Bulletin 62 February 2014 Community Interest Company Switching Tramacet to paracetamol alone or paracetamol and codeine This is one of a number of bulletins providing further information on medicines contained in the PrescQIPP DROP-List (DRugs of low Priority). This bulletin focuses on Tramacet (paracetamol 325mg/ tramadol 37.5mg) and provides the rationale for new patients to be initiated on paracetamol or those requiring a weak opioid to be commenced on paracetamol with codeine. Current patients should be considered for a switch to paracetamol alone or paracetamol with codeine. Information on adverse effects of Tramacet, options for dose conversion in support of the switch and potential switch savings are provided. Further bulletins, including the DROP-List, are available on the PrescQIPP website: http://www.prescqipp.info/resources/viewcategory/171-drop-list Recommendations Commence new patients requiring analgesia on paracetamol taken on a regular basis. Those requiring a weak opioid analgesic can have codeine added to their paracetamol. Review all patients on Tramacet or its generic equivalent for suitability for switching to paracetamol, alone or paracetamol with codeine. Switch all suitable patients to paracetamol alone or paracetamol and codeine. As with all switches, these should be tailored to the individual patient. Background Tramacet features as No.15 in the PrescQIPP DROP-List. 1 The DROP-List is an accumulation of medicines that are regarded as low priority, poor value for money or medicines for which there are safer alternatives. In the PrescQIPP membership area (November 2013, population-18.4 million patients), using the three month spend between September and November 2013 and multiplying up, 960,148 will be spent on Tramacet and its generic equivalent over the course of a year. Switching to paracetamol alone at its optimal dose could save up to 777,169 across the PrescQIPP membership. 2 As with all switches, individual patient circumstances need to be borne in mind, however, with tight switching criteria, assistance from practice nurses, support from your local CCG prescribing teams and the experiences of CCGs/GPs that have already undertaken this work, it is hoped that GPs will participate in realising the cost savings. Rationale for switching to paracetamol alone or with codeine Tramacet contains tramadol 37.5mg and 325mg of paracetamol and is licensed for use in moderate to severe pain. 3, 4 The strength of both drugs in Tramacet is not optimal for either one. Tramacet has been found to have similar efficacy to ibuprofen 400mg for acute pain and co-codamol 30/300mg in chronic pain. 5, 6 1 of 5
There is no evidence that Tramacet is more effective or safer than paracetamol 500mg and codeine 30mg (both as individual drugs, or combined as co-codamol 30/500). 3-6 Tramadol is licensed for treatment of moderate to severe pain but it has not been shown to be either more effective or better tolerated than other weak opioid analgesics, such as codeine. For severe pain, strong opioids are more effective. 5 Tramadol is not included in the advice given by the British Pain Society and Medicines and Healthcare Regulatory Agency (MHRA) for options in the management of mild to moderate pain. 7 Tramadol appears on the World Health Organisation s (WHO) pain ladder as a weak opioid between the WHO step two analgesics for moderate pain (such as dihydrocodeine) and the WHO step three analgesics (strong opioids such as morphine) for severe pain. However, there is little evidence of the efficacy of tramadol from clinically useful trials (particularly in primary care, chronic pain and cancer pain). 8 The place in therapy of tramadol in cancer pain seems limited. It is neither more effective nor better tolerated than other, less expensive step two analgesics and, in severe pain, strong opioids are likely to be more effective. 8 Tramacet costs substantially more than other drugs which would be considered at step two of the WHO analgesic ladder drugs without evidence of improved efficacy or safety. 