Consumer medicine information

Microgynon 20 ED

Ethinylestradiol; Levonorgestrel

BRAND INFORMATION

Brand name

Microgynon 20 ED

Active ingredient

Ethinylestradiol; Levonorgestrel

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Microgynon 20 ED.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Microgynon 20 ED. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Microgynon 20 ED against the benefits they expect it will have for you.

If you have any concerns, or are unsure about taking this medicine, ask your doctor or pharmacist for more advice.

Keep this leaflet with the medicine. You may need to read it again.

WHAT MICROGYNON 20 ED IS USED FOR

Microgynon 20 ED is a combined oral contraceptive, commonly known as a ‘birth control pill’ or ‘the Pill’.

Microgynon 20 ED is used to prevent pregnancy.

You may also experience the following benefits:

  • more regular and lighter periods – potentially resulting in a decrease in anaemia (iron deficiency)
  • a decrease in period pain.

Some conditions such as pelvic inflammatory disease, ovarian cysts, ectopic pregnancy (where the foetus is carried outside of your womb), lumpy breasts, acne and cancer of the uterus (womb) and ovaries may be less common in women taking the Pill.

When taken correctly, Microgynon 20 ED prevents you from becoming pregnant in several ways, including:

  • inhibiting ovulation (egg release)
  • changing the cervical mucus consistency, making it more difficult for the sperm to reach the egg
  • changing the lining of the uterus, making it less suitable for implantation.

When the Pill is taken by women under close observation in clinical trials, it is more than 99% effective in preventing pregnancy. However, in real life the Pill is around 92% effective. This is because pills might have been missed, may have been taken with medicines that interfere with their effectiveness, or may not be absorbed due to vomiting or diarrhoea.

Like all oral contraceptives, Microgynon 20 ED is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted infections.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

BEFORE YOU TAKE MICROGYNON 20 ED

When you must not take it

Do not take Microgynon 20 ED if you have an allergy to:

  • ethinylestradiol and/or levonorgestrel (the active ingredients in Microgynon 20 ED)
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty in breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take Microgynon 20 ED if you have or have had a blood clot in:

  • the blood vessels of the legs (deep vein thrombosis - DVT)
  • the lungs (pulmonary embolism - PE)
  • the heart (heart attack)
  • the brain (stroke)
  • other parts of the body.

Do not take Microgynon 20 ED if you have or are concerned about an increased risk of blood clots. Blood clots are rare. Very occasionally blood clots may cause serious permanent disability, and may even be fatal.

You are more at risk of having a blood clot when you take the Pill. However, the risk of having a blood clot when taking the Pill is less than the risk of having a blood clot during pregnancy.

Do not take Microgynon 20 ED if you are concerned about an increased risk of blood clots because of age or smoking. The risk of having a heart attack or stroke increases as you get older. It also increases if you smoke. You should stop smoking when taking the Pill, especially if you are older than 35 years of age.

Do not take Microgynon 20 ED if you are taking any antiviral medicines which contain ombitasvir, paritaprevir and/or dasabuvir. These antiviral medicines are used to treat chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus (HCV)).

Do not take Microgynon 20 ED if you have, or have had:

  • any blood clotting disorders such as Protein C deficiency, Protein S deficiency, Leiden Factor V mutation, Antithrombin III deficiency or other inherited blood clotting conditions
  • a confirmed blood test showing:
    - increased levels of homocysteine
    - antiphospholipid antibodies (APLAs) e.g.anticardiolipin-antibodies and lupus anticoagulant. These may increase your risk for blood clots or pregnancy losses (miscarriage)
  • major surgery after which you have not been able to move around for a period of time
  • angina (chest pain)
  • a mini-stroke (also known as TIA or transient ischaemic attack)
  • migraine, where you have also had problems with seeing, speaking or had or weakness or numbness in any part of your body
  • high risk of blood clots due to conditions such as diabetes with blood vessel damage, severe high blood pressure or severe high or low level of fats in your blood
  • pancreatitis (an inflammation of the pancreas) associated with high levels of fatty substances in your blood
  • severe liver disease and your liver function has not returned to normal
  • cancer that may grow under the influence of sex hormones (e.g. of the breast or the genital organs)
  • a benign or malignant liver tumour
  • unexplained vaginal bleeding.

