Alternatives to prescribing unlicensed pharmaceutical special-order products (‘specials’) for adults

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Disclaimer

The information contained within is intended for use by healthcare professionals within Coastal West Sussex Clinical Commissioning Group (CCG). The decision to alter the formulation of a medicine must be taken by the prescriber, where clinically appropriate for the individual patient concerned as this is usually outside of the terms of the product license. Not all medicines are suitable for crushing/dispersing/opening and it is important to check beforehand for each individual medicine.

We have made every effort to check that all information is correct at the time of publication. Coastal West Sussex CCG does not accept any responsibility for loss or damage caused by reliance on this information. Where alternative agents are suggested, therapeutic equivalence is not implied and patients will require monitoring and possible dose titration when switching to a different medicine. The need for a pharmaceutical ‘special’ or crushing tablets or opening capsules should be reviewed regularly.

Please note that some of the possible alternatives suggested in this booklet may contain alcohol, sodium, lactose and other excipients that may not be clinically appropriate for all patients. Refer to the medicines’ Summary of Product Characteristics (SPC) or the British National Formulary (BNF). Alternatively, contact the Medicines Management Team should you require further advice.

If unsure, please seek further advice from a pharmacist. Please note that when dispensing an unlicensed/special medicine, pharmacists will also bear responsibility for that product.

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Introduction

This booklet aims to provide prescribers with alternatives to pharmaceutical special-order products (commonly referred to as ‘specials’). This booklet does not include specific recommendations relating to the suitability of administration via enteral feeding tubes and as such, prescribers are advised to contact the Coastal West Sussex Medicines Management Team, using the contact details listed below, for additional information relating to individual patients where the medication is to be administered via an enteral feeding tube.

Definition: Pharmaceutical ‘specials’ are unlicensed medicines that are commercially made-to-order to satisfy an individual patient’s specific clinical need.

Pharmaceutical specials are unlicensed medicines that have not been assessed for safety, quality or efficacy by the relevant licensing authorities and are not required to be manufactured to the same standards of Good Manufacturing Practice (GMP) that is normal for pharmaceuticals. The prescriber takes responsibility for the quality of the medicine and any adverse effects experienced by the patient when prescribing 'specials' and they represent a considerable cost to the NHS.

Prescribers and pharmacists have a responsibility to ensure that ‘specials’ are only prescribed and dispensed where there is no suitable licensed alternative available. Where appropriate, off-label use of a licensed product (such as crushing tablets or opening capsules) may be preferable to prescribing a wholly unlicensed pharmaceutical 'special'.

Some patients, in particular paediatric patients, may require liquid formulations in order to allow a measurable dose to be administered. In such cases, it is not routinely advisable to crush tablets / open capsules or use dispersible formulations with a view to administering a proportion of the dose.

Contact details for additional advice

If you are looking for a medicine that is not listed in this booklet, require advice on the administration of medicines via enteral feeding tubes, or any additional information, please refer to Coastal West Sussex (CWS) Local Health Economy Formulary (http://www.coastalwestsussexformulary.nhs.uk/). Alternatively, contact CWS Medicines Management Team via [email protected] or by phone: (01903) 707416

Feedback on the Booklet

The reviewer of this booklet is keen to have your feedback and would genuinely welcome any comments you may have. In addition, if there are products that you feel should be considered for inclusion when this booklet is next reviewed, please send them at any time to:

Coralia Wukovich RegPharmTech Medicines Management Technician E-mail to: [email protected] Page 3 of 21 Version 24 – July 2015 This document is regularly reviewed in line with any significant changes

Choosing medicines for patients unable to take solid oral dosage forms

A stepwise approach is suggested:

STEP 1

I f the medicine is still needed, use a STEP 2 licensed medicine in a suitable Use a licensed medicine in an

formulation. unlicensed manner, for example by

For example: crushing / dispersing tablets in water STEP 3  Licensed liquid preparation or by opening capsules.  Licensed soluble tablets In the few situations where there  Licensed powders or granules for suspension Not all medicines are suitable for administration in is no licensed option, consider  Licensed patches this way and it is important to check beforehand. See

overleaf for where to get advice. using a ‘special’. In order to use a licensed medicine, consider switching to a different agent in the same class, or to As before, consider switching to a different agent or Special-order (‘special’) medicines are a different route of administration. unlicensed and expensive. They should only be route of administration in order to use a licensed used if there is no licensed medicine that meets product. the patient’s needs.

In most cases a licensed preparation will be available that meets the patients’ needs.

Licensed medicines should be used where possible.

Special-order medicines are unlicensed and expensive and should only be used if there is no licensed alternative.

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Sussex Partnership NHS Foundation Trust has developed a ‘Swallowing pills (tablets and capsules) Patient Information Leaflet’ (PIL) which aims to provide some simple techniques to help make swallowing pills easier – available from the links below.

Swallowing pills - adults Swallowing pills - children

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Choosing medicines for patients unable to take solid oral dosage forms

Practical directions

Always check beforehand if a Crushing / dispersing tablets and opening capsules

tablet is suitable for For medicines that are suitable for crushing, this should be done by using a pestle and mortar, a tablet crusher or dispersing / crushing, or a between two metal spoons. Tablets should NOT be crushed in plastic containers as the drug may adhere to the plastic. capsule is suitable for opening. The equipment used to crush tablets should be rinsed well and the rinsings administered as well to ensure the entire dose is taken.

Only crush/dissolve/disperse medicines one tablet at a time; do NOT mix different medicines together. Care staff may only administer medicines in an unlicensed manner Crushing, dispersal or opening of capsules should only be performed immediately before administration to reduce the on the instruction of the risk of the medicine becoming unstable. prescriber. Patients should be advised to rinse their mouth with water after taking crushed tablets/opened capsules to reduce the

risk of any local irritation or anaesthetic effect in the mouth.

