Medicines - achieving value and sustainability in prescribing: guidance

Prescribing Guidance for Medicines of Low or Limited Clinical Value

Items of low clinical value

Items where no prescribing is appropriate because either there are significant safety concerns, no evidence of clinical effectiveness or no additional benefits compared with cost-effective alternatives.

Recommendations

• do not initiate in primary or secondary care
• deprescribe where safe in individuals currently prescribed this item

These recommendations apply to:

• co-proxamol
• glucosamine and chondroitin
• herbal treatments
• homeopathy
• minocycline for acne
• aliskiren
• dipipanone hydrochloride and cyclizine combination product
• doxazosin modified release preparation
• lutein and antioxidants
• omega-3 fatty acids (excluding Vazkepa®)
• oxycodone and naloxone combination product
• paracetamol and tramadol combination product
• perindopril arginine
• probiotics (VSL#3® and Vivomixx™)
• rubefacients (excluding capsaicin and topical NSAID)

Co-proxamol

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• co-proxamol was fully withdrawn from the UK market in 2007 by the Medicines and Healthcare products Regulatory Agency (MHRA) due to safety concerns regarding toxicity and risk of fatal overdose.
• there is no licensed preparation available in the UK therefore any existing prescribing is on an unlicensed basis
• the cost of prescribing co-proxamol as an unlicensed ‘special’ is significantly higher than the licensed cost-effective alternatives as it requires to be imported for individual use at a cost to the NHS and the environment.
• the paracetamol dose in each tablet is at a lower dose (325mg) than in standard paracetamol preparations (500mg).
• there is no robust evidence that co-proxamol is more effective than full strength paracetamol.
• there is a risk of addiction and abuse associated with co-proxamol.
• co-proxamol is potentially fatal in overdose. The lethal dose is relatively low and can be potentiated by alcohol and other central nervous system depressants.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Glucosamine and Chondroitin

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• glucosamine and chondroitin supplements are often taken for pain associated with arthritis and can be purchased from pharmacies, supermarkets, and health food stores.
• glucosamine is deemed less suitable for prescribing by the British National Formulary (BNF) as the mechanism of action is not understood and there is limited evidence to show it is effective.
• NICE guidance on osteoarthritis care and management recommends: Do not offer glucosamine or chondroitin products for the management of osteoarthritis.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Herbal treatments

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• there is a lack of robust evidence of the clinical effectiveness of herbal treatments. Herbal treatments come in a variety of formulations, such as tablets, capsules, powders, and sprays. and can be and can be purchased from pharmacies, supermarkets, and health food stores.
• there is a lack of scientific evidence required to register these products with the MHRA. Under a traditional herbal registration (THR) there is no requirement to prove scientifically that a product works; the registration is based on longstanding use of the product as a traditional medicine.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Homeopathy

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• homeopathy is a complementary or alternative therapy that seeks to treat individuals with highly diluted substances that are administered orally. Homeopathy is mainly available in tablet form but also comes in drops, capsules, and powders and can be purchased from pharmacies, supermarkets, and health food stores.
• there is a lack of robust evidence for its clinical effectiveness.
• the specialist pharmacist service (SPS) reviewed the evidence for homeopathy for the NHS England ‘Items which should not be routinely prescribed in primary care’ consultation and found no clear or robust evidence to support the use of homeopathy on the NHS.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Minocycline for acne

Recommendation:

• do not initiate for treatment of acne.
• deprescribe in individuals currently prescribed this item for treatment of acne.

Exceptions:

• indications other than acne

Background and rationale for recommendation:

• minocycline is a tetracycline antibiotic that is mainly prescribed for acne in primary care but does have other indications. There are various safety risks associated with its use.
• the BNF states that minocycline is less suitable for prescribing compared with other tetracyclines, as it is associated with a greater risk of lupus-erythematosus-like syndrome, and it sometimes causes irreversible pigmentation
• and if treatment is continued for longer than 6 months, monitor every 3 months for hepatotoxicity, pigmentation and for systemic lupus erythematosus.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Aliskiren

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item. If initiated by cardiology, discussion must be undertaken with specialists prior to deprescribing.

