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LOGYNON ED TABLETS

Active substance(s): ETHINYLESTRADIOL / ETHINYLOESTRADIOL / LEVONORGESTREL / NO ACTIVES PRESENT / ETHINYLESTRADIOL / ETHINYLOESTRADIOL / LEVONORGESTREL / NO ACTIVES PRESENT / ETHINYLESTRADIOL / ETHINYLOESTRADIOL / LEVONORGESTREL / NO ACTIVES PRESENT

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Logynon ® ED

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Calendar pack containing 6 light brown tablets, 5 white tablets and 10 ochre-coloured
tablets containing the following ingredients.
Each Light Brown Tablet contains:
Actives
Levonorgestrel
Ethinylestradiol

50 micrograms
30 micrograms

Excipients
Lactose
Sucrose

33.07 mg
19.297 mg

Each White Tablet contains:
Actives
Levonorgestrel
Ethinylestradiol

75 micrograms
40 micrograms

Excipients
Lactose
Sucrose

33.035 mg
19.660 mg

Each Ochre Tablet contains:
Actives
Levonorgestrel
Ethinylestradiol

125 micrograms
30 micrograms

Excipients
Lactose
Sucrose

32.995 mg
19.223 mg

Loygnon ED also contains 7 large white placebo tablets.
Each placebo tablet contains:

Excipients
Lactose
Sucrose

48.250 mg
33.980 mg

For full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM

Sugar-coated tablets.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Oral contraception and the recognised gynaecological indications for such oestrogenprogesterone combinations.
The decision to prescribe Logynon ED should take into consideration the individual
woman’s current risk factors, particularly those for venous thromboembolism (VTE),
and how the risk of VTE with Logynon ED compares with other combined hormonal
contraceptives (CHCs) (see sections 4.3 and 4.4).
4.2

Posology and method of administration
Tablets must be taken orally in the order directed on the blister package at about the
same time every day, with some liquid if necessary.
First treatment cycle: 1 tablet daily for 28 days, starting on the first day of the
menstrual cycle. 21 (small) active tablets are taken followed by 7 (larger) placebo
tablets. Contraceptive protection begins immediately.
Subsequent cycles: Tablet taking is continuous, which means that the next pack of
Logynon ED follows immediately without a break. A withdrawal bleed usually
occurs when the white placebo tablets are being taken.
Changing from 21-day combined oral contraceptives: The first tablet of Logynon ED
should be taken on the first day immediately after the end of the previous oral
contraceptive course. Additional contraceptive precautions are not required.
Changing from a combined Every Day pill (28 -day pill): Logynon ED should be
started after taking the last active tablet from the previous Every Day pill pack. The
first Logynon ED tablet is taken the next day. Additional contraceptive precautions
are not then required.

