• Which of the anti-epileptic drugs affect the metabolism of the Pill (oral contraceptive) and what are the implications of this? Which drugs are safe to use in combination with the Pill? 
• Phenobarbitone
• Phenytoin
• Carbamazepine
• Oxcarbazepine
• Topiramate
• Perampenel decreases levonorgestrel-containing contraceptives

As listed above these medications decrease the pill effectiveness by increasing liver metabolism via isozyme CYP450 especially of these drugs.Another mechanism this can happen by is via increased sex0hormone binding globulins leaving less free active ingredients. Decreased effectiveness of oral contraceptives will lead to increased amounts of unwanted pregnancy and the possibility of teratogenicity effects in these pregnancies.

Drugs safe to use in combination with the Pill includes: valproate, lamotrigine, gabapentin, leviteracetam and vigabatrin however oral contraception can decrease plasma serum levels in combination with lamotrigine and valproate that in turn can cause breakthrough seizures due to decreased serum levels.

Preverred contraceptive methods for women on anti-epileptic drugs of child bearing age include Depo-provera injections, levonorgestrel IUD (Mirena), Copper IUD as well as progestin only pills instead of combined contraceptives.

• Can oral contraceptives also affect the effectivity of the anti-epileptic drugs?

Yes oral contraceptives can decreased the serum levels of drugs such as lamotrigine and valproate, causing breakthrough seizures and sub therapeutic levels due to increased glucuronation of free and total valproate and lamotrigine concentrations.

• How does age affect the kinetics of these drugs (from neonates to old age)?

Neonates- slower metabolism thus lower dosages

Babies and children- faster metabolism than adults thus higher dosages required

Geriatrics- decreased liver metabolism and renal function thus lower dosages

• In which cases is plasma blood level monitoring indicated

Plasma blood monitoring is required where protein binding is involved. Almost all anti-epileptic agents effect protein binding except gabapentin, ethosuximide and topiramate.

In cases where diseases affect protein binding, plasma blood monitoring is thus needed and includes chronic kidney failure, liver diseases, hypoalbuminemia, severe burns, pregnancy, malnutrition, age and where displacement drugs are used. Also when combination therapy is used between enzyme inducers (carbamazepine, phenobarbitone, phenytoin) with lamotrigine or other drugs metabolised by CYP P450 enzymes as well as during perimenopause stages and the use of valproate (enzyme inhibitor) with lamotrigine to ensure the levels are within the therapeutic index range and not near toxic levels.

Brand, L. 2021. Antiepileptic drugs. Study unit 4 [PowerPoint Presentation]. Unpublished lecture notes on eFundi, FKLG312. Potchefstroom: NWU

https://www.uspharmacist.com/article/antiepileptic-drugs-and-contraception#:~:text=ABSTRACT%3A%20Certain%20antiepileptic%20drugs%20(AEDs,of%20seizure%20control%20or%20toxicity.