Exceptions:

• none

Background and rationale for recommendation:

• aliskiren is a renin inhibitor which inhibits renin directly.
• it is licensed for essential hypertension either alone or in combination with other antihypertensives.
• Scottish Medicines Consortium (SMC) advice states that aliskiren (Rasilez®) is not recommended for use within NHS Scotland for the treatment of essential hypertension. Aliskiren has shown comparable efficacy to other antihypertensive agents in terms of blood pressure reduction, though its effects on mortality and long-term morbidity are currently unknown.
• in 2014 the Medicines and Healthcare products Regulatory Agency (MHRA) recommended caution with aliskiren following the ALTITUDE study for the following patients:
  • Patients taking aliskiren in combination with an ACE inhibitor or an ARB.
  • Patients with severe renal impairment—i.e. eGFR <30mL/min per 1.73 m2

Category:

• Items which are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation.

Dipipanone hydrochloride and cyclizine combination product

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• dipipanone is a strong opioid analgesic drug, used for acute pain and is only licensed for short term use.
• there is no evidence to suggest that dipipanone & cyclizine combination product offers any additional clinical benefit or is superior to alternative opioids.
• dipipanone is a short acting opiate. The short acting effects of both dipipanone and cyclizine increase the risk of both physical and psychological dependency.
• the summary of product characteristics (smpc) recommends to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.
• Diconal® which was the branded version of dipipanone and cyclizine was discontinued in 2011. The cost is now 40 times more expensive - £440.65 for 50 tablets versus £9.57 for 50 tablets.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Doxazosin modified release (MR) preparation

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• doxazosin is an alpha-adrenoceptor blocking drug that can be used to treat hypertension and benign prostatic hyperplasia. It is available as a prolonged release and an immediate release preparation, both of which are taken once daily.
• the long half-life of the immediate release (IR) preparation allows for once daily dosing and the prolonged release preparation offers no advantage in efficacy in comparison.
• MR doxazosin is approximately six times the cost of IR doxazosin.
• the SPS- switching doxazosin XL tablets to doxazosin standard tablets document states that Doxazosin XL tablets are as effective as doxazosin standard release tablets in the management of hypertension and BPH, as demonstrated by randomised, double-blind, parallel-group trials and that both formulations are well tolerated and there are no apparent differences in the types of adverse effects. It gives advice on how to switch from XL to standard tablets.

Category:

• Items which are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation..

Lutein and antioxidants

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• Lutein and antioxidants (e.g. vitamin A, C, E, and zinc) are supplements used for age-related macular degeneration and are not licensed medicines and can be purchased from pharmacies, supermarkets, and health food stores.
• PrescQIPP CIC has issued a bulletin which found no evidence to support routine prescribing of Lutein and antioxidants.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Omega-3 fatty acids excluding icosapent ethyl (Vazkepa®)

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• Omega-3 fatty acid compounds are essential fatty acids which can be obtained from the diet. They are licensed for adjunct to diet and statin in hypertriglyceridemia; adjunct to diet in type IV hypertriglyceridemia. Omega-3 fatty acid compounds can be purchased from pharmacies, supermarkets, and health food stores.
• a recent MHRA drug safety update highlighted a dose-dependent increased risk of atrial fibrillation in individuals with established cardiovascular diseases or cardiovascular risk factors taking Omega-3-acid ethyl ester medicines (Omacor®/Teromeg® 1000mg capsules).
• omega-3-acid ethyl esters (Omacor®) is not recommended by the SMC for use within the NHS Scotland for hypertriglyceridaemia.
• there is no good quality data for the use of omega-3 fatty acid compounds in prevention of dementia, pre-menstrual syndrome, attention-deficit hyperactivity disorder (ADHD), atrial fibrillation, eczema, osteoarthritis, or age-related macular degeneration.
• individuals currently prescribed omega-3 fatty acids should be reviewed. Acute pancreatitis can be precipitated on withdrawal in those prescribed omega-3 fatty acids for disorders of triglyceride metabolism, therefore, any review in these individuals should be made in conjunction with relevant specialist teams.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Oxycodone and naloxone combination product

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• oxycodone and naloxone combination product is used to treat severe pain and is licensed as a second line treatment of symptomatic severe to very severe idiopathic restless legs syndrome after failure of dopaminergic therapy. The opioid antagonist naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut.
• SMC advice states that oxycodone/naloxone prolonged release tablets are not recommended for use within NHS Scotland for the treatment of severe pain which can be adequately managed only with opioid analgesics. The addition of naloxone to oxycodone did not impair analgesia and improved bowel function when individuals were not receiving regular laxative therapy. However, the clinical benefit in individuals receiving regular laxative therapy is uncertain.
• the cost of the combination product is significantly more expensive than alternative opioids.
• oxycodone/naloxone combination product should not be stopped abruptly. The smpc states “it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.”

