Clinical Off-label and Unlicensed Medicines Policy Document Control Summary Status: Version: Author/Owner/Title: Approved by: Ratified: Related Trust Strategy and/or Strategic Aims Implementation Date: Review Date: Key Words: Associated Policy or Standard Operating Procedures Contents Replacement superseding the Policy for Medicines Used Outside Terms of Product Licence or Without a Product Licence. 6 Date: December 2015 Mo Azar, Deputy Director of Pharmacy Policy and Procedures Committee Date: 18/02/2016 Trust Board Date: 25/02/2016 Medicines Optimisation Strategy 2013 to 2018 January 2016 January 2019 product licence, high dose antipsychotics (HDAP), monitoring, approved list, unlicensed medicines, SPC, off-label. Medicines Code Trust Formulary Non-Medical Prescribing Policy Medicines Used Outside Product Licence Approved List Medicines Used Outside Product Licence Notification Form Medicines Used Outside Product Licence Patient Leaflet High Dose Antipsychotics Prescribing SOP High Dose Antipsychotics Monitoring Form 1. Introduction... 3 2. Purpose... 4 3. Scope... 4 4. Responsibilities... 4 5. Specific Guidance... 6 6. Process for Monitoring Compliance and Effectiveness... 7 7. References... 7 Appendix 1... 8 Appendix 2... 10 Appendix 3... 14
Change Control Amendment History Version Dates Amendments 6 December 2015 Converted to Trust s approved layout. NMP and Pharmacy responsibilities added. Clinical trial medication added and cross-referenced to Research and Innovation procedures. Approved List updated to include GUM service s prescribing. High Dose Antipsychotic guidance removed to separate SOP High Dose Antipsychotic Monitoring Form reformatted. Page 2 of 14
1. Introduction For a medicine to be marketed in the United Kingdom, it must have a Product Licence, now called a Marketing Authorisation, which is overseen by the Medicines and Healthcare Products Regulatory Agency (MHRA). It is then classed as a licensed medicine. The licence will normally specify the indication, route, dose, and age range of the patients for which the medicine is intended to be used. The Medicines Act (1968) and other associated regulations provide specific exemptions which enable prescribers to: Use (or advise the use of) medicines for indications, doses, routes of administration outside the recommendations of the licence. Override the warnings and precautions given in the licence Use (or advise the use of) medicines for which there is no Marketing Authorisation in the United Kingdom i.e. an unlicensed medicine. These items may require importing to the United Kingdom via specialist wholesalers and permission from the MHRA. In each case the prescriber has to be able to justify the action taken as being in accordance with a respected, responsible body of professional opinion. The prescriber should also be able to justify their selection of a drug in light of an informed risk/benefit assessment. In secondary care, it is common practice to use medicines outside their product licence, often due to a pharmaceutical company's decision not to seek such a licence in a limited group of patients or conditions; unlicensed medicines may also be prescribed by specialists. In most cases there is adequate expert opinion to support such use. In some fields of practice, e.g. paediatrics and learning disabilities, there may be only a few medicines actually fully licensed and marketed for use. The majority of treatments being used will fall outside the terms of the product licence, or may not even have a UK licence, but nevertheless it is still good medical practice to use them. Informed consent to treatment is a key area of prescribing. However, consent to a medicine being used outside of its product licence or without a licence is difficult, as misunderstandings of a medicine s safety profile might undermine a patient's confidence, causing unnecessary alarm. The unlicensed situation may be because of lack of clinical data, or be economically unfeasible to obtain, rather than evidence of harm. Nevertheless, a patient or their carer has the right to participate in decisions regarding healthcare, including having the knowledge of a drug's licensed indications. Patients have a right to a Patient Information Leaflet (PIL) with their dispensed medicine and the licensing criteria will be stated in this document rather than the purposes discussed with the prescriber. This may lead to a patient deciding not to take a particular medicine. In this situation, it will therefore almost always be beneficial to raise the licensing issue when the medicine is prescribed. An information leaflet is available from the Trust to support this matter. This policy should be read in conjunction with all medicines policies and procedures, particularly the Medicines Code and Trust Formulary. Non-medical Prescribers should also refer to the Non-medical Prescribing Policy and associated procedures. Page 3 of 14
