Journal of Family Planning and Reproductive Health Care, October 2010

The main article is a review of use of hormonal contraception in women taking enzyme-inducing anti-epileptic drugs (abbreviated to EIEAD, which meant I kept getting ‘Old Macdonald’ running through my head as I was reading it). For reference, a list of the drugs that can reduce the efficacy of hormonal contraceptives:

Carbamazepine

Oxcarbazepine

Felbamate (moot point as not available in the UK)

Lamotrigine (reduces progestagen only so probably OK, but complicated for other reasons – see below)

Phenobarbital (is anyone of childbearing age still even on that?  Oh, well, probably someone somewhere)

Primidone

Rufinamide

Topiramate at doses of 200 mg/day or above (below that, effect is negligible)

And, just for double-checking, a list of antiepileptics that do not affect hormonal contraception:

Acetazolamide

Benzodiazepines

Ethosuccimide

Gabapentin

Lacosamide

Levetiracetam

Pregabalin

Sodium valproate (which, if anything, is likely to increase COC levels.  However, the horrible teratogenicity can be problematic in women of childbearing age)

Tiagabine

Vigabatrine

Zonisamide (never heard of it, but there it is for the sake of completeness)

(However, if you do prescribe hormonal contraception to a woman whose regime is drawn exclusively from List 2, don’t assume you’re home free – do bear in mind that regimes change, and warn her to check her contraception any time her regime changes.)

OK. What do we need to do when prescribing hormonal contraception to women taking any of the drugs from the first list?  When doing so, it’s useful to divide hormonal contraceptives into three groups: Use With Impunity, Use With Caution, and Best Avoided.

The ‘Use With Impunity’ group includes Depo-Provera (surprising, I know, but it seems that Depo is in fact so effectively metabolised on first pass that enzyme induction just doesn’t add anything significant – what it does, it does before it ever gets to the liver).  The other hormonal contraceptive on this list, less surprisingly, is the Mirena.  And, of course, you can use any non-hormonal contraceptives.  The ‘Use with caution’ list seems to consist of TLAs: the COC, POP, and PCC.  ‘Best avoided’ includes Implanon (except in the case of Lamotrigine, which apparently doesn’t affect Implanon), Evra, and the NuvaRing, as there is no recognised way of increasing the dose of any of these to compensate for the enzyme induction.

What precautions to take with the ‘Use with caution’ group?

The COC

Traditional advice on this one (to start with 50 mcg EE and keep increasing until you find a dose that stops breakthrough bleeding after three months) is now outdated.  For starters, you can no longer start with 50 mcg EE, as Ovran is no more, has ceased to be, has run down the curtains and joined the choir invisible, and is, in short, an ex-Pill.  (Norinyl-1, which I always wondered about, doesn’t count as mestranol is a prodrug and comes out as rather less than 50 mcg EE once converted.)

So, what you do is:

1. Go straight in at 60 mcg EE, for the simple practical reason that making up the dose with two of the same 30 mcg pill is easier than expecting a woman to take two different ones

2. Cut waaaaaay back on those PFIs.  As always, they’re the weak point, and in women on EIEADs you can’t afford any other weak points.  So – 3 days, 4 at absolute most, to be taken after tricycling or quadricycling (or letting the woman figure out the X in X-cycling by keeping going until the breakthrough bleeding becomes unacceptable, taking a 3 – 4 day break, and starting again).

And, having started with that dose, stick to it.  Almost always, anyway.  The tiresome uptitration regimes that were described to me during training are, fortunately, a thing of the past.  Going up to 90 mcg is only recommended in rare circumstances in women with no risk factors for thrombosis, and is the absolute limit in any circumstances.

By the way, don’t forget to explain specifically to the patient that, although this seems like an unnervingly large dose, the speeding-up effect that the EIEAD has on her metabolism ensures that the levels circulating in her bloodstream at any given time are going to be the same as those in women on a more conventional regime.  Even if she doesn’t query it at the time, you want to avoid the possibility of her getting home, having an omigod-what-the-hell-was-that-doctor-DOING double-take, and stopping the regime without further consultation.

One final point: Don’t forget that enzyme induction has a time lag effect.  Or, in other words, when a woman on a COC and EIEAD is changed off her EIEAD onto a different medication, don’t rush to cut down on the COC dose immediately – the enzyme-inducing effect will take 28 days to wear off, so continue the higher dose for that long before reducing.

The POP

Very nearly in the ‘Best Avoided’ category, but you can just about get away with a double dose of Cerazette, though it’s not ideal.  Taking it as one pill twice daily rather than two pills once daily may be worth considering, as it produces smoother blood levels and may fit well with an already-bd medication regime.

PCC

Emergency IUCD insertion is the best bet, but, if that’s not possible/not acceptable, give a double dose of the emergency hormonal contraceptive (either Levonelle or EllaOne).

Finally, interactions can work both ways, and the one to watch for here is Lamotrigine – the COC interferes drastically with its effectiveness, and a woman on Lamotrigine who starts the COC will need to retitrate her Lamotrigine.  Doubling the dose at the time of starting the COC will probably do the trick, but there is huge variation between patients and a very real risk of ending up with either convulsions or excess side-effects while trying to get it right.  There’s also the problem of the PFI, when the level of Lamotrigine that was needed to maintain control while taking the COC suddenly becomes far too high.

The reverse situation (a woman on the COC starting Lamotrigine) is far less of a problem as the Lamotrigine will need titrating on initiation whether or not a woman is on the COC and you simply titrate it to her current needs (though you still have the PFI problem).  However, you’re storing up potential problems for the future if and when she stops the COC and finds her Lamotrigine levels suddenly going through the roof.

Add in the fact that pregnancy has the same effect on Lamotrigine levels, plus the fact that a lot of it gets into breast milk, and you can see why Lamotrigine isn’t considered the ideal choice in women of childbearing age.

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About Dr Sarah

I'm a GP with a husband and two young children.
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