Category:

• Items which are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation.

Paracetamol and tramadol combination product

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• paracetamol and tramadol are both commonly available analgesics. This recommendation relates to where both chemical ingredients are used together in a single combination product (Tramacet®).
• the SMC has advised that tramadol 37.5mg/paracetamol 325mg tablet (Tramacet®) is not recommended for use within NHS Scotland for the symptomatic treatment of moderate to severe pain.
• Tramacet® costs significantly more than its individual components prescribed separately.
• no evidence that the combination product is more effective or safer than the individual preparations and it contains a sub-therapeutic dose of paracetamol.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Perindopril arginine

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• perindopril arginine (coversyl®) is an angiotensin-converting enzyme inhibitor (ACEi) licensed for use in the treatment of hypertension, treatment of symptomatic heart failure for reduction of risk of cardiac events in individuals with a history of myocardial infarction and/or revascularisation.
• the perindopril arginine salt version was developed as it is more stable in extremes of climate than the perindopril erbumine salt, which results in a longer shelf-life however in the context of the UK climate and supply chain this benefit is not significant.
• perindopril arginine is more expensive than perindopril erbumine and a PrescQIPP bulletin stated there was no clinical advantage of the arginine salt.

Category:

• Items which are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation.

Probiotics (VSL#3® and Vivomixx™)

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• probiotics are live micro-organisms that are thought to restore the natural balance of bacteria in the gut, there are currently no probiotic products licensed as medicines. Probiotic preparations are available to purchase over the counter as supplements but PrescQIPP state patients should be advised of the lack of sufficient evidence to support their use.

• the Advisory Committee on Borderline Substances (ACBS) reviewed the probiotic products VSL#3® and Vivomixx™ and concluded that the evidence available did not sufficiently demonstrate that the products are clinically effective resulting in their removal from the drug tariff.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Rubefacients (excluding capsaicin and topical NSAIDs)

Recommendation:

• do not initiate in primary or secondary care.
• deprescribe where safe in individuals currently prescribed this item

Exceptions:

• none

Background and rationale for recommendation:

• rubefacients are topical preparations that may contain nicotinate compounds, salicylate compounds, essential oils, and camphor. They cause irritation and reddening of the skin due to increased blood flow. They are used to relieve pain in various musculoskeletal conditions and can be purchased from pharmacies and supermarkets.
• the BNF states: “The evidence available does not support the use of topical rubefacients in acute or chronic musculoskeletal pain”.
• NICE has recommended: Do not offer rubefacients for treating osteoarthritis.
• a Cochrane review found the evidence does not support the use of topical rubefacients containing salicylates for acute injuries or chronic conditions.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Items of limited clinical effectiveness, where prescribing may be appropriate in some exceptional circumstances

If no other item is clinically indicated or available, it may be appropriate to prescribe these items, either through specialist initiation or in some cases following a shared decision-making conversation between the prescriber and individual. This should be decided using best available evidence, clinical judgement and taking a person-centred approach.

Recommendations

The following recommendations apply to items in the limited value category:

• prescribe only if the item is for an exception named in this guidance or

no other item or intervention is clinically appropriate or available

• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

These recommendations apply to:

• alimemazine
• ascorbic acid
• bath and shower emollients
• buprenorphine patches
• chloral hydrate/cloral betaine
• dosulepin
• immediate release fentanyl
• lidocaine plasters
• liothyronine
• nefopam
• trimipramine

Alimemazine

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• as a premedication to anaesthesia in children two to six years old.

Background and rationale for recommendation:

• alimemazine is a first generation H1 sedating antihistamine and is a phenothiazine derivative. It is licensed in children aged three to seven years for pre-medication sedation before general anaesthesia and in adults and children aged three years and over for second-line treatment in the symptomatic relief of urticaria and pruritus.
• no evidence available to state that alimemazine is superior to other sedating antihistamines.
• alternative first-generation antihistamines, such as chlorphenamine or promethazine, offer a more cost-effective option.
• alimemazine is unlicensed in the UK for insomnia and this indication is not included within the BNF for children
• the BNF states that “Expert sources advise alimemazine tartrate is used in children from the age of six months to two years for the treatment of urticaria and pruritus, but it is not licensed for this age group”. Alimemazine is contraindicated in children under two due to respiratory depression except on specialist advice.
• following discontinuation of the Vallergan® brand, over the last two years the cost of alimemazine has increased by more than 1500%.