2. Purpose This policy aims to ensure that when medicines are used outside of their product licence ( off-label ) or without a product licence (unlicensed), patients are appropriately informed, and that clinical risks and liability for the Trust are minimised. This policy specifically covers the management of prescribing high dose antipsychotics in an associated procedure. 3. Scope This policy applies to all prescribers working within the Trust. Non-Medical Prescribers (NMPs) may also prescribe medicines outside the terms of, or without, a product licence provided that they work within the scope of their formulary and in accordance with the Nonmedical Prescribing Policy. Pharmacy and Medicines Optimisation department staff will also need to ensure the additional documentation required when dispensing unlicensed medicines is completed and that all reasonable steps are taken to source products with a UK Marketing Authorisation where such products exist. Pharmacy and Medicines Optimisation department staff should be prepared to challenge the prescribing of medicines outside the terms of, or without, a product licence where it is not considered usual practice to prescribe such items. Neither they nor the Trust are liable for the decision to prescribe medicines described in the procedure and full liability remains with the individual prescriber. 4. Responsibilities Prescribers should, whenever possible, prescribe medicines that are appropriately licensed for the condition and patient they are intending to treat and should follow the manufacturer s recommendations. If prescribing outside or without a product licence, prescribers should follow the guidelines in an established reference source. Ideally, this would be from published prescribing guidelines including those published by NICE, although it could be from a scientific paper from a reputable journal. Prescribers should follow advice from their Royal College (Appendix 1). Normally, only consultants, associated specialists, GPs with Special Interest or independent non-medical prescribers (when working within their own formulary) should initiate prescribing outside or without a product licence; the prescribing should be within their field of expertise. Junior medical staff or supplementary non-medical prescribers may only initiate prescribing outside of a medicine s product licence, or a product without a licence, if there is an established protocol that has been endorsed by a medical consultant or clinical lead. The Medicines Optimisation Committee should be notified of such practice unless the medication/indication appears the approved list associated with this Policy and is being prescribed in this way. Page 4 of 14
Junior medical staff prescribing to continue the off-label or unlicensed treatment may do so provided it is still within the specialist s ongoing treatment plan. They should, however, be aware of their own liability around the prescribing of such treatments. Service users and/or their carers should be informed of the reason why the treatment is being used and should be informed that the Patient Information Leaflet, within the medicines pack, might not be in accordance with the prescriber's intended use of the drug. They should be offered the Trust s Unlicensed Medication leaflet as part of the consultation process to support this explanation. The Pharmacy and Medicines Optimisation Department (or community pharmacist) has a responsibility of notifying a prescriber if a medicine requested is clearly being used significantly outside the terms of its product licence, or without a product licence, and there is no clear precedent for its use. The prescriber has a responsibility to the Trust of justifying his/her action, and this being subject to scrutiny by the Medicines Optimisation Committee. However, if such use is likely to be fairly common practice it would be more appropriate for the medication or indication to be added to the approved list associated with this policy (Appendix 2). Such cases should be made by the specialist to the chair of Medicines Optimisation Committee (or nominated deputy) and will only be added to the approved list if supporting evidence is provided and it is agreed by the Committee. Whether advised by the Pharmacy and Medicines Optimisation Department or not, if prescribing a medicine subject to this policy but not included on the approved list, Trust prescribers are required to complete a Medicines Used Outside of a Product Licence Notification Form (Appendix 3), and submit it to the Director of Pharmacy (or nominated deputy). Such instances will be submitted to the Medicines Optimisation Committee to provide an opportunity for peer review scrutiny within the Trust. In all cases of prescribing off-label or unlicensed medicines (whether on the approved list or not and irrespective of noting by the Committee), the prescriber retains full responsibility for their clinical decisions made in this area. Investigational Medicinal Products (IMPs) being prescribed as part of a formal clinical trial will be dealt with separately as part of the Research and Innovation Department s agreed policies and procedures in accordance with Good Clinical Practice standards. As part of the approval process, the trial will be assessed at the Medicines Optimisation Committee and prescribing will be limited to those on the Principal