Drug Treatment

Drugs in common use are here listed in alphabetical order for ease of reference.

Acetarsol Suppositories

What is Acetarsol?

Acetarsol may be provided by the pharmacies of certain specialist hospitals but is not available on general prescription. It is a substance derived from arsenic. However, although arsenic is a poison, it has been found to be very effective in some cases of resistant proctitis.

Is it safe?

Acetarsol has proved safe and effective in clearly defined doses. Some cases of poisoning have occurred with prolonged courses (greater than 4 years in both cases) or with large doses (3.5-7.9 g). Levels in the blood and urine may be initially high but rapidly fall (usually after 1 week) as the lining of the rectum heals. When treatment is stopped there should be no further trace of the drug after approximately 4 weeks

Indications for use

This treatment is usually only prescribed when the standard treatments for colitis, (mesalazine or steroids) have failed to settle the symptoms.

Dosage & administration

The treatment should be prescribed by your specialist and taken according to instructions. Suppositories will usually be prescribed as 250 mg morning and evening, for up to 1 month. The suppositories should be lubricated with a little K Y jelly or water and then inserted into the back passage.

Are there any side effects?

Acetarsol is generally safe to use if taken correctly according to your doctor's instructions. Possible side effects may occur and would be related to arsenic toxicity.

Adalimumab

What is Adalimumab?

Adalimumab is a fully human monoclonal antibody against Tumour Necrosis factor - alpha (TNF-a), the chemical which is at the heart of many inflammatory diseases (See infliximab). When successful it may induce and prolong remission of CD. It use in CD is relatively new but it is also valuable in the treatment of rheumatoid arthritis. It has the advantages that the patient may be able to give his own injections at home at intervals of one to two weeks.

Like other monoclonal antibodies against TNF-alpha it may reduce defences against infection. Patients must be checked for tuberculosis before starting treatment and it must not be given to pregnant or breast-feeding women. It may make congestive cardiac failure and multiple sclerosis worse. It must be used with care in patients with chronic infection such as leg ulcers, perianal disease and indwelling urinary catheters.

Are there any side effects?

Common side effects include pain at the injection site, respiratory infections, nausea and abdominal pain, headache and rash. Systemic infections e.g. candidiasis and influenza may occur. Rarely, treatment with adalimumab may lead to the development of lymphoma, lupus or neurological disease.

Adalimumab has been shown to be effective in cases which have failed to respond to other treatments but your doctor will decide if it is appropriate to your case.

Asacol

What is it?

Asacol is mesalazine in a resin coated designed to release the active ingredient 5-Aminosalicylic acid (5-ASA) in the terminal ileum where the pH is above 7. The active ingredients are then dispersed throughout the colon.

What is it used for?

Asacol is used in the treatment and maintenance of mild to moderately acute ulcerative colitis and CD

How do I take them?

Asacol is presented in several forms:

Tablet: to be swallowed whole with plenty of water.
Suppositories: inserted into the rectum up to 3 times daily, last dose at bedtime.
Enema: mesalazine foam with disposable applicators and plastic bags. The applicator is inserted into the rectum and the foam is introduced in a metered aerosol.

The above medications will be prescribed according to the site and severity of the inflammation and may be used in combination.

The enemas are used to act directly on inflammation in left-sided disease and suppositories for rectal inflammation. Once the symptoms have been controlled, you will be given a lower maintenance dose. Although you might feel better it is important to continue taking the medication as instructed to prevent the symptoms from coming back.

Are there any precautions?

Asacol should not be taken if you are allergic to aspirin. It is not recommended if the kidneys are not working properly. Its effect may be reduced by medications, which alter the pH of the intestine and affect its absorption e.g. lactulose.

Asacol is safe to use during pregnancy and it is better for both you and your baby that active disease is treated vigorously and effectively. The lowest effective dose will always be used. Low levels of mesalazine have been detected in breast milk, but it is safe to continue.

Are there any side effects?

Asacol is generally well tolerated but, if side effects were to happen, these could include:

Nausea
diarrhoea
Abdominal pain
Headache

It may also cause a worsening of the colitis in a very few sensitive people. Impairment of kidney function occurs very rarely but everyone on mesalazine should have an annual blood test to check their kidney function.

Side effects tend to be related to the dose and can be minimised by gradually building it up. If side effects continue, the drug should be stopped.

*Important note
If you have any unexplained bleeding, bruising, a sore throat, fever or generally feel unwell whilst taking the medication, you should stop immediately and see your doctor for a blood test and further advice.

You may see what appears to be the tablet in your motions but should be reassured that the active molecules have usually been released, leaving the resin case. If you consistently see the grey powder still contained within the case, it will probably be worthwhile switching to a different 5-ASA preparation.

Azathioprine (Imuran)

What is it?

Azathioprine is a drug that affects the immune response in the body (i.e. an immunosuppressant).

Indications for use

The main use is in organ transplantation to prevent rejection of the donor organ. However, it has proved beneficial in patients with severe chronic inflammatory bowel disease which has not responded to steroids alone, or in patients who are dependent on high dose steroids to control symptoms. It is useful in those patients who frequently relapse on reducing the dose of steroids and thus has a steroid sparing effect.

How is it taken?

It is taken as a tablet that must be swallowed whole with plenty of water. The dosage is calculated according to your body weight - usually 2 mg per kg, however your doctor will tell you the correct dose for you. Some people have lower levels of the enzyme which metabolises azathioprine (TPMT) and they will be given lower doses.

