Questions about AEDs (part 2)

Questions about AEDs (part two)

Taking and monitoring AEDs

In this article we answer some of the most commonly asked questions about taking AEDs, including:

• To take or not to take?
• How often should AEDs be taken each day?
• What is the average dose range of an AED?
• What is 'blood-level testing'?
• When you increase a dose, how long does it take to start working?
• What are side effects?
• Why do side effects happen?
• Do side effects always happen?
• What do terms like 'common' and 'rare' actually mean?
• Are the side effects the same for all AEDs?
• What should I do if I have side effects not listed in the patient information leaflet? 

To take or not to take?

One of the questions people often ask is: 'Will I have to take this medication for the rest of my life?' Read that sentence again. It’s interesting that they use the term ‘have to’.

The ‘old style’ of patient/doctor interaction was called adherence because patients were expected to stick to the course of treatment their doctor prescribed, without question. In this relationship the doctor ‘knew best’ and the patient ‘did as they were told’. In other words, the patient wasn’t really involved in making decisions about their treatment.

Today, many doctors recognise that people know a lot about their medical condition and want to play a part in any decisions about treating it. For some of us this approach can feel strange; obviously, a doctor has trained for years in medical school to learn about conditions and treatments whereas we, as patients, don’t have that training — so how can we know which treatment is right?

The basis of this new approach is called concordance, or informed decision-making, in which the doctor gives enough information about the options for treatment so that we can decide, in partnership with the doctor, what we want to do.

The keys to concordance are information and choice: knowing the risks and benefits of taking — or not taking — treatments so that together we can discuss the options and together decide what we want to do.

With regard to epilepsy and AEDs, weighing up the risks and benefits of taking or not taking treatments can include the following issues:

• the possible risks of taking AEDs, including side effects
• the possible benefits of taking AEDs, including stopping seizures
• the possible risks of not taking AEDs, including continuing to have seizures (and accidents and injuries because of them)
• the possible benefits of not taking AEDs, including not having side effects.

How important these risks and benefits are will vary from one person to another and will depend on individual circumstances: the risk of accidents or injuries due to seizures will depend on the type of seizures you have, how often they happen, and how they affect you; the effects of taking AEDs will vary depending on the AED and how your body responds to it. Ultimately the decision is yours, but having the input and support from your doctors can help you to weigh up these points and come to a decision that you are happy with. Taking part in making this choice may also help you to feel more in control, which might be important if your epilepsy makes you feel you have lost some control over your life.

How often should AEDs be taken each day?

How often you take an AED (once, twice or possibly three times each day) depends on its half-life. The half-life of a drug is the length of time it takes for the original amount of the drug to reduce by half. The half-life is used to measure the concentration of the drug in the blood, which is not exactly the same as the dose of drug you take.

When you take a drug it takes time to be absorbed into your blood. When it is in your blood the amount can be measured; this is expressed as the drug’s ‘concentration’ or ‘level’, which relates to how much of the active ingredient of the drug is available to work. Once the drug has done its work it becomes metabolised (broken down) and eliminated (removed) from the body. In simple terms, when the drug reaches its half-life half of it is still in the blood and half of it has been metabolised and eliminated.

The aim of taking AEDs regularly is to keep the level in the blood as stable as possible. Some AEDs have a half-life of 24 hours so they are taken once a day. Those that have a half-life of 12 hours are taken twice a day, and those with a half-life of eight hours are taken three times a day. The shorter the half-life of the AED the more often it is taken.

What is the average dose range of an AED?

When considering how much medication someone takes we look at two different things. Firstly, we look at their ‘average’ dose — this is a measure of the number of tablets they take and how much active ingredient each tablet contains. For example, for an adult an average dose range for carbamazepine is 600–2000mg per day and for sodium valproate it is 400–2000mg per day. But how helpful is this? These figures are a very general guide but they are not individualised to each person: some people may have their seizures controlled on a dose lower than the bottom dose or higher than the top dose.

The second way of monitoring medication is to look at the amount of an AED in the blood (see What is ‘blood-level testing’?, below) and compare this to a reference range. The reference range is a range of concentrations of an AED within which most people will get a benefit from the drug (that is, it will stop the seizures). Below the reference range the drug is unlikely to work (that is, it will not stop the seizures) whereas above it, toxic effects (that is, reactions because the dose is too high) are likely to happen. Again, this is a general guide and not specific to an individual.

By monitoring drug levels in an individual and seeing what amount of an AED gives them the best seizure control, it is possible to work out an individualised therapeutic range for them. This range will vary from one person to another but will often fall within the general reference range for that AED. 

What is ‘blood-level testing’?

Blood-level testing, or therapeutic drug monitoring (TDM), is a system of monitoring the AED levels in an individual to help manage their epilepsy treatment.

TDM involves taking blood samples to measure the amount of the drug in the blood that is ‘available’ to work (its bioavailability). So this is a good way of measuring how much of the drug your body is getting. This is not the same as looking at how much of the drug you take (that is, your daily dose), although they are connected: the higher the dose you take the more you would expect to be in your blood.

Although we call it ‘blood-level’ testing it is sometimes also referred to as ‘plasmalevel’ or ‘serum-level’ testing because the drug is measured in the liquid part of the blood (the plasma or serum) and not the blood cells.

At the moment blood-level testing is not done very often, but there are many situations in which it can help to manage epilepsy treatment. For example, it can be used to see if you are getting the right amount of a drug for you, or if you are taking toxic amounts of drugs, or to monitor how different situations affect your medication (for example, if you are a woman and you become pregnant, or you start  taking medication for another condition which might affect your AEDs). 

When you increase a dose, how long does it take to start working?

