IMPLANON NXT

Etonogestrel molecule is a 3-ketodesogestrel or 19-nortestosterone which is a synthetic biologically active metabolite of progestin desogestrel.

The first product including etonogestrel was developed by the Merck subsidiary Organon and FDA approved in 2001.

Etonogestrel is administered in subdermal implants as long-acting reversible contraception. 9, 10 It is known to be effective in postpartum insertion including breastfeeding women.

Etonogestrel is part of the long-acting contraceptive implants that prevent pregnancy.

The implant's effect can remain for 5 years.

Etonogestrel attains its therapeutic effect inhibiting fertility by impairing the release of the luteinizing hormone which is one of the most important reproductive hormones for ovulation.

As well, etonogestrel is known to increase the viscosity of the cervical mucus hindering the passage of the spermatozoa and altering the lining in the uterus to prevent the implantation of the fertilized eggs in the endometrium.

In clinical trials, etonogestrel was implanted and reported to avoid 100% of pregnancies over a three year period.

When the implant was removed, normal periods were reinstalled within 90 days in 91% of the individuals.

Fertility was established quickly with 20 reported pregnancies within 3 months of implant removal.

The implants of etonogestrel release 40 mcg of etonogestrel daily and they usually provide a continuous contraception effect for 3 years.

When the implant is administered, the failure rate is reported to be 0.1%.

Some non-contraceptive effects are improved dysmenorrhea.

All data of etonogestrel comes from patients between 80-130% of the body mass.

Vaginal administration of etonogestrel is known to be significantly absorbed through the vaginal epithelium but it does not increase the levels of etonogestrel in the urine.

On the other hand, oral administration is absorbed in the GI tract and it goes through the first-pass metabolism.

When etonogestrel is administered subdermally it is absorbed rapidly into the bloodstream and it presents a bioavailability of 82%.

It is reported that the implant releases around 60 mcg per day in the first 3 months and then decreases steady reaching a concentration of 30 mcg at the end of year 2.

The apparent volume of distribution of etonogestrel is of around 201 L.

Etonogestrel is highly metabolized in the liver by the action of the cytochrome isoenzyme 3A4 mainly by the presence of hydroxylation, sulfate conjugation and glucuronide conjugation reactions.

Hover over products below to view reaction partners Etonogestrel Etonogestrel sulfate Etonogestrel glucuronide.

The elimination of etonogestrel and its metabolites is mainly done renally.

The elimination half-life of etonogestrel is reported to be of 25 hours which indicates a reversible contraceptive effect.

The clearance rate of etonogestrel is reported to be of 7.5 L/h.

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The reported

LD50 of oral etonogestrel in the rat is reported to be higher than 2000 mg/kg.

In cases of overdose, removal of the implant is recommended.

There aren't reports relating etonogestrel with carcinogenesis, mutagenesis or impaired fertility.

Etonogestrel and ethinyl estradiol vaginal ring is contraindicated in females who are known to have or develop the following conditions: A high risk of arterial or venous thrombotic diseases.

Examples include women who are known to: Smoke, if over age 35 Have deep vein thrombosis or pulmonary embolism, now or in the past Have cerebrovascular disease Have coronary artery disease Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) Have inherited or acquired hypercoagulopathies Have uncontrolled hypertension Have diabetes mellitus with vascular disease Have headaches with focal neurological symptoms or migraine headaches with aura Women over age with any migraine headaches Liver tumors, benign or malignant, or liver disease Undiagnosed abnormal uterine bleeding Pregnancy, because there is no reason to use CHCs during pregnancy Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Hypersensitivity reactions, including anaphylaxis and angioedema, to any of the components of Etonogestrel and ethinyl estradiol vaginal ring Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations.

A high risk of arterial or venous thrombotic diseases Breast cancer Liver tumors or liver disease Undiagnosed abnormal uterine bleeding Pregnancy Hypersensitivity, including anaphylaxis and angioedema, to any of the components of Etonogestrel and ethinyl estradiol vaginal ring Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.

Etonogestrel and ethinyl estradiol vaginal ring is inserted in the vagina.

The ring must remain in place continuously for three weeks, followed by a one-week ring-free interval. 2.1 How to Use Etonogestrel and ethinyl estradiol vaginal ring To achieve maximum contraceptive effectiveness, Etonogestrel and ethinyl estradiol vaginal ring must be used as directed.

The ring is to remain in place continuously for three weeks.

It is removed for a one-week break, during which a withdrawal bleed usually occurs.

A new ring is inserted one week after the last ring was removed.

The user can choose the insertion position that is most comfortable to her, for example, standing with one leg up, squatting, or lying down.

The ring is to be compressed and inserted into the vagina.

