Microlite 100/20 microgram Tablets

  • Name:

    Microlite 100/20 microgram Tablets

  • Company:
    info
  • Active Ingredients:

    Ethinylestradiol, Levonorgestrel

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 23/05/19

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Summary of Product Characteristics last updated on medicines.ie: 22/5/2019

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Bayer Limited

Bayer Limited

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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 23 May 2019 PIL

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 6 - date of revision

Updated on 22 May 2019 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

SPC updated in line with new PRAC update regarding depression

Section 4.4

Depressed mood and depression

Depressed mood and depression are well-known undesirable effects of hormonal

contraceptive use (see section 4.8). Depression can be serious and is a well-known

risk factor for suicidal behaviour and suicide.

Women should be advised to contact their physician in case of mood changes and

depressive symptoms, including shortly after initiating the treatment.

Updated on 5 September 2017 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 5 September 2017 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

The text below in red has been added.

4.3 Contraindications

[…]

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

4.4 Special warnings and precautions for use

 […]

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.

[…]

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.

[…]

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, Microlite 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. Microlite can be restarted 2 weeks following completion of treatment with this combination drug regimen.

4.9 Overdose

There have been no reports of serious deleterious effect from overdose. Symptoms that may occur in this case are: nausea, vomiting and, in young girls, slight vaginal bleeding, withdrawal bleeding. Withdrawal bleeding may even occur in girls before their menarche, if they accidentally take the medicinal product. There are no antidotes and further treatment should be symptomatic.

Updated on 24 August 2017 PIL

Reasons for updating

  • New PIL for new product

Updated on 24 August 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 3 - overdose, missed or forgotten doses
  • Change to section 6 - date of revision

Updated on 29 March 2017 PIL

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 18 August 2015 PIL

Reasons for updating

  • Correction of spelling/typing errors

Updated on 30 July 2015 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text
  • 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.
  • 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 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.
  • Liver tumors (benign and malignant)

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Microlite – 1410/7/1
BP14034 & BP14065
www.medicines.ie

(Inserted Text; Deleted Text)

 

4.1          Therapeutic indications

Oral contraception

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

 

4.2          Posology and method of administration

Dosage regimen

How to start Microlite

·         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). Starting on days 2-5 is allowed but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking.

 

·         Changing from a combined hormonal contraceptive (combined oral contraceptive/COC), vaginal ring or transdermal patch.

The woman should start with Microlite preferably on the day after the last hormone-containing tablet of her previous COC, but at the latest on the day following the usual tablet-free or hormone-free tablet interval of her previous COC.  In case a vaginal ring or transdermal patch has been used, the woman should start using Microlite preferably on the day of removal of the last ring or patch of a cycle pack, but at the latest when the next application would have been due.

 

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

The woman may switch any day from the minipill (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 does not need additional contraceptive measures. 

 

·         Following delivery or second-trimester abortion

For breastfeeding women see Section 4.6

Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet-taking.  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. 

 

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.

Advice in case of gastro-intestinal disturbances

In case of severe gastro-intestinal disturbance, absorption may not be complete and additional contraceptive measures should be taken.

If vomiting or severe diarrhoea occurs within 3-4 hours after tablet-taking, the advice concerning missed tablets, as given in 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) needed from another pack.

 

4.3          Contraindications

Combind oralhormonal contraceptives (COCsCHCs) should not be used in the presence of any of the following conditionslisted below. Should any of the conditions appear for the first time during COCCHC use, the 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])

o   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

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

·         Presence or history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident.

·         Presence or history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris).

·         The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see “Special warnings and precautions for use”).

·         History of migraine with focal neurological symptoms.

·         Diabetes mellitus with vascular involvement.

·         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.

·         Known or suspected pregnancy.

·         Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

 

 

4.4          Special warnings and precautions for use

Warnings

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

If any of the conditions/risk factors mentioned below is present, the benefits of COC use should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether COC use should be discontinued.

 

Risk of venous thromboembolism (VTE)

Circulatory Disorders

Epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, deep venous thrombosis, pulmonary embolism and of cerebrovascular accidents. These events occur rarely.

The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism (VTE) compared with no use. The decision to use Microlite should be taken after a discussion with the woman to ensure she understands the risk of VTE with Microlite, 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.

 

Epidemiological studies have shown that the incidence of VTE in users of oral contraceptives with low oestrogen content (<50 µg ethinylestradiol) ranges from about 20 to 40 cases per 100,000 women-years, but this risk estimate varies according to the progestogen. This compares with 5 to 10 cases per 100,000 women-years for non-users. The use of any combined oral contraceptive (COC) carries an increased risk of venous thromboembolism (VTE) compared with no use.

The excess risk of VTE is highest during the first year a woman initially starts using a COC or when she restarts COC use after a pill-free interval of at least a month. This increased risk is less than the risk of VTE associated with pregnancy, which is estimated as 60 cases per 100,000 pregnancies.

VTE is fatal in 1-2 % of the cases.

The overall absolute risk (incidence) of VTE for levonorgestrel containing combined oral contraceptives with 30 µg ethinylestradiol is approximately 20 cases per 100,000 women-years of use. Epidemiological studies have also associated the use of combined COCs with an increased risk for myocardial infarction, transient ischaemic attack and for stroke.

 

Extremely rarely, thrombosis has been reported to occur in CHC users in in other blood vessels e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs..

 

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).

Microlite 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 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.

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.

Antithrombotic treatment should be considered if Microlite 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). Microlite 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.

