Advertisement

Der Gynäkologe

, Volume 52, Issue 2, pp 117–125 | Cite as

Arzneimittelwechselwirkungen bei oralen Kontrazeptiva

  • Mazyar Mahmoudi
  • Walter E. HaefeliEmail author
Leitthema
  • 110 Downloads

Zusammenfassung

Arzneimittelwechselwirkungen („drug-drug interactions“, DDI) können den Arzneistoffmetabolismus der Kontrazeptiva verändern (Kontrazeptiva als Opfer) und zum Wirkverlust der Kontrazeptiva mit ungewollten Schwangerschaften führen. Wirkverlust tritt umso eher ein, je stärker die Ausscheidung durch die Begleitmedikation beschleunigt wird und je niedriger die Kontrazeptiva dosiert sind. Zu den Substanzen, welche die Ausscheidung relevant beschleunigen (sog. Induktoren), gehören neben enzyminduzierenden Antiepileptika (Carbamazepin, Eslicarbazepin, Oxcarbazepin, Phenobarbital, Phenytoin), Rifamycinantibiotika (Rifampicin, Rifabutin) und Efavirenz auch frei verkäufliche Antidepressiva, z. B. Johanniskraut. In diesen Kombinationen ist die Sicherheit der Kontrazeption oft nicht mehr gegeben, entsprechend sind andere Verhütungsmethoden zu wählen. Andererseits können zahlreiche Substanzen v. a. den Abbau von Gestagenen hemmen, der meist über Cytochrom P450 3A4 vermittelt ist. Wichtige Tätersubstanzen an dieser Zielstruktur sind Azolfungistatika (z. B. Fluconazol), HIV(humanes Immundefizienzvirus)-Proteaseinhibitoren (z. B. Ritonavir) und einige Makrolidantibiotika (z. B. Clarithromycin, Erythromycin). Mit den heute gebräuchlichen niedrigdosierten Kontrazeptiva sind die Expositionsanstiege meist klinisch unbedeutend und die sichere Kontrazeption weiterhin gegeben. Darüber hinaus können Kontrazeptiva auch die Pharmakokinetik der Begleitmedikation beschleunigen (Kontrazeptiva als Tätersubstanz). Dies betrifft die vorwiegend glukuronidierten Antiepileptika Valproinsäure und Lamotrigin, deren Konzentrationen erheblich abfallen können (Risiko erneuter epileptischer Anfälle), weshalb Kontrollen der Antiepileptikakonzentration und -wirksamkeit oder alternative Verhütungsmethoden notwendig werden.

Schlüsselwörter

Antiepileptika HIV-Proteaseinhibitoren  Orale Kontrazeptiva Arzneimittelinteraktionen Cytochrome-P-450-Enzymsystem 

Drug interactions with oral contraceptives

Abstract

Drug–drug interactions (DDI) can alter the metabolism of oral contraceptives (OC) and lead to treatment failure and unintended pregnancies (OC as “victim” drugs). The likelihood of such a loss of efficacy increases if elimination of the OC is substantially accelerated through comedication and the maintenance dose of the contraceptive is low. Among the drugs that accelerate this elimination in a relevant manner (so-called inductors) are enzyme-inducing antiepileptics (e. g., carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin), rifamycin antibiotics (rifampicin, rifabutin), efavirenz, and over-the-counter medicines such as the antidepressant St. John’s wort. Combined with these substances, effective hormonal contraception is no longer guaranteed and OC have to be replaced by other contraceptive methods. On the other hand, numerous drugs are known to inhibit the elimination of progestogens, which are mainly metabolized by the cytochrome P450 3A4 isozymes. Relevant inhibitors for this isozyme (perpetrator drugs) are triazoles (e. g., fluconazole), HIV protease inhibitors (e. g., ritonavir), and some macrolide antibiotics (such as clarithromycin, erythromycin). With the current low-dose OC formulations, the observed increase in drug exposure due to DDI neither leads to acute toxicity nor does it impair contraception. Finally, OC can also induce the elimination of co-administered drugs (OC as a perpetrator) and substantially decrease the plasma concentrations of antiepileptic drugs that are mainly eliminated by glucuronidation such as valproic acid and lamotrigine (potentially leading to seizure recurrence). If such combinations cannot be avoided, antiepileptic concentrations and effects must be closely monitored or alternative contraception methods should be selected.

