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5 Clinical Pearls for Contraception and Preconception Counseling

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5 Clinical Pearls for Contraception and Preconception Counseling EDITORIAL Women with epilepsy: 5 clinical pearls for contraception and preconception counseling For women with epilepsy, intrauterine devices are the optimal reversible contraceptive, and, preconception, the use of antiepileptic drugs with the lowest teratogenic potential should be considered Robert L. Barbieri, MD Editor in Chief, OBG MANAGEMENT Chair, Obstetrics and Gynecology Brigham and Women’s Hospital, Boston, Massachusetts Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology Harvard Medical School, Boston n 2015, 1.2% of the US population bazepine (Aptiom), felbamate (Fel- becoming pregnant while taking the was estimated to have active epi- batol), oxcarbazepine (Trileptal), oral contraceptive.6 Carbamazepine, Ilepsy.1 For neurologists, key goals perampanel (Fycompa), phenobarbi- a strong inducer of hepatic enzymes, in the treatment of epilepsy include: tal, phenytoin (Dilantin), primidone was the most frequently used AED in controlling seizures, minimizing (Mysoline), rufinamide (Banzel), this sample. adverse effects of antiepileptic drugs and topiramate (Topamax) (at dos- Many studies report that carba- (AEDs) and optimizing quality of ages >200 mg daily). According to mazepine accelerates the metabo- life. For obstetrician-gynecologists, Lexicomp, the following AEDs do not lisms of estrogen and progestins and women with epilepsy (WWE) have cause clinically significant changes reduces contraceptive efficacy. For unique contraceptive, preconcep- in hepatic enzymes that metabolize example, in one study 20 healthy tion, and obstetric needs that require steroid hormones: acetazolamide women were administered an ethi- highly specialized approaches to (Diamox), clonazepam (Klonopin), nyl estradiol (20 µg)-levonorgestrel care. Here, I highlight 5 care points ethosuximide (Zarontin), gabapentin (100 µg) contraceptive, and randomly that are important to keep in mind (Neurontin), lacosamide (Vimpat), assigned to either receive carbamaze- when counseling WWE. levetiracetam (Keppra), pregabalin pine 600 mg daily or a placebo pill.7 In (Lyrica), tiagabine (Gabitril), viga- this study, based on serum progester- 1 Enzyme-inducing AEDs batrin (Vigadrone), and zonisamide one measurements, 5 of 10 women in reduce the effectiveness (Zonegran).2,3 In addition, lamotrig- the carbamazepine group ovulated, of estrogen-progestin and ine (Lamictal) and valproate (Depa- compared with 1 of 10 women in the some progestin contraceptives. kote) do not significantly influence placebo group. Women taking car- AEDs can induce hepatic enzymes the metabolism of contraceptive bamazepine had integrated serum that accelerate steroid hormone steroids,4,5 but contraceptive steroids ethinyl estradiol and levonorgestrel metabolism, producing clinically significantly influence their metabo- concentrations approximately 45% important reductions in bioavail- lism (TABLE 2, page 16). lower than women taking placebo.7 able steroid hormone concentra- For WWE taking an AED that Other studies also report that carbam- tion (TABLE 1, page 10). According accelerates steroid hormone metab- azepine accelerates steroid hormone to Lexicomp, AEDs that are induc- olism, estrogen-progestin contracep- metabolism and reduces the circulat- ers of hepatic enzymes that metab- tive failure is common. In a survey of ing concentration of ethinyl estradiol, olize steroid hormones include: 111 WWE taking both an oral con- norethindrone, and levonorgestrel by carbamazepine (Tegretol), eslicar- traceptive and an AED, 27 reported about 50%.5,8 CONTINUED ON PAGE 10 mdedge.com/obgyn Vol. 31 No. 9 | September 2019 | OBG Management 9 EDITORIAL CONTINUED FROM PAGE 9 WWE taking an AED that induces an estrogen-progestin contracep- The effectiveness of levonorg- hepatic enzymes should be coun- tive is to be prescribed, safeguards to estrel emergency contraception seled to use a copper or levonorg- reduce the risk of pregnancy include: may also be reduced in WWE tak- estrel (LNG) intrauterine device • prescribe a contraceptive with ing an enzyme-inducing AED. In (IUD) or depot medroxyprogesterone ≥35 µg of ethinyl estradiol these cases, some experts recom- acetate (DMPA) for contraception.9 • prescribe a contraceptive with mend a regimen of two doses of WWE taking AEDs that do not induce the highest dose of progestin with levonorgestrel 1.5 mg, separated by hepatic enzymes can be offered the a long half-life (drospirenone, 12 hours.10 The effectiveness of pro- full array of contraceptive options, as desogestrel, levonorgestrel) gestin subdermal contraceptives outlined in Table 1. Occasionally, a • consider continuous hormonal may be reduced in women tak- WWE taking an AED that is