 

Symptoms of venous or arterial thrombotic/thromboembolic events or of a cerebrovascular accident can include:

·         unusual unilateral leg pain and/or swelling

·         sudden severe pain in the chest, whether or not it radiates to the left arm

·         sudden breathlessness

·         sudden onset of coughing

·         vertigo

·         collapse with or without focal seizure

·         weakness or very marked numbness suddenly affecting one side or one part of the body

·         motor disturbances

·         ‘acute’ abdomen.

 

Symptoms of deep venous thrombosis (DVT) can include: unilateral swelling of the leg 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 discolored 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 bring up blood; sharp chest pain which may increase with deep breathing; sense of anxiety; 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).

 

An arterial thromboembolic event can include cerebrovascular accident, vascular occlusion or myocardial infarction (MI).  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 confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no known cause; loss of consciousness or fainting with or without seizure. Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity; acute abdomen.

 

Symptoms of 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; fullness, indigestion or choking feeling; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats.

 

Arterial thromboembolic events may be life threatening or may have a fatal outcome.

 

The potential for an increased synergistic risk of thrombosis should be considered in women who possess a combination of risk factors or exhibit a greater severity of an individual risk factor. This increased risk may be greater than a simple cumulative risk of the factors. A COC should not be prescribed in case of a negative risk benefit assessment (see section 4.3)

 

The risk for venous thromboembolic complications in COCs users increases with:

·         increasing age

·         a positive family history (venous thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use.

·         prolonged immobilisation, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue the pill (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilisation.

·         obesity (body mass index over 30 kg/m²).

·         there is no consensus about the possible role of varicose veins  and superficial thrombophlebitis in the onset or progression of venous thrombosis.

The risk of arterial thromboembolic complications or of a cerebrovascular accident in COC users increases with:

·           increasing age

·           smoking (women over 35 years should be strongly advised not to smoke if they wish to use an COC)

·           dyslipoproteinemia

·           hypertension

·           migraine

·           valvular heart disease

·         atrial fibrillation

 

The increased risk of thromboembolism in the puerperium must be considered (for information on “Pregnancy and lactation” see Section 4.6);

 

Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) and sickle cell disease.

 

An increase in the frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.

 

...

 

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.

 

 

Malignancies may be life-threatening or may have a fatal outcome.

 

Other conditions

 

 

Herbal preparations containing St. John’s Wort (Hypericum perforatum) should not be used while taking Microlite due to the risk of decreased plasma concentrations and reduced clinical effects of Microlite (see section 4.5 Interactions).

 

Medical examination/consultation

It is important to draw a woman’s attention to the information on venous and arterial thrombosis, including the risk of Microlite 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.

Women should be advised that oral hormonal contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.

 

4.5          Interaction with other medicinal products and other forms of interaction

 

Effects of other medicaments medicinal products on Microlite

Interactions of other drugs (enzyme inducers, some antibiotics) with oral contraceptives may impair the contraceptive efficacy and/orInteractions 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 contraceptive failure. Women on treatment with any of these drugs should temporarily use a barrier method in addition to the COC or choose another method of contraception.  With liver enzyme-inducing drugs, tThe barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation.

 

Women on treatment with antibiotics (except rifampicin and griseofulvin) should use the barrier method during the use of the antibiotics and until 7 days after discontinuation.  If the period during which the barrier method is used runs beyond the end of the tablets in the COC pack, the next COC pack should be started without the usual tablet-free interval.

 

Substances diminishing the efficacy of COCs (enzyme-inducers and  antibiotics)Substances increasing the clearance of COCs (dimished efficacy of COCs by enzyme –induction), e.g.:

 

Enzyme induction (increase of hepatic metabolism): Interactions can occur with drugs that induce hepatic microsomal enzymes which can result in increased clearance of sex hormones (e.g. pPhenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St. John’s wort.

4.6          Pregnancy and lactation

 

Pregnancy

Microlite is not indicated during pregnancy. If pregnancy occurs during treatment with Microlite, 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 Microlite (see section 4.2 and 4.4)

4.8          Undesirable effects

 

Summary of the safety profile

The most commonly reported adverse reactions with Microlite 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.

Tabulated list of adverse reactions

Side effects that have been reported in users of COCs but for which the association has been neither confirmed nor refuted are *:

System Organ Class

(MedDRA)

Common ( ³ 1/100 )

Uncommon

( ³ 1/1000 and

< 1/100 )

Rare ( < 1/1000 )

Eye disorders

 

 

Contact lens intolerance

Gastrointestinal disorders

Nausea,

Abdominal pain

Vomiting,

Diarrhoea

 

Immune system disorders

 

 

Hypersensitivity

Investigations

Weight increased

 

Weight decreased

Metabolism and nutrition disorders

 

Fluid retention

 

Nervous system disorders

Headache

Migraine

 

Psychiatric disorders

Depressed mood,

Mood altered

 

Libido decreased

Libido increased

Reproductive system and breast disorders

Breast pain,

Breast tenderness

Breast hypertrophy

Vaginal discharge, Breast discharge

Skin and subcutaneous tissue disorders

 

Rash,

Urticaria

Erythema nodosum, Erythema multiforme

Vascular system disorders

 

 

Arterial thromboembolism (ATE),

Venous thromboembolism (VTE)**

* The most appropriate MedDRA term (version 12.0) to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed but should be taken into account as well.

 

**           - Estimated frequency, from epidemiological studies encompassing
a group of combined oral contraceptives.
- ‘Venous and arterial thromboembolic events’ summarizes the following Medical Entities:
Peripheral deep venous occlusion, thrombosis and embolism/Pulmonary vascular occlusion,
thrombosis, embolism and infarction/Myocardial infarction/Cerebral infarction and stroke not specified as hemorrhagic

 

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.

