IMPLANON is a non-biodegradable white to off-white flexible rod. Each implant contains 68 mg of etonogestrel.

Therapeutic indications
Contraception.

Pregnancy should be excluded before insertion of IMPLANON.

One implant is inserted subdermally. The user should be informed that she can request the removal of IMPLANON at any time but the implant should not be left in place more than three years. Clinicians may consider earlier replacement of the implant in heavier women. Only a physician who is familiar with the removal technique should perform, on request or at the end of the 3 years of use, the removal of IMPLANON. After the removal of the implant, immediate insertion of another implant will result in continued contraceptive protection.

Some cases have been reported in which the implant was not inserted on the correct day or was not properly inserted or was not inserted at all. Incidentally, this has resulted in unintended pregnancy. The occurrence of such incidents can be minimized when the instructions for insertion are strictly followed. The presence of the implant should be verified by palpation directly after insertion. In case the implant cannot be palpated or when the presence of the implant is doubtful, other methods must be applied to confirm its presence. Until the presence of IMPLANON has been verified a contraceptive barrier method must be used.

It is strongly recommended that physicians, prior to practicing the insertion of IMPLANON, participate in training sessions organized by the company supplying IMPLANON.

Selected Safety Information About IMPLANON

Contraindications
Progestagen-only contraceptives should not be used in the presence of any of the following conditions. Should any of the conditions appear for the first time during the use of IMPLANON, the product should be stopped immediately.

  • Known or suspected pregnancy
  • Active venous thromboembolic disorder
  • Presence or history of severe hepatic disease as long as liver function values have not returned to normal
  • Known or suspected sex-steroid sensitive malignancies
  • Undiagnosed vaginal bleeding
  • Hypersensitivity to the active substance or to any of the excipients of IMPLANON

Warnings
If any of the following conditions/risk factors is present, the benefits of progestagen use should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start with IMPLANON. In the event of aggravation, exacerbation or first appearance of any of these conditions, the woman should contact her physician. The physician should then decide on whether the use of IMPLANON should be discontinued.

The risk for breast cancer increases in general with increasing age. During the use of oral contraceptives (OCs) the risk of having breast cancer diagnosed is slightly increased. This increased risk disappears gradually within 10 years after discontinuation of OC use and is not related to the duration of use, but to the age of the woman when using the OC. The expected number of cases diagnosed per 10,000 women who use combined OCs (up to 10 years after stopping) relative to never users over the same period have been calculated for the respective age groups to be: 4.5/4 (16-19 years), 17.5/16 (20-24 years), 48.7/44 (25-29 years), 110/100 (30-34 years), 180/160 (35-39 years) and 260/230 (40-44 years). The risk in users of contraceptive methods, which only contain progestagens, is possibly of similar magnitude as that associated with combined OCs. However, for these methods, the evidence is less conclusive. Compared to the risk of getting breast cancer ever in life, the increased risk associated with OCs is low. The cases of breast cancer diagnosed in OC users tend to be less advanced than in those who have not used OCs. The increased risk observed in OC users may be due to an earlier diagnosis, biological effects of the OC or a combination of both. Since a biological effect of hormones cannot be excluded, an individual benefit/risk assessment should be made in women with pre-existing breast cancer and in women in whom breast cancer is diagnosed while using IMPLANON.

Since a biological effect of progestagens on liver cancer cannot be excluded, an individual benefit/risk assessment should be made in women with liver cancer.

Epidemiological investigations have associated the use of combined OCs with an increased incidence of venous thromboembolism (VTE, deep venous thrombosis and pulmonary embolism). Although the clinical relevance of this finding for etonogestrel (the biologically active metabolite of desogestrel) used as a contraceptive in the absence of an estrogenic component is unknown, IMPLANON should be removed in the event of a thrombosis. Removal of IMPLANON should also be considered in case of long-term immobilization due to surgery or illness. Women with a history of thromboembolic disorders should be made aware of the possibility of a recurrence.

The protection with traditional progestagen-only contraceptives against ectopic pregnancies is not as good as with combined OCs, which has been associated with the frequent occurrence of ovulations during the use of these methods. Despite the fact that IMPLANON consistently inhibits ovulation, ectopic pregnancy should be taken into account in the differential diagnosis if the woman gets amenorrhea or abdominal pain.

If a sustained hypertension develops during the use of IMPLANON, or if a significant increase in blood pressure does not adequately respond to antihypertensive therapy, discontinuation with the use of IMPLANON should be considered.

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst using IMPLANON.

The contraceptive effect of IMPLANON is related to the plasma levels of etonogestrel, which are inversely related to body weight, and decrease with time after insertion. The clinical experience with IMPLANON in heavier women in the third year of use is limited. Therefore, it can not be excluded that the contraceptive effect in these women during the third year of use may be lower than for women of normal weight. Clinicians may therefore consider earlier replacement of the implant in heavier women.

The following conditions have been reported both during pregnancy and during sex steroid use, but an association with the use of progestagens has not been established: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemiclupus erythematosus; hemolytic uraemic syndrome; Sydenham’s chorea; herpesgestationis; otosclerosis-related hearing loss.

