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 2 3
Summary Product Information

1
ame of the
N
Medicinal
Product
Implanon NXT, 68 mg
etonogestrel implant for
subdermal use
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 g/day in weeks 5-6 and
has decreased to approximately
35-45 g/day at the end of the
first year, to approximately 30-40
g/day at the end of the second
year and to approximately 25-30
g/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.
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.
4 - 4.2.1
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
4.2.2

4.2.2
When to insert Implanon NXT
IMPORTANT: Rule out pregnancy before inserting

the implant.
Timing of insertion depends on the womans 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.

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.

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.

Postpartum
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.
4.2.3

4.2.3
How to insert Implanon NXT

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
womans 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.
4.2.3
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.
Figure 6
4.2.3
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 womans

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 womans 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.
4.2.4

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
4.2.4
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
4.2.4 - 4.4.1
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.
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
4.4.1

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.
11
4.4.1 - 4.4.4

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; Sydenhams 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 womans 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.
4.5 - 4.6

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
13
4.6 - 4.8.2

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.
4.8.2

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
<1/100 1/1000
Pharyngitis; rhinitis; urinary
tract infection;
Immune system disorders
Hypersensitivity;
Metabolism and nutritional

disorders
increased appetite;
Psychiatric disorders
affect lability; depressed

mood; nervousness; libido
decreased;
Anxiety; insomnia;
Dizziness;
Migraine; somnolence;
Nervous system disorders
Headache;
Vascular disorders
hot flush;
Gastrointestinal disorders
abdominal pain; nausea;

flatulence
Vomiting; constipation;
diarrhea
Alopecia
hypertrichosis, rash;
pruritus
Skin and subcutaneous

tissue disorders
Acne
Musculoskeletal and
connective tissue disorders
back pain; arthralgia;

myalgia; musculoskeletal
pain
Renal and urinary disorders
Dysuria
Reproductive system and

breast disorders
breast tenderness;
breast pain; menstruation
irregular
General disorders and

administration site condition
Investigations
weight increased
Dysmenorrhea;
ovarian cyst
genital discharge;
vulvovaginal discomfort;
galactorrhea; breast
enlargement; pruritus
genital
implant site pain; implant

site reaction; fatigue;
influenza like illness; pain
Pyrexia; edema
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.
1
In a clinical trial of Implanon NXT, in which investigators

were asked to examine the implant site after insertion,
implant site reactions were reported in 8.6% of women.
Erythema was the most frequent implant site complication,
reported during and/or shortly after insertion, occurring in

3.3% of subjects. Additionally, hematoma (3.0%), bruising
(2.0%), pain (1.0%), and swelling (0.7%) were reported.
15
4.8.2 - 5.1

During postmarketing surveillance, a clinically relevant
rise in blood pressure has been observed in rare cases.
Seborrhea has also been reported. Anaphylactic reactions,
urticaria, angioedema, aggravation of angioedema and/or
aggravation of hereditary angioedema may occur. Insertion
or removal of the implant may cause some bruising, slight
local irritation, pain or itching. Fibrosis at the implant site
may occur, a scar may be formed or an abscess may
develop. Paresthesia or paresthesia-like events may occur.
Expulsion or migration of the implant may be possible (see
also section 4.4.1 Warnings). Surgical intervention might
be necessary when removing the implant.
4.9
deleterious effects from an overdose of contraceptives in

general.
Pharmacological Properties
5.1
Pharmacodynamic properties
(Pharmacotherapeutic group: progestagens, ATCclassification G03AC08)

The Implanon NXT implant is a non-biodegradable,
radiopaque, etonogestrel-containing implant for subdermal
use, preloaded in a sterile, innovative, disposable
applicator. Etonogestrel is the biologically active metabolite
of desogestrel, a progestagen widely used in OCs. It is
structurally derived from 19-nortestosterone and binds
with high affinity to progesterone receptors in the target
organs. The contraceptive effect of etonogestrel is primarily
achieved by inhibition of ovulation. Ovulations were not
observed in the first two years of use of the implant and
only rarely in the third year. Besides inhibition of ovulation,
etonogestrel also causes changes in the cervical mucus,
which hinders the passage of spermatozoa. Clinical
trials were conducted in women between 18 and 40
years. Although no direct comparison was made, the
contraceptive efficacy appeared to be at least comparable
to that known for combined OCs (over 99%). The high
16
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, some of
which are discussed in more detail Section 4.4 Special
Warnings and Special Precautions for Use.
Overdose
An implant should always be removed before inserting a