An optional alternative is to insert the ring using the applicator for Etonogestrel and ethinyl estradiol vaginal ring.

The exact position of

Etonogestrel and ethinyl estradiol vaginal ring inside the vagina is not critical for its function.

The vaginal ring must be inserted on the appropriate day and left in place for three consecutive weeks.

This means that the ring should be removed three weeks later on the same day of the week as it was inserted and at about the same time.

Etonogestrel and ethinyl estradiol vaginal ring can be removed by hooking the index finger under the forward rim or by grasping the rim between the index and middle finger and pulling it out.

The used ring should be placed in the sachet (foil pouch) and discarded in a waste receptacle out of the reach of children and pets (do not flush in toilet).

After a one-week break, during which a withdrawal bleed usually occurs, a new ring is inserted on the same day of the week as it was inserted in the previous cycle.

The withdrawal bleed usually starts on

Day 2-3 after removal of the ring and may not have finished before the next ring is inserted.

In order to maintain contraceptive effectiveness, the new ring must be inserted exactly one week after the previous one was removed even if menstrual bleeding has not finished. 2.2 How to Start Using Etonogestrel and ethinyl estradiol vaginal ring IMPORTANT: Consider the possibility of ovulation and conception prior to the first use of Etonogestrel and ethinyl estradiol vaginal ring.

No Hormonal Contraceptive Use in the Preceding Cycle: The woman should insert Etonogestrel and ethinyl estradiol vaginal ring on the first day of her menstrual bleeding.

Etonogestrel and ethinyl estradiol vaginal ring may also be started on Days 2-5 of the woman’s cycle, but in this case a barrier method, such as male condoms with spermicide, should be used for the first seven days of Etonogestrel and ethinyl estradiol vaginal ring use in the first cycle.

The woman may switch from her previous CHC on any day, but at the latest on the day following the usual hormone-free interval, if she has been using her hormonal method consistently and correctly, or if it is reasonably certain that she is not pregnant.

Method (progestin-only pill [POP], Implant, or Injection or a Progestin-Releasing Intrauterine System [IUS]): The woman may switch from the POP on any day; instruct her to start using Etonogestrel and ethinyl estradiol vaginal ring on the day after she took her last POP.

She should switch from an implant or the IUS on the day of its removal, and from an injectable on the day when the next injection would be due.

In all of these cases, the woman should use an additional barrier method such as a male condom with spermicide, for the first seven days.

The woman may start using Etonogestrel and ethinyl estradiol vaginal ring within the first five days following a complete first trimester abortion or miscarriage, and she does not need to use an additional method of contraception.

If use of

Etonogestrel and ethinyl estradiol vaginal ring is not started within five days following a first trimester abortion or miscarriage, the woman should follow the instructions for “No Hormonal Contraceptive Use in the Preceding Cycle.” In the meantime, she should be advised to use a non-hormonal contraceptive method.

Etonogestrel and ethinyl estradiol vaginal ring no earlier than four weeks after a second trimester abortion or miscarriage, due to the increased risk of thromboembolism.

The use of Etonogestrel and ethinyl estradiol vaginal ring may be initiated no sooner than four weeks postpartum in women who elect not to breastfeed, due to the increased risk of thromboembolism in the postpartum period.

Advise women who are breastfeeding not to use Etonogestrel and ethinyl estradiol vaginal ring but to use other forms of contraception until the child is weaned.

If a woman begins using

Etonogestrel and ethinyl estradiol vaginal ring postpartum, instruct her to use an additional method of contraception, such as male condoms with spermicide, for the first seven days.

If she has not yet had a period, consider the possibility of ovulation and conception occurring prior to initiation of Etonogestrel and ethinyl estradiol vaginal ring. 2.3 Deviations from the Recommended Regimen To prevent loss of contraceptive efficacy, advise women not to deviate from the recommended regimen.

Etonogestrel and ethinyl estradiol vaginal ring should be left in the vagina for a continuous period of three weeks.

Advise women to regularly check for the presence of Etonogestrel and ethinyl estradiol vaginal ring in the vagina (for example, before and after intercourse).

Etonogestrel and ethinyl estradiol vaginal ring can be accidentally expelled, for example, while removing a tampon, during intercourse, or with straining during a bowel movement.

If the ring is accidentally expelled and is left outside of the vagina for less than three hours, contraceptive efficacy is not reduced.

Etonogestrel and ethinyl estradiol vaginal ring can be rinsed with cool to lukewarm (not hot) water and reinserted as soon as possible, but at the latest within three hours.

If Etonogestrel and ethinyl estradiol vaginal ring is lost, a new vaginal ring should be inserted and the regimen should be continued without alteration.