Changing from a progestogen-only pill (POP):
The first tablet of Logynon ED should be taken on the first day of bleeding, even if a
POP has already been taken on that day. Additional contraceptive precautions are not
then required. The remaining progestogen-only pills should be discarded.
Post-partum and post-abortum use: After pregnancy, Logynon ED can be started 21
days after a vaginal delivery, provided that the patient is fully ambulant and there are
no puerperal complications. Additional contraceptive precautions will be required for
the first 7 days of tablet taking. Since the first post-partum ovulation may precede the
first bleeding, another method of contraception should be used in the interval between
childbirth and the first course of tablets. After a first-trimester abortion, oral
contraception may be started immediately in which case no additional contraceptive
precautions are required.
Special circumstances requiring additional contraception:
Incorrect administration: Errors in taking the 7 inactive white placebo tablets (i.e.
the larger white tablets in the last row) can be ignored. A single delayed active
(small) tablet should be taken as soon as possible, and if this can be done within 12
hours of the correct time, contraceptive protection is maintained.
With longer delays in taking active tablets, additional contraception is needed. Only
the most recently delayed tablet should be taken, earlier missed tablets being omitted,
and additional non-hormonal methods of contraception (except the rhythm or
temperature methods) should be used for the next 7 days, while the next 7 active
(small) tablets are being taken. Therefore, if the 7 days additional contraception will
extend beyond the last active (small) tablet, the user should finish taking all the active
tablets, discard the placebo tablets and start a new pack of Logynon ED the next day
with an appropriate active (small) tablet. Thus, active tablet follows active tablet with
no 7 day break. In this situation, a withdrawal bleed should not be expected until the
end of the second pack. Some breakthrough bleeding may occur on pill taking days
but this is not clinically significant. If the patient does not have a withdrawal bleed
following the end of the second pack, the possibility of pregnancy must be ruled out
before starting the next pack.
Gastro-intestinal upset: Vomiting or diarrhoea may reduce the efficacy of oral
contraceptives by preventing full absorption. If vomiting or diarrhoea occurs within 4
hours of tablet taking from the current pack should be continued. Additional nonhormonal methods of contraception (except the rhythm or temperature methods)
should be used during the gastro-intestinal upset and for 7 days following the upset.
If these 7 days extend beyond the last active (small) tablet the user should finish
taking all the active tablets, discard the placebo tablets and start a new pack of
Logynon ED the next day with an appropriate active (small) tablet. In this situation,
a withdrawal bleed should not be expected until the end of the second pack. If the
patient does not have a withdrawal bleed at the end of the second pack, the possibility
of pregnancy must be ruled out before starting the next pack. Other methods of
contraception should be considered if the gastro-intestinal disorder is likely to be
prolonged.
Children: Not applicable

Elderly: Not applicable

4.3

Contraindications

Combined hormonal contraceptives (CHCs) should not be used in the following
conditions. Should any of the conditions appear for the first time during CHC use, the
product 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-III-deficiency, 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)
o Arterial thromboembolism – current arterial thromboembolism, history of
arterial thromboembolism (e.g. myocardial infarction) or prodromal
condition (e.g. angina pectoris)
o Cerebrovascular disease – current stroke, history of stroke or prodromal
condition (e.g. transient ischaemic attack, TIA)
o Known hereditary or acquired predisposition for arterial thromboembolism,
such as hyperhomocysteinaemia and anti-phospholipid antibodies
(anticardiolipin-antibodies, lupus anticoagulant)
o History of migraine with focal neurological symptoms
o 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, e.g. active viral hepatitis and
severe cirrhosis, as long as liver function values have not returned to normal.



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



Current or history of breast cancer.



Hypersensitivity to the active substance(s) or to any of the excipients.

Logynon ED is contraindicated for concomitant use with the medicinal products
containing ombitasvir/paritaprevir/ritonavir and dasabuvir (see sections 4.4 and 4.5).

Relevant UK clinical guidance should also be consulted.

4.4

Special warnings and precautions for use

Warnings



If any of the conditions or risk factors mentioned below is present, the
suitability of Logynon ED 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 Logynon ED should be discontinued.

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, such as Logynon ED, norgestimate or norethisterone are
associated with the lowest risk of VTE. The decision to use Logynon ED should
be taken after a discussion with the woman to ensure she understands the risk of
VTE with Logynon ED, 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 estimated that out of 10,000 women who use a CHC that contains levonorgestrel,
about 61 will develop a VTE in a year.
This number of VTEs per year is fewer than the number expected in women 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

1 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.

Extremely rarely, thrombosis has been reported to occur in CHC users in other blood
vessels, e.g. hepatic, mesenteric, renal, cerebral 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).
Logynon ED 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

Comment

Obesity (body mass index over
30 kg/m²)

Risk increases substantially as BMI rises.

Prolonged immobilisation, major
surgery, any surgery to the legs or
pelvis, neurosurgery, or major
trauma

In these situations it is advisable to discontinue use
of the pill (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.