Adverse reactions with very low frequency or with delayed onset of symptoms which are considered to be related to the group of combined oral contraceptives are listed below (see also sections ”Contraindications”, “Special warnings and precautions for use”):

Tumors

  • 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.
  • Liver tumors (benign and malignant)

Other conditions

·        Women with hypertriglyceridemia (increased risk of pancreatitis when using COCs)

·        Hypertension

·        Occurrence or deterioration of conditions for which association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss

·        In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema

·        Liver function disturbances

·        Changes in glucose tolerance or effect on peripheral insulin resistance

·        Crohn’s disease, ulcerative colitis.

·        Chloasma

Interactions

Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme inducers) with oral contraceptives (see section ‘Interaction with other medicinal products and other forms of interaction’).

 

The following serious adverse events have been reported in women using COCs, which are discussed in section ‘Special warnings and precautions for use’:

·         Venous thromboembolic disorders

·         Arterial thromboembolic disorders

·         Cerebrovascular accidents

·         Hypertension

·         Hypertriglyceridemia

·         Changes in glucose tolerance or effect on peripheral insulin resistance

·         Liver tumours (benign and malignant)

·         Liver function disturbances

·         Chloasma

·         In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema

·         Occurrence or deterioration of conditions for which association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss, Crohn’s disease, ulcerative colitis, cervical cancer

 

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 ‘Contraindications’ and ‘Special warnings and precautions for use’.

 

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie

 

5              Pharmacological properties

5.1          Pharmacodynamic properties

Post Authorization Safety Studies (PASS) have A large, prospective 3-armed cohort study has shown that the frequency of VTE diagnosis ranges between 8 to 107-10  per 10,000 woman years in low estrogen dose (< 50 µg ethinylestradiol) COC users. The most recent data suggest that the frequency of VTE diagnosis is approximately 4.4 per 10,000 woman years in non-pregnant non-COC users, and ranges between  20 to 30 per 10,000 pregnant women or post partum.

 

5.2          Pharmacokinetic properties

Levonorgestrel

Metabolism

Levonorgestrel is extensively metabolized. The major metabolites in plasma are the unconjugated and conjugated forms of 3a, 5b-tetrahydrolevonorgestrel. Based on in vitro and in vivo studies, CYP3A4 is the main enzyme involved in the metabolism of levonorgestrel. Levonorgestrel is completely metabolised by the known pathways of steroid metabolism.  The clearance rate from serum is approximately 1.0 ml/min/kg.

 

10           Date of revision of the text

March 2013July 2015

Updated on 30 July 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to side-effects
  • Change to drug interactions
  • Change to date of revision
  • Change to improve clarity and readability
  • Addition of information on reporting a side effect.

Updated on 2 May 2013 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4.2. Posology and method of administration

 Advice in case of gastro-intestinal disturbances

If vomiting or severe diarrhoea occurs within 3-4 hours

 

4.3 Contraindications

·      Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

 

4.4 Special warnings and precautions for use

Circulatory Disorders

 

Epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism and of cerebrovascular accidents. These events occur rarely.

Epidemiological studies have shown that the incidence of VTE in users of oral contraceptives with low oestrogen content (<50 µg ethinylestradiol) ranges from about 20 to 40 cases per 100,000 women-years, but this risk estimate varies according to the progestogen. This compares with 5 to 10 cases per 100,000 women-years for non-users. The use of any combined oral contraceptive (COC) carries an increased risk of venous thromboembolism (VTE) compared with no use.

The excess risk of VTE is highest during the first year a woman initially starts using a COC or when she restarts COC use after a pill-free interval of at least a month. This increased risk is less than the risk of VTE associated with pregnancy, which is estimated as 60 cases per 100,000 pregnancies.

VTE is fatal in 1-2 % of the cases.

The overall absolute risk (incidence) of VTE for levonorgestrel containing combined oral contraceptives with 30 µg ethinylestradiol is approximately 20 cases per 100,000 women-years of use. Epidemiological studies have also associated the use of combined COCs with an increased risk for myocardial infarction, transient ischaemic attack and for stroke.

The risk of VTE is highest during the first year of use. This increased risk is present after initially starting a COC or restarting (following a 4 week or greater pill free interval) the same or a different COC. Date from a large, prospective 3-armed cohort study suggest that this increased risk is mainly present during the first 3 months.

Overall the risk for venous thromboembolism (VTE) in users of low estrogen dose (<50µg ethinylestradiol) COCs is two-to-threefold higher than for non-users of COCs who are not pregnant and remains lower than the risk associated with pregnancy and delivery.

VTE may be fatal (in 1-2% of the cases).

Venous thromboembolism (VTE), manifesting as deep venous thrombosis and/or pulmonary embolism, may occur during the use of all COCs.

Extremely rarely, thrombosis has been reported to occur in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.

Symptoms of venous or arterial thrombotic/thromboembolic events or of a cerebrovascular accident can include:

·         unusual unilateral leg pain and/or swelling

·         sudden severe pain in the chest, whether or not it radiates to the left arm

·         sudden breathlessness

·         sudden onset of coughing

·         vertigo

·         collapse with or without focal seizure

·         weakness or very marked numbness suddenly affecting one side or one part of the body

·         motor disturbances

·         ‘acute’ abdomen.

 

 

Symptoms of 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; fullness, indigestion or choking feeling; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats.