Investigator s delegation log. Patients admitted to Trust premises who are taking part in another organisation s clinical trial may continue to take part in that study provided: it is appropriate, the study team are aware of the situation and that the case has been brought to the attention of both the Research and Innovation Department and the Pharmacy and Medicines Optimisation Department. If it is the intention that the drug is to be prescribed in primary care, then the GP must be informed of the unlicensed or off-label use of the medicine by the Trust prescriber; NB GPs may not be prepared to prescribe such products. In these cases, the Trust prescriber should initially offer the availability of an Essential Shared Care Agreement (ESCA), where one exists (normally those drugs that have been pronounced on by NICE as appropriate for GP prescription once the patient is stabilised). ESCAs have previously been approved by the Trust and relevant Clinical Commissioning Group, to further support the GP in taking on prescribing responsibility; support is available from the Pharmacy and Medicines Optimisation Department. If the GP refuses to prescribe the treatment then the Trust prescriber will be expected to continue with the long-term prescribing. In situations where an ESCA is available, complete an ESCA refusal form and send to the Pharmacy and Page 5 of 14
Medicines Optimisation Department. In situations where there is no ESCA in place, the unlicensed/off-label treatment should remain with the specialist and not be transferred to primary care. 5. Specific Guidance The majority of medicines used within adult mental health, substance misuse and sexual health services have a Marketing Authorisation, which sets out the manufacturer s conditions of use and for which, if followed, they will take legal liability for the safety of the product. The prescriber is still liable for the use of the medicines they prescribe (as per the GMC s Good Medical Practice). If a medicine is prescribed for a condition for which it is not licensed then the prescriber must take full legal responsibility for the product as well. A drug can be mentioned in the BNF but not have a licence. It is possible to access up-to-date Summaries of Product Characteristics (Product Licence information) for medicines on the electronic medicines compendium http://www.medicines.org.uk/emc/ Prescribers may recommend the use of medicines outside their licence ( off label ). In such cases, the evidence will have been assessed and a judgement made that the use of such medications is of benefit to the service user, outweighing any risks that might apply. The service user should be fully informed of the benefits and adverse effects of the medication. The Trust has agreed to support prescribers carry out their standard practice by acknowledging the use of a limited list of treatments (both unlicensed medicines for the listed indications, or unlicensed uses of licensed medication) as they can occur commonly and have evidence to support their use; individual notifications to the Medicines Optimisation Committee are not required in these instances. However, the Trust does not: accept liability for their use; seek to promote as a corporate body their use; and does not consider the list suitable for citing as a reference by another person or organisation. The intention of the list is solely to reduce internal procedural burden for prescribers undertaking standard practice. The off-label use of licensed medicines within Child and Adolescent Mental Health Services is also supported by the Trust, when used in concordance with the current version of the BNF for Children. The use of medicines within the Community Paediatrics service and Community Children s Nursing team is so specialised that it would be impractical to set an approved list. Paediatricians are advised to follow the guidance from their Royal College. Children s nurses should liaise with the specialist paediatricians and the Pharmacy and Medicines Optimisation Department to maintain and follow a local formulary and any specific shared care protocols approved by the Medicines Optimisation Committee. The list is constantly under review; please contact the Director of Pharmacy and Medicines Optimisation (or nominated deputy) if it is felt that there are any inaccuracies or medicines/indications that should be included or removed. Page 6 of 14
6. Process for Monitoring Compliance and Effectiveness This policy will be monitored by the Medicines Optimisation Committee through submission of Medicines Used Outside of Product Licence Forms and requests for amendment to the approved list, clinical pharmacist supervision identifying trends in practice and information obtained from prescription data / prescribing indicator reports. When dispensing unlicensed medicinal products, the Trust s dispensary teams will follow their local procedure and document the supplies made as stipulated by the MHRA and retain those records for the required period of five years from the last entry. 7. References Medicines Act 1968 and Regulations. The Use of Unlicensed Medicines or Licensed Medicines for Unlicensed Applications in Paediatric Practice, Policy Statement. Royal College of Paediatrics and Child Health and Neonatal and Paediatrics Pharmacist Group Standing Committee on Medicines. December 2013. Use of Licensed Medicines for Unlicensed Applications in Psychiatric Practice. CR142, Royal College of Psychiatrists, January 2007. Good Medical Practice: Prescribing and Managing Medicines and Devises: Prescribing Unlicensed Medicines. General Medical Council, 2013. The Supply of Unlicensed Medicinal Products (specials). Guidance Note 14, Medicines and Healthcare Regulatory Agency, May 2014. Page 7 of 14