Note: temporary immobilisation
including air travel >4 hours can

Particularly important to consider if other risk
factors also present.

also be a risk factor for VTE,
particularly in women with other
risk factors.

Antithrombotic treatment should be considered if
Logynon ED has not been discontinued in advance.

Positive family history (venous
thromboembolism ever in a sibling
or parent especially at a relatively
early age e.g. before 50).

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

Other medical conditions
associated with VTE

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

Increasing age

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 “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). Logynon ED 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

Comment

Increasing age

Particularly above 35 years

Smoking

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.

Hypertension
Obesity (body mass index over
30 kg/m2)

Risk increases substantially as BMI increases.

Positive family history (arterial
thromboembolism ever in a sibling
or parent especially at relatively
early age e.g. below 50).

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

Migraine

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

Other medical conditions
associated with adverse vascular
events

Diabetes mellitus, hyperhomocysteinaemia,
valvular heart disease and atrial fibrillation,
dyslipoproteinaemia and systemic lupus

Particularly important in women with additional
risk factors

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.
Medical Examination/Consultation
Prior to the initiation or reinstitution of Logynon ED 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 Logynon ED 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.

Undiagnosed vaginal bleeding that is suspicious for underlying conditions should be
investigated.
Conditions which require strict medical supervision
The decision to prescribe the COC must be made using clinical judgement and in
consultation with the woman. Exacerbation or first appearance of any of these
conditions or risk factors may indicate that use of the oral contraceptive should be
discontinued. The woman should contact her physician, who should then decide on
whether COC use should be discontinued:







Diabetes mellitus with mild vascular disease or mild nephropathy, retinopathy
or neuropathy
Hypertension that is adequately controlled, i.e. systolic >140 to 159 mm Hg or
diastolic > 90 to 94 mm Hg (see also Section 4.4 ‘Reasons for stopping oral
contraception immediately’)
porphyria
obesity
migraine
cardiovascular diseases

Reasons for stopping oral contraception immediately:
When stopping oral contraception non-hormonal contraception should be used to
ensure contraceptive protection is maintained.
1.

Occurrence for the first time, or exacerbation, of migrainous headaches or
unusually frequent or unusually severe headaches

2.

Sudden disturbances of vision, of hearing or other perceptual disorders

3.

First signs of thrombosis or blood clots (e.g. unusual pains in or swelling of
the leg(s), stabbing pains on breathing or coughing for no apparent reason).
Feeling of pain and tightness in the chest

4.

Six weeks before an elective major operation (e.g. abdominal, orthopaedic),
any surgery to the legs, medical treatment for varicose veins or prolonged
immobilisation, e.g. after accidents or surgery. Do not restart until 2 weeks
after full ambulation. In case of emergency surgery, thrombotic prophylaxis is
usually indicated e.g. subcutaneous heparin

5.

Onset of jaundice, hepatitis, itching of the whole body

6.

Significant rise in blood pressure

7.

Severe upper abdominal pain or liver enlargement

8.

Clear exacerbation of conditions known to be capable of deteriorating during
oral contraception or pregnancy (see section 4.4 ‘Conditions which deteriorate
in pregnancy or during previous COC use’ under 'Other conditions')

Tumours
Numerous epidemiological studies have been reported on the risks of ovarian,
endometrial, cervical and breast cancer in women using combined oral contraceptives.
The evidence is clear that high dose combined oral contraceptives offer substantial
protection against both ovarian and endometrial cancer. However, it is not clear
whether low dose COCs confer protective effects to the same level.


