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LESTRAMYL 150 MICROGRAM/30 MICROGRAM TABLETS

Active substance(s): DESOGESTREL / ETHINYL ESTRADIOL / DESOGESTREL / ETHINYL ESTRADIOL / DESOGESTREL / ETHINYL ESTRADIOL

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Lestramyl 150 microgram/30 microgram Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 150 micrograms desogestrel and 30 micrograms
ethinylestradiol.
Excipients: 1 uncoated tablet contains 58 mg of lactose anhydrous
For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Tablet
Each tablet is round, white to off-white, 5.00 mm, uncoated, biconvex,
debossed with ‘142’ on one side and other side plain.

4.1

Therapeutic indications
Oral contraception.
The decision to prescribe Lestramyl 150 microgram/30 microgram Tablets should
take into consideration the individual woman’s current risk factors, particularly those
for venous thromboembolism (VTE), and how the risk of VTE with Lestramyl 150
microgram/30 microgram Tablets compares with other CHCs (see sections 4.3 and
4.4).

4.2

Posology and method of administration
Posology
How to take Lestramyl 150 microgram/30 microgram Tablets
The tablets must be taken every day at about the same time, if necessary with a little
liquid, in the order shown on the blister pack. One tablet is to be 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
after the last tablet and may not have finished before the next pack is started.
How to start Lestramyl 150 microgram/30 microgram Tablets
• No preceding hormonal contraceptive use (in the past month)
Tablet-taking has to start on day 1 of the woman’s natural cycle (i.e. the first day of
her 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
contraceptive (COC), vaginal ring or transdermal patch)

(combined

oral

The woman should start taking Lestramyl 150 microgram/30 microgram Tablets
preferably on the day after the last active tablet (the last tablet containing the active
substances) of her previous COC, but at the latest on the day following the usual
tablet-free or placebo tablet interval of her previous COC. In case a vaginal ring or a
transdermal patch has been used, the woman should start using Lestramyl 150
microgram/30 microgram Tablets preferably on the day of removal, but at the latest
when the next application would have been due.
Under no circumstances should the hormone-free period of her previous method be
extended beyond the recommended duration.
If the woman consistently and correctly used her previous combined hormonal
contraceptive during the previous 7 days, and it is reasonably certain that she is not
pregnant she may switch to Lestramyl 150 microgram/30 microgram Tablets at any
day of the cycle of her previous combined hormonal contraceptive method.
It is possible that not all the described methods of contraception (e.g. vaginal ring,
transdermal patch) are available in all EU countries.


Changing from a progestogen-only-method (progestogen-only-pill, injection,
implant) or from a progestogen-releasing intrauterine system (IUS)

The woman may switch any day from the progestogen-only pills (from an implant or
the IUS on the day of its removal; from an injectable when the next injection would
be due) but should in all of these cases be advised to additionally use a barrier method
for the first 7 days of tablet-taking.


Following first-trimester abortion

The woman may start immediately. When doing so, she need not take additional
contraceptive measures.


Following delivery or second-trimester abortion

The woman should be advised to start at day 21 to 28 after delivery or secondtrimester abortion. When starting later, the woman should be advised to additionally
use a barrier method for the first 7 days. However if intercourse has already occurred,
pregnancy should be excluded before the actual start of COC use or the woman has to
wait for her first menstrual period.
For breast-feeding women - see section 4.6.
Management of missed tablets
If the user is less than 12 hours late in taking any tablet, contraceptive protection is
not reduced.
The woman should take the tablet as soon as she remembers, and should take further
tablets at the usual time.
If she is more than 12 hours late in taking any tablet, contraceptive protection may
be reduced. The management of missed tablets can be guided by the following two
basic rules:
1.
2.

tablet-taking must never be interrupted for longer than 7 days
7 days of uninterrupted tablet-taking are required to attain adequate
suppression of the hypothalamus-pituitary-ovarian-axis.

Accordingly the following advice can be given in daily practice:

Week 1
The user should take the last missed tablet as soon as she remembers, even if this
means taking two tablets at the same time. She then continues to take tablets at her
usual time. In addition, a barrier method such as a condom should be used for the next
7 days. If intercourse took place in the preceding 7 days, the possibility of a
pregnancy should be considered. The more tablets are missed and the closer they are
to the regular tablet-free interval, the higher the risk of a pregnancy.