new one. There are no data available on overdose with
etonogestrel. There have been no reports of serious
On rare occasions, ectopic pregnancies have been

reported (see Section 4.4.1 Warnings).
degree of protection against pregnancy is obtained,

amongst other reasons, because the contraceptive action
of Implanon NXT is not dependent on adherence
to a daily, weekly, or monthly dosing regimen by the
woman herself. The contraceptive action of etonogestrel
is reversible, which is apparent from the rapid return of
the normal menstrual cycle after removal of the implant.
Although etonogestrel inhibits ovulation, ovarian activity is
not completely suppressed. Mean estradiol concentrations
remain above the level seen in the early-follicular phase. In
a two-year study, in which the bone mineral density in 44
users has been compared to that in a control group of 29
IUD-users no adverse effects on bone mass have been
observed. No clinically relevant effects on lipid metabolism
have been observed. The use of progestagen-containing
contraceptives may have an effect on insulin resistance and
glucose tolerance. Clinical trials further indicate that users
of Implanon NXT often have a less painful menstrual
bleeding (dysmenorrhea).
5.1 - 5.2

Implant insertion and removal characteristics
In a clinical trial, Implanon NXT was inserted in 301
women. The mean insertion time (from the removal of the
protection cap of the applicator until retraction of the needle
from the arm) was 27.9 seconds (standard deviation (SD)
= 29.3, n=291). After insertion, 300 out of 301 (99.7%)
Implanon NXT implants were palpable. The single,
non-palpable implant was not inserted according to the
instructions. For 293 of the 301 subjects, data on palpability
was gathered before removal. The implant was palpable for
all 293 subjects with data on palpability. For four subjects,
palpability was not assessed and another four subjects
were lost to follow-up before removal.
5.2
In two clinical trials with Implanon NXT implants, a

total of 116 subjects underwent two-dimensional x-ray
assessments at (after) insertion and/or (before) removal.
For 101 out of 103 (98.1%) subjects for whom x-ray
assessments were performed at insertion and before
removal, Implanon NXT implants were clearly visible;
for two subjects the implants were not clearly visible after
insertion but were clearly visible before removal. The
implants of the 13 subjects with x-ray assessment only at
insertion (n=12) or only before removal (n=1) were all clearly
visible.
Pharmacokinetic properties
Absorption
After the insertion of the implant, etonogestrel is rapidly
absorbed into the circulation. Ovulation-inhibiting
concentrations are reached within 1 day. Maximum
serum concentrations (between 472 and 1270 pg/ml) are
reached within 1 to 13 days. The release rate of the implant
decreases with time. As a result, serum concentrations
decline rapidly over the first few months. By the end of
the first year a mean concentration of approximately 200

pg/ml (range 150-261 pg/ml) is measured, which slowly
decreases to 156 pg/ml (range 111-202 pg/ml) by the
end of the third year. The variations observed in serum
concentrations can be partly attributed to differences in
body weight.
Distribution
Etonogestrel is for 95.5-99% bound to serum proteins,
predominantly to albumin and to a lesser extent to sex
hormone binding globulin. The central and total volume
of distribution are 27 l and 220 l, respectively, and hardly

change during the use of Implanon NXT.
Metabolism
Etonogestrel undergoes hydroxylation and reduction.
Metabolites are conjugated to sulfates and glucuronides.
Animal studies show that enterohepatic circulation probably
does not contribute to the progestagenic activity of

etonogestrel.
Elimination
After intravenous administration of etonogestrel, the mean
elimination half-life is approximately 25 hours
and the serum clearance is approximately 7.5 l/hour.
Both clearance and elimination-half-life remain constant
during the treatment period. The excretion of etonogestrel
and its metabolites, either as free steroids or as conjugates,
is with urine and feces (ratio 1.5:1). After insertion in
lactating women, etonogestrel is excreted in breast
milk with a milk/serum ratio of 0.44-0.50 during the first

four months. In lactating women, the mean transfer of
etonogestrel to the infant is approximately 0.2% of the
estimated absolute maternal etonogestrel daily dose
(2.2% when values are normalized per kg body weight).
Concentrations show a gradual and statistically significant
decrease over the time.
17
5.3 - 6.6

