'If the disease doesn’t kill me the drugs probably will...’ For those who are allergic to penicillin and other active drugs this is a well recognised and justifiable fear. But what of those who are allergic or intolerant to the other, non-active ingredients in standard medications ? the lactose, the glucose, the preservatives or the colourings? Michelle Berriedale-Johnson describes what should happen; John Scott and Jacqie Broadway give their experiences.

Reacting to the ‘other things’ in prescribed medication is yet another hazard that confronts those suffering from allergies and intolerances. For some a reaction will come as an upset stomach, a wheezing attack or an eruption of eczema or urticaria. For hyperactive children it may result in serious deterioration in behaviour. But for some being treated with standard medication could be fatal.

The problem lies in the non-active materials, known as excipients. These carry or contain the active drugs, give the drugs shelf life (often several years of shelf life) and colour them to make them look appealing and to distinguish them from each other.

Drug Formulation & Manufacture
In olden days, when chemists in white coats weighed and pounded their powders and potions at the back of their pharmacies, they could, and did, make up medicines to suit the individual needs of their customers. However, times have changed and the risks of inaccurate dosages and contamination inherent in making up medicines in small individual pharmacies are too great. As a result medicines must now be licensed before they can be sold to the public – which means that they can only be manufactured by those who hold a license to do so. Manufacturing requirements are, rightly, stringent and licenses to manufacture drugs are only held by pharmaceutical manufacturing companies and some of the larger hospitals where their drug requirements justify the expense of a full pharmaceutical manufacturing department.

Because the development of drugs is an extremely costly, if also profitable, business drug companies develop specific formulations, which include both active and non-active ingredients. These are then granted a license to be prescribed and sold.

However, the license is specific to that formulation. Changing anything in the formulation, even if it is only a colouring agent, means that its license is no longer valid and that a new license would need to be obtained for the new formulation.

Nonetheless, most drugs, especially the common ones, are available in a number of licensed formulations, often both in tablet/capsule and in liquid form. A little research on the part of the doctor or pharmacist may unearth a licensed formulation which does not contain the ingredient to which you react.

‘Specials’
However this is not always the case. When no appropriate formulation is available medicines legislation (Medicines for Human Use Regulations 1994/SI 3144) allows the ‘manufacture and supply of unlicensed medical products (known as ‘specials’) provided that:
• there is a bona fide unsolicited order
• the product is formulated in accordance with the requirement of a doctor or dentist registered in the UK
• the product is for use by their individual patients on their direct personal responsibility
• if the 'special' is manufactured in the UK the manufacturer holds a “specials” license issued by the MCA
• an equivalent licensed product is not available
• essential records are kept and serious adverse drug reactions are report to the MCS.’

Specials manufacturers tell us that, provided they have access to the active ingredients (occasionally the manufacturer is not prepared to release these) they can make up drugs to suit virtually any restricted diet, no matter how bizarre the restriction may be.

However... There are two stumbling blocks for those who might want to make use of this provision. One is that very few GPs appear to be aware that, if they provide the appropriate prescription, it is possible to get ‘special’ drugs made up.

The second is that, even if they do know about ‘specials’, they are often reluctant to prescribe them as the cost of manufacturing (often very high as each drug has to be individually made up under full clinical conditions) has to come out of their budget.

Problem ingredients
The five non-active ingredients in most drug formulations that are likely to cause problems are:
• Colourings
• Preservatives
• Lactose
• Starch
• Glucose

Finding out about Excipients
Drug companies are required by law to list all the ingredients, both active and non-active, on the sheet of information that comes with the drug. You should be able to discover from your local pharmacy what the ingredients of any specific drug your doctor wishes to prescribe may be. If not, some searching on the web should unearth them. Some ingredients may be classified by their E numbers.

Colourings
Colourings are used to differentiate one drug from another and to make the tablets, capsules or liquid medicines look more ‘appealing’. Because they produce brighter colours, azo or coal tar dyes are often used even though azo dyes are known to affect hyperactive children. To avoid possible allergic reactions, antihistamine type medications normally use natural colours. Colours are not integral to the formulation and can just be left out.