Category:

• Items which are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation.

Ascorbic acid

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• treatment of scurvy.
• medically diagnosed deficiency, including for those individuals who may have a lifelong or chronic condition or have undergone surgery that results in malabsorption. Continuing need should however be reviewed on a regular basis.

Background and rationale for recommendation:

• ascorbic acid (vitamin C) tablets are licensed for the prevention and treatment of scurvy.
• the Department of Health and Social Care recommends that people should be able to get all the vitamin C they need by eating a varied and balanced diet.
• there is some evidence to indicate a minor benefit in using ascorbic acid in the prevention and treatment of the common cold however routine supplementation cannot be justified.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Bath and shower emollients

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• bath and shower emollient preparations should be reserved for situations where the use of regular emollient preparations are not sufficient e.g. individuals with severe disease who may require a combination of treatment modalities.
• in most cases, regular emollient preparations are suitable for use as bath additives and soap substitutes.

Background and rationale for recommendation:

• emollient bath and shower preparations are used for dry and pruritic skin conditions including eczema and dermatitis.
• ‘leave-on’ emollient moisturisers are still recommended for the management of eczema and can be used as soap substitutes.
• the BATHE randomised control trial: Adding emollient bath additives to standard eczema management for children with eczema showed that there was no evidence of clinical benefit for including emollient bath additives in the standard management of childhood eczema.
• the specialist pharmacist service (SPS) reviewed the evidence for bath and shower emollients for the NHSE ‘Items which should not be routinely prescribed in primary care’ consultation

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Buprenorphine patches (7-day transdermal patch – 5 to 20 micrograms)

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• 7-day transdermal patches (5 to 20 micrograms) when prescribed in line with SMC restriction: For use in elderly individuals (over 65 years) for the treatment of non-malignant pain of moderate intensity when an opioid is necessary for obtaining adequate analgesia.
• where the decision to prescribe is in line with the Scottish Palliative Care guideline.

Background and rationale for recommendation:

• there are several brands of buprenorphine transdermal patches. They are available in different strengths and are not all interchangeable.
• 7- day transdermal buprenorphine patches are licensed for treatment of non-malignant pain of moderate intensity when an opioid is necessary for obtaining adequate analgesia.
• various brands of ‘higher’ strength buprenorphine patches (3-to 4-day patches) are available and licensed for moderate to severe cancer pain and severe pain which does not respond to non-opioid analgesics. These are not included in this guidance.
• to avoid confusion and the potential for dosing errors, buprenorphine transdermal patches should be prescribed by brand name.
• they are not appropriate for individuals with acute pain and those who need rapid dose escalation.
• Butec® patches are restricted by the SMC for use in elderly individuals (over 65 years) for the treatment of non-malignant pain of moderate intensity, when an opioid is necessary for obtaining adequate analgesia

Category:

• Items which are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation.

Chloral hydrate/Cloral betaine

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• short term use (less than two weeks) in adults initiated by a specialist for severe insomnia, when insomnia is interfering with daily life and other therapies have failed
• Short term use (less than two weeks) in children and adolescents with a suspected or definite neurodevelopmental disorder, which has been initiated by a specialist for severe insomnia, where the benefits of short-term use outweigh any potential risk.
• off-label use of chloral hydrate in the management of children and young people with movement disorders initiated, monitored and reviewed by a specialist.