Week 2
The user should take the last missed tablet as soon as she remembers, even if this
means taking two tablets at the same time. She then continues to take tablets at her
usual time. Provided that the woman has taken her tablets correctly in the 7 days
preceding the first missed tablet, there is no need to use extra contraceptive
precautions. However, if she has missed more than 1 tablet, the woman should be
advised to use extra contraceptive precautions for 7 days.

Week 3
The risk of reduced reliability is imminent because of the forthcoming 7-day tabletfree interval. However, by adjusting the tablet-intake schedule, reduced contraceptive
protection can still be prevented. By adhering to either of the following two options,
there is no need to use extra contraceptive precautions, provided that in the 7 days
preceding the first missed tablet the woman has taken all tablets correctly. If this is
not the case, she should follow the first of these two options and use extra
contraceptive precautions for the next 7 days as well.
1. The user should take the last missed tablet as soon as she remembers, even if this
means taking two tablets at the same time. She then continues to take tablets at her
usual time. The next blister pack must be started as soon as the current blister pack
is finished, i.e., no gap should be left between packs. The user is unlikely to have a

withdrawal bleed until the end of the second pack, but she may experience spotting
or breakthrough bleeding on tablet-taking days.
2. The user may also be advised to discontinue tablet-taking from the current blister
pack. She should then have a tablet-free interval of up to 7 days, including the
days she missed tablets, and subsequently continue with the next blister pack.
If the woman missed tablets and subsequently has no withdrawal bleed in the first
normal tablet-free interval, the possibility of a pregnancy should be considered.
Advice in case of gastrointestinal disturbances
In case of severe gastrointestinal disturbances (e.g. vomiting or diarrhoea), absorption
may not be complete and additional contraceptive measures should be taken.
If vomiting occurs within 3-4 hours after tablet-taking, a new (replacement) tablet
should be taken as soon as possible. The new tablet should be taken within 12 hours
of the usual time of tablet-taking if possible. If more than 12 hours elapse, the advice
concerning missed tablets, under section “Management of missed tablets”, is
applicable. If the woman does not want to change her normal tablet-taking schedule,
she has to take the extra tablet(s) from another blister pack.
How to postpone a withdrawal bleed
Delaying the monthly bleed is not an indication for the product. However, to delay a
period in exceptional cases the woman can continue with another blister pack of
Lestramyl 150 microgram/30 microgram Tablets without a tablet-free interval. The
extension can be carried on for as long as wished, but not longer than the end of the
second pack. During the extension the woman may experience breakthrough-bleeding
or spotting. Regular intake of Lestramyl 150 microgram/30 microgram Tablets 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/ethinylestradiol in adolescents below 18 years
has not yet been established. No data are available.
Method of administration
Oral use.

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 COC use, the
medicinal product should be stopped immediately.
• Presence or risk of venous thromboembolism (VTE)
o 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
o Major surgery with prolonged immobilisation (see section 4.4)
o 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 antiphospholipid-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
Pancreatitis or a history thereof if associated with severe hypertriglyceridaemia
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)
Undiagnosed vaginal bleeding.
Endometrial hyperplasia
Hypersensitivity to the active substances or to any of the excipients listed in
section 6.1.
o











4.4

Special warnings and precautions for use
Warnings
If any of the conditions or risk factors mentioned below is present, the suitability of <
Lestramyl 150 microgram/30 microgram Tablets 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 Lestramyl 150 microgram/30 microgram Tablets 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, norgestimate or norethisterone are associated with the lowest
risk of VTE. Other products such as Lestramyl 150 microgram/30 microgram
Tablets 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 Lestramyl 150
microgram/30 microgram Tablets, 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 drospirenone,
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.
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

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

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).
Lestramyl 150 microgram/30 microgram Tablets 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.

Particularly important to consider if other
risk factors also present.
Prolonged immobilisation, major surgery, any In these situations it is advisable to
surgery to the legs or pelvis, neurosurgery, or discontinue use of the patch/pill/ring (in the
major trauma
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 also be a risk factor for
VTE, particularly in women with other risk
factors

Antithrombotic treatment should be
considered if Lestramyl 150 microgram/30
microgram Tablets 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.
Occurrence of one or more of these symptoms may be a reason for immediate
discontinuation of Lestramyl 150 microgram/30 microgram Tablets usage.
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). Lestramyl 150
microgram/30 microgram Tablets 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.
Particularly important in women with
additional risk factors

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
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.

