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GEDAREL 20/150 MICROGRAM FILM-COATED TABLETS

Active substance(s): DESOGESTREL / ETHINYLESTRADIOL / DESOGESTREL / ETHINYLESTRADIOL / DESOGESTREL / ETHINYLESTRADIOL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Gedarel 20/150 microgram film-coated tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 20 micrograms ethinylestradiol and 150 micrograms
desogestrel
Excipient with known effect: 64.3 mg lactose (as lactose monohydrate).
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Film-coated tablet
Slightly yellow, round shaped, biconvex film-coated tablets of about 6 mm diameter,
with P9 sign on one side and RG sign on other side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Oral contraception
The decision to prescribe Gedarel should take into consideration the individual
woman’s current risk factors, particularly those for venous thromboembolism
(VTE), and how the risk of VTE with Gedarel compares with other combined
hormonal contraceptives (CHCs) (see sections 4.3 and 4.4).

4.2

Posology and method of administration
Posology
How to take Gedarel
Tablets must be taken in the order directed on the package every day at about the
same time. One tablet is taken daily for 21 consecutive days. Each subsequent pack is
started after a 7-day tablet-free interval; during which time a withdrawal bleed usually

occurs. This usually starts on day 2-3 day after the last tablet and may not have
finished, before the next pack is started.
How to start Gedarel
No preceding hormonal contraceptive use [in the past month]
The tablet intake must be started on day 1 of the normal menstrual cycle (i.e. on the
first day on which the woman has a menstrual bleeding). Tablet intake is also allowed
to start on day 2-5, but during the first cycle concurrent use of a barrier method for
the first 7 days of tablet intake is advisable.
Changing from a combined hormonal contraceptive (combined oral contraceptive
(COC), combined contraceptive vaginal ring or transdermal patch)
The woman should start taking Gedarel on the day after the last active tablet (the last
tablet containing the active substance) of her previous COC, but at the latest on the
day following the usual tablet-free interval or following the last placebo tablet of her
previous COC.
In case a vaginal ring or a transdermal patch has been used, the woman should start
using Gedarel preferably on the day of removal.
The woman may also start using Gedarel on the day the new vaginal ring or a
transdermal patch would have been due, but no later that this day.
If the woman has been using her previous method consistently and correctly and if it
is reasonably certain that she is not pregnant she may also switch from her previous
hormonal contraception on any day of the cycle.
The hormone -free period from the previous contraception method must not be
extended for longer than recommended.
Not all administration methods of hormonal contraception (transdermal patch, vaginal
ring) is necessarily marketed in all EU countries.
Changing from progestogen only products (progestogen-only-pills, injection, implant
or a progestogen-releasing intrauterine system (IUS))
The woman can change from progestogen-only pills on any day (changing from
implant or IUS on the day of its removal; changing from injection when the next
injection should have been given) but should in all of these cases be advised to
additionally use a barrier method for the first 7 days of tablet-taking.
After abortion in the 1st trimester
Tablet intake should start immediately. In this case no further contraceptive measures
are necessary.
After delivery or abortion in the 2nd trimester
For breast-feeding women - see section 4.6.
The woman should be advised to start the pill on day 21-28 after delivery or abortion
in the 2nd trimester. She should be advised to use a barrier method concurrently
during the first 7 days of tablet intake if she starts the pill later. In case she has
already had intercourse, pregnancy should be excluded before she starts taking
Gedarel, or she should wait for her first menstrual bleeding.
Forgotten tablets
If the tablet intake is forgotten for less than 12 hours, contraceptive protection is not
reduced. The woman should take the forgotten tablet as soon as she remembers, and
the remaining tablets are taken as usual.