Recently there has been interest in the possibility of reducing the risk of side effects on azathioprine by giving a small dose (one quarter of the normal level) together with another drug, allopurinol which is widely used to treat gout, but which reduces the breakdown of azathioprine and thus promotes its therapeutic effect. Allopurinol must never be taken by persons on full doses of azathioprine as this could lead to the build-up of toxic levels.

The tablets may be taken altogether, although taking them in divided doses and after meals may reduce any associated nausea.

You will not usually notice any effects straight away, as it can take up to 6 weeks before it begins to work and the real benefits may not be noticed for 3 months or more. For this reason treatment is often commenced in conjunction with oral steroids for more immediate relief of symptoms with the dose gradually being tapered as the azathioprine begins to exert its effect.

Monitoring

Due to the potential risk of treatment on the bone marrow and the liver, it is extremely important to have regular blood checks whilst taking the treatment. Full blood counts and liver function tests should be taken on a weekly basis for the first 2 months, then 3 monthly thereafter whilst taking the treatment.
Results should be recorded in the monitoring book given to you by the doctor. Tests can be carried out at the hospital or GP surgery, but it is important that the doctor, or nurse, tells you that it is safe to continue.

Contraindications

You should not take this drug if you have previously had a reaction to this or to 6 mercaptopurine.

*Special precautions

If you are considering becoming pregnant, or become pregnant whilst taking azathioprine treatment, speak to your doctor or nurse as soon as possible. Your doctor may well tell you to continue t, particularly if you have troublesome disease that has only been under control on this treatment. If you are planning a pregnancy, and you have been in remission for some time, you may be advised to try stoppingazaathioprine before trying to become pregnant. However, there is as yet no definite evidence that azathioprine, when used to treat IBD, increases the risk of damaging the baby.Nevertheless, treatment should not be initiated during pregnancy.

Azathioprine should be stopped in all but minor infections as the body defences may be reduced and delay your recovery or cause a worsening of the condition. Speak to the nurse or doctor before stopping any treatment and you will be advised when it is safe to restart.

Are there any side effects?

Azathioprine can be very effective in providing remission from the symptoms caused by inflammatory bowel disease, and in allowing smaller doses of steroids to be used effectively whilst reducing the risk of relapse and steroid induced side effects. However it is possible that some side effects may occur during treatment. Symptoms, such as diarrhoea, nausea, mild aches and pains may occur initially but should settle within 2 weeks. Others, which are potentially more serious, may occur. These may include some of the following:

Feeling generally unwell
Dizziness
Vomiting
Fever
Rigors
Muscle pains
Joint pains
Abnormal liver function
Jaundice
Disturbances in heart rhythm
Low blood pressure
Kidney problems
Skin rash

These may be due to a hypersensitivity reaction and you may need to stop the treatment. You must contact your doctor or IBD nurse immediately for further advice.

Other reactions may occur such as:

Reduced bone marrow activity i.e. low white cells [neutrophils are particularly important in fighting infection], low platelets [important in helping the blood to clot], low haemoglobin [iron in the blood].
Hair loss

These may respond to a dose reduction or temporarily stopping treatment and reintroducing at a lower dose.

It may rarely cause inflammation of the pancreas or lungs. This is reversible on stopping treatment, but the drug should not be restarted on recovery.

Although these side effects may sound quite alarming, many patients manage to take the drug safely with little, or no, trouble. You should be reassured that you will be monitored closely whilst taking this treatment and that if side effects do arise, they will be dealt with accordingly.

Your compliance with the monitoring programme is essential in the safety of your treatment.

Are there any interactions?

Azathioprine may react with other drugs and it is therefore important that you tell your doctor about any other tablets you may be taking. You should not start any new medication before discussing this with your doctor or IBD nurse first. Interactions include:

Allopurinol- given for gout. Enhances the effect and therefore, increases the toxicity of Azathioprine. However it has recently been suggested that by giving small doses of azathioprine together with allopurinol, the beneficial effects may be achieved using a smaller dose and thus reducing the risk of side effects.
Antibacterials - given to treat infection e.g. rifampicin.

Anion-exchange resins - Cholestyramine (Questran) and Colestipol

What are they?

These are bile acid sequestrants, i.e. they 'mops up' excess bile salts.

What are they used for?

Principally to control diarrhoea caused by excessive amounts of bile salts spilling over into the large bowel and irritating its lining.
This can occur if the terminal ileum, where these salts are normally absorbed has to be removed due to CD which is not responding to medical treatment.

How is it taken?

Cholestyramine is a powder which is dissolved in water and taken as a drink. Colestipol comes as granules to be taken with liquid.

Are there any special precautions?

Supplements of the vitamins A, D, E and K may need to be taken ifthese preparations have been used for a long time in high doses (i.e. 3 or more sachets daily).
If you take any of the following drugs:

Digoxin
Antibiotics
Diuretics (water tablets)
Warfarin
Thyroxine

They should be taken either 1 hour before or 4 - 6 hours after taking It may be used during pregnancy and breastfeeding if the doctor considers that the benefits outweigh any potential harm that may be caused.

Are there any adverse reactions?

If these resins are taken for a long period of time, it can lead to delayed clotting of the blood due to a lack of Vitamin K.

They can also cause constipation, but this usually resolves on continued usage.

Colifoam Enema

What is it?

Colifoam is a steroid foam (hydrocortisone) in an aerosol canister which delivers a metered dose.

What is it used for?

It is used in the treatment of mild to moderate UC affecting the rectum and sigmoid colon. The foam acts directly on the area of inflammation.