If any of these conditions appear for the first time while using the Pill, stop taking it at once and tell your doctor. In the meantime, use non-hormonal (barrier) methods of contraception (such as condoms or a diaphragm).

Do not take this medicine if you are pregnant or think you might be pregnant.

Do not give this medicine to a child.

Microgynon 20 ED is not intended for use in females whose periods have not yet started.

Do not take this medicine after the expiry date printed on the pack and blister. The expiry date is printed on the carton and on each blister after “EXP” (e.g. 11 18 refers to November 2018). The expiry date refers to the last day of that month. If it has expired return it to your pharmacist for disposal.

Do not take this medicine if the packaging is torn or shows signs of tampering. If the packaging is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if:

  • you smoke
  • you or anyone in your immediate family has had blood clots in the legs (DVT), or lungs (PE), a heart attack, a stroke, breast cancer or high cholesterol.

Tell your doctor if you have, or have had any of the following medical conditions:

  • diabetes
  • high blood pressure
  • heart valve disorders or certain heart rhythm disorders
  • migraine
  • cancer
  • hyperhomocysteinaemia, a condition characterised by high levels of the amino acid homocysteine in the blood.
  • high or low level of fats in your blood.

Ask your doctor to check if you:

  • are overweight
  • have any hereditary or acquired conditions that may make it more likely for you to get blood clots
  • have high cholesterol or triglycerides
  • have liver disease
  • have gall bladder disease
  • have jaundice (yellowing of the skin) and/or pruritus (itching of the skin) related to cholestasis (condition in which the flow of bile from the liver stops or slows)
  • have Crohn’s disease or ulcerative colitis (chronic inflammatory bowel disease)
  • have systemic lupus erythematosus (SLE – a disease affecting the skin all over the body)
  • have haemolytic uraemic syndrome (HUS – a disorder of blood coagulation causing failure of the kidneys)
  • have sickle cell disease
  • have a condition that occurred for the first time, or worsened during pregnancy or previous use of sex hormones (e.g. hearing loss, a metabolic disease called porphyria, a skin disease called herpes gestationis, a neurological disease called Sydenham’s chorea)
  • have chloasma (yellowish-brown pigmentation patches on the skin, particularly of the face) – if so, avoid exposure to the sun or ultraviolet radiation
  • have hereditary angioedema – you should see your doctor immediately if you experience symptoms of angioedema, such as swollen face, tongue and/or pharynx and/or difficulty swallowing, or hives together with difficulty in breathing.

If any of the above conditions appear for the first time, recur or worsen while taking Microgynon 20 ED, you should tell your doctor.

Tell your doctor if you are breastfeeding. Microgynon 20 ED is generally not recommended if you are breastfeeding.

Microgynon 20 ED contains lactose. If you have an intolerance to some sugars, tell your doctor before you start taking Microgynon 20 ED.

If you have not told your doctor about any of the above, tell him/her before you start taking Microgynon 20 ED.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Microgynon 20 ED may interfere with each other. These include:

  • medicines used to treat tuberculosis such as rifampicin, rifabutin
  • a class of antibiotics known as macrolides, such as clarithromycin, erythromycin
  • medicines used to treat fungal infections, such as ketoconazole, griseofulvin
  • medicines used to treat HIV, such as ritonavir, nevirapine
  • some medicines used to treat HCV, such as boceprevir, telaprevir, ombitasvir, paritaprevir, dasabuvir
  • medicines used to treat epilepsy such as phenytoin, primidone, barbiturates (e.g. phenobarbitone), carbamazepine, oxcarbazepine, topiramate, felbamate, lamotrigine
  • ciclosporin, an immunosuppressant medicine
  • etoricoxib, a medicine used to treat painful joint disease
  • melatonin, a hormone used as a sleep aid
  • midazolam, a medicine used as a sedative
  • theophylline, a medicine used to treat respiratory disease
  • tizanidine, a medicine used as a muscle relaxant
  • some medicines used to treat high blood pressure, chest pain or irregular heartbeats such as diltiazem, verapamil
  • herbal medicines containing St John’s Wort
  • grapefruit juice.

These medicines may be affected by Microgynon 20 ED, or may affect how well it works. Your doctor may need to alter the dose of your medicine, or prescribe a different medicine.

