Final Implanon Product Monograph

Product Monograph

Implanon NXT™: Product Monograph

Table of Contents Part I: Health Care Professional Information

2-19

Summary Product Information 1 2 3 2 Indication 4.1 3 Posology and Administration 4.2 3-10 Contraindications 4.3 10 Warnings and Precautions 4.4 10-12 Drug Interactions 4.5 13 Pregnancy and Lactation 4.6 13-14 Adverse Effects 4.8 14-16 Overdose 4.9 16 Pharmacodynamic Properties 5.1 16-17 Pharmacokinetic Properties 5.2 17 Preclinical Safety Data 5.3 18 Pharmaceutical Particulars 6 18 Storage and Handling 6.4 - 6.6 18

Part II: Select Clinical Trials

21-31

Bioequivalence

21

Tolerability and Clinical Safety

24

Management of Bleeding Patterns

26

Clinician Satisfaction

29

References

31

Part III: Consumer Information

33-50

1

Implanon NXT™: Product Monograph

1 2 3

Part I: Health Care Professional Information

Summary Product Information 1

 ame of the N Medicinal Product Implanon NXT, 68 mg etonogestrel implant for subdermal use

2

 ualitative and Q Quantitative Composition Implanon NXT is a radiopaque, non-biodegradable, progestogen-only, flexible implant preloaded in a sterile, ready-for-use, disposable applicator. Each radiopaque implant contains 68 mg of etonogestrel; the release rate is approximately 60-70 µg/day in weeks 5-6 and has decreased to approximately 35-45 µg/day at the end of the first year, to approximately 30-40 µg/day at the end of the second year and to approximately 25-30 µg/day at the end of the third year. The innovative applicator is designed to be operated with one hand and to help facilitate correct subdermal insertion of the implant. For a full list of excipients, see section 6.1 “List of excipients”.

2

3

Pharmaceutical Form Implant for subdermal use Radiopaque, non-biodegradable, white to off-white, soft, flexible rod with a length of 4 cm and 2 mm in diameter.

Implanon NXT™: Product Monograph

4 - 4.2.1

Part I: Health Care Professional Information

4

Clinical Particulars

4.1

Therapeutic indication

Contraception.

4.2

Posology and method of administration

Pregnancy should be excluded before insertion of Implanon NXT. Healthcare professionals (HCPs) are strongly recommended to participate in a training session to become familiar with the use of the Implanon NXT applicator and techniques for insertion and removal of the Implanon NXT implant and where appropriate, request supervision prior to inserting or removing the implant.

4.2.1

Additional information and more detailed instructions concerning the insertion and removal of the implant will be sent on request free of charge Please contact MSD Office at (632) 784-9500 Prior to inserting the implant, carefully read and follow the instructions for insertion and removal of the implant in section 4.2.3 “How to insert Implanon NXT” and section 4.2.4 “How to remove Implanon NXT”.

How to use Implanon NXT

Implanon NXT is a long-acting hormonal contraceptive. A single implant is inserted subdermally and can be left in place for three years. Remove the implant no later than three years after the date of insertion. The user should be informed that she can request the removal of the implant at any time. HCPs may consider earlier replacement of the implant in heavier women (see section 4.4.1 “Warnings”). After the removal of the implant, immediate insertion of another implant will result in continued contraceptive protection. If the woman does not wish to continue using Implanon NXT, but wants to continue preventing pregnancy, another contraceptive method should be recommended. The basis for successful use and subsequent removal of the Implanon NXT implant is a correct and carefully performed subdermal insertion of the implant in accordance with the instructions. If the implant is not inserted in accordance with the instructions (section 4.2.2 “When to insert Implanon NXT” and 4.2.3 “How to insert Implanon NXT), and on the correct day, this may result in an unintended pregnancy.

upper arm to avoid the large blood vessels and nerves that lie deeper in the connective tissue between the biceps and triceps muscles. Immediately after insertion, the presence of the implant should be verified by palpation. 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 (see section 4.2.3 “How to insert Implanon NXT”). Until the presence of the implant has been verified, the woman should be advised to use a non-hormonal contraceptive method. The Implanon NXT package contains a User Card intended for the woman which records the batch number of the implant. HCPs are requested to record the date of insertion, the arm of insertion and the intended day of removal on the User Card. The package also includes adhesive labels intended for HCP records showing the batch number.

The Implanon NXT implant should be inserted subdermally just under the skin at the inner side of the

3

Implanon NXT™: Product Monograph

4.2.2

Part I: Health Care Professional Information 4.2.2

When to insert Implanon NXT

IMPORTANT: Rule out pregnancy before inserting the implant.

Timing of insertion depends on the woman’s recent contraceptive history, as follows:

No preceding hormonal contraceptive use in the past month The implant should be inserted between Day 1 (first day of menstrual bleeding) and Day 5 of the menstrual cycle, even if the woman is still bleeding.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Switching contraceptive method to Implanon NXT Changing from a combined hormonal contraceptive method (combined oral contraceptive (COC), vaginal ring or transdermal patch) The implant should be inserted preferably on the day after the last active tablet (the last tablet containing the active substances) of the previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of the previous COC. In case a vaginal ring or transdermal patch has been used, the implant should be inserted preferably on the day of removal, but at the latest when the next application would have been due.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Changing from a progestagen-only contraceptive method (e.g. progestagen-only pill, injectable, implant, or intrauterine system [IUS]) As there are several types of progestagen-only methods, the insertion of the implant must be performed as follows: • Injectable contraceptives: Insert the implant on the day the next injection is due. •

 rogestagen-only pill: A woman may switch from the P progestagen-only pill to Implanon NXT on any day of the month. The implant should be inserted within 24 hours after taking the last tablet.

•

Implant/Intrauterine system (IUS): Insert the implant on the same day the previous implant or IUS is removed.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Following abortion or miscarriage •

 irst trimester: The implant should be inserted within 5 F days following a first trimester abortion or miscarriage.

•

 econd trimester: Insert the implant between 21 to 28 S days following second trimester abortion or miscarriage.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Postpartum •

4

 reast-feeding: The implant should be inserted after the B fourth postpartum week (see Section 4.6 “Pregnancy and lactation”). The woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

•

Not breast-feeding: The implant should be inserted between 21 to 28 days postpartum. If inserted as recommended, back-up contraception is not necessary. If the implant is inserted later than 28 days postpartum, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Implanon NXT™: Product Monograph

4.2.3

Part I: Health Care Professional Information 4.2.3

How to insert Implanon NXT

The basis for successful use and subsequent removal of Implanon NXT is a correct and carefully performed subdermal insertion of the implant in the non-dominant arm in accordance with the instructions. Both the HCP and the woman should be able to feel the implant under the woman’s skin after placement. The implant should be inserted subdermally just under the skin. If the implant is inserted too deep, neural or vascular damage may occur. Too deep or incorrect insertions have been associated with paresthesia (due to neural damage) and migration of the implant (due to intramuscular or fascial insertion), and in rare cases

with intravascular insertion. Moreover, when the implant is inserted too deep, it may not be palpable and the localization and/or removal can be difficult. Insertion of Implanon NXT should be performed under aseptic conditions and only by a qualified HCP who is familiar with the procedure. Insertion of the implant should only be performed with the preloaded applicator. It is recommended that the HCP is in a seated position during the entire insertion procedure so that the insertion site and the movement of the needle just under the skin can be clearly seen from the side.

• Have the woman lie on her back on the examination table with her non-dominant arm flexed at the elbow and externally rotated so that her wrist is parallel to her ear or her hand is positioned next to her head (Figure 1).

Figure 1

• Identify the insertion site, which is at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus (Figure 2). The implant should be inserted subdermally just under the skin to avoid the large blood vessels and nerves that lie deeper in the subcutaneous tissue in the sulcus between the triceps and biceps muscles (see section 4.4.1 “Warnings”).

Guiding Mark

• Make two marks with a sterile marker: first, mark the spot where the implant will be inserted, and second, mark a spot a few centimeters proximal to the first mark (Figure 2). This second mark will later serve as a direction guide during insertion.