How do I take it?

Insert lubricated spout into the back passage whilst lying on your left hand side and apply 1-2 metered doses as directed by the doctor

If you forget to apply a dose do not worry, but be sure to apply the next dose at the right time. You must complete the course that the doctor has prescribed and not stop the medicine because you are feeling better.

It is usually used 1-2 times daily for 2-4 weeks, then on alternate days before stopping.

Are there any precautions?

Colifoam may be used in small amounts for short periods of time in pregnancy and in children with inflammatory bowel disease.

You should let your doctor know if:

you are pregnant or thinking of becoming pregnant
you are suffering from an infection (e.g. thrush, a viral infection or you have TB)
if you are allergic to any medications

It should not be used if:

you have a known obstruction (e.g. stricture)
you have an abscess
you have had recent surgery to the lower bowel
you have a bowel infection

Are there any side effects?

Side effects are relatively rare as the steroid drug acts locally on the site of inflammation and very little is absorbed into the body.

Corticosteroids

What are they?

These are groups of steroid hormones, (e.g. cortisol); produced by the outer layer (cortex) of the adrenal glands, which are located on top of the kidneys.
Synthetic preparations are usually more powerful than the normally occurring hormones and are given to enhance their effect on disease in the body. These include:

Hydrocortisone
Dexamethasone
Prednisolone
Budesonide

What are they used for?

They are used mainly to control inflammation and the immune response in the body. They can also be used to replace low levels of naturally occurring steroids in the body when production of these is insufficient.

How do I take them?

They can be given in various forms depending on the severity of the condition and the site of the disease:

1. Tablet (e.g. Prednisolone, Dexamethasone)
This is swallowed and may be sugar coated or uncoated. It is absorbed through the stomach into the bloodstream and so has an effect throughout the body.

2. Injection (e.g. Hydrocortisone, Dexamethasone, Methylprednisolone)
The steroid is injected into a vein or muscle to allow a more rapid effect. Again, it has effects throughout the body. This form of treatment is used in severe cases of inflammatory bowel disease.

3. Topical preparations
These are applied directly to the area to be treated, thus causing minimal effects on other areas of the body. As treatment is direct, dosage is usually lower. Examples of these preparations include:

Steroid enemas and suppositories, (e.g. Predsol, Predfoam, Colofoam).
Hydrocortisone anal and rectal creams.
5-Aminosalicylic Acid enemas and suppositories, (e.g. Asacol, Pentasa).

At the beginning of treatment it is usual to give a large dose to achieve remission. Once the disease is under control the dosage can gradually be reduced to prevent side effects.

You should not suddenly stop corticosteroids if you have been taking them for more than a few days as they usually cause the body's own adrenal gland to stop working. Sudden withdrawal may result in steroid deficiency, which can be dangerous, causing fatigue, vomiting and diarrhoea. Your doctor will advise you on how to reduce the dosage safely.

Are there any precautions?

You should avoid contact with chicken pox or Herpes zoster (shingles) whilst taking treatment and for three months after stopping it. If you should come into contact with these diseases, you may need to be given an injection of immunogloblins (antibodies against shingles or chicken pox) as your own immunity may be greatly reduced due to the steroids. If you have had the diseases or have been immunised against them you need not worry.

You must let your doctor know all the medications you are taking as steroids can also have an effect on these, especially:

Aspirin or other non-steroidal anti-inflammatory drugs e.g. Voltarol.
Warfarin.
Diabetic tablets.
Blood pressure tablets.
Diuretics (water tablets).

Use in pregnancy

Studies have shown that the reported incidence of increased risk of spontaneous miscarriage, stillborn babies and premature labour is likely to be secondary to the disease rather than to the treatment. Active disease itself can be harmful to the foetus therefore controlling the disease may outweigh any potential side effects from these drugs.

Are there any side effects?

There are many side effects, which may occur from taking steroids, and the aim of treatment is to achieve maximum benefit with minimum side effects. Side effects most often occur when doses greater than 12.5 mg are given daily for prolonged periods. The doctor should monitor such doses very closely.

Courses of drugs tend to be short and sharp and often in combination with other drugs in order to further reduce the likelihood of long-term side effects. However, some of the side effects, which may occur, could include:

Excessive weight gain (referral to a dietitian may help).
The face becomes reddened and rounded (moon face).
Suppression of growth in children.
Raised blood pressure.
Fluid retention due to increased sodium (a salt) in the body.
Muscle weakness due to potassium loss (a salt) from the blood.
Thinning of the bones (osteoporosis).
Raised blood sugar causing diabetes.
Mood changes (depression or euphoria).
Stomach ulcers.
Cataracts.
Increased risk of infection.
Increase in body hair (hirsutism).

Entocort (Budesonide)

What is it?

Entocort is a capsule containing Budesonide which is a glucocorticosteroid, previously successful in the treatment of asthma in an inhaled formula due to its anti-inflammatory properties. It is released above pH 5.5, (i.e. out of the stomach), and its optimum effect is in the terminal ileum and caecum (60-70%) before being distributed throughout the large intestine. It has the advantage over other corticosteroids of being broken down almost completely on its first pass through the liver, and thus it is much less likely to get into the general circulation and cause side-effects. On the other hand it is therefore only effective in treating IBD in that limited part of the bowel where it is released, that is the ileo-caecal area.

What is it used for?

Trials have shown it to be as effective as oral prednisolone in causing a remission of mild to moderate CD affecting the ileum and/or ascending colon. Trials for usage in long-term maintenance are planned but, as yet, it is indicated for the acute phase only.