A written direction to crush or Medicines should only be administered in food with the patient’s knowledge and consent. Hiding medication in food is disperse tablets or to open considered ‘covert administration’ and is only allowed in certain circumstances. capsules must be documented in the patient’s care plan. Tablets/capsule contents/crushed tablets should be dissolved in at least 15-30ml water, unless otherwise stated.

The NPC has published ‘Prescribing Specials – Five guiding principles for prescribers’. These principles are based on good prescribing practice and Appendix 2 contains a quick practical checklist for prescribers that can be used as a tool when prescribing. Guidance available at: http://www.npc.nhs.uk/improving_safety/prescribing_specials/ Page 6 of 21 Version 24 – July 2015 This document is regularly reviewed in line with any significant changes

The decision to prescribe any medicines is down to the individual prescriber - as is always the case, the prescriber signing the prescription must bear the full responsibility for that treatment. The GMC guidance on good practice in prescribing and managing medicines and devices (2013) states that prescribers should be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate its safety and efficacy.

In addition, the GMC guidance states that when prescribing a medicine that is being used outside the terms of its UK licence or which does not have a license for use in the UK, a practitioner must: a) Be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate its safety and efficacy; b) Take responsibility for prescribing the medicine and for overseeing the patient’s care, monitoring, and any follow up treatment, or ensure that arrangements are made for another suitable doctor to do so; c) Make a clear, accurate and legible record of all medicines prescribed and, where you are not following common practice, your reasons for prescribing an unlicensed medicine.

Prescribers must give patients (or their parents or carers) sufficient information about the medicines they propose to prescribe to allow them to make an informed decision.

Furthermore, the GMC states that when prescribing at the recommendation of another doctor, nurse or other healthcare professional, prescribers must satisfy themselves that the prescription is needed, appropriate for the patient and within the limits of their competence.

Coastal West Sussex (CWS) Local Health Economy Formulary – Traffic Light Status Information (http://www.coastalwestsussexformulary.nhs.uk/).

GREEN BLUE AMBER RED BLACK NON-FORMULARY

Initiation and on-going Specialist only initiation. Prescribing under CWS Specialist prescribing Not to be routinely Not to be routinely prescribing may occur in May be prescribed in APC approved Effective only. prescribed in any care prescribed. any care setting. primary care once Shared Care setting. Funding via patient is stable. Arrangement (ESCA) Individual Funding only. Request (IFR) only. Page 7 of 21 Version 24 – July 2015 This document is regularly reviewed in line with any significant changes

NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE

Acetazolamide Liquid Special Acetazolamide standard-release tablets can be dispersed in water. Alendronic acid Liquid Alendronic acid is available as 70mg/100mL sugar-free oral solution (4 x 100mL bottles). Special Allopurinol Liquid Special Allopurinol tablets can be crushed well and mixed with water.

Amiloride HCl Liquid Special Amiloride is available as licensed 5mg/5mL sugar-free oral solution. Amiodarone tablets can be crushed and mixed with water. Without crushing, they disperse in approximately 5 minutes. The crushed tablets Amiodarone Liquid Special may have a bitter taste and they can be mixed with fruit juice for patients with swallowing difficulties, if required. However, grapefruit juice should not be used due to the possible interaction. Amisulpride Liquid Special Amisulpride is available as licensed 100mg/mL sugar-free oral solution.

Amitriptyline Liquid Special Amitriptyline is available as a licensed 25mg/5mL or 50mg/5mL sugar-free oral solution.

Amlodipine Liquid Special Amlodipine is available as 1mg/mL oral solution. Atenolol Liquid Special Atenolol is available as a licensed 25mg/5mL sugar-free oral solution. Atorvastatin is available as 10mg and 20mg chewable sugar-free tablets. Alternatively, consider switching to the licensed simvastatin Atorvastatin Liquid Special 20mg/5mL or 40mg/5mL sugar-free oral suspension. N.B. Within CWS, azathioprine is coded as Amber for rheumatoid arthritis, dermatology and inflammatory bowel disease, and Red for Azathioprine Liquid Special all other indications. Bendroflumethiazide Liquid Bendroflumethiazide tablets can be dispersed in water. Special Betahistine Liquid Special Betahistine tablets can be crushed and mixed with water. Bisacodyl Liquid Special Consider using bisacodyl suppositories or switching to docusate sodium licensed sugar-free oral solution 12.5mg/5mL or 50mg/5mL. Bisacodyl Special Order Consider using bisacodyl suppositories. These are available as 5mg and 10mg. Rectal Solution Bisoprolol Liquid Special Bisoprolol tablets can be crushed finely and mixed with water. Captopril Special Order Captopril is available as a 12.5mg, 25mg and 50mg licensed tablet. Capsules Captopril Liquid Special Captopril is available as licensed 5mg/5mL and 25mg/5mL sugar-free oral solution.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE Carbamazepine is available as a licensed 100mg/5mL sugar-free oral suspension. Carbamazepine Liquid Special N.B. MHRA/CHM Advice – Category 1: For Category 1 drugs, doctors are advised to ensure that their patient is maintained on a specific manufacturer’s product Carbimazole Liquid Special Carbimazole tablets can be crushed and dispersed in water. N.B. within CWS formulary, doses above 40mg are coded as Red.