Keywords

Anticonvulsants HIV protease inhibitors Contraceptives, oral  Drug interactions Cytochrome P‑450 enzyme system 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

M. Mahmoudi und W.E. Haefeli geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Draper MW, Flowers DE, Neild JA, Huster WJ, Zerbe RL (1995) Antiestrogenic properties of raloxifene. Pharmacology 50:209–217PubMedGoogle Scholar
  2. 2.
    Scarsi KK, Darin KM, Chappell CA, Nitz SM, Lamorde M (2016) Drug-drug interactions, effectiveness, and safety of hormonal contraceptives in women living with HIV. Drug Saf 39:1053–1072PubMedPubMedCentralGoogle Scholar
  3. 3.
    Petitti DB (2003) Clinical practice. Combination estrogen-progestin oral contraceptives. N Engl J Med 349:1443–1450PubMedGoogle Scholar
  4. 4.
    Kuohung W, Borgatta L, Stubblefield P (2000) Low-dose oral contraceptives and bone mineral density: an evidence-based analysis. Contraception 61:77–82PubMedGoogle Scholar
  5. 5.
    Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL (2005) Interaction of St. John’s Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 71:402–408PubMedGoogle Scholar
  6. 6.
    Gallo MF, Nanda K, Grimes DA, Lopez LM, Schulz KF (2013) 20 µg versus >20 µg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev xx:CD3989Google Scholar
  7. 7.
    Crosignani PG, Testa G, Vegetti W, Parazzini F (1996) Ovarian activity during regular oral contraceptive use. Contraception 54:271–273PubMedGoogle Scholar
  8. 8.
    Baerwald AR, Olatunbosun OA, Pierson RA (2004) Ovarian follicular development is initiated during the hormone-free interval of oral contraceptive use. Contraception 70:371–377PubMedGoogle Scholar
  9. 9.
    Allen HH (1974) Clinical assessment of a low-dose oestrogen, low-dose progestogen combined oral contraceptive. Curr Med Res Opin 2:101–108PubMedGoogle Scholar
  10. 10.
    Cullberg G, Samsioe G, Andersen RF, Bredesgaard P, Andersen NB, Ernerot H, Fanøe E, Fylling P, Haack-Sørensen PE, Klottrup P, Pedersen JH, Sandager T (1982) Two oral contraceptives, efficacy, serum proteins, and lipid metabolism. A comparative multicentre study on a triphasic and a fixed dose combination. Contraception 26:229–243PubMedGoogle Scholar
  11. 11.
    Tomson T, Battino D (2012) Teratogenic effects of antiepileptic drugs. Lancet Neurol 11:803–813PubMedGoogle Scholar
  12. 12.
    Vajda FJ (2014) Effect of anti-epileptic drug therapy on the unborn child. J Clin Neurosci 21:716–721PubMedGoogle Scholar
  13. 13.
    Coulam CB, Annegers JF (1979) Do anticonvulsants reduce the efficacy of oral contraceptives? Epilepsia 20:519–525PubMedGoogle Scholar
  14. 14.
    Kaneko S (1998) Pregnancy and quality of life in women with epilepsy. Clin Ther 20(Suppl. A):A30–A47 (Discussion A58–A60)PubMedGoogle Scholar
  15. 15.
    Sabers A, Buchholt JM, Uldall P, Hansen EL (2001) Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res 47:151–154PubMedGoogle Scholar
  16. 16.
    Reimers A, Brodtkorb E, Sabers A (2015) Interactions between hormonal contraception and antiepileptic drugs: clinical and mechanistic considerations. Seizure 28:66–70PubMedGoogle Scholar
  17. 17.
    Krauss GL, Brandt J, Campbell M, Plate C, Summerfield M (1996) Antiepileptic medication and oral contraceptive interactions: a national survey of neurologists and obstetricians. Neurology 46:1534–1539PubMedGoogle Scholar
  18. 18.
    Fairgrieve SD, Jackson M, Jonas P, Walshaw D, White K, Montgomery TL et al (2000) Population based, prospective study of the care of women with epilepsy in pregnancy. BMJ 321:674–675PubMedPubMedCentralGoogle Scholar
  19. 19.
    Elger CE et al (2017) S1-Leitlinie Erster epileptischer Anfall und Epilepsien im Erwachsenenalter. www.dgn.org/leitlinien. Zugegriffen: 21. Sept. 2018 (Deutsche Gesellschaft für Neurologie, Hrsg. Leitlinien für Diagnostik und Therapie in der Neurologie)Google Scholar