How do I take it?

Entocort is presented in a hard gelatin capsule protecting it from the acid in the stomach and allowing a controlled release. The tablets should be swallowed whole with plenty of water and is generally unaffected by food.

If taking cholestyramine (Questran) absorption may be affected, therefore it should be taken one hour before this.

Are there any precautions?

Blood levels of Entocort are significantly lower than they would be with conventional steroid treatment but should still be used with caution in certain circumstances, and you should let the doctor know if you have any of the following:

Tuberculosis.
High blood pressure.
Diabetes.
Osteoporosis (thinning of the bones).
Stomach ulcers.
Eye problems such as glaucoma or cataracts.
Chicken pox and measles.
Someone in the family with diabetes or glaucoma.

You should let the doctor know if you are pregnant or breastfeeding. It is not known whether Budesonide passes into breast milk.

No studies have been performed on usage in childhood CD

Are there any side effects?

Steroid side effects of Budesonide have been reported to be very much lower than conventional steroids as the dose is delivered in a controlled release and has a topical effect on a specific site (greater than 95% of the drug), rather than being absorbed into the blood stream first and thus having a general effect on the body. Once broken down in the liver, the amount of steroid available in the system is less than 10% of the original drug. Side effects are less than half those seen with conventional steroids.

However, some adverse reactions have been reported other than effects of steroids, and these could include:

Indigestion
Muscle cramps
Tremor
Palpitations
Nervousness
Blurred vision
Skin rashes
Period problems

However, many of these problems were also found in placebo treatment during clinical trials.

Fybogel

What is it?

Fybogel is made up of granules of effervescent i ispaghula husk. It is free from gluten and sugar. It is available in plain, lemon or orange flavours.

What is it used for?

It is a bulk-forming laxative used to relieve constipation. It works by increasing the mass of stool which then presses against the intestinal wall stimulating peristalsis, thus promoting a bowel motions.

It may take a few days before it is fully effective and sufficient bulk has built up to cause a bowel motion. This is quite usual and you should continue with the treatment.

How do I take it?

One sachet is emptied into a large tumbler full of water, rapidly stirred and drunk immediately, (if left to stand it will solidify into a thick gel). For greater effect a further glass of water should follow.

The sachets should be taken twice daily following breakfast and the evening meal.

The dose may be adjusted once a regular soft stool is achieved, i.e. one sachet daily or 1-2 sachets on alternate days, and continued as necessary.

Are there any precautions?

Insufficient fluid intake with Fybogel can occasionally lead to obstruction of the bowel. It should not be taken immediately before bedtime when fluid consumption is normally considerably reduced.

Are there any side effects?

As Fybogel is sometimes fermented by bacteria in the colon it may lead to flatulence and bloating.

It may also cause:

Abdominal distension.
Obstruction (if inadequate fluids are taken).

Infliximab (Remicade)

What is it?

Tumour necrosis factor alpha (TNFa) is a potent pro-inflammatory cytokine - a substance produced by the white blood cells in response to inflammation leading to ulceration & tissue damage. Infliximab is an antibody (a special kind of protein), which binds and neutralises TNFa.

Indications for use

Infliximab is licensed for the treatment of moderate to severely active CD not responding to steroids and/or immunosuppressants, or for fistulizing disease

How is it given?

It is given as an infusion into the vein over a period of approximately two hours. During this time you will be closely monitored in case of possible infusion reactions. It will be necessary to check the blood pressure, pulse, and temperature at half hourly intervals during the infusion and for around one or two hours afterwards.

The dose is calculated according to body weight (5 mg/kg). It is given as a single infusion or may be repeated in eight weekly cycles if signs of relapse occur.

To heal fistulae the same dosage is given, but repeated at two and six weeks after the initial infusion.

Recent research has shown that infliximab is even more effective if it is given at regular intervals, every eight weeks for a full year.

What are the effects?

TNFais produced very early on in the so-called inflammatory chain and is responsible for many other events that occur afterwards. Thus, if TNFa is blocked, events leading to tissue damage may be prevented.

Evidence of a response to the treatment, with a reduction, or complete resolution of symptoms, is usually noted at around two to four weeks after the infusion, the benefits lasting for some eight to twelve weeks. A repeat infusion at this time can restore the initial benefits or enhance the effects if only a partial
response has been achieved. For some patients a single infusion may be all that is needed.

Will I still need to take my usual medication?

The answer is yes. Despite very promising results Infliximab is not a cure for CD. Once remission has been achieved this will be maintained by your previous medication, diet, or a combination of both.

Research has shown that patients taking drugs such as azathioprine, have a reduced incidence of relapse following treatment with Infliximab.

Are there any side effects?

Infliximab is a new treatment for CD and therefore the full safety profile remains unclear. However patients have been followed up in clinical trials for a period of two years in order to determine safety of treatment and re-treatment.

Patients with heart failure should not takeinfliximab. As TNFa is normally produced as part of the body's defence against infection, infliximab may allow infections to become more severe. This is particularly important in the case of tuberculosis (TB). Some people with past exposure to TB may find that the disease becomes reactivated, and all patients should have tests to exclude tubercule before treatment with infliximab is started. Sepsis may also occur. If you have lived in a region where histoplasmosis is common or if you have any disease that affects the nervous system you should tell you doctor before starting treatment.

