Special Population

Question 1

[Women of childbearing age]

Women with epilepsy should be referred to specialist care for discussion on:

Answer 1

Fertility, contraception, family planning

Question 2

[Women of childbearing age]

What are the potential risk to fetus?

Answer 2

1. Uncontrolled seizures
2. Teratogenic potential of ASMs: neonatal congenital defects

• Major malformation risk (Valproate, Phenobarbital, Topiramate, Phenytoin, Carbamazepine)
• Neonatal cognition (Valproate, Phenytoin, Phenobarbital, Topiramate)

Question 3

[Women of childbearing age]

Use of oral contraception with ASMs

Answer 3

1. Carbamazepine, Phenytoin, Phenobarbital

• Oral contraceptives are substrates of CYP3A4, efficacy of OC may be reduced in the presence of enzyme inducers

2. Lamotrigine

• Oral contraceptives may lower Lamotrigine concentrations, resulting in breakthrough seizures
• FYI: most likely mechanism for this interaction is enhanced lamotrigine glucuronidation (possibly via UGT1A4) by estrogens

3. Oxcarbazepine, Topiramate, can also impair effectiveness of hormonal contraceptives

Question 4

[Women of childbearing age]

Besides oral contraception, what other methods would be preferred in women taking ASMs?

Answer 4

• IUD
• Progesterone depot injection + barrier method
• Continuous cycle estrogen-progestin pill + barrier method

Question 5

[Women of childbearing age]

Use of Sodium Valproate

Answer 5

Sodium valproate should NOT be used in women of childbearing potential unless other treatments are ineffective or not tolerated

• Children exposed in utero to valproate are at high risk of serious developmental disorders (neonatal cognition) + congenital malformations

*Review alternatives if possible
*Communicate risk to fetus and need for contraception

Question 6

Is sodium valproate use in women of childbearing age/pregnant women an absolute contraindication?

Answer 6

EPILEPSY:

• NOT an absolute contraindication for use in epilepsy, may be used if there are no other suitable alternatives for pregnant women + conditions of pregnancy prevention program fulfilled for women of childbearing potential

BIPOLAR:

• CI in pregnancy
• NOT an absolute CI in women of childbearing potential if conditions of pregnancy prevention program fulfilled

MIGRAINE PROPHYLAXIS:

• CI in pregnancy
• CI in women of childbearing age not on contraception

Question 7

[Women of childbearing age]

Use of Carbamazepine

Management

Answer 7

• Carbamazepine is CYP3A4 inducer, while ethinyl estradiol is CYP3A4 substrate
• Consider alternative
• Use backup contraceptive method during coadministration and at least 28 days after discontinuing CBZ

Question 8

[Pregnancy]

• What ASMs are safer options in pregnancy?

Answer 8

• Levetiracetam
• Lamotrigine

Question 9

[Lactation]

• Is ASM contraindicated in breastfeeding?

Answer 9

No, breastfeeding women on ASM treatment are encouraged to breastfeed

Question 10

[Lactation]

• which drug reported higher infant levels (may want to avoid)

Answer 10

• Phenobarbital
• Ethosuximide
• Zonisamide