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Ortho-Novum (Norethindrone / Mestranol) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

8. DRUG INTERACTIONS

Changes in contraceptive effectiveness associated with co-administration of other products:

Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding. Examples include rifampin, barbiturates, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and griseofulvin. Several cases of contraceptive failure and breakthrough bleeding have been reported in the literature with concomitant administration of antibiotics such as ampicillin and tetracyclines. However, clinical pharmacology studies investigating drug interaction between combined oral contraceptives and these antibiotics have reported inconsistent results.

Several of the anti-HIV protease inhibitors have been studied with co-administration of oral combination hormonal contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of oral contraceptive products may be affected with co-administration of anti-HIV protease inhibitors. Healthcare professionals should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information.

Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.

Increase in plasma levels associated with co-administered drugs:

Co-administration of atorvastatin and certain oral contraceptives containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation. CYP 3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels.

Changes in plasma levels of co-administered drugs:

Combination hormonal contraceptives containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporin, prednisolone, and theophylline have been reported with concomitant administration of oral contraceptives. Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic acid, morphine and clofibric acid, due to induction of conjugation, have been noted when these drugs were administered with oral contraceptives.

OVERDOSAGE

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.

NON-CONTRACEPTIVE HEALTH BENEFITS

The following non-contraceptive health benefits related to the use of combination oral contraceptives are supported by epidemiological studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg mestranol.73–78

Effects on menses:

  • increased menstrual cycle regularity
  • decreased blood loss and decreased incidence of iron deficiency anemia
  • decreased incidence of dysmenorrhea

Effects related to inhibition of ovulation:

  • decreased incidence of functional ovarian cysts
  • decreased incidence of ectopic pregnancies

Other effects:

  • decreased incidence of fibroadenomas and fibrocystic disease of the breast
  • decreased incidence of acute pelvic inflammatory disease
  • decreased incidence of endometrial cancer
  • decreased incidence of ovarian cancer

CONTRAINDICATIONS

Oral contraceptives should not be used in women who currently have the following conditions:

  • Thrombophlebitis or thromboembolic disorders
  • A past history of deep vein thrombophlebitis or thromboembolic disorders
  • Cerebral vascular or coronary artery disease (current or history)
  • Valvular heart disease with complications
  • Severe hypertension
  • Diabetes with vascular involvement
  • Headaches with focal neurological symptoms
  • Major surgery with prolonged immobilization
  • Known or suspected carcinoma of the breast
  • Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
  • Undiagnosed abnormal genital bleeding
  • Cholestatic jaundice of pregnancy or jaundice with prior pill use
  • Acute or chronic hepatocellular disease with abnormal liver function
  • Hepatic adenomas or carcinomas
  • Known or suspected pregnancy
  • Hypersensitivity to any component of this product