You may need to use additional barrier methods of contraception (such as condoms or a diaphragm) while you are taking any of these medicines with Microgynon 20 ED and for some time after stopping them. Your doctor will be able to tell you how long you will need to use additional contraceptive methods.

Your doctor and pharmacist have more information on medicines that you need to be careful with or avoid while taking this medicine.

HOW TO TAKE MICROGYNON 20 ED

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How to take it

Take one tablet daily at about the same time every day. You must take Microgynon 20 ED every day regardless of how often you have sex. This will also help you remember when to take it.

Swallow the tablet whole with a full glass of water. It does not matter if you take it before or after food.

Each blister pack is marked with the day of the week. Take your first pink (active) tablet from the green area on the blister pack corresponding to the day of the week.

Follow the direction of the arrows on the blister pack until all the tablets have been taken.

A period should begin 2 to 3 days after starting to take the white inactive tablets (last row) and may not have finished before the next pack is started.

Always start a new blister pack on the same day of the week as your previous pack.

Taking Microgynon 20 ED for the first time

If you are starting Microgynon 20 ED after a natural cycle, and you have not used a hormonal contraceptive in the past month, start on the first day of your period, i.e. the first day of menstrual bleeding.

You may also start on days 2-5 of your period, but in that case make sure you also use additional barrier contraceptive precautions (e.g. condoms or a cap or diaphragm with spermicide) for the first 7 days of tablet-taking.

Your doctor will advise you when to start if you:

  • are taking Microgynon 20 ED after having a baby
  • have had a miscarriage or an abortion.

Changing from another contraceptive

Changing from a combined oral contraceptive:
Start taking Microgynon 20 ED on the day after taking the last active tablet in your previous Pill pack. Bleeding may not occur until the end of the first pack of Microgynon 20 ED.

You can also switch to Microgynon 20 ED after taking one or more inactive tablets in your previous Pill pack, but no later than the day after taking the last inactive tablet.

If you are not sure which were the active/inactive tablets in your previous Pill pack, ask your doctor or pharmacist. Your previous Pill pack may have different colour tablets to those of Microgynon 20 ED.

Changing from a vaginal ring:
Start taking Microgynon 20 ED on the day of removal of the ring but at the latest when the next application would have been due.

Changing from a progestogen-only pill (‘minipill’):
Stop taking the minipill on any day and start taking Microgynon 20 ED at the same time the day after your last minipill.

You must also use additional barrier contraceptive precautions (e.g. condoms or a diaphragm) for the first 7 days of tablet-taking when having intercourse.

Changing from a progestogen-only injection, implant or intrauterine system (IUS):
Start taking Microgynon 20 ED when your next injection is due, or on the day that your implant or IUS is removed.

You must also use additional barrier contraceptive precautions (e.g. condoms or a diaphragm) for the first 7 days of tablet-taking when having intercourse.

Stopping Microgynon 20 ED

You can stop taking Microgynon 20 ED at any time. If you are considering becoming pregnant, it is recommended that you begin taking a vitamin supplement containing folic acid. It is best that you start taking folic acid tablets before you stop taking Microgynon 20 ED and not stop until your doctor advises this. Ask your doctor or pharmacist about suitable supplements. It is both safe and recommended that you take folic acid during pregnancy.

Additional contraceptive precautions

When additional contraceptive precautions are required you should either abstain from sex, or use a barrier method of contraception, a cap (or diaphragm) plus spermicide, or a condom. Rhythm methods are not advised as the Pill disrupts the cyclical changes associated with the natural menstrual cycle e.g. changes in temperature and cervical mucus.

If you forget to take Microgynon 20 ED

If you miss a tablet and take the missed tablet within 12 hours of missing it, you should still be protected against pregnancy.

If you are more than 12 hours late follow these detailed instructions:

For Microgynon 20 ED to be most effective, pink active tablets need to be taken uninterrupted for 7 days.

If you have been taking the pink active tablets for 7 uninterrupted days and miss a pink active tablet, take the missed tablet as soon as you remember, then go back to taking your Pill as you would normally, even if this means taking two tablets in one day, at the same time. You should still be protected against pregnancy.

The chance of pregnancy after missing a pink active tablet depends on when you missed the tablet. There is a higher risk of becoming pregnant if you miss a tablet at the beginning or end of a pack.

