Oct 29, 2016 - Folic acid, 5mg daily. Wendy found out this week that she is pregnant. She saw the consultant yesterday.
UPDATE Clinical chemistanddruggist.co.uk/update-plus
Module 1809
Problems with antiepileptic drugs
October Clinical: Case study: Childhood rashes
1 October*
Medicine use in older adults: Part one 15 October Medicine use in older adults: Part two 22 October
From this module you will learn:
●●How a change in prescription can cause problems for patients with epilepsy
Problems with antiepileptic scripts
●●That there can be serious changes in mood with some antiepileptic drugs
Conflict resolution
●●Some of the risks seen in pregnant women with epilepsy
29 October
Practical: 8 October
*Online-only for Update Plus subscribers
Trudy Thomas and Chris Chapman
Case study one
Could a revised prescription for Tegretol be the cause of a problem for this teenage customer? Mary, 18, is a student at the local college and was diagnosed with focal seizures with secondary generalisation when she was 16. Mary has been taking lamotrigine 250mg twice daily and Tegretol prolonged release 200mg twice daily for six months. However, this week she was seen by the neurologist and her Tegretol dose was increased. She presents a new prescription for Tegretol prolonged release at a dose of 300mg – once in the morning and 200mg at night – to the pharmacist, Gerald.
What are focal seizures with secondary generalisation? Focal – sometimes also called partial – seizures occur when there is uncontrolled electrical activity in a small area of the brain. How the seizure manifests itself depends on where in the brain it is focussed on. People remain conscious during focal seizures. However, in a complex focal seizure, they may not be aware of their surroundings and can be unresponsive if spoken to. They may also not remember the event afterwards. Sometimes a person will have a focal seizure Some prolonged release tablets can be split
Chemist+Druggist 29.10.2016
that will spread to the whole brain, resulting in a convulsive seizure, where consciousness is lost and the body undergoes rapid, rhythmic and often violent shaking. This is sometimes referred to as a secondary generalised seizure.
Gerald speaks to Mary and explains the new dose and the need to split her tablets, as well as emphasising that she should not chew the medication.
Is there an issue with Mary’s new prescription?
The following week, Mary comes back to the pharmacy and asks for some advice about a rash that started two days ago – just after she started using some new makeup. On examination, Gerald sees that Mary has a fine, itchy rash around her chin and cheeks. Gerald is aware of the rare, but serious, adverse skin effects associated with both lamotrigine and carbamazepine. This, alongside Mary’s recently increased Tegretol dose, causes him concern. The summary of medicine characteristics in the EMC states that serious and potentially life-threatening cutaneous reactions, including toxic epidermal necrolysis (TEN) and StevensJohnson syndrome (SJS), have been reported with carbamazepine. A quick visit to skin disease website dermnet.com to look at these conditions convinces Gerald that Mary has not got this kind of reaction at the moment. The EMC states that mild skin reactions can also occur with carbamazepine and are mostly transient and not hazardous, usually disappearing within a few days or weeks. However, it also states that differential diagnosis of this harmless reaction and the early signs of more serious skin reactions is difficult and that the patient should be kept under close surveillance, with advice to seek immediate help if the rash develops further. Gerald recommends that Mary does not apply anything to the rash, but to seek urgent medical help if it doesn’t improve or gets any worse in the next two days. Mary pops into the pharmacy three days later to report that the rash has all but gone.
Tegretol prolonged release tablets only come in 200mg and 400mg forms. However, the prescription indicates that Mary should be getting 300mg in the morning. Gerald is unsure whether it is appropriate to break Tegretol prolonged release tablets. However, he remembers that sustained release products can be formulated in different ways and that some can be broken without interfering with release characteristics, while others cannot. He looks at the tablets and can see they are scored, which makes him think they may be breakable. To confirm this, he looks in the electronic medicines compendium (EMC) (tinyurl.com/TegretolLeaflet) which says the tablets can be divided in half along the scored line. However, he notes the halved tablet should not be chewed.