REFERENCES

  1. 1. Trussel J. Contraceptive efficacy. In Hatcher RA, Trussel J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers, 1998, in press
  2. 2.Stadel BV, Oral contraceptives and cardiovascular disease. (Pt. 1). N Engl J Med 1981; 305:612–618.
  3. 3.Stadel BV, Oral contraceptives and cardiovascular disease. (Pt. 2). N Engl J Med 1981; 305:672–677.
  4. 4.Adam SA, Thorogood M. Oral contraception and myocardial infarction revisited: the effects of new preparations and prescribing patterns. Br J Obstet Gynaecol 1981; 88:838–845.
  5. 5.Mann JI, Inman WH. Oral contraceptives and death from myocardial infarction. Br Med J 1975; 2(5965):245–248.
  6. 6.Mann JI, Vessey MP, Thorogood M, Doll R. Myocardial infarction in young women with special reference to oral contraceptive practice. Br Med J 1975; 2(5956):241–245.
  7. 7.Royal College of General Practitioners' Oral Contraception Study: further analyses of mortality in oral contraceptive users. Lancet 1981; 1:541–546.
  8. 8.Slone D, Shapiro S, Kaufman DW, Rosenberg L, Miettinen OS, Stolley PD. Risk of myocardial infarction in relation to current and discontinued use of oral contraceptives. N Engl J Med 1981; 305:420– 424.
  9. 9.Vessey MP. Female hormones and vascular disease – an epidemiological overview. Br J Fam Plann 1980; 6 (Supplement): 1–12.
  10. 10.Russell-Briefel RG, Ezzati TM, Fulwood R, Perlman JA, Murphy RS. Cardiovascular risk status and oral contraceptive use, United States, 1976–80. Prevent Med 1986; 15:352–362.
  11. 11.Goldbaum GM, Kendrick JS, Hogelin GC, Gentry EM. The relative impact of smoking and oral contraceptive use on women in the United States. JAMA 1987; 258:1339–1342.
  12. 12.Layde PM, Beral V. Further analyses of mortality in oral contraceptive users; Royal College of General Practitioners' Oral Contraception Study. (Table 5) Lancet 1981; 1:541–546.
  13. 13.Knopp RH. Arteriosclerosis risk: the roles of oral contraceptives and postmenopausal estrogens. J Reprod Med 1986; 31(9) (Supplement): 913–921.
  14. 14.Krauss RM, Roy S, Mishell DR, Casagrande J, Pike MC. Effects of two low-dose oral contraceptives on serum lipids and lipoproteins: Differential changes in high-density lipoproteins subclasses. Am J Obstet 1983; 145:446–452.
  15. 15.Wahl P, Walden C, Knopp R, Hoover J, Wallace R, Heiss G, Rifkind B. Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol. N Engl J Med 1983; 308:862–867.
  16. 16.Wynn V, Niththyananthan R. The effect of progestin in combined oral contraceptives on serum lipids with special reference to high density lipoproteins. Am J Obstet Gynecol 1982; 142:766– 771.
  17. 17.Wynn V, Godsland I. Effects of oral contraceptives on carbohydrate metabolism. J Reprod Med 1986; 31(9)(Supplement):892–897.
  18. 18.LaRosa JC. Atherosclerotic risk factors in cardiovascular disease. J Reprod Med 1986; 31(9)(Supplement):906–912.
  19. 19.Inman WH, Vessey MP. Investigation of death from pulmonary, coronary, and cerebral thrombosis and embolism in women of child-bearing age. Br Med J 1968; 2(5599):193–199.
  20. 20.Maguire MG, Tonascia J, Sartwell PE, Stolley PD, Tockman MS. Increased risk of thrombosis due to oral contraceptives: a further report. Am J Epidemiol 1979; 110(2):188–195.
  21. 21.Petitti DB, Wingerd J, Pellegrin F, Ramacharan S. Risk of vascular disease in women: smoking, oral contraceptives, noncontraceptive estrogens, and other factors. JAMA 1979; 242:1150–1154.
  22. 22.Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. Br Med J 1968; 2(5599):199–205.
  23. 23.Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report. Br Med J 1969; 2(5658):651–657.