If after taking your missed tablet you have less than 7 days of pink active tablets left in a row, you should finish the active tablets in your pack but skip the white inactive tablets. Start taking the pink active tablets in your next pack corresponding to the correct day of the week. This is the best way to maintain contraceptive protection. However, you may not have a period until the end of the pink active tablets of the second pack. You may have spotting or breakthrough bleeding on tablet-taking days.

If you have been taking the pink active tablets for less than 7 days and miss a pink active tablet, take the missed tablet as soon as you remember, then go back to taking your Pill as you would normally, even if this means taking two tablets in one day, at the same time. In addition, you must also use additional barrier contraceptive precautions (e.g. condoms or a diaphragm) for the next 7 days.

If you have had sexual intercourse in the preceding 7 days, there is a possibility of pregnancy and you may need emergency contraception. You should discuss this with your doctor or pharmacist.

If you forget to take more than one pink active tablet, seek advice from your doctor or pharmacist about what to do.

If you have had sexual intercourse in the week before missing your tablets, there is a possibility of becoming pregnant.

If you miss a large white inactive tablet, you do not need to take them later because they do not contain any active ingredients. However, it is important that you discard the missed white tablet(s) to make sure that the number of days between taking active tablets is not increased as this would increase the risk of pregnancy. Continue with the next tablet at the usual time.

Please see the table at the end of this leaflet, “Summary of advice if you missed a pink active tablet more than 12 hours ago”.

Ask your doctor or pharmacist to answer any questions you may have.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (13 11 26) for advice, or go to the Accident and Emergency Department at your nearest hospital, if you think that you or anyone else may have taken too much Microgynon 20 ED. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

WHILE YOU ARE TAKING MICROGYNON 20 ED

Things you must do

Tell any doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Have regular check-ups with your doctor. When you are taking the Pill, your doctor will tell you to return for regular check-ups, including getting a Cervical Screening Test. Your doctor will advise how often you need a Cervical Screening Test. A Cervical Screening Test can detect abnormal cells lining the cervix. Sometimes abnormal cells can progress to cancer.

If you are about to start on any new medicine, remind your doctor and pharmacist that you are taking Microgynon 20 ED.

Stop taking Microgynon 20 ED and see your doctor immediately if you notice the following signs:

  • one-sided 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
  • sudden onset of unexplained shortness of breath or rapid breathing
  • sudden coughing or coughing up of blood
  • sharp chest pain or sudden severe pain in the chest which may increase with deep breathing
  • severe light headedness or dizziness
  • rapid or irregular heartbeat
  • sudden pain, swelling and slight blue discoloration of an extremity
  • 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, slurred speech or aphasia; sudden partial or complete loss of vision, double vision, painless blurring of vision which can progress to loss of vision
  • 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
  • extreme weakness and anxiety.

If you are going to have surgery, tell the surgeon or anaesthetist beforehand that you are taking Microgynon 20 ED. The risk of having blood clots is temporarily increased as a result of major surgery, any surgery to the legs or pelvis, neurosurgery or major trauma. In women who take Microgynon 20 ED, the risk may be higher.

In women at risk of prolonged immobilisation (including major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma), your doctor may tell you to stop taking (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. Your doctor may prescribe other treatment (e.g. treatment for blood clots) if Microgynon 20 ED has not been discontinued in advance.

Other risk factors for blood clotting include temporary immobilisation including air travel of greater than 4 hours, particularly in women with other risk factors. Consult your doctor if you plan to air travel for greater than 4 hours.

Consult your doctor if you develop high blood pressure while taking Microgynon 20 ED – you may be told to stop taking it.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you vomit within 3 to 4 hours, or have severe diarrhoea after taking a pink active tablet, the active ingredients may not have been completely absorbed. This is like missing a tablet. Follow the advice for missed tablets.

If you have unexpected bleeding and it continues, becomes heavy, or occurs again, tell your doctor. When taking this Pill for the first few months, you can have irregular vaginal bleeding (spotting or breakthrough bleeding) between your periods. You may need to use sanitary products, but continue to take your tablets as normal. Irregular vaginal bleeding usually stops once your body has adjusted to the Pill, usually after about 3 months.

If you have missed a period, but you have taken all your tablets, it is unlikely that you are pregnant, as long as:

  • you have taken the pink active tablets at the right time
  • you have not been taking a medicine(s) that may interfere with your Pill
  • you have not vomited or had severe diarrhoea during this cycle.