Breast cancer

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 observed pattern of
increased risk may be due to an earlier diagnosis of breast cancer in COC users, the
biological effects of COCs or a combination of both. The additional breast cancers
diagnosed in current users of COCs or in women who have used COCs in the last ten
years are more likely to be localised to the breast than those in women who never
used COCs.
Breast cancer is rare among women under 40 years of age whether or not they take
COCs. Whilst this background risk increases with age, the excess number of breast
cancer diagnoses in current and recent COC users is small in relation to the overall
risk of breast cancer (see bar chart).
The most important risk factor for breast cancer in COC users is the age women
discontinue the COC; the older the age at stopping, the more breast cancers are
diagnosed. Duration of use is less important and the excess risk gradually disappears
during the course of the 10 years after stopping COC use such that by 10 years there
appears to be no excess.
The possible increase in risk of breast cancer should be discussed with the user and
weighed against the benefits of COCs taking into account the evidence that they offer
substantial protection against the risk of developing certain other cancers (e.g. ovarian
and endometrial cancer).
Estimated cumulative numbers of breast cancers per
10,000 women diagnosed in 5 years of use and up to 10
years after stopping COCs, compared with numbers of
breast cancers diagnosed in 10,000 women who had
never used COCs

300
262
250

230

200
Number of breast
cancers

181
160

150

Never took COCs
Used COCs for 5 years

100

0

4 4.5

16 17.5

Under 20

20-24

25-29

30-34

30

35

40

45

Cancers found up to the age of:



111

44 48.7

50

Took the Pill at these ages:

100

35-39

40-44

50

55

Cervical Cancer

The most important risk factor for cervical cancer is persistent HPV infection. Some
epidemiological studies have indicated that long-term use of COCs may further
contribute to this increased risk but there continues to be controversy about the extent
to which this finding is attributable to confounding effects, e.g., cervical screening
and sexual behaviour including use of barrier contraceptives.


Liver Cancer

In rare cases benign and, in even rarer cases, malignant liver tumours leading in
isolated cases to life-threatening intra-abdominal haemorrhage have been observed
after the use of hormonal substances such as those contained in Logynon ED. If
severe upper abdominal complaints, liver enlargement or signs of intra-abdominal
haemorrhage occur, the possibility of a liver tumour should be included in the
differential diagnosis.
Other conditions
The possibility cannot be ruled out that certain chronic diseases may occasionally
deteriorate during the use of combined oral contraceptives.


Known hyperlipidaemias

Women with hypertriglyceridemia, or a family history thereof, may be at an increased
risk of pancreatitis when using COCs.
Women with hyperlipidaemias are at an increased risk of arterial disease (see section
4.4 ‘Risk of arterial thromboembolism (ATE)’). However routine screening of women
on COCs is not appropriate.


Blood pressure

Hypertension is a risk factor for stroke and myocardial infarction (see section 4.4
‘Risk of arterial thromboembolism (ATE)’). Although small increases in blood
pressure have been reported in many women taking COCs, clinically relevant
increases are rare. However, if sustained hypertension develops during the use of a
COC, antihypertensive treatment should normally be instigated at a level of 160/100
mm Hg in uncomplicated patients or at 140/90 mm Hg in those with target organ
damage, established cardiovascular disease, diabetes or with increased cardiovascular
risk factors. Decisions about the continued use of the COC should be made at lower
BP levels, and alternative contraception may be advised.


Conditions which deteriorate in pregnancy or during previous COC use

The following conditions have been reported to occur or deteriorate with both
pregnancy and COC use. Consideration should be given to stopping Logynon ED if
any of the following occur during use:











jaundice and/or pruritus related to cholestasis
COCs may increase the risk of gallstone formation and may worsen existing
disease.
systemic lupus erythematosus
herpes gestationis
otosclerosis-related hearing loss
sickle cell anaemia
renal dysfunction
hereditary angioedema
any other condition an individual woman has experienced worsening of during
pregnancy or previous use of COCs.

Disturbances of liver function

Acute or chronic disturbances of liver function may necessitate the discontinuation of
COC use until markers of liver function return to normal. Recurrence of cholestatic
jaundice and/or cholestasis-related pruritus which occurred during pregnancy or
previous use of sex steroids necessitates the discontinuation of COCs.


