Oral Contraceptives and GeneMedRx

Christopher E. Stephens
UW Doctor of Pharmacy Candidate 2007

July 26th 2006

Why I chose oral contraceptives

Oral contraceptives are a fact of life for a large portion of the population that a pharmacist will encounter. Men, even male medical practitioners, often feel uncomfortable talking to women about contraception, and women often have less confidence that a man can answer their questions on the topic.

Why I chose oral contraceptives

I want to be able to serve all of my patients, not shy away from a topic because I am unfamiliar with it, or come off as uneducated to my female patients.
Nothing in life is to be feared. It is only to be understood. Marie Curie

Whats in an oral contraceptive?

Oral contraceptives contain either a combination of estrogen and progestin or a progestin alone. Estrogen, usually as ethinyl estradiol, prevents the development of follicles by suppressing FSH; increases the effect of progestins; and stabilizes the endometrial lining. Progestins block ovulation by suppressing the LH surge and contributes to contraception by thickening cervical mucus

What is GeneMedRx?
GeneMedRx is a software tool designed to help physicians predict whether or not drugs are safe and effective for patients.1

1http://www.genemedrx.com/public/home.html

How does it work?

GeneMedRx is designed to predict drug interactions based upon how drugs are metabolized and what enzymes or transporters are usually involved in that metabolism. The program can take into account a persons genetics, the genes that affect each persons ability to make specific enzymes or express transporters, in predicting these drug interactions. If you do not know your genetic information, Genelex, the company that created GeneMedRx, offers genetic testing

Contraceptive Drug Interaction

A search of PubMed was conducted using the keywords Contraceptive Drug Interaction 692 results were found that were accessible through the University of Washington. 100 of those summaries were reviewed 41 Abstracts were evaluated 31 Full text articles were selected

Sixty Five Drug Interactions were Identified and processed through GeneMedRx
12 Predicted by GeneMed Rx 35 18 Not Predicted Needed changes

72% of all information found was already being predicted by the GeneMedRx program!
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Total 18% 28%

54%

Not already entered Entered but changed Already entered

Keeping GeneMedRx Current

The most recent article suggesting a drug interaction was only published Mar 2006 Sixty five potential interactions were found on PubMed and this translated into over 30 new notes added to GeneMedRx to ensure that all drug/drug, drug/class and drug/enzyme interactions were updated.

Oral contraceptives and GeneMedRx

Estrogen Estrogen Estrogen Progestin some metabolized Inhibits: Induces: metabolized Progestins by: by: Inhibit: UGT1A1 CYP1A2 UGT1A4 CYP2C9 CYP2C9 CYP3A CYP2C9 CYP2C19 CYP2C19 CYP1A2 CYP2C19 CYP3A CYP3A CYP2B6 CYP3A

Beneficial Metabolism
Estrogen increases the effect of progestins; as you can see from the previous table, progestins are metabolized by the CYPs 2C9, 2C19, and the 3A series, but estrogen inhibits those same enzymes, this means that progestins are not metabolized as quickly in the presence of estrogen and therefore have more time to act in the body.

When interactions go bad

Estrogens ability to boost progestins is beneficial, but that same trait turns out to be harmful when the drug that is inhibited has side effects or toxicities. If ethinyl estradiol is given with the drug clozapine, which is metabolized in part by 3A4, the concentrations of clozapine increase in the body and can lead to increased side effects, including drowsiness, tremor or nausea.

Drugs that may have increased plasma levels because of oral contraceptives
Caffeine Carisoprodol Chlorpromazine Clozapine Naratriptan Omeprazole Tizanidine
Dose reduction may be required for these medications while on contraceptives

Drugs that may have decreased plasma levels from oral contraceptives
Dextromethorphan Lamotrigine Valproic acid Warfarin
Dose adjustments may be required for these medications while on oral contraceptives

Drugs that can decrease the effectiveness of oral contraceptives

Antibiotics Felbamate Kaletra Nelfinavir Oxcarbazepine Phenytoin Ritonavir Tegaserod Carbamazepine Griseofulvin Lamotrigine Nevirapine Phenobarbitol Rifampin St. Johns Wort Topiramate

Alternate methods of contraception should be suggested while on these medications.

Drug Interaction Trends

25 20 15 10 5 0
No Change in either drug Increase in OC levels Increase in non-OC drug Decrease in OC Decrease in non-OC Other

Culprits and Victims

The ethinyl estradiol component of oral contraceptives was the primary culprit/victim in most drug interactions; 46 of the 65 drug interactions found involved ethinyl estradiol!
The drug class most often the culprit/victim of drug interactions were the anticonvulsant drugs, such as topiramate, lamotrigine and phenobarbital.

So what does this mean?

A decrease in the efficacy of oral contraceptives was the primary result of many drug interactions, leading to unplanned pregnancies. Increased toxicity or side effects of some medications was another potential drug/drug interaction problem A third problem is sub-therapeutic doses being given because the OC is causing a decrease in the levels of treatment drug; for example, when dosing lamotrigine and OCs.

So what can we do?

Practitioners should be aware of all medications that their patients are taking and not forget to or feel uncomfortable with inquiring about contraception. Patients should be sure to tell their doctor/pharmacist all of the drugs that they are taking, including contraceptives or herbal products. The one drug you forget to mention will probably be the one that causes problems!

How can GeneMedRx help?

The list of drugs that exist and can potentially interact is long and keeps growing. New studies are being done and new articles are published frequently that tell of new drugs or new interactions. The GeneMedRx program is useful in actually predicting these interactions before they occur and thereby informing the patient/practitioner before a drug interaction may occur. The program also provides notes about and references to articles that list specific drug interactions.

Learn more about GeneMedRx

http://www.genemedrx.com/demo.html

Special thanks to Genelex, Seattle

References
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