Side effects which have occurred during or shortly after the infusion because of hypersensitivity have included:

Joint and muscle pain
Fever
Rash
Pruritis (itchy skin)
Facial, hand or lip swelling
Difficulty in swallowing
Sore throat and/or headache

Infusions may need to be slowed down, discontinued or antihistamine treatment given.

Other reported reactions during clinical trials include:

Viral infection
Fever
Headache
Vertigo/dizziness
Raised blood pressure
Flushing
Chest infection
Shortness of breath
Sinusitis
Diarrhoea
Abdominal pain
Nausea
Indigestion
Rash
Itchy/dry skin
Increased sweating
Chest pain
Fatigue

Other effects may occur due to an increased susceptibility to infection or masking of the normal signs of infection due to the blocking of TNF. Speak to your doctor or nurse immediately if you are concerned about any possible side affects you may be experiencing.

Occasionally patients may develop antibodies to the antibody, which may cause allergic reactions. These will need to be dealt with accordingly and treatment with Infliximab stopped.

During clinical trials, one case of lymphoma (cancer of the lymph glands) has been reported nine months after treatment in a patient with longstanding CD and a long history of treatment with steroids and immunosuppressants. This may have been due to the illness itself rather than Infliximab as it is well within the reported incidence of lymphoma in CD. However, this highlights the need for continued monitoring.

Infliximab should be reserved for unresponsive disease.

Although, these potential side effects might seem quite alarming, this treatment is prescribed for difficult disease which needs to be controlled in order to prevent further complications from developing. If you are anxious about any aspect of your treatment discuss these with the doctor or nurse as soon as possible.

Are there any contraindications?

Infliximab must not be given if there is evidence of infection or the presence of abscesses, or if there have been hypersensitivity reactions on previous infusions.

6-mercaptopurine (6-MP)(Puri-Nethol)

This drug is a metabolite of azathioprine - indeed azathioprine is converted to 6-mercaptopurine in the body. For this reason some physicians prefer to use 6-MP rather than azathioprine itself. It is given in a slightly lower dose (1 - 1.5 mg/kg body weight each day) and some believe it is less likely than azathioprineto produce side-effects. The clinical indications for use are identical to azathioprine and the precautions and possible side-effects are also the same.

Methotrexate

What is it?

Methotrexate is a drug that affects the immune system (i.e. an immunosuppressant) and is useful for its steroid sparing effect.

Indications for use

The main use is in treating some types of cancer, but it has been used in chronic inflammatory conditions, such as rheumatoid arthritis, with very beneficial effects. Its use in other conditions, such as Crohn's disease and ulcerative colitis has also proved beneficial in some cases, particularly those cases not responding to other immunosuppressants.

How is it taken?

It is usually taken in tablet form on a weekly basis. It should be taken with or after food. The tablets should be swallowed whole and not crushed or chewed. Methotrexate can also be given by injection.

The initial starting dose will usually be 7.5 mg weekly. This may be increased by 2.5-5 mg on a monthly basis up to a maximum of 20 mg weekly, depending on how you respond.

It is possible to have a course of 3 treatments in divided doses of 2.5 mg at 12 hourly intervals once weekly. This may be better tolerated if side effects have occurred. A test dose of 5-10 mg may be given one week prior to the start of your treatment to see if any reactions occur.

The lowest effective dose will be given to you but you will not notice a difference straight away. A response can usually be expected by 4-6 weeks, but this may take as long as 12 weeks.

Monitoring

Due to the potentially serious adverse effects on other systems in the body, it is extremely important that you have regular blood tests whilst taking the treatment. The type and frequency of monitoring should be as follows:

Full blood count and liver function tests every 2 weeks for the first 2 months then monthly thereafter. Inflammatory markers, such as ESR and CRP should be taken to assess response to treatment.
Urine should be tested regularly.
Results should be recorded in the monitoring booklet given to you by the doctor or nurse.

NB: Any abnormality on testing should be reported to the doctor or IBD nurse immediately for further advice.

Contraindications

Methotrexate should not be used if you have kidney problems or pre-existing liver disease. It is known to have harmful effects on ova and sperm; therefore it is extremely important that reliable contraceptive methods are used during treatment and for at least 6 months afterwards. It must never be taken in pregnancy or by breast-feeding women.

Are there any side effects?

It is possible that some side effects may occur during treatment. These may include some of the following:

Nausea
Loss of appetite
Mouth ulcers
Thinning of the hair
Abdominal discomfort
Diarrhoea
Headaches

Less commonly other effects may occur as a result of bone marrow suppression, such as:

A rash
Increased bruising
Increased tendency towards infections
Anaemia

Rarely, it may cause liver fibrosis/cirrhosis. If alcohol is avoided this has been proven to be rare. Acute inflammation or chronic fibrosis of the lungs may occur. If you get a dry cough in association with breathing difficulties and fever, contact the doctor immediately for further assessment.

Fertility may be affected, but this is reversible on stopping treatment.

Although this list of side effects may seem quite alarming, it does not mean that you will have all, or indeed any of them. The fact that your doctor has decided that this treatment is required to help control your symptoms means that you have a difficult disease that needs strong medication to keep it under control and therefore reduce the risks of complications and possibly avoid the need for surgery.

You should be reassured that you will be closely monitored whilst you are taking the treatment and if any side effects do arise that these will be dealt with accordingly.

Are there any special precautions?

Methotrexate interacts with some drugs so it is important that you tell your doctor about all your other medications so that these are taken into account. The following should be avoided whilst taking methotrexate:

Alcohol
Live vaccines
Anticonvulsants. (e.g phenytoin).
Non-steroidal anti-inflammatories [NSAIDS] and aspirin-like drugs.
Penicillins
Anti-malarial drugs
Cyclosporin
Drugs taken for gout

There may be other important drugs to avoid so please speak to your doctor before starting any new treatment.

