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Epilepsy > Epilepsy and Women's Health > Flashcards

Epilepsy and Women's Health Flashcards

1
Q

What are the risks of taking Sodium Valproate in pregnancy?

A

1/9 of babies born from mothers taking sodium Valproate in pregnancy will be born with birth defects
4/10 will display developmental disorders which includes lower intelligence, poor speech and languages skills

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2
Q

What did the MHRS warning state in January 2024 about who should not be prescribed sodium valproate?

A

All products containing sodium valproate/valproic acid should not be prescribed to under 55s unless:
Two specialists independently consider and document other treatments to be ineffective/intolerant or
Compelling reason that the reproductive risks do not apply (hysterectomy)

If sodium valproate is decided to be supplied to women and girls of a reproductive age, it must be in line with the pregnancy prevention programme.

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3
Q

If women and girls are currently taking sodium valproate should they stop taking it?

A

No, they should not stop taking it unless advised by their specialist, due to the risk of loss of seizure control.

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4
Q

If patients are taking sodium valproate what procedure is required?

A

For all patients (including males) under 55* it is advised that:
They have an annual review, with a risk acknowledgment form completed
If the treatment is to continue a second independent opinion from a specialist is required

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5
Q

What does the pregnancy prevention programme involve?

A

Women and girls of a childbearing age who are taking sodium valproate, must be on the pregnancy prevention programme, which involves:
Excluding pregnancy before starting
Signing the risk acknowledgement form after counselling the patient on the risk vs benefits of the medications
Being on highly effective contraception during treatment

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6
Q

Which contraception is classed as highly effective pregnancy prevention programme?

A

Long-acting reversible contraception:
Copper intrauterine device
Levonorgestrel intrauterine device
Progesterone only implant

Male and Female sterilisation

Combined hormonal contraception (pill, patch, ring), progesterone only pill, progesterone only injection IM or subcutaneous depot medroxyprogesterone acetate IF used with additional barrier methods e.g. condoms

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7
Q

What other considerations do you have to make about choice of contraception for PPP when the patient is taking valproate?

A

It is important to note that ethinylestradiol (present in most combined contraceptive pills, the combined transdermal patch and the combined vaginal ring) may modestly reduce valproate levels.
The contraceptive effectiveness of combined hormonal contraceptives, progesterone only pill and implant is not reduced by valproate, but may be reduced by use of other medications that induce liver enzymes. If the patient is taking multiple AEDs one of which in a CYP inducer; intrauterine contraception (IUC) both copper and levonorgestrel and the DMPA are not affected.

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8
Q

Which changes to the actual medication itself supports the MHRA warning?

A

Smaller box sizes to encourage monthly prescribing
Special containers - patients have to receive a whole pack
Warnings on the outside of the box and leaflets

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9
Q

At which stages of life should women and girls be counselled on for epilepsy and AED therapy?

A

Contraception
Pregnancy
Breastfeeding
Menopause

All of which are important considerations for both epilepsy management and mitigating seizure risk and therefore it is important to ensure treatment is personalised to individual needs.

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10
Q

What are the important discussion points of AED therapy with women and girls of childbearing potential?

A

Risk of AEDs in general causing malformations and other developmental disorders in unborn children
Lack of information regarding risks in the newer AEDs
Risk vs benefit of individual AEDs

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11
Q

What contraception discussions points are important to counsel a patient on regarding AED therapy?

A

AED interactions with oral contraceptives
Risk vs benefit of treatment
Individual AED treatment regimen
Risk vs benefit of different contraceptive methods

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12
Q

Which AEDs are enzyme inducers?

A

Category 1 AEDs essentially:
Carbamazepine
Eslicarbazepine (pro-drug of Carbamazepine)
Oxcarbazepine (pro-drug of Carbamazepine)

Phenobarbital
Phenytoin
Primidone

Others:
Perampanel (>12mg)
Rufinamide
Topiramate (>200mg)

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13
Q

Which AEDs are non-enzyme inducers?

A

Acetazolamide
Clobazam
Clonazepam
Ethosuiximide
Gabapentin
Lacosamide
Lamotrigine
Levetiracetam
Perampenal (<12mg)
Pregabalin
Sodium Valproate
Tiagabine
Topiramate (<200mg)
Vigabatrin
Zonisamide

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14
Q

What is an important consideration for Lamotrigine regarding contraception?

A

Whilst Lamotrigine is not an enzyme inducer the combined oral contraception affects Lamotrigine’s metabolism by inducing glucuronidation, reducing the therapeutic effect of the AED.

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15
Q

How should use of Lamotrigine be managed on patients on AEDs?

