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Coll. Antropol. 36 (2012) 4: 1475–1476

Case report
Ectopic Pregnancy as Contraceptive Failure

in Patient with Epilepsy
Branko Radakovi} and Marina [prem Gold{tajn
University of Zagreb, School of Medicine, Department for Gynecology and Obstetrics, Zagreb, Croatia
ABSTRACT
Epilepsy is a common neurologic condition which includes many women’s health issues. Menstrual disorders, repro-
ductive endocrinological disturbances, ovulatory dysfunction and infertility appear to be relatively frequent in women
with epilepsy. Clinical decision making which contraceptive regimen is optimal for an individual woman with epilepsy
is one of the most challenging tasks when taking care of women with epilepsy. A higher incidence of breakthrough bleed-
ing and contraceptive failure was determined among women using antiepileptic drugs. There is the increased risk for
contraceptive failure with the use of P450 3A4 enzyme-inducing antiepileptic drugs (AEDs) such as phenobarbital, car-
bamazepine, phenytoin, felbamate, topiramate and oxcarbazepine. Therefore, it is recommended to use noninducing
AEDs, or for those who use inducing AEDs, the use of oral hormonal contraceptive pills which contained equal or more
than 50 mg of estrogen, or intrauterine devices. The aim of the article is to present woman with epilepsy who was used
combined low dose oral contraceptive pills containing 20 mg of ethinyl estradiol which in interaction with carbamazepine
resulted with ectopic tubar pregnancy.
Key words: tubar pregnancy, epilepsy, oral contraceptives, drug interaction
Introduction
Epilepsy is a common neurologic condition which in- versity of Zagreb due to abdominal pain, amenorrhoea
cludes many women’s health issues1,2. Menstrual disor- and vaginal bleeding. She has a decade history of epilepsy
ders, reproductive endocrine disturbances, ovulatory dys- as a result of trauma injury. The patient is treated with
function, and infertility appear to be relatively common carbamazepine in a daily dose of 800 mg. She was treated
in women with epilepsy2. Clinical decision making which for seven months by her general practitioner with mono-
contraceptive regimen is optimal for an individual wo- phasic, combined, low-dose oral contraceptive pills which
man with epilepsy is one of the most challenging tasks contained 20 mg of ethinylestradiol and 75 mg of gestoden.
when taking care of women with epilepsy3,4. A higher in- During the gynecological exam tha patient signalized ex-
cidence of breakthrough bleeding and contraceptive fail- tremely painful sensation in the projection of right fallo-
ure was determined among women using antiepileptic pian tube. Ultrasound was performed, and suspect ecto-
drugs. There is the increased risk for contraceptive fail- pic right tubar pregnancy was determined with empty
ure with the use of P450 3A4 enzyme-inducing antiepi- endometral cavity. The level of b-human chorionic go-
leptic drugs (AEDs) such as phenobarbital, carbamaze- nadotropin was 1368 IJ/L, and was significantly lower for
pine, phenytoin, felbamate, topiramate and oxcarbaze- expected eight weeks amenorrhoea duration. The patient
pine1,2. The aim of the article is to present woman with underwent urge laparoscopic surgery. Intraoperatively,
epilepsy who used combined low dose oral contraceptive right fallopian tube was thicker, with haemorrhagic con-
pills which interacted with carbamazepine, resulting tent and incipient expulsion of ectopic pregnancy through
with ectopic tubar pregnancy. the abdominal tubar orifice, with 250 mL of coaguls and
blood in the coul de sac. Right salpingectomia was per-
formed. There was no immediate and late postoperative
Case Report complications. Pathologist confirmed the diagnosis of
A 26-year multiparous was submitted to the Depart- ectopic tubar pregnancy. The patient was released from
ment for Gynecology and Obstetrics Medical School Uni- the Department after two days.
Received for publication November 2, 2009
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B. Radakovi} and M. [prem Gold{tajn: Ectopic Pregnancy and Epilepsy, Coll. Antropol. 36 (2012) 4: 1475–1476
Discussion and Conclusion tive failures rates1,2. Although depo medroxyprogeste-