Methylcellulose (Celevac)

What is it?

Celevac is a tablet of methylcellulose (a plant fibre), which absorb water and swell into a soft gel.

What is it used for?

It is used as a 'bulking' agent in the treatment of diarrhoea or constipation often associated with inflammatory bowel disease. It has the advantage of not being fermented by colonic bacteria and is therefore less likely to lead to excess wind.

How do I take it?

Tablets are usually chewed and swallowed with varying amounts of water depending on usage for constipation or diarrhoea:
a) Constipation
3-6 tablets twice daily with a large amount of liquid (at least 300 ml). This forms a soft bulk in the bowel which is easy to pass. The dose can be reduced when normal bowel movements occur.
b) Diarrhoea
3-6 tablets taken twice daily with minimal liquid (i.e. enough to swallow the tablets with). Liquid should be avoided for half an hour before and after each dose. The dose can be adjusted to give the motions the required consistency.

It may be used in the same way to keep control of colostomies and ileostomies

Control of colostomy and ileostomy is as above.

Are there any precautions?

You should not take Celevac if you have a narrowing of the bowel which may obstruct with treatment.

Are there any side effects?

There are no reported side effects from taking Celevac, but abdominal swelling may occur if levels build up in the bowel due to overdosing.

Metronidazole (Flagyl)

What is it?

Flagyl is an antibiotic used to treat infections caused by anaerobic bacteria, (i.e. bacteria not requiring oxygen to survive), particularly in the bowel.

What is it used for?

It has been shown to be effective in the treatment of anal complications of CD, such as infected fistulae and fissures. It has also been shown to be as effective as sulfasalazine in reducing mild to moderate inflammation in CD.

How do I take it?

It can be taken as a:

Tablet an initial 'loading dose' is given, then 1 tablet 3 times daily
Injection it can be given by intravenous infusion followed by tablets
Suppository it can be given via the rectum

Are there any special precautions?

Flagyl interacts with certain drugs such as:

oral anticoagulants (drugs that thin the blood)
Phenobarbitone (an anti-epileptic drug)
Lithium (an antidepressant drug)

Therefore careful monitoring during treatment may be required.

You should not drink alcohol when taking Flagyl as Flagyl blocks the breakdown of alcohol in the liver, and this can lead to very unpleasant symptoms.

Studies have shown that the drug has no adverse effect in pregnancy on the developing foetus and the small amounts found in breast milk are far less than the normal paediatric dose and is unlikely to cause harm.

Are there any side effects?

Most people are able to take Flagyl without major problems, but some of the following side effects may occur:

Nausea and vomiting
Diarrhoea
Abdominal pain
Furred tongue and unpleasant taste in the mouth
Reduced white cells in the blood
Peripheral neuropathy (numbness and tingling in the fingers and toes) has been reported in long-term treatment

Side effects are usually reversible on stopping the drug, although peripheral neuropathy can occasionally persist.

Mycophenolate Mofetil

What is it?

Mycophenolate is a drug that affects the immune response in the body (i.e. an immunosuppressant).

Indications for use

The main use is in organ transplantation for prevention of donor organ rejection. It is being increasingly used to treat severe active inflammation in the bowel that does not respond to anti-inflammatory (5-ASA) drugs and also in steroid refractory or dependent disease. It is also used for patients who are allergic or sensitive to Azathioprine.

How is it taken?

It is taken by mouth in either tablet or capsule form. The dose is usually 1 g twice daily.

Monitoring

Due to the potential risk of bone marrow suppression it is extremely important to have regular blood checks whilst taking the medication. The type and frequency of monitoring should be as follows:

FBC+LFT'S on a weekly basis for 1 month, then 2 weekly for 2 months and monthly thereafter if all remains well during the first year.

NB: signs of bone marrow suppression e.g. infection [particularly opportunistic organisms, such as cytomegalovirus] and unexplained bruising or bleeding, should be reported to the doctor or IBD nurse immediately.

Contraindications

Pregnancy must be excluded prior to treatment and conception avoided until 6 weeks after treatment has finished. Breast feeding is also contraindicated.

Are there any side effects?

It is possible that side effects may occur during treatment. These may include some of the following:

GI upsets e.g. diarrhoea, constipation, nausea/vomiting, indigestion and abdominal pain
Disturbances in salt and water balance leading to raised blood pressure or swelling of the feet and ankles
Breathing difficulties
Chest pain
Cough
Runny nose
Dizziness
Poor sleep pattern
Headaches
Tremors
Infection
Blood disorders e.g. reduced white cells (leukopoenia), anaemia or reduced platelets (thrombocytopaenia)
Raised blood sugar
Raised cholesterol
Decreased kidney function
Acne

Other side effects may occur, but less frequently, such as:

Low blood sugars
GI perforation
Abnormal liver function
Hepatitis (inflammation of the liver)
Inflamed gums
Mouth ulcers
Reduced blood pressure
Cardiac arrhythmias(abnormal beats)
Weight gain

Although this list of possible side effects may seem quite alarming it does not mean that you will have all, or indeed any of them. The fact that your doctor has decided that this medication is required to help control your symptoms means that you have difficult disease that needs strong medication to bring it under control and therefore reduce the risks of complications and possibly avoid the need for surgery.

