Focus on ‘specials’

Specials are unlicensed medicinal products manufactured in the UK for human use which have been 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.”

Specials come with a number of considerations; Specials products will not have been assessed by the licensing authority for safety, quality and efficacy. Depending on the manufacturer, may also vary in formulation and hence efficacy, bioavailability and excipients. Special medicines can be very expensive (several hundred pounds for one bottle) and may not represent a cost effective treatment. A special may have a short expiry date e.g. seven days.

The GMC have produced some guidance on prescribing specials http://www.gmc-uk.org/guidance/ethical_guidance/14327.asp/ which states, that wherever possible, licensed products should be used in preference to unlicensed ‘specials’

The prescriber therefore, needs to decide whether the patient has special pharmaceutical needs which a licensed product cannot meet, e.g. can a soluble tablet be prescribed instead of a liquid medicine? Indeed, in many cases, a licensed tablet will disperse in water which is preferable to an unlicensed product.

Specials can be difficult to identify at the point of prescribing and prescribers may be unaware that they are considering prescribing one. If a medicine is not in the British National Formulary (BNF) it could be a Special. E.g. Dermatology products, eye drops and liquid preparations are more commonly formulated as Specials.

Electronic prescribing systems may not identify Specials however some systems may use the letter ‘U’ to indicate an unlicensed medicine, or misleadingly highlight the cost of Specials as ‘zero’.

Prescribers and Community pharmacists should check and discuss alternatives if they think a prescribed product is a Special.

If a “special” is unavoidable; check with your pharmacist for a cost effective choice.

TOP 6 SPECIALS

1.  PPI oral suspensions

Over the 3 months from January 2015 to March 2015 NH CCG spent £28,761 on lansoprazole and omeprazole unlicensed liquid specials. This is an area where there may be a suitable licensed alternative product. Omeprazole is available as dispersible tablets and lansoprazole as orodispersible tablets.

Omeprazole oral suspension (Drug Tariff Part VIIIB Special Prices Mar 15):1

Strength / Min volume / Supply at 5ml daily dose / Price per min volume / Cost of omeprazole dispersible tablets (Losec MUPs) for equivalent length of supply*
10mg/5ml / 75ml / 15 days / £110.73 / £4.15
20mg/5ml / 150ml / 30 days / £135.16 / £12.43
40mg/5ml / 100ml / 20 days / £182.08 / £16.57
5mg/5ml / 75ml / 15 days / £114.63 / No licensed equivalent**
Lansoprazole oral suspension (Drug Tariff Part VIIIB Special Prices Mar 15)
Strength / Min volume / Supply at 5ml daily dose / Price per min volume / Cost of lansoprazole orodispersible tablets for equivalent length of supply*
15mg/5ml / 100ml / 20 days / £145.04 / £2.26
30mg/5ml / 100ml / 20 days / £145.46 / £3.88
5mg/5ml / 100ml / 20 days / £145.33 / No licensed equivalent**

*Omeprazole capsules containing the granules can be opened and mixed with fruit juice or yoghurt. Please switch to this formulation if appropriate.

**Please check dose and switch to alternative licenced formulation if appropriate.

For patients who are unable to swallow tablets, these formulations may provide a suitable alternative option. Please seek advice from your Medicines Management Pharmacist or Technician if you are unsure about changing formulations for patients who have enteral feeding tubes.

For all patients, ongoing need should be reviewed regularly and medicines that are no longer required should be stopped.

There is a price in the Drug Tariff for the unlicensed oral suspension.

1Acknowledgement to West Hampshire Clinical Commissioning Group

2.  Melatonin Preparations

Firstly, review the use as there is limited evidence to support the use of melatonin.

Circadin® 2mg MR is licensed and is indicated as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over.

