Specials Prescribing Optimisation Tool (SPOT)

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Specials Prescribing Optimisation Tool (SPOT)

Products which are unlicensed and are prescribed for individuals are called specials. A pharmaceutical special as defined by law is a medicine made to satisfy an individual patient need. The Medicines Act allows appropriate prescribers to prescribe medicines without a licence providing they are happy to assume full liability for the prescription.

The Specials Prescribing Optimisation Tool (SPOT) is based on the national specials prescribing data. This list includes specials that appear regularly in the top ten specials prescribed list, those where there has been a significant growth in prescribing and those that may not appear very often but when they do pose significant cost pressure due to their expense.

This bulletin aims to provide information on how to optimise prescribing either by offering alternatives or by suggesting how to contain prescribing of the particular special. Further supporting resources and bulletins will be developed to support implementation of the recommendations within this bulletin. However, as with all prescribing, these bulletins are general recommendations and any decisions on what to prescribe should be tailored to the individual patient. The prescriber is directly responsible for the prescribing of these products and will be liable for adverse effects or harm resulting from the use of that product.1

Background

There are several issues that are associated with specials, which affect both prescribers and pharmacists.

Licensing

Specials are unlicensed medicines, and so will not have been assessed by the licensing authority for safety, quality and efficacy. Usually they are specially prepared to meet a prescription ordered for individual patients without the need for the manufacturer to hold a marketing authorisation for the medicinal product concerned.

Legal

If a prescriber uses a medicine within the terms of the licence as specified in the Summary of Product Characteristics (SPC) any untoward effects are the legal responsibility of the manufacturer. If a patient experiences a side effect (even one not specified in the SPC) then the patient would have grounds to prosecute the manufacturer.

This is not the case for a pharmaceutical special. As there is no SPC the prescriber takes full

responsibility in law for any adverse effect caused by the medicine unless it can be demonstrated that the medicine was faulty. Given the uncertainties explained above this should not be underestimated. The prescriber should be able to justify and feel competent in using such medicines.1_{The prescriber is}

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Professional responsibility and accountability

The primary professional responsibility of a prescriber and pharmacist is to ensure the safety of the patient. It is the pharmacist’s professional responsibility to assist prescribers and ensure that when a special is prescribed that:

• There is no licensed alternative • It is safe and efficacious

• It is cost-effective

• It meets the prescriber’s specification and the patients needs.

It is the prescriber’s responsibility to ensure the patient is aware of, and consents to, taking an

unlicensed medication. The patient should also to be made aware of the risks associated with taking that unlicensed medicine.1-3_{The General Medical Council has prescribing guidance for unlicensed medicines}

it can be accessed via http://www.gmc-uk.org/guidance/ethical_guidance/14327.asp

Quality and efficacy

Specials are sourced from a variety of suppliers and consequently the quality and consistency of the product can vary considerably, this can lead to potential differences in pharmacokinetics and clinical responses which may have a negative impact on patient safety. This is particularly important for drugs with narrow therapeutic windows.

Cost

There is no set pricing for pharmaceutical specials, and there is no national pricing structure governing these products or local regulation of the cost of products to the NHS. As use of specials increases, there is a growing financial burden on the NHS. Part VIIIB of the Drug Tariff (the ‘Specials Tariff’) is a tariff of high volume and high cost unlicensed specials and imports, with set reimbursement prices on a selection of specials. The prices are set by analysis of a selection of unlicensed specials manufacturer’s prices, with a margin included for pharmacy purchase profit.1,2

Considerations

When choosing suitable preparations for a patient the prescriber must consider: • Clinical appropriateness for the patient

• Product quality and licensed status • Cost.