Appendix 1: Use of unlicensed medicines or licensed medicines for unlicensed applications (Royal Colleges) Summary of the recommendations from the joint Royal College of Paediatrics and Child Health and the Neonatal and Paediatric Pharmacists Group standing committee on medicines (Royal College of Paediatrics and Child Health, 2013) Those who prescribe for a child should choose the medicine which offers the best prospect for that child, aware that such prescribing may be constrained by the availability of resources. Children should be able to receive medicines that are safe, effective, appropriate for their condition, palatable and available with minimal clinical risk. The informed use of some unlicensed medicines or licensed medicines for unlicensed applications is necessary in paediatric practice. Health professionals should have access to reliable and up-to-date information, where possible, on any medicine they prescribe, dispense or administer, and on its availability. In general, it is not necessary to take additional steps, beyond those taken when prescribing licensed medicines, to obtain the consent of parents, carers and child patients to prescribe or administer unlicensed medicines or licensed medicines for unlicensed applications. NHS Organisations should support therapeutic practices that are advocated by a respectable, responsible body of professional opinion. Where available an appropriate licensed preparation should be prescribed and supplied in preference to an unlicensed preparation. Use of licensed medicines for unlicensed applications in psychiatric practice (CR142, Royal College of Psychiatrists, January 2007) 1) Check that medicines with a product licence have either had a proper therapeutic trial or been considered, but excluded on clinical grounds (such as contraindications and risk of interactions). 2) Familiarise yourself with the evidence about the proposed drug, including any possible drug interactions and potential adverse effects. 3) If the medicine to be used does not have a substantial evidence base supporting its use for the proposed indication, or if you are not sufficiently expert in this field, or have particular concerns, obtain the advice of another doctor or specialist pharmacist. 4) Consider the risks and benefits of the proposed treatment. Particular consideration is needed with children, older patients, and in those with impaired insight and judgement. Document this. 5) Give the patient (or his/her relative, when relevant) a full explanation, including the information that the drug will be used outside its product licence. Document this explanation. 6) If agreement from the patient (or his/her relative, when needed) is obtained, document this approval. If a patient is unable to consent to a necessary treatment, note that it has not been possible to obtain consent. 7) Begin a cautious trial of treatment with the medicine. In out-patients, consider sending the patient a copy of any letter sent to his/her general practitioner, summarising why this approach has been adopted. 8) Monitor the patient closely. Continue with full documentation of its effectiveness and tolerance. Page 8 of 14
9) If the treatment proves unsuccessful, withdraw it, gradually if needed. Document the reason for the withdrawal of treatment and then consider alternatives, using the same process. 10) Consider writing up the case, to add to knowledge about the drug and its use. Page 9 of 14
Appendix 2: Medicines Used Outside Product License Approved List Mental Health Services Drug or Group Unlicensed condition or use Comments Antidepressants Anxiety/ Panic disorder Some licensed for these indications; try these first All antipsychotics Excluding new products subject to a managed entry scheme within the Trust where specific criteria are in place Haloperidol, Risperidone Atypical antipsychotics Antipsychotics Acetylcholinesterase inhibitors All hypnotics and benzodiazepines beyond short-term Clonazepam, Midazolam Doses above SPC limits (as single agents or in combination) Use in bipolar affective disorder and schizoaffective disorder Insomnia (in individuals prone to dependence with hypnotics), agitation, anxiety, aggression Adults with a learning difficulty with behavioural problems Tourette s and other tic disorders Children and adolescents To manage behavioural and psychological symptoms in dementia To manage behavioural and psychological symptoms in dementia Mania / acute psychiatric condition In accordance with Royal College of Psychiatrists advice and Trust guidance: High Dose Antipsychotic Prescribing SOP. Some are licensed for mania and prophylaxis Only for short-term use (e.g. 4 weeks) with appropriate review Caution if history of stroke or TIA, or risk factors for cardiovascular disease. See the Trust s Antipsychotics in Dementia Guidance. Risperidone has a very limited licence When risk assessed, and involuntary addiction minimised through a clear management plan Baclofen Alcohol dependence Third line Page 10 of 14
