www.kirklees.nhs.uk
July 09 • Issue 25
Prescribing & Medicines Management Newsletter NEW: Prasugrel (Efient ▼) tabs: • Thienopyridine (like clopidogrel) anti-platelet agent for CV prophylaxis (+ low dose aspirin) in ACS with PCI. • NICE guidance due Oct 09, but evidence review group report states: “from the trial evidence it is difficult for clinicians to choose between prasugrel and clopidogrel” (prasugrel efficacy (mainly by non-fatal MI) BUT also major bleeds; clopidogrel loading dose/timing in study questioned). • Prasugrel licensing aims to reduce bleeding risk (by contraindication in prior stroke/TIA, not recommended ≥ 75yrs + reduced dose if < 60kg) BUT • prasugrel is more expensive than clopidogrel (£47.56 v £33.93 for 28 days supply) + generic clopidogrel appears to be on the way • Under intensive monitoring by CHM/ MHRA (▼). Action: For specialist initiation only (await NICE guidance)
Tadalafil (Cialis Once-A-Day) tabs: • Continuous (daily) erectile dysfunction (ED) treatment (2.5 or 5mg tabs) [v standard on-demand regime = 10 or 20mg tabs] • Licensed for tadalafil responders having intercourse ≥ 2/wk • Not for treatment naïve patients, patients who currently use less than two treatments per week, or for patients who do not meet the DH criteria for ED prescribing • No direct head-to-head clinical trial evidence comparing once daily with on-demand or with other PDE5 inhibitors (not clear whether there are any difference in efficacy/tolerability) • Daily regimen may allow separation of sexual activity from the process of tablet taking, but clinical significance? • Appropriateness of continued use of the daily regimen should be reassessed periodically (long term safety data is lacking) Drug Sildenafil 50mg Vardenafil 10mg Tadalafil 10mg / 20mg Tadalafil Once-aDay 2.5mg / 5mg
Quantity 4/8 4/8 4/8
Cost (DT Jun 09) £21.27 / £42.54 £22.24 / £44.47 £26.99 / £53.98
28
£54.99
• Patent expiries: sildenafil 2013, tadalafil 2017 (on-demand), vardenafil 2018 • DH recommendation (HSC1999/148) = 1 ED therapy/wk for patients who fulfill the criteria for NHS prescribing. In response to queries about Cialis Once-A-Day the DH state that, in exercising their clinical judgment, GPs may consider this suitable for a small number of patients. Action: This suggests a very limited use for a more expensive product. Prescribers should also be vigilant for diversion as ED treatments have street value.
Oxycodone MR/naloxone MR tabs (Targinact ▼):
Agomelatine (Valdoxan ▼) tabs:
• Severe pain where opioid analgesic required to achieve adequate management • bd dosing (NB ORAL MORPHINE remains FIRST LINE choice) • Naloxone added to counteract opioid-induced constipation (analgesic efficacy not affected) • Trial evidence of clinically relevant improvement in bowel function (versus immediate release oxycodone alone in patients previously constipated on opioids), although regular laxative usage was still required by about 10% of patients in long term studies • Safety & efficacy NOT established in cancer patients and/or liver metastasis (trial data lacking) • Short term nature of double-blind placebocontrolled trials may be an issue if Targinact used for chronic pain • 40mg = max daily dose of oxycodone available via Targinact (separate oxycodone MR alone must be added in if higher dose required; likely effect on bowel function?) • More expensive than MR oxycodone or MR morphine ± laxative (e.g. 28 days supply: Targinact 20/10mg bd £70.22 v Zomorph 30mg + 10mg bd + senna 7.5mg 2on £14.69. Action: Not recommended for routine prescribing (MYHT: • declined by DTC • not stocked by pharmacy • individual patient supply needs Chairman’s approval + pain team consultant request).
• Major depressive episodes in adults • Novel action (melatonin agonist/5-HT2c antagonist) • Contraindicated: hepatic impairment + concomitant use of potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) • Not recommended for < 18yrs • Caution required: > 65 yrs + if large alcohol consumption. • Liver function monitoring required on initiation and after 6, 12 and 24wks (stop treatment if serum transaminases > 3 x upper limit of normal). • Common side effects include GI disturbances, headache, dizziness, insomnia, somnolence and liver function changes. • Expensive compared to generic SSRIs e.g. 28 days’ supply: sertraline 50-100mg tab 1 daily £1.36£1.67 v agomelatine 25mg tab 1 (-2) nocte £38.53 (– £77.06) Action: place in therapy currently unclear and therefore it may be prudent to restrict use to specialists only and continue to follow existing NICE/local depression guidelines.
System(One)-atic choice: unless for clinical reasons (e.g. to avoid known intolerance), please try not to prescribe generic drugs with a particular manufacturer’s name in brackets on System One e.g. ‘simvastatin 40mg tabs (AAH Pharmaceuticals Ltd)’ as the pharmacy will only be able to supply that particular company’s generic. Choose generic drugs with no brackets.