When considering whether to prescribe an unlicensed product, the first consideration should be to determine if a medicine is needed at all. Any unnecessary medicines should be stopped. If a liquid formulation of a medication is required, consider agents with a prolonged therapeutic effect (but not modified or slow-release preparations) to reduce the frequency of dose administration.4_{These can be}

crushed and dispersed in a compatible liquid before administration. In some cases, modified release or slow release preparations may be used in this way, but the manufacturer would need to be contacted on a case by case basis to ensure this is appropriate.

If the patient requires an oral dosage form, it is important to consider the hierarchy of risk on the basis of product origin (chart 1, adapted from MHRA guidance).2_{Enteral feeding is outside the scope}

of this bulletin. For detailed information about specific drugs, please refer to the Handbook of Drug Administration via Enteral Feeding Tubes.

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The ideal situation is to switch the patient to an appropriate UK licensed medication. If this is not possible then other options need to be considered. The hierarchy of risk diagram shows the preferred choice with the lowest risk at the top of the chart. If a licensed product is not suitable; consider off-label use of a UK licensed medication, e.g.by crushing and dispersing the tablet or opening the capsule. Consult product literature to see if this is a licensed option. This may not be suitable option for all patients;

consideration should be given to whether the patient or carer is able to administer medication in this manner and the dose required as drawing off aliquots from a dispersed product is not ideal but may sometimes be necessary.

Where healthcare staff are administering these medicines, consideration should be given to providing written information or a protocol for the administration of medicines by unlicensed methods of administration. Individuals may require training and may need advice on health and safety issues particularly if medication is to be crushed or capsules opened. It is important that the prescriber writes brief instructions for administration on the prescription, e.g. “via PEG”

Useful resources to identify the ability of crushing, dispersing tablets/ capsules for nasogastric (NG) feeding are:

• Handbook of Drug Administration via Enteral Feeding Tubes • The NEWT Guidelines

The MHRA published guidance in May 2014 on the supply of unlicensed medicinal products (“specials”) which can be found at:

https://www.gov.uk/government/publications/supply-unlicensed-medicinal-products-specials

Hierachy of risk on basis of product origin

Adapted from MHRA guidance

UK-licensed medicine

Off-label use of a UK-licensed medicine

An imported product licensed in the country of origin

A UK manufactured special made in MHRA licensed facilities

An extemporaneously dispensed medicine

An imported product not licensed in the country of origin

A non-UK made unlicensed medicine or food supplement

A

B

C

D

E

F

G

HIGHEST NET RISK LAST CHOICE LOWEST NET RISK PREFERRED CHOICE

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SPOT-List

The SPOT-List contains the top ten medicines (all formulations and strengths) supplied as specials ranked by total spend nationally. The total national annual spend on these ten specials is approximately £44.1 million (based on April 14 to Jan 15 ePACT). For some of the items listed in the top ten, there are several formulations and strengths within the indicator.

The chemical substances covered in the SPOT-List are:

Acetylcysteine Diltiazem Glycopyrronium bromide Magnesium glycerophosphate/ magnesium oxide Melatonin Midodrine Midazolam buccal Omeprazole Sodium chloride (including eye preparations) Vitamin D prescribed as cholecalciferol or ergocalciferol

SPOT-List supporting information

The supporting information provided in the tables on the following pages is intended as a guide for healthcare professionals reviewing prescribing of specials.

Please note this is not an exhaustive list of products available.

Prices of medicines may vary depending on handling fees and changes in Drug Tariff price. The use of the potential licensed alternative product may be outside of its license, but a preferred option based on the hierarchy of risk. Please refer to the SPC or manufacturer for licensing information.

For all the specials listed, the continued need for the special should be the first consideration when reviewing treatment. See the PrescQIPP optimising safe and appropriate medicines use bulletin for further guidance available at http://www.prescqipp.info/safe-appropriate-medicines-use-deprescribing/viewcategory/190-safe-and-appropriate-medicines-use

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Drug Potential licensed alternative (this may be off-label use or consider unlicensed use)

Information for oral use (for enteral feeding please consult The Handbook of Drug Administration via Enteral Feeding Tubes)

Average cost per item (based on April 14 to Jan 15)

Total spend in England (across all strengths and quantities, based on April 14 to Jan 15) Hierarchy of risk on basis of product origin (adapted from MHRA

guidance code A-G)

Melatonin Circadin® 2mg MR tablets

• Review use, limited evidence to support usage.