8-10 cm Insertion Site

Medial Epicondyle

Figure 2

• Clean the insertion site with an antiseptic solution. • Anesthetize the insertion area (for example, with anesthetic spray or by injecting 2 ml of 1% lidocaine just under the skin along the planned insertion tunnel). • Remove the sterile preloaded disposable Implanon NXT applicator carrying the implant from its blister. The applicator should not be used if sterility is in question.

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Implanon NXT™: Product Monograph

4.2.3

Part I: Health Care Professional Information

• Hold the applicator just above the needle at the textured surface area. Remove the transparent protection cap by sliding it horizontally in the direction of the arrow away from the needle (Figure 3). If the cap does not come off easily, the applicator should not be used. You may see the white colored implant by looking into the tip of the needle. Do not touch the purple slider until you have fully inserted the needle subdermally, as it will retract the needle and prematurely release the implant from the applicator.

Purple Slider

Figure 3

• With your free hand, stretch the skin around the insertion site with thumb and index finger (Figure 4).

Figure 4

• Puncture the skin with the tip of the needle angled about 30° (Figure 5).

Figure 5

• Lower the applicator to a horizontal position. While lifting the skin with the tip of the needle (Figure 6), slide the needle to its full length. You may feel slight resistance but do not exert excessive force. If the needle is not inserted to its full length, the implant will not be inserted properly. Y  ou can best see movement of the needle if you are seated and are looking at the applicator from the side and NOT from above. In this position, you can clearly see the insertion site and the movement of the needle just under the skin.

6

Figure 6

Implanon NXT™: Product Monograph

4.2.3

Part I: Health Care Professional Information

• Keep the applicator in the same position with the needle inserted to its full length. If needed, you may use your free hand to keep the applicator in the same position during the following procedure. Unlock the purple slider by pushing it slightly down. Move the slider fully back until it stops (Figure 7). The implant is now in its final subdermal position, and the needle is locked inside the body of the applicator. The applicator can now be removed. If the applicator is not kept in the same position during this procedure or if the purple slider is not completely moved to the back, the implant will not be inserted properly.

Figure 7

• Always verify the presence of the implant in the woman’s arm immediately after insertion by palpation. By palpating both ends of the implant, you should be able to confirm the presence of the 4 cm rod (Figure 8).

Figure 8

If you cannot feel the implant or are in doubt of its presence, • Check the applicator. The needle should be fully retracted and only the purple tip of the obturator should be visible. • Use other methods to confirm the presence of the implant. Suitable methods are: two-dimensional X-ray, X-ray computerized tomography (CT scan), ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHz or greater) or magnetic resonance imaging (MRI). Prior to the application of X-ray CT, USS or MRI for the localization of the implant, it is recommended to consult the local supplier of Implanon NXT for instructions. In case these imaging methods fail, it is advised to verify the presence of the implant by measuring the etonogestrel level in a blood sample of the subject. In this case the local supplier will provide the appropriate procedure. Until you have verified the presence of the implant, a non-hormonal contraceptive method must be used. • Apply a small adhesive bandage over the insertion site. Request that the woman palpate the implant. • Apply sterile gauze with a pressure bandage to minimize bruising. The woman may remove the pressure bandage in 24 hours and the small bandage over the insertion site after 3-5 days. • Complete the User Card and give it to the woman to keep. Also, complete the adhesive labels and affix it to the woman’s medical record. • The applicator is for single use only and must be adequately disposed of, in accordance with local regulations for the handling of biohazardous waste.

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Implanon NXT™: Product Monograph

4.2.4

Part I: Health Care Professional Information 4.2.4

How to remove Implanon NXT

Before initiating the removal procedure, the HCP should consult the User Card for the location of the Implanon NXT implant. Verify the exact location of the implant in the arm by palpation. If the implant is not palpable, two-dimensional X-ray can be performed to verify its presence. A non-palpable implant should always be first located prior to removal. Suitable methods for localization include, X-ray computer tomography (CT), ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHZ or greater) or magnetic resonance imaging (MRI). If these imaging methods fail to locate the implant, etonogestrel blood level determination can be used for verification of the presence of the implant. Please contact your local supplier for further guidance.

After localization of a non-palpable implant, consider conducting removal with ultrasound guidance. There have been occasional reports of migration of the implant; usually this involves minor movement relative to the original position unless inserted too deeply (see also section 4.4.1 “Warnings”). This may complicate localization of the implant by palpation, USS and/or MRI, and removal may require a larger incision and more time. Removal of the implant should only be performed under aseptic conditions by a HCP who is familiar with the removal technique.

Exploratory surgery without knowledge of the exact location of the implant is strongly discouraged. Removal of deeply inserted implants should be conducted with caution in order to prevent damage to deeper neural or vascular structures in the arm and should be performed by HCPs familiar with the anatomy of the arm.

If the implant cannot be removed, please contact your local supplier for further guidance.

• Clean the site where the incision will be made and apply an antiseptic. Locate the implant by palpation and mark the distal end (end closest to the elbow), for example, with a sterile marker (Figure 9).

Figure 9

• Anesthetize the arm, for example, with 0.5 to 1 ml 1% lidocaine at the marked site where the incision will be made (Figure 10). Be sure to inject the local anesthetic under the implant to keep it close to the skin surface.

Figure 10

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Implanon NXT™: Product Monograph

4.2.4

Part I: Health Care Professional Information

• Push down the proximal end of the implant (Figure 11) to stabilize it; a bulge may appear indicating the distal end of implant. Starting at the distal tip of the implant, make a longitudinal incision of 2 mm towards the elbow.

Figure 11

• Gently push the implant towards the incision until the tip is visible. Grasp the implant with forceps (preferably curved mosquito forceps) and remove the implant (Figure 12).

Figure 12

• If the implant is encapsulated, make an incision into the tissue sheath and then remove the implant with the forceps (Figures 13 and 14).

Figure 13

Figure 14

• If the tip of the implant does not become visible in the incision, gently insert a forceps into the incision (Figure 15). Flip the forceps over into your other hand (Figure 16). With a second pair of forceps carefully dissect the tissue around the implant and grasp the implant (Figure 17). The implant can then be removed.

Figure 15

Figure 16

Figure 17

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Implanon NXT™: Product Monograph

4.2.4 - 4.4.1

Part I: Health Care Professional Information

• Confirm that the entire implant, which is 4 cm long, has been removed by measuring its length. If a partial implant (less than 4 cm) is removed, the remaining piece should be removed by following the instructions in section 4.2.4 “How to remove Implanon NXT”. • If the woman would like to continue using Implanon NXT, a new implant may be inserted immediately after the old implant is removed using the same incision (Section 4.2.5 “How to replace Implanon NXT”). • After removing the implant, close the incision with a steri-strip and apply an adhesive bandage. • Apply sterile gauze with a pressure bandage to minimize bruising. The woman may remove the pressure bandage after 24 hours and the small bandage after 3-5 days.

4.2.5

How to replace Implanon NXT

Immediate replacement can be done after removal of the previous implant and is similar to the insertion procedure described in section 4.2.3 “How to insert Implanon NXT”. The new implant may be inserted in the same arm, and through the same incision from which the previous

4.3

implant was removed. If the same incision is being used to insert a new implant, anesthetize the insertion site (e.g. 2 ml lidocaine (1%)) applied just under the skin commencing at the removal incision along the ‘insertion canal’ and follow the subsequent steps in the insertion instructions.

Contraindications

Progestagen-only contraceptives should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during the use of Implanon NXT, the product should be stopped immediately.

• Presence or history of liver tumours (benign or malignant).

• Known or suspected pregnancy.

• Hypersensitivity to the active substance or to any of the excipients of Implanon NXT.

• Active venous thromboembolic disorder.

• Presence or history of severe hepatic disease as long as liver function values have not returned to normal. • Undiagnosed vaginal bleeding.

• Known or suspected sex steroid sensitive malignancies.