If the tablet intake is forgotten for more than 12 hours, contraceptive protection may
be reduced. The following two basic rules should be considered in case of forgotten
tablets:
1.
Continuous tablet intake must not be interrupted for longer than a period of 7
days.
2.
7 days of uninterrupted tablet intake are required to achieve sufficient
suppression of the hypothalamus-pituitary-ovarian-axis.
Thus, the following advice may be given for daily practice:
Week 1
The woman should take the last forgotten tablet as soon as she remembers, even if
this means that she has to take 2 tablets at the same time. Then, she continues taking
the tablets at the usual time of the day. She should concurrently use a barrier method,
e.g. a condom, for the next 7 days. If intercourse has taken place during the preceding
7 days, the possibility of pregnancy should be considered. The more tablets are
forgotten and the closer they are to the regular tablet-free period, the higher the risk of
pregnancy is.
Week 2
The woman should take the last forgotten tablet as soon as she remembers, even if
this means that she has to take 2 tablets at the same time. Then, she continues taking
the tablets at the usual time of the day. Provided that the tablets have been taken in a
correct manner during the 7 days preceding the forgotten tablet, it is not necessary to
take further contraceptive measures. However, if this is not the case, or if more than 1
tablet has been forgotten, the woman should be advised to use another contraceptive
method for 7 days.
Week 3
The risk of reduced contraceptive protection is imminent due to the next tablet-free
period. However, this risk may be prevented by adjusting tablet intake. Thus, it is not
necessary to take further contraceptive measures if one of the two alternatives below
is followed, provided that all tablets have been taken in a correct manner during the 7
days preceding the forgotten tablet. If this is not the case, the woman should be
advised to follow the first of the two alternatives and concurrently use another
contraceptive method for the next 7 days.
1.

2.

The user should take the last forgotten tablet as soon as she remembers even if
it means that she has to take 2 tablets at the same time. Then she continues
taking the tablets at the usual time of the day. She will begin taking the next
pack immediately after taking the last tablet in the present pack, i.e. there is no
break between the packs. It is not very likely that the user will have her
menstrual bleeding until the end of the second pack, but she may experience
spotting or break-through bleeding on the days she is taking tablets.
The woman may also be advised to stop taking tablets from the present pack. In
that case she should keep a tablet-free period of up to 7 days, including those
days when she forgot tablets, and then continue with the next pack.

In case the woman has forgotten tablets and then does not have her menstrual
bleeding in the first normal tablet-free period, the possibility of pregnancy should be
considered
Advice in case of gastrointestinal disturbances

In case of severe gastro-intestinal disturbances, absorption may not be complete and
additional contraceptive measures should be taken.
If vomiting occurs within 3-4 hours after taking the active tablets, the advice
concerning missed tablets, as given below, is applicable. If the woman does not want
to change her normal tablet-taking schedule, she has to take the extra tablet(s) needed
from another pack.
How to induce or postpone a withdrawal bleed
There is no indication for this product to postpone menstruation. However, in
extraordinary cases, if postponing menstruation is required the woman should
continue with another blister pack of Gedarel without a tablet-free interval. The
extension can be carried on for as long as wished until the end of the second pack.
During the extension the woman may experience breakthrough-bleeding or spotting.
Regular intake of Gedarel is then resumed after the usual 7-day tablet-free interval.
To shift her periods to another day of the week than the woman is used to with her
current scheme, she can be advised to shorten her forthcoming tablet-free interval by
as many days as she likes. The shorter the interval, the higher the risk that she does
not have a withdrawal bleed and will experience breakthrough-bleeding and spotting
during the subsequent pack (just as when delaying a period).
Paediatric population
The safety and efficacy of desogestrel in adolescents below 18 years has not yet been
established. No data are available.
Method of administration
For oral administration.

4.3

Contraindications

-

-

Combined hormonal contraceptives (CHCs) should not be used in the following
conditions.
Should any of the condition appear for the first time while taking oral contraceptives,
the use of oral contraceptives should be stopped immediately.
Presence or risk of venous thromboembolism (VTE)
- Venous thromboembolism – current VTE (on anticoagulants) or history of
(e.g. deep venous thrombosis [DVT] or pulmonary embolism [PE]).
- Known hereditary or acquired predisposition for venous thromboembolism,
such as APC-resistance, (including Factor V Leiden), antithrombin-IIIdeficiency, protein C deficiency, protein S deficiency.
- Major surgery with prolonged immobilisation (see section 4.4).
- A high risk of venous thromboembolism due to the presence of multiple risk
factors (see section 4.4).
Presence or risk of arterial thromboembolism (ATE)
- Arterial thromboembolism – current arterial thromboembolism, history of
arterial thromboembolism (e.g. myocardial infarction) or prodromal condition
(e.g. angina pectoris).
- Cerebrovascular disease – current stroke, history of stroke or prodromal
condition (e.g. transient ischaemic attack, TIA).
- Known hereditary or acquired predisposition for arterial thromboembolism,
such as hyperhomocysteinaemia and antiphospholipid-antibodies
(anticardiolipin-antibodies, lupus anticoagulant).
- History of migraine with focal neurological symptoms.