This varies from one AED to another and depends on the half-life of the drug. Generally, you can see the effect of an increase in five half-lives’ time, so if the half-life of the AED is 24 hours you will see the effect five days (that is, 5 x 24 hours) later. If the half-life is 12 hours you will see the effect two-and-a-half days (that is, 5 x 12 hours) later. 

Side effects

One of the biggest concerns people have when taking medication is the risk of side effects. But what, exactly, are side effects, why do they happen, and will you always get them?

What are side effects?

Side effects (also called adverse drug reactions) are the unexpected or unintended effects of a drug. Generally, these are not the effects you want to happen. However, while some side effects (for example, feeling tired or drowsy) may be unwelcome, some can have a beneficial effect (for example, by reducing your appetite if you are overweight, or by lowering your cholesterol).

Why do side effects happen?

When you take a prescribed drug you are obviously taking it for a reason, which is to make something happen such as preventing a condition or treating a symptom. The aim of AEDs is to stop seizures happening. But when you take a drug — any drug — there is also a possibility of side effects.

Medication usually needs to get into your body, and around it, in your bloodstream to reach the area it needs to work on (the so-called site of action) before it is removed from the body. As the medication makes this journey it can have other, sometimes unwelcome, effects.

Do side effects always happen?

The list of side effects for any drug, including AEDs, can be very long and quite off-putting. But side effects are only possible effects: they do not always happen. Generally, most people take drugs without having serious side effects (that is, side effects that mean they want, or need, to stop taking the drug). Whether these side effects happen or not depends on the individual because different people can respond differently to the same drug.

Patient information leaflets use terms like ‘common' and ‘rare’. But what do these terms actually mean?

These terms are the same for all drugs and refer to the likelihood that a side effect will happen. This likelihood is shown by how many people will get it:

• Very common means that more than one-in-10 people will get it
• Common means that one-in-100 to one-in-10 people will get it
• Occasional means that one-in-1,000 to one-in-100 people will get it
• Rare means that less than one-in-1,000 people will get it
• Very rare means that less than one-in-10,000 people will get it
• Extremely rare means that less than one-in-100,000 people will get it

These terms tell you how many people are likely to get the side effect, but they cannot tell you how likely you are to get it.

Knowing what these terms actually mean may help you to put side effects into perspective. This can be helpful when you are making decisions about taking — or not taking — medication.

Are side effects the same for all AEDs?

No, they vary from one drug to another. When drugs are developed they are tested on many people and the common side effects are listed on the drug’s patient information leaflet (PIL). If the side effects are very serious the drug may not continue to be developed.

Although the tests are done on many people, once a drug is licensed and prescribed it may be used by thousands of people over long periods of time. Some side effects, particularly those that are extremely rare or ‘idiosyncratic’ (that is, unique to you) may not have come to light during the trials and may not be seen until the drug is being widely used. Also, some side effects only happen if the drug is taken over a very long period of time, possibly over many years or decades, and so will not be seen during the trials.

What should I do if I have a side effect that is not listed in the PIL?

If you have a side effect that is not listed in the drug’s PIL you can report it to the Medicines and Healthcare products Regulatory Agency (MHRA), the government agency which makes sure that drugs work and are safe to use. The MHRA runs the Yellow Card scheme for reporting side effects from drugs, including prescription drugs, over-the-counter medicines and herbal remedies. If you think you have a side effect from a drug you can complete a Yellow Card by:

• asking your pharmacist or GP for one
• calling the Yellow Card hotline on 0808 100 3352
• going to www.mhra.gov.uk and clicking the Yellow Card link on the side bar.

The MHRA looks at all the side effects reported through this scheme and, if necessary, can take action — for example, by making sure that a new side effect is listed in the PIL, or by issuing a warning to particular people who may experience the side effect. 

Glossary

Active ingredient: the chemical compound in a drug that makes it work for the reason you take it. For example, the active ingredient in Nurofen® is ibuprofen.

Bioavailability: this refers to the presence in your body of the active ingredient of a drug that is ‘available to use’ where it is needed (with AEDs, for instance, this is in the brain).

Half-life: the time taken for the amount of the active ingredient of a drug in the blood to reduce by half.

Medicines and Healthcare products Regulatory Agency (MHRA) — the organisation that licenses and regulates medicines in the UK. It makes sure that these products work and are safe to use.

Patient information leaflet (PIL): the leaflet that comes with every drug which says what the drug is, how it should be taken and what the possible side effects are.

Reference range: the range of drug concentrations in the blood below which the AED is unlikely to work and above which toxic effects are likely to occur.

Side effects: an unintended effect of any medication. Side effects are not the expected action of the medication (that is, the reason you take it). Also called ‘adverse effects’ (although they are not always unwelcome).

Site of action: the place in the body where the drug works. In the case of AEDs this is the brain.

Therapeutic drug monitoring (TDM): the method of measuring the levels of AEDs in the body. TDM is used to monitor the drug dose (the amount you take), its concentration (the amount in your body) and its effects (whether it stops seizures).

Individualised therapeutic range: the range of drug concentrations in the blood which relate to the best seizure control with the fewest side effects for an individual.

Further reading

For more information on TDM see ‘Anti-epileptic drugs — best practice guidelines for therapeutic drug monitoring: A position paper by the Subcommission on Therapeutic Drug Monitoring, ILAE Commission on Therapeutic Strategies’ (2008) by Patsalos PN, Berry DJ, Bourgeois BFD, Cloyd JC, Glauser TA, Johannessen SI, Leppik LE, Tomson T and Perucca E in the journal Epilepsia 49 (7): 1239–1276.

© Epilepsy Society
November 2008