Diabetes (without vascular involvement)

Insulin-dependent diabetics without vascular disease can use COCs. However it
should be remembered that all diabetics are at an increased risk of arterial disease and
this should be considered when prescribing COCs. Diabetics with existing vascular
disease are contraindicated from using COCs (see section 4.3 Contraindications).
Although COCs 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 low-dose COCs (containing < 0.05 mg ethinylestradiol). However, diabetic
women should be carefully observed while taking COCs.


Chloasma

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 COCs.


Menstrual Changes

Reduction of menstrual flow: This is not abnormal and it is to be expected in some
patients. Indeed, it may be beneficial where heavy periods were previously
experienced.
Missed menstruation: Occasionally, withdrawal bleeding may not occur at all. If the
tablets have been taken correctly, pregnancy is very unlikely. If withdrawal bleeding
fails to occur at the end of a second pack, the possibility of pregnancy must be ruled
out before resuming with the next pack.
Intermenstrual bleeding: 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
non-hormonal causes should be considered and adequate diagnostic measures are
indicated to exclude malignancy or pregnancy. This may include curettage.
Some women may experience amenorrhoea or oligomenorrhoea after discontinuation
of oral contraceptives, especially when these conditions existed prior to use. Women
should be informed of this possibility.


Lactose and Sucrose Intolerance

Each light brown tablet contains 33.07 mg lactose and 19.297 mg sucrose per tablet.
Each white tablet contains 33.035 mg lactose and 19.66 mg sucrose per tablet. Each
ochre tablet contains 32.995 mg lactose and 19.223 mg sucrose per tablet. Each
placebo tablet contains 48.25 mg lactose and 33.98 mg sucrose per tablet. Patients
with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency,
fructose intolerance or glucose-galactose malabsorption or sucrase-isomaltase should
not take this medicine.


Reduced efficacy

The efficacy of COCs may be reduced, in the event of missed tablets, vomiting or
diarrhoea, or concomitant medication.
ALT elevations
During clinical trials with patients treated for hepatitis C virus infections (HCV) with
the medicinal products containing ombitasvir / paritaprevir / ritonavir and dasabuvir
with or without ribavirin, transaminase (ALT) elevations higher than 5 times the
upper limit of normal (ULN) occurred significantly more frequent in women using
ethinylestradiol-containing medications such as combined hormonal contraceptives
(CHCs) (see sections 4.3 and 4.5).

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.


Interactions

Enzyme inducers
Interactions can occur with drugs that induce microsomal enzymes (especially
cytochrome P450 3A4) which can result in increased clearance of sex hormones and
which may lead to breakthrough bleeding and/or contraceptive failure.
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.
Women on short term treatment with any of these drugs should temporarily use a
barrier method in addition to the COC or choose another method of contraception.
The barrier method should be used during the time of concomitant drug
administration and for 28 days after their discontinuation. If the period during which
the barrier methods is used runs beyond the last active (small) tablet, the user should
finish taking all the active tablets, discard the placebo (large) tablets and start a new
pack of Logynon ED the next day with an appropriate active (small) tablet. In this
situation, a withdrawal bleed should not be expected until the end of the second pack.
If the patient does not have a withdrawal bleed at the end of the second pack, the
possibility of pregnancy must be ruled out before resuming with the next pack.
For women receiving long-term therapy with enzyme inducers, another method of
contraception should be used.
The following have been shown to have clinically important interactions with COCs:
Anticonvulsants: barbiturates (including phenobarbitone), primidone, phenytoin,
carbamazepine, oxcarbazepine, topiramate.
Antibiotics/antifungals: griseofulvin, rifampacin.
Herbal remedies: St John’s wort (Hypericum perforatum)
Antiretroviral agents: ritonavir, nelfinavir, nevirapine.
Note: There are other antiretroviral agents that may increase plasma concentration of
sex hormones.
Substances decreasing the clearance of COCs (enzyme inhibitors)
Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole,
voriconazole, fluconazole) and macrolides (e.g. erythromycin) can increase plasma
concentrations of the oestrogen or the progestin or both.
Etoricoxib doses of 60 to 120 mg/day have been shown to increase plasma
concentrations of ethinylestradiol 1.4 to 1.6-fold, respectively when taken
concomitantly with a combined hormonal contraceptive containing 0.035 mg
ethinylestradiol.