  20. 20.
    Back DJ, Bates M, Bowden A, Breckenridge AM, Hall MJ, Jones H, MacIver M, Orme M, Perucca E, Richens A, Rowe PH, Smith E (1980) The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy. Contraception 22:495–503PubMedGoogle Scholar
  21. 21.
    Sonnen AEH (1982) Sodium valproate and the pill. In: Akimoto H, Kazamatsuri H, Seino M, Ward A (Hrsg) Advances in Epileptology. Raven Press, New York, S 429–432Google Scholar
  22. 22.
    Hempel E, Böhm W, Carol W, Klinger G (1973) Medikamentöse Enzyminduktion und hormonale Kontrazeption. Zentralbl Gynakol 95:1451–1457PubMedGoogle Scholar
  23. 23.
    Crawford P, Chadwick DJ, Martin C, Tjia J, Back DJ, Orme M (1990) The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids. Br J Clin Pharmacol 30:892–896PubMedPubMedCentralGoogle Scholar
  24. 24.
    Back DJ, Grimmer SF, Orme ML, Proudlove C, Mann RD, Breckenridge AM (1988) Evaluation of committee on safety of medicines yellow card reports on oral contraceptive-drug interactions with anticonvulsants and antibiotics. Br J Clin Pharmacol 25:527–532PubMedPubMedCentralGoogle Scholar
  25. 25.
    Kenyon IE (1972) Unplanned pregnancy in an epileptic. BMJ 1:686–687PubMedGoogle Scholar
  26. 26.
    Wang B, Sanchez RI, Franklin RB, Evans DC, Huskey SE (2004) The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol. Drug Metab Dispos 32:1209–1212PubMedGoogle Scholar
  27. 27.
    Zhang H, Cui D, Wang B, Han YH, Balimane P, Yang Z, Sinz M, Rodrigues AD (2007) Pharmacokinetic drug interactions involving 17alpha-ethinylestradiol: a new look at an old drug. Clin Pharmacokinet 46:133–157PubMedGoogle Scholar
  28. 28.
    Davis AR, Westhoff CL, Stanczyk FZ (2011) Carbamazepine coadministration with an oral contraceptive: effects on steroid pharmacokinetics, ovulation, and bleeding. Epilepsia 52:243–247PubMedPubMedCentralGoogle Scholar
  29. 29.
    Doose DR, Wang S‑S, Padmanabhan M, Schwabe S, Jacobs D, Bialer M (2003) Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 44:540–549PubMedGoogle Scholar
  30. 30.
    Falcão A, Vaz-da-Silva M, Gama H, Nunes T, Almeida L, Soares-da-Silva P (2013) Effect of eslicarbazepine acetate on the pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive in healthy women. Epilepsy Res 105:368–376PubMedGoogle Scholar
  31. 31.
    Fattore C, Cipolla G, Gatti G, Limido GL, Sturm Y, Bernasconi C, Perucca E (1999) Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women. Epilepsia 40:783–787PubMedGoogle Scholar
  32. 32.
    Klosterskov Jensen P, Saano V, Haring P, Svenstrup B, Menge GP (1992) Possible interaction between oxcarbazepine and an oral contraceptive. Epilepsia 33:1149–1152PubMedGoogle Scholar
  33. 33.
    Sidhu J, Job S, Singh S, Philipson R (2006) The pharmacokinetic and pharmacodynamics consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. Br J Clin Pharmacol 61:191–199PubMedGoogle Scholar
  34. 34.
    Herzog AG, Blum AS, Farina EL, Maestri XE, Newman J, Garcia E et al (2009) Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use. Neurology 72:911–914PubMedGoogle Scholar
  35. 35.
    Galimberti CA, Mazzucchelli I, Arbasino C, Canevini MP, Fattore C, Perucca E (2006) Increased apparent oral clearance of valproic acid during intake of combined contraceptive steroids in women with epilepsy. Epilepsia 47:1569–1572PubMedGoogle Scholar
  36. 36.
    Eldon MA, Underwood BA, Randinitis EJ, Sedman AJ (1998) Gabapentin does not interact with a contraceptive regimen of norethindrone acetate and ethinyl estradiol. Neurology 50:1146–1148PubMedGoogle Scholar
  37. 37.
    Ragueneau-Majlessi I, Levy RH, Janik F (2002) Levetiracetam does not alter the pharmacokinetics of an oral contraceptive in healthy women. Epilepsia 43:697–702PubMedGoogle Scholar