The follow up
UPDATE Clinical chemistanddruggist.co.uk/update-plus
Looking for tips to get the most out of your MURs? Try C+D’s popular MUR Zone ▶▶ chemistanddruggist.co.uk/mur-zone
Case study two
Could epilepsy drugs be causing this increased aggression? Pharmacist Fiona is working when regular patient Terry, aged 31, arrives for his prescription. Terry is arguing with his partner Maria and, after much shouting, pushes past her and storms out. Maria is clearly upset and Fiona takes her into the consultation room. “I just don’t recognise him any more,” Maria sobs. “He used to be such a gentle man, but now he is so aggressive. Last week, he got into an argument with our eight-year-old son and Terry threatened to hit him. He was so angry, I thought I was going to have to call the police.” After further questioning, Fiona establishes that the change in Terry’s behaviour appears to have occurred three months ago – around the same time as he started his new epilepsy medication. “His seizures are so much better. It is the first medication that has really worked for him since he was diagnosed with epilepsy 13 years ago, after he had meningitis. Can medication actually change someone’s personality?” When Fiona looks at Terry’s patient medication record (PMR), it shows that he takes several antiepileptic drugs (AEDs):
●●Tegretol 400mg in the morning and 600mg at night, and lamotrigine 200mg twice daily, both of which he has been taking for more than two years. ●●Levetiracetam, which was introduced 12 weeks ago by the consultant at a dose of 250mg twice a day, and has been titrated up to its current dose of 1.5g twice a day.
Can you answer Maria’s question based on Terry’s medication? Aggression is a recognised side effect of a number of AEDs, including lamotrigine and levetiracetam. Terry has developed aggressive behaviour since starting levetiracetam, so this would appear to be the issue, although the effect of the combination of the two drugs may be exacerbating matters further. The incidence of behavioural side effects may be as high as 7‑10% for levetiracetam and 7% for lamotrigine. Behavioural effects are often poorly defined in studies, as aggression may be coded as “personality change”, “irritation” or “behaviour change”. This makes it difficult to isolate the true incidence of aggression. It is also hard
Aggression is a recognised side effect of a number of AEDs
to tell exactly how many patients experience this side effect; in some patients it may go unnoticed, particularly if the person with epilepsy also has learning disabilities. In other cases, aggression and behaviour change may be associated with a change or worsening of seizures themselves. The behavioural effects of AEDs differ, depending on the underlying condition being treated. For example, there is a different pattern when lamotrigine is used for bipolar disorder.
How do you know it was the medication that caused this change? As with Terry’s case, it is usually the patient’s partner or family who identify a change in behaviour – such as severe aggression – rather than the person with epilepsy themselves. The aggression side effect is dose-related and some patients – and their family or friends – are able to recognise the dose at which aggression became troublesome or apparent. Dose reduction may therefore be an option.
What are the next steps for Terry? Due to the noticeable change in his behaviour, Terry needs to be urgently referred back to the specialist who is managing his epilepsy before the situation worsens. Fiona should speak to Terry’s GP, ideally with Terry’s consent. However, there is a potential safeguarding issue here, so the referral may have to be done without consent or via Maria. AEDs should not be stopped suddenly because of the risk of rebound seizures, but it is necessary to urgently address this issue, due to Terry’s behaviour towards Maria and their son. If there is a significant delay in Terry getting an appointment with the specialist, his GP might consider speaking urgently on his behalf to agree a way forward.
Case study three
What are the risks of antiepileptics during pregnancy? Pharmacist Max is asked to see Wendy Campbell, 28, for whom he regularly dispenses antiepileptic medication. Max is aware Wendy has been trying for her second child. Over the past six months her medication, which originally included valproate and lamotrigine, has been gradually changed. She now takes only the following: ●●Levetiracetam 750mg, twice daily ●●Folic acid, 5mg daily. Wendy found out this week that she is pregnant. She saw the consultant yesterday. He is happy with everything and has reassured her
that her chances of having a normal, healthy baby are good. However, she has a few concerns. The epileptologist – an expert in epileptic seizures and seizure disorders – told her that she will, in all likelihood, stay on this medicine, at this dose, throughout her pregnancy. When she was pregnant with her son, six years ago, she was taking lamotrigine and she had to have regular dose changes throughout the nine months. “I was under the impression that epilepsy drugs got used up quicker by your body when you are pregnant and that in order not to have a seizure, I had to keep upping the dose every
month or so. Won't I need to do that this time?” she asks. “Also, is this new medicine safe, and if so, why am I still having to take the folic acid?”
What is the risk of major congenital malformations in pregnancy? The majority of women with epilepsy will have a normal pregnancy and delivery, as well as an unchanged seizure frequency while pregnant. The fact that Wendy has consulted the specialist before getting pregnant, so that her medication could be changed, has helped to minimise her risk of problems. Max looks in the British National Formulary (BNF) and 29.10.2016 Chemist+Druggist
UPDATE Clinical chemistanddruggist.co.uk/update-plus
Table 1: Approximate percentage risks of major congenital malformation during pregnancy Medicine
Daily dose
Risk (%)
Carbamazepine
any
2.6
Lamotrigine
any
2-3
Levetiracetam
any
2
Topiramate
any
4-5
Sodium valproate
< 1,000mg
6
Sodium valproate
> 1,000mg
10
Sodium valproate + any other
N/A
8.9
Any other combination
N/A
4.2
Source: Epilepsy Action
endure. But the rate varies in woman who have epilepsy, depending on the amount of, and the combination of, AEDs they take (see table 1).