Drug or Group Benzodiazepines Unlicensed condition or use As required tranquillisation for challenging behaviour Comments As part of Trust s rapid tranquillisation policy Memantine Lorazepam In combination with an acetylcholinesterase inhibitor This combination is excluded from the essential shared care agreement (ESCA) so prescribing remains the responsibility of the Trust Injection given orally Unlicensed injection imported during licenced version s supply problem Propranolol Akathisia Buprenorphine Substance Misuse Crushing of tablets for supervised consumption in individuals known to divert medication Carbamazepine Clonazepam Clonidine Methylphenidate/ Atomoxetine/ Dexamfetamine (NB: non-formulary) Bipolar affective disorder (non-lithium resistant cases) Aggression and impulsive behaviour Behavioural control Anxiety Tardive dyskinesia REM Sleep Behaviour Disorder in Parkinson s and Dementia with Lewy Bodies ADHD and Tourette s Treatment of ADHD in working age adults Only licensed for use in lithium non-responsive cases Skills and supervision arrangements required. ESCAs are developed for adult use for Methylphenidate and Atomoxetine Page 11 of 14
Drug or Group Hyoscine hydrobromide (Kwells, Scopoderm patches), Pirenzepine Unlicensed condition or use Hypersalivation Comments Side effect of antipsychotics esp. clozapine. See hypersalivation guidance within the clozapine policy. (Other unlicensed treatments included within this guide). Lamotrigine Modafinil Beta blockers Sodium Valproate (Epilim) (all formulations) Wider use in bipolar affective disorder Sleep problems in Parkinson s Tachycardia when seen as a side effect of clozapine Use in bipolar affective disorder Licensed for prevention of depressive episodes in bipolar I only Midazolam Status epilepticus Buccal Licensed product: Buccolam preferred Diazepam Rescue medication for clusters of epileptic seizures Oral instead of rectal is useful in patients who are having repeated seizures with complete recovery in between. Naltrexone Alcohol dependence At a dose of 50mg daily, and unlicensed low-strength tablets and injection Melatonin All medicines containing nonsustained release ingredients, where safety and appropriateness have been discussed with pharmacy Insomnia in children and adolescents, and adult users of DNLD services (without primary insomnia). Crushed Please check with Pharmacy before crushing any medicines See ESCA and Prescribing Guidance. Licensed product (Circadin) preferred for offlabel use, rather than unlicensed products. For patients under the MHA 1983, if non-concordant and necessary. NOT COVERT. For physical health treatments (and also for Page 12 of 14
Drug or Group Quetiapine Intravenous fluids: Sodium Chloride 0.9% Glucose 5% Unlicensed condition or use All indications for modifiedrelease (XL) formulation being used with the immediate release formulation. Sub-cutaneous administration Comments other informal patients) administered under the Mental Capacity Act. Includes covert use see separate guidance. For patients who have a swallowing difficulty. For management of dehydration i.e. hypodermoclysis GUM Services Drug or Group Unlicensed condition or use Comments Benzathine Penicillin Syphilis Standard antibacterial treatment for syphilis Clobetasol Propionate 0.05% cream or ointment Tricholoracetic Acid 90% Solution Post Exposure Prophylaxis (PEP) Pack Truvada (245mg tenofovir disoproxil and 200mg emtricitabine) + raltegravir Vulval Conditions (Genital dermatosis, lichen sclerosis, lichen planus) Chemical cauterisation of anogenital warts HIV prophylaxis Ointment generally preferred, creams have preservatives which can be irritant For use in specialist setting only Special packs procured which utilise licensed products packed down for specific courses. Page 13 of 14
Appendix 3 Medicines Used Outside Terms of (or Without) a Product Licence Please complete and submit to the Medicines Optimisation Committee Post: Director of Pharmacy and Medicines Optimisation, Pharmacy Department, St George s Hospital, Stafford, ST16 3AG Fax: 01785 783005 NHS Number: Date of Initiation: Name of Prescribing Clinician (Holds full liability for prescribing) Contact details and base of Prescriber: Medicine Prescribed: Please state formulation and strength. Indication for Prescription: Dose, frequency and route prescribed: This represents: (please tick) A licensed medicine used outside of its Marketing Authorisation (off-label) An unlicensed medicine Rationale for offlabel or unlicensed use: Please give full information, so that rationale can be understood. References: If an established protocol or reference source is followed, please supply details. Page 14 of 14