-

-

4.4

A high risk of arterial thromboembolism due to multiple risk factors (see
section 4.4) or to the presence of one serious risk factor such as:
- diabetes mellitus with vascular symptoms
- severe hypertension
- severe dyslipoproteinaemia.
Presence or history of severe hepatic disease as long as liver function values have not
returned to normal.
Presence or history of liver tumours (benign or malignant).
Known or suspected sex steroid-influenced malignancies (e.g. of the genital organs or
the breasts).
Endometrial hyperplasia.
Undiagnosed vaginal bleeding.
Known or suspected pregnancy.
Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
Hypersensitivity to the active substances or to any of the excipients listed in section
6.1.

Special warnings and precautions for use
Warnings
If any of the conditions or risk factors mentioned below is present, the suitability of
Gedarel should be discussed with the woman.
In the event of aggravation, or first appearance of any of these conditions or risk
factors, the woman should be advised to contact her doctor to determine whether the
use of Gedarel should be discontinued.
Circulatory disorders
Risk of venous thromboembolism (VTE)
The use of any combined hormonal contraceptive (CHC) increases the risk of venous
thromboembolism (VTE) compared with no use. Products that contain
levonorgestrel, norgestimate or norethisterone are associated with the lowest
risk of VTE. Other products such as Gedarel may have up to twice this level of
risk. The decision to use any product other than one with the lowest VTE risk
should be taken only after a discussion with the woman to ensure she
understands the risk of VTE with Gedarel, how her current risk factors
influence this risk, and that her VTE risk is highest in the first ever year of use.
There is also some evidence that the risk is increased when a CHC is re-started
after a break in use of 4 weeks or more.
In women who do not use a CHC and are not pregnant about 2 out of 10,000 will
develop a VTE over the period of one year. However, in any individual woman the
risk may be far higher, depending on her underlying risk factors (see below).
It is estimated1 that out of 10,000 women who use a CHC containing desogestrel
between 9 and 12 women will develop a VTE in one year; this compares with about
62 in women who use a levonorgestrel-containing CHC.

1

These incidences were estimated from the totality of the epidemiological study data, using relative
risks for the different products compared with levonorgestrel-containing CHCs. 2 Mid-point of range of
5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel versus non-use of
approximately 2.3 to 3.6.

In both cases, the number of VTEs per year is fewer than the number expected during
pregnancy or in the postpartum period.
VTE may be fatal in 1-2% of cases.
Number of VTE events per 10,000 women in one year
Number of
VTE
14 events

12

10

8

6

4

2

0

Non-CHCuser (2 events)

Levonorgestrel-containing CHC(5-7
event s)

Desogest rel-containing CHC(9-12
events)

Extremely rarely, thrombosis has been reported to occur in CHC users in other blood
vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries.
Risk factors for VTE
The risk for venous thromboembolic complications in CHC users may increase
substantially in a woman with additional risk factors, particularly if there are multiple
risk factors (see table).
Gedarel is contraindicated if a woman has multiple risk factors that put her at high
risk of venous thrombosis (see section 4.3). If a woman has more than one risk factor,
it is possible that the increase in risk is greater than the sum of the individual factors –
in this case her total risk of VTE should be considered. If the balance of benefits and
risks is considered to be negative a CHC should not be prescribed (see section 4.3).
Table: Risk factors for VTE
Risk factor
Obesity (body mass index over 30
kg/m²).
Prolonged immobilisation, major
surgery, any surgery to the legs or
pelvis, neurosurgery, or major
trauma.

Note: temporary immobilisation
including air travel >4 hours can also
be a risk factor for VTE, particularly
in women with other risk factors.
Positive family history (venous
thromboembolism ever in a sibling or
parent especially at a relatively early

Comment
Risk increases substantially as BMI rises.
Particularly important to consider if other risk factors
also present.
In these situations it is advisable to discontinue use
of the patch/pill/ring (in the case of elective surgery
at least four weeks in advance) and not resume until
two weeks after complete remobilisation. Another
method of contraception should be used to avoid
unintentional pregnancy.
Antithrombotic treatment should be considered if
Gedarel has not been discontinued in advance.