Carvedilol Liquid Special Carvedilol tablets can be dispersed in water to form a suspension. They disperse in one to five minutes. Use immediately. N.B. Within CWS formulary, chloral hydrate is coded as Red for procedural sedation in paediatrics only. Chloral Hydrate Liquid There is no convincing evidence that they are particularly useful in the elderly and their role as hypnotics is now very limited. Chloral hydrate Special is not recommended for routine prescribing. Consider an alternative. Chlorpromazine Liquid Chlorpromazine is available as a licensed 25mg/5mL or 100mg/5mL oral solution. Special Chlortalidone Liquid Special Chlortalidone tablets can be dispersed in water. Clindamycin capsules can be opened and the contents dispersed in water. They may taste unpleasant and may be mixed with grape juice or Clindamycin Liquid Special maple syrup to overcome this for patients with swallowing difficulties. Clobazam Liquid Special Clobazam is available as a licensed 5mg/5mL or 10mg/5mL sugar-free oral suspension.

Clomipramine Liquid Special Clomipramine capsules can be opened and the contents dispersed in water. The modified-release tablets should not be crushed. Clonazepam Special Order Clonazepam is available as licensed 500mcg/5mL and 2mg/5mL sugar-free oral solution. Drops / Liquid Special N.B. Within CWS formulary, clonazepam is coded as Red for status epilepticus, and Blue for epilepsy. Clopidogrel Liquid Special Clopidogrel tablets are film-coated, but can be dispersed in or crushed and mixed with water. They disperse in 1 to 5 minutes.

Amiloride is available as licensed 5mg/5mL sugar-free oral solution. Furosemide is available as licensed 20mg/5mL, 40mg/5mL, and 50mg/5mL Co-amilofruse Liquid Special sugar-free oral solution. Please prescribe as separate items.

Co-beneldopa Liquid Special Co-beneldopa is available as licensed 12.5mg/50mg and 25mg/100mg dispersible tablets.

Co-Careldopa standard-release tablets (not modified-release / controlled-release) can be dispersed in water and taken immediately. Co-Careldopa Liquid Special Alternatively, consider switching to co-beneldopa dispersible tablets. Consider switching to co-codamol 30/500 dispersible tablets or prescribe separately as paracetamol 120mg/5mL, 250mg/5mL, or 500mg/5mL Co-Dydramol Liquid Special sugar-free oral suspension and dihydrocodeine 10mg/5mL oral solution.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE Colecalciferol 20mcg (800 units) are available as licensed tablets (Desunin®) which can be crushed and given with food (not suitable for those with fructose intolerance). Colecalciferol is also available as licensed capsules (Fultium-D3® - as 800iu, 3,200iu and 20,000iu and Aviticol® - as 20,000iu) - N.B. Although recently re-formulated to remove arachis oil as excipient, some Fultium-D3® formulations currently on the market may still contain arachis (peanut) oil. Also, serum calcium values must be monitored during long-term treatment with a daily dose exceeding 1,000 IU vitamin D.

Colecalciferol is also available as licensed 25,000IU/mL (68.5mcg) sugar-free oral solution (InVita® D3 – as 3x1mL amps), as well as 2740iu/ml Colecalciferol Liquid Special (68.5mcg) oral solution (Fultium-D3® Drops – as 25mL). / Special Order Capsules Colecalciferol 15,000units/5mL oral solution (i.e. colecalciferol 3,000units/mL oral solution) is now available as a licensed medicine and is listed in Drug Tariff Part VIIIA, whereas colecalciferol 15,000units/5mL oral suspension (i.e. colecalciferol 3,000units/mL oral suspension) is only available as a Special Order product.

N.B. With the exception of frank osteomalacia, in the absence of clear guidance, it has been agreed by consultants at WSHfT that at least 300,000

units of vitamin D3 per course should be sufficient to correct true deficiency. Licensed Desunin® / Fultium-D3® 800 unit tablets / capsules at a dose of 3200 units daily for 12 weeks should be sufficient. Cyclizine tablets can be crushed and dispersed in water. They may have a bitter taste. Alternatively, consider switching to an alternative Cyclizine Liquid Special antiemetic. Promethazine, prochlorperazine and metoclopramide are available as licensed oral liquids. Domperidone is available as licensed liquid, orodispersible tablets, or suppositories.

Dantrolene Liquid Special Dantrolene capsules can be opened and the contents dispersed in water or acidic fruit juice (e.g. orange juice).

CD Sch 2. Dexamfetamine is available as 5mg/5mL sugar-free oral solution. Dexamfetamine Liquid N.B. Within CWS formulary, dexamfetamine is coded as Amber for attention deficit hyperactivity disorder in children and young people; for Special narcolepsy, dexamfetamine is coded as Red. Dexamethasone Liquid Dexamethasone is available as licensed 2mg/5mL and 10mg/5mL sugar-free oral solution. Special Dexamethasone Special Dexamethasone eye drops are available as licensed 0.1% preservative-free unit doses. Alternatively, dexamethasone is available 0.1% eye Order Eye Drops 0.1% drops (5mL) Preservative-Free Diazoxide Liquid Special N.B. Within CWS formulary, diazoxide is coded as Red for chronic hypoglycaemia. Diazoxide has no place in treatment for acute hypoglycaemia.

Diazepam Liquid Special Diazepam is available as a licensed 2mg/5mL oral solution.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE Consider a topical NSAID for mild, localised pain. Where oral NSAID is required, consider switching to ibuprofen 100mg/5mL oral suspension Diclofenac Liquid Special (CWS formulary first choice). Diclofenac dispersible tablets may be considered if ibuprofen is unsuitable (prescribe the lowest effective dose for the shortest duration necessary). The enteric-coated or modified-release preparations should not be crushed. Dihydrocodeine Liquid Dihydrocodeine tartrate is available as 10mg/5mL oral solution. Special Consider switching to amlodipine tablets, which can be dispersed in or crushed and mixed with water. The modified-release diltiazem capsules can be opened and the contents mixed with soft food or water for administration but the capsule contents (pellets) must not be crushed or Diltiazem Liquid Special chewed.