If this is so, continue to take Microgynon 20 ED as usual. If you have any concerns consult your doctor or pharmacist.

If you miss your period twice in a row, you may be pregnant, even if you have taken the Pill correctly. Stop taking Microgynon 20 ED and seek advice from your doctor. You must use a non-hormonal method of contraception, (such as condoms or a diaphragm) until your doctor rules out pregnancy.

Microgynon 20 ED will not protect you from HIV-AIDS or any other sexually transmitted infections (STIs), such as chlamydia, genital herpes, genital warts, gonorrhoea, hepatitis B, human papillomavirus and syphilis.

To protect yourself from STIs, you will need to use additional barrier contraceptives (e.g. condoms).

Things you must not do

Do not take Microgynon 20 ED to treat any other conditions, unless your doctor tells you to.

Do not give your medicine to anyone else.

Do not stop taking your medicine or change the dosage without checking with your doctor. You may become pregnant if you are not using any other contraceptive and you stop taking Microgynon 20 ED, or do not take a tablet every day.

SIDE EFFECTS

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Microgynon 20 ED. This Pill helps most women, but it may have unwanted side effects in some women.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

The following list includes the more common side effects of your Pill. These are usually mild and lessen with time.

If you notice any of the following side effects and they worry you, tell your doctor or pharmacist:

  • acne
  • nausea
  • stomach pain
  • changes in weight
  • headache, including migraines
  • mood changes, including depression
  • breast tenderness or pain
  • hair loss or hair growth.

The following list includes very serious but rare side effects. You may need urgent medical attention or hospitalisation.

If you experience any of the following, tell your doctor immediately, or go to the Accident and Emergency Department at your nearest hospital:

  • pain in the chest, arm or below the breastbone
  • pain or discomfort that goes to your back
  • breathlessness and/or difficulty breathing
  • swelling, pain or tenderness of one leg
  • sudden weakness, numbness or bad ‘pins and needles’ of the face, arm or leg, especially on one side of the body
  • sudden trouble walking, dizziness, loss of balance or coordination
  • severe, sudden stomach pains
  • a fainting attack or you collapse
  • unusual headaches or migraines that are worse than usual
  • sudden problems with speaking, seeing or understanding what people are saying to you
    The side effects listed above are possible signs of a blood clot (thrombosis).
  • jaundice (yellowing skin or yellowing eyes)
  • you cough up blood
  • breast lumps
  • unexplained vaginal bleeding.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

Blood clots and the Pill

Blood clots may block blood vessels in your body. This type of blood clot is also called thrombosis.

Blood clots sometimes occur in the deep veins of the legs. If a blood clot breaks away from the veins where it has formed, it may reach and block the blood vessels of the lungs, causing pulmonary embolism.

Blood clots can also occur in the blood vessels of the heart (causing a heart attack) or the brain (causing a stroke).

Blood clots are a rare occurrence and can develop whether or not you are taking the Pill. They can also happen during pregnancy. The risk of having blood clots is higher in Pill users than in non-users, but not as high as during pregnancy.

The risk of a blood clot is highest during the first year of taking the Pill for the first time, or after having a break from the Pill for 4 weeks or more.

If you notice possible signs of a blood clot, stop taking Microgynon 20 ED and consult your doctor immediately. To prevent pregnancy, you must also use additional barrier contraceptive precautions (e.g. condoms or a diaphragm).

If you are concerned about an increased risk of blood clots while on Microgynon 20 ED, speak to your doctor.

Cancer and the Pill

Breast cancer has been diagnosed slightly more often in women who take the Pill than in women of the same age who do not take the Pill.

This slight increase in the numbers of breast cancer diagnoses gradually disappears during the course of the 10 years after women stop taking the Pill.

It is not known whether the difference is caused by the Pill. It may be that these women were examined more often, so that the breast cancer was noticed earlier.

It is important that you check your breasts regularly and contact your doctor if you feel any lumps.

In rare cases benign liver tumours and, even more rarely, malignant liver tumours have been reported in users of the Pill. These tumours may lead to internal bleeding.

Contact your doctor immediately if you have severe pain in your abdomen.

Cervical cancer has been reported to occur more often in women who have been taking the Pill for a long time. This finding may not be caused by the Pill, but may be related to sexual behaviour and other factors.