4.4

Special warnings and special precautions for use

4.4.1

Warnings

If any of the conditions / risk factors mentioned below 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 NXT. In the event of aggravation, exacerbation or first appearance of any of

10

these conditions, the woman should contact her HCP. The HCP should then decide on whether the use of Implanon NXT should be discontinued. • The risk for breast cancer increases in general with increasing age. During the use of (combined) oral contraceptives (OCs) the risk of having breast cancer

Implanon NXT™: Product Monograph

4.4.1

Part I: Health Care Professional Information 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. • When acute or chronic disturbances of liver function occur the woman should be referred to a specialist for examination and advice. • 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, the implant should be removed in the event of a confirmed thrombosis. Removal of the implant should also be considered in case of long-term immobilization due to surgery or illness. Although Implanon NXT is a progestagen-only contraceptive, it is recommended to assess risk factors which are known to increase the risk of venous and arterial thromboembolism. Women with a history of thromboembolic disorders should be made aware of the possibility of a recurrence. • There have been postmarketing reports of serious arterial and venous thromboembolic events, including cases of pulmonary emboli (some fatal), deep vein thrombosis, myocardial infarction, and strokes, in women using the non-radiopaque etonogestrel implant. Implanon NXT should be removed in the event of a thrombosis.

• If a sustained hypertension develops during the use of Implanon NXT, or if a significant increase in blood pressure does not adequately respond to antihypertensive therapy, Implanon NXT should be removed. • Although progestagens may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using progestagen-only contraceptives. However, diabetic women should be carefully observed while using progestagen-only contraceptives. •W  omen who are being treated for hyperlipidemia should be followed closely if they elect to use Implanon NXT. Some progestagens may elevate LDL levels and may render the control of hyperlipidemia more difficult. •C  hloasma 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 NXT. •T  he contraceptive effect of Implanon NXT is related to the plasma levels of etonogestrel, which are inversely related to body weight, and decrease with time after insertion. The clinical experience in heavier women in the third year of use is limited. Therefore it cannot be excluded that the contraceptive effect in these women during the third year of use may be lower than for women of normal weight. HCPs may therefore consider earlier replacement of the implant in heavier women. •E  xpulsion may occur especially if the implant is inserted not according to the instructions given in section 4.2.3 “How to insert Implanon NXT”, or as a consequence of a local inflammation. • In rare cases, mostly related to either a too deep initial insertion (see also section 4.2.3 “How to insert Implanon NXT”) 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 also section 4.2.4 “How to remove Implanon NXT”). If the implant is not removed, contraception and the risk of progestagenrelated undesirable effects may continue beyond the time desired by the woman.

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Implanon NXT™: Product Monograph

4.4.1 - 4.4.4

Part I: Health Care Professional Information • With all low-dose hormonal contraceptives, follicular development may occur 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. • 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

4.4.2

• 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; systemic lupus erythematosus; hemolytic uraemic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss and (hereditary) angioedema.

Medical examination/consultation

Prior to the initiation or reinstitution of Implanon NXT a complete medical history (including family medical history) should be taken and pregnancy should be excluded. Blood pressure should be measured and a physical examination should be performed, guided by the contraindications (Section 4.3 “Contraindications”) and warnings (Section 4.4.1 “Warnings”). It is recommended that the woman returns for a medical check-up three months after insertion of Implanon NXT.

4.4.3

NXT will consistently inhibit ovulation, ectopic pregnancy should be taken into account in the differential diagnosis if the woman gets amenorrhea or abdominal pain.

During this check-up, the blood pressure should be measured and an enquiry should be made after any questions, complaints or the occurrence of undesirable effects. The frequency and nature of further periodic checks should be adapted to the individual woman, guided by clinical judgement. Women should be advised that Implanon NXT does not protect against HIV (AIDS) and other sexually transmitted diseases.

Reduced efficacy

The efficacy of Implanon NXT may be reduced when concomitant medication is used (See section 4.5.1 “Interactions”).

4.4.4

Changes in the menstrual bleeding pattern

During the use of Implanon NXT, women are likely to have changes in their menstrual bleeding pattern. These may include changes in bleeding frequency (absent, less, more frequent or continuous), intensity (reduced or increased) or duration. Amenorrhea was reported in about 1 of 5 women while another 1 of 5 women reported frequent and/or prolonged bleeding. Dysmenorrhea tended to improve while using Implanon NXT. The bleeding

12

pattern experienced during the first three months is broadly predictive of future bleeding patterns for many women. Information, counseling and the use of a bleeding diary can improve the woman’s acceptance of a bleeding pattern. Evaluation of vaginal bleeding should be done on an ad hoc basis and may include an examination to exclude gynaecological pathology or pregnancy.

Implanon NXT™: Product Monograph

4.5 - 4.6

Part I: Health Care Professional Information 4.5

Interaction with other medicinal products and other forms of interaction

4.5.1

Interactions

• Influence of other medicinal products on Implanon NXT Interactions between hormonal contraceptives and other medicinal products may lead to menstrual bleeding and / or contraceptive failure. No specific interaction studies have been performed with Implanon NXT. The following interactions have been reported in the literature (mainly with combined contraceptives but occasionally also with progestagen-only 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, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and the herbal remedy St. Johns wort). Also HIV protease (e.g., ritonavir, nelfinavir) and nonnucleoside reverse transcriptase inhibitors (e.g., nevirapine, efavirenz), and combinations of them, have been reported to potentially affect hepatic metabolism. Women on treatment with any of the above mentioned drugs should use a non-hormonal contraceptive

4.5.2

In women on long-term treatment with hepatic enzymeinducing drugs, it is recommended to remove the implant and to prescribe a non-hormonal method. Increase in plasma hormone levels associated with coadministered drugs: Drugs (e.g., ketoconazole) that inhibit microsomal enzymes, such as CYP3A4, may increase plasma hormone levels. • Influence of Implanon NXT on other medicinal products Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g., ciclosporin) or decrease (e.g., lamotrigine). 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 affect some laboratory parameters, 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

4.6

method in addition to Implanon NXT. With microsomal enzyme-inducing drugs, the non-hormonal contraceptive method should be used during the time of concomitant drug administration and for 28 days after their discontinuation.

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 NXT is not indicated during pregnancy. If pregnancy occurs during use of Implanon NXT, the implant should be removed. Animal studies have shown that very high doses of progestagenic substances may

cause masculinization of female fetuses. Extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used OCs prior to pregnancy, nor of a teratogenic effect when

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Implanon NXT™: Product Monograph

4.6 - 4.8.2

Part I: Health Care Professional Information OCs were inadvertently used during pregnancy. Although this probably applies to all OCs, it is not clear whether this is also the case for Implanon NXT. Pharmacovigilance data with various etonogestrel- and desogestrel-containing products (etonogestrel is a metabolite of desogestrel) do not indicate an increased risk. Clinical data indicate that Implanon NXT 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 an average daily milk ingestion of 150 ml/kg, the mean daily infant etonogestrel dose calculated after one month of etonogestrel release is approximately 27 ng/kg/day. This corresponds to approximately 2.2% of the weight-adjusted

4.7

maternal daily dose and to approximately 0.2% of the estimated absolute maternal daily dose. Subsequently the milk etonogestrel concentration decreases with time during the lactation period. Long-term data are available on 38 children, whose mothers had an implant inserted during the 4th to 8th week postpartum. They were breast-fed for a mean duration of 14 months and followed-up to 36 months of age. Evaluation of growth, and physical and psychomotor development did not indicate any differences in comparison to nursing infants whose mothers used an IUD (n=33). Nevertheless, development and growth of the child should be carefully followed. Based on the available data, Implanon NXT may be used during lactation and should be inserted after the 4th post partum week.

Effects on ability to drive and use machines

No observed effects

4.8

Undesirable effects

4.8.1

Serious undesirable effects

See Section 4.4.1 (“Warnings”)

4.8.2

Other possible undesirable effects

During the use of Implanon NXT, women are likely to have changes in their menstrual bleeding pattern. These may include changes in bleeding frequency (absent, less, more frequent or continuous), intensity (reduced or increased) or duration. Amenorrhea was reported in about 1 of 5 women while another 1 of 5 women reported frequent and/or prolonged bleeding. Occasionally, heavy bleeding

14

has been reported. In clinical trials, bleeding changes were the most common reason for stopping treatment (about 11 %). Dysmenorrhea tended to improve while using Implanon NXT. The bleeding pattern experienced during the first three months is broadly predictive of future bleeding patterns for many women.