If a hereditary predisposition is suspected, the
woman should be referred to a specialist for advice
before deciding about any CHC use.

age e.g. before 50).
Other medical conditions associated
with VTE.

Increasing age.

Cancer, systemic lupus erythematosus, haemolytic
uraemic syndrome, chronic inflammatory bowel
disease (Crohn’s disease or ulcerative colitis) and
sickle cell disease.
Particularly above 35 years.

There is no consensus about the possible role of varicose veins and superficial
thrombophlebitis in the onset or progression of venous thrombosis.
The increased risk of thromboembolism in pregnancy, and particularly the 6 week
period of the puerperium, must be considered (for information on “Fertility,
pregnancy and lactation” see section 4.6).
Symptoms of VTE (deep vein thrombosis and pulmonary embolism)
In the event of symptoms women should be advised to seek urgent medical attention
and to inform the healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include:
- unilateral swelling of the leg and/or foot or along a vein in the leg;
- pain or tenderness in the leg which may be felt only when standing or walking;
- increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include:
- sudden onset of unexplained shortness of breath or rapid breathing;
- sudden coughing which may be associated with haemoptysis;
- sharp chest pain;
- severe light headedness or dizziness;
- rapid or irregular heartbeat.
Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific
and might be misinterpreted as more common or less severe events (e.g. respiratory
tract infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue
discoloration of an extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of
vision which can progress to loss of vision. Sometimes loss of vision can occur
almost immediately.
Risk of arterial thromboembolism (ATE)
Epidemiological studies have associated the use of CHCs with an increased risk for
arterial thromboembolism (myocardial infarction) or for cerebrovascular accident
(e.g. transient ischaemic attack, stroke). Arterial thromboembolic events may be fatal.
Risk factors for ATE
The risk of arterial thromboembolic complications or of a cerebrovascular accident in
CHC users increases in women with risk factors (see table). Gedarel is
contraindicated if a woman has one serious or multiple risk factors for ATE that puts
her at high risk of arterial thrombosis (see section 4.3). If a woman has more than one
risk factor, it is possible that the increase in risk is greater than the sum of the
individual factors - in this case her total risk should be considered. If the balance of
benefits and risks is considered to be negative a CHC should not be prescribed (see
section 4.3).
Table: Risk factors for ATE

Risk factor
Increasing age.
Smoking.

Hypertension.
Obesity (body mass index over 30
kg/m2).
Positive family history (arterial
thromboembolism ever in a sibling or
parent especially at relatively early
age e.g. below 50).
Migraine.

Other medical conditions associated
with adverse vascular events.

Comment
Particularly above 35 years.
Women should be advised not to smoke if they wish
to use a CHC. Women over 35 who continue to
smoke should be strongly advised to use a different
method of contraception.
Risk increases substantially as BMI increases.
Particularly important in women with additional risk.
factors.
If a hereditary predisposition is suspected, the woman
should be referred to a specialist for advice before
deciding about any CHC use.
An increase in frequency or severity of migraine
during CHC use (which may be prodromal of a
cerebrovascular event) may be a reason for
immediate discontinuation.
Diabetes mellitus, hyperhomocysteinaemia, valvular
heart disease and atrial fibrillation,
dyslipoproteinaemia and systemic lupus
erythematosus.

Symptoms of ATE
In the event of symptoms women should be advised to seek urgent medical attention
and to inform the healthcare professional that she is taking a CHC.
Symptoms of a cerebrovascular accident can include:
- sudden numbness or weakness of the face, arm or leg, especially on one side of
the body;
- sudden trouble walking, dizziness, loss of balance or coordination;
- sudden confusion, trouble speaking or understanding;
- sudden trouble seeing in one or both eyes;
- sudden, severe or prolonged headache with no known cause;
- loss of consciousness or fainting with or without seizure.
Temporary symptoms suggest the event is a transient ischaemic attack (TIA).
Symptoms of myocardial infarction (MI) can include:
- pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the
chest, arm, or below the breastbone;
- discomfort radiating to the back, jaw, throat, arm, stomach;
- feeling of being full, having indigestion or choking;
- sweating, nausea, vomiting or dizziness;
- extreme weakness, anxiety, or shortness of breath;
- rapid or irregular heartbeats.
Tumours
Epidemiological studies indicate that the long-term use of oral contraceptives displays
an additional risk factor for the development of cervical cancer in women infected
with human papillomavirus (HPV). However, there is still uncertainty about the
extent to which this finding may be influenced by confounding effects (e.g.
differences in number of sexual partners or in use of barrier contraceptives).