If Etonogestrel and ethinyl estradiol vaginal ring is out of the vagina for more than three continuous hours: During Weeks and 2: Contraceptive efficacy may be reduced.

The woman should reinsert the ring as soon as she remembers.

A barrier method such as male condoms with spermicides must be used until the ring has been used continuously for seven days.

Week 3: The woman should discard that ring.

One of the following two options should be chosen: 1.

Insert a new ring immediately.

Inserting a new ring will start the next three-week use period.

The woman may not experience a withdrawal bleed from her previous cycle.

However, breakthrough spotting or bleeding may occur. 2.

Insert a new ring no later than seven days from the time the previous ring was removed or expelled, during which time she may have a withdrawal bleed.

This option should only be chosen if the ring was used continuously for at least seven days prior to inadvertent removal/expulsion.

In either case, a barrier method such as male condoms with spermicides must be used until the new ring has been used continuously for seven days.

If Etonogestrel and ethinyl estradiol vaginal ring was out of the vagina for an unknown amount of time, the possibility of pregnancy should be considered.

A pregnancy test should be performed prior to inserting a new ring.

If the ring-free interval has been extended beyond one week, consider the possibility of pregnancy, and an additional method of contraception, such as male condoms with spermicide, MUST be used until Etonogestrel and ethinyl estradiol vaginal ring has been used continuously for seven days.

Prolonged Use of Etonogestrel and ethinyl estradiol vaginal ring: If Etonogestrel and ethinyl estradiol vaginal ring has been left in place for up to one extra week (i.e., up to four weeks total), the woman will remain protected.

Etonogestrel and ethinyl estradiol vaginal ring should be removed and the woman should insert a new ring after a one-week ring-free interval.

If Etonogestrel and ethinyl estradiol vaginal ring has been left in place for longer than four weeks, instruct the woman to remove the ring, and rule out pregnancy.

If pregnancy is ruled out, Etonogestrel and ethinyl estradiol vaginal ring may be restarted, and an additional method of contraception, such as male condoms with spermicide, MUST be used until a new Etonogestrel and ethinyl estradiol vaginal ring has been used continuously for seven days.

There have been reported cases of Etonogestrel and ethinyl estradiol vaginal ring disconnecting at the weld joint.

This is not expected to affect the contraceptive effectiveness of Etonogestrel and ethinyl estradiol vaginal ring.

In the event of a disconnected ring, vaginal discomfort or expulsion (slipping out) is more likely to occur.

Vaginal injury associated with ring breakage has been reported.

If a woman discovers that her

Etonogestrel and ethinyl estradiol vaginal ring has disconnected, she should discard the ring and replace it with a new ring. 2.4 In the Event of a Missed Menstrual Period 1.

If the woman has not adhered to the prescribed regimen (Etonogestrel and ethinyl estradiol vaginal ring has been out of the vagina for more than three hours or the preceding ring-free interval was extended beyond one week), consider the possibility of pregnancy at the time of the first missed period and discontinue Etonogestrel and ethinyl estradiol vaginal ring use if pregnancy is confirmed. 2.

If the woman has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. 3.

If the woman has retained one

Etonogestrel and ethinyl estradiol vaginal ring for longer than four weeks, rule out pregnancy. 2.5 Use with Other Vaginal Products Etonogestrel and ethinyl estradiol vaginal ring may interfere with the correct placement and position of certain female barrier methods such as a diaphragm, cervical cap or female condom.

These methods are not recommended as back-up methods with Etonogestrel and ethinyl estradiol vaginal ring use.

Pharmacokinetic data show that the use of tampons has no effect on the systemic absorption of the hormones released by Etonogestrel and ethinyl estradiol vaginal ring.

Etonogestrel and ethinyl estradiol vaginal ring is individually packaged in an aluminum laminate sachet consisting of three layers, from outside to inside: polyester, aluminum foil, and low-density polyethylene.

The ring should be replaced in this foil pouch after use and discarded in a waste receptacle out of the reach of children and pets.

It should not be flushed down the toilet.

Box of 3 sachets NDC 42291-478-03 16.1 Storage Prior to dispensing to the user, store refrigerated 2-8°C (36-46°F).

After dispensing to the user, Etonogestrel and ethinyl estradiol vaginal ring can be stored for up to 4 months at 25°C (77°F); excursions permitted between to 30°C (59 to 86°F) .

Avoid storing

Etonogestrel and ethinyl estradiol vaginal ring in direct sunlight or at temperatures above 30°C (86°F).

When Etonogestrel and ethinyl estradiol vaginal ring is dispensed to the user, place an expiration date on the label.

The date should not exceed either 4 months from the date of dispensing or the expiration date, whichever comes first.