Arterial thromboembolic events may be fatal.

The risk for venous thromboembolic complications in COCs users increases with:

·         increasing age

·         a positive family history (venous thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use.

·         prolonged immobilisation, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue the pill (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilisation.

·         obesity (body mass index over 30 kg/m²).

·         there is no consensus about the possible role of varicose veins  and superficial thrombophlebitis in the onset or progression of venous thrombosis.

The risk of arterial thromboembolic complications or of a cerebrovascular accident in COC users increases with:

·         increasing age

·         smoking (women over 35 years should be strongly advised not to smoke if they wish to use an COC)

·         dyslipoproteinemia

·         hypertension

·         migraine

·         valvular heart disease

·         atrial fibrillation

The risk of venous or arterial thrombotic/thromboembolic events or of a cerebrovascular accident increases with:

     age;

     obesity (body mass index over 30 kg/m²);

     a positive family history (i.e. venous or arterial thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is known or suspected, the woman should be referred to a specialist for advice before deciding about any COC use;

     prolonged immobilization, major surgery, any surgery to the legs or major trauma. In these situations it is advisable to discontinue COC use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilization.

     smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age);

     dyslipoproteinemia;

     hypertension;

     migraine;

     valvular heart disease;

     atrial fibrillation;

 

There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.

 

Tumours

An increased risk of cervical cancer in long-term users of COCs has been reported in some epidemiological studies, but there continues to be controversy about the extent to which this finding is attributable to the confounding effects of sexual behavior and other factors such as human papilloma virus (HPV).

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.

 

Other conditions

...

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 first during pregnancy or 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 regimen in diabetics using low-dose COCs (containing < 0.05 mg ethinylestradiol). However, diabetic women should be carefully observed while taking COCs monitored, particularly in the early stage of COC use.

 

Crohn’s Worsening of crohn’s disease and of ulcerative colitis have has been associated with reported during COC use.

 

Medical examination/consultation

Prior to the initiation or reinstitution of COC use, a .A complete medical history and physical examination should be taken prior to the initiation or reinstitution of COC use, guided by the contraindications (Section 4.3) and warnings (section ‘Warnings’) and should be repeated periodically and pregnancy must be ruled out. Periodic medical assessment is also of importance because contraindications (e.g. a transient ischaemic attack, etc.) or risk factors (e.g. a family history of venous or arterial thrombosis) may appear for the first time during the use of a COC.

 

 

Reduced efficacy

The efficacy of COCs may be reduced in the event of e.g. missed tablets (section ‘Management of missed tablets’), vomiting or diarrhea gastro-intestinal disturbances (section ‘Advice in case of  gastro-intestinal disturbances’) during tablet taking or concomitant medication (Section 4.5).

 

4.5 Interaction with other medicinal products and other forms of interaction

Effects of other medicaments on Logynon

Interactions of other drugs (enzyme inducers, some antibiotics) with oral contraceptives may impair the contraceptive efficacy and/or may lead to breakthrough bleeding and/or contraceptive failure. Women on treatment with any of these drugs should temporarily use a barrier method in addition to the COC or choose another method of contraception. With microsomal liver enzyme-inducing drugs, the barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation.

Women on treatment with antibiotics (except rifampicin and griseofulvin) should use the barrier method during the use of the antibiotics and until 7 days after discontinuation. If the period during which the barrier method is used runs beyond the end of the tablets in the COC pack, the next COC pack should be started without the usual tablet-free interval.

Substances diminishing the efficacy of COCs (enzyme-inducers and  antibiotics)

 

Enzyme induction (increase of hepatic metabolism): Interactions can occur with drugs that induce hepatic microsomal enzymes which can result…

Troleandomycin may increase the risk of intrahepatic cholestasis during coadministration with COCs.

 

4.6 Pregnancy and lactation

Lactation

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 with the milk. These amounts may affect the child.

 

10. Date of Revision of the Text

November 2010 March 2013

Updated on 24 April 2013 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to date of revision
  • Change to further information section

Updated on 1 June 2011 PIL

Reasons for updating

  • Introduction of new pack/pack size

Updated on 1 February 2011 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to instructions about missed dose
  • Change to side-effects
  • Change of special precautions for disposal
  • Change due to user-testing of patient information

Updated on 26 November 2010 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 

Superceded text

Updated text

4.1 Therapeutic indications

 

4.1 Therapeutic indications

 

Hormonal contraception.

Oral contraception

4.2 Posology and method of administration

 

4.2 Posology and method of administration

 

4.2.1 How to take Microlite

Combined oral contraceptives, when taken correctly, have a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly.

 

Tablets must be taken in the order directed on the package every day at about the same time with some liquid as needed. 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.

 

4.2.2 How to start Microlite

  • 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).

 

Starting on days 2-5 is allowed but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking.

 

  • Changing from a combined hormonal contraceptive (combined oral contraceptive/COC), vaginal ring or transdermal patch.

 

The woman should start with Microlite 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 transdermal patch has been used, the woman should start using Microlite preferably on the day of removal but at the latest when the next application would have been due.

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

The woman may switch any day from the minipill (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

For breastfeeding women see Section 4.6

Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet-taking.  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. 

 

4.2.3 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. tablet-taking must never be discontinued for longer than 7 days.
  2. 7 days of uninterrupted tablet-taking are required to attain adequate suppression of the hypothalamic-pituitary-ovarian- axis.

Accordingly the following advice can be given in daily practice.