Implanon NXT™: Product Monograph

4.8.2

Part I: Health Care Professional Information Possibly related undesirable effects reported in clinical trials have been listed in the Table below. Adverse reaction in MedDRA Term1 System Organ Class Infections and Infestations

Very Common > 1/10

Common < 1/10 ≥ 1/100

vaginal infection;

Uncommon 1 sanitary towel or tampon per day) • Spotting day (requiring at most 1 sanitary towel or tampon per day) • Bleeding-free day • B-S episodes (≥ 1 consecutive day of bleeding or spotting surrounded by bleeding-free days).

26

Implanon NXT™: Product Monograph

3

Part II: Select Clinical Trials Clinically important bleeding patterns were based on the World Health Organization (WHO)-recommended definitions: • Amenorrhea (no bleeding or spotting days during a 90-day reference period [RP]) • Infrequent bleeding (5 B-S episodes during an RP) • Prolonged bleeding (a B-S episode [uninterrupted] lasting >14 days during a 90-day RP) Changes from baseline to end-of-study in dysmenorrhea by presence and severity (none, mild, severe, very severe) and patterns of discontinuation of IMPLANON were also analyzed. Results: During days 29–118 after IMPLANON implantation (reference period RP 1.1), more subjects reported 0–14 B-S days than 15–28, 29–49, or ≥50 B-S days (Figure 3). The data shown are not statistically significant. Bleeding patterns were consistent during the subsequent follow-up (RP 2 – RP 12), with a mean number of B-S episodes of 2.4 per RP and a median number of B-S days ranging from 13 to 16 per RP. Figure 3. Number of Bleeding-Spotting Days With IMPLANON in Reference Period 1.1 (90-Day Period, Days 29–118)3 40

37.5

35

n=808

30

Patients, %

25

21.7

21.2

15-28 Days

29-49 Days

20

19.7

15 10 5 0 0-14 Days

≥50 Days

Categories of Bleeding-Spotting Days

The group of women with favourable bleeding patterns in the first RP tended to continue with this pattern throughout the first two years of use, whereas the group with unfavourable patterns had at least a 50% chance that the patterns would subsequently improve.

27

Implanon NXT™: Product Monograph

3

Part II: Select Clinical Trials Approximately one-half (48.7%) of women reported dysmenorrhea at baseline, and during the subsequent 3-year follow-up, dysmenorrhea resolved in most patients (Figure 4). Figure 4. Change in Dysmenorrhea From Baseline After up to 3 Years of Use of IMPLANON (Adapted from Mansour et al.)3 Women With Dysmenorrhea at Baseline (n=315)

100 77

Patients, %

80 60 40 20

6 0

Resolved

11.5

5.5

Developed or No Change Worsened Change in Dysmenorrhea From Baseline Decreased Severity

Across the studies, 11.3% of subjects discontinued IMPLANON because of bleeding irregularities, primarily frequent irregular bleeding and prolonged menstrual flow (Table 6). Table 6. Discontinuation Rates With IMPLANON Due to Bleeding Irregularity3 Bleeding Irregularity All irregularities

28

Discontinuation Rate (N=923), % 11.3

Frequent irregular bleeding

4.2

Prolonged menstrual flow

3.4

Spotting

1.4

Heavy menstrual flow

0.9

Amenorrhoea

0.8

Other bleeding problems

0.7

Implanon NXT™: Product Monograph

3 - 4

Part II: Select Clinical Trials Conclusion: The bleeding pattern within the first 3 months of using IMPLANON was in many cases predictive of bleeding patterns observed over subsequent months. Favorable bleeding patterns tended to persist, while women with initially unfavorable bleeding patterns had at least a 50% chance of subsequent improvement. In most patients with dysmenorrhea at baseline who received IMPLANON, this symptom resolved over the 3 years of follow-up. Use of IMPLANON was associated with bleeding pattern irregularities that led to an 11.3% discontinuation rate over 3 years. Physicians administering IMPLANON should educate their patients about the expected changes in bleeding patterns, because such counseling may improve continuation rates.

4

Physician Satisfaction With IMPLANON4

Clinician satisfaction and insertion characteristics of a new applicator to insert radiopaque IMPLANON: an open-label noncontrolled, multicenter trial. Mansour D et al. Contraception. 2010;82(3):243–249.

Objective: To evaluate the satisfaction of investigators performing IMPLANON insertions, and the insertion characteristics and x-ray visibility of IMPLANON NXT. Design and Methods: Twenty-three experienced or inexperienced investigators performed insertions of IMPLANON NXT in 301 women after undergoing training for proper procedures with a next-generation applicator (NGA). After each insertion, characteristics including reported investigator experience, insertion time, implant site reactions, and x-ray detection of the radiopaque implant were recorded. Clinician satisfaction questionnaires following the 4th, 8th, and 12th insertions were also administered. Results: After the first insertion the majority of investigators were satisfied/very satisfied with the applicator; by the 12th insertion, all investigators were satisfied or very satisfied overall, and nearly all were satisfied or very satisfied with functionality, design and technical aspects, safety, and time required for the insertion (Figure 5). Figure 5. Frequency Distribution of Clinician Satisfaction Questionnaire Scoresa (N=23) (Adapted from Mansour et al.)4 Very satisfied

Satisfied

Not satisfied or dissatisfied

Dissatisfied

Very dissatisfied

Overall Satisfaction Functionality Design and Technical Aspects Safety Used Time 0

20

40

60 80 100

Responses After 4 Insertions, %

0

20

40

60 80 100

Responses After 8 Insertions, %

0

20

40

60 80 100

Responses After 12 Insertions, %

Each domain consisted of one or more questions: overall satisfaction:1 question; functionality: 6 questions; design and technical aspects: 5 questions; safety: 3 questions; used time: 1 question.

a

29

Implanon NXT™: Product Monograph

4

Part II: Select Clinical Trials All investigators were satisfied or very satisfied with the insertion time from the first insertion onwards, as well as with the retraction of the needle into the applicator after the insertion and with the color contrast between the obturator and implant. Ease of use, one-handed action, and fast insertion time were the most frequently reported advantages of the new applicator, with 98% of insertions considered easy. Both experienced and inexperienced investigators performed the insertions rapidly, although the experienced investigators completed the insertions faster (Table 7). Table 7. Insertion Time With IMPLANON NXT by All, Experienced, and Inexperienced Users4 Insertion Time (seconds) Subjects (n)

Mean (SD)

Median

Minimum

Maximum

All users (23)

291

27.9 (29.3)

19.0

2

300

Inexperienced users (12)

150

36.6 (36.1)

25.0

7

300

Experienced users (11)

141

18.7 (15.1)

15

2

95

SD = standard deviation. No implant site reactions on the day of insertion were reported for 91.4% of the subjects; redness (4.0%), hematoma (3.3%), pain (1.0%), and swelling (0.7%) were reported in the remaining subjects. Sixty-two subjects underwent 2 dimensional x-ray evaluations, and all implants were clearly visible on x-ray (Figure 6). In one case, the implant was not palpable after insertion but was clearly visible by x-ray. This single non-palpable implant was inserted by an inexperienced investigator who performed the insertion incorrectly, ie, in a standing position instead of sitting, and in a poorly illuminated room. Conclusion: All investigators, regardless of insertion experience, were satisfied with IMPLANON NXT, which is designed for rapid, single-handed use. Difficulties with insertion were related to failure to correctly follow insertion instructions. X-ray visibility was excellent, including detection of an improperly inserted implant that was not palpable after insertion.

30

Figure 6. X-ray visibility of radiopaque IMPLANON NXT implant4

Implanon NXT™: Product Monograph Part II: Select Clinical Trials References: 1. Schnabel P, Merki-Feld GS, Malvy A, et al. Bioequivalence and x-ray visibility of a radiopaque etonogestrel implant versus a non-radiopaque implant: a 3-year, randomized, double-blind study. Clin Drug Investig. 2012;32(6):413-422. 2. Blumenthal PD, Gemzell-Danielsson K, Marintcheva-Petrova M. Tolerability and clinical safety of Implanon. Eur J Contracept Reprod Health Care. 2008;13 Suppl 1:29-36. 3. Mansour D, Korver T, Marintcheva-Petrova M, Fraser IS. The effects of Implanon on menstrual bleeding patterns. Eur J Contracept Reprod Health Care. 2008;13 Suppl 1:13-28. 4. Mansour D, Mommers E, Teede H, et al. Clinician satisfaction and insertion characteristics of a new applicator to insert radiopaque Implanon: an open-label, noncontrolled, multicenter trial. Contraception. 2010;82(3):243-249.

