Drug interactions and OCs — Base decisions on facts

Do you still recommend that women use backup contraception when prescribed antibiotics during oral contraceptive use? If you do, it's time to check your approach, according to information presented at the Contraceptive Technology conference.1

There is no evidence that shows that antibiotics will reduce estrogen and progestin in a clinically significant way or increase pregnancy rates, says Michael Policar, MD, MPH, associate clinical professor in the department of obstetrics, gynecology and reproductive sciences at the University of California San Francisco. Policar presented information at the 2007 Contraceptive Technology Quest for Excellence conference in Atlanta.

"In the absence of pharmacokinetic, observational or epidemiological data, it is no longer accepted that an interaction between antibiotics and OCs exists," he notes.

In hormonal contraceptive users taking a short or long course of antibiotics, there is no evidence-based reason to routinely recommend backup contraception or a change to a more effective method, says Policar. If a woman is informed of a potential interaction, the extremely low magnitude of risk must be stressed. Pregnancies that occur in women using both hormonal contraceptives and antibiotics are due to other factors, he adds.

Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine in Atlanta, offers the following case study when it comes to OC use and drug interactions:

A 23-year-old woman has had a history of seizures and depression. She has a serious problem with drugs and alcohol. She is on carbamazepine and topiramate (Topamax, Ortho-McNeil Neurologics; Titusville, NJ), as well as oral contraceptives. She became pregnant during the last cycle of a stormy relationship. She is in her first trimester.

Look for these types of "red-flag" medical conditions when it comes to potential drug interactions, says Policar. Such conditions include seizure disorder/epilepsy, tuberculosis, skin and nail fungal infections, depression (use of St. John's Wort) and HIV infection.

With anti-epileptic drugs (AEDs), certain enzyme-inducing drugs can reduce hormonal contraceptive efficacy by increasing the secondary metabolism of estrogen and progestin by induction of CYP450 enzymes and increasing sex hormone-binding globulin (SHBG), which decreases free progestin. The risk of ovulation is more dependent on reduction in the progestin level than the estrogen level. Enzyme-inducing AEDs include: carbamazepine (Tegretol), felbamate (Felbatol, MedPointe Pharmaceuticals; Somerset, NJ), lamotrigine (Lamictal, GlaxoSmithKline), oxcarbazine (Trileptal, Novartis), phenobarbital (generic), phenytoin (Dilantin, Pfizer; New York City), and topiramate (Topamax, Ortho-McNeil).2

Look for use of AED drugs beyond treatment of seizures, says Policar. For example, carbamazepine is now used for treatment of trigeminal neuralgia, schizophrenia, and bipolar disorder, while topiramate is being used in treatment of migraines, bipolar disorder, and obesity.

Pills are so complex, notes Hatcher. While the patient in the case study above may have understood that the AED drugs she was taking might cause birth defects, she did not understand that they may also make her oral contraceptive less effective. The woman opted to have an abortion and chose a more effective birth control method. Such options would include intrauterine contraception (Mirena, Bayer HealthCare Pharmaceuticals; Wayne, NJ, and ParaGard, Barr Pharmaceuticals, Pomona, NY) and the contraceptive injection depot medroxyprogesterone acetate (DMPA; Depo Provera, Pfizer.)

Look for use of rifampin (generic) and rifampin-containing drugs [Rifadin (Sanofi-Aventis; Bridge-water, NJ); Rimactane (Novartis); Rifamate (Sanofi-Aventis), Rifater (Sanofi-Aventis)], as well as rifapentine (Priftin, Sanofi-Aventis), commonly used in tuberculosis treatment, says Policar. These drugs are enzyme inducers. Rifampin also is being used as a treatment for methicillin-resistant Staph aureus (MRSA) skin infections.

Clinical recommendations for birth control for patients on rifampin for tuberculosis treatment include intrauterine contraception and DMPA. Patients on a short-term course of the drug for MRSA should use backup contraception, advises Policar.

What about women with skin and nail fungal infections? Griseofulvin (generic), once used for treatment of ringworm and nail infections, has been linked to induction of hepatic enzymes, but only insufficient, outdated data are available, says Policar. Newer antifungal drugs such as fluconazole (generic), itraconazole (generic), and ketoconazole (generic) have no hormonal drug interaction, he states.

Caution: St. John's Wort

When asking patients about drug use, don't forget to check over-the-counter drugs, says Policar. One such drug is St. John's Wort, now widely used for depression. Research shows induction of the CYP450 enzyme, comparable to rifampin and carbamazepine when given for 10 or more days.3 Caution patients that oral contraceptive effectiveness may be reduced if St. John's Wort is used, says Policar.

How about drugs used for treatment of HIV infection? Data from a few small unpublished studies show that OC metabolism may be altered when using antiretroviral drugs; however, there are no studies of clinical effect, he notes. The World Health Organization eligibility criteria classes use of oral contraceptives in women using antiretroviral drugs, as a "2," in which the advantages of using the method generally outweigh the theoretical or proven risks.4 Clinicians need to stay tuned for more research in this area, says Policar.

References

  1. Policar MS. Drug interactions with contraceptives: EBM or urban legend? Presented at the 2007 Contraceptive Technology Quest for Excellence conference. Atlanta; November 2007.
  2. Thorneycroft I, Klein P, Simon J. The impact of antiepileptic drug therapy on steroidal contraceptive efficacy. Epilepsy Behav 2006; 9:31-39.
  3. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St. John's Wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290:1,500-1,504.
  4. World Health Organization. Medical Eligibility Criteria for Contraceptive Use. Geneva: World Health Organization; 2004.