 

If the woman forgets to take an active Microlite tablet then it must be taken within 12 hours of the usual time for taking it. If a missed tablet is not taken within 12 hours then it should be taken when remembered and the remaining tablets taken as usual with extra non-hormonal contraceptive measures (except rhythm or temperature method) used for the next 7 days. If these seven days extend beyond the end of the pack then the next pack of tablets should be commenced at once with no tablet-free interval. 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 during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be excluded before resuming with the next pack.

 

4.2.4 Advice in case of gastro-intestinal disturbances 

In case of severe gastro-intestinal disturbance, absorption may not be complete and additional contraceptive measures should be taken.

 

If vomiting occurs within 3-4 hours after tablet-taking, the advice concerning missed tablets, as given in Section 4.2.3, is applicable. Tablet-taking from the current pack should be continued. Additional non-hormonal 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 overrun the end of a pack, the next pack should be started without a break. 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 during the tablet-free interval following the end of the second pack, the possibility of pregnancy must be ruled out before resuming with the next pack. Other methods of contraception should be considered if the gastro-intestinal disorder is likely to be prolonged.

 

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.

 

In case of persisting or recurrent gastrointestinal disturbances, additional contraceptive measures should be taken and the physician should be informed.

 

4.2.5 How to shift periods or how to delay a period

To delay a period the woman should continue with another pack of Microlite 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 Microlite 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 second pack (just as when delaying a period). 

 

Method of administration

Oral use

 

Dosage regimen

 

How to take Microlite

 

Combined oral contraceptives, when taken correctly, have a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly.

 

Tablets must be taken in the order directed on the package every day at about the same time with some liquid as needed. 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 coated tablet and may not have finished before the next pack is started.

 

How to start Microlite

 

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). Starting on days 2-5 is allowed but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet-taking.

 

Changing from a combined hormonal contraceptive (combined oral contraceptive/COC), vaginal ring or transdermal patch.

The woman should start with Microlite preferably on the day after the last hormone-containing tablet of her previous COC, but at the latest on the day following the usual tablet-free or hormone-free tablet interval of her previous COC.  In case a vaginal ring or transdermal patch has been used, the woman should start using Microlite preferably on the day of removal but at the latest when the next application would have been due.

 

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

The woman may switch any day from the minipill (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

For breastfeeding women see Section 4.6

Women should be advised to start at day 21 to 28 after delivery or second-trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet-taking.  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. 

 

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:

3.       tablet-taking must never be discontinued for longer than 7 days.

4.       7 days of uninterrupted tablet-taking are required to attain adequate suppression of the hypothalamic-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 this is not the case, or if she missed more than 1 tablet, the woman should be advised to use extra precautions for 7 days.

 

·     Week 3

The risk of reduced reliability is imminent because of the forthcoming tablet-free 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 therefore 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, the woman should be advised to follow the first of these two options and to use extra 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 pack must be started as soon as the current 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 woman may also be advised to discontinue tablet-taking from the current 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 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 gastro-intestinal disturbances

 In case of severe gastro-intestinal disturbance, absorption may not be complete and additional contraceptive measures should be taken.

 

If vomiting occurs within 3-4 hours after tablet-taking, the advice concerning missed tablets, as given in 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) needed from another pack.

 

In case of persisting or recurrent gastrointestinal disturbances, additional contraceptive measures should be taken and the physician should be informed.

 

How to shift periods or how to delay a period

To delay a period the woman should continue with another pack of Microlite 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 Microlite 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 second pack (just as when delaying a period). 

 

Additional information on special populations

Children and adolescents
Miranova is only indicated after menarche.

Geriatric patients
Not applicable. Miranova is not indicated after menopause.

Patients with hepatic impairment
Miranova is contraindicated in women with severe hepatic diseases. See also section ‘Contraindications’.

Patients with renal impairment
Miranova has not been specifically studied in renally impaired patients. Available data do not suggest a change in treatment in this patient population.

 

 

4.3 Contraindications

 

4.3 Contraindications

 

Combined oral contraceptives (COCs) should not be used in the presence of any of the conditions listed below.  Should any of the conditions appear for the first time during COC use, the product should be stopped immediately.

 

  • Presence or history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident.
  • Presence or history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris).
  • History of migraine with focal neurological symptoms.
  • Diabetes mellitus with vascular involvement.
  • The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see under “Special warnings and precautions for use”).
  • Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
  • 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.
  • Known or suspected pregnancy.
  • Hypersensitivity to the active substances or to any of the excipients.

 

Combined oral contraceptives (COCs) should not be used in the presence of any of the conditions listed below.  Should any of the conditions appear for the first time during COC use, the product should be stopped immediately.

  • Presence or history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident.
  • Presence or history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris).
  • The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see “Special warnings and precautions for use”).
  • History of migraine with focal neurological symptoms.
  • Diabetes mellitus with vascular involvement.
  • 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.
  • Known or suspected pregnancy.
  • Hypersensitivity to the active substances or to any of the excipients.

 

4.4 Special warnings and precautions for use

 

4.4 Special warnings and precautions for use

 

4.4.1 Warnings

If any of the conditions/risk factors mentioned below is present, the benefits of COC use should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether COC use should be discontinued.

 

·                Circulatory Disorders

 Epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism. These events occur rarely.

 

Venous thromboembolism (VTE), manifesting as deep venous thrombosis and/or pulmonary embolism, may occur during the use of all COCs. The risk for venous thromboembolism is highest during the first year a woman ever uses a COC. The approximate incidence of VTE in users of low oestrogen dose (< 0.05 mg ethinylestradiol) OCs is up to 4 per 10 000 woman years compared to 0.5 – 3 per 10 000 woman years in non-OC users. The incidence of VTE associated with pregnancy is 6 per 10 000 pregnant woman years.