Background and rationale for recommendation:

• chloral hydrate is licensed for the short-term treatment of severe insomnia which is interfering with normal daily life and where other therapies have failed; as an adjunct to non-pharmacological therapies. It is used for a range of indications including nighttime sedation; management of dystonia and other movement disorders; sedation in critical care; and sedation for painless procedures.
• the BNF classes chloral hydrate/cloral betaine as being less suitable for prescribing in insomnia. It has a narrow therapeutic index and has been associated with individual fatalities.
• due to the potential for carcinogenic effects, based on animal data, a MHRA drug safety update in October 2021 further restricted the paediatric indication for chloral hydrate/cloral betaine to only children and adolescents with a suspected or definite neurodevelopmental disorder where the benefits of short-term use outweigh any potential risk.
• treatment for insomnia should be for the shortest duration possible, should not exceed two weeks and should be under the supervision of a medical specialist.
• following prolonged treatment the dose should be slowly tapered down as abrupt discontinuation can lead to delirium.
• following above MHRA advice, the Neonatal and Paediatric Pharmacist Group (NPPG) in conjunction with the British Academy of Childhood Disability (BACD) and the British Paediatric Neurology Association (BPNA) issued a position statement aimed to help clarify the off-label use of chloral hydrate in the management of children and young people with movement disorders. It states: “When using chloral hydrate for movement disorders, use the lowest effective dose, at the lowest frequency and for the shortest period possible. The need for ongoing use should be regularly assessed and documented”.

Category:

• Items of limited clinical effectiveness, where there is a lack of robust evidence of their effectiveness or significant safety concerns.

Dosulepin

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. If initiated by psychiatry, discussion with specialists is advised prior to deprescribing.

Exceptions:

• none – should only be initiated in exceptional circumstances following specialist advice and under regular review.

Background and rationale for recommendation:

• dosulepin is a tricyclic antidepressant and is licensed for the treatment of symptoms of depressive illness especially where sedation is required.
• in December 2007, the MHRA issued safety advice around prescribing of dosulepin, related to the narrow margin between therapeutic doses and potentially fatal doses.
• it is marked as ‘less suitable for prescribing’ in the BNF because relative incidence and severity of side effects is higher than other antidepressants, together with the risk of toxicity, and potential drug interactions.
• dosulepin should not be initiated in primary care for any indication and existing individuals should be reviewed for suitability for switching to a safer agent. This may require consultation with a specialist.
• dosulepin should not be stopped abruptly unless serious side effects have occurred.

Category:

• Items of limited clinical effectiveness, where there is a lack of robust evidence of their clinical effectiveness or significant safety concerns.

Immediate release (IR) fentanyl

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• restricted for use for the management of breakthrough pain in adults using opioid therapy for chronic cancer pain, when other short-acting opioids are unsuitable.
• where the decision to prescribe is in line with the Scottish Palliative Care guideline.

Background and rationale for recommendation:

• fentanyl is a strong opioid analgesic. It is available in various forms, such as tablets, lozenges, film, and nasal spray, and is licensed for the treatment of breakthrough pain in adults with cancer who are already receiving at least 60mg oral morphine daily or equivalent.
• IR fentanyl products have different absorption and elimination characteristics and are not interchangeable.
• the SMC have advised that Abstral® sublingual tablets, Effentora® buccal tablets, Instanyl® nasal spray and PecFent® nasal spray, should be restricted for use within NHS Scotland for the management of breakthrough pain in adults using opioid therapy for chronic cancer pain, when other short-acting opioids are unsuitable.

Category:

• Items that are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation.

Lidocaine plasters

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• prescribe to individuals who have been treated in line with SMC guidance and are still experiencing neuropathic pain associated with previous herpes zoster infection (post-herpetic neuralgia, PHN).
• Where the decision to prescribe is in line with the Scottish Palliative Care guideline.

Background and rationale for recommendation:

• lidocaine plasters can be applied for pain relief and are licensed for symptomatic relief of neuropathic pain associated with previous herpes zoster infection (post-herpetic neuralgia, PHN) in adults.
• lidocaine 5% medicated plaster is accepted by the SMC for restricted use within NHS Scotland for the treatment of neuropathic pain associated with previous herpes zoster infection (post-herpetic neuralgia).
• NICE guidance on chronic pain does not recommend lidocaine plasters for treating neuropathic pain.
• the place in therapy of lidocaine medicated plasters is currently unclear. Evidence supporting both their licensed use in PHN and in other unlicensed indications is limited. Off label use should be in line with MHRA guidance on the use of off label and unlicensed medicine and follow locally agreed unlicensed processes. See prescriber responsibilities (link to start)

Category:

• Items of limited clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness or significant safety concerns.

