A statement from the Food and Drug Administration regarding NuvaRing:

At the present time, we continue to monitor adverse event reports for NuvaRing as we do for all approved combination hormonal contraceptive products. The label for NuvaRing includes an additional warning that is included in labeling for all combination hormonal contraceptives that contain a third generation progestin. The warning is as follows:

Several epidemiology studies indicate that third generation oral contraceptives, including those containing desogestrel (etonogestrel, the progestin in NuvaRing., is the biologically active metabolite of desogestrel), are associated with a higher risk of venous thromboembolism than certain second generation oral contraceptives. In general, these studies indicate an approximate two-fold increased risk, which corresponds to an additional one to two cases of venous thromboembolism per 10,000 women-years of use. However, data from additional studies have not shown this two-fold increase in risk. It is unknown if NuvaRing(r) has a different risk of venous thromboembolism than second generation oral contraceptives.

There also is a precaution about the potential for toxic shock syndrome in the NuvaRing label that reads as follows:

TOXIC SHOCK SYNDROME (TSS) Cases of toxic shock syndrome have been associated with tampons and certain barrier contraceptives. Very rare cases of TSS have been reported by NuvaRing users; in some cases the women were also using tampons. No causal relationship between the use of NuvaRing and TSS has been established. If a patient exhibits signs or symptoms of TSS, the possibility of this diagnosis should not be excluded and appropriate medical evaluation and treatment initiated.

Questions Submitted To Organon And The Company's Responses:

1. A healthy 26-year-old non-smoking woman in San Diego was hospitalized for 12 days with deep vein thrombosis and pulmonary embolism. She is on a blood thinner (Coumadin) and still has clots in her lungs and calf. The doctor said the clotting was a result of her using NuvaRing. Is this an unusual or a more common problem for NuvaRing users?
Let me begin by expressing my sympathy to the woman whom you have indicated experienced the thrombotic events while using NuvaRing. NuvaRing is an effective and safe method of contraception; however, as with all hormonal contraception is associated with a low risk of thrombosis. It should be noted, that the risk of thrombosis exists regardless of whether a woman is on hormonal contraception, and increases for women who are pregnant.

2. Has Organon monitored how many users of NuvaRing have reported pulmonary embolism and thrombosis-related conditions since its approval by the FDA in October 2001?
Organon continuously monitors reported adverse events of all its products worldwide, including the occurrence of thromboembolic events in association with its contraceptives. In order to continue to evaluate the safety profile of NuvaRing, Organon has collected information relating to adverse events and reported them to the Food and Drug Administration (FDA), since market introduction in 2001.

3. An analysis of some of the FDA raw data for Adverse Events reported showed the following results for NuvaRing: From October 2005 through June 2006, 24 reported incidents of pulmonary embolism (do you agree with that figure?). Is this expected or is this excessive?
Evidence from our own postmarketing surveillance data - which incorporates data on around two million women-years of use worldwide – does not indicate that the risk associated with NuvaRing is higher than combined oral contraceptives (the Pill). The data reported in the FDA adverse event database are consistent with the data in our own Safety Database.

4. The use of oral contraceptives, as well as NuvaRing, is associated with an increased risk of getting blood clots. Is a woman at greater risk of developing blood clots by using NuvaRing than by using an oral contraceptive? If so, how much greater is that risk? If it’s unknown whether the risk is greater or not, why?
Our safety data do not indicate that the risk of thrombotic events associated with NuvaRing is higher than that associated with combined oral contraceptives.

5. Do you feel NuvaRing is safe for women to use?
NuvaRing and combined oral contraceptives are safe products, researched, developed and marketed according to the highest standards of scientific knowledge. However, women should be aware that thrombosis is a rare event associated with their use. Women are strongly encouraged to become aware of all risks and benefits of all contraceptive options available. The foundation of this undertaking is provided in the product labeling from which a dialogue with their health care providers is strongly encouraged.

6. Are people being properly warned about the potential serious risks of using NuvaRing?
Yes, this information is available to prescribers from a number of sources including the full Prescribing Information. It is also available to users in the patient package insert. Any woman who is concerned about thrombosis or about the risk factors associated with it should discuss this matter with her healthcare provider.

Can Organon tell us how many users of NuvaRing have reported pulmonary embolism as an adverse event since October 2001?
It is Organon's policy to not provide this information as a simple absolute number of reports will not provide an accurate picture of safety or risk; it is more appropriate to provide an incidence or reporting rate, as this puts the number of reports in the context of patient exposure. In the US, the overall reporting rate of venous thromboembolism since the introduction of the product is around 1 per 10,000 women years.

On your question for clarification:
10,000 women years stands for 10,000 women using the product for one year. In terms of cycles this would translate to 130,000 cycles. However, incidences of rare conditions are usually expressed per number of women years.