• If patient can swallow, consider off-label use of Circadin®.

• Circadin® tablets can be crushed; the release characteristics are similar to an immediate release dose form.5

• Consider discussion with secondary care specialist, consider shared care.

• Price in Drug Tariff for liquid specials.

£88.29 £10,597,859

B

(If used in children it would be unlicensed use) Glycopyrronium bromide 1mg & 2mg tablets are licensed in UK 200mcg/ml injection Licensed liquid in USA

• The BNF for Children states for administration by mouth, injection solution may be given or crushed tablets suspended in water.6_{This is outside the}

licensed indication, so would be considered unlicensed use.

• 1mg/5ml oral solution (Cuvposa®) has been approved for use in the United States to reduce chronic severe drooling in patients aged 3-16 years with neurological disorders.7 _{This will vary in cost as it needs}

to be imported.

£220.55 £5,704,753

Tablets: B

(Tablets only licensed for adults for add on therapy in the treatment of peptic ulcer.)

Injection: B Liquid: C

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Magnesium

glycerophosphate/ oxide

No

• A summary of magnesium preparations available in the UK for the treatment and prevention of hypomagnesaemia did not find any significant difference in the efficacy or safety of the different oral magnesium preparations although there might be differences in bioavailability. Factors that could affect choice include local availability, patient tolerability, and price.8

• Magnaphate® 4mmol tablets (Arjun Products Limited): £20.96 for 50 tablets.8

• Price in Drug Tariff.

£140.48 (magnesium glycerophosphate) £239.24 (magnesium oxide) £3,461,911 (magnesium glycerophosphate) £634,236 (magnesium oxide) D Omeprazole Omeprazole orodispersible tablets. Some capsules can be opened and contents sprinkled on food (see PIL)

• Dispersible tablets (Losec MUPS)

disintegrate to give a dispersion of small granules.9_{Generic dispersible tablets are}

also available. Losec MUPS/orodispersible tablets can also be dispersed in water or suspended in a small amount of yoghurt or fruit juice after gentle mixing.9_{It is important}

that the tablets shouldn’t be crushed or chewed.9

• Price in Drug Tariff is available for unlicensed oral solution. £125.42 £3,280,059 Losec MUPS: A Dispersible tablets: A Capsules : B

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Vitamin D (prescribed as colecalciferol (D3) and ergocalciferol (D2)) Desunin tablets Fultium-D3 capsules Invita oral solution Aviticol capsules

• High dose: InVita D3 25,000 IU oral solution, Fultium D3 20,000 IU capsules, Avitcol (D3) 20,000 IU capsules.10

• Maintenance dose: Fultium-D3 3200 IU & 800 IU capsules, Desunin (D3) 800 IU tablets, InVita D3 25,000 IU oral solution,10

the high dose products listed above can also be taken at longer intervals, see product details.

• Prices in Drug Tariff for unlicensed variations. £18.84 (colecalciferol) £132.62 (ergocalciferol) £3,142,606 (colecalciferol) £863,252 (ergocalciferol) A Midodrine Imported licensed product in country of origin, unlicensed in UK.

• In the USA, midodrine is licensed by the Food and Drug Administration (FDA) for the treatment of symptomatic postural hypotension. It is also licensed for use in several EU countries, such as Germany, France, Ireland, Italy and Spain.11

• Can be crushed and mixed with water for administration, this is considered off-label use.12

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Acetylcysteine

Not available Self care suggested

• Holland and Barrett £8.19 (for 30 capsules). This is a food supplement, and has not undergone a quality assurance assessment as licensed medicines do. Patient to buy.

http://www.hollandandbarrett.com/shop/ product/holland-barrett-n-acetyl-cysteine-nac-capsules-600mg-60000211

• IDIS are able to order as a special if prescribed.