You should be reassured that you will be closely monitored whilst taking this treatment and that if side effects do arise that these will be dealt with accordingly.

Your compliance with the monitoring programme is essential in the safety of your treatment.

Natalizumab

Natalizumab is a specific humanised monoclonal antibody, which inhibits a4-integrins.

These affect the migration of leucocytes from the circulation into the tissues to set up inflammatory reactions.

A multi-centre trial of its effectiveness in severe Crohn's disease was performed. After 2 infusions, 71% of patients showed a response and 44% achieved clinical remission at 6 weeks. Inflammatory protein levels in the blood improved.

The long term effectiveness is as yet unknown and this remains an experimental treatment, which is not as yet generally available.

Normacol

What is it?

Normacol is made up of granules of gluten-free sterculia. It has the appearance of 'bird seed.'

What is it used for?

It is a bulk-forming laxative used to relieve constipation. It works by increasing the mass of stool which presses on the intestinal wall stimulating peristalsis, thus promoting a bowel motions.

It may take a few days before sufficient bulk has built up to cause a bowel movement. This is quite usual and you should continue with the treatment.

How do I take it?

5-10 ml is taken twice daily following breakfast and the evening meal. The granules are swallowed whole with 1-2 large glasses of water. It can also be sprinkled on food or taken in yoghurt etc. to help it 'slip' down.

The dose can be adjusted once a regular soft stool has been achieved.

Are there any precautions?

Insufficient fluid intake can occasionally lead to obstruction of the bowel. Fluid intake should usually be at least one and a half litres daily (and not limited to tea and coffee).

It should not be taken immediately before bedtime when fluid consumption is normally considerably reduced.

Are there any side effects?

Normacol may cause:

Flatulence (wind)
Abdominal distension
Obstruction (if inadequate fluids are taken).

Olsalazine (Dipentum)

What is it?

Olsalazine consists of 2 molecules of 5-ASA linked by a chemical bond which is split in the lower colon by colonic bacteria.

What is it used for?

It is used to treat and maintain remission in acute mild to moderate UC.

How do I take them?

Olsalazine is presented in tablet form and is to be swallowed whole with plenty of water and with food. Watery diarrhoea is a common side effect but can be reduced if the dose is increased slowly. Once the symptoms have been controlled, you will be given a lower maintenance dose. Although you might feel better, it is important to continue taking the medication as instructed to prevent the symptoms from coming back.

Are there any special precautions?

You should not take this drug if you are allergic to aspirin. It is not recommended for use if you have poorly functioning kidneys.

Use in pregnancy

It is safe to take olsalazine during pregnancy as it is better for both you and your baby to treat active disease vigorously and effectively. The lowest effective dose will always be used.

Are there any side effects?

Olsalazine is generally well tolerated and side effects are not often reported as the 5-ASA molecule remains intact until it reaches the colon (99%). However, some effects which may occur could include:

Watery diarrhoea (common, occurs in around 15% of patients)
Headache
Nausea
Indigestion
Joint pains
Rash (not significant)

It may also cause a worsening of the colitis in a very few sensitive people.

Side effects tend to be related to the dose and can be minimised by gradually building up the dose. If side effects continue, the drug should be stopped.

NB: If you have any unexplained bleeding, bruising, sore throat, fever or generally feel unwell whilst taking the medication, you should see your doctor for a blood test and further advice who may stop treatment.

Pentasa

What is it?

Pentasa is a slow release tablet form of mesalazine containing ethylcellulose coated granules of 5-aminosalicylic acid which are broken down in the stomach releasing the granules throughout the small and large intestine. Unlike other drugs in the group, it is unaffected by changes in the gut flora, pH of the surroundings or transit time (speed in which a substance takes to pass through the intestines).

What is it used for?

Pentasa is used for the treatment and maintenance of remission in UC and CD. Due to its early breakdown in the stomach, it is particularly useful in small bowel Crohn's disease.

How do I take them?

Pentasa is presented in the following forms:

Slow release tablets These should be taken with plenty of water and swallowed whole. They can be put into a small amount of water if you have difficulty in swallowing whole tablets. This causes dispersion of the granules but they do not completely dissolve. Alternatively 1g sachets are now available. (Tablets should be stored at room temperature away from direct light).
Enema These are used to act directly on inflammation affecting the left side of the colon. This is given at bedtime. It has been shown to reach inflammation beyond the splenic flexure in 67% of cases. (Enemas should be stored at room temperature out of direct light and used immediately after opening).
Suppositories These are used to act directly on inflammation affecting the rectum and sigmoid colon. Taken once daily, after a bowel motion.

The above medications will be prescribed according to the site and severity of the inflammation and may be used in combination.
Once symptoms have been controlled, you will be given a lower maintenance dose. Although you might feel better, you must continue taking the medication as instructed to prevent the symptoms from coming back.

Are there any special precautions?

You should not take Pentasa if you are allergic to aspirin. It is not recommended if the kidneys are not working properly.

Pentasa can be used safely during pregnancy. It is better for both you and your baby that active disease is treated vigorously and effectively. The lowest effective dose will always be used. Negligible amounts may also be detected in breast milk but it is safe to continue.

Are there any side effects?

Because of its slow release form, Pentasa has had few reported side effects, the most common of these being:

Diarrhoea
Nausea
Headaches

It may also cause a worsening of the colitis in sensitive people. If side effects occur, the dose can be reduced and gradually built up to tolerance levels. If they continue, the drug should be stopped.

NB: If you have any unexplained bleeding, bruising, sore throat, fever or generally feel unwell taking the medication, you should see your doctor for a blood test and further advice stop who may stop treatment.