The presence of one serious risk factor or multiple risk factors for venous or arterial
disease, respectively, can also constitute a contra-indication. The possibility of
anticoagulant therapy should also be taken into account. COC users should be
specifically pointed out to contact their physician in case of possible symptoms of
thrombosis. In case of suspected or confirmed thrombosis, COC use should be
discontinued. Adequate alternative contraception should be initiated because of the
teratogenicity of anticoagulant therapy (coumarins).
Tumours
Epidemiological studies indicate that the long-term use of oral contraceptives displays
a 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 is 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 COC. The excess risk gradually disappears during the course of
the 10 years after cessation of COC use. Because breast cancer is rare in women
under 40 years of age, the excess number of breast cancer diagnoses in current and
recent users of COC is small in relation to the overall risk of breast cancer. These
studies do not provide evidence for causation. The observed pattern of increased risk
may be due to an earlier diagnosis of breast cancer in users of COC, the biological
effects of COCs or a combination of both. The breast cancers diagnosed in ever-users
tend to be less advanced clinically than the cancers diagnosed in never-users.
In rare cases, benign liver tumours, and even more rarely malignant liver tumours
have been reported in users of COCs. 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 COCs.
Other conditions
Women with hypertriglyceridaemia or a family history thereof may be at an increased
risk of pancreatitis when using COCs.
Although small increases in blood pressure have been reported in many women
taking COCs, clinically relevant increases are rare. Only in these rare cases an
immediate discontinuation of COC use is justified. A systematic relationship between
COC use and clinical hypertension has not been established. However, if sustained
clinically significant hypertension develops during the use of a COC then it is prudent
for the physician to withdraw the COC and treat the hypertension. Where considered
appropriate, COC 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 an association with COC use is
inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation;
porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham’s
chorea; herpes gestationis; otosclerosis-related hearing loss.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate
symptoms of angioedema.
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 which occurred first during pregnancy or and/or cholestasis-related pruritus
which previously occurred during pregnancy or during previous use of sex steroids
necessitates the discontinuation of COCs.
Although COCs may have an effect on peripheral insulin resistance and glucose
tolerance, there is no evidence for a need to alter the therapeutic regime in diabetics
using COCs. However, diabetic women should be carefully observed while taking
COCs, particularly in the early stage of COC use.
Worsening of endogenous depression, of epilepsy, of Crohn’s disease and ulcerative
colitis have been associated with COC use.
Chloasma may occasionally occur, especially in women with a medical history of
chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to
the sun or ultraviolet radiation whilst taking COCs.
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 Lestramyl 150 microgram/30 microgram
Tablets a complete medical history (including family history) should be taken and
pregnancy must be ruled out. Blood pressure should be measured and if clinically
indicated a physical examination should be performed, guided by the
contraindications (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 Lestramyl 150 microgram/30 microgram Tablets compared with
other COCs, 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 further periodic examinations should
be based on established practice guidelines and be adapted to the individual woman.
Women should be advised that oral contraceptives do not protect against HIV
infections (AIDS) and other sexually transmitted diseases.
Reduced efficacy
The efficacy of COCs may be reduced in the event of e.g. missed tablets (see section
4.2 “Management of missed tablets”), gastro-intestinal disturbances (see section 4.2
“Advice in case of gastrointestinal disturbances”) or concomitant medication (see
section 4.5).

Herbal preparations containing St. John's wort (Hypericum perforatum) should not be
used while taking Lestramyl 150 microgram/30 microgram Tablets due to the risk of
decreased plasma concentrations and reduced clinical effects of Lestramyl 150
microgram/30 microgram Tablets (see section 4.5).
Reduced cycle control
With all COCs, irregular bleeding (spotting and 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 3 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 COC 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 COC use is
continued.
Lestramyl 150 microgram/30 microgram Tablets contains lactose. Patients with rare
hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicinal product.

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
Interactions between oral contraceptives and other medicinal products may lead to
breakthrough bleeding and/or contraceptive failure. The following interactions have
been reported in the literature.
Hepatic metabolism
Interactions can occur with medicinal products that induce hepatic enzymes which
can result in increased clearance of sex hormones (e.g. hydantoins, barbiturates,
primidone, carbamazepine, rifampicin, bosentan, rifabutin and possibly also
oxcarbazepine, modafinil, topiramate, felbamate, griseofulvin and medicinal products
containing the herbal remedy St. John's wort (Hypericum perforatum). Also HIV
protease inhibitors with an inducing potential (e.g. ritonavir and nelfinavir) and nonnucleoside reverse transcriptase inhibitors (e.g. nevirapine and efavirenz), may affect
hepatic metabolism.
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.
Influence of Lestramyl 150 microgram/30 microgram Tablets on other medicinal
products
Oral contraceptives may affect the metabolism of certain other active substances.
Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin)
or decrease (e.g. lamotrigine).
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; plasma
levels of (carrier) proteins, e.g. corticosteroid-binding globulin and lipid/lipoprotein
fractions, parameters of carbohydrate metabolism and parameters of coagulation and
fibrinolysis. Changes generally remain within the normal laboratory range.