5,6 Tramacet was reviewed by the Scottish Medicines Consortium (SMC) in 2006 and they did not recommend it for use within NHS Scotland for the treatment of moderate to severe pain. Tramacet had similar efficacy to co-codamol 30/300mg in clinical studies, though the dose of paracetamol in the co-codamol preparation it was compared to was lower than that usually used in the UK. The SMC also noted that Tramacet costs significantly more than its individual components (i.e. tramadol and paracetamol) prescribed separately. 9 Tramacet has a similar profile of side effects and possible interactions as tramadol. 3-6 Dizziness and constipation are very common side effects of Tramacet and tramadol, occurring in more than 10% of patient. 3,4,10 Hallucinations, confusion and convulsions, as well as rare cases of drug dependence and withdrawal, have been reported with tramadol at therapeutic doses. 8,10 To minimise the risk of convulsions, the Committee on Safety of Medicines (CSM) recommended that patients with a history of epilepsy take tramadol only if there are compelling reasons. In addition, tramadol should be used with caution in patients taking concomitant drugs that can lower the seizure threshold, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. 11 There has been an increased incidence of tramadol related deaths which has led to the Advisory Council on the Misuse of Drugs recommending that tramadol is reclassified as a Class C substance under the Misuse of Drugs Act 1971 and is listed in Schedule III of the Misuse of Drugs Regulations 2001. These tighter controls would have consequences for the prescribing of tramadol and, therefore, also Tramacet. 12 Compound analgesic preparations that contain a simple analgesic (such as paracetamol) with an opioid component reduce the scope for effective titration of the individual components in the management of pain of varying intensity. 13 Furthermore, the dose of paracetamol contained in Tramacet is not optimal. The advantages of using compound analgesic preparations have not been substantiated. The addition of a low dose of an opioid can result in opioid side-effects (e.g. constipation) and can complicate treatment of overdose without any additional pain relief. The elderly are particularly susceptible to the side effects of opioids. 13 The effects of opioid analgesia are increased and prolonged, and there is increased cerebral sensitivity when patients with renal impairment are treated with opioid analgesics; avoid use or reduce dose. 13 2 of 5
Costs B62. Switching Tramacet to paracetamol alone or paracetamol and codeine 2.1 There is a significant difference in cost between Tramacet and its generic equivalent compared to paracetamol and codeine. Table 1 below illustrates the cost differences. Table 1: Tramacet product and price comparison Drug Tariff November 2013 14 Product Cost per 28 days Tramacet (37.5mg tramadol/325mg paracetamol) tablets, 60 tab pack 36.14 Tramacet (37.5mg tramadol/325mg paracetamol) effervescent tablets, 60 tab pack 36.14 Tramadol 37.5mg/paracetamol 325mg tablets, 60 tab pack 35.02 *Co-codamol (30mg codeine/500mg paracetamol) effervescent tablets, 100 tab pack Paracetamol 500mg tablets (1g QDS) + codeine 30mg tablets (60mg prn up to max of 240mg daily) 19.11 17.36 Codeine 30mg tablets, 100 tab pack 11.20 *Co-codamol (30mg codeine/500mg paracetamol) 100 cap pack 9.59 Paracetamol 500mg tablets, 100 tab pack 6.16 *See information above in Rationale for switching to paracetamol alone or paracetamol and codeine relating to compound analgesics. Switching options There are three potential switch options from Tramacet or its generic equivalent product (at a dose of tramadol 75mg/ paracetamol 650mg QDS), although clinicians may choose other options according to the clinical need of the patient. These include: 1. Paracetamol 1g QDS* 2. Codeine 30mg-60mg QDS* 3. Paracetamol 1g QDS with codeine 30mg-60mg prn (max 240mg daily)* *For frail elderly patients with low bodyweight, a lower maximum dose of paracetamol and opioids should be considered. Switch savings There is a significant difference in cost between Tramacet and paracetamol or codeine. In the PrescQIPP membership area, around 960,648 is spent on Tramacet and its generic equivalent per year. Switching from both Tramacet and its generic equivalent to paracetamol alone could release savings of up to 779,169 across the PrescQIPP membership. Table 2 on the following page illustrates the savings that can be made by switching from Tramacet to paracetamol alone or with codeine. 3 of 5