Better Care, Better Value primary care indicators (prescribing) Q3 08 NHS Kirklees (PCT) - for more detail see: www.productivity.nhs.uk (below national average) % simvastatin/pravastatin as all statins (inc. ezetimibe combinations) % ACEI as total renin-angiotensin % lansoprazole/omperazole as all PPIs
National Local SHA Potential position out of position out of savings/year 152 PCTs 14 SHAs 9th 118th £817,117 Part of local incentive scheme 14th 127th £388,933 8th 130th £315,790
www.productivity.nhs.uk
We’ll be ‘awash’ with cost saving tips for liquid meds next issue, but as a ‘taster’ there is a new form of metformin (powder for oral solution 500mg & 1g sachets) which is significantly less costly than metformin liquid: Metformin (Glucophage) sachets 500mg x 84: Metformin liquid 500mg/5ml (84 x 5ml):
£9.21 £228.20-£260.53
The rock & its hard place (or what to do about clopidogrel + PPIs)! • Although there are conflicting viewpoints about the validity of the (exclusively epidemiological) evidence base for the purported CV impact of the interaction between clopidogrel and PPIs (clopidogrel effect/thrombotic risk e.g. of MI), the MHRA has indicated that use of the combination is discouraged ‘unless absolutely necessary.’ • Of course, one person’s ‘absolutely necessary’ may not be another’s and careful assessment of individual patient risk of taking or not taking PPI is required (impact of potential CV protection v GI risk e.g. if a PPI is needed for the aspirin in combined antiplatelet therapy (no evidence for PPI reduction of clopidogrel GI bleed risk) • Interaction is thought to reduce clopidogrel activation but as PPIs differ in their capacity to affect this process and this is not fully mirrored in outcome studies, there is uncertainty over whether one PPI might offer an advantage over another in relation to clopidogrel • H2-antagonists do not appear to interact but confirmatory studies are required. At high dose H2-antagonists (e.g. ranitidine 300mg bd) may be an alternative for aspirin gastroprotection but evidence is lacking (only available for NSAID-induced ulceration) compared to PPIs. www.npci.org.uk/blog/?p=354.
More ‘Webbed Wonders’: 1) www.evidence.nhs.uk NHS Evidence: an online source of “fast, free, relevant and trustworthy” information for health and social care staff has been launched by NICE. It will help users identify the best evidence by sorting, sifting and prioritizing a range of information and awarding an accreditation mark to the most reliable and trustworthy sources of guidance. 2) Nice Bites: available via searching on the National electronic Library for Medicines site (www.nelm.nhs.uk): a monthly bulletin which summarises key prescribing points from NICE guidance. 3) http://therapeuticseducation.org Therapeutics Education Collaboration: Canadian-based, excellent double act podcasts (which can be listened to on your computer directly or downloaded). Tag line: “EvidenceBased Drug Therapy Made Practical and Fun”….quite an achievement if you can manage it and they do better than most!! 4) www.cancerscreening.nhs.uk NHS Cancer Screening Programmes: provides information for patients regarding screening programmes for cervical, breast and bowel cancers. 5) www.bettertesting.org.uk Better testing. org.uk: provides information for healthcare staff on all forms of laboratory testing (question/answer style to around 120 clinical scenarios frequently seen in general practice).
It’s all ‘swine’ for Emergency POM Supplies! New regulations have been introduced as part of the government’s response to the Influenza A H1N1 outbreak including a permanent change to the rules governing emergency supply by community pharmacists of Prescription Only Medicines (POMs):
Be kind (‘Hero-in’ reducing opioid dosing errors) Rewind to: Jul 08, NPSA reported 5 deaths & > 4,200 dose-related opioid patient safety incidents and issued guidance re buprenorphine, diamorphine, dipipanone, fentanyl, hydromorphone, meptazinol, methadone, morphine, oxycodone, papaveretum & pethidine: • All healthcare professionals involved in prescribing, dispensing or administering opioid medicines must ensure they confirm the patient’s previous dose (+ any other prescribed analgesics) in order to guard against overdose • Care particularly with patients discharged from secondary/other care environments as significant changes to medication regimes common • Where dose increase is intended, ensure calculated dose is safe (e.g. for oral morphine or oxycodone in adult patients, not normally > 50% higher than the previous dose) • Significant number of incorrect dose conversions from oral morphine to fentanyl patches (detailed knowledge of new formulation and/or opioid must be acquired) [NB NPSA database of guidance, alerts & documents is available which allows users to find guidance by type, care setting or date of publication. www.npsa.nhs.uk/patientsafety/alerts-anddirectives/patient-safety-informationdatabase/]
Getting good ‘rep’-resentation 5 essential questions to ask: 1. Is there evidence to back claims for benefit/effect of drug being promoted? If not, why continue the conversation? 2. Was the study design valid? • RCT or meta-analyis = best; case control/reports, observational = less reliable • Appropriate comparator? Often placebo used whereas preferred option = best practice treatment • Relevance? e.g. ARB versus unrelated antihypertensive (rather than ACEI) • Study size/ duration? Size can be everything! Too small/short = may not to be statistically powered to detect desired change • Primary or secondary outcome? Studies are usually designed/powered to detect primary outcomes. A non-significant primary outcome makes any secondary analysis potentially unreliable – beware ‘data-dredging’ for a positive result to sell! 3. Statistical significance? p<0.05 is considered statistically significant (but p ≤ 0.001 preferred to be pretty certain of a significant difference). Statistical significance may not mean clinical significance (beware surrogate markers e.g. cholesterol lowering, instead of preferred patient-oriented outcomes such as reduction in cardiovascular disease/mortality) 4. Absolute Risk Reduction (ARR)? Relative Risk Reduction (RRR) looks more impressive but gives no indication of the underlying incidence of the event being examined e.g. CLASS study (Celecoxib vs ibuprofen or diclofenac), RRR for ulcer complications in patients with OA or RA not taking aspirin was 65% but the ARR was only 0.83%! 5. Are the graphs telling the truth? • Does Y-axis start at zero and end at 100%, if not, graph may exaggerate the treatment effect • ▪Does the graph extend beyond the study period? What guarantee is there that the trend will continue (e.g. CLASS 6 mths vs 12 mths data)? • How many patients were in the treatment and control arms at the beginning and end of the study? Ideally studies should be Intention to Treat (ITT) where all involved whether still taking study/control drug or not are included in the results; not doing so may cause exaggeration, particularly graphically.