N.B. Bioavailability varies among the modified-release diltiazem preparations. Diltiazem 2% Special Order The BNF advises that diltiazem cream may be a suitable alternative for the management of anal fissures in patients unresponsive to topical Cream / Ointment nitrates. Please consider whether GTN 0.4% ointment (which is a licensed preparation) is clinically appropriate. Dipyridamole is available as licensed 50mg/5mL sugar-free oral suspension.

N.B. National recommendations only support the use of modified-release, not standard-release dipyridamole preparations for the prevention of Dipyridamole Liquid Special vascular events.

Dipyridamole modified-release capsules may be opened and the modified-release granules mixed with soft food, juice or water. However, the granules must not be crushed or chewed. Donepezil is available as licensed orodispersible 5mg or 10mg tablets. Alternately, donepezil is also available as licensed 1mg/mL sugar-free Donepezil Liquid Special oral solution.

Dosulepin capsules can be opened and the contents mixed with water for oral administration. The contents can also be sprinkled on food, but Dosulepin HCl Liquid Special may have a local anaesthetic action. Dosulepin tablets can be crushed but do not disperse in water easily.

Doxazosin Mesilate Liquid Doxasozin standard-release tablets (not modified-release) disperse readily in water. Most disperse within one minute. Special Enalapril tablets may be crushed and dispersed in water. They may have a bitter after-taste.

Enalapril Liquid Special Alternatively, consider switching to ramipril capsules, which can be opened and placed directly into the mouth, onto bread or mixed with apple juice or apple sauce. The capsule contents may taste unpleasant. Entacapone tablets may be crushed and given in jam, honey or orange juice. Take care when crushing as the red powder produced may stain Entacapone Liquid Special the mouth.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE

Ephedrine Special Order Ephedrine is available as licensed 0.5% and 1% nasal drops. Nasal Drops Colecalciferol 20mcg (800 units) are available as licensed tablets (Desunin®) which can be crushed and given with food (not suitable for those with fructose intolerance). Colecalciferol is also available as licensed capsules (Fultium-D3® - as 800iu, 3,200iu and 20,000iu and Aviticol® - as 20,000iu) - N.B. Although recently re-formulated to remove arachis oil as excipient, some Fultium-D3® formulations currently on the market may still contain arachis (peanut) oil. Also, serum calcium values must be monitored during long-term treatment with a daily dose exceeding 1,000 IU vitamin D.

Colecalciferol is also available as licensed 25,000IU/mL (68.5mcg) sugar-free oral solution (InVita® D3 – as 3x1mL amps), as well as 2740iu/ml Ergocalciferol Liquid Special (68.5mcg) oral solution (Fultium-D3® Drops – as 25mL).

Colecalciferol 15,000units/5mL oral solution (i.e. colecalciferol 3,000units/mL oral solution) is now available as a licensed medicine and is listed in Drug Tariff Part VIIIA, whereas colecalciferol 15,000units/5mL oral suspension (i.e. colecalciferol 3,000units/mL oral suspension) is only available as a Special Order product.

N.B. With the exception of frank osteomalacia, in the absence of clear guidance, it has been agreed by consultants at WSHfT that at least 300,000

units of vitamin D3 per course should be sufficient to correct true deficiency. Licensed Desunin® / Fultium-D3® 800 unit tablets / capsules at a dose of 3200 units daily for 12 weeks should be sufficient. Erythromycin Special Order Erythromycin is available as topical solution 2% in an alcoholic basis. Gel Consider switching to the equivalent dose of sodium feredetate elixir (55mg/10mL elemental iron) or ferrous fumarate 140mg/5mL syrup (45mg/5mL elemental iron). Ferrous Sulphate Liquid Special N.B. 5ml of ferrous sulphate (60mg/5mL) liquid contains 12mg elemental iron (EI) and 200mg dried ferrous sulphate tablets contain 65mg EI.

Ferrous sulphate is also available as 125mg/mL oral drops (25mg elemental iron/mL). Flecainide Acetate Liquid Flecainide tablets can be crushed and dispersed in water. N.B. Some sources do not recommend this. Special Fludrocortisone Liquid Fludrocortisone tablets can be dispersed in water. They will disperse within 1 minute. Special Fluoxetine Special Order Fluoxetine is available as licensed 20mg or 60mg capsules. Alternatively, fluoxetine is available as licensed 20mg sugar-free dispersible tablets Tablets (which are scored and can be halved in order to administer a 10mg dose); fluoxetine is also available as licensed 20mg/5mL oral solution. Folic Acid Liquid Special Folic acid is available as licensed 2.5mg/5mL sugar-free oral solution.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE

Fosfomycin Trometamol For use only under recommendation of microbiologists for ESBL producing organisms; available from community pharmacies.

Furosemide Liquid Special Furosemide is available as licensed 20mg/5mL, 40mg/5mL or 50mg/5mL sugar-free oral solution.

Gabapentin Liquid Special Gabapentin is available as licensed 50mg/mL sugar-free oral solution.

Gliclazide Liquid Special Gliclazide standard-release tablets (not modified-release) can be crushed and mixed well with water or orange juice.

