Pharmacodynamics

The contraceptive effect of IMPLANON™ (etonogestrel implant) is achieved by several mechanisms that include suppression of ovulation, increased viscosity of the cervical mucus, and alterations in the endometrium.

Pharmacokinetics

Absorption

After subdermal insertion of IMPLANON™, ENG is released into the circulation and is approximately 100% bioavailable.

The mean peak serum concentrations in three pharmacokinetic studies ranged between 781 and 894 pg/mL and were reached within the first few weeks after insertion. The mean serum ENG con- centration decreases gradually over time declining to 192-261 pg/mL at 12 months (n=41), 154-194 pg/mL at 24 months (n=35), and 156-177 pg/mL at 36 months (n=17). The pharmacokinetic pro- file of IMPLANON™ from one of three pharmacokinetic studies is shown in Figure 2.

Figure 2. Mean serum concentration-time profile of ENG during two years of IMPLANON™ use and after removal in 20 healthy women.

Figure 2

Distribution

The apparent volume of distribution averages about 201 L. ENG is approximately 32% bound to sex hormone binding globulin (SHBG) and 66% bound to albumin in blood.

Metabolism

In vitro data shows that ENG is metabolized in liver microsomes by the cytochrome P450 3A4 isoenzyme. The biological activity of ENG metabolites is unknown.

Excretion

The elimination half-life of ENG is approximately 25 hours. Excretion of ENG and its metabolites, either as free steroid or as conjugates, is mainly in urine and to a lesser extent in feces. After removal of IMPLANON™, ENG concentrations decreased below sensitivity of the assay by one week.

Special Populations

Overweight Women

The effectiveness of IMPLANON™ in overweight women has not been defined because women who weighed more than 130% of their ideal body weight were not studied. However, serum con- centrations of ENG are inversely related to body weight and decrease with time after insertion. It is therefore possible that, with time, IMPLANON™ may be less effective in overweight women, especially in the presence of other factors that decrease etono- gestrel concentrations such as concomitant use of hepatic enzyme inducers.

Race

No formal studies were conducted to evaluate the effect of race on the pharmacokinetics of IMPLANON™.

Hepatic Insufficiency

No formal studies were conducted to evaluate the effect of hepatic disease on the pharmacokinetics of IMPLANON™. However, ENG is metabolized by the liver, and therefore, use in patients with active liver disease is contraindicated.

Renal Insufficiency

No formal studies were conducted to evaluate the effect of renal dis- ease on the pharmacokinetics of IMPLANON™.

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