Calpol Paediatric suspension (it’s all over bar the wailing and gnashing of tiny gums!) The manufacturers have
• The maximum quantity of a POM that can be supplied at the request of a patient has been increased from 5 to 30 days • But remains 5 days for the controlled drugs (CDs) which can be supplied in this manner (i.e. phenobarbitone for epilepsy & Schedule 4/5 CDs) • An emergency supply can be made at the request of a UK registered dentist, or of a patient who has been previously prescribed the requested POM by a UK registered dentist. • Whether to provide an emergency supply and for how long remains at the professional discretion of the pharmacist. • This is not a directly funded NHS service and thus patients may be charged. Alternatively, the supply may be loaned on agreement that an NHS prescription will be furnished to cover the costs.
confirmed that recent supply problems with Calpol Paediatric are a forerunner to the discontinuation of this product. Please now issue all paracetamol suspension prescriptions generically to avoid community pharmacies having to contact surgeries to request alternatives. The OTC version of this product marketed as Calpol Infant will remain available but is NOT allowable on FP10.
Action: Prescribers need to be aware of this change and its potential consequences (pandemic conditions may lead to requests for prescriptions of up to 30 days supply to cover emergency supplies (including from community pharmacists other than patients’ usual ones))
GREEN (specialist initiation): aliskiren, amiodarone, clopidogrel, exenatide, fosterodine, ivadrabine, lacosamide, naltrexone, rotigotine patches, sitagliptan, testosterone gel/patches.
www.rpsgb.org/pdfs/LEBchangesesl.pdf www.opsi.gov.uk/si/si2009/pdf/ uksi_20091165_en.pdf
Just a reminder of the local (SWY APC) ‘traffic light’ (RAG) status of some new(-ish) drugs: RED (hospital only): alitretinoin, dabigatran, deferasirox, octreotide (unlicensed indications), methotrexate injection, rivaroxaban, Sativex, sevelamer. AMBER (shared care): cinacalet, darbepoetin, venlafaxine.
Using the internet is the easiest way to keep up to date with SWY APC RAG listings: www.formulary.cht.nhs.uk/Guidelines/APC/ Main_Index.htm
A gentle tug of the shoulders reminder that… Patients undergoing treatment for cancer (inc. effects of cancer or of current/previous cancer treatment) are now exempt from prescription charges for 5 years (with renewal possible)
• Doctors are requested to advise patients concerned of their entitlement/give them form FP92A once a relevant diagnosis is made (supplies of updated form were sent to oncology departments & all GPs Jan 09 – destroy old version) • Exemption certificates (ECs) only apply to NHS prescription charges but cover all prescriptions not just cancer-related • Prior to receiving EC, advise patients to ask dispenser for an NHS receipt (FP57) (which is also a refund claim form) for any prescription charges paid. • EC is backdated 1mth from the date the application is received • The following do NOT qualify for exemption: 1) advisory sunscreen for skin cancer risk 2) pre-cancerous cells e.g. smear or suspected cancer 3) single episode of treatment e.g. nitrogen freezing of a skin lesion. • However, lymphoedema garments needed as an effect of cancer/its treatment would be covered; also mental health changes directly related to cancer.
The information contained in this newsletter is issued on the understanding it is the best available from the resources at our disposal at the time of going to print. For further information or to share any suggestions of your own please contact the Prescribing Team on 01484 344352.
Produced by NHS Kirklees Medicines Management & Prescribing Team. This newsletter is available to download from the intranet: nww.kirklees.nhs.uk