5.3
Preclinical safety data
Toxicological studies did not reveal any effects other than

those, which can be explained on the basis of the hormonal
properties of etonogestrel, regardless of the route of

administration.
Pharmaceutical Particulars
6.1
List of excipients
Implant
Core: Ethylene vinylacetate copolymer (28% vinyl acetate,
43 mg) barium sulfate (15 mg), magnesium stearate
(0.1 mg).
6.2
Skin: Ethylene vinylacetate copolymer (15% vinyl acetate,

15 mg).
Incompatibilities
No incompatibilities are known
6.3
Shelf life
The shelf life of Implanon NXT is 5 years when stored

as indicated under Section 6.4 Special precautions for
storage.
6.4
Implanon NXT should not be inserted after the expiry

date as indicated on the primary package.
Special precautions for storage
Store in the original package at 2 to 30C.
6.5
Nature and contents of container
The pack contains one implant (4 cm in length and 2

mm in diameter) which is preloaded in the stainless steel
needle of a ready-for-use, disposable, sterile applicator. The
applicator containing the implant is packed in a blister pack
6.6
Instructions for use and handling
See Section 4.2 (Posology and Method of Administration).
18
made of transparent polyethyleneterephtalate glycol (PETG)

sealed with a foil lidding. The blister pack is packed in a box
together with the package leaflet.
The applicator is for single use only.
7 - 10

7
Zinc Approval Number
WOMN-1025058-0064
May 2013
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
19
20
Select Clinical Trials

The following section summarizes 4 additional clinical
trials that were not referred to in Part 1: investigating
the bioequivalence and x-ray visibility of radiopaque
(IMPLANON NXT) and non-radiopaque (IMPLANON)
etonogestrel implants (Schnabel et al, 2012)1; the tolerability
and clinical safety of IMPLANON (Blumenthal et al, 2008)2;
the impact of IMPLANON on menstrual bleeding

patterns (Mansour et al, 2008)3 and physician satisfaction;
characteristics of a new applicator to insert
IMPLANON NXT; and the x-ray visibility of IMPLANON NXT
(Mansour et al, 2010).4
Bioequivalence of IMPLANON NXT and IMPLANON1
Bioequivalence and x-ray visibility of a radiopaque etonogestrel implant versus a non-radiopaque implant: a 3-year,
randomized, double-blind study.
Schnabel P et al. Clin Drug Investig. 2012;32(6):413422.
Objective: To determine whether IMPLANON NXT is bioequivalent in situ to IMPLANON, as well as to assess the x-ray
visibility of IMPLANON NXT.
Design and Methods: IMPLANON NXT and IMPLANON were evaluated in a 3-year, randomized, double-blind,
parallel-group study (N=108). Serum etonogestrel concentrations were measured throughout the study and
bioequivalence determined based on peak concentration (Cmax) and area under the concentration-time curve at
6, 24, or 36 months (AUC6 mo, AUC24 mo, and AUC36 mo). Efficacy was measured by the occurrence of pregnancy,
and safety by the occurrence of adverse events (AEs).
Results: A total of 32 women receiving either IMPLANON or IMPLANON NXT implants completed the 3-year study
(Table 1).
Table 1. Study Population1
IMPLANON
IMPLANON NXT
All treated subjects
56
52
Subjects completing trial
32
32
Subjects who discontinued:
24
20
Due to AE/serious AE
17
15
Due to pregnancy
For other reason
Serum etonogestrel concentrations measured throughout the trial were similar for both IMPLANON and IMPLANON NXT
groups (Figure 1). Key pharmacokinetic parameters, Cmax and AUC6 mo, AUC24 mo, and AUC36 mo, were also similar between
the 2 groups, with 90% confidence intervals (CIs) for the ratios of the geometric means of these parameters for IMPLANON
and IMPLANON NXT being within the predetermined range for bioequivalence (ie, 0.801.25) (Table 2). Thus, the implants
are considered bioequivalent to each other.
21
Serum Etonogestrel, pg/mL
Figure 1. Serum Etonogestrel Concentrations Recorded in Subjects With IMPLANON (Non-radiopaque) or IMPLANON NXT
(Radiopaque) Etonogestrel Implants1
1,100
1,000
900
IMPLANON (n=53)
IMPLANON NXT (n=50)
800
700
600
500
400
300
200
100
0
0
12
15
18
21
24
27
30
33
36
Months After Insertion
Table 2. Results for Pharmacokinetic Parameters Evaluated to Determine the Bioequivalence of IMPLANON NXT
and IMPLANON1
IMPLANON NXT
geometric mean
IMPLANON
geometric mean
Point Estimate Ratio