Effects on other drugs
Oral contraceptives may affect the metabolism of certain other drugs. Accordingly,
plasma and tissue concentrations may either increase (e.g. cyclosporin, tizanidine,
theophylline) or decrease (e.g. lamotrigine).
Pharmacodynamic interactions
Concomitant use with the medicinal products containing
ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin may increase
the risk of ALT elevations (see sections 4.3 and 4.4).
Therefore, Logynon ED-users must switch to an alternative method of contraception
(e.g., progestagen-only contraception or non-hormonal methods) prior to starting
therapy with this combination drug regimen. Logynon ED can be restarted 2 weeks
following completion of treatment with this combination drug regimen.


Laboratory tests

The use of oral contraceptives may influence the results of certain laboratory tests
including biochemical parameters of liver, thyroid, adrenal and renal function, plasma
levels of carrier proteins, e.g. corticosteroid binding globulin and lipid/lipoprotein
fractions, parameters of carbohydrate metabolism and parameters of coagulation and
fibrinolysis. Laboratory staff should therefore be informed about oral contraceptive
use when laboratory tests are requested.

4.6

Fertility, pregnancy and lactation

Logynon ED is not indicated during pregnancy. If pregnancy occurs during treatment
with Logynon ED, further intake must be stopped. However, extensive
epidemiological studies have revealed neither an increased risk of birth defects in
children born to women who used COCs prior to pregnancy, nor a teratogenic effect
when COCs were taken inadvertently during early pregnancy.
The increased risk of VTE during the postpartum period should be considered when
re-starting Logynon ED (see section 4.2 and 4.4).
The use of Logynon ED during lactation may lead to a reduction in the volume of
milk produced and to a change in its composition. Minute amounts of the active
substances are excreted with the milk. These amounts may affect the child
particularly in the first 6 weeks post-partum. Mothers who are breast-feeding may be
advised instead to use another method of contraception.
4.7

Effects on ability to drive and to use machines
Ethinylestradiol / levonorgestrel has no effects or negligible influence on the ability to
drive and use machines.

4.8

Undesirable Effects

Summary of the safety profile
The most commonly reported adverse reactions with Logynon ED are nausea,
abdominal pain, increased weight, headache, depressed mood, altered mood, breast
pain, breast tenderness. They occur in ≥1% of users.
Serious adverse reactions are arterial and venous thromboembolism.
The following adverse events have been reported during use of ethinylestradiol /
levonorgestrel:

Adverse events reported in clinical trials
System Organ
Class

Common
(≥ 1/100)

Uncommon
(≥ 1/1000,
<1/100)

nausea,
abdominal
pain

Metabolism and
nutrition
disorders
Nervous system
disorders

Crohn’s disease,
ulcerative colitis

vomiting, diarrhea

Immune system
disorders
Investigations

Rare
(< 1/1000)

contact lens
intolerance

Eye disorders
Gastrointestinal
disorders

hypersensitivity
weight
increased

Hypertriglyce
ridemia

fluid retention
headache

exacerbation of
chorea

migraine
Venous
thromboembolism
(VTE),
Arterial
thromboembolism
(ATE)

Hepatobiliary
disorders

Reproductive
system and
breast disorders

exacerbation of
hereditary
angioedema

weight decreased

Vascular system
disorders

Psychiatric
disorders

Adverse events
reported post
marketing

liver function
disturbances
depressed
mood,
mood altered

breast pain,
breast
tenderness

libido decreased

breast
hypertrophy

libido increased

vaginal
discharge,
breast
discharge

reduced
menstrual flow,
spotting,
breakthrough
bleeding and
missed
withdrawal
bleeding, post
pill
amenorrhoea