31

32

Implanon NXT™: Product Monograph Part III: Consumer Information

Package Leaflet For The User IMPLANON NXT, 68 mg implant for subdermal use Etonogestrel

Read all of this leaflet carefully before you start using this medicine. • The presented information may help you to decide to use Implanon NXT and to use it properly and safely. • Keep this leaflet. You may need to read it again during the use of Implanon NXT, since it is important to remain aware of potential future issues. • This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. • If you have any further questions, ask your doctor or pharmacist. • If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet: 1. What Is IMPLANON NXT and What Is It Used for? 2. What Do You Have to Know Before IMPLANON NXT Is Inserted?

34 34-37

3. How to Use IMPLANON NXT

38

4. Possible Side Effects

39

5. How to Store IMPLANON NXT

40

6. Further Information

40-43

7. Information for the Health Care Professional

45-50

The name of your contraceptive implant is: Implanon NXT, implant for subdermal use Composition in full • The active substance is: Etonogestrel (68 mg) • The other ingredients are: ethylene vinyl acetate copolymer barium sulfate magnesium stearate The following company is responsible for marketing Implanon NXT: Merck Sharp & Dohme (I.A.) Corporation a Philippine subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A. 26/F Philam Tower 8767 Paseo de Roxas, Makati City 1226 Manufacturer: Implanon NXT is produced by Merck Sharp & Dohme (I.A.) Corporation a Philippine subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A. 26/F Philam Tower 8767 Paseo de Roxas, Makati City 1226

33

Implanon NXT™: Product Monograph

1 - 2

Part III: Consumer Information 1

What Is IMPLANON NXT and What Is It Used for?

Implanon NXT is a contraceptive implant preloaded in a disposable applicator. The implant is a small, soft, flexible, plastic rod, 4 cm in length and 2 mm in diameter which contains 68 milligrams of the active substance, etonogestrel. The applicator allows the healthcare professional to insert the implant just under the skin of your upper arm. Etonogestrel is a synthetic female hormone

resembling progesterone. A small amount of etonogestrel is continuously released into the bloodstream. The implant itself is made of ethylene vinyl acetate copolymer, a plastic that will not dissolve in the body. It also contains a small amount of barium sulfate (which renders it visible under X-ray), and magnesium stearate.

Implanon NXT is used to prevent pregnancy. How does Implanon NXT work? The implant is inserted just below the skin. The active compound, etonogestrel, works in two ways: • It prevents the release of an egg cell from the ovaries. • It causes changes in the cervix that make it difficult for sperm to enter the womb. As a result, Implanon NXT protects you against pregnancy for a period of three years, but if you are overweight the doctor may advise you to replace the implant earlier. Implanon NXT is one of several means of preventing pregnancy. Another frequently used birth control method is the combined Pill. In contrast to combined Pills, Implanon NXT can be used by women

2

who may not, or do not want to use estrogens. When you use Implanon NXT you do not have to remember to take a pill every day. This is one of the reasons that Implanon NXT is very reliable (over 99% effective). If in rare cases the implant is not inserted correctly or is not inserted at all, you may not be protected against pregnancy. When you are using Implanon NXT, your menstrual bleeding may change and become absent, irregular, infrequent, frequent, prolonged, or rarely heavy. The bleeding pattern that you experience during the first three months generally indicates your future bleeding pattern. Painful periods may improve. You may stop using Implanon NXT at any time (See also ‘When you want to stop using Implanon NXT’).

 hat Do You Have to Know Before IMPLANON NXT W Is Inserted?

Hormonal contraceptives, also including Implanon NXT, do not protect against HIV infection (AIDS) or any other sexually transmitted disease. Do not use Implanon NXT Do not use Implanon NXT if you have any of the conditions listed below. If any of these conditions apply to you, tell your doctor before Implanon NXT is inserted. Your doctor may advise you to use a non-hormonal method of birth control.

• if you have or have had jaundice (yellowing of the skin) or severe liver disease (when the liver is not functioning properly), or a liver tumour.

• if you are allergic to etonogestrel or any of the other ingredients of Implanon NXT.

• if you have any unexplained vaginal bleeding.

• if you have a thrombosis. Thrombosis is the formation of a blood clot in a blood vessel [for example in the legs (deep venous thrombosis) or the lungs (pulmonary embolism)].

34

• if you have (had) or if you may have cancer of the breast or of the genital organs.

• if you are pregnant or think you might be pregnant. If any of these conditions appear for the first time while using Implanon NXT, consult your doctor immediately.

Implanon NXT™: Product Monograph

2

Part III: Consumer Information Take special care with Implanon NXT If Implanon NXT is used in the presence of any of the conditions listed below, you may need to be kept under close observation. Your doctor can explain to you what to do. If any of these apply to you, tell your doctor before Implanon NXT is inserted. Also if the condition develops or gets worse while you are using Implanon NXT you must tell your doctor. • you have had cancer of the breast; • you have or have had a liver disease; • you have ever had a thrombosis;

• you have diabetes; • you are overweight; • you have high cholesterol or triglycerides • you suffer from epilepsy; • you suffer from tuberculosis; • you have high blood pressure; • you have or have had chloasma (yellowish-brown pigmentation patches on the skin, particularly of the face); if so avoid too much exposure to the sun or ultraviolet radiation

Possible serious conditions Cancer The information presented below has been obtained in studies with women who daily take an oral combined contraceptive containing two different female hormones (“the Pill”). It is not known whether these observations are also applicable to women who use a different hormonal contraceptive, such as implants containing only a progestagen. Breast cancer has been found slightly more often in women using oral combined pills, but it is not known whether this is caused by the treatment. For example, it may be that tumors are found more in women on combined pills, because they are examined by the doctor more often. The increased

occurrence of breast cancer becomes gradually less after stopping the combined pill. It is important to regularly check your breasts and you should contact your doctor if you feel any lump in your breasts. You should also tell your doctor if a close relative has or ever had breast cancer. In rare cases, benign and even more rarely malignant liver tumors have been reported in women using the Pill. If you experience severe abdominal pain, you should contact your doctor immediately.

Thrombosis A blood clot in a vein (known as a ‘venous thrombosis’) can block the vein. This can happen in veins in the leg (a deep vein thrombosis), the lung (a lung embolus), or other organs. A blood clot in an artery (known as ‘arterial thrombosis’) can block the artery. For example, a blood clot in an artery may cause a heart attack, or in the brain may cause a stroke.

clot during pregnancy. The risk with progestagen-only methods like Implanon NXT, is believed to be lower than in users of Pills that also contain estrogens. There have been reports of blood clot formation like lung emboli, deep vein thrombosis, heart attacks and strokes in women using etonogestrel implants.

Using any combined hormonal contraceptive increases a woman’s risk of developing such clots compared with a woman not taking any combined hormonal contraceptive. The risk is not as high as the risk of developing a blood

If you notice suddenly possible signs of a thrombosis, you should see your doctor immediately. (See also “When should you contact your doctor”?).

Menstrual bleeding pattern changes Like with other progestagen-only contraceptives, your menstrual bleeding pattern may change when using Implanon NXT. You may experience a change in

frequency (absent, less, more frequent or continuous), intensity (reduced or increased) or in duration. Absence of bleeding was reported in about 1 of 5 women while another

35

Implanon NXT™: Product Monograph

2

Part III: Consumer Information 1 of 5 women reported frequent and/or prolonged bleeding. Occasionally heavy bleeding has been observed. In clinical trials, bleeding changes were the most common reason for stopping treatment (about 11 %). The bleeding pattern that you experience during the first three months generally indicates your future bleeding pattern.

A changing bleeding pattern does not mean that Implanon NXT does not suit you or is not giving you contraceptive protection. In general, you do not need to take any action. You should consult your doctor if menstrual bleeding is heavy or prolonged.