of IMPLANON NXT/
IMPLANON
Cmax (pg/mL)
1,083
(n=50)
1,021
(n=53)
1.06
(95% CI: 0.891.27)
AUC6 mo (pgmonth/mL)
2,212
(n=46)
2,210
(n=46)
1.00
(95% CI: 0.891.12)
5,783
(n=37)
5,874
(n=32)
0.98
(95% CI: 0.871.12)
7,453
(n=32)
7,487
(n=30)
1.00
(95% CI: 0.871.14)
Implants in subjects receiving IMPLANON were not visible with x-ray imaging either after insertion or before removal.
In contrast, IMPLANON NXT was visible in 50 of 52 women (96.2%) after insertion and in all women before removal.
In the 2 cases in which the implant was not visible after insertion, the x-ray imaging was determined to have been
performed incorrectly
None of the women became pregnant after insertion or before removal of either IMPLANON or IMPLANON NXT.
One woman in each group became pregnant within one month after implant removal, and both women discontinued
contraception treatment due to their wish to become pregnant.
22

The incidence of drug-related adverse events (AEs) was similar between the 2 treatment groups (Table 3). Virtually all
(106 of 108) women receiving an implant reported at least 1 AE during the study. The most common drug-related AEs in
either implant group were genital haemorrhage, vaginal haemorrhage, and implant site haematoma (Table 3).
Table 3. Drug-related AEsa Occurring in 5% of Women in Either Treatment Group1

Non-radiopaque ENG implant
(n=56)
Radiopaque ENG implant (n=52)
Total
49 (88%)
47 (90%)
Acne
15 (26.8)
11 (21.2)
Amenorrhoea
5 (8.9)
3 (5.8)
Breast tenderness
1 (1.8)
4 (7.7)
Breast pain
4 (7.1)
2 (3.8)
Dysmenorrhoea
4 (7.1)
5 (9.6)
Genital haemorrhage
23 (41.1)
24 (46.2)
Headache
7 (12.5)
7 (13.5)
Implant site haematoma
16 (28.6)
16 (30.8)
Implant site pain
6 (10.7)
1 (1.9)
Metrorrhagia
8 (14.3)
9 (17.3)
Nausea
3 (5.4)
3 (5.8)
Oligomenorrhoea
3 (5.4)
0 (0.0)
Pelvic pain
4 (7.1)
2 (3.8)
Polymenorrhoea
0 (0.0)
3 (5.8)
Vaginal discharge
1 (1.8)
3 (5.8)
18 (32.1)
21 (40.4)
Vulvovaginal candidiasis
1 (1.8)
3 (5.8)
Weight gain
5 (8.9)
4 (7.7)
Drug-related AEs
Viginal haemorrhage
based on the Medical Directory for Regulatory Activities version 11.1.

AEs=adverse events; ENG=etonogestrel.
a
23
1 - 2

In vitro release rates of etonogestrel from the IMPLANON and IMPLANON NXT implants, as measured throughout the
study, were essentially the same (Figure 2).
Figure 2. In Vitro Release Rate of Etonogestrel Over 3 Years for IMPLANON and IMPLANON NXT (Adapted from
Schnabel et al.)1
160
In vitro release of ENG,

g/day
140
IMPLANON
IMPLANON NXT
120
100
80
60
40
20
0
0
180
360
540
720
900
1080
1260
Days
Conclusion: IMPLANON NXT is bioequivalent and exhibits similar total etonogestrel exposure and peak etonogestrel
concentration as IMPLANON and is clearly visible with x-ray imaging. The efficacy and safety profiles of the 2
implants in this study were comparable.
Tolerability and Clinical Safety of IMPLANON2
Tolerability and clinical safety of IMPLANON.