  24. 24.Porter JB, Hunter JR, Danielson DA, Jick H, Stergachis A. Oral contraceptives and non-fatal vascular disease – recent experience. Obstet Gynecol 1982; 59(3):299–302.
  25. 25.Vessey M, Doll R, Peto R, Johnson B, Wiggins P. A long-term follow-up study of women using different methods of contraception: an interim report. J Biosocial Sci 1976; 8:375–427.
  26. 26.Royal College of General Practitioners: Oral Contraceptives, venous thrombosis, and varicose veins. J Royal Coll Gen Pract 1978; 28:393–399.
  27. 27.Collaborative Group for the Study of Stroke in Young Women: Oral contraception and increased risk of cerebral ischemia or thrombosis. N Engl J Med 1973; 288:871–878.
  28. 28.Petitti DB, Wingerd J. Use of oral contraceptives, cigarette smoking, and risk of subarachnoid hemorrhage. Lancet 1978; 2:234–236.
  29. 29.Inman WH. Oral contraceptives and fatal subarachnoid hemorrhage. Br Med J 1979; 2(6203):1468–1470.
  30. 30.Collaborative Group for the Study of Stroke in Young Women: Oral Contraceptives and stroke in young women: associated risk factors. JAMA 1975; 231:718–722.
  31. 31.Inman WH, Vessey MP, Westerholm B, Engelund A. Thromboembolic disease and the steroidal content of oral contraceptives. A report to the Committee on Safety of Drugs. Br Med J 1970; 2:203–209.
  32. 32.Meade TW, Greenberg G, Thompson SG. Progestogens and cardiovascular reactions associated with oral contraceptives and a comparison of the safety of 50- and 35-mcg oestrogen preparations. Br Med J 1980; 280(6224):1157–1161.
  33. 33.Kay CR. Progestogens and arterial disease – evidence from the Royal College of General Practitioners' Study. Am J Obstet Gynecol 1982; 142:762– 765.
  34. 34.Royal College of General Practitioners: Incidence of arterial disease among oral contraceptive users. J Royal Coll Gen Pract 1983; 33:75–82.
  35. 35.Ory HW. Mortality associated with fertility and fertility control: 1983. Family Planning Perspectives 1983; 15:50–56.
  36. 36.The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development: Oral contraceptive use and the risk of breast cancer. N Engl J Med 1986; 315:405–411.
  37. 37.Pike MC, Henderson BE, Krailo MD, Duke A, Roy S. Breast cancer in young women and use of oral contraceptives: possible modifying effect of formulation and age at use. Lancet 1983; 2:926–929.
  38. 38.Paul C, Skegg DG, Spears GFS, Kaldor JM. Oral contraceptives and breast cancer: A national study. Br Med J 1986; 293:723–725.
  39. 39.Miller DR, Rosenberg L, Kaufman DW, Schottenfeld D, Stolley PD, Shapiro S. Breast cancer risk in relation to early oral contraceptive use. Obstet Gynecol 1986; 68:863–868.
  40. 40.Olsson H, Olsson ML, Moller TR, Ranstam J, Holm P. Oral contraceptive use and breast cancer in young women in Sweden (letter). Lancet 1985; 1(8431):748–749.
  41. 41.McPherson K, Vessey M, Neil A, Doll R, Jones L, Roberts M. Early contraceptive use and breast cancer: Results of another case-control study. Br J Cancer 1987; 56:653–660.
  42. 42.Huggins GR, Zucker PF. Oral contraceptives and neoplasia: 1987 update. Fertil Steril 1987; 47:733–761.
  43. 43.McPherson K, Drife JO. The pill and breast cancer: why the uncertainty? Br Med J 1986; 293:709–710.
  44. 44.Shapiro S. Oral contraceptives – time to take stock. N Engl J Med 1987; 315:450–451.
  45. 45.Ory H, Naib Z, Conger SB, Hatcher RA, Tyler CW. Contraceptive choice and prevalence of cervical dysplasia and carcinoma in situ. Am J Obstet Gynecol 1976; 124:573–577.
  46. 46.Vessey MP, Lawless M, McPherson K, Yeates D. Neoplasia of the cervix uteri and contraception: a possible adverse effect of the pill. Lancet 1983; 2:930.
  47. 47.Brinton LA, Huggins GR, Lehman HF, Malli K, Savitz DA, Trapido E, Rosenthal J, Hoover R. Long term use of oral contraceptives and risk of invasive cervical cancer. Int J Cancer 1986; 38:339–344.