Table 2: Potential savings when switching from Tramacet to paracetamol alone or paracetamol and codeine.** Tramacet switch Minimum saving per 28 days Annual switch savings per 100,000 patients per year across PrescQIPP membership Switch from Tramacet to paracetamol 500mg, 2 tablets QDS 29.98 4,228 Switch from Tramacet to codeine 30mg, 2 tablets QDS 24.94 3,424 Switch from Tramacet to paracetamol 500mg tablets (1g QDS) + codeine 30mg tablets (30mg-60mg prn up to max of 240mg daily) 18.78 2,442 **See information above in Rationale for switching to paracetamol alone or paracetamol and codeine relating to compound analgesics. References 1. PrescQIPP DROP-List January 2012. Bulletin available at http://www.prescqipp.info/resources/viewcategory/171-drop-list 2. PrescQIPP subscriber prescribing data taken from epact September to November 2013. 3. Summary of Product Characteristics - Tramacet 37.5mg/ 325mg film-coated tablets. Last updated: 07/05/2010. Accessed: 16/10/2013. http://www.medicines.org.uk/emc/medicine/22196/spc/tramacet+37.5+mg++325+mg+filmcoated+tablets/ 4. Summary of Product Characteristics - Tramacet 37.5mg/ 325mg effervescent tablets. Last updated: 28/04/2010. Accessed: 16/10/2013. http://www.medicines.org.uk/emc/medicine/22691/spc/ Tramacet+37.5+mg+325+mg+effervescent+tablets/ 5. National Prescribing Centre. Pain Overview Data Focused Commentary: Use of Opioids. 2010. Accessed 16/10/2013. http://www.npc.nhs.uk/therapeutics/pain/overview/resources/dfc_pain_overview.pdf 6. National Prescribing Centre. The withdrawal of co-proxamol: alternative analgesics for mild to moderate pain. MeReC Bulletin 2006;16(4). Accessed 17/10/2013. http://www.npc.nhs.uk/merec/pain/otherback/resources/merec_bulletin_vol16_no4.pdf 7. British Pain Society/ Medicines and Healthcare Products Regulatory Agency. January 2006. Advice from the CSM Expert Working Group on analgesic options in treatment of mild to moderate pain. Accessed 17/10/2013 www.mhra.gov.uk/home/groups/pl-a/documents/websiteresources/con2023013.pdf 8. National Prescribing Centre: The use of strong opioids in palliative care. MeReC Briefing 22, 2003. Accessed 17/10/2013. http://www.npc.nhs.uk/merec/pain/otherback/resources/merec_briefing_no22.pdf 9. Scottish Medicines Consortium Assessment. Tramadol 37.5mg/paracetamol 325mg (Tramacet ). Janssen-Cilag No. (236/06). 6th January 2006. Accessed 17/10/2013. 4 of 5
http://www.scottishmedicines.org.uk/files/tramadol_hci_paracetamol_l_tramacet 236-06_.pdf 10. Summary of Product Characteristics - Tramadol hydrochloride 50mg capsules. Last updated: 12/06/2013. Accessed 18/10/2013. http://www.medicines.org.uk/emc/medicine/24186/spc/ Tramadol+Hydrochloride+50mg+Capsules/#UNDESIRABLE_EFFECTS 11. In focus: Tramadol (Zydol, Tramake and Zamadol). Current Problems in Pharmacovigilance 1996;22:11. Accessed 18/10/2013. www.mhra.gov.uk/publications/safetyguidance/currentproblemsinpharmacovigilance/ CON007485. 12. Advisory Council on the Misuse of Drugs (ACMD) consideration of tramadol. February 2013. Accessed 18/10/2013. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/144116/advicetramadol.pdf 13. BNF 66. Accessed 31/10/2013. http://www.bnf.org/bnf/index.htm 14. Drug Tariff October 2013. Accessed 23/10/2013. http://www.ppa.org.uk/ppa/edt_intro.htm Additional resources Briefing Data pack Available for download here: http://www.prescqipp.info/-tramacet/viewcategory/180 Information compiled by Melitta Mudaly, PrescQIPP Pharmacist Project Manager, November 2013, and reviewed by Katie Smith, East Anglia Medicines Information Service, January 2014. Non-subscriber publication June 2014. This document represents the view of PrescQIPP at the time of publication, which was arrived at after careful consideration of the referenced evidence, and in accordance with PrescQIPP s quality assurance framework. The use and application of this guidance does not override the individual responsibility of health and social care professionals to make decisions appropriate to local need and the circumstances of individual patients (in consultation with the patient and/or guardian or carer). Terms and conditions 5 of 5