• Some NHS hospitals may manufacturer this product.

• Oronac is also available via Fontus Health in various formulations.

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Information for oral use (for enteral feeding please consult The Handbook of Drug Administration via Enteral Feeding Tubes)

Average cost per item (based on April 14 to Jan 15) Total spend in England (across all strengths and quantities, based on April 14 to Jan 15) Hierarchy of risk on basis of product origin (adapted from MHRA guidance code A-G) Midazolam maleate Buccolam Oromucosal solution

• Licensed for the treatment of prolonged, acute, convulsive seizures in infants, toddlers, children and adolescents (from 3 months to <18 years).13

• Buccolam must only be used by parents/carers where the patient has been diagnosed to have epilepsy.13

• For infants between 3-6 months of age, treatment should be in a hospital setting where monitoring is possible and resuscitation equipment is available.13

• Buccal midazolam may be considered as an alternative to rectal diazepam for the treatment of prolonged seizures. Various buccal midazolam preparations have been used in children as unlicensed medicines, including Buccolam prior to receiving market authorisation.15

• Doses available as 2.5mg, 5mg, 7.5mg & 10mg pre-filled syringes.14

• Buccolam is half the strength of some other unlicensed preparations. It contains the hydrochloride salt. Some other preparations contain the maleate salt of midazolam. Although there is some suggestion that the maleate salt may be better absorbed in the buccal cavity, there are adequate studies with midazolam hydrochloride to support the dosing schedule authorised for Buccolam.15

• A hospital paediatric unit has recently published its experience of transferring patients to licensed Buccolam. One of the key points raised was the requirement to have only one product (specifically only one strength of product available for use).16 _{This would be to}

ensure no confusion during dosing, and should be considered prior to switching patients to licensed product.

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Information for oral use (for enteral feeding please consult The Handbook of Drug Administration via Enteral Feeding Tubes)

Average cost per item (based on April 14 to Jan 15) Total spend in England (across all strengths and quantities, based on April 14 to Jan 15) Hierarchy of risk on basis of product origin (adapted from MHRA guidance code A-G) Diltiazem hydrochloride Rectogesic (GTN 0.4% Cream)

• Most of the spend on diltiazem is for topical preparations, so the recommendations are for topical products only.

• Rectogesic® 4mg/g rectal ointment can be used as a licensed alternative, a finger cap should be used when applying.17 _Please

note that topical glyceryl trinitrate 2mg/g (0.2%) ointment does not currently have a UK licence for treating chronic anal fissures, or for any other indication. Therefore, its use is unlicensed.18

• Unlicensed 2% diltiazem hydrochloride cream (Anoheal®) is available on a named-patient basis from S.L.A. Pharma (UK) Ltd at £42.00 plus VAT per 30 g tube. Costs of products obtained from other sources may differ.19

£81.04 £1,369,580 Rectogesic®: A

Anoheal®: D

Sodium chloride

No

For oral preparations

• Liquid is not available, consider if the tablet formulation is an option.

• Licensed tablets available as Slow Sodium 600mg (approx. 10 mmol each of Na+ and Cl-).14 £82.39 £1,347,240 Tablets: A Liquid: D Sodium chloride 5%w/v eye drops and sodium chloride 5%w/w eye ointment

For eye preparations

• UK Ophthalmic Pharmacy Group suggest that other strengths such as 0.45% w/v likely to be an error in strength.20_{Check if 5% w/v}

or other strength intended - if other strength, suggest 5% w/v as licenced products should be prescribed in preference to unlicensed