rone acetate injections are effective, they are not recom-
Pre-pregnancy councelling in women with epilepsy
mended as the first contraceptive choice due to serious
includes information on interactions of antiepileptic drugs
side effects such as delayed return to fertility, and im-
and oral contraceptives in order to prevent contraceptive
paired bone health2,5,6. The use of intrauterine devices
failure, and to decrease the risk of unplanned or ectopic
appeared to be good alternative for contraception in pa-
pregnancy in women with epilepsy. An interaction be-
tients receiving enzyme induced AEDs due to the lack of
tween AEDs and combined oral contraceptive pills was
side effects. During the past decade, new antiepileptic
first proposed when the dose of estradiol in the oral con-
drugs have been introduced1–3. They exhibit lower poten-
traceptive pills was reduced from 100 to 50 micrograms1,2.
Since then, interaction studies have been undertaken to tial for drug interactions than classic AEDs, mostly be-
look for possible interactions between AEDs and the cause of their pharmacokinetic characteristics. For ex-
combined oral contraceptive pills. AEDs that induce he- ample, vigabatrin, levetiracetam and gabapentin, exhibit
patic microsomal enzymes may interact with hormonal few or no interactions with other AEDs. Furthermore,
contraception resulting in high contraceptive failure3. there are no interactions between the combined oral con-
They increased estrogen metabolism and progesteron traceptive pill, progesteron only pill, medroxyprogeste-
protein binding, decreased the concentration of both hor- rone injections or levonorgestrel implants and the AEDs
mones and thus reducing contraceptive efficacy2,4. If valproic acid, vigabatrin, tamotrigine, gabapentin, tiaga-
woman, who is received enzyme induce AEDs (phenobar- bine, levetiracetam, zonisamide, ethosuximide and the
bital, carbamazepine, phenytoin, felbamate, topiramate benzodiazepines1,7,8. Therefore, physicians have a duty to
and oxcarbazepine), wanted to use oral hormonal contra- offer appropriate and accurate counselling to epileptic
ception, it is recommended to take preparation contain- patient concerning optimal choice for the use of oral con-
ing at least 50 micrograms of ethinylestradiol1,5. Pro- traceptives for those considering this method as contra-
gestin only pills are likely to be ineffective if used in ception. Recommendations included possible use of a
combination with enzyme induced AEDs. Subdermal noninducing AEDs, or for those who use inducing AEDs-
progestogen implants are not recommended in patients -use of an oral contraceptive pills containing equal or
with enzyme induced AEDs because of high contracep- more than 50 micrograms of estrogen1–4.
REFERENCES
1. SCHWENKHAGEN AM, STODIECK SR, Seizure, 17 (2008) 145. LOS PN, FROSCHER W, PISANI F, VAN RIJN CM, Epilepsia, 43 (2002)
— 2. O BRIEN MD, GUILLEBAUD J, Epilepsia, 47 (2006) 1419. — 3. 365. — 7. CRAWFORD P, CNS Drugs, 16 (2002) 263. — 8. HACHAD H,
CRAWFORD P, Epilepsia, 46 (2005) 117. — 4. BEYENBURG S, SCH- RAGGUENEAU-MAJLESSI I, LEVY RH, Ther Drug Monit, 24 (2002)
MULTZLER AG, Zentralbl Gynakol, 126 (2004) 112. — 5. MC AULEY 91.
JW, ANDERSON GD, Clin Pharmacokinet, 41 (2002) 559. — 6. PATSA-
M. [prem Gold{tajn
University of Zagreb, School of Medicine, Department for Gynecology and Obstetrics, Petrova 13, 10 000 Zagreb, Croatia
e-mail: [email protected]
EKTOPI^NA TRUDNO]A – KONTRACEPCIJSKA GRE[KA U BOLESNICE S EPILEPSIJOM
SA@ETAK
Epilepsija je relativno ~est neurolo{ki poreme}aj koji bitno utje~e na razli~ite aspekte zdravlja ène. Poreme}aj men-
struacijskog ciklusa, reprodukcijski endokrinolo{ki poreme}aji i neplodnost zna~ajno utje~u na kvalitetu ìvota ène s
epilepsijom. Klini~ka procjena i izbor optimalnog kontracepcijskog protokola u èna s epilepsijom je veliki izazov s
obzirom na ~esta probojna krvarenja i kontracepcijski neuspjeh koji se javljaju u èna koje koriste antiepileptike i
oralnu hormonsku kontracepciju. S obzirom na pove}ani rizik kontracepcijskog neuspjeha u èna koje koriste antiepi-
leptike koji induciraju jetrene mikrosomalne enzime (phenobarbital, karbamazepin, fenitoin, felbamat, topiramat i
okskarbazepin), preporuka je kori{tenje oralne hormonske kontracepcije koja sadrì 50 ili vi{e mikrograma etinil estra-
diola, materni~nog ulo{ka ili promjena osnovne terapije epilepsije primjenom nove generacije antiepileptika koji ne
induciraju jetrene mikrosomalne enzime. Cilj ovog rada je prikazati ènu s epilepsijom koja je koristila kombiniranu
niskodoza`nu oralnu hormonsku kontracepciju koja sadrì 20 mg etinil estradiola i antiepileptik karbamazepin, {to je
rezultiralo kontracepcijskim neuspjehom i ektopi~nom tubarnom trudno}om.
1476
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Color profile: Disabled

Composite 150 lpi at 45 degrees

Coll. Antropol. 36 (2012) 4: 1475–1476

Ectopic Pregnancy as Contraceptive Failure

Key words: tubar pregnancy, epilepsy, oral contraceptives, drug interaction

Received for publication November 2, 2009

Discussion and Conclusion tive failures rates1,2. Although depo medroxyprogeste-

EKTOPI^NA TRUDNO]A – KONTRACEPCIJSKA GRE[KA U BOLESNICE S EPILEPSIJOM

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