A

For patients on enzyme-inducing AEDs and non-enzyme inducing AEDs:
As mentioned combined oral contraceptives induce metabolism of Lamotrigine (induce glucuronidation) meaning that if used together there will be an increased risk of seizures in Days 1-21 due to reduced effect of Lamotrigine and then potential for Lamotrigine toxicity in the pill free period as level of the AED would increase as there are no hormones inducing its metabolism, resulting in a longer half-life.

To overcome fluctuations in vivo concentrations of Lamotrigine across a monthly cycle, use a continuous cycle however monitor plasma-drug concentrations of Lamotrigine closely, and adjust the dose accordingly.

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16
Q

Is it only combined oral contraceptives that induce Lamotrigine’s metabolism?

A

Yes, however progesterone only contraceptive Desorgesterol increase the exposure of Lamotrigine and therefore monitoring is required again due to the potential for toxic levels to be reached.

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17
Q

Despite not being an enzyme inducer is there any evidence to suggest that Lamotrigine affects types of contraception?

A

Although there are no studies to prove it, the effectiveness of combined oral contraception, progesterone only pill and progesterone only implant is reduced with Lamotrigine.

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18
Q

If a patient is taking Lamotrigine what are the most appropriate methods of contraception, and which should be avoided?

A

It is preferred to use alongside Lamotrigine:
Depo-Provera s/c injection
Intrauterine Copper device
Intrauterine Levonorgestrel

Combined oral contraception
Progesterone only pill
Progesterone only implant
Should all be used alongside barrier methods

This is the same as requiring ‘highly effective contraception’ for the pregnancy prevention programme for Sodium Valproate.

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19
Q

If patient is on an enzyme inducing AED, which contraception methods are and are not appropriate?

A

Are appropriate:
Progesterone only injections
Levonorgestrel intrauterine device
Copper intrauterine device

Not appropriate:
Oral progesterone only pills
Progesterone only implants
Combined oral contraceptives with less than 50mcg of ethinylestradiol

20
Q

In which circumstances may the combined oral contraceptive be used?

A

Taking ethinylestradiol of 50mcg or more a day alongside an enzyme inducing AED is said to provide enough contraceptive cover.
The tricyclic regimen should be used followed by a short end break of only 4 days before restarting.
To achieve a dose of 50mcg or more daily may mean taking two pills daily.

21
Q

What considerations need to be made if a patient is essentially double dosing COC?

A

Increased risk of adverse effects, for example a greater risk of thrombosis.
This is an unlicensed regimen and therefore contraceptive cover is not guaranteed

22
Q

How long should a patient maintain on contraception even after stopping AEDs?

A

Following withdrawal of AEDs, the enzyme induction effect lasts for 4 weeks after discontinuation so continue contraception.

23
Q

In terms of emergency contraception, what is appropriate for patients on enzyme inducing AEDs?

A

1st line treatment: Copper intrauterine device

If not appropriate a double dose of Levonorgestrel 1.5mg however again it is not guaranteed cover.

Ulipristal acetate 30mg (EllaOne) effect is unknown and inappropriate as you cannot double dose this medication.

24
Q

Summarise, the methods of contraception advised for patients on enzyme inducing and non-enzyme inducing AEDs.

A

Non-enzyme AEDs:
Methods of contraception can be treated the same as in individuals not on AEDs.
With the exception of patients on Lamotrigine in which Depo-Provera, Intrauterine Copper device, Intrauterine Levonorgestrel is preferred.

Enzyme-inducing AEDs:
Not appropriate:
Oral progesterone only pills
Progesterone only implants
Combined hormonal contraception with less than 50mcg of ethinylestradiol

Appropriate:
Depo-Provera
Copper intrauterine device
Levonorgestrel intrauterine device

Limited evidence:
Ethinylestradiol over 50mcg or more daily, tricyclic regimen followed by a shortened 4-day break
Double dose of Levonorgestrel 1.5mg tablets (emergency use)
EllaOne (emergency use)

25
Q

In patients with epilepsy planning to conceive what advice/counselling should be provided?

A

A discussion must take place with the Doctor in order for the pregnancy to be planned.
The patient should be counselled on:
Importance of taking AEDs
Discussion of the risk vs benefit of adjusting medication with the patient planning to get pregnant, this includes:
- Risk of seizure reoccurrence vs harm to Mother and baby
- Risk of Status Epileptics and SUDEP
- Risk of fetal malformations related to the type, dose of AED, the risk of fetal malformations is higher with use of AEDs

26
Q

Is the risk of SUDEP higher or lower during pregnancy?