  38. 38.
    Griffith SG, Dai Y (2004) Effect of zonisamide on the pharmacokinetics and pharmacodynamics of a combination ethinyl estradiol-norethindrone oral contraceptive in healthy women. Clin Ther 26:2056–2065PubMedGoogle Scholar
  39. 39.
    Cawello W, Rosenkranz B, Schmid B, Wierich W (2013) Pharmacodynamic and pharmacokinetic evaluation of coadministration of lacosamide and an oral contraceptive (levonorgestrel plus ethinylestradiol) in healthy female volunteers. Epilepsia 54:530–536PubMedGoogle Scholar
  40. 40.
    Global tuberculosis report 2018. Geneva: World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGOGoogle Scholar
  41. 41.
    Schadberg T et al (2017) S2k Leitlinie: Tuberkulose im Erwachsenenalter. Pneumologie 71:325–397.  https://doi.org/10.1055/s-0043-105954 CrossRefGoogle Scholar
  42. 42.
    Simmons KB, Haddad LB, Nanda K, Curtis KM (2018) Drug interactions between rifamycin antibiotics and hormonal contraception: a systematic review. BJOG 125:804–811PubMedGoogle Scholar
  43. 43.
    LeBel M, Masson E, Guilbert E, Colborn D, Paquet F, Allard S, Vallée F, Narang PK (1998) Effects of rifabutin and rifampicin on the pharmacokinetics of ethinylestradiol and norethindrone. J Clin Pharmacol 38:1042–1050PubMedGoogle Scholar
  44. 44.
    Barditch-Crovo P, Trapnell CB, Ette E, Zacur HA, Coresh J, Rocco LE, Hendrix CW, Flexner C (1999) The effects of rifampin and rifabutin on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive. Clin Pharmacol Ther 65:428–438PubMedGoogle Scholar
  45. 45.
    Back DJ, Breckenridge AM, Crawford F, MacIver M, Orme ML, Park BK, Rowe PH, Smith E (1979) The effect of rifampicin on norethisterone pharmacokinetics. Eur J Clin Pharmacol 15:193–197PubMedGoogle Scholar
  46. 46.
    Back DJ, Breckenridge AM, Crawford FE, Hall JM, MacIver M, Orme ML, Rowe PH, Smith E, Watts MJ (1980) The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women. Contraception 21:135–143PubMedGoogle Scholar
  47. 47.
    Joshi JV, Joshi UM, Sankolli GM, Gupta K, Rao AP, Hazari K, Sheth UK, Saxena BN (1980) A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drugs. Contraception 21:617–629PubMedGoogle Scholar
  48. 48.
    Meyer B, Müller F, Wessels P, Maree J (1990) A model to detect interactions between roxithromycin and oral contraceptives. Clin Pharmacol Ther 47:671–674PubMedGoogle Scholar
  49. 49.
    Dickinson BD, Altman RD, Nielsen NH, Sterling ML (2001) Drug interactions between oral contraceptives and antibiotics. Obstet Gynecol 98:853–860PubMedGoogle Scholar
  50. 50.
    Simmons KB, Haddad LB, Nanda K, Curtis KM (2018) Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review. Am J Obstet Gynecol 218:88–97.e14PubMedGoogle Scholar
  51. 51.
    Joshi JV, Joshi UM, Sankholi GM, Krishna U, Mandlekar A, Chowdhury V, Hazari K, Gupta K, Sheth UK, Saxena BN (1980) A study of interaction of low-dose combination oral contraceptive with Ampicillin and Metronidazole. Contraception 22:643–652PubMedGoogle Scholar
  52. 52.
    Back DJ, Breckenridge AM, MacIver M, Orme M, Rowe PH, Staiger C, Thomas E, Tjia J (1982) The effects of ampicillin on oral contraceptive steroids in women. Br J Clin Pharmacol 14:43–48PubMedPubMedCentralGoogle Scholar
  53. 53.
    Adlercreutz H, Pulkkinen MO, Hämäläinen EK, Korpela JT (1984) Studies on the role of intestinal bacteria in metabolism of synthetic and natural steroid hormones. J Steroid Biochem 20:217–229PubMedGoogle Scholar
  54. 54.
    Murphy AA, Zacur HA, Charache P, Burkman RT (1991) The effect of tetracycline on levels of oral contraceptives. Am J Obstet Gynecol 164:28–33PubMedGoogle Scholar
  55. 55.