Skin and
subcutaneous
tissue disorders

rash, urticaria

erythema
nodosum,
erythema
multiforme

chloasma

Description of selected adverse reactions
An increased risk of arterial and venous thrombotic and thrombo-embolic events,
including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis
and pulmonary embolism has been observed in women using CHCs, which are
discussed in more detail in section 4.4.
The following serious adverse events have been reported in women using COCs,
which are discussed in section 4.4 'Special warnings and precautions for use':






Venous thromboembolic disorders
Arterial thromboembolic disorders
Strokes (e.g. transient ischemic attack, ischemic stroke, haemorrhagic stroke)
Hypertension
Liver tumours (benign and malignant)

The frequency of diagnosis of breast cancer is very slightly increased among COC
users. As breast cancer is rare in women under 40 years of age the excess number is
small in relation to the overall risk of breast cancer. Causation with COC use is
unknown. For further information, see sections 4.3 ‘Contraindications’ and 4.4
‘Special warnings and precautions for use’.
Conditions reported to deteriorate with pregnancy or previous COC use
Jaundice and/or pruritus related to cholestasis; gallstone formation; systemic lupus
erythematosus; herpes gestationis; otosclerosis-related hearing loss; sickle cell
anaemia; renal dysfunction; hereditary angioedema; porphyria; cervical cancer.
Changes in glucose tolerance or effect on peripheral insulin resistance have been
reported in women using COCs (see section 4.4).
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.

4.5

Overdose

There have been no reports of serious effects from overdose. Overdosage may cause
nausea, vomiting and withdrawal bleeding. Withdrawal bleeding may even occur in
girls before their menarche, if they accidentally take the medicinal product.

There are no specific antidotes and treatment should be symptomatic.

5

PHARMACOLOGICAL PROPERTIES

5.1
Pharmacodynamic properties
Logynon ED is an oestrogen-progestogen combination which acts by inhibiting
ovulation by suppression of the mid-cycle surge of luteinising hormone, the
inspissation of cervical mucus so as to constitute a barrier to sperm, and the rendering
of the endometrium unreceptive to implantation.

5.2

Pharmacokinetic properties

Levonorgestrel
Orally administered levonorgestrel is rapidly and completely absorbed. Following
ingestion of 0.125mg levonorgestrel together with 0.03mg ethinylestradiol (which
represents the combination with the highest levonorgestrel content of the tri-step
formulation), maximum drug serum levels of about 4.3ng/ml are reached at 1.0 hour.
Thereafter, levonorgestrel serum levels decrease in two phases, characterized by halflives of 0.4 hours and about 22 hours. For levonorgestrel, a metabolic clearance rate
from serum of about 1.5ml/min/kg was determined. Levonorgestrel is not excreted in
unchanged form but as metabolites. Levonorgestrel metabolites are excreted in about
equal proportions with urine and faeces. Levonorgestrel is extensively metabolised.
The major metabolites in plasma are the unconjugated and conjugated forms of 3α,
5β-tetrahydrolevonorgestrel. Based on in vitro and in vivo studies, CYP3A4 is the
main enzyme involved in the metabolism of levonorgestrel.
Levonorgestrel is bound to serum albumin and to SHBG. Only 1.4% of the total
serum drug levels are present as free steroid, but 55% are specifically bound to
SHBG. The relative distribution (free, albumin-bound, SHBG-bound) depends on the
SHBG concentrations in the serum. Following induction of the binding protein, the
SHBG-bound fraction increases while the unbound fractions decrease.
Following daily repeated administration of Logynon ED, levonorgestrel
concentrations in the serum increase by a factor of about 4. Steady-state conditions
are reached during the second half of a treatment cycle. The pharmacokinetics of
levonorgestrel is influenced by SHBG serum levels. Under treatment with Logynon
ED, an increase in the serum levels of SHBG by a factor of about 2 occurs during a
treatment cycle. Due to the specific binding of levonorgestrel to SHBG, the increase
in SHBG levels is accompanied by an almost parallel increase in levonorgestrel serum
levels. The absolute bioavailability of levonorgestrel was determined to be almost
100% of the dose administered.
Ethinylestradiol