In preference to an unlicensed oral liquid, prescribe Circadin® 2mg MR. For children with difficulties swallowing, the tablet can be crushed to a fine powder and mixed with water or given with cold soft food such as a teaspoon of yoghurt or jam. Use a small amount of food to ensure the full dose is taken. The prescription should state that the medication is to be crushed prior to administration.1 When crushed; the release characteristics are similar to an immediate-release dosage form (an off- label use), or if halved using a tablet cutter it will retain its slow release characteristics. The use of Circadin® 2mg MR in children is off- label.1

Special order liquid medicines and capsules are unlicensed and expensive and should ONLY be used where absolutely necessary.

Prescribe licensed product Circadin® 2mg MR £15.39/ 30 tablets in preference to unlicensed oral solutions and suspensions.

There are drug tariff prices for unlicensed melatonin oral suspensions (prices June 2015):

Melatonin Strength / Formulation / Minimum volume / Price per minimum volume / Price for each extra ml/g above the minimum
volume
Melatonin 10mg/5ml oral solution / STD, SF, LF, CF, NSF / 100ml / £136.92 / £0.05
Melatonin 10mg/5ml oral suspension / STD, SF, LF, CF, NSF / 100ml / £239.13 / £0.25
Melatonin 2mg/5ml oral solution / STD, SF, LF, CF, NSF, AF / 100ml / £91.22 / £0.04
Melatonin 2mg/5ml oral suspension / STD, SF, LF, CF, NSF, AF / 100ml / £164.23 / £0.23
Melatonin 2.5mg/5ml oral solution / STD, SF, LF, CF, NSF, AF, FF / 100ml / £103.41 / £0.05
Melatonin 2.5mg/5ml oral suspension / STD, SF, LF, CF, NSF, AF, FF / 100ml / £260.25 / £0.30
Melatonin 3mg/5ml oral solution / STD, SF, LF, CF, NSF, FF / 100ml / £107.69 / £0.09
Melatonin 3mg/5ml oral suspension / STD, SF, LF, NSF / 100ml / £198.15 / £0.25
Melatonin 5mg/5ml oral solution / STD, SF, LF, CF, NSF, FF / 200ml / £80.48 / £0.10
Melatonin 5mg/5ml oral suspension / STD, SF, LF, CF, NSF, AF, FF / 100ml / £108.17 / £0.10

1 Basingstoke, Southampton & Winchester District Prescribing Committee Melatonin Shared Care Guidelines May 2015

STD Standard formulation including standard flavours, SF Sugar free, AF Alcohol free, CF Colour free, FF Flavour free, LF Lactose free, PF Preservative free, NSF Non- standard flavours.

Melatonin immediate- release caps and tablets are not licensed preparations and not covered in the drug tariff. The variation in price may be considerable even for the same item. The cost to the CCG >£100K per year.

Examples of variations in the cost of immediate- release melatonin (based on specials prescribed by the CCG March 2015):

BNF Name / Variations in Total Act Cost / Quantity
Melatonin_Cap 5mg / £48.90- £101.53 / 28
Melatonin_Cap 3mg / £23.14- £285.71 / 60
Melatonin_Cap 2mg / £38.36- £210.64 / 60
Melatonin_Tab 3mg / £59.42- £94.44 / 60
Melatonin_Tab 1mg / £26.31- £66.70 / 60

3.  Midodrine Preparations

Midodrine does not have marketing authorisation in the UK for the treatment of postural hypotension or for any other indication, therefore it is an unlicensed medicine in the 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.

In line with guidance from the General Medical Council (GMC), it is the responsibility of the prescriber to determine the clinical need of the patient and the suitability of using midodrine as an unlicensed treatment for postural hypotension. No other drugs have UK marketing authorisation for postural hypotension.

Two double-blinded randomised controlled trials (RCTs) provided some limited evidence that midodrine may improve some patient-rated symptoms of postural hypotension, such as syncope (fainting) and low energy levels.

The most common side effects seen with midodrine are piloerection (goose bumps), pruritus and paraesthesia (particularly of the scalp), urinary retention or urgency, and supine hypertension.

The longer-term efficacy and safety of midodrine has not been assessed in the RCTs, nor has its effect on activities of daily living.

