Contraindications to Sodium Valproate in Females of Reproductive Age
Sodium valproate is absolutely contraindicated in women of childbearing potential due to its significant teratogenic effects and risk of developmental disorders in exposed children. 1
Primary Contraindication
- Sodium valproate must not be used in females of reproductive age unless there is no suitable alternative and a pregnancy prevention program is implemented 1
- It is classified as having an absolute contraindication for women who are or may become pregnant 1
Risks Associated with Valproate Use in Pregnancy
- Approximately three-fold increase in major congenital malformations, particularly neural tube defects 2
- Significant risk of cognitive, language, and psychomotor developmental delays in exposed children 3
- Increased risk of autism spectrum disorders in children exposed in utero 3, 2
- Dose-dependent teratogenic effects, with higher risks at doses above 1000 mg/day 4
- Greater teratogenic potential compared to other antiepileptic drugs 3
Reproductive Endocrine Effects
- Valproate use in women is associated with menstrual irregularities (amenorrhea, oligomenorrhea, prolonged cycles) 1
- Approximately 45% of women on valproate monotherapy experience menstrual irregularities 1
- Increased incidence of polycystic ovaries (60% of women with menstrual irregularities) 1
- Elevated serum testosterone levels in 30% of women taking valproate 1
Regulatory Responses
- Many regulatory bodies worldwide have banned or severely restricted valproate use in women of childbearing potential 3
- The UK has banned valproate use in women who are not enrolled in a pregnancy prevention program 5
- Despite known risks, valproate continues to be inappropriately prescribed to women of reproductive age 6
Alternative Medications
- For migraine prevention: beta-blockers (propranolol, metoprolol), candesartan, or topiramate are preferred first-line options 1
- For epilepsy: alternative anticonvulsants should be considered based on seizure type and individual factors 1
- For bipolar disorder: alternative mood stabilizers should be used when treating women of reproductive age 7
Clinical Practice Recommendations
- Comprehensive preconception counseling is essential for all women with epilepsy or other conditions typically treated with valproate 1
- If a woman is already taking valproate and planning pregnancy, medication should be switched to a safer alternative before conception 1
- When valproate absolutely cannot be avoided, use the lowest effective dose (ideally <1000 mg/day) with appropriate folic acid supplementation 4
- Regular pregnancy testing and effective contraception must be ensured for any woman of reproductive age who must take valproate 5
Documentation Requirements
- Any prescription of valproate to women of reproductive age requires thorough documentation of:
In summary, sodium valproate should be considered absolutely contraindicated in women of childbearing potential unless all other treatment options have failed, a pregnancy prevention program is implemented, and the woman has provided fully informed consent after comprehensive counseling about the risks.