Predfoam Enemas

What is it?

Predfoam is a steroid foam containing prednisolone in a 20mg metered dose.

What is it used for?

It is used in the treatment of left-sided colitis and rectal inflammation (proctitis).

How do I use it?

Whilst lying on your left side, the lubricated applicator (disposable) is inserted through the anus into the rectum and the foam is released in a metered dose.

It is applied 1 - 2 times daily for 2 weeks and continued for a further 2 weeks if effective. You should continue taking the medication, even if you feel better, until instructed otherwise by your doctor.

Are there any precautions?

It can generally be used safely and effectively to treat all cases of left-sided disease, even in pregnancy. However, Predfoam should not be used if:

You have an obstruction such as a stricture
You have a bowel infection
You have a fistula
You have previously reacted badly to steroids

Are there any side effects?

Side effects are relatively rare as the steroid drug acts locally on the site of inflammation and very little is absorbed into the body. However, it may cause similar effects to those of steroids taken by mouth, such as:

High blood pressure
Diabetes
Osteoporosis
Mood changes
Weight gain

Predsol Enemas

What is it?

This is a steroid enema in the form of a liquid containing prednisolone 20 mg.

What is it used for?

It is used in the treatment of ulcerative colitis and is usually given at night time. The enema is retained in the bowel acting directly on the inflamed tissue. It is used in the treatment of left-sided colitis or rectal inflammation.

How do I use it?

For the best results, you should be on your left side in bed with the end of the bed propped up if possible to help you hold the enema in better. Lubricate and insert the applicator through the anus and up into the rectum. Squeeze the bag gently ensuring all the liquid is expelled. Ideally it is held in the bowel overnight and any residual liquid will be passed when going to the toilet in the morning. However, if this is not possible, you should try and hold the liquid in for at least one hour so that it can act with effect on the inflamed area.

It should not cause you to have a bowel motion but you may find it difficult to hold if your bowel is very inflamed.
It may help to warm the enemas before use by immersing the unopened container in a jug of warm water.
To ensure that the enema reaches as high as possible, it will help to roll over on to your other side once the fluid is instilled into the rectum.

Are there any precautions?

You should not use this enema if you have a bowel infection.
Predsol can be used with caution during pregnancy if the doctor feels that the benefits outweigh any potential hazards.

Are there any side effects?

High blood pressure
Diabetes
Osteoporosis
Mood changes
Weight gain

Other preparations of Predsol

Predsol suppositories - used in treatment of proctitis and anal complications of CD. The same precautions apply. The suppositories are to be inserted morning and evening after having the bowels opened. Length of treatment will be determined by the doctor but will usually be for approximately one month.

Sulfasalazine (Salazopyrine) - Azulfidine in USA

What is it?

It is a chemical combination of a substance called sulphapyridine (a sulpha antibiotic) and 5-aminosalicylic acid (5-ASA, an aspirin-like compound) linked by a chemical bond which is split in the colon by colonic bacteria, releasing the active 5-ASA.

The sulfapyridine ensures the active ingredient of the drug (5-ASA) reaches the colon without being broken down in the small intestine.

What is it used for?

It is used for the treatment and maintenance of remission in ulcerative colitis and CD affecting the large intestine.

How do I take them?

Salazopyrin is presented in several forms:

Tablet (oval shaped and yellow (enteric coated) or brown coloured). These are to be swallowed whole with plenty of water, and are available coated or uncoated.
Suspension Orange-lemon flavoured liquid.
Enema The enemas are used to act directly on the inflammation in left-sided colitis. They should be taken last thing at night and to be retained for 1 hour.
Suppository These act directly on recto-sigmoid inflammation taken morning and night following a bowel movement.

The above medications will be prescribed according to the site and severity of the inflammation and may be used in combination.

Once symptoms have been controlled, you will be given a lower maintenance dose. Although you might feel better, you must continue taking the medication as instructed to prevent the symptoms from coming back.

Are there any precautions?

You should not take this drug if you are allergic to sulphonamides or aspirin. A blood test should be taken every month for 5 months after starting treatment.

Are there any side effects?

Salazopyrin has been known to cause certain side effects in some people. However, some of these tend to only occur when starting the treatment and should soon disappear once tolerance is established, e.g. nausea and headaches. They are usually dose related and it may help to start with a lower dose and build it up.

Most patients experiencing gastric problems with uncoated Salazopyrin improve when switched to the enteric coated version. Other reactions are due to hypersensitivity patients should contact their doctor immediately, e.g. vomiting, stomach pain, skin rashes.

(Unpleasant side effects tend to be associated with the sulfapyridine portion of the drug).

Other reported side effects include:

Fever
Anaemia, (possibly due to impaired folic acid absorption)
Low white blood cells
Reduced sperm production (reversible on stopping treatment)

It rarely causes:

Inflammation of the pancreas.
Inflammation of the liver.
Kidney damage.
A worsening of the symptoms of colitis.

Use in pregnancy

Long-term clinical use and experimental studies have shown no adverse effects during pregnancy and the developing foetus.

A small amount does pass into breast milk, but should not cause any harm to the baby.

Other information

Urine may become orange coloured.
Soft contact lenses may become stained.
In the USA it is known as Azulfidine.
It is recommended that folic acid supplements are taken.

NB: If you have any unexplained bleeding, bruising, sore throat, fever or generally feel unwell whilst taking the treatment, you should see your doctor for a blood test and further advice who may stop the treatment.