 

 Extremely rarely, thrombosis has been reported to occur in other blood vessels e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.

 

Symptoms of venous or arterial thrombotic/thromboembolic events or of a cerebrovascular accident can include: unilateral leg pain and / or swelling: sudden severe pain in the chest, whether or not it radiates to the left arm; sudden breathlessness, sudden onset of coughing; any unusual, severe, prolonged headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; vertigo; collapse with or without focal seizure; weakness or very marked numbness suddenly affecting one side or one part of the body; motor disturbances; “acute” abdomen.

 

The risk of venous or arterial thrombotic/thromboembolic events or of a cerebrovascular accident increases with:

-          Age;

-          Smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age);

- A positive family history (i.e. venous thromboembolism ever in a sibling or parent    at a relatively early age).  If a hereditary predisposition is suspected the woman should be referred to a specialist for advice before deciding about any COC use;

-          Obesity (body mass index over 30 kg/m2);

-          Dyslipoproteinaemia

-          Hypertension

-          Migraine

-          Valvular heart disease

-          Atrial fibrillation

-          Prolonged immobilization, major surgery, any surgery to the legs or major trauma. In these situations it is advisable to discontinue COC use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilization;

-          There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.

-          The increased risk of venous thromboembolism in the puerperium must be considered (for information on “Pregnancy and lactation” see Section 4.6);

 

Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) and sickle cell disease.

 

An increase in the frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.

 

Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyperhomocysteinaemia, antithrombin – III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

 

When considering risk/benefit, the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with low-dose COCs (< 0.05 mg ethinylestradiol).

 

·         Tumours

Some epidemiological studies indicate that the long-term use of oral contraceptives (> 5 years) displays a risk factor for the development of cervical cancer in women infected with human papillomavirus (HPV).  However, there continues to be controversy about the extent to which this finding is influenced by other factors (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 COCs.  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 COC users 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 COC users, 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 life-threatening 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 hypertriglyceridemia, 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.  However, if a 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 uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss, depression. 

In women with hereditary angioedema, exogenous oestrogens 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 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 of 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.

Crohn’s disease and ulcerative colitis have been associated with COC 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 while taking COCs. 

 

This product contains lactose and sucrose. Patients with rare hereditary problems of galactose intolerance, fructose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

 

Herbal preparations containing St. John’s Wort (Hypericum perforatum) should not be used while taking Microlite due to the risk of decreased plasma concentrations and reduced clinical effects of Microlite (see 4.5 Interactions).

 

4.4.2 Medical examination/consultation

A complete medical history and physical examination should be taken prior to the initiation or reinstitution of COC use, guided by the contraindications (Section 4.3) and warnings (Section 4.4.1) and should be repeated periodically.  Periodic medical assessment is also of importance because contraindications (e.g. a transient ischaemic attack, etc.) or risk factors (e.g. a family history of venous or arterial thrombosis) may appear for the first time during the use of a COC.  The frequency and nature of these assessments should be based on established practice guidelines and be adapted to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology. 

Women should be advised that oral contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases. 

  4.4.3 Reduced efficacy

The efficacy of COCs may be reduced in the event of e.g. missed tablets (Section 4.2.3), gastro-intestinal disturbances (Section 4.2.4) or concomitant medication (Section 4.5). 

4.4.4 Reduced cycle control

With all COCs, 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.  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.

 

Warnings

 

If any of the conditions/risk factors mentioned below is present, the benefits of COC use should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether COC use should be discontinued.

 

Circulatory Disorders

 

Epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, deep venous thrombosis, pulmonary embolism and of cerebrovascular accidents. These events occur rarely.

 

The risk of VTE is highest during the first year of use. This increased risk is present after initially starting a COC or restarting (following a 4 week or greater pill free interval) the same or a different COC. Data from a large, prospective 3-armed cohort study suggest that this increased risk is mainly present during the first 3 months.

Overall the risk for venous thromboembolism (VTE) in users of low estrogen dose (< 50 µg  ethinylestradiol) COCs is two to threefold higher than for non-users of COCs who are not pregnant and remains lower than the risk associated with pregnancy and delivery.

VTE may be fatal (in 1-2 % of the cases).

Venous thromboembolism (VTE), manifesting as deep venous thrombosis and/or pulmonary embolism, may occur during the use of all COCs.

 

Extremely rarely, thrombosis has been reported to occur in other blood vessels e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.

 

Symptoms of deep venous thrombosis (DVT) can include: unilateral swelling of the leg 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 discolored 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 bring up blood; sharp chest pain which may increase with deep breathing; sense of anxiety; 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).

An arterial thromboembolic event can include cerebrovascular accident, vascular occlusion or myocardial infarction (MI).  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 confusion, trouble speaking or understanding; sudden trouble seeing in one or both eyes; sudden trouble walking, dizziness, loss of balance or coordination; sudden, severe or prolonged headache with no known cause; loss of consciousness or fainting with or without seizure. Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity; acute abdomen.

Symptoms of 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; fullness, indigestion or choking feeling; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats.

Arterial thromboembolic events may be fatal.