Glyceryl Trinitrate Special Glyceryl trinitrate is available as a licensed 0.4% ointment. Order Ointment 0.2% Glycopyrronium bromide Glycopyrronium bromide is available as licensed 1mg and 2mg tablets. Specials Order Tablets Glycopyrronium bromide Glycopyrronium bromide is available as licensed 1mg and 2mg tablets. The tablets are scored. Liquid Special

Haloperidol Liquid Special Haloperidol is available as licensed 5mg/5mL or 10mg/5mL sugar-free liquid/oral solution. Hydralazine HCl Liquid Hydralazine tablets can be crushed and mixed in water. N.B. Crushing the tablets may alter the absorption rate - monitor blood pressure. Special The BNF states that hydrochlorothiazide offers no significant advantage over other diuretics. NICE CG127 states that if treatment with a Hydrochlorothiazide Liquid diuretic is being changed offer a thiazide-like diuretic, such as chlortalidone (12.5–25.0 mg once daily) or indapamide (1.5 mg modified-release Special once daily or 2.5 mg once daily) in preference to a conventional thiazide diuretic. Both chlortalidone and indapamide (standard-release) tablets disperse in water.

Hydrocortisone Liquid Hydrocortisone tablets are insoluble but they can be dispersed in water – they disperse within 1 minute. Alternatively, hydrocortisone sodium Special phosphate 100mg/mL injection (Efcortesol®) can be administered orally, but the phosphate content should be considered.

Hyoscine Hydrobromide Use the transdermal patch where clinically appropriate – 1mg/72 hours. Hyoscine hydrobromide is available as licensed 150mcg chewable Liquid Special tablets.

Hypromellose Special Order Hypromellose is available as licensed 0.3% eye drops. If preservative-free eye drops are required, hypromellose is available as licensed 0.3% Eye Drops preservative-free 0.4mL unit doses, or as 0.3% 10 mL preservative-free bottles (please refer to CWS formulary for products available). Isosorbide Mononitrate Consider Glyceryl Trinitrate transdermal patch. Liquid Special Page 13 of 21 Version 24 – July 2015 This document is regularly reviewed in line with any significant changes

NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE

Lamotrigine is available as 5mg, 25mg, and 100mg dispersible tablets.

Lamotrigine Liquid Special N.B. MHRA/CHM Advice – Category 2: For Category 2 drugs, the need for continued supply of a particular manufacturer's product should be based on clinical judgment and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. Lansoprazole is available as licensed orodispersible tablets, which are designed to dissolve on the tongue. The orodispersible tablets can also be dispersed in water if necessary. This is the most cost-effective option.

Lansoprazole Liquid Special Alternatively, omeprazole is available as MUPS tablets which can be dispersed in 10mL of still water and mixed with a small amount of acidic fruit juice (apple, orange or pineapple), apple sauce or yoghurt (off-label) – the solid pieces of the tablet must not be crushed or chewed. N.B. Do not disperse omeprazole tablets in milk. Levomepromazine Special Levomepromazine is available as licensed 25mg tablets, which are scored. Order Tablets Levothyroxine Special Order Levothyroxine is available as licensed 25mcg, 50mcg and 100mcg tablets. Capsules Levothyroxine Sodium Liquid Levothyroxine is available as licensed 25mcg/5mL, 50mcg/5mL and 100mcg/5mL sugar-free oral solution. Special Lidocaine Special Order 5% Lidocaine is available as licensed 5% ointment. Gel Lisinopril tablets can be dispersed in water. Alternatively, consider switching to ramipril which is available as licensed 2.5mg/5mL Lisinopril Liquid Special sugar-free oral solution. Lofepramine Liquid Special Lofepramine is available as a licensed 70mg/5mL sugar-free oral suspension.

Loperamide Liquid Special Loperamide is available as 1mg/5mL oral solution sugar-free or as 2mg oral lyophilisates sugar-free.

Lorazepam Liquid Special Lorazepam tablets may be crushed and mixed with water. Without crushing, they disperse in 1 to 5 minutes.

Megestrol Acetate Liquid Megestrol acetate tablets can be crushed and given in fruit juice or jam. Tablets should be crushed in water to reduce dust production. Special Where standard-release melatonin is indicated, the Coastal West Sussex Effective Shared Care Agreement (CWS ESCA) states that the Bio- Melatonin Special Order Melatonin® brand (3mg tablets) should be prescribed. Capsules / Tablets Although not licensed in the UK, Bio-Melatonin® (coded as Amber within CWS) is licensed elsewhere in Europe.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE

Where standard-release melatonin is indicated, the Coastal West Sussex Effective Shared Care Agreement (CWS ESCA) states that the Bio- Melatonin® brand (3mg tablets) should be prescribed. Melatonin Liquid Special Although not licensed in the UK, Bio-Melatonin® (coded as Amber within CWS) is licensed elsewhere in Europe. These tablets can be crushed and mixed with water. Mepacrine Special Order N.B. Within CWS formulary, mepacrine hydrochloride is coded as Red for giardiasis. Tablets Mercaptopurine is available as licenced 50mg tablets and 20mg/mL oral solution.

N.B. Puri-Nethol® tablets and Xaluprine® oral suspension are not bioequivalent – haematological monitoring is advised when switching Mercaptopurine Specials formulations. Order Capsules N.B. Within CWS formulary, mercaptopurine is coded as Amber for inflammatory bowel disease; for acute leukaemias and chronic myeloid leukaemia, mercaptopurine is coded as Red.

Metformin Liquid Special Metformin is available as licensed 500mg/5mL sugar-free oral solution.

N.B. Within CWS formulary, methotrexate is coded as Amber for dermatology and rheumatology related indications and Red for inflammatory Methotrexate Liquid Special bowel disease (IBD).

Metoprolol Liquid Special Metoprolol standard-release tablets (not modified-release) can be crushed and mixed with water.

Metronidazole Liquid Special Metronidazole (as benzoate) is available as licensed 200mg/5mL oral suspension.

Buccolam® (buccal midazolam) is available as a licensed product for children aged 3 months to 18 years as 2.5mg/0.5mL; 5mg/1mL; 7.5mg/1.5mL; 10mg/2mL. However, it is not directly interchangeable with unlicensed preparations. This is due to the difference in strengths and rates of absorption.