A meta-analysis from 54 epidemiological studies reported that there is a slightly
increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who
are currently using combined oral contraceptives (COCs). The increased risk
gradually declines for 10 years after cessation of COC use. Since breast cancer is a
rare condition in women below 40 years of age, the increase in the number of
diagnosed cases of breast cancer in present and former users of COCs is low
compared to the risk of breast cancer in their entire lifetime. These studies do not put
forward evidence of a causal relationship. The observed pattern of an increased risk
may be due to an earlier diagnosing of breast cancer in users of COCs, the biological
effects of COCs or a combination of both. The diagnosed cases of breast cancer in
users of COCs have a tendency to be less clinically advanced compared to the
diagnosed cases of breast cancer in never-users.
In rare cases, benign liver tumours, and even more rarely, malignant liver tumours
have been reported in users of CHCs. In isolated cases, these tumours have led to lifethreatening intra-abdominal haemorrhages. A hepatic tumour should be considered in
the differential diagnosis when severe upper abdominal pain, liver enlargement or
signs of intra-abdominal haemorrhage occur in women taking CHCs.
Other conditions
Women with hypertriglyceridaemia or a family history thereof, may be at an
increased risk of pancreatitis when taking CHCs.
Although small increases in blood pressure have been reported in many women
taking CHCs, clinically relevant increases are rare. A systemic relationship between
CHC use and clinical hypertension has not been established. However, if a sustained
clinically significant hypertension develops during the use of a CHC then it is prudent
for the physician to withdraw the CHC and treat the hypertension. Where considered
appropriate, CHC use may be resumed if normotensive values can be achieved with
antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both
pregnancy and COC use, but the evidence of a relationship with CHC use is
inconclusive: Jaundice and/or itching in connection with cholestasis; gallstone
formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome;
Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss; (hereditary)
angioedema.
Acute or chronic disturbances of liver function may necessitate discontinuation of
COC use until liver function parameters have been normalised. Recurrence of
cholestatic jaundice which occurred first during pregnancy or previous use of sex
steroids necessitates the discontinuation of COCs.
Although CHCs may have an effect on peripheral insulin resistance and glucose
tolerance, there is no evidence for a need to alter the therapeutic regimen in well
controlled diabetics using CHCs. However, diabetic women should be carefully
observed while taking CHCs.
Crohn’s disease and ulcerative colitis have been reported during CHC use.
Chloasma may occasionally occur, especially in women with a history of chloasma
gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or
ultraviolet radiation whilst taking CHCs.

This medicinal product contains <65 mg lactose. Patients with rare hereditary
problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose
malabsorption should not take this medicine.
When counselling the choice of contraceptive method(s), all the above information
should be taken into account.
Medical examination/consultation
Prior to the initiation or reinstitution of Gedarel a complete medical history (including
family history) should be taken and pregnancy must be ruled out. Blood pressure
should be measured and a physical examination should be performed, guided by the
contra-indications (see section 4.3) and warnings (see section 4.4). It is important to
draw a woman’s attention to the information on venous and arterial thrombosis,
including the risk of Gedarel compared with other CHCs, the symptoms of VTE and
ATE, the known risk factors and what to do in the event of a suspected thrombosis.
The woman should also be instructed to carefully read the user leaflet and to adhere
to the advice given. The frequency and nature of examinations should be based on
established practice guidelines and be adapted to the individual woman.
Women should be advised that hormonal contraceptives do not protect against HIV
infections (AIDS) and other sexually transmitted diseases.
Reduced efficacy
The efficacy of Gedarel may be reduced in the event of e.g., missed tablets (section
4.2), gastro-intestinal disturbances (section 4.2) or concomitant medication (section
4.5).
Herbal preparations containing St. John's wort (Hypericum perforatum) should not be
used while taking Gedarel due to the risk of decreased plasma concentrations and
reduced clinical effects of Gedarel (see section 4.5).
Reduced cycle control
With all CHCs, irregular bleeding (spotting or breakthrough bleeding) may occur,
especially during the first months of use. Therefore, the evaluation of any irregular
bleeding is only meaningful after an adaptation interval of about three cycles.
If bleeding irregularities persist or occur after previously regular cycles, then nonhormonal causes should be considered and adequate, diagnostic measures are
indicated to exclude malignancy or pregnancy. These may include curettage.
In some women withdrawal bleeding may not occur during the tablet-free interval. If
the COC has been taken according to the directions described in section 4.2, it is
unlikely that the woman is pregnant. However, if the CHC has not been taken
according to these directions prior to the first missed withdrawal bleed or if two
withdrawal bleeds are missed, pregnancy must be ruled out before CHC use is
continued.

