Severe decompensated cirrhosis. Liver tumours: hepatocellular adenoma and malignant hepatoma. Systemic Lupus Erythematosus with positive anti-phospholipid antibodies; severe thrombocytopaenia. History of or current breast cancer. Sever side-effects from other Progestogen containing medications. For longer term use: Dose Adverse Effects Timing 31 Significant multiple risk factors for arterial cardiovascular disease (such as age, smoking, diabetes, hypertension and obesity). Vascular disease including coronary heart disease presenting with angina; peripheral vascular disease presenting with intermittent claudication; hypertensive retinopathy. Past history of ischaemic heart disease. History of cerebrovascular disease, including transient ischaemic attack. Dosage single dose of 150mg every 12 weeks (the license allows intervals of up to 12 weeks and five days). Injections should be repeated at 12 week intervals although they may be administered up to 14 weeks after the last injection. This protocol is for a maximum of two consecutive injections, while patients are assisted to access existing contraceptive services. Deep intra-muscular injection slowly into the gluteal muscle. The deltoid may be used if the patient refuses a gluteal injection. (see Trust Protocol on intra-muscular and intravenous injectables.) Specifically discuss and document the possibility of menstrual irregularities and amenorrhoea, weight gain (mean weight gain of 3kg at two years use), skin and mood changes, slow return to fertility (up to one year) and the effects on bone density. General – Day 1-5 of menstrual cycle. Amenorrhoea – Pregnancy Test. Post-partum – up to 21 days post-delivery. Miscarriage/Termination – same day. Drug Interactions 32 Women should be informed that the efficiency of progestogenonly injectable contraception is not reduced with concurrent use of medication (including antibiotics and liver enzyme-inducing drugs) and the injection intervals do not need to be reduced. Appendix 1 – QTc Prolongation Risk factors for QTc Prolongation Modifiable Electrolyte Disturbances (e.g. hypokalemia) Bradycardia Concomitant use of more than one drug that prolongs the QT interval Non-modifiable Female Sex Age over 65 years Congenital Long QT Syndrome Cardiac Disease (e.g. congestive heart failure, ventricular hypertrophy) Impaired hepatic/renal function (due to effects on drug metabolism) Thyroid Disease (e.g. untreated hypothyroidism) Common drugs that may cause prolongations QTc: Antimicrobials Erythromycin, Clarithromycin, Moxiflozacin, Fluconaole, Ketoconazole Antipsychotics All have some risk Risperidone, Fluphennazine, Haloperidol, Pimozide, Chlorpormazine, Quetiapine, Clozapine Antiarrhythmics Sotalol, Quinidine, Amiodarone, Flecanide, Dronedarone Antidepressants Citalopram/Escitalopram, Amitriptyline, Clomipramine, Dosulepin, Doxepin, Imipramine, Lofepramine Antiemetics Domeperidone, Droperidol, Ondansetron/Granisetron Others Methadone Protein kinese inhibitors Some Antimalarials Some Antiretrovirals 33 Telaprevir, Boceprevir – Hepatitis C Treatment Appendix 2 – DVLA Guidance DVLA Drugs and Driving DRUG MISUSE AND DEPENDENCE Reference to ICD10 F10.1F10.7 inclusive is relevant. CANNABIS AMPHETAMINES ECSTASY KETAMINE & other psychoactive substances, including LSD and HALLUCINOGENS HEROIN MORPHINE METHADONE* COCAINE METHAMPHETAMINE 34 GROUP 1 ENTITLEMENT ODL - CAR, M/CYCLE GROUP 2 ENTITLEMENT VOC – LGV/PCV Persistent use of or dependence on these substances, confirmed by medical enquiry, will lead to licence refusal or revocation until a minimum six month period free of such use has been attained. For Ketamine misuse, 6 months off driving, drug-free, is required, and 12 months in the case of dependence. Independent medical assessment and urine screen arranged by DVLA, may be required. Persistent use of or dependence on these substances will lead to refusal or revocation of a vocational licence for a minimum one year period free of such use has been attained. Independent medical assessment and urine screen arranged by DVLA, will normally be required. Persistent use of, or dependence on these substances, confirmed by medical enquiry, will lead to licence refusal or revocation until a minimum one year period free of such use has been attained. Independent medical assessment and urine screen arranged by DVLA, may be required. In addition favourable Consultant or Specialist report may be required on reapplication. Applicants or drivers complying fully with a Consultant supervised oral Methadone maintenance programme may be licensed, subject to favourable assessment and, normally, annual medical review. Applicants or drivers on an oral Buprenorphine programme Persistent use of, or dependence on these substances, will require revocation or refusal of a vocational licence until a minimum three year period free of such use has been attained. Independent medical assessment and urine screen arranged by DVLA, will normally be required. In addition favourable Consultant or Specialist report will be required before relicensing. Applicants or drivers complying fully with a Consultant supervised oral Methadone maintenance programme may be considered for an annual review licence once a minimum three year period of stability on the BENZODIAZEPINES The non-prescribed use of these drugs and/or the use of supra-therapeutic dosage, whether in a substance withdrawal or maintenance programme or otherwise, constitutes misuse/dependence for licensing purposes. The prescribed use of these drugs at therapeutic doses (BNF), without evidence of impairment, does not amount to misuse/dependence for licensing purposes (although clinically dependence may exist). 35 may be considered applying the same criteria. There should be no evidence of continuing use of other substances, including cannabis. maintenance programme has been established, with favourable random urine tests and assessment. Expert Panel advice will be required in each case. Persistent misuse of, or dependence on these substances, confirmed by medical enquiry, will lead to licence refusal or revocation until a minimum one year period free of such use has been attained. Independent medical assessment and urine screen arranged by DVLA, may be required. In addition favourable Consultant or Specialist report may be required on reapplication. Persistent misuse of, or dependence on these substances, will require revocation or refusal of a vocational licence for a minimum three-year period. Independent medical assessment and urine screen arranged by DVLA, will normally be required. In addition favourable Consultant or Specialist report will be required before relicensing. Drugs and Driving Blood concentration limits to be set for certain controlled drugs in a new legal offence: The Department for Transport has introduced a new offence of driving with certain controlled drugs above specified limits in the blood; this is likely to come into force on 2 March 2015. The list of drugs includes some licensed medicines. Anyone found to have any of these drugs in their blood above the specified limits will be guilty of an offence, whether their driving was impaired or not. However, there is a medical defence for people taking the drugs for medical reasons, if their ability to drive was not impaired. Advise patients to continue taking their medicines as prescribed. A new offence of driving with certain controlled drugs above specified limits in the blood is expected to come into force on 2 March 2015. These drugs include some prescribed medicines. Anyone found to have any of the drugs above specified limits in their blood will be guilty of an offence, whether their driving was impaired or not. A preliminary, non-specific roadside test may be used to detect if an individual has any of the drugs in their body. To identify the particular drug taken and quantify blood levels, a blood sample will be taken at a police station and sent for forensic analysis. The legislation provides a statutory “medical defence” for people taking the drugs for medical reasons, if their driving was not impaired. The conditions of the medical defence state that the individual is not guilty of an offence if: The medicine was prescribed, supplied, or sold to treat a medical or dental problem, and It was taken according to the instructions given by the prescriber or the information provided with the medicine. The individual may need to provide written evidence to satisfy the points above (e.g. the tear-off section of a prescription or the medicine’s patient information leaflet). If the individual’s driving is impaired, they can be found guilty of an offence under the current law, which has no statutory medical defence and will not change. 36 Drugs included in the new offence that might be used for medicinal purposes: Amphetamine* Methadone Morphine Clonazepam Diazepam Lorazepam Oxazepam Temazepam *Amphetamine will not be included in the current regulations to go before Parliament in 2014 but it is expected to be included later in 2015 once a limit has been agreed. Although only a few benzodiazepines and opioids are included in the list above, all benzodiazepines and opioids can impair driving ability. The risk of driving impairment is increased if the medicine is taken with alcohol. Warnings on the risks of driving impairment are already in the patient information leaflet. Advice for healthcare professionals: Any condition that requires medicinal treatment may itself pose a risk to driving ability if left untreated. Therefore it is important to advise people who use our services to continue their treatment. Advice to give to people who use our services taking any medicine: Continue taking your medicine as prescribed Check the leaflet that comes with your medicine for information on how your medicine may affect your driving ability It is against the law to drive if your driving ability is impaired by this medicine Do not drive while taking this medicine until you know how it affects you (especially just after starting or changing the dose of the medicine) Do not drive if you feel sleepy, dizzy, unable to concentrate or make decisions, or if you have blurred or double vision Please discuss the implications of this new law with any person who use our services who are taking one of more of the above drugs: There is an information leaflet for patients at: http://www.mhra.gov.uk/home/groups/dsu/documents/publication/con437439.pdf Further details of the new law and advice for healthcare professionals can be found at: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/325275/healthcareprofs-drug-driving.pdf 37 Appendix 3 – Opioids: Important Drug Interactions Opioid Interaction Examples Opioids Affected Mechanism Effect Other opioids Benzodiazepines Tricyclic Antidepressant Antipsychotics Antihistamines Alcohol All Increased CNS depression Addictive effect – potentiation of respiratory depression. Medicines that increase opioid levels. Medicines that increase opioid levels Cimetidine Ciprofloxacin Erythromycin Clarithromycin Fluconazole Ketoconazole Fluvoxamine and possibly other SSRIs Methadone Buprenorphine Increased blood levels of methadone or buprenorphine by inhibition of the enzyme CYP3A4 Dose of methadone or buprenorphine may need to be decreased to prevent toxicity or overdose AND may need to be increased to prevent withdrawal symptoms when the enzyme inhibitor is stopped. Medicines that decrease opioid levels Anticonvulsants (e.g. barbiturates, carbamazepine, phenytoin) HIV Medicines (e.g. efavirenz, nevirapine) Rifampicin Spironolactone St John’s Wort Methadone Buprenorphine Decreased blood levels of methadone or buprenorphine by induced of enzyme CYP3A4 Dose of methadone or buprenorphine may need to be increased to preventwithdrawal symptoms AND decreased to prevent overdose when the enzyme inducer is stopped. Opioids that act as partial agonists Buprenorphine and other partial opioid agonists Methadone Diamorphine Other full agonists Buprenorphine is a partial agonist and displaces other opioids from receptor sites. Can precipate withdrawal symptoms – advise waiting until opioid is excreted (confirmed by presence of withdrawal symyptoms) before taking Other medicines (and substances) that depress the CNS 38 buprenorphine. Opioid antagonists Naltrexone Naloxone – IV, IM and SC All Naltrexone and Naloxone are full antagonists and displace other opioids from receptor sites Will precipitate withdrawal symptoms if taken when agonist or partial agonists have recently been taken Medicines affecting urine pH Vitamin C Sodium bicarbonate (antacids) Methadone Affects excretion of methadone – increased excretion in acidic urine, decreased excretion in alkaline urine Increased excretion may cause withdrawal. Decreased excretion may cause toxicity 39 Appendix 4 – Benzodiazepine Withdrawal Scale Guide to the use of the clinical withdrawal assessment scale for Benzodiazepines Person report: For each of the following items, circle the number that best describes how you feel. Do you feel irritable? 0 1 2 3 Not at all Do you feel fatigued? 0 Very much so 1 2 3 Not at all Do you feel tense? 0 0 Do you have any loss of appetite? 0 1 2 3 1 2 3 Do you feel you heart racing? (palpitations) 0 Does your head feel full or achy? 0 1 2 3 1 2 3 1 2 3 0 1 2 3 40 4 Severe headache 1 2 3 Not at all Not at all 4 Constant racing Not at all Do you feel anxious, nervous or jittery? 4 Intense burning/numbness No disturbance 0 4 No appetite, unable to eat No numbness Do you feel muscle aches or stiffness? 4 Unable to concentrate Not at all 0 4 Very much so Not at all Have you any numbness or burning on your face, hands or feet? 4 Unable to function Not at all Do you have difficulties concentrating? 4 4 Severe stiffness or pain 1 2 3 4 Very much so Do you feel upset? 0 1 2 3 Not at all How restful was your sleep last night? 0 Do you feel weak? 0 Very much so 1 2 3 Very restful 0 Do you have any visual disturbances? (sensitivity to light, blurred vision) 0 Are you fearful? 0 1 2 3 1 2 3 Very much so 41 Not at all 4 Not at all 1 2 3 Not at all 0 4 Very much so 4 Very sensitive to light, blurred vision 1 2 3 Not at all Have you been worrying about possible misfortunes lately? 4 Not at all Not at all Do you think you didn’t have enough sleep last night? 4 4 Very much so 1 2 3 4 Very much so Clinical observations Observe behaviour for sweating, restlessness and agitation 0 None, normal activity 1 2 Restless 3 4 Paces back and forth, unable to sit still Observe tremor Observe feel palms 0 No tremor 0 No sweating visible 1 Not visible, can be felt in fingers 1 Barely perceptible sweating, palms moist 2 Visible but mild 2 Palms and forehead moist, reports armpit sweating 3 Moderate with arms extended 3 Beads of sweat on forehead 4 Severe, with arms not extended 4 Severe drenching sweats Total Score Items 1 - 20 1 – 20 Mild withdrawal 21-40 Moderate withdrawal 41-60 Severe withdrawal 61-80 Very severe withdrawal Source: Adapted from Busto, U.E., Sykora, K & Sellers, E.M. (1989). A clinical scale to assess benzodiazepine withdrawal. Journal of Clinical Psychopharmacology, 9 (6). 412 - 416. 42