Insertion and removal related events The implant may migrate from the original insertion site, if not correctly or too deeply inserted and/or due to external forces (e.g. manipulation of the implant or contact sports). In these cases localization of the implant may be more

difficult and removal may require a larger incision. If the implant cannot be found, and there is no evidence it has been expelled, contraception and the risk of progestagenrelated undesirable effects may last longer than you want.

Ovarian cysts During the use of all low-dose hormonal contraceptives, small fluid-filled sacs may develop in the ovaries. These are called ovarian cysts. They usually disappear on their own.

Sometimes they cause mild abdominal pain. Only rarely, they may lead to more serious problems.

Using other medicines Please tell your doctor if you are taking or have recently taken any other medicines or herbal products, including medicines obtained without a prescription. Some medicines may stop Implanon NXT from working properly. These include medicines used for the treatment of • epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate, felbamate), • tuberculosis (e.g. rifampicin), • HIV infections (e.g. ritonavir, nelfinavir, nevirapine, efavirenz), • other infectious diseases (e.g. griseofulvin), • high blood pressure in the blood vessels of the lungs (bosentan), • depressive moods (the herbal remedy St. John’s wort).

Using Implanon NXT with food and drink There are no indications of any effect of food and drink on the use of Implanon NXT.

36

Implanon NXT may also interfere with the working of other medicines; e.g. increase the activity of ciclosporin and decrease the effect of lamotrigine. Always tell the doctor, who prescribes Implanon NXT, which medicines or herbal products you are already using. Also tell any other doctor or dentist who prescribes another medicine (or the dispensing pharmacist) that you use Implanon NXT. They can tell you if you need to take additional non-hormonal contraceptive precautions and if so, for how long, since the interaction may last up to four weeks after stopping with the medicine. If there are medicines that you have been taking for a long time, that make Implanon NXT less effective, your doctor may also advise that the implant is removed and recommend a birth control method that can be used effectively with these medicines. If you want to use herbal products containing St. John’s wort while you are already using Implanon NXT you should consult your doctor first.

Implanon NXT™: Product Monograph

2

Part III: Consumer Information Pregnancy and Breast-feeding You must not use Implanon NXT when you are pregnant, or think you may be pregnant. In case you doubt whether you are pregnant or not, you should perform a pregnancy test before starting using Implanon NXT. Implanon NXT may be used while you are breastfeeding. Although a small amount of the active substance of

Implanon NXT passes over into the breast milk, there is no effect on the production or the quality of breast milk, nor on the growth and development of the child. If you are breast-feeding and want to use Implanon NXT, please inform your healthcare professional.

Driving and using machines There are no indications of any effect of the use of Implanon NXT on alertness and concentration. When should you contact your doctor?

Regular check-ups Before Implanon NXT is inserted, your healthcare professional will ask you some questions about your personal health history and that of your close relatives. The healthcare professional will also measure your blood pressure, and depending on your personal situation, may also carry out some other tests. When you are using Implanon NXT, your healthcare professional may ask you to return for a (routine) medical check-up some time after insertion of the implant. The frequency and nature of further check-ups will depend on your personal situation. Contact your doctor as soon as possible if: • you notice any changes in your own health, especially involving any of the items mentioned in this leaflet (see also ”Do not use Implanon NXT” and “Take special care with Implanon NXT”; do not forget about the items related to your immediate family); • you notice possible signs of a thrombosis such as severe pain or swelling in either of your legs, unexplained pains in the chest, breathlessness, an unusual cough, especially if you cough up blood; • you have a sudden, severe stomach ache or look jaundiced; • you feel a lump in your breast (see also “Cancer”); • you have a sudden or severe pain in the lower part of your belly or stomach; • you have unusual, heavy vaginal bleeding; • you are to be immobilized (for example being confined to bed) or are to have surgery (consult your doctor at least four weeks in advance); • you suspect that you are pregnant.

37

Implanon NXT™: Product Monograph

3

Part III: Consumer Information 3

How to Use Implanon Nxt

Please tell your healthcare professional if you are pregnant or think you might be pregnant before Implanon NXT is inserted (e.g. if you had unprotected intercourse during the current menstrual cycle). How to use Implanon NXT should be inserted and removed only by a healthcare professional who is familiar with procedures as described on the other side of this leaflet. The healthcare professional will decide in consultation with you the most suitable time for insertion. This depends on your personal situation (for example on the birth control method that you are currently using). Unless you are switching from another hormonal contraceptive method, the insertion should be performed on day 1-5 of your spontaneous menstrual bleeding to rule out pregnancy.

Your healthcare professional will advise you (for more information see overleaf Section 7.1 “When to insert Implanon NXT”). Before inserting or removing Implanon NXT, your healthcare professional will give you a local anesthetic. Implanon NXT is inserted directly under the skin, on the inside of your upper non-dominant arm (the arm that you do not write with). A description of the insertion and the removal procedure of Implanon NXT is shown in section 6.

Implanon NXT should be removed or replaced no more than three years after insertion. To help you remember when and where Implanon NXT was inserted, and when Implanon NXT must be removed at the latest, your healthcare professional will give you a User Card that shows this information. Store the card in a safe place! At the end of the insertion procedure, the healthcare professional will ask you to feel the implant by palpation. A correctly inserted implant should be clearly palpable by the healthcare professional as well as by you, certainly if both ends can be lifted between thumb and finger. It should be realized that palpation is not suitable for 100% verification of the presence of the implant. In case of the slightest doubt

you have to use a barrier method (e.g. a condom) until the healthcare professional and you are absolutely sure that the implant has been inserted. In rare cases the healthcare professional may have to use X-rays, ultrasound or magnetic resonance imaging, or may have to take a blood sample, to make sure that the implant is inside your arm. In case you would like to have Implanon NXT replaced, a new implant may be inserted immediately after the old implant is removed. The new implant may be inserted in the same arm and at the same site as the previous implant. Your healthcare professional will advise you.

When you want to stop using Implanon NXT You can ask your healthcare professional to remove the implant at any time you want. If the implant cannot be localized by palpation, the healthcare professional may use X-rays, ultrasound or magnetic resonance imaging to locate the implant. Depending on the exact position of the implant, removal may be a little difficult and may require minor surgery. If you do not want to become pregnant after removal of Implanon NXT, ask your healthcare professional about other reliable methods of birth control.

38

If you stop using Implanon NXT because you want to get pregnant, it is generally recommended that you wait until you have had a natural period before trying to conceive. This helps you to work out when the baby will be due.

Implanon NXT™: Product Monograph

4

Part III: Consumer Information 4

Possible Side Effects

Like all medicines, Implanon NXT can cause side effects, although not everybody gets them. Menstrual bleeding may occur at irregular intervals during the use of Implanon NXT. This may be just slight staining which may not even require a pad, or heavier bleeding,

which looks rather like a scanty period and requires sanitary protection. You may also not have any bleeding at all. The irregular bleedings are not a sign that the contraceptive protection of Implanon NXT is decreased. In general, you need not take any action. If, however, bleeding is heavy or prolonged consult your doctor.

Possible serious side effects Serious undesirable effects are described in the paragraphs of section 2 “Cancer” and “Thrombosis”. Please read this section for additional information and consult your doctor at once where appropriate. The following side effects have been reported: Very Common > 1/10 acne; headache; increase in body weight; breasts tenderness and pain; irregular bleeding; infection of the vagina.

Common 1/10 - 1/100 hair loss; dizziness; depressive moods; emotional lability; nervousness; decreased sexual drive; increased appetite; abdominal pain; nausea; gas in stomach and intestines; painful menstruation; decrease in body weight; influenza-like symptoms; pain; fatigue; hot flushes; implant site pain; implant site reaction; ovarian cyst.

Uncommon 1/100 - 1/1000 Itching; itching in the genital area; rash; excessive hair growth; migraine; anxiety; sleeplessness; sleepiness; diarrhea; vomiting; constipation; urinary tract infection; vaginal discomfort (e.g. vaginal secretion); breast enlargement; breast secretion; back pain; fever; fluid retention; difficult or painful urination; allergic reactions; inflammation and pain of the throat; rhinitis; joint pain; muscle pain; skeletal pain.