4.6

Fertility, pregnancy and lactation
Pregnancy
Lestramyl 150 microgram/30 microgram Tablets is not indicated in pregnancy.
If pregnancy occurs during treatment with Lestramyl 150 microgram/30 microgram
Tablets, further intake should be stopped. However, most 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 Lestramyl 150 microgram/30 microgram Tablets (see sections 4.2 and
4.4).
Breast-feeding
Lactation may be influenced by COCs as they may reduce the quantity and change
the composition of breast milk. Therefore, the use of COCs 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 in the
milk however, there is no evidence that this has a detrimental effect on the child's
health.

4.7

Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been
performed. No effects on ability to drive and use machines have been observed
in users of COCs.

4.8

Undesirable effects
As with all COCs, 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
desogestrel/ethinylestradiol or COC users in general are listed in the table below1. 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 (<1/1,000).

System Organ Class

Very
common

Infections and infestations
Immune system disorders
Metabolism and nutrition
disorders
Psychiatric disorders

Common

Uncommon

Rare
Vaginal candidiasis
Hypersensitivity

Fluid retention
Depressed mood
Mood altered
Headache
Dizziness
Nervousness

Nervous system disorders

Libido decreased

Libido increased

Migraine

Eye disorders

Contact lens
intolerance
Otosclerosis

Ear and labyrinth disorders
Vascular disorders

Hypertension

Gastrointestinal disorders

Nausea
Abdominal pain
Acne

Vomiting
diarrhoea
Rash
Urticaria

Breast pain
Breast tenderness
Amenorrhea
Metrorrhagia

Breast enlargement

Skin and Subcutaneous
tissue disorders

Reproductive system and
breast disorders

Irregular
bleeding

Investigations

Weight
increased

1

Thromboembolism
(VTE or ATE)

Erythema nodosum
Erythema
multiforme
Pruritus
Alopecia
Vaginal discharge
Breast discharge

Weight decreased

The most common 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.
Description of selected adverse reactions

An increased risk of arterial and venous thrombotic and thrombo-embolic 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.
The following serious adverse events have been reported in women using COCs and
are also discussed in section 4.4:
-

-

Hypertension;
Hormone-dependent tumours (e.g. liver tumours, breast cancer, cervical
cancer);
Occurrence or deterioration of conditions for which an association with OC
use is not conclusive: Crohn's disease, ulcerative colitis, pancreatitis,
epilepsy, migraine, endometriosis, uterine myoma, porphyria, systemic lupus
erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uraemic
syndrome, cholestatic jaundice;
Chloasma;
Acute or chronic disturbances of liver function may necessitate the
discontinuation of COC use until markers of liver function return to normal.
In women with hereditary angioedema exogenous estrogens may induce or
exacerbate symptoms of angioedema.

The frequency of diagnosis of breast cancer is very slightly increased among OC
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 and 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.

4.9

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

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Progestogens and estrogens, fixed combinations, ATC
code: G03AA09

The contraceptive action of COCs is based on interaction of different factors, out of
which the most important is the inhibition of ovulation and changes in the cervical
secretion. Besides protection against pregnancy, COCs 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. In the largest multicenter trial (n=23
258 cycles), the uncorrected Pearl Index is estimated at 0.1 (95% confidence interval
0.0-0.3). Furthermore, 4.5% of the women reported absence of withdrawal bleeding
and 9.2% reported occurrence of irregular bleeding after 6 treatment cycles.
Lestramyl 150 microgram/30 microgram Tablets is a COC with ethinylestradiol and
the progestogen desogestrel. Ethinylestradiol is a well known synthetic estrogen.
Desogestrel is a synthetic progestogen. After oral administration it has a strong
ovulation-inhibiting activity.
With the use of the higher-dosed COCs (50 μg ethinylestradiol) the risk of
endometrial and ovarian cancer is reduced. Whether this also applies to lower-dosed
COCs remains to be confirmed.
Paediatric population
No clinical data on efficacy and safety are available in adolescents below 18 years.