Orally administered ethinylestradiol is rapidly and completely absorbed. Following
ingestion of 0.03mg ethinylestradiol together with 0.125mg levonorgestrel, maximum
drug serum levels of about 116 pg/ml are reached at 1.3 hours. Thereafter,
ethinylestradiol serum levels decrease in two phases characterized by half-lives of 1 2 hours and about 20 hours. For technical reasons, these parameters can only be
calculated following the administration of higher doses. For ethinylestradiol an
apparent volume of distribution of about 5 l/kg and a metabolic clearance rate from
serum of about 5 ml/min/kg were determined. Ethinylestradiol is highly but nonspecifically bound to serum albumin. About 2% of drug levels are present unbound.
During absorption and first liver passage, ethinylestradiol is metabolized resulting in a
reduced absolute and variable oral bioavailability. Unchanged drug is not excreted.
Ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6 with a halflife of about 1 day.
Due to the half-life of the terminal disposition phase from serum and the daily
ingestion, steady-state serum levels are reached after 3-4 days and are higher by 30 40% as compared to a single dose. The absolute bioavailability of ethinylestradiol is
subject to a considerable interindividual variation. Following oral administration, the
mean bioavailability was found to be about 40 - 60% of the administered dose.
During established lactation, 0.02% of the daily maternal dose could be transferred to
the newborn via milk.
The systemic availability of ethinylestradiol might be influenced in both directions by
other drugs. There is, however, no interaction with high doses of vitamin C.
Ethinylestradiol induces the hepatic synthesis of SHBG and CBG during continuous
use. The extent of SHBG induction, however, depends on the chemical structure and
the dose of the co-administered progestogen. During treatment with Logynon ED,
SHBG concentrations in the serum increased from about 76 nmol/l to 164 nmol/l and
the serum concentrations of CBG increased from about 48 μg/ml to 111 μg/ml.
5.3
Preclinical safety data
There are no preclinical safety data which could of relevance to the prescriber and
which are not already included in other relevant sections of the SPC

6

PHARMACEUTICAL PARTICULARS

6.1
List of excipients
Excipients included in both active and placebo tablets:
Active tablets Placebo tablets
lactose lactose
maize starch maize starch
povidone
povidone
magnesium stearate (E 572) magnesium stearate (E 572)

sucrosesucrose
polyethylene glycol 6000
polyethylene glycol 6000
calcium carbonate (E 170) calcium carbonate (E 170)
talc
talc
montan glycol wax montan glycol wax
glycerin (E 422)
titanium dioxide (E 171)
ferric oxide pigment (red and yellow) (E 172)

6.2
Incompatibilities
None known

6.3
Shelf life
5 years

6.4
Special precautions for storage
Not applicable

6.5
Nature and contents of container
Deep drawn strips made of polyvinyl chloride film with counter-sealing foil made of
aluminium with heat sealable coating.
Presentation:
Cartons containing 3 blister memo-packs. Each memo-pack contains 21 active tablets
and 7 placebo tablets (total 28 tablets).

6.6

Special precautions for disposal
No special requirements.

7.

MARKETING AUTHORISATION HOLDER

Bayer plc
Bayer House
Strawberry Hill
Newbury
Berkshire RG14 1JA

United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)

PL 00010/0541

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
06/03/2009

10

DATE OF REVISION OF THE TEXT
03/08/2017

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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