4.5

Interaction with other medicinal products and other forms of interaction
Note: The prescribing information of concomitant medications should be consulted to
identify potential interactions.
Effects of other medicinal products on Gedarel

Interactions can occur with drugs that induce microsomal enzymes which can result
in increased clearance of sex hormones and which may lead to breakthrough bleeding
and/or oral contraceptive failure.
Management
Enzyme induction can already be observed after a few days of treatment. Maximal
enzyme induction is generally seen within a few weeks. After the cessation of drug
therapy enzyme induction may be sustained for about 4 weeks.
Short-term treatment
Women on treatment with enzyme inducing drugs should temporarily use a barrier
method or another method of contraception in addition to the COC. The barrier
method must be used during the whole time of the concomitant drug therapy and for
28 days after its discontinuation.
If the drug therapy runs beyond the end of the tablets in the COC pack, the next COC
pack should be started right after the previous one without the usual tablet-free
interval.
Long-term treatment
In women on long-term treatment with enzyme-inducing active substances, another
reliable, non-hormonal, method of contraception is recommended.
The following interactions have been reported in the literature.
Substances increasing the clearance of COCs (diminished efficacy of COCs by
enzyme-induction), e.g.:
Barbiturates, bosentan, carbamazepine, phenytoin, primidone, rifampicin, and HIV
medication ritonavir, nevirapine and efavirenz and possibly also felbamate,
griseofulvin, oxcarbazepine, topiramate and products containing the herbal remedy
St. John's Wort (hypericum perforatum).
Substances with variable effects on the clearance of COCs:
When co-administered with COCs, many combinations of HIV protease inhibitors
and non-nucleoside reverse transcriptase inhibitors, including combinations with
HCV inhibitors can increase or decrease plasma concentrations of estrogen or
progestins. The net effect of these changes may be clinically relevant in some cases.
Therefore, the prescribing information of concomitant HIV/HCV medications should
be consulted to identify potential interactions and any related recommendations. In
case of any doubt, an additional barrier contraceptive method should be used by
women on protease inhibitor or non-nucleoside reverse transcriptase inhibitor
therapy.
Effects of Gedarel on other medicinal products
Oral contraceptives may affect the metabolism of other drugs. Accordingly, plasma
and tissue concentrations may be affected.
Ciclosporin
Oral contraceptives may inhibit the metabolism of ciclosporin in the liver resulting in
increased incidence of adverse events.
Lamotrigine
Combined oral contraceptives have been shown to induce the metabolism of

lamotrigine which may result in subtherapeutic plasma levels of lamotrigine.
Tizanidine
Oral contraceptives may enhance the blood pressure lowering effect of titazinidine
due to inhibition of the metabolism of tizanidine via CYP1A2.
Caution should be exercised when prescribing tizanidine to users of oral
contraceptives due to the narrow therapeutic window of tizanidine.
Levothyroxine
Oestrogen therapy may lead to a reduction of free thyroxine and increase of TSH in
hypothyroid women treated with levothyroxine.
The combination may be used with dose adjustment.
Laboratory tests
The use of contraceptive steroids may influence the results of certain laboratory tests,
including biochemical parameters of liver, thyroid, adrenal and renal function, the
plasma levels of (carrier) proteins, e.g. corticosteroid binding globulin and
lipid/lipoprotein fractions, parameters for carbohydrate metabolism and parameters of
coagulation and fibrinolysis. Changes generally remain within the normal laboratory
range.