It is recommended that if buccal midazolam is required, new patients should be prescribed the licensed preparation (unless there is a clinical Midazolam Oromucosal reason why this would not be appropriate) and any existing patients continue on their present form unless there is a clinical need to change. Solution NICE 2012 - Administer buccal midazolam as first-line treatment in children, young people and adults with prolonged or repeated seizures. Administer rectal diazepam if preferred or if buccal midazolam is not available. If intravenous access is already established and resuscitation facilities are available, administer intravenous lorazepam. Only prescribe buccal midazolam or rectal diazepam for use in the community for children, young people and adults who have had a previous episode of prolonged or serial convulsive seizures.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE Midodrine Special Order N.B. Within CWS formulary, midodrine is coded as Red. Tablets Morphine HCl Liquid Special Morphine is available as licensed 10mg/5mL, 20mg/5mL (CD – sugar-free) or 100mg/5mL (CD – sugar-free, concentrated) oral solution. Naproxen standard-release tablets (not enteric-coated or modified-release) can be crushed and dispersed in water. Alternatively, consider switching to ibuprofen 100mg/5mL oral suspension (first choice in CWS formulary). Naproxen Liquid Special Diclofenac dispersible tablets may be considered if ibuprofen is unsuitable (prescribe the lowest effective dose for the shortest duration necessary). Nitrazepam Liquid Special Nitrazepam is available as a licensed 2.5mg/5mL oral suspension. Nitrofurantoin Liquid Special Nitrofurantoin is available as a licensed 25mg/5mL sugar-free oral suspension.

Nystatin Sugar-Free Oral Nystatin sugar-free oral suspension is no longer available as a licensed product. Consider whether the sugar-containing nystatin oral Suspension suspension is clinically appropriate. Consider using the licensed olanzapine orodispersible tablets which are designed to dissolve on the tongue. They can also be dispersed in Olanzapine Liquid Special water, orange juice, apple juice or milk. Consider changing to licensed lansoprazole orodispersible tablets, which are designed to dissolve on the tongue. The orodispersible tablets can be dispersed in water if necessary. This is the most cost-effective option.

Omeprazole Liquid Special Alternatively, omeprazole is available as MUPS tablets which can be dispersed in 10mL of still water and mixed with a small amount of acidic fruit juice (apple, orange or pineapple), apple sauce or yoghurt (off-label) – the solid pieces of the tablet must not be crushed or chewed. N.B. Do not disperse omeprazole tablets in milk. Ondansetron is available as licensed 4mg/5mL sugar-free oral suspension. Alternatively, ondansetron is available as 4mg and 8mg Ondansetron Liquid Special orodispersible tablets. Oxybutynin Liquid Special Oxybutynin is available as licensed 2.5mg/5mL oral solution. Oxybutynin is also available as licensed 36mg patches. Paracetamol is available as a licensed 120mg/5mL, 250mg/5mL, or 500mg/5mL (sugar-free) oral suspension. Alternatively, paracetamol is Paracetamol Liquid Special available as licensed 500mg soluble tablets.

N.B. Paracetamol soluble tablets contain a large amount of sodium, which may not be clinically appropriate in some patients. Perindopril Arginine Liquid Consider switching to perindopril erbumine; these tablets can be crushed and mixed with water. Special Perindopril Erbumine Liquid Perindopril erbumine tablets can be crushed and mixed with water. Special

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE Phenobarbital is available as a licensed 15mg/5mL elixir. However, this formulation contains 38% alcohol and is not considered suitable for use Phenobarbital in children. Alternatively, phenobarbital tablets can be crushed and mixed with water. (phenobarbitone) Liquid Special N.B. MHRA/CHM Advice – Category 1: For Category 1 drugs, doctors are advised to ensure that their patient is maintained on a specific manufacturer’s product. Phenytoin is available as licensed 30mg/5mL oral suspension.

N.B. The BNF states: Suspension of phenytoin 90 mg in 15 mL may be considered to be approximately equivalent in therapeutic effect to capsules or tablets containing phenytoin sodium 100 mg, but nevertheless, care is needed in making changes.

Alternatively, phenytoin is available as licensed 50mg chewable tablets. However, care is needed on switching to / from the chewable tablets Phenytoin Liquid Special due to differences in bioequivalence (as they contain phenytoin and not phenytoin sodium).

N.B. Within CWS formulary, phenytoin is coded as Red for trigeminal neuralgia.

N.B. MHRA/CHM Advice – Category 1: For Category 1 drugs, doctors are advised to ensure that their patient is maintained on a specific manufacturer’s product.

Phytomenadione Special The colloidal Konakion MM paediatric injection, which contains 2mg phytomenadione in each 0.2mL ampoule (10mg/mL), is licensed for oral Order Drops and Tablets administration. Alternatively, phytomenadione is available as licensed 1mg capsules.

Pilocarpine Special Order Pilocarpine is available as licensed 1%, 2% or 4% eye drops. If preservative-free eye drops are needed, pilocarpine (as nitrate) is available as Eye Drops licensed preservative-free 2% single dose units (0.5mL).

Pizotifen Liquid Special The tablets have been crushed and mixed with water for administration.

Prednisolone Sodium Prednisolone sodium phosphate is available as licensed 0.5% ear drops. Phosphate Ear Drops

Prednisolone Sodium Prednisolone sodium phosphate is available as licensed 0.5% and 1% eye drops. If preservative-free eye drops are required, prednisolone is Phosphate Eye Drops available as licensed 0.5% preservative-free 0.5mL unit dose eye drops.

Pregabalin Liquid Special Pregabalin is available as licensed 20mg/1mL sugar-free oral solution.

Procainamide Liquid Special Procainamide tablets can be crushed and mixed with water.