Midodrine acts as an alpha adrenergic receptor agonist. It stimulates the sympathetic part of the autonomic nervous system, resulting in an increase in the resistance of blood vessel walls and an increase in blood pressure[8]. Midodrine is reported to only cross the blood–brain barrier poorly and so it is not associated with effects on the central nervous system[9].

The evidence showed that 10 mg midodrine taken orally 3 times a day for 3 to 4 weeks increases standing blood pressure 1 hour post-dose more than placebo in people with symptomatic postural hypotension due to dysfunction in the autonomic nervous system. Midodrine also increases supine (lying) blood pressure more than placebo. These results may only apply to people who can stay on the medication.

A number of drug and non-drug approaches have been used to treat postural hypotension. Non-drug therapies include increasing water and salt intake, or using compression garments or bandages and physical manoeuvres to counter the drop in blood pressure.

Many medicines have been considered or studied for potential use in postural hypotension, including drugs that target the autonomic nervous system (such as phenylephrine, ephedrine, pseudoephedrine, droxidopa and phenylpropanolamine), pyridostigmine, domperidone, non-steroidal anti-inflammatory drugs, erythropoietin and fludrocortisone.

Some of these drugs, such as fludrocortisone, domperidone and pyridostigmine, have licenses for other indications in the UK, therefore use in postural hypotension is off-label.

One systematic review concluded that many commonly used interventions for postural hypotension have a limited evidence base supporting their use.

4.  Magnesium Glycerophos cap 48.6mg/Chble 97.2mg S/F

¨  Magnesium-L-aspartate (Magnaspartate®) is the preferred choice for the treatment and prevention of magnesium deficiency when clinically appropriate as it is the only UK licensed oral magnesium preparation

¨  If magnesium-L-aspartate (Magnaspartate®) is not effective in raising magnesium levels or if it is poorly tolerated it is reasonable to try an alternative oral magnesium preparation, if the patient’s condition allows

¨  Robust evidence of the superiority of one oral magnesium preparation over another does not exist; therefore it is not possible to recommend one particular preparation over another on the basis of efficacy and safety

¨  Large scale clinical outcome studies are needed to compare the different oral magnesium preparations in patients with hypomagnesaemia

¨  Information from the small studies available suggests there are differences in the bioavailability of some magnesium salts

¨  Factors affecting the choice of a second line preparation may include local availability, patient tolerability, and price. Examples of oral magnesium preparations which are available in the UK are given in Table 1

¨  Caution should be exercised when switching between magnesium preparations. Swapping on a mmol for mmol basis may not result in an equivalent therapeutic effect as magnesium preparations have differing bioavailability. The new preparation needs to be titrated to the maximum tolerated dose with monitoring of magnesium serum levels. Tolerability of a particular preparation may limit the dosage.

¨  The use of sustained-release preparations (e.g. Mag-Tab SR® containing Magnesium L-lactate dihydrate) may allow the use of lower doses, which minimises the risk of diarrhoea

5.  Levomepromazine 6mg

A phenothiazine used widely in palliative care to treat intractable nausea or vomiting, and for severe delirium/ agitation in the last days of life.

A licensed 25mg tablet (Nozinan®) is available and is scored, so may be cut in half or quarters; thus a comparable dose of 6.25mg or 12.5mg is achievable.

In cases where a dose of less than 6mg is desired, or where it is uncertain that a patient is able to safely cut the tablets in half or quarters, an unlicensed product, levomepromazine 6mg (Levinan®) is obtainable but is significantly more expensive than its licensed counterpart.

6.  Topiramate 25mg/5ml suspension

Topamax® hard capsules 15mg/25mg/50mg may be swallowed whole or may be opened and sprinkled on a teaspoon of soft food of any type. Examples are applesauce, custard, ice cream, porridge, pudding or yogurt. It is also advisable to drink plenty of fluids after ingesting Topamax.

Only consider the unlicensed topiramate suspension in instances where the specified dose is not 15mg, 25mg, 30mg or 50mg.