  48. 48.WHO Collaborative Study of Neoplasia and Steroid Contraceptives: Invasive cervical cancer and combined oral contraceptives. Br Med J 1985; 290:961–965.
  49. 49.Rooks JB, Ory HW, Ishak KG, Strauss LT, Greenspan JR, Hill AP, Tyler CW. Epidemiology of hepatocellular adenoma: the role of oral contraceptive use. JAMA 1979; 242:644–648.
  50. 50.Bein NN, Goldsmith HS. Recurrent massive hemorrhage from benign hepatic tumors secondary to oral contraceptives. Br J Surg 1977; 64:433–435.
  51. 51.Klatskin G. Hepatic tumors: possible relationship to use of oral contraceptives. Gastroenterology 1977; 73:386–394.
  52. 52.Henderson BE, Preston-Martin S, Edmondson HA, Peters RL, Pike MC. Hepatocellular carcinoma and oral contraceptives. Br J Cancer 1983; 48:437–440.
  53. 53.Neuberger J, Forman D, Doll R, Williams R. Oral contraceptives and hepatocellular carcinoma. Br Med J 1986; 292:1355–1357.
  54. 54.Forman D, Vincent TJ, Doll R. Cancer of the liver and oral contraceptives. Br Med J 1986; 292:1357–1361.
  55. 55.Harlap S, Eldor J. Births following oral contraceptive failures. Obstet Gynecol 1980; 55:447–452.
  56. 56.Savolainen E, Saksela E, Saxen L. Teratogenic hazards of oral contraceptives analyzed in a national malformation register. Am J Obstet Gynecol 1981; 140:521–524.
  57. 57.Janerich DT, Piper JM, Glebatis DM. Oral contraceptives and birth defects. Am J Epidemiol 1980; 112:73–79.
  58. 58.Ferencz C, Matanoski GM, Wilson PD, Rubin JD, Neill CA, Gutberlet R. Maternal hormone therapy and congenital heart disease. Teratology 1980; 21:225–239.
  59. 59.Rothman KJ, Fyler DC, Goldblatt A, Kreidberg MB. Exogenous hormones and other drug exposures of children with congenital heart disease. Am J Epidemiol 1979; 109:433–439.
  60. 60.Boston Collaborative Drug Surveillance Program: Oral contraceptives and venous thromboembolic disease, surgically confirmed gallbladder disease, and breast tumors. Lancet 1973; 1:1399–1404.
  61. 61.Royal College of General Practitioners: Oral contraceptives and health. New York, Pittman 1974.
  62. 62.Layde PM, Vessey MP, Yeates D. Risk of gallbladder disease: a cohort study of young women attending family planning clinics. J Epidemiol Community Health 1982; 36:274–278.
  63. 63.Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO): Prevalence of gallstone disease in an Italian adult female population. Am J Epidemiol 1984; 119:796–805.
  64. 64.Storm BL, Tamragouri RT, Morse ML, Lazar EL, West SL, Stolley PD, Jones JK. Oral contraceptives and other risk factors for gallbladder disease. Clin Pharmacol Ther 1986; 39:335–341.
  65. 65.Wynn V, Adams PW, Godsland IF, Melrose J, Niththyananthan R, Oakley NW, Seedj A. Comparison of effects of different combined oral contraceptive formulations on carbohydrate and lipid metabolism. Lancet 1979; 1:1045–1049.
  66. 66.Wynn V. Effect of progesterone and progestins on carbohydrate metabolism. In: Progesterone and Progestin. Bardin CW, Milgrom E, Mauvis-Jarvis P. eds. New York, Raven Press, 1983; pp. 395–410.
  67. 67.Perlman JA, Roussell-Briefel RG, Ezzati TM, Lieberknecht G. Oral glucose tolerance and the potency of oral contraceptive progestogens. J Chronic Dis 1985; 38:857–864.
  68. 68.Royal College of General Practitioners' Oral Contraception Study: Effect on hypertension and benign breast disease of progestogen component in combined oral contraceptives. Lancet 1977; 1:624.
  69. 69.Fisch IR, Frank J. Oral contraceptives and blood pressure. JAMA 1977; 237:2499–2503.
  70. 70.Laragh AJ. Oral contraceptive induced hypertension – nine years later. Am J Obstet Gynecol 1976; 126:141–147.