Propantheline Liquid Special Propantheline tablets can be crushed and mixed with water. They may have a bitter taste.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE

Propranolol Liquid Special Propranolol is available as a licensed 5mg/5mL, 10mg/5mL, 40mg/5mL and 50mg/5mL oral solution. Pyrazinamide Special Order N.B. Within CWS formulary, pyrazinamide is coded as Red for tuberculosis in combination with other drugs. Tablets

Quetiapine Liquid Special Quetiapine immediate-release (not modified-release) tablets can be crushed and added to soft food e.g. yoghurt. They may have a bitter taste.

Quinine Sulphate Liquid Quinine tablets can be crushed well and dispersed in a large volume of water (200mL). They may have a bitter taste, which can be masked Special by mixing the water with syrup.

Ramipril Liquid Special Ramipril is available as licensed 2.5mg/5mL sugar-free oral solution.

Ranitidine is available as a licensed 75mg/5mL sugar-free oral solution. It is also available as licensed 150mg or 300mg effervescent tablets, Ranitidine Liquid Special which should be dissolved in at least 75mL water.

N.B. Oral solution excipients may contain alcohol - please check the Summary of Product Characteristics (SPC). Sertraline tablets can be dispersed or crushed and mixed with water. Crushed tablets can be mixed with food, but they may have a bitter taste Sertraline Liquid Special and an anaesthetic effect on the tongue and patients should be advised to take care with hot food and drink after administration. Consider switching to an alternative drug available as oral liquid – e.g. fluoxetine.

For erectile dysfunction only, sildenafil is available as 25mg, 50mg and 100mg chewable tablets.

Sildenafil Liquid Special For pulmonary arterial hypertension only, sildenafil is available as 10mg/mL oral suspension. N.B. Within CWS formulary, for pulmonary arterial hypertension, sildenafil is coded as Red.

Consider switching to atorvastatin (NICE CG 181) which is available as licensed 10mg and 20mg chewable sugar-free tablets. Simvastatin Liquid Special Alternatively, simvastatin is available as a licensed 20mg/5mL and 40mg/5mL sugar-free oral suspension. Sodium bicarbonate is available as licensed 500mg capsules or 600mg tablets. Sodium Bicarbonate Special Order Capsules N.B. In view of the lack of evidence base and availability over-the-counter, this product should not be prescribed on the NHS for urinary tract infections. Sodium bicarbonate capsules (available as licensed 500mg) can be opened and the contents mixed with water. Sodium Bicarbonate Liquid Special N.B. In view of the lack of evidence base and availability over-the-counter, this product should not be prescribed on the NHS for urinary tract infections.

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NAME OF ‘SPECIAL’ POSSIBLE ALTERNATIVE Sodium chloride is available as licensed 0.9% single use (preservative-free) eye drops. It is also available as licensed 5% eye drops and as 5% Sodium Chloride Special preservative-free eye drops (NaCl 5% - 20 x 0.45mL preservative free single dose unit and PF Drops Sodium Chloride 5% x 10ml bottle). This Order Drops product is now available as a registered medical device and can be found in Part IXA of the Drug Tariff. Prescriptions need to be endorsed with one of the products listed in Part IXA. Sodium Chloride Special Sodium Chloride 5% ointment is available as licensed 5g preservative-free tube. Order Eye Ointment Sodium Cromoglicate Sodium cromoglicate is available as licensed 2% eye drops. If preservative-free eye drops are required, sodium cromoglicate is available as Preservative-Free Eye Drops licensed 2% preservative-free 0.3mL unit doses – please prescribe as Catacrom® to ensure that the licensed product is dispensed. Sotalol Liquid Special Sotalol tablets can be crushed and mixed with water.

Spironolactone Liquid Spironolactone tablets can be crushed and mixed with water. Special Sulfasalazine is available as a licensed 250mg/5mL sugar-free oral suspension. Sulfasalazine Liquid Special N.B. Excipients may contain alcohol. Tamoxifen Liquid Special Tamoxifen (as citrate) is available as licensed 10mg/5mL oral solution. Tacrolimus is available as licensed sugar-free granules (Modigraf®). However, different formulations of tacrolimus are not interchangeable, and any changes should be made under specialist supervision. If the liquid 'special' is preferred, the patient should be advised that the pharmacy Tacrolimus Liquid Special should obtain it from the same manufacturer each time.

N.B. Within CWS formulary, tacrolimus is coded as Red for renal transplantation. Temazepam Liquid Special Temazepam is available as a licensed 10mg/5mL oral solution (sugar-free available as well). Terbinafine Liquid Special Terbinafine tablets can be crushed and mixed with water. Tetrabenazine Liquid Special Tetrabenazine tablets can be crushed and mixed with water.

Thiamine HCl Liquid Special Thiamine HCl tablets (available as 50mg and 100mg) can be crushed and dispersed in water.

Tizanidine Liquid Special Tizanidine tablets can be crushed and mixed with water.

Tocopherol Acetate D-Alpha (as tocofersolan) tocopherol acetate (Vitamin E) is available as a licensed 50mg/mL oral solution.

Chewable Tablets N.B. Tocofersolan is a water-soluble form of D-alpha tocopherol

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Tolterodine Liquid Special Tolterodine standard-release tablets can be dispersed in water. They disperse within one minute. Consider using the licensed sprinkle capsules (available as 15mg, 25mg and 50mg), which can be opened and the contents sprinkled on a small amount of food, swallowed immediately, but must not be chewed.