 

The risk of venous or arterial thrombotic/thromboembolic events or of a cerebrovascular accident increases with:

-          Age;

-          Obesity (body mass index over 30 kg/m2);

-          A positive family history (i.e. venous thromboembolism ever in a sibling or parent    at a relatively early age).  If a hereditary predisposition is suspected the woman should be referred to a specialist for advice before deciding about any COC use;

-          Prolonged immobilization, major surgery, any surgery to the legs or major trauma. In these situations it is advisable to discontinue COC use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilization;

-          Smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age);

-          Dyslipoproteinaemia

-          Hypertension

-          Migraine

-          Valvular heart disease

-          Atrial fibrillation

 

There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.

 

The increased risk of thromboembolism in the puerperium must be considered (for information on “Pregnancy and lactation” see Section 4.6);

 

Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) and sickle cell disease.

 

An increase in the frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.

 

Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyperhomocysteinaemia, antithrombin – III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

 

When considering risk/benefit, the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with low-dose COCs (< 0.05 mg ethinylestradiol).

 

Tumours

 

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.

 

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 COCs.  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 COC users 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 COC users, 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 life-threatening intra-abdominal haemorrhages.  A liver 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 hypertriglyceridemia, 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.  However, if a 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 uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss, depression. 

In women with hereditary angioedema, exogenous oestrogens 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 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 of 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.

 

Crohn’s disease and ulcerative colitis have been associated with COC 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 while taking COCs. 

 

Each coated tablet of this medicinal product contains 33 mg lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption who are on a lactose-free diet should take this amount into consideration.

 

Herbal preparations containing St. John’s Wort (Hypericum perforatum) should not be used while taking Microlite due to the risk of decreased plasma concentrations and reduced clinical effects of Microlite (see 4.5 Interactions).

 

Medical examination/consultation

A complete medical history and physical examination should be taken prior to the initiation or reinstitution of COC use, guided by the contraindications (Section 4.3) and warnings (section ‘Warnings‘), and should be repeated periodically.  Periodic medical assessment is also of importance because contraindications (e.g. a transient ischaemic attack, etc.) or risk factors (e.g. a family history of venous or arterial thrombosis) may appear for the first time during the use of a COC.  The frequency and nature of these assessments should be based on established practice guidelines and be adapted to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology. 

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 (section ‘Management of missed tablets’), gastro-intestinal disturbances (section ‘Advice in case of  gastro-intestinal disturbances’) during tablet taking or concomitant medication (Section 4.5). 

 

Reduced cycle control

With all COCs, 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.  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.

 

4.5 Interaction with other medicinal products and other forms of interaction

 

4.5 Interaction with other medicinal products and other forms of interaction

 

  • Interactions

Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.

 

Hepatic metabolism: Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of sex hormones (e.g. phenytoin,   barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate,  griseofulvin and products containing St. John’s Wort.

 

Also HIV protease (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) and combinations of them, have been reported to potentially affect hepatic metabolism.

 

Interference with Enterohepatic Circulation:  Some clinical reports suggest that enterohepatic circulation of oestrogens may decrease when certain antibiotic agents are given, which may reduce ethinylestradiol concentrations (e.g. penicillins, tetracyclines).

 

Women on treatment with any of these drugs should temporarily use a barrier method in addition to the COC or choose another method of contraception.  With microsomal enzyme-inducing drugs, the barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation.  Women on treatment with antibiotics (except rifampicin and griseofulvin) should use the barrier method until 7 days after discontinuation.  If the period during which the barrier method is used runs beyond the end of the tablets in a COC pack, the next COC pack should be started without the usual tablet-free interval. 

Oral contraceptives may affect the metabolism of certain other drugs.  Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine). 

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions. 

 

  • 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.

 

Effects of other medicaments on Microlite

Interactions of other drugs (enzyme inducers, some antibiotics) with oral contraceptives may lead to breakthrough bleeding and/or contraceptive failure. Women on treatment with any of these drugs should temporarily use a barrier method in addition to the COC or choose another method of contraception.  With microsomal enzyme-inducing drugs, the barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation. 

 

Women on treatment with antibiotics (except rifampicin and griseofulvin) should use the barrier method until 7 days after discontinuation.  If the period during which the barrier method is used runs beyond the end of the tablets in the COC pack, the next COC pack should be started without the usual tablet-free interval. 

 

Substances diminishing the efficacy of COCs (enzyme-inducers and  antibiotics)

 

·         Enzyme induction (increase of hepatic metabolism): Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of sex hormones (e.g. phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St. John’s wort).

 

Also HIV protease (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and combinations of them, have been reported to potentially increase hepatic metabolism.

 

·         Antibiotics (interference with enterohepatic circulation): Some clinical reports suggest that enterohepatic circulation of estrogens may decrease when certain antibiotic agents are given, which may reduce ethinylestradiol concentrations (e.g. penicillins, tetracyclines).

 

Effects of COCs on other medicaments

Oral contraceptives may affect the metabolism of certain other drugs.  Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).

 

Other forms of interactions

·       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.

 

Note: The prescribing information of concomitant medications should be consulted to identify potential interactions. 

 

4.6 Pregnancy and lactation

 

4.6 Pregnancy and lactation

 

Microlite is not indicated during pregnancy. If pregnancy occurs during medication with Microlite, further intake should 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. 

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 with the milk but there is no evidence that this adversely affects infant health. 

 

Pregnancy

Microlite is not indicated during pregnancy. If pregnancy occurs during treatment with Microlite, 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. 

 

Lactation

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 with the milk. 

 

4.7 Effects on ability to drive and use machines

 

4.7 Effects on ability to drive and use machines

 

No observed effects.

 

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

 

4.8 Undesirable effects

 

The most serious undesirable effects associated with the use of COCs are listed in section 4.4.1.