Preservatives
Preservatives are found mainly in creams, ointments and liquids. Because licensed drugs are required to have long, often very long, shelf lives preservatives are needed to inhibit microbial growth and prevent the drugs themselves becoming toxic.

Although a number of different preservatives are used the most common are benzoates, known to cause a number of allergic reactions.

If a patient has a problem with the available preservatives, a specials manufacturer will simply leave them out, making up only a small amount of the drug - enough for a maximum of 28 days - so that preservation is no longer an issue.

Lactose
One of the problems that drug manufacturers and pharmacists face is that the active ingredient in a drug is often tiny in volume so they need to ‘bulk it out’ into a pill or capsule that the patient can handle safely and easily.

Lactose is very widely used in the drug industry for ‘bulking out’ both tablets and capsules because it is inert, stable and manageable. It can also be relied on to maintain its consistency until it gets to the part of the digestion where it is required to disintegrate. Where licensed lactose free formulations are not readily available, a specials manufacturer can, provided they can obtain the active ingredient, formulate the medication without lactose, often as a liquid.

Starch
Starch (wheat or corn based) can also be used as a bulking agent although it is more often used as a disintegrant – to ensure that the tablet disintegrates in the stomach releasing the active ingredient. The level of protein which remains in the starch is extremely low; so low that it is questionable whether it would retain any allergenicity. However, those who are particularly sensitive should still beware.

A specials manufacturer would probably formulate the drug as a liquid preparation.

Sugar/Glucose/Sweeteners
Sugar and sweeteners are used mainly in liquid formulations (especially for children) to make them more palatable – even though a substantial number of children may react to both sweeteners and sugar.

Sugar-free formulations of a number of licensed drugs do exist but if your doctor or pharmacist cannot locate any, a specials manufacturer will make up your drug in a sugar-free liquid formulation.

Persuading your Doctor
• Persuading your doctor that you really are allergic/intolerant to the relevant ingredient may be the hardest part of the job. Even if they understand and accept that you really are allergic to what you say you are, having 'specials' made up is very expensive (whether the very high cost is really justifiable is another matter) and, especialy in these straightened times, they will be anxious to avoid the expenditure unless there is absolutely no other option.

• If they do not know about ‘specials’ refer them to the Medicines Control Agency for verification that ‘specials’ exist and are legal. They can look on the MCA website www.mhra.gov.uk for general information and specficic guidance notes. (Just put 'specials' into the search box if the link does not take you straight there.) They can also call on 020 3080 6844. They could also check in with the Association of Specials Manufacturers – www.acsm.uk.com.

• Ask your pharmacist what they know about ‘specials’. They should know all about them but (see John's Scott's comments below) do not always appear to do so.

• Talk to the 'specials' manufacturers yourself. You will need to make it very clear that you are only looking for information to relay back to your doctor/pharmacist and that you know that they cannot supply you direct. You also need to be sure that you understand all the shades of your intolerance (see Jacquie Boradway's experience below) as they may well suggest alternative excipients that they think would be problem free but which you know will not be!

The following companies all manufacture 'specials' medicines and, according to Jacquie Broadway, were very helpful.

BCM Specials

The Specials Laboratory

Nova Laboratories

Penn Specials

• Be persistent - advice that is scarcely needed by most allergic or intolerant people for whom ‘ Persistence’ has become their middle name!

Free-from medicines - best-keep secret of the NHS

Shortly after this article was first published in 2005 John Scott tried to put Michelle's advice into practice – but with only limited success.

I heard recently, for the first time, of the existence of 'specials' - medicines manufactured on an individual basis to specific requirements, such as the omission of specified allergens.

Overjoyed to discover that there is the option to obtain 'free-from' versions of medicines, I tried to find out more about this from the people who should know - pharmacists - but the responses of pharmacists I contacted locally were not encouraging.