  71. 71.Ramcharan S, Peritz E, Pellegrin FA, Williams WT. Incidence of hypertension in the Walnut Creek Contraceptive Drug Study cohort: In: Pharmacology of steroid contraceptive drugs. Garattini S, Berendes HW. Eds. New York, Raven Press, 1977; pp. 277–288, (Monographs of the Mario Negri Institute for Pharmacological Research Milan.)
  72. 72.Stockley I. Interactions with oral contraceptives. J Pharm 1976; 216:140–143.
  73. 73.The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development: Oral contraceptive use and the risk of ovarian cancer. JAMA 1983; 249:1596– 1599.
  74. 74.The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development: Combination oral contraceptive use and the risk of endometrial cancer. JAMA 1987; 257:796–800.
  75. 75.Ory HW. Functional ovarian cysts and oral contraceptives: negative association confirmed surgically. JAMA 1974; 228:68– 69.
  76. 76.Ory HW, Cole P, MacMahon B, Hoover R. Oral contraceptives and reduced risk of benign breast disease. N Engl J Med 1976; 294:419–422.
  77. 77.Ory HW. The noncontraceptive health benefits from oral contraceptive use. Fam Plann Perspect 1982; 14:182–184.
  78. 78.Ory HW, Forrest JD, Lincoln R. Making choices: Evaluating the health risks and benefits of birth control methods. New York, The Alan Guttmacher Institute, 1983; p. 1.
  79. 79.Schlesselman J, Stadel BV, Murray P, Lai S. Breast cancer in relation to early use of oral contraceptives. JAMA 1988; 259:1828–1833.
  80. 80.Hennekens CH, Speizer FE, Lipnick RJ, Rosner B, Bain C, Belanger C, Stampfer MJ, Willett W, Peto R. A case-control study of oral contraceptive use and breast cancer. JNCI 1984; 72:39– 42.
  81. 81.LaVecchia C, Decarli A, Fasoli M, Franceschi S, Gentile A, Negri E, Parazzini F, Tognoni G. Oral contraceptives and cancers of the breast and of the female genital tract. Interim results from a case-control study. Br J Cancer 1986; 54:311–317.
  82. 82.Meirik O, Lund E, Adami H, Bergstrom R, Christoffersen T, Bergsjo P. Oral contraceptive use and breast cancer in young women. A Joint National Case-control study in Sweden and Norway. Lancet 1986; 11:650–654.
  83. 83.Kay CR, Hannaford PC. Breast cancer and the pill – A further report from the Royal College of General Practitioners' oral contraception study. Br J Cancer 1988; 58:675–680.
  84. 84.Stadel BV, Lai S, Schlesselman JJ, Murray P. Oral contraceptives and premenopausal breast cancer in nulliparous women. Contraception 1988; 38:287–299.
  85. 85.Miller DR, Rosenberg L, Kaufman DW, Stolley P, Warshauer ME, Shapiro S. Breast cancer before age 45 and oral contraceptive use: New Findings. Am J Epidemiol 1989; 129:269–280.
  86. 86.The UK National Case-Control Study Group, Oral contraceptive use and breast cancer risk in young women. Lancet 1989; 1:973–982.
  87. 87.Schlesselman JJ. Cancer of the breast and reproductive tract in relation to use of oral contraceptives. Contraception 1989; 40:1–38.
  88. 88.Vessey MP, McPherson K, Villard-Mackintosh L, Yeates D. Oral contraceptives and breast cancer: latest findings in a large cohort study. Br J Cancer 1989; 59:613–617.
  89. 89.Jick SS, Walker AM, Stergachis A, Jick H. Oral contraceptives and breast cancer. Br J Cancer 1989; 59:618–621.
  90. 90.Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies. Lancet 1996; 347:1713–1727.
  91. 91.Palmer JR, Rosenberg L, Kaufman DW, Warshauer ME, Stolley P, Shapiro S. Oral Contraceptive Use and Liver Cancer. Am J Epidemiol 1989; 130:878–882.
  92. 92.Improving access to quality care in family planning: Medical eligibility criteria for contraceptive use. Geneva, WHO, Family and Reproductive Health, 1996.

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