4.6

Fertility, pregnancy and lactation
Pregnancy
Gedarel is not indicated in pregnancy.
If pregnancy occurs during treatment with Gedarel, further intake should be stopped.
However, extensive epidemiological studies have neither showed an increased risk of
birth defects in children born to women taking CHCs before pregnancy, nor any
teratogenic effect when CHCs were taken inadvertently during early pregnancy.
The increased risk of VTE during the postpartum period should be considered when
re-starting Gedarel (see sections 4.2 and 4.4).
Breastfeeding
Lactation may be influenced by CHCs as they may reduce the quantity and change
the composition of breast milk. Therefore, the use of CHCs should generally not be
recommended until the nursing mother has completely weaned her child. Small
amounts of the contraceptive steroids and/or their metabolites may be excreted with
the milk, but there is no evidence that this adversely affects infant health.

4.7

Effects on ability to drive and use machines
Gedarel has no influence or negligible influence on the ability to drive and use
machines.

4.8

Undesirable effects

In the first part of the treatment period a large number (10-30%) of women may
expect to get side effects such as breast tenderness, malaise and spot bleedings.
However, these side effects are usually temporary and disappear within 2-4 months.
Description of selected adverse reactions
An increased risk of arterial and venous thrombotic and thromboembolic events,
including myocardial infarction, stroke, transient ischaemic attacks, venous
thrombosis and pulmonary embolism has been observed in women using CHCs,
which are discussed in more detail in section 4.4.
Other side effects have been reported in women using combined hormonal
contraceptives. These are described in section 4.4.
As with all CHCs, changes in vaginal bleeding patterns may occur, especially during
the first months of use. These may include changes in bleeding frequency (absent,
less, more frequent or continuous), intensity (reduced or increased) or duration.
Possibly related undesirable effects that have been reported in users of Gedarel and of
combined hormonal contraceptives in general are listed in the table below3. All ADRs
are listed by system organ class and frequency; very common (≥1/10), common
(≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and rare (≥1/10,000 to
<1/1,000).
Systems Organ
Class
Immune system
disorders
Metabolism and
nutrition disorders
Psychiatric
disorders
Nervous system
disorders
Eye disorders

Very common
>1/10

Common
>1/100 to <1/10

Reproductive
system and breast

Rare
≥1/10,000 to
<1/1,000
Hypersensitivity
reaction

Fluid retention
Depressed mood, Libido decreased
Mood altered
Nervousness
Headache,
Migraine
Dizziness

Libido increased

Contact lens
intolerance
Otosclerosis

Ear and labyrinth
disorders
Vascular disorders

Gastrointestinal
disorders
Skin and
subcutaneous
tissue disorders

Uncommon
>1/1,000 to
<1/100

Hypertension

Nausea,
Abdominal pain
Acne

Irregular bleeding Breast pain,
Breast

Vomiting,
Diarrhoea
Rash,
Urticaria

Breast
enlargement

Venous
thromboembolis
m (VTE),
Arterial
thromboembolis
m (ATE)

Erythema
nodosum,
Erythema
multiforme,
Chloasma
Vaginal secretion
Breast secretion

disorders

tenderness,
Amenorrhea,
Dysmenorrhea,
Premenstrual
syndrome

Weight increased
Weight decreased
General disorders
and
administration site
conditions
3
The most appropriate MedDRA term to describe a certain adverse reaction is listed.
Synonyms or related conditions are not listed, but should be taken into account as well.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
There have been no reports of serious, harmful effects after overdose.
Symptoms
Symptoms that may occur in this case are: nausea, vomiting and, in young girls, slight
vaginal bleeding.
Treatment
There are no antidotes, and further treatment should be symptomatic.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Hormonal contraceptives for systemic use, Progestogens
and estrogens, fixed combinations; ATC code: G03AA09
Mechanism of action
The contraceptive effect of CHCs is based on the interaction of different factors, out
of which the most important is the inhibition of ovulation and the changes in the
cervical secretion. Besides protection against pregnancy, CHCs have several positive
properties which, next to the negative properties (see sections 4.4 and 4.8), can be
useful in deciding on the method of birth control. The cycle is more regular and the
menstruation is often less painful and bleeding is lighter.
The latter may result in a decrease in the occurrence of iron deficiency.
Paediatric population
No clinical data on efficacy and safety are available in adolescents below 18 years.