Blumenthal PD et al. Eur J Contracept Reprod Health Care. 2008;13(suppl 1):2936.
Objective: To assess the tolerability and clinical safety profile of IMPLANON.
Design and Methods: Safety data for IMPLANON from 11 international clinical trials, including 10 completed phase
2 and phase 3 studies and one completed phase 4 study, were analyzed in 942 healthy, sexually active women of
childbearing potential, 18 to 40 years of age with normal menstrual cycles (24 to 35 days). All placements of
IMPLANON were conducted by trained physicians during an office visit between the first and fifth day of menstrual
flow or 8 weeks after delivery in postpartum women. Assessments included (1) AEs, defined as any new complaint/
symptom arising during treatment or any baseline complaint/symptom worsened in severity or frequency, (2) reasons
for and rates of discontinuation, (3) insertion/removal complications, and (4) the condition of the implant site.
Results: Women were exposed to IMPLANON over a total of 24,679 cycles over the course of 1 to 5 years, of which
11,066 were in the first year.
24

Headache was the most commonly reported AE, affecting nearly a quarter of women, although it was judged by the
investigators to be drug-related in only 15.3% of women (Table 4). The most common drug-related AEs included
weight gain, acne, breast pain, emotional lability, and abdominal pain (Table 4). Fifty-six patients (of 942) reported a
total of 77 serious AEs, the most common being gastrointestinal system disorders, which affected 10 patients (1.1%).
Ten serious AEs were considered by the investigator to be possibly, probably, or definitely drug-related.
Table 4. All AEs and AEs Related to Study Drug2
All studies (N=942)
WHO preferred term
All AEs n (%)
Related AEs n (%)
Headache
233 (24.7)
144 (15.3)
Vaginitis
136 (14.4)
13 (1.4)
Weight increases
126 (13.4)
111 (11.8)
Acne
123 (13.1)
107 (11.4)
Breast pain
121 (12.8)
96 (10.2)
Upper respiratory
Tract infection
119 (12.6)
0 (0)
Abdominal pain
103 (10.9)
49 (5.2)
Pharyngitis
99 (10.5)
6 (0.6)
Leukorrhoea
90 (9.6)
10 (1.1)
Influenza-like symptoms
72 (7.6)
18 (1.9)
Dizziness
68 (7.2)
46 (4.9)
Dysmenorrhoea
68 (7.2)
41 (4.4)
Back pain
64 (6.8)
10 (1.1)
Emotional lability
60 (6.4)
54 (5.7)
Nausea
58 (6.2)
24 (2.5)
Pain
53 (5.6)
17 (1.8)
Sinusitis
53 (5.6)
0 (0)
Nervousness
53 (5.6)
33 (3.5)
Depression
52 (5.5)
33 (3.5)
Injection site pain
49 (5.2)
43 (4.6)
AEs=adverse events; WHO=World Health Organization.
25
2 - 3

A total of 308 participants (32.7%) discontinued use of IMPLANON prior to completing their respective trial, including 23
women who were lost to follow-up before IMPLANON removal (Table 5). Adverse events and bleeding irregularities were
the most common reasons for discontinuations (Table 5).
Table 5. Discontinuation Rate by Reason2
Primary reason for discontinuation
Implanon (N=942) n (%)
Adverse events
131 (13.9)
Bleeding irregularities
98 (10.4)
Planning pregnancy
39 (4.1)
Other reasons
33 (3.5)
Lost to follow-up
23 (2.4)
Amenorrhoea
7 (0.7)
The rate of complications was low during both insertion (1.0%) and removal (1.7%), and insertion site pain at any time was
reported in 3% of patients.
Conclusion: Multinational, clinical safety data integrated from 11 clinical trials demonstrated that treatment with IMPLANON
over a total of 24,679 cycles of exposure was well-tolerated.
Impact of IMPLANON on Bleeding Patterns3
The effects of IMPLANON on menstrual bleeding patterns.

Mansour D et al. Eur J Contracept Reprod Health Care. 2008;13(suppl 1):1328.
Objective: To analyze bleeding patterns associated with use of IMPLANON in 11 clinical trials conducted worldwide and to
provide recommendations to physicians for optimized patient counseling.
Design and Methods: Bleeding patterns over 3 years from 11 clinical trials (N=923) with IMPLANON were analyzed using
bleeding-spotting (B-S) records, changes in dysmenorrhoea from baseline, and discontinuation rates due to irregular
bleeding. Reference period (RP) analysis was used to segment the bleeding information into 12 90-day periods. Bleeding
patterns were classified as follows:
Bleeding day (requiring > 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

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 (<3 bleeding-spotting [B-S] episodes during an RP, excluding amenorrhea)
Normal frequency (35 B-S episodes during an RP)
Frequent 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 29118 after IMPLANON implantation (reference period RP 1.1), more subjects reported 014 B-S
days than 1528, 2949, 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 29118)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

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
3 - 4

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.
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):243249.
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, %
20
40
60 80 100
Responses After
8 Insertions, %
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.
29

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
300
Inexperienced
users (12)
150
36.6 (36.1)
25.0
300
Experienced
users (11)
141
18.7 (15.1)
15
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

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

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:
Manufacturer: Implanon NXT is produced by
33
1 - 2

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
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.