5.2

Pharmacokinetic properties
Desogestrel
Absorption
After oral administration of Lestramyl 150 microgram/30 microgram Tablets,
desogestrel is rapidly and completely absorbed and converted to etonogestrel. Peak
plasma levels of approximately 2 ng/mL are reached after 1.5 hours. Bioavailability is
62-81 %.
Distribution
Etonogestrel is bound to the plasma proteins, mainly serum albumin and to sex
hormone-binding globulin (SHBG). Only 2-4 % of the total serum concentrations are
present as free steroid; 40-70 % are specifically bound to SHBG. The
ethinylestradiol-induced increase in SHBG influences the distribution over the serum
proteins, causing an increase of the SHBG-bound fraction and a decrease of the
albumin-bound fraction. The volume of distribution of desogestrel is 1.5 L/kg.
Biotransformation
Etonogestrel is completely metabolised by the known pathways of steroid
metabolism. Etonorgestrel is reduced and its degradation products are conjugated to
sulfate and glucuronides. The metabolic clearance rate of etonogestrel from serum is
about 2 mL/min/kg. Animal studies indicate that the enterohepatic circulation has no
relevance for the gestagenic activity of desogestrel. No interaction was found with coadministered ethinylestradiol.
Elimination
The serum concentration of etonogestrel decreases in two phases. The terminal
elimination phase is characterised by a half-life of approximately 30 hours and

plasma clearance varies from 5.0-9.5 l/hour. Desogestrel and its metabolites are
excreted at a urinary/biliary ratio of approximately 6:4.
Steady-State Conditions
Etonogestrel pharmacokinetics are influenced by SHBG levels, which are increased
by a factor of three by ethinylestradiol. Following daily ingestion, serum levels
increase by a factor of two to three, reaching steady-state conditions during the
second half of a treatment cycle.
Ethinylestradiol
Absorption
Ethinylestradiol is rapidly and completely absorbed after oral administration.
Following ingestion of a single dose peak plasma levels of approximately 45 pg/mL
are reached after 1-2 hours. Absolute bioavailability as a result of presystemic
conjugation and first-pass metabolism is 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. Distribution volume has been determined as approximately 5 L/kg.
Biotransformation
Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa
and the liver. Ethinylestradiol is primarily metabolised by aromatic hydroxylation, but
a wide variety of hydroxylated and methylated metabolites are formed, which occur
as free metabolites or as glucuronide or sulfate conjugates. The metabolic clearance
rate of ethinylestradiol from serum is approximately 5 mL/min/kg.
Elimination
Ethinylestradiol serum concentration decreases in two phases; the terminal
disposition phase is characterised by a half-life of approximately 24 hours.
Unchanged ethinylestradiol is not excreted. The metabolites of ethinylestradiol are
excreted at a urinary/biliary ratio of 4:6. The half-life of metabolite excretion is
approximately 1 day.
Steady-state conditions
Steady-state conditions are obtained after 3 to 4 days, when the serum drug level is
approx. 30 to 40% higher than after the administration of a single dose.

5.3

Preclinical safety data
Preclinical data shows no particular risk to humans when COCs are used according to
instructions. This conclusion is based on conventional studies of repeated dose
toxicity, genotoxicity, carcinogenic studies and reproduction toxicity studies.
However, it must be remembered that sex hormones can promote the growth of
certain hormone-dependent tissues and tumours.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
all-rac-alpha-tocopherol
Potato starch
Povidone (E1201)
Stearic acid (E570)
Silica, colloidal anhydrous (E551)
Lactose, anhydrous

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
2 years

6.4

Special precautions for storage
Do not store above 25°C and store in the original package in order to protect
from moisture and light.

6.5

Nature and contents of container
Clear transparent PVC/PVdC- Aluminium blister of 21 tablets per calender
blister strip available in packs containing 1x21, 3x21 or 6x21 tablets. Each
blister is packed in trilaminated pouch.
Clear transparent PVC/PVdC- Aluminium blister of 21 tablets per calender
blister strip available in packs containing 1x21, 3x21 or 6x21 tablets. Each
blister is packed in trilaminated pouch along with 2g molecular sieve.
Not all pack sizes may be marketed.

6.6

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

7

MARKETING AUTHORISATION HOLDER
Generics [UK] Limited t/a Mylan,
Station Close,
Potters Bar,
Hertfordshire
EN6 1TL

8

MARKETING AUTHORISATION NUMBER(S)
PL 04569/1342

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
15/12/2011

10

DATE OF REVISION OF THE TEXT
12/02/2017

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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