    Neely JL, Abate M, Swinker M, D’Angio R (1991) The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone. Obstet Gynecol 77:416–420PubMedGoogle Scholar
  56. 56.
    Scholten PC, Droppert RM, Zwinkels MG, Moesker HL, Nauta JJ, Hoepelman IM (1998) No interaction between ciprofloxacin and an oral contraceptive. Antimicrob Agents Chemother 42:3266–3268PubMedPubMedCentralGoogle Scholar
  57. 57.
    Droppert RA, Scholten PC, Zwinkels M, Hoepelman IM, Te Velde ER (1993) Lack of influence of ciprofloxacin on the effectiveness of oral contraceptives. Drugs 46:286–287Google Scholar
  58. 58.
    Maggiolo F, Puricelli G, Dottorini M, Caprioli S, Bianchi W, Suter F (1991) The effect of ciprofloxacin on oral contraceptive steroid treatments. Drugs Exp Clin Res 17:451–454PubMedGoogle Scholar
  59. 59.
    Csemiczky G, Alvendal C, Landgren BM (1996) Risk for ovulation in women taking a low-dose oral contraceptive (Microgynon) when receiving antibacterial treatment with a fluoroquinolone (ofloxacin). Adv Contracept 12:101–109PubMedGoogle Scholar
  60. 60.
    Back DJ, Tjia J, Martin C, Millar E, Salmon P, Orme M (1991) The interaction between clarithromycin and combined oral-contraceptive steroids. J Pharm Med 1:81–87Google Scholar
  61. 61.
    Blode H, Zeun S, Parke S, Zimmermann T, Rohde B, Mellinger U, Kunz M (2012) Evaluation of the effects of rifampicin, ketoconazole and erythromycin on the steady-state pharmacokinetics of the components of a novel oral contraceptive containing estradiol valerate and dienogest in healthy postmenopausal women. Contraception 86:337–344PubMedGoogle Scholar
  62. 62.
    Meyer B, Müller F, Wessels P, Maree J (1990) A model to detect interactions between roxithromycin and oral contraceptives. Clin Pharmacol Ther 47:671–674PubMedGoogle Scholar
  63. 63.
    Baxter K, Preston CL (Hrsg) (2018) Stockley’s drug interactions. http://www.new.medicinescomplete.com/. Zugegriffen: 21. Sept. 2018Google Scholar
  64. 64.
    Helms SE, Bredle DL, Zajic J, Jarjoura D, Brodell RT, Krishnarao I (1997) Oral contraceptive failure rates and oral antibiotics. J Am Acad Dermatol 36:705–710PubMedGoogle Scholar
  65. 65.
    Koopmans PC, Bos JH, de Jong van den Berg LT (2012) Are antibiotics related to oral combination contraceptive failures in the Netherlands? A case-crossover study. Pharmacoepidemiol Drug Saf 21:865–871PubMedGoogle Scholar
  66. 66.
    Jick SS, Hagberg KW, Kaye JA, Jick H (2009) The risk of unintended pregnancies in users of the contraceptive patch compared to users of oral contraceptives in the UK General Practice Research Database. Contraception 80:142–151PubMedGoogle Scholar
  67. 67.
    Toh S, Mitchell AA, Anderka M, de Jong-van__PARTICLESPACE__den Berg LT, Hernández-Díaz S (2011) Antibiotics and oral contraceptive failure—a case-crossover study. Contraception 83:418–425PubMedGoogle Scholar
  68. 68.
    Andrews E, Damle BD, Fang A, Foster G, Crownover P, LaBadie R, Glue P (2008) Pharmacokinetics and tolerability of voriconazole and a combination oral contraceptive co-administered in healthy female subjects. Br J Clin Pharmacol 65:531–539PubMedPubMedCentralGoogle Scholar
  69. 69.
    Hilbert J, Messig M, Kuye O, Friedman H (2001) Evaluation of interaction between fluconazole and an oral contraceptive in healthy women. Obstet Gynecol 98:218–223PubMedGoogle Scholar
  70. 70.
    Van Puijenbroek EP, Egberts AC, Meyboom RH, Leufkens HG (1999) Signalling possible drug-drug interactions in a spontaneous reporting system: delay of withdrawal bleeding during concomitant use of oral contraceptives and itraconazole. Br J Clin Pharmacol 47:689–693PubMedPubMedCentralGoogle Scholar
  71. 71.
    World Health Organization (2015) Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. World Health Organization, GenevaGoogle Scholar
  72. 72.