AFTER TAKING MICROGYNON 20 ED

Storage

Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store your tablets or any other medicine in the bathroom, near a sink, or on a window-sill. Do not leave medication in the car. Heat and damp can destroy some medicines.

Keep Microgynon 20 ED where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Return any unused medicine to your pharmacist.

PRODUCT DESCRIPTION

What Microgynon 20 ED looks like

Microgynon 20 ED active tablets are pink and round.

Microgynon 20 ED inactive tablets are white and round.

Microgynon 20 ED comes in a box containing 1, 2, 3 or 4 blister packs. Not all pack sizes may be marketed.

Each blister pack contains 21 pink active tablets and 7 white inactive tablets.

Ingredients

Each pink active tablet contains:

Active ingredients:

  • 20 micrograms of ethinylestradiol
  • 100 micrograms of levonorgestrel

Inactive ingredients:

  • calcium carbonate
  • glycerol
  • glycol montanate
  • iron oxide red
  • iron oxide yellow
  • lactose monohydrate
  • macrogol 6000
  • magnesium stearate
  • maize starch
  • povidone
  • pregelatinised starch
  • purified talc
  • sucrose
  • titanium dioxide

Each white inactive tablet contains:

  • calcium carbonate
  • glycol montanate
  • lactose monohydrate
  • macrogol 6000
  • magnesium stearate
  • maize starch
  • povidone
  • purified talc
  • sucrose

Tablets do not contain gluten. Tablets also do not contain tartrazine or any other azo dyes.

Supplier

Made in Germany for:

Bayer Australia Ltd
ABN 22 000 138 714
875 Pacific Highway
Pymble NSW 2073

Australian Registration Number

Microgynon 20 ED - AUST R 63484

Date of Preparation

March 2020

See TGA website (www.ebs.tga.gov.au) for latest Australian Consumer Medicine Information.

Missed a pill?
See the end of this leaflet.

® Registered Trademark of the Bayer Group, Germany

© Bayer Australia Ltd All rights reserved.

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Microgynon 20 ED

Active ingredient

Ethinylestradiol; Levonorgestrel

Schedule

S4

 

1 Name of Medicine

Ethinylestradiol and levonorgestrel.

6.7 Physicochemical Properties

Ethinylestradiol is a white to creamy white, odourless, crystalline powder. It is practically insoluble in water and soluble in alcohol, chloroform, ether, vegetable oils and aqueous solutions of alkali hydroxides.
Levonorgestrel is a white or almost white, odourless or almost odourless, crystalline powder. Practically insoluble in water; slightly soluble in alcohol, acetone and ether; soluble in chloroform; sparingly soluble in methylene chloride.

Chemical structure.

Ethinylestradiol.

The chemical name for ethinylestradiol is 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3, 17β-diol and has the following structural formula:
Chemical Formula: C20H24O2. Molecular Weight: 296.41. Melting Point: 181-185°C.

Levonorgestrel.

The chemical name for levonorgestrel is 13β-ethyl-17β -hydroxy-18, 19-dinor-17α-pregn-4- en-20-yn-3-one and has the following structural formula:
Chemical Formula: C21H28O2. Molecular Weight: 312.45. Melting Point: 232-239°C.

CAS number.

Ethinylestradiol: 57-63-6.
Levonorgestrel: 797-63-7.

2 Qualitative and Quantitative Composition

Microgynon 20 ED is a combined oral contraceptive (COC) tablet containing the synthetic estrogen, ethinylestradiol and the synthetic progestogen, levonorgestrel.
Each pink active tablet contains ethinylestradiol 20 microgram and levonorgestrel 100 microgram.

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tablet, sugar coated.
Microgynon 20 ED tablets are available in blister packs. Each blister contains 28 tablets consisting of 21 small round pink active tablets, followed by 7 large round white placebo tablets.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The hormonal components of Microgynon 20 ED inhibit ovulation by suppressing gonadotrophin release. Secondary mechanisms which may contribute to the effectiveness of Microgynon 20 ED as a contraceptive include changes in the cervical mucus (which increase the difficulty of sperm penetration) and changes in the endometrium (which reduce the likelihood of implantation).

Clinical trials.

An open label, noncomparative multicentre phase III clinical study was conducted in 820 women receiving Microgynon 20 for a planned individual maximum of 6 cycles. Six cycles were completed by 680 women. 4,400 cycles in which no alