NHS Fife Community Health Partnerships Addiction Services Guidelines for the use of unlicensed and off label medication within NHS Fife Addiction Services Intranet Procedure No. A11 Author Dr A. Baldacchino Copy No 1 Reviewer Lead Clinician Implementation Date April 2011 Status Authorised 2011 Last Review Date Approved By Medical Director Primary Care Next Review Date April 2013 Head of Nursing NHS Fife 1 Function 1.1 To ensure safe and effective prescribing of unlicensed and off-label medicaton to patients being treated for substance misuse. 2 Location 2.1 NHS Fife out-patient and in-patient services 3 Responsibility 3.1 Prescribing of unlicensed medication is restricted to Consultant Psychiatrists and is to be in accordance with NHS Fife Policy for the use of Unlicensed Medicines. 3.2 Medical and non medical prescribers in Fife NHS Addiction Service may prescribe off-label medication in accordance with NHS Fife Policy for the use of unlicensed medicines 4 Operational System 4.1 In addition to those indications where the use of off-label medication has become accepted practice, the use of unlicensed and off-label medication is a treatment option for: Patients who have failed to respond to licensed medication. Patients who have had a partial response to licensed medication, but a trial of a higher than the maximum licensed dose is considered appropriate. Page 1 of 9
4.2 It is essential that all patients give informed consent to off-label prescribing. This should be clearly documented in the clinical records. Where available, patients should be given a patient information leaflet prior to off-label prescribing. (See example Appendix 1) 4.3 The following medications may be initiated and continued without Consultant Psychiatrist authorisation: Diazepam only for detoxification in benzodiazepine dependence. Naltrexone for use as an adjunct to maintaining abstinence in alcohol misuse disorders. Acamprosate for use during alcohol detoxification for patients who have had frequent detoxification from alcohol. Suboxone up to 32mg daily when used in accordance to the relevant NHS Fife guidance document on buprenorphine titration. Guidance on off-label use of these drugs is given below. 4.4 All other off-label prescribing must be authorised by a Consultant Psychiatrist and supported by a Prescribing Review plan with medical review date clearly stated. Treatments that have accepted off-label for treatment of substance misuse within NHS Fife Addiction Services are: Baclofen for use in alcohol dependence Diazepam in benzodiazepine dependence 4.5 Communication with GP: Prior to transferring the prescribing to a patient s GP, a letter explaining the rationale for offlabel prescribing in that case should be sent. A copy of the prescribing review sheet should also be enclosed. If the GP is willing to take on prescribing, a date for transfer of prescribing should be agreed. 5 Diazepam for use in benzodiazepine withdrawal 5.1 Diazepam may be prescribed as a medically supported detoxification regimen using the appropriate NHS Fife guidance document. Regimens outside this document must be authorised by the prescribing doctor. Slower detoxification courses must only be considered if one of the following apply: Deterioration in mental health resulting in undue distress and increased risk of self harm. Unacceptable objective alcohol withdrawal symptoms. Iatrogenic dependence greater that three years in which case suggested length of detoxification is one month per year of iatrogenic dependence, up to a maximum of twelve months duration of treatment. 5.2 Patients who require stabilisation of diazepam for more than three months should be referred to senior medical staff for assessment. 6 Naltrexone as an adjunct in relapse prevention for alcohol dependence 6.1 Naltrexone hydrochloride tablets are licensed as an adjunct in relapse prevention of detoxified opioid dependent patients (who have remained opiate free for at least 7 10 days). 6.2 Naltrexone is not licensed for the treatment of alcohol dependence in the UK. Page 2 of 9
6.3 Naltrexone is a long acting opioid antagonist and is given in tablet form. If taken on a regular basis after detoxification from alcohol, it can assist in relapse prevention as an adjunct to psychosocial intervention. 6.4 Several studies on naltrexone found this opioid antagonist to be more effective than placebo in reducing relapse rates, increasing the percentage of non drinking days and reducing craving for alcohol in heavy drinkers; however, some other studies failed to demonstrate a significant difference from placebo. 6.5 Due to its scarce evidence this treatment should only be considered if disulfiram and acamprosate have not been successful or are contra-indicated. 6.6 Naltrexone is extensively metabolised by the liver and excreted predominately in the urine. It should be used with caution in patients with impaired hepatic and/or renal function. Liver function tests (LFTs) should be monitored before commencing treatment, and at one and six month intervals. According to this, treatment with naltrexone should be discontinued if there is evidence of progressive hepatic impairment. Arrangements for LFT monitoring should be made available regularly for patients prior to commencing treatment as well as for its entire duration. This pre-treatment monitoring will determine the suitability of patients for this medication and will also establish a baseline for comparison with future tests. 6.7 Treatment plans for patients who are under medical care for liver disease should be discussed with the responsible physician prior to initiating treatment. 6.8 Naltrexone is contraindicated in patients: With acute hepatitis or liver failure Currently dependant on opioids or taking an opioid-containing medication 6.9 The patient should be given a caution card as issued by the drug manufacturer. 6.10 Dosing regime: The initial dose should be 25mg (half a tablet) followed by 50mg daily. The total weekly dose may be divided and be given 3 times a week to improve compliance. For example, 100mg on Mondays and Wednesdays and 150mg on Fridays. 6.11 Success of treatment should be assessed by using alcohol diary, Audit and SADQ. These must be completed prior to commencement of treatment. A lack of significant improvement in both of these measures after three months of treatment will lead to discontinuation. 6.12 If there is evidence of clinical benefit, naltrexone prescribing should continue for at least 6 12 months. 7 Acamprosate for use during Alcohol Detoxification Page 3 of 9
7.1 A number of studies have evidenced that acamprosate may protect against neurotoxicity under the conditions of high polyamine activation that occurs during alcohol withdrawal, which possibly contributes to neuronal loss occasionally seen in chronic alcohol dependence. 7.2 Acamprosate administered during withdrawal states does not appear to cause any unwanted effects. 7.3 In alcohol dependent patients exposed to repeated detoxifications from alcohol, the use of acamprosate during detoxification for neuroprotection may be warranted and should be discussed with senior medical staff. The adequate dose should then be prescribed; four or six 333mg tablets daily (dependent upon weight) in divided doses. The continued use post detoxification should be assessed depending on treatment needs. 8 Suboxone up to 32mg daily 8.1 Where a patient has been commenced on Suboxone and has not stabilised on a dose of 24mg, a trial period of one month on 32mg may be warranted: If the patient fails to stabilise on 32mg then titration onto methadone should be considered. If the patient stabilises on 32mg then switching to buprenorphine alone should be considered. Prolonged use of doses above 24mg must be authorised at consultant level. 9 Baclofen for use in alcohol dependence 9.1 Baclofen has been shown to reduce alcohol craving and intake, and enhance abstinence in alcohol-dependent patients. 9.2 Baclofen has low liver metabolism (about 15%) and is mainly eliminated unmodified by the kidneys, and can therefore be used in individuals affected by liver cirrhosis for whom licensed medication is contraindicated. 9.3 Clinical trials have shown baclofen to reduce anxiety levels in patients with alcohol related difficulties. 9.4 Inclusion Criteria For maintenance of abstinence after detoxification in alcohol-dependent patients: Where licensed medications acamprosate and disulfiram are contraindicated or not tolerated. Who have relapsed on previous attempts using psychosocial treatment and licensed medication. Who have previously relapsed due to severe anxiety symptoms 9.5 Exclusion Criteria Under 16 years of age Unable to give informed consent 9.6 Baclofen is contraindicated in patients with peptic ulceration Page 4 of 9
9.7 Patients should receive the patient information leaflet (Appendix 1) and sign a treatment contract prior to commencement of treatment. 9.8 Dosage regime Side effects are more likely to occur if a very high a dose is initiated or if the dose is increased very rapidly. Recommended initial dose of 5mg three times daily for three days Increasing the dose to 10mg three times a day if side effects are minimal. Further titration by increments of 5mg three times daily every three days can be arranged in response to continued craving and monitored side effects. Doses of up to 100mg per day may be required however doses above 100mg should be authorised by the Consultant. 9.9 Monitoring Response to baclofen will be monitored using the SADQ, Audit, alcohol diaries, alcohol craving questionnaire, liver function tests and Mean Corpuscular Volume (MCV). These will be completed prior to commencing treatment and monthly for the first three months. In clinical practice if there is no positive effect after one month on maximum dose baclofen, treatment will be discontinued. If a therapeutic trial shows a good response, there will be a review within six months and a total duration of treatment up to one year may be suggested. Relapse after cessation of treatment may warrant further treatment. Side effects from medication are dose related and should be recorded at each patient review. 9.10 Special warnings and precautions 9.10.1 Baclofen stimulates gastric acid secretion and should be used with caution in patients with a history of peptic ulcer and avoided in those with active peptic ulcer disease. 9.10.2 Use with caution in patients with severe psychiatric disorders or epilepsy or convulsive disorders as these disorders may be exacerbated by baclofen. Slower titration and weekly monitoring during titration must be implemented in this patient group. 9.10.3 As baclofen is excreted mainly unchanged by the kidneys, patients with renal impairment will only tolerate lower doses. 9.10.4 Liver function should be monitored in patients with liver disease 9.10.5 Use with caution in patients with: Respiratory impairment Diabetes mellitus Cerebrovascular diseases 9.10.6 Baclofen may cause drowsiness; patients affected should not drive or operate machinery. Page 5 of 9
9.10.7 Abrupt withdrawal. Serious side effects can occur on abrupt withdrawal of baclofen; to minimise risk, it is recommended discontinuation by gradual dose reduction over at least 1-2 weeks (longer if symptoms occur). 9.11 Interactions Concomitant treatment with antihypertensive medication is likely to enhance the hypotensive effect. Blood pressure must be monitored weekly during titration and dose of antihypertensive adjusted accordingly. The muscle relaxant effect of baclofen may be enhanced by tricyclic antidepressants. Ibuprofen and other drugs that produce renal insufficiency may reduce baclofen excretion leading to toxicity. Increased sedation may occur if taken with medications acting on the CNS (for example: opioids and alcohol). Baclofen will be prescribed for patients to promote total abstinence from alcohol and will not be continued in patients who resume drinking. 10 References Policy for the use of Unlicensed Medicines. NHS Fife 2008. www.fifeadtc.scot.nhs.uk BNF current edition. Section 4.1 Hypnotics and anxiolytics: Dependence amd withdrawal. Lingford-Hughes, A., Welch, S., Nutt, D., Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from the British Association for Psychpharmacology. Journal of Psychpharmacology 18(3) 2004, 293-335 Koob, G., Mason, B., De Witte, P., et al Potential Neuroprotective Effects of Acamprosate. Alcoholism: Clinical and Experimental Research. Vol. 26, No. 4, April 2002: pp 586-592. Gual, A., and Lehert, P., Acamprosate during and after acute alcohol withdrawal: adouble blind placebo-controlled study in Spain. Alcohol & Alcoholism, Vol. 36, No. 5, 2001, pp 413 418. Slattery, J., Chick, J., Cochrane, M., et al Prevention of relapse in alcohol dependence Health Technology Assessment report 3. Health Technology Board of Scotland, December 2003. Addolorato, G., Leggio, L., Ferruli, A., et al. Effectiveness and safety of baclofen for maitenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis:randomised, double-blind controlled study. The Lancet 370, 2007; 1915-1922. Page 6 of 9
Appendix 1 Information leaflet for Baclofen NHS Fife Addiction Services PATIENT INFORMATION LEAFLET BACLOFEN IN THE TREATMENT OF ALCOHOL DEPENDENCE Three published studies from Italy have suggested that Baclofen reduces the relapse rate in patients with a drinking problem who are trying to abstain from alcohol. It also appears to reduce the sense of craving for alcohol that some patients experience. It has been used safely in patients who have liver damage due to alcohol. It is not yet licensed for alcohol related disorders in the UK. It has been licensed as a muscle relaxant for some 30 years and is widely used in multiple sclerosis, after strokes, sometimes after spinal injury such as slipped disc to relieve spasms, cramping, and tightness of muscles. Baclofen does not cure these problems, but it may allow other treatment, such as physical therapy, to be more helpful. SIDE EFFECTS Baclofen acts on the central nervous system (CNS) to produce its muscle relaxant effects. Its actions on the CNS may also cause some of the medicine's side effects: drowsiness, dizziness, vision problems, or clumsiness or unsteadiness, or a feeling of muscle weakness. A rare side effect has been to increase the possibility that someone will have a seizure. One patient had temporary bladder weakness with incontinence, which ceased when the dose was reduced. As with most medicines which act on the CNS, such as antidepressants, tranquillisers, sleeping tablets, or anticonvulsants, we advise: Know how you react to this medicine before you drive, or use machines. What if I drink alcohol after taking Baclofen? The clumsiness or unsteadiness would be more likely if alcohol was consumed on a day when the person had taken a Baclofen tablet. Do not drink alcohol with the tablets. Baclofen is prescribed to help abstinence from alcohol. If you do take a drink, try and put the brakes on immediately, and resume taking the Baclofen. Does Baclofen interact with my other medication? There are possible interactions with medications used to treat high blood pressure or certain analgesics and a few other medicines. These are listed in the Patient information Leaflet issued by the manufacturer. If you are taking the older tricyclic antidepressants, such as amitriptyline or Imipramine, with Baclofen it may cause unsteadiness or a feeling of muscle weakness. Please advise your doctor of all other medications you take. Page 7 of 9
Is Baclofen addictive? It is not known to be abused, or addictive. There have been a few cases where an individual increased the dose beyond the prescribed dose. Withdrawal symptoms have been described in the days following a large overdose, however we recommend that Baclofen should not be stopped suddenly, rather, gradual decrease over a few days is recommended What dose is prescribed? The usual starting dose is 5mg three times per day increasing gradually to 10 mg three times daily, but your doctor may advise gradual increase to a higher dose, up to a maximum of 100 mg in one day. What can I expect when I start Baclofen? In the beginning of the treatment you might have to be patient. Everybody is different and will need a different dose to decrease and stop craving and symptoms of alcoholism. To avoid side effects (mainly tiredness); we have to increase the dose slowly (typically every 3 days). If you feel craving or you get in a particularly difficult situation it might be good for you to take an extra dose (usually half your normal dose is all that is needed). You should not increase by more than two tablets per day without discussion with the prescribing doctor. If there is no positive effect seen after 1 month, Baclofen treatment will usually be discontinued. The aim is to find a dosing schedule (number and timing of tablets) of Baclofen with which you do not have any craving or thoughts of alcohol. We would expect your body to get used to the dose and not feel tired with this schedule. In situations which have caused cravings in the past (such as passing by the off licence you regularly went to, a party, an anniversary, passing or going to a pub) you might still feel some craving if you don t take an extra dose of Baclofen. It is therefore good to always have some Baclofen with you and take a dose in these situations as soon as possible. Be aware that it takes some time (from about half an hour to about 3 hours) to work. If you do take an additional dose, be extra careful because of the sleepiness it may cause. Driving in these situations is certainly dangerous! I also smoke or have other addiction and psychiatric problems. Does the treatment deal with all of them at once? Baclofen may help you get off these addictive substances, but it might be best concentrate on one addiction at a time. It is important though to not replace one addiction with another. In your case you and your doctor have come to the conclusion that the alcohol problem is most damaging for your body and should be tackled at the moment. Some people notice a benefit on their anxiety or mood levels. This obviously helps with staying off the alcohol. How do I stop baclofen? If a therapeutic trial shows a good response, there will be a review at 6 months, and a total duration of up to one year may be suggested. The body gets used to baclofen (but not addicted). Therefore baclofen must not be stopped suddenly and your doctor will reduce the dose before stopping it. What if I still have strong craving or drink despite taking the baclofen? If you have strong thoughts and urges to drink, of if you lapse and drink alcohol, this may mean that you need a higher dose of baclofen. Speak to your doctor to decide whether to increase your regular doses or whether to take extra doses in certain situations (or both). Page 8 of 9
Why have I not been given baclofen before? Baclofen is a drug we have a lot of experience with in different patients, but it was only relatively recently considered to be potentially helpful in addictions including alcoholism. Is it a magic bullet? No! It helps you to overcome the craving and thoughts about alcohol. It does not work if you are not motivated to reduce and stop drinking. Remember why you decided to do something about your drinking! What else do I need to do? Alcohol causes damage to your body; your alcohol consumption therefore has to change and from the assessment, your doctor knows that you are able to overcome the addiction. Therefore you are already closer to abstinence and a healthier life than many other people. When you take the medication you need to work together with your doctor to help you. This means telling your doctor when you had problems taking the medication or when you found it difficult to stay off the alcohol as soon as possible. Everybody in your situation has tried stopping drinking alcohol, but for one reason or another, started drinking again (relapsed). To be able to stop relapses from happening it is important to find out for yourself in which situations you are most likely to relapse. In the beginning you will certainly need to avoid these difficult situations which might start you on the alcohol again. Also, always have some baclofen with you just in case. Have activities and relationships that you enjoy and that do not involve alcohol. You can discuss with your doctor, the hospital alcohol nurse and your GP which help is available (e.g. Community alcohol team, self help groups such as AA) and what would suit you. They can put you in touch with the help you need. Further information NHS Fife Addiction Service 01592 716446 Page 9 of 9