39

Implanon NXT™: Product Monograph

5 - 6

Part III: Consumer Information Apart from these side effects, a rise in blood pressure has occasionally been observed. Also oily skin has been observed. You should seek immediate medical attention if you experience symptoms of a severe allergic reaction, such as (i) swollen face, tongue or pharynx; (ii) trouble swallowing; or (iii) hives and trouble breathing. During the insertion or removal of Implanon NXT, some bruising, pain, swelling, or itching

5

may occur and, in rare cases, infection. A scar may be formed or an abscess may develop at the implantation site. A numb feeling or sensation of numbness (or lack of feeling) may occur. Expulsion or migration of the implant is possible, especially if it has not been inserted properly. Surgery might be necessary when removing the implant. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

How to Store Implanon NXT

Keep out of the reach and sight of children. Do not use after the expiry date which is stated on the blister and carton.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Store in the original package at 2° to 30°C.

6

Further Information

What Implanon NXT contains One applicator containing one implant with •

The active substance is: etonogestrel (68 mg)

•

 he other ingredients are: ethylene vinyl acetate T copolymer, barium sulfate, and magnesium stearate.

What Implanon NXT looks like and the content of the pack Implanon NXT is a subdermal long acting hormonal contraceptive. It consists of a radiopaque progestagen-only implant preloaded in an innovative, ready-for-use, userfriendly, disposable applicator. The off-white implant is 4 cm in length and 2 mm in diameter and contains etonogestrel and barium sulfate. The applicator has been designed to facilitate the insertion of the implant just below the skin of your inner upper (non dominant) arm. The implant is to be inserted and removed by a healthcare professional who is familiar with the procedures. For uncomplicated removal it is necessary that the implant is inserted just below the skin (see other side of the leaflet). Local anesthetic should be used before inserting or removing the implant. The risk of complications is small if the provided instructions are followed.

40

This leaflet was last approved in May 2012 Note: These pictograms are only meant to illustrate the insertion and removal procedures for the woman who will be receiving the implant. The exact procedures for the insertion and removal of Implanon NXT by the qualified healthcare professional are described in the Summary of Product Characteristics (SmPC) and in section 7 of this user package leaflet.

Implanon NXT™: Product Monograph

6.1

Part III: Consumer Information 6.1

How is Implanon NXT inserted?

• Insertion of Implanon NXT should only be performed by a qualified healthcare professional who is familiar with the procedure. • To facilitate the insertion of the implant, you should lie on your back, with your arm slightly bent at the elbow and turned outwards. Figure 1

• The implant will be inserted at the inner side of your upper non-dominant arm (the arm that you do not write with). • The insertion site will be indicated on the skin, the site is disinfected and anesthetized.

Figure 2

• The skin is stretched and the needle is inserted, directly under the skin. Once the tip is inside the skin the needle is completely inserted in a movement parallel to the skin.

Figure 3

Figure 4

41

Implanon NXT™: Product Monograph

6.1 - 6.2

Part III: Consumer Information

• The purple slider is unlocked by pushing it slightly down and fully pushing it backwards until it is arrested in the back in order to retract the needle. The implant will remain in the upper arm when the needle is withdrawn. • The presence of the implant should be verified by feeling it (palpation) immediately following insertion. A correctly inserted implant can be felt between thumb and finger by both the healthcare professional and by you. It should be realized that palpation is not suitable for 100% verification of the presence of the implant. • In case the implant can not be palpated or when its presence is doubtful other methods must be used to confirm the presence of the implant. • Until the presence of the implant has been verified you may not be protected against pregnancy and a contraceptive barrier method (e.g. condoms) must be used. • You will be given sterile gauze with a pressure bandage to minimize bruising. You may remove the pressure bandage in 24 hours and the small bandage over the insertion site in 3-5 days. • After insertion of the implant, the healthcare professional will give you a User Card with the insertion site, insertion date and the latest date on which the implant has to be removed or replaced. Put it in a safe place, since the information on the card may facilitate removal later on.

6.2

How should Implanon NXT be removed?

• The implant should only be removed by a qualified healthcare professional who is familiar with the procedure. • The implant is removed at your request or -at the latest- three years after insertion. • The location of the insertion site of the implant is indicated on the User card. • The healthcare professional will locate the implant. If the implant can not be located the healthcare professional may have to use X-ray, ultrasound or magnetic resonance imaging techniques.

• Your upper arm will be disinfected and anesthetized.

Figure 5

42

Implanon NXT™: Product Monograph

6.2

Part III: Consumer Information

• A small incision will be made along the arm just below the tip of the implant.

Figure 6

• The implant is gently pushed towards the incision and removed with a forceps.

Figure 7

• Occasionally, the implant may be surrounded by hard tissue. If this is the case, a small cut needs to be made into the tissue before the implant can be removed. • If you want your healthcare professional to replace Implanon NXT with another implant, the new implant may be inserted using the same incision. • The incision will be closed by a steri-strip. • You will be given sterile gauze with a pressure bandage to minimize bruising. You may remove the pressure bandage in 24 hours and the small bandage over the insertion site in 3-5 days.

The following information is intended for the healthcare professional. This section does not take the place of consulting the Summary of

Product Characteristics (SmPC). Please read the entire Implanon NXT labelling carefully before inserting or removing Implanon NXT.

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Part III: Consumer Information 7

Information for the Health Care Professional

7.1

When to insert Implanon NXT

IMPORTANT: Rule out pregnancy before inserting the implant.

Timing of insertion depends on the woman’s recent contraceptive history, as follows:

No preceding hormonal contraceptive use in the past month: The implant should be inserted between Day 1 (first day of menstrual bleeding) and Day 5 of the menstrual cycle, even if the woman is still bleeding.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Switching contraceptive method to Implanon NXT Changing from a combined hormonal contraceptive method (combined oral contraceptive (COC), vaginal ring or transdermal patch) The implant should be inserted preferably on the day after the last active tablet (the last tablet containing the active substances) of the previous COC, but at the latest on the day following the usual tablet-free or placebo tablet interval of the previous COC. In case a vaginal ring or transdermal patch has been used, the implant should be inserted preferably on the day of removal, but at the latest when the next application would have been due.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Changing from a progestagen-only contraceptive method (e.g. progestagen-only pill, injectable, implant, or intrauterine system [IUS]) As there are several types of progestagen-only methods, the insertion of the implant must be performed as follows: •

Injectable contraceptives: Insert the implant on the day the next injection is due.

•

 rogestagen-only pill: A woman may switch from the P progestagen-only pill to Implanon NXT on any day of the month. The implant should be inserted within 24 hours after taking the last tablet.

•

Implant/Intrauterine system (IUS): Insert the implant on the same day the previous implant or IUS is removed.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Following abortion or miscarriage •

 irst trimester: The implant should be inserted within 5 F days following a first trimester abortion or miscarriage.

•

 econd trimester: Insert the implant between 21 to 28 S days following second trimester abortion or miscarriage.

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If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Implanon NXT™: Product Monograph

7.1 - 7.2

Part III: Consumer Information Postpartum •

 reast-feeding: The implant should be inserted after B the fourth postpartum week (see Section 4.6 “Pregnancy and Lactation” in the SmPC). The woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

7.2

•

Not breast-feeding: The implant should be inserted between 21 to 28 days postpartum. If inserted as recommended, back-up contraception is not necessary. If the implant is inserted later than 28 days postpartum, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

How to insert Implanon NXT

The basis for successful use and subsequent removal of Implanon NXT is a correct and carefully performed subdermal insertion of the implant in the non-dominant arm in accordance with the instructions. Both the HCP and the woman should be able to feel the implant under the woman’s skin after placement. The implant should be inserted subdermally just under the skin. If the implant is inserted too deep, neural or vascular damage may occur. Too deep or incorrect insertions have been associated with paresthesia (due to neural damage) and migration of the implant (due to intramuscular or fascial insertion), and in rare cases with intravascular insertion.