Comments ranged from the unequivocal ‘The option does not exist...your doctor needs to find an alternative drug’ through ‘Can't really say...I'd need to enquire’, to the irrational ‘It would depend on what the (allergic) reaction is’ and even the astonishing opinion that the production of an allergen-free medicine is ‘simply a matter of grinding up a tablet and mixing it with water!’

According to the only pharmacist I could find who did know, in detail, about 'specials' (and she was a locum who just happened to be on duty when I called), the procedure should be straightforward. All that is required is for a GP to write out a normal NHS prescription, stating the drug required and clearly specifying the allergen(s) to be omitted during preparation. The prescription is then presented to any high street pharmacy, which will place an order with a 'specials' manufacturer.

Judging from my straw poll of local pharmacies, the patient may need to inject a little encouragement and even guidance at this point, but my contact is adamant that all pharmacists should know of 'specials' manufacturers.

Provided that the drug is available in its pure form, a preparation will be made up containing this, but omitting the specified allergen(s). As it is not practical to prepare tablets in very small quantities, such 'specials' are likely to be dispensed in liquid form, so may contain such additional items as sugar, unless these are also specified for exclusion.

My contact says that allergy specialists should obviously be aware of the allergen-free option and that their patients may be able to have their special medicines made up by the hospital pharmacy, if this has a manufacturing unit. Even sterile 'specials', such as injectables, can be prepared in some larger hospital pharmacies if they have the requisite licence. The hospital's Drug Information Unit (a valuable source of information on all things medicinal) should be able to confirm whether this is the case.

The 'specials' option appears, therefore, to be an existing path, within the NHS, which has become overgrown from lack of use. It is in need of the efforts of a few intrepid trekkers to reclaim it by putting it into regular service, then flagging up its existence for the benefit of others. I'm sure there will be resistance, especially on the grounds of cost, something to which several of the pharmacists I contacted were quick to draw my attention, but this is a route which we desperately need to reopen and place firmly on the map.

The system in practice

In early 2012 Jacquie Broadway who is extremely allergic to sugar and grain starch, especially corn starch (and also to moulds) and has severe malabsorption and digestive problems, had a hip replacement. She has had an on-going battle to get a supply of antibiotics that she could tolerate but now she was faced with trying to get some pain killers that would not contain either starch or sugar.

Jacquie's GP has known her for many years so is aware of her allergies and digestive problems, but had managed, mainly by being unavailable, to avoid addressing the problem of getting her some pain killers that she could tolerate.

Her local Boots pharmacist was helpful and did know about 'specials'. However, she did not know about severe allergy or digestive peoblems, so she offered alternative versions of standard painkillers including, for example, one based on lactitol. But lactitol is a sugar alcohol which is well known to cause diarrhoea – totally inappropriate for someone with Jacquie's history. (This is why, if you are to go down this route, you need to know exactly what you can and cannot tolerate.)

Finally, she called up the 'specials' manufacturers listed above who, she said, were very helpful, especially The Specials Laboratory. But even with the manfuacturers, it took her some time to persuade them that such was her sensitivitiy to corn that, even if it had been hydrolysed (the protein broken down into tiny molecules) she would still react to it.

However, they did come up with two formulations for paracetomol, one as a liquid (with only a few weeks shelf life) and one as crystals, which would last rather longer but would be quite unpleasant to take.

Armed with this information, Jacquie got back onto her GP. After further delay, the practice secretary came back to her to say that the drugs would cost around £300 and 'couldn't she make do with something else'.... At which point, her husband lost his cool, marched into the surgery and demanded that they get her some drugs that she could use without them making her seriously ill and risking killing her. She now has her paracetomol crystals....

The main part of this article was first published in 2005; it was revised in 2012.

• If this article was of interest you will find many other articles on unlikely allergies and allergy connections here – and links to many relevant research studies here.

• For more on the more 'mainstream' allergies check in to our 'allergy and intolerance home page' – and for ideas on alternative foods go here.

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