"The U.S. Food and Drug Administration today announced that it has approved an amended application submitted by Teva Women's Health, Inc. to market Plan B One-Step (active ingredient levonorgestrel) for use without a prescription by women 15 years"...
Mechanism of Action
Emergency contraceptive pills are not effective if a woman is already pregnant. Next Choice™ is believed to act as an emergency contraceptive principally by preventing ovulation or fertilization (by altering tubal transport of sperm and/or ova). In addition, they may inhibit implantation (by altering the endometrium). It is not effective once the process of implantation has begun.
No specific investigation of the absolute bioavailability of levonorgestrel tablets in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability about 100%) and is not subject to first pass metabolism.
After a single dose of levonorgestrel tablets (0.75 mg) administered to 16 women under fasting conditions, the mean maximum serum concentration of levonorgestrel was 14.1 ng/mL at an average of 1.6 hours. See Table 2.
Table 2: Pharmacokinetic Parameter Values Following Single
Dose Administration of Levonorgestrel Tablets 0.75 mg to Healthy Female Volunteers
under Fasting Conditions
|Mean (± SD)|
|Levonorgestrel||14.1 (7.7)||1.6 (0.7)||7.7 (2.7)||260.0||24.4 (5.3)||123.1 (50.1)|
|Cmax = maximum concentration
Tmax = time to maximum concentration
CL = clearance
Vd = volume of distribution
t½ = elimination half life
AUCinf= area under the drug concentration curve from time 0 to infinity
Effect of Food: The effect of food on the rate and the extent of levonorgestrel absorption following single oral administration of levonorgestrel has not been evaluated.
The apparent volume of distribution of levonorgestrel is reported to be approximately 1.8 L/kg. It is about 97.5 to 99% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin.
Following absorption, levonorgestrel is conjugated at the 17β-0H position to form sulfate conjugates and, to a lesser extent, glucuronide conjugates in plasma. Significant amounts of conjugated and unconjugated 3α, 5β-tetrahydro levonorgestrel are also present in plasma, along with much smaller amounts of 3α, 5α-tetrahydro levonorgestrel and 16β hydroxy levonorgestrel. Levonorgestrel and its phase I metabolites are excreted primarily as glucuronide conjugates. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users.
Pediatric: This product is not intended for use in the premenarcheal population, and pharmacokinetic data are not available for this population.
Geriatric: This product is not intended for use in postmenopausal women and pharmacokinetic data are not available for this population.
Race: No formal studies have evaluated the effect of race on pharmacokinetics of levonorgestrel tablets. However, clinical trials demonstrated a higher pregnancy rate in Chinese women with both levonorgestrel tablets and the Yuzpe regimen (another form of emergency contraception). The reason for this apparent increase in the pregnancy rate with emergency contraceptives in Chinese women is unknown [see Use In Specific Populations].
Hepatic Impairment: No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablets.
Renal Impairment: No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablets.
No formal drug-drug interaction studies were conducted with levonorgestrel tablets [see DRUG INTERACTIONS].
A double-blind, randomized, multinational controlled clinical trial in 1,955 evaluable women (mean age 27) compared the efficacy and safety of levonorgestrel tablets (one 0.75 mg tablet of levonorgestrel taken within 72 hours of unprotected intercourse, and one tablet taken 12 hours later) to the Yuzpe regimen (two tablets each containing 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol, taken within 72 hours of intercourse, and two additional tablets taken 12 hours later). After a single act of intercourse occurring anytime during the menstrual cycle, the expected pregnancy rate of 8% (with no contraceptive use) was reduced to approximately 1% with levonorgestrel tablets. Emergency contraceptives are not as effective as routine hormonal contraception since their failure rate, while low based on a single use, would accumulate over time with repeated use [see INDICATIONS].
At the time of expected menses, approximately 74% of women using levonorgestrel tablets had vaginal bleeding similar to their normal menses, 14% bled more than usual, and 12% bled less than usual. The majority of women (87%) had their next menstrual period at the expected time or within + 7 days, while 13% had a delay of more than 7 days beyond the anticipated onset of menses.
Last reviewed on RxList: 7/19/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Next Choice Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.