Topiramate Liquid Special N.B. MHRA/CHM Advice – Category 2: For Category 2 drugs, the need for continued supply of a particular manufacturer's product should be based on clinical judgment and consultation with the patient and/or carer taking into account factors such as seizure frequency and treatment history. Tranexamic Acid Liquid Tranexamic acid tablets (available as 500mg) can be crushed and mixed with water. Without crushing, they disperse in 2 to 5 minutes. Special

Trazodone Liquid Special Trazodone hydrochloride is available as licensed 50mg/5mL sugar-free oral solution.

Trihexyphenidyl HCl Liquid Trihexyphenidyl is available as a licensed 5mg/5mL oral solution. Special Venlafaxine standard-release tablets (not modified-release) can be crushed and administered in jam. Venlafaxine Liquid Special The modified-release capsules can be opened and the contents emptied out and given in smooth food (e.g. yoghurt). However, the capsule contents must be swallowed whole. Warfarin is available as a licensed 1mg/1mL sugar-free oral suspension.

Warfarin Liquid Special N.B. Putting warfarin into solution will lead to an alteration in the proportion of the two enantiomers (which differ in potency). INR should be monitored closely following any changes, including a change to warfarin suspension / liquid ‘special’. Zolpidem Liquid Special Zolpidem tablets can be crushed and mixed with water. Consider changing to zolpidem or temazepam. Zopiclone Liquid Special Zolpidem tablets can be crushed and mixed with water. Temazepam is available as licensed 10mg/5mL oral solution.

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References:

1. Coastal West Sussex Local Health Economy Formulary. http://www.coastalwestsussexformulary.nhs.uk/default.asp 2. Coastal West Sussex. Medicines Management section. http://www.coastalwestsussexccg.nhs.uk/medicines-management (log-in required). 3. General Medical Council, Good practice in prescribing and managing medicines and devices (2013). Available from: http://www.gmc- uk.org/guidance/ethical_guidance/14316.asp 4. Betsi Cadwaladr University Health Board (Eastern Division) (Previously North East Wales NHS Trust). The Newt Guidelines for administration of medication to patients with enteral feeding tubes or swallowing difficulties. Smyth J Ed. 2nd ed. 2010. 5. Pharmaceutical Press. Handbook of Drug Administration via enteral feeding tubes. Bradnam V, White R. 2007. 6. British National Formulary. BNF 66. September 2013. London: British Medical Association and Royal Pharmaceutical Society. www.bnf.org 7. British National Formulary. BNF 67. March 2014. London: British Medical Association and Royal Pharmaceutical Society. www.bnf.org 8. CWS CCG Effective Shared Care Agreement (ESCA): Melatonin (Bio-Melatonin®) for persistent sleep onset disorders in children and adolescents with a range of neuro- developmental problems. Version 3. January 2014. www.coastalwestsussexformulary.nhs.uk 9. Pharma Nord UK Ltd. Bio-Melatonin® Summary of Product Characteristics (SPC). October 2012. 10. National Institute for Health and Clinical Excellence. Hypertension – Clinical management of primary hypertension in adults. NICE CG127. August 2011. http://www.nice.org.uk/nicemedia/live/13561/56015/56015.pdf 11. Department of Health. Drug Tariff. April 2014. http://www.ppa.org.uk/ppa/edt_intro.htm 12. Department of Health. Drug Tariff. November 2014. http://www.ppa.org.uk/ppa/edt_intro.htm 13. AstraZenica. Losec MUPS tablets 10mg, 20mg and 40mg (omeprazole). Patient Information Leaflet (PIL). Updated 06/11/2013. http://www.medicines.org.uk/emc/medicine/3487/XPIL/Losec+MUPS+Tablets+10mg%2c+20mg+%26+40mg/ 14. UK Medicines Information. UKMi. Medicines Q&As: What are the therapeutic options for patients unable to take solid oral dosage forms? Published on-line on 22/08/2013. http://www.ukmi.nhs.uk/ukmi/ukminews/default.asp?pageRef=1&sortorder=1 15. Rosemont Pharmaceuticals Ltd. Warfarin Sodium 1mg/1ml Oral Suspension Summary of Product Characteristics (SPC). Updated 19/04/2012. http://www.medicines.org.uk/emc/medicine/23933/SPC/Warfarin+Sodium+1mg+1ml+Oral+Suspension/ 16. Electronic Medicines Compendium. Patient Information Leaflet (PIL). Clanazepam 0.5mg/5ml and 2mg/5ml oral solution. Updated 02/02/2012. http://www.medicines.org.uk/EMC/searchresults.aspx?term=Clonazepam&searchtype=QuickSearch 17. Sussex Community NHS Trust. Medicines Management News Letter, Issue 13, July/August 2012 18. National Institute for Health and Care Excellence (NICE), The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care Clinical Guidance (CG137, January 2012; last modified December 2013. http://www.nice.org.uk/cg137 19. Medicines and Healthcare Products Regulatory Agency (MHRA). Antiepileptics: changing products. Product specific information and advice. Issued 25/11/2013. http://www.mhra.gov.uk/Safetyinformation/Generalsafetyinformationandadvice/Product-specificinformationandadvice/Product-specificinformationandadvice-A- F/Antiepilepticschangingproducts/index.htm 20. MIMS Online. 2014. http://www.mims.co.uk/home/ (log-in required) 21. Personal telephone conversation with Internis Pharmaceuticals Ltd Medicines Information Department regarding excipients of Fultium-D3® excipients and confirmation of arachis (peanut oil) removal from contents list. As Fultium-D3® shelf life is 2 years, there may be some formulations that still contain arachis oil – however, this is clearly marked on the packaging – 02/03/2015. 22. Electronic Medicines Compendium. Summary of Product Characteristics Amlodipine 1mg/mL oral –solution, Rosemont Pharmaceutical Ltd, updated 18/06/2015. http://www.medicines.org.uk/emc/medicine/30460.

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