Moreover, when the implant is inserted too deep, it may not be palpable and the localization and/or removal can be difficult. Insertion of Implanon NXT should be performed under aseptic conditions and only by a qualified HCP who is familiar with the procedure. Insertion of the implant should only be performed with the preloaded applicator. It is recommended that the HCP is in a seated position during the entire insertion procedure so that the insertion site and the movement of the needle just under the skin can be clearly seen from the side.

• Have the woman lie on her back on the examination table with her non-dominant arm flexed at the elbow and externally rotated so that her wrist is parallel to her ear or her hand is positioned next to her head (Figure 8).

Figure 8

• Identify the insertion site, which is at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus (Figure 9). The implant should be inserted subdermally just under the skin to avoid the large blood vessels and nerves that lie deeper in the subcutaneous tissue in the sulcus between the triceps and biceps muscles (see section 4.4.1 “Warnings” in the SmPC).

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Part III: Consumer Information

• Make two marks with a sterile marker: first, mark the spot where the implant will be inserted, and second, mark a spot a few centimeters proximal to the first mark (Figure 9). This second mark will later serve as a direction guide during insertion.

Guiding Mark

8-10 cm Insertion Site

Medial Epicondyle

Figure 9

• Clean the insertion site with an antiseptic solution. • Anesthetize the insertion area (for example, with anesthetic spray or by injecting 2 ml of 1% lidocaine just under the skin along the planned insertion tunnel). • Remove the sterile preloaded disposable Implanon NXT applicator carrying the implant from its blister. The applicator should not be used if sterility is in question. Purple Slider

• Hold the applicator just above the needle at the textured surface area. Remove the transparent protection cap by sliding it horizontally in the direction of the arrow away from the needle (Figure 10). If the cap does not come off easily, the applicator should not be used. You may see the white colored implant by looking into the tip of the needle. Do not touch the purple slider until you have fully inserted the needle subdermally, as it will retract the needle and prematurely release the implant from the applicator.

Figure 10

• With your free hand, stretch the skin around the insertion site with thumb and index finger (Figure 11).

Figure 11

• Puncture the skin with the tip of the needle angled about 30° (Figure 12).

Figure 12

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Implanon NXT™: Product Monograph

7.2

Part III: Consumer Information

• Lower the applicator to a horizontal position. While lifting the skin with the tip of the needle (Figure 13), slide the needle to its full length. You may feel slight resistance but do not exert excessive force. If the needle is not inserted to its full length, the implant will not be inserted properly.  ou can best see movement of the needle if you are seated Y and are looking at the applicator from the side and NOT from above. In this position, you can clearly see the insertion site and the movement of the needle just under the skin. • Keep the applicator in the same position with the needle inserted to its full length. If needed, you may use your free hand to keep the applicator in the same position during the following procedure. Unlock the purple slider by pushing it slightly down. Move the slider fully back until it stops (Figure 14). The implant is now in its final subdermal position, and the needle is locked inside the body of the applicator. The applicator can now be removed. If the applicator is not kept in the same position during this procedure or if the purple slider is not completely moved to the back, the implant will not be inserted properly.

Figure 13

Figure 14

• Always verify the presence of the implant in the woman’s arm immediately after insertion by palpation. By palpating both ends of the implant, you should be able to confirm the presence of the 4 cm rod (Figure 15).

Figure 15

If you cannot feel the implant or in doubt of its presence, • Check the applicator. The needle should be fully retracted and only the purple tip of the obturator should be visible. • Use other methods to confirm the presence of the implant. Suitable methods are: two-dimensional X-ray, X-ray computerized tomography (CT scan), ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHz or greater) or magnetic resonance imaging (MRI). Prior to the application of X-ray CT, USS or MRI for the localization of the implant, it is recommended to consult the local supplier of Implanon NXT for instructions. In case these imaging methods fail, it is advised to verify the presence of the implant by measuring the etonogestrel level in a blood sample of the subject. In this case the local supplier will provide the appropriate procedure. Until you have verified the presence of the implant, a non-hormonal contraceptive method must be used.

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7.2 - 7.3

Part III: Consumer Information • Apply a small adhesive bandage over the insertion site. Request that the woman palpate the implant. • Apply sterile gauze with a pressure bandage to minimize bruising. The woman may remove the pressure bandage in 24 hours and the small bandage over the insertion site after 3-5 days. • Complete the User Card and give it to the woman to keep. Also, complete the adhesive labels and affix it to the woman’s medical record. • The applicator is for single use only and must be adequately disposed of, in accordance with local regulations for the handling of biohazardous waste.

7.3

How to remove Implanon NXT

Before initiating the removal procedure, the HCP should consult the User Card for the location of the Implanon NXT implant. Verify the exact location of the implant in the arm by palpation. If the implant is not palpable, two-dimensional X-ray can be performed to verify its presence. A non-palpable implant should always be first located prior to removal. Suitable methods for localization include, X-ray computer tomography (CT), ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHZ or greater) or magnetic resonance imaging (MRI). If these imaging methods fail to locate the implant, etonogestrel blood level determination can be used for verification of the presence of the implant. Please contact your local supplier for further guidance.

After localization of a non-palpable implant, consider conducting removal with ultrasound guidance. There have been occasional reports of migration of the implant; usually this involves minor movement relative to the original position unless inserted too deeply (see also section 4.4.1 “Warnings” in the SmPC). This may complicate localization of the implant by palpation, USS and/or MRI, and removal may require a larger incision and more time. Removal of the implant should only be performed under aseptic conditions by a HCP who is familiar with the removal technique.

Exploratory surgery without knowledge of the exact location of the implant is strongly discouraged. Removal of deeply inserted implants should be conducted with caution in order to prevent damage to deeper neural or vascular structures in the arm and should be performed by HCPs familiar with the anatomy of the arm.

If the implant cannot be removed, please contact your local supplier for further guidance.

• Clean the site where the incision will be made and apply an antiseptic. Locate the implant by palpation and mark the distal end (end closest to the elbow), for example, with a sterile marker (Figure 16).

Figure 16

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Part III: Consumer Information

• Anesthetize the arm, for example, with 0.5 to 1 ml 1% lidocaine at the marked site where the incision will be made (Figure 17). Be sure to inject the local anesthetic under the implant to keep it close to the skin surface.

Figure 17

• Push down the proximal end of the implant (Figure 18) to stabilize it; a bulge may appear indicating the distal end of implant. Starting at the distal tip of the implant, make a longitudinal incision of 2 mm towards the elbow.

Figure 18

• Gently push the implant towards the incision until the tip is visible. Grasp the implant with forceps (preferably curved mosquito forceps) and remove the implant (Figure 19).

Figure 19

• If the implant is encapsulated, make an incision into the tissue sheath and then remove the implant with the forceps (Figures 20 and 21).

Figure 20

Figure 21

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Part III: Consumer Information

• If the tip of the implant does not become visible in the incision, gently insert a forceps into the incision (Figure 22). Flip the forceps over into your other hand (Figure 23). With a second pair of forceps carefully dissect the tissue around the implant and grasp the implant (Figure 24). The implant can then be removed.

Figure 22

Figure 23

Figure 24

• Confirm that the entire implant, which is 4 cm long, has been removed by measuring its length. If a partial implant (less than 4 cm) is removed, the remaining piece should be removed by following the instructions in section 7.3 “How to remove Implanon NXT”. • If the woman would like to continue using Implanon NXT, a new implant may be inserted immediately after the old implant is removed using the same incision (Section 7.4 “How to replace Implanon NXT”). • After removing the implant, close the incision with a steri-strip and apply an adhesive bandage. • Apply sterile gauze with a pressure bandage to minimize bruising. The woman may remove the pressure bandage after 24 hours and the small bandage after 3-5 days.

7.4

How to replace Implanon NXT

Immediate replacement can be done after removal of the previous implant and is similar to the insertion procedure described in section 7.2 “How to insert Implanon NXT”. The new implant may be inserted in the same arm, and through the same incision from which the previous implant was removed.

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If the same incision is being used to insert a new implant, anesthetize the insertion site (e.g. 2 ml lidocaine (1%)) applied just under the skin commencing at the removal incision along the ‘insertion canal’ and follow the subsequent steps in the insertion instructions.

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Before prescribing IMPLANON NXT™, please read the Prescribing Information.

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