    Tittle V, Bull L, Boffito M, Nwokolo N (2015) Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives. Clin Pharmacokinet 54:23–34PubMedGoogle Scholar
  73. 73.
    Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, Weinstein MC, Freedberg KA (2006) The survival benefits of AIDS treatment in the United States. J Infect Dis 194:11–19PubMedGoogle Scholar
  74. 74.
    Sekar VJ, Lefebvre E, Guzman SS, Felicione E, De Pauw M, Vangeneugden T, Hoetelmans RM (2008) Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women. Antivir Ther (Lond) 13:563–569Google Scholar
  75. 75.
    Vogler MA, Patterson K, Kamemoto L, Park JG, Watts H, Aweeka F, Klingman KL, Cohn SE (2010) Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr 55:473–482PubMedPubMedCentralGoogle Scholar
  76. 76.
    Mikus G, Heinrich T, Bödigheimer J, Röder C, Matthee AK, Weiss J, Burhenne J, Haefeli WE (2017) Semisimultaneous midazolam administration to evaluate the time course of CYP3A activation by a single oral dose of efavirenz. J Clin Pharmacol 57:899–905PubMedGoogle Scholar
  77. 77.
    - (2018) Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Zugegriffen: 21. Sept. 2018 (Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States)Google Scholar
  78. 78.
    Sevinsky H, Eley T, Persson A, Garner D, Yones C, Nettles R, Krantz K, Bertz R, Zhang J (2011) The effect of efavirenz on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy HIV-negative women. Antivir Ther (Lond) 16:149–156Google Scholar
  79. 79.
    Carten ML, Kiser JJ, Kwara A, Mawhinney S, Cu-Uvin S (2012) Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel (Plan B), and efavirenz. Infect Dis Obstet Gynecol 2012:137192PubMedPubMedCentralGoogle Scholar
  80. 80.
    Landolt NK, Phanuphak N, Ubolyam S, Pinyakorn S, Kerr S, Ahluwalia J, Thongpaeng P, Thammajaruk N, Cremers S, Thomas T, Chaithongwongwatthana S, Lange JM, Ananworanich J (2014) Significant decrease of ethinylestradiol with nevirapine, and of etonogestrel with efavirenz in HIV-positive women. J Acquir Immune Defic Syndr 66:e50–e52PubMedGoogle Scholar
  81. 81.
    Landolt NK, Phanuphak N, Ubolyam S, Pinyakorn S, Kriengsinyot R, Ahluwalia J, Thongpaeng P, Gorowara M, Thammajaruk N, Chaithongwongwatthana S, Lange JM, Ananworanich J (2013) Efavirenz, in contrast to nevirapine, is associated with unfavorable progesterone and antiretroviral levels when coadministered with combined oral contraceptives. J Acquir Immune Defic Syndr 62:534–539PubMedGoogle Scholar
  82. 82.
    FDA Food and Drug Administration (FDA) (2011) Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir). http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203100Orig1s000ClinPharmR.pdf. Zugegriffen: 21. Sept. 2018Google Scholar
  83. 83.
    Lee JS, Calmy A, Andrieux-Meyer I, Ford N (2012) Review of the safety, efficacy, and pharmacokinetics of elvitegravir with an emphasis on resource-limited settings. HIV AIDS (Auckl) 4:5–15Google Scholar
  84. 84.
    Hilli J, Korhonen T, Turpeinen M, Hokkanen J, Mattila S, Laine K (2008) The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C〉A polymorphism. J Clin Pharmacol 48:986–994PubMedGoogle Scholar
  85. 85.
    Berry-Bibee EN, Kim MJ, Tepper NK, Riley HE, Curtis KM (2016) Co-administration of St. John’s wort and hormonal contraceptives: a systematic review. Contraception 94:668–677PubMedGoogle Scholar
  86. 86.
    Will-Shahab L, Bauer S, Kunter U, Roots I, Brattström A (2009) St John’s wort extract (Ze 117) does not alter the pharmacokinetics of a low-dose oral contraceptive. Eur J Clin Pharmacol 65:287–294PubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Abteilung Klinische Pharmakologie und PharmakoepidemiologieUniversitätsklinikum HeidelbergHeidelbergDeutschland

Personalised recommendations