an inducer contraception rather than 4 or ing phenytoin. In one study of 9 of hepatic enzymes may strongly pre- 7 days off hormones and WWE using a progestin subdermal fer to use an estrogen-progestin con- • recommend use of a barrier con- implant, phenytoin reduced the traceptive and decline the preferred traceptive in addition to the hor- circulating levonorgestrel level by option of using an IUD or DMPA. If monal contraceptive. approximately 40%.11 TABLE 1 Lexicomp risk, severity, and reliability rating of potential interactions between AED and accelerated metabolism of estrogen and progestin contraceptive hormones2,a Is the antiepileptic medication an inducer of hepatic enzymes that can accelerate the inactivation of estrogen and/or progestin contraceptive hormones? YES NO Lexicomp risk (letter grade), severity, and reliability rating for Antiepileptic AED interaction with estrogen- Antiepileptic Lexicomp rating- interaction with medication progestin contraceptive medication estrogen-progestin contraceptive Carbamazepine D rating-consider therapy modification, Acetazolamide A rating. No known interactions with (Tegretol) Severity Major, Reliability Good (Diamox) estrogen or progestin hormones Eslicarbazepine D rating-consider therapy modification, Clonazepam A rating. No known interactions with (Aptiom) Severity Major, Reliability Good (Klonopin) estrogen or progestin hormones Felbamate (Felbatol) D rating-consider therapy modification, Ethosuximide A rating. No known interactions with Severity Major, Reliability Good (Zarontin) estrogen or progestin hormones Oxcarbazepine D rating-consider therapy modification, Gabapentin A rating. No known interactions with (Trileptal) Severity Major, Reliability Good (Neurontin) estrogen or progestin hormones Perampanel D rating-consider therapy modification, Lacosamide B rating. May increase the serum (Fycompa) Severity Major, Reliability Fair (Vimpat) concentration of ethinyl estradiol by 20%. Severity Minor, Reliability Fair Phenobarbital D rating-consider therapy modification, Levetiracetam A rating. No known interactions with Severity Major, Reliability Fair. Also (Keppra) estrogen or progestin hormones induces CYP3A4 Phenytoin (Dilantin) D rating-consider therapy modification, Pregabalin (Lyrica) A rating. No known interactions with Severity Major, Reliability Fair estrogen or progestin hormones Primidone (Mysoline) D rating-consider therapy modification, Tiagabine (Gabitril) A rating. No known interactions with Severity Major, Reliability Fair estrogen or progestin hormones Rufinamide (Banzel) D rating-consider therapy modification, Vigabatrin A rating. No known interactions with Severity Major, Reliability Fair (Vigadrone) estrogen or progestin hormones Topiramate D rating-consider therapy modification, Zonisamide A rating. No known interactions with (Topamax) Severity Major, Reliability Good (Zonegran) estrogen or progestin hormones aLamotrigine (Lamictal) and valproate (Depakote) are not strong inducers of hepatic enzymes. Hence, they do not accelerate the metabolism of estrogen and progestin contraceptive hormones. However, the metabolism of lamotrigine and valproate is accelerated by estrogen (see Table 2). Abbreviation: AED, antiepileptic drug. CONTINUED ON PAGE 16 10 OBG Management | September 2019 | Vol. 31 No. 9 mdedge.com/obgyn EDITORIAL CONTINUED FROM PAGE 10 TABLE 2 Metabolism effects of lamotrigine and valproate by estrogen medicationsa Antiepileptic medication Lexicomp risk (letter grade), severity, and reliability rating Lamotrigine (Lamictal) Estrogen may reduce lamotrigine levels. D rating-consider therapy modification, Severity Major, Reliability Good Valproate (Depakote) Estrogen may reduce valproate levels. C rating-monitor therapy. Severity Moderate, Reliability Fair aThe metabolism of lamotrigine and valproate is accelerated by estrogen medications, resulting in a possible reduction in circulating medication concentration, increasing the risk of seizure. Lamotrigine and valproate do not significantly accelerate the metabolism of ethinyl estradiol or levonorgestrel. 14,15 2 Do not use lamotrigine concentration, as noted in Table 2. major congenital malformations: with cyclic estrogen- In one study, estrogen-progestin spina bifida, ventricular and atrial progestin contraceptives. contraceptive was associated with septal defects, pulmonary valve atre- Estrogens, but not progestins, are 18% and 29% decreases in total sia, hypoplastic left heart syndrome, known to reduce the serum con- and unbound valproate concen- cleft palate, anorectal atresia, and centration of lamotrigine by about trations, respectively.14 Valproate hypospadias.18 50%.12,13 This is a clinically sig- may induce polycystic ovary syn- In a study of 7,555 pregnan- nificant pharmacologic interac- drome in women.16 Therefore, it cies in women using a single AED,
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