Eye

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References

1. PrescQIPP NHS programme and the NHS East of England Collaborative Procurement Hub. Information and Guidance on the Prescribing and Use of Unlicensed Specials v3.1. March 2013 available at

www.prescqipp.info/specials-toolkit

2. Royal Pharmaceutical Society of Great Britain. Dealing with Specials. Pharmacy Professional June 2010, updated June 2011 available at http://www.rpharms.com/support-pdfs/ppjune2010-specials-june2011updatefinal.pdf

3. General Medical Council. Good Practice in Prescribing Medicines and Devices: Unlicenced Medicines. 2013, Updated April 2014. Available at http://www.gmc-uk.org/guidance/ethical_guidance/14327.asp

4. UKMI Q&A 294.3. What are the therapeutic options for patients unable to take solid oral dosage forms? Date prepared: July 2013

5. Email correspondence. Flynn Pharma, August 2014.

6. British National Formulary for Children. British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary.BMJ Group and RPS Publishing. London; December 2014. Accessed via: https://www.medicinescomplete.com/mc/bnfc/current/index.htm BNF for Children, December 2014.

7. National Institute of Health and Care Excellence. ESUOM15 Hypersalivation: Oral glycopyrronium bromide. July 2013 available at http://www.nice.org.uk/advice/esuom15

8. UKMI Q&A 111.2. What oral magnesium preparations are available in the UK and which preparation is preferred for the treatment and prevention of hypomagnesaemia. Date prepared: 22nd April 2013

9. White, R. Bradnam, V. Handbook of Drug Administration via Enteral Feeding Tubes, Second edition. The Pharmaceutical Press. November 2010.

10. Monthly Index of Medical Specialities (MIMS ). Accessed online via: http://www.mims.co.uk/ on 23rd Feburary 2015.

11. National Institute of Health and Care Excellence. ESUOM5Postural hypotension in adults: midodrine. February 2013 available at http://www.nice.org.uk/advice/esuom5?UNLID=8371375622014622145549

12. Wrexham Maelor Hospital Pharmacy Department. The NEWT Guidelines for Administration of Medication to Patients with Enteral Feeding Tubes or Swallowing Difficulties. April 2012.

13. Summary Product Characteristics; Buccolam Oromucosal Solution. ViroPharma Ltd. Last revised on the emc 03 October 2014. Accessed via https://www.medicines.org.uk/emc/medicine/25538 on 17th March 2015

14. British National Formulary . British Medical Association and Royal Pharmaceutical Society of Great Britain. BMJ Group and RPS Publishing. London; December 2014. Accessed via https://www.medicinescomplete.com/ mc/bnf/current

15. Drug Safety Update: Buccal midazolam (Buccolamq): new authorised medicine for paediatric use. October 2011. Accessed via: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON131931

16. Tomlin, S. Medicines Tailored for Children: The Introduction of Buccal Midazolam. The Pharmaceutical Journal. 4 August 2011; 287: 161.

17. Summary Product Characteristics. Rectogesic 4 mg/g Rectal Ointment. ProStrakan. Last revised 07/2017. Accessed 24/04/2015 available at https://www.medicines.org.uk/emc/medicine/16174

18. National Institute of Health and Care Excellence. ESUOM3 Chronic anal fissure: 2% topical diltiazem hydrochloride. Published date: January 2013. Accessed via http://www.nice.org.uk/Advice/esuom3

19. National Institute of Health and Care Excellence. ESUOM07 Chronic anal fissure: 0.2% topical glyceryl trinitrate ointment. Published date:March 2013. Accessed via https://www.nice.org.uk/advice/esuom7

20. Ophthalmic Special Order Products, General Principles. The Royal Collage Ophthalmologists, .UK Ophthalmic Pharmacy Group. April 2014

Additional PrescQIPP resources

There aren’t any other resources available yet but further SPOT-List bulletins and resources will be following this introductory bulletin very soon.

Information compiled by Rakhi Aggarwal PrescQIPP Programme, March 2015 and reviewed by Katie Smith, East Anglia Medicines Information Service, April 2015.