5.2

Pharmacokinetic properties
Desogestrel
Absorption
Orally administered desogestrel is rapidly and completely absorbed and converted to
etonogestrel. Following ingestion of a single dose, peak serum concentrations of
about 2 ng/mL are reached within 1.5 hours. Bioavailability is 62-81 %.
Distribution
Etonogestrel is bound to serum albumin and to sex hormone binding globulin
(SHBG). Only 2-4 % of the total serum drug concentrations are present as free
steroid, 40-70 % are specifically bound to SHBG. The ethinylestradiol-induced
increase in SHBG influences the distribution of the serum proteins, causing an
increase of the SHBG-bound fraction and a decrease of the albumin-bound fraction.
The apparent volume of distribution of desogestrel is 1.5 l/kg.
Biotransformation
Etonogestrel is completely metabolized by the known pathways of steroid
metabolism. The metabolic clearance rate from serum is about 2 ml/min/kg. No
interaction was found with the co-administered ethinylestradiol.
Elimination
Etonogestrel serum levels decrease in two phases. The terminal disposition phase is
characterized by a half-life of approximately 30 hours. Desogestrel and its
metabolites are excreted at a urinary to biliary ratio of about 6:4.
Steady-state conditions
Etonogestrel pharmacokinetics are influenced by SHBG levels, which are increased
threefold by ethinylestradiol. Following daily ingestion, drug serum levels increase
about two- to threefold, reaching steady state conditions during the second half of a
treatment cycle.
Ethinylestradiol
Absorption
Orally administered ethinylestradiol is rapidly and completely absorbed. Following
ingestion of a single dose, peak serum concentrations of about 45 pg/mL are reached
within 1-2 hours. Absolute bioavailability as a result of presystemic conjugation and
first-pass metabolism is approximately 60%.
Distribution
Ethinylestradiol is highly but non-specifically bound to serum albumin
(approximately 98.5%) and induces an increase in the serum concentrations of
SHBG. An apparent volume of distribution of about 5 l/kg was determined.
Biotransformation
Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa
and the liver. Ethinylestradiol is primarily metabolized by aromatic hydroxylation but
a wide variety of hydroxylated and methylated metabolites are formed, and these are
present as free metabolites and as conjugates with glucuronides and sulfate. The
metabolic clearance rate is about 5 ml/min/kg.

Elimination
Ethinylestradiol serum levels decrease in two phases, the terminal disposition phase is
characterized by a half-life of approximately 24 hours. Unchanged drug is not
excreted, ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6.
The half-life of metabolite excretion is about 1 day.
Steady-state conditions
Steady state concentrations are reached after 3-4 days when serum drug levels are
higher by 30-40% as compared to single dose.

5.3

Preclinical safety data
Preclinical studies on ethinylestradiol and desogestrel revealed no special hazard for
humans based on conventional studies of repeated dose toxicity, genotoxicity,
carcinogenic potential and toxicity to reproduction.
However, it must be borne in mind that sex steroids can promote the growth of certain
hormone-dependent tissues and tumours.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Tablet core:
Potato starch;
stearic acid;
all-rac-alpha-tocopherol;
lactose monohydrate;
magnesium stearate;
silica colloidal anhydrous;
povidone K 30;
quinoline yellow (E 104);
Tablet coating:
Hypromellose;
Macrogol 6000;
Propylene glycol.

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
3 years.

6.4

Special precautions for storage
Store below 30ºC. Store in the original package.

6.5

Nature and contents of container
PVC/PVDC-Aluminium blisters of 21 tablets per calendar blister strip available in
packs containing 1x21, 3x21, 6x21 or 13x21 tablets.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling
No special requirements.
Any unused product or waste material should be disposed of in accordance with local
requirements.

7

MARKETING AUTHORISATION HOLDER
Gedeon Richter Plc.
1103 Budapest, Gyömrői út 19-21.
Hungary

8

MARKETING AUTHORISATION NUMBER(S)
PL 04854/0060

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
05/07/2013

10

DATE OF REVISION OF THE TEXT
16/03/2017

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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