Liothyronine

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• these recommendations do not apply to individuals who have already been reviewed by an NHS consultant endocrinologist.
• new patients with overt hypothyroidism whose symptoms persist on levothyroxine may be prescribed liothyronine after a three-month or longer review by an NHS consultant endocrinologist.
• these recommendations do not apply to individuals with thyroid cancer where liothyronine is used in preparation for radioiodine ablation, iodine scanning, or stimulated thyroglobulin test.
• these recommendations do not apply to individuals where liothyronine is prescribed for the treatment of depression only, in certain settings under the care of an NHS consultant psychiatrist.

Background and rationale for recommendation:

• liothyronine (also known as T3) is used to treat hypothyroidism. It has a similar action to levothyroxine (T4) but is more rapidly metabolised and has a more rapid effect. Levothyroxine is the first line treatment for thyroid hormone replacement. It has a long half-life which enables once daily dosing and stable plasma T4 levels. Liothyronine has a shorter half-life and steady state levels cannot be achieved with once daily dosing.
• the majority of people with hypothyroidism can be managed with levothyroxine. However, a small proportion of individuals treated with levothyroxine continue to suffer with symptoms despite adequate biochemical correction.
• T4 monotherapy should be considered first line in the treatment of primary hypothyroidism as it remains the safest and most effective treatment for most individuals.
• the combined use of levothyroxine and liothyronine should only be initiated by an endocrinologist.
• the price of liothyronine has fallen but it is still significantly higher than the price of levothyroxine tablets.
• the British Thyroid Association (BTA) and Society for Endocrinologists 2023 joint consensus statement states “There is no convincing evidence to support routine use of thyroid extracts, L-T3 monotherapy, compounded thyroid hormones, iodine containing preparations, dietary supplementation and over the counter (OTC) preparations in the management of hypothyroidism”.
• individuals who have not had a review and are already established on liothyronine as monotherapy or in combination with levothyroxine should have a review by an NHS consultant endocrinologist.

Category:

• Items which are clinically effective but more cost-effective products are available, including products that have been subject to excessive price inflation.

Nefopam

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• nefopam may be considered for specific individuals, when choice of alternative analgesia is limited due to other co-morbidities e.g. patients with renal failure.
• particular caution should be used in adults who would be at elevated risk of anticholinergic side effects e.g. older adults or in cognitive impairment.

Background and rationale for recommendation:

• nefopam is a centrally acting non-opioid analgesic with associated antimuscarinic and antihistaminergic effects. It is licensed for the relief of acute and chronic pain, including post-operative pain, dental pain, musculoskeletal pain, acute traumatic pain, and cancer pain.
• in December 2013, the SIGN guideline “Management of Chronic Pain” identified insufficient evidence on the use of nefopam for chronic pain relief to support a recommendation.
• the Specialist Pharmacy Service (SPS):Use of nefopam for chronic pain review found no evidence that nefopam is more potent than non-steroidal anti-inflammatory drugs (NSAIDs), but that it is commonly associated with adverse drug reactions and is toxic in overdose.
• nefopam scores 2 on the anticholinergic burden scale (ACB) therefore sympathomimetic and antimuscarinic side-effects may be troublesome.
• adverse effects are common and include nausea, sweating, dizziness, vomiting, hallucinations, confusion, urinary retention, headache, insomnia, tachycardia, palpitations, convulsions and anaphylaxis.
• when abused, nefopam has primarily psychostimulant-like effects, which are probably linked to its dopamine reuptake inhibition properties.

Category:

• Items of low clinical effectiveness, where there is a lack of robust evidence of clinical effectiveness, or significant safety concerns.

Trimipramine

Recommendation:

• prescribe only if the item is for an exception named in this guidance or no other item or intervention is clinically appropriate or available
• consider deprescribing where safe and appropriate in individuals currently prescribed this item. Continued prescribing of these medicines should be subject to regular review.

Exceptions:

• none – should only be initiated in exceptional circumstances following specialist advice and under regular review.

Background and rationale for recommendation:

• trimipramine is a tricyclic antidepressant (TCA) with sedative properties. It is licensed for the treatment of depressive illness, especially where sleep disturbance, anxiety or agitation are presenting symptoms.
• trimipramine is significantly more expensive than other antidepressants.
• trimipramine should not be stopped abruptly unless serious side effects have occurred. The dose should preferably be reduced gradually.

Category:

• Items which are clinically effective, but more cost-effective products are available, including products that have been subject to excessive price inflation.