Expulsion may occur especially if the implant is not inserted according to the instructions (see Insertion instructions from the IMPLANON Product Labeling), or as a consequence of a local inflammation.

In rare cases, mostly related to either a too deep initial insertion and/or to external forces (e.g., manipulation of the implant or contact sports) the implant may migrate from the insertion site. In these cases localization of the implant may be more difficult and removal may require a larger incision (see Removal instructions from the IMPLANON Product Labeling). If IMPLANON cannot be found, contraception and the risk of progestagen-related undesirable effects may continue beyond the time desired by the woman.

Women should be advised that IMPLANON does not protect against HIV (AIDS) and other sexually transmitted diseases.

With all low-dose hormonal contraceptives, follicular development occurs and occasionally the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally, these enlarged follicles disappear spontaneously. Often, they are asymptomatic; in some cases they are associated with mild abdominal pain. They rarely require surgical intervention.

Interaction With Other Medicinal Products and Other Forms of Interaction
Interactions between hormonal contraceptives and other medicinal products may lead to breakthrough bleeding and/or contraceptive failure. No specific interaction studies have been performed with IMPLANON. The following interactions have been reported in the literature (mainly with combined contraceptives but occasionally also with progestagenonly contraceptives).

Hepatic metabolism:
Interactions can occur with medicinal products that induce microsomal enzymes, specifically cytochrome P450 enzymes, which can result in increased clearance of sex hormones (e.g., phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, ritonavir, nelfinavir, nevirapine, griseofulvin, and the herbal remedy St. Johns wort). Women on treatment with any of these drugs should temporarily use a barrier method in addition to IMPLANON. With microsomal enzyme-inducing drugs, the barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation. In women on long-term treatment with hepatic enzyme-inducing drugs, it is recommended to remove IMPLANON and to prescribe a nonhormonal method.

Influence of IMPLANON on other medicinal products:
Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g., cyclosporin) or decrease (e.g., Iamotrigine).

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions.

Laboratory parameters:
Data obtained with combined OCs have shown that contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, serum levels of (carrier) proteins (e.g., corticosteroid binding globulin and lipid/lipoprotein fractions), parameters of carbohydrate metabolism, and parameters of coagulation and fibrinolysis. The changes generally remain within the normal range. To what extent this also applies to progestagen-only contraceptives is not known.

Pregnancy and Lactation
IMPLANON is not indicated during pregnancy. If pregnancy occurs during use of IMPLANON, the implant should be removed.

IMPLANON does not influence the production or the quality (protein, lactose or fat concentrations) of breast milk. However, small amounts of etonogestrel are excreted in breast milk. Based on the available data, IMPLANON may be used during lactation.

Undesirable effects
During the use of IMPLANON, women are likely to have changes in their vaginal bleeding patterns which are often unpredictable. These may include changes in bleeding frequency (absent, less, more frequent, or continuous), intensity (reduced or increased), or duration. Amenorrhoea was reported in about 1 of 5 women while another 1 of 5 women reported frequent and/or prolonged bleeding. Occasionally, heavy bleeding has been reported. In clinical trials, bleeding changes were the most common reason for stopping treatment with IMPLANON (about 11%). Dysmenorrhoea tends to improve while using IMPLANON. The bleeding pattern experienced during the first three months is broadly predictive of future bleeding patterns for many women.

Possibly related undesirable effects reported commonly or very commonly in clinical trials with IMPLANON have been listed in the following paragraph. An association has been neither confirmed nor refuted.

The following very common (>1/10) undesirable effects possibly related to the use of IMPLANON were reported in clinical trials: vaginal infection, headache, acne, breast tenderness, breast pain, menstruation irregular, and weight increased. In the same clinical trials, common (<1/10 >1/100) undesirable effects possibly related to the use of IMPLANON included increased appetite, affect lability, depressed mood, nervousness, libido decreased, dizziness, hot flush, abdominal pain, nausea, flatulence, alopecia, dysmenorrhoea, ovarian cyst, implant site pain, implant site reaction, fatigue, influenzalike illness, pain, and weight decreased. The most appropriate MedDRA term (version 10.1) to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well.

In rare cases, a clinically relevant rise in blood pressure has been observed during the use of IMPLANON. Urticaria and (aggravation of) angioedema and/or aggravation of hereditary angioedema may occur. Insertion or removal of IMPLANON may cause some bruising, slight local irritation, pain, or itching. Occasionally fibrosis at the implant site may occur, a scar may be formed or an abscess may develop. In rare cases, paresthesia or paresthesia-like events may occur. Expulsion or migration of IMPLANON may be possible. Minor surgical intervention might be necessary when removing IMPLANON.

In women using (combined oral) contraceptives, a number of (serious) undesirable effects have been reported. These include venous thromboembolic disorders, arterial thromboembolic disorders, hormone-dependent tumours (e.g., liver tumours, breast cancer), and chloasma.