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

womans 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

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. Johns 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. Johns wort while you are already using Implanon NXT
you should consult your doctor first.

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

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.

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
5 - 6

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
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 30C.
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.
6.1

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
6.1 - 6.2
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
6.2
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.
43
7 - 7.1

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 womans 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.

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.

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.

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.
44

7.1 - 7.2

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
How to insert Implanon NXT

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
womans 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).
45
7.2
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
46
7.2
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 womans

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.
47
7.2 - 7.3

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 womans
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
48
7.3
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
49
7.3 - 7.4
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.
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.
50
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.
51
Before prescribing IMPLANON NXT,

please read the Prescribing Information.
Copyright 2012 MSD Oss B.V., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.
WOMN-1025058-0064
Merck Sharp and Dohme (I.A.) Corporation

a Philippine subsidiary of Merck & Co., Inc.
26/F Philamlife Tower,
8767 Paseo de Roxas, Makati City
Trunk Line : (632)784-9500
Fax number: (632) 8850773
www.msd.com.ph

Final Implanon Product Monograph

Caricato da

Informazioni sul documento

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

Final Implanon Product Monograph

Caricato da

Copyright:

Formati disponibili

Product Monograph

Implanon NXT: Product Monograph

Summary Product Information 1 2 3 2

Part II: Select Clinical Trials

Tolerability and Clinical Safety

Management of Bleeding Patterns

Part III: Consumer Information

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

Summary Product Information

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

Posology and method of administration

Pregnancy should be excluded before insertion of

Additional information and more detailed instructions

How to use Implanon NXT

Implanon NXT is a long-acting hormonal contraceptive.

The Implanon NXT implant should be inserted

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

When to insert Implanon NXT

IMPORTANT: Rule out pregnancy before inserting

Timing of insertion depends on the womans recent

No preceding hormonal contraceptive use in the past month

If inserted as recommended, back-up contraception is not

Switching contraceptive method to Implanon NXT

If inserted as recommended, back-up contraception is not

 rogestagen-only pill: A woman may switch from the

Implant/Intrauterine system (IUS): Insert the implant on the

If inserted as recommended, back-up contraception is not

Following abortion or miscarriage

 irst trimester: The implant should be inserted within 5

 econd trimester: Insert the implant between 21 to 28

If inserted as recommended, back-up contraception is not

 reast-feeding: The implant should be inserted after the

Not breast-feeding: The implant should be inserted

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

How to insert Implanon NXT

The basis for successful use and subsequent removal

with intravascular insertion. Moreover, when the implant

Have the woman lie on her back on the examination table

Clean the insertion site with an antiseptic solution.

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

Puncture the skin with the tip of the needle angled

Lower the applicator to a horizontal position. While lifting the

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

Always verify the presence of the implant in the womans

If you cannot feel the implant or are in doubt of its presence,

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

How to remove Implanon NXT

Before initiating the removal procedure, the HCP should

After localization of a non-palpable implant, consider

If the implant cannot be removed, please contact your local

Anesthetize the arm, for example, with 0.5 to 1 ml 1% lidocaine

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

Implanon NXT: Product Monograph

Part I: Health Care Professional Information

How to replace Implanon NXT

Immediate replacement can be done after removal

rogestagen-only pill: A woman may switch from the

Implant/Intrauterine system (IUS): Insert the implant on the

irst trimester: The implant should be inserted within 5

econd trimester: Insert the implant between 21 to 28

reast-feeding: The implant should be inserted after the

Not breast-feeding: The implant should be inserted

Have the woman lie on her back on the examination table

Clean the insertion site with an antiseptic solution.

Puncture the skin with the tip of the needle angled

Lower the applicator to a horizontal position. While lifting the

Always verify the presence of the implant in the womans

Anesthetize the arm, for example, with 0.5 to 1 ml 1% lidocaine

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

Hypersensitivity to the active substance or to any of the

Presence or history of severe hepatic disease as long as

Known or suspected sex steroid sensitive malignancies.

If a sustained hypertension develops during the

The following conditions have been reported both during

Interaction with other medicinal products and other forms of

Influence of other medicinal products on

Pregnancy and lactation

Effects on ability to drive and use machines