Does levetiracetam require dose adjustments during pregnancy? Wendy is right, in that lamotrigine is metabolised faster during pregnancy, so dose adjustments and blood monitoring are usually required. This is not the case for levetiracetam and routine monitoring of this drug is not recommended, unless there are problems with seizure control. Max tells Wendy that the her GP and specialist will keep an eye on her and she can help by reporting any odd sensations or other changes she notices at once.
What is the UK Epilepsy and Pregnancy Register? This register, established in 1996, has data on several thousand pregnancies and is designed to gather information about the course of pregnancy in women with epilepsy, such as whether they take AEDs or not, to inform the medical profession. Max mentions this to Wendy – who is keen to take part – and gives her the web address (epilepsyandpregnancy. co.uk).
Why is Wendy taking folic acid? confirms that of the antiepileptics available, valproate appears to be associated with the greatest teratogenicity – birth defects in the unborn child. Relatively newer AEDs cause fewer problems during pregnancy. Max discusses this with Wendy, but adds that no medicine taken in pregnancy could ever be said to be completely safe. He refers her to the Epilepsy Action website (epilepsy.org.uk), which has a good explanation of the situation a pregnant epileptic faces. It states that the risks of major congenital malformations (eg problems of the heart or spine) occurring in a foetus of a non-epileptic woman is 1-2% – similar to the 2% rate that women using levetiracetam
Folic acid is given to try to reduce the risk of a particular type of malformation that affects the spinal cord or brain, such as spina bifida. Although women in general are recommended to take 400mcg of folic acid for the first 12 weeks of their pregnancy, women with epilepsy are advised to take 5mg folic acid for the first three months of their pregnancy, and for three months before becoming pregnant.
What are the next steps for Wendy? Max explains his findings to Wendy and recommends she keeps in contact with her doctor – as would be the case with anyone with epilepsy who is pregnant. In addition, he can refer her to the UK Epilepsy and Pregnancy Register.
Lamotrigine is metabolised faster during pregnancy
Take the 5-minute test 1. A focal seizure causes loss of consciousness and rapid, often violent, shaking. True or false?
5. Aggression is a recognised side effect of lamotrigine and levetiracetam. True or false?
2. Tegretol prolonged release tablets should not be broken in half. True or false?
6. The incidence of behavioural side effects in people taking levetiracetam is around 20%. True or false?
3. Tegretol prolonged release tablets should not be chewed before swallowing. True or false?
7. Antiepileptic drugs should not be stopped suddenly because of the risk of rebound seizures. True or false?
4. Serious cutaneous reactions caused by carbamazepine include toxic epidermal necrolysis and Stevens-Johnson syndrome. True or false?
8. The antiepileptic drug associated with the greatest risk of teratogenicity is lamotrigine. True or false? 9. For a non-epileptic woman the risk of major congenital malformations is 3.5%. True or false? 10. Women with epilepsy are advised to take 400mcg folic acid for the first three months of their pregnancy. True or false?
Problems with antiepileptic drugs CPD Reflect What skin reactions can carbamazepine
rashes and mood changes. Some of the risks
Find out more about epilepsy and pregnancy
cause? Which antiepileptic drugs have aggression as a side effect? How can women taking antiepileptic medication and planning a pregnancy reduce the risk of major congenital malformations?
seen in pregnant women with epilepsy are
on the Epilepsy Society website at tinyurl.com/
also discussed.
epilepsy113
Act Read more about epilepsy on the NHS
Read the MUR tips for epilepsy on the C+D
Plan This article contains information about how prescription changes may cause problems for patients with epilepsy and the side effects of antiepileptic drugs, such as skin Chemist+Druggist 29.10.2016
Choices website at tinyurl.com/epilepsy111
website at tinyurl.com/epilepsy114
Revise your knowledge of the drugs used to
Evaluate Are you now confident in your
treat epilepsy and their interactions and side
knowledge of side effects of antiepileptic
effects from the BNF Section 4.8 Antiepileptic
drugs? Could you give advice to women about
drugs at tinyurl.com/epilepsy112
epilepsy and pregnancy?
