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


METHODS
Prospective observational study.


METHODS
Two clinical sites in the United States.


METHODS
Thirty-nine healthy, fertile, sexually active women.


METHODS
Nineteen women received a four-pellet system containing 174 mg NET; 20 women received a five-pellet system containing 266.5 mg NET.


METHODS
Contraceptive efficacy, median serum NET levels, adverse events.


RESULTS
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.


CONCLUSIONS
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.
Raymond
E G
EG
Family Health International, Research Triangle Park, North Carolina 27709, USA. braymond@fhi.org
Singh
M
M
Archer
D F
DF
Saxena
B B
BB
Baker
J
J
Cole
D
D
D000293:Adolescent; D000328:Adult; D001673:Biodegradation, Environmental; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000009:adverse effects / Q000097:blood* / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood; D014592:Uterine Hemorrhage / Q000139:chemically induced
D003280:Contraceptives, Oral, Synthetic; D004343:Drug Implants; D011374:Progesterone; D004958:Estradiol; D009640:Norethindrone