A

The risk is higher in pregnant epileptics

27
Q

When should changes to AED medication be made for pregnancy?

A

Any changes to medication should be done ideally before pregnancy to assess tolerance and minimise seizure risk.

28
Q

What considerations regarding dose and number of AEDs should be made before pregnancy?

A

Aim to establish a patient on the lowest effective dose of AED before and during pregnancy.
Ideally the patient should be only on one AED (monotherapy).

29
Q

What monitoring does NICE recommend regarding AED and pregnancy?

A

NICE recommends monitoring AED levels in women and children planning to get pregnant and are a risk of their seizures worsening for a baseline level.

30
Q

Which AEDs should specifically be monitored?

A

Carbamazepine
Oxcarbamazepine
Lamotrigine
Levetiracetam
Phenobarbital
Phenytoin

These AEDs plasma-drug concentrations should be monitored and dose adjusted during pregnancy and ante-natal care, when dosages can then return to their pre-conception doses.

31
Q

Which medication should also be considered in pre-conception?

A

Take folic acid 5mg daily before pregnancy and for at least the first trimester to reduce the risk of neural tube defects (often seen with AEDs)

32
Q

Which are the safest AEDs to use in pregnancy?

A

Lamotrigine and Levetiracetam
They do not impose an increased risk of birth malformations compared to the general population.

33
Q

Which AEDs have an increased risk of physical birth abnormalities when used during pregnancy?

A

Carbamazepine (4 to 5 out of 100)
Phenobarbital (6 to 7 out of 100)
Phenytoin (6 out of 100)
Topiramate (4 to 5 out of 100)

Reference general population: 2 to 3 out of 100

34
Q

Which AEDs have an increased risk of the child having neurodevelopmental disorders?

A

Phenytoin
Phenobarbital

(Difficulty learning and thinking associated with use in pregnancy)

35
Q

Which AEDs have an increased risk of the baby being born smaller?

A

Phenobarbital
Topiramate
Zonisamide

36
Q

Aside from those mentioned are there other AEDs which have increased risk when used during pregnancy?

A

There may be however but there there isn’t sufficient studies/enough information to draw conclusions on.

37
Q

Who should be notified if a women with epilepsy becomes pregnant?

A

It is encouraged UK Epilepsy Pregnancy register
Helps to gather information around malformations frequency in babies from women who take one or more AED during pregnancy

Alongside their specialist so a care plan between the patient, family members, specialist, midwife/obstetrician and primary care team can be established for follow ups.

38
Q

What should ante-natal monitoring involve?

A

Establishing seizure type and frequency
Recognising any triggers for seizures
Adherence to AED

Also offers detailed ultrasound at 18-20 weeks to screen for any malformations

39
Q

In which patient groups require more frequent ante-natal reviews?

A

Active epilepsy (seizure within the last 12 months)
Under 16
Learning disabilities
Bilateral tonic-clonic seizures
Modifiable risk factors for SUDEP

40
Q

What may also be offered during ante-natal care for women with epilepsy?

A

Genetic counselling if there are known risk factors or fear of inheritance in epilepsy.
Especially with idiopathic and family history of epilepsy.

41
Q

Is the risk of seizures increased during pregnancy?

A

No women with epilepsy are unlikely to experience an increase in seizure frequency while pregnant or a few months post birth.

42
Q

Which seizure type has the highest risk of malformations?

A

Generalised tonic-clonic seizures have a higher relative risk of fetus harm during a seizure and is dependent on the seizure frequency.
Myoclonic, focal and absence seizures have no relative risk from the seizure itself but may be affected if the mother falls or sustains an injury.

43
Q

Is there an increased risk of seizure during birth?

A

Seizures during labour risk is low but it is advised women with epilepsy give birth in a hospital - in an open bay and not in a room alone.

44
Q

What medication is given at delivery for women with epilepsy?

A

Mothers on enzyme inducing AEDs are given parental 1mg Vitamin K.

45
Q

Should mothers be advised to breast feed whilst on AEDs?

A

Yes it is generally safe and recommended however always check individual emc and advise of the risk vs benefits.

46
Q

What safety precautions should you advise mothers with epilepsy of with babies/young children?

A

Showering with the baby instead of having a bath, as if the Mother has a seizure whilst bathing the baby, the baby could drown.
If bathing the baby, somebody else must always be present.

If feeding the baby try and do it against the wall with cushions either side due to the reduced risk of a baby falling on to the hard fall.

Nappy changes on the fall instead of a changing stand.

If going outside, a cord should be attached to the Mother to stop the pram going far if the mother has a seizure.

Epilepsy (6 decks)

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