 

Other side effects that have been reported in users of COCs are*:

 

Side effects that have been reported in users of COCs but for which the association has been neither confirmed nor refuted are *:

 

Note: no change to table

Note: no change to table

* The most appropriate MedDRA term (version 7.0) to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed but should be taken into account as well.

 

In women with hereditary angioedema exogenous oestrogens may induce or exacerbate symptoms of angioedema.

 

* The most appropriate MedDRA term (version 12.0) to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed but should be taken into account as well.

 

The following serious adverse events have been reported in women using COCs, which are discussed in section ‘Special warnings and precautions for use’:

·         Venous thromboembolic disorders

·         Arterial thromboembolic disorders

·         Cerebrovascular accidents

·         Hypertension

·         Hypertriglyceridemia

·         Changes in glucose tolerance or effect on peripheral insulin resistance

·         Liver tumours (benign and malignant)

·         Liver function disturbances

·         Chloasma

·         In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema

·         Occurrence or deterioration of conditions for which association with COC use is not conclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; hemolytic uremic syndrome; Sydenham’s chorea; herpes gestationis; otosclerosis-related hearing loss, Crohn’s disease, ulcerative colitis, cervical cancer

 

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 ‘Contraindications’ and ‘Special warnings and precautions for use’. 

 

 

5.1 Pharmacodynamic properties

 

5.1 Pharmacodynamic properties

 

The contraceptive effect of COCs is based on the interaction of various factors, the most important of which are seen as the inhibition of ovulation and the changes in the cervical secretion. As well as protection against pregnancy, COCs have several positive properties which, next to the negative properties (see Warnings, Undesirable effects), can be useful in deciding on the method of birth control. The cycle is more regular and the menstruation is often less painful and the bleeding is lighter.

 

The latter may result in a decrease in the occurrence of iron deficiency. Apart from this, there is evidence of a reduced risk of endometrial cancer and ovarian cancer. Furthermore, the higher dosed COCs (0.05 mg ethinylestradiol) have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Whether this also applies to lower-dosed COCs remains to be confirmed.

 

Pharmacotherapeutic group (ATC): Progestogens and estrogens, fixed combinations
ATC Code: G03AA

 

The contraceptive effect of COCs is based on the interaction of various factors, the most important of which are seen as the inhibition of ovulation and the changes in the cervical secretion.

 

A large, prospective 3-armed cohort study has shown that the frequency of VTE diagnosis ranges between 8 to 10 per 10,000 woman years in low estrogen dose (< 50 µg ethinylestradiol) COC users. The most recent data suggest that the frequency of VTE diagnosis is approximately 4.4 per 10,000 woman years in non-pregnant non-COC users, and ranges between  20 to 30 per 10,000 pregnant women or post partum.

 

As well as protection against pregnancy, COCs have several positive properties which, next to the negative properties (see Warnings, Undesirable effects), can be useful in deciding on the method of birth control. The cycle is more regular and the menstruation is often less painful and the bleeding is lighter.

The latter may result in a decrease in the occurrence of iron deficiency. Apart from this, there is evidence of a reduced risk of endometrial cancer and ovarian cancer. Furthermore, the higher dosed COCs (0.05 mg ethinylestradiol) have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Whether this also applies to lower-dosed COCs remains to be confirmed.

 

5.2 Pharmacokinetic properties

 

5.2 Pharmacokinetic properties

 

Only changes to the following sentence in this section:

Levonorgestrel is bound to serum albumin and to serum hormone binding globulin (SHBG).

Only changes to the following sentence in this section:

Levonorgestrel is bound to serum albumin and to sex hormone binding globulin (SHBG).

10. Date of Revision of the Text

June 2008

 

10. Date of Revision of the Text

November 2010

 

 

Updated on 28 November 2008 PIL

Reasons for updating

  • Change to date of revision
  • Change to improve clarity and readability
  • Change of contraindications
  • Change to instructions about missed dose
  • Change to side-effects
  • Change to instructions about overdose

Updated on 14 August 2008 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Please see SPC for updates as numerous sections were updated.

Updated on 5 November 2007 PIL

Reasons for updating

  • Change to date of revision
  • Change to name of manufacturer
  • Change to marketing authorisation holder

Updated on 9 October 2007 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - MA number
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 7:  Marketing authorisation has been transferred to Bayer Limited, The Atrium, Blackthorn Road, Dublin 18
 
Section 8: New MA number is 1410/7/1
 
Section 10: Date of revision is now September 2007.

Updated on 13 November 2006 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Main changes to the SPC include:

 

Section 4.4. Special Warnings and Precautions for Use

Updated information regarding the role of long-term contraceptive use on the risk of development of cervical cancer.

 

Section 4.8. Undesirable Effects

Undesirable effects have been tabulated according to the System Organ Class affected and the frequency of occurrence.

In addition, the following possible undesirable effects have been included: breast pain, breast hypertrophy, migraine, vaginal discharge, breast discharge, hypersensitivity,

Updated on 13 November 2006 PIL

Reasons for updating

  • Change to side-effects
  • Change to warnings or special precautions for use

Updated on 20 June 2006 PIL

Reasons for updating

  • Change to marketing authorisation holder

Updated on 16 June 2006 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 7. Marketing Authorisation Holder
Change of address to 72 Heather Road, Dublin 18

Updated on 26 October 2005 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 6 August 2004 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 19 February 2004 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 3 July 2003 SmPC

Reasons for updating

  • Improved electronic presentation

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 6 June 2003 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may be renewed (B)