Contraceptive efficacy, pharmacokinetics, and safety of Annuelle biodegradable norethindrone pellet implants.

ABSTRACT

OBJECTIVE: To evaluate the contraceptive efficacy, pharmacokinetics, and safety of two formulations of Annuelle (Endocon, Inc., South Walpole, MA) biodegradable norethindrone (NET) SC pellet implants. DESIGN: Prospective observational study. SETTING: Two clinical sites in the United States. PATIENT(S) Thirty-nine healthy, fertile, sexually active women. INTERVENTION(S) Nineteen women received a four-pellet system containing 174 mg NET; 20 women received a five-pellet system containing 266.5 mg NET. MAIN OUTCOME MEASURE(S) Contraceptive efficacy, median serum NET levels, adverse events. RESULT(S) No pregnancies were observed in 293 woman-months in the four-pellet group or in 375 woman-months in the five-pellet group. An initial burst in median serum NET levels occurred in the first 24 hours postinsertion followed by a steady decline over the next 3 years. Norethindrone levels varied considerably among women. The main side effect was bleeding abnormalities, which persisted in half the participants for up to 2 years. No serious adverse events were reported that were related to the pellets. Pellet insertion and removal generally were uncomplicated. CONCLUSION(S) Annuelle shows potential as an effective, safe contraceptive with distinct advantages over other long-acting agents, because it is biodegradable but can be removed if problems arise or if fertility is desired.

ABSTRACT

PIP The contraceptive efficacy, pharmacokinetics, bleeding profiles, and safety of two formulations of the Annuelle contraceptive implant system were investigated in a prospective study conducted at two clinical sites in the US. 19 women received a four-pellet system containing 174 mg of norethindrone (NET) and 20 women received a five-pellet system containing 266.5 mg of NET. Participants were followed quarterly for up to 39 months. No pregnancies were recorded during 293 woman-months in the four-pellet group and 375 woman-months in the five-pellet group. Most women exhibited a burst in NET levels (values equal to or exceeding 2 ng/ml) 24 hours after pellet insertion, followed by a steady decline over the next 3 years. Ovulation was inhibited in most participants in both groups at 9 months after insertion, and this protective effect persisted as long as 2 years in 16 of the 39 subjects. More than 80% of women in both groups had at least one clinically important bleeding pattern (e.g., frequent, irregular, or prolonged bleeding) in the first 90-day interval; this percentage dropped over time, but persisted in half the participants for up to 2 years. Serum levels of total cholesterol, low density lipoproteins, and triglycerides dropped substantially after pellet insertion in both groups, while high density lipoprotein levels remained fairly constant. Overall, the Annuelle system is considered to have potential as a safe, long-acting contraceptive agent capable of being surgically removed before complete absorption. Of concern, however, is the relatively long period during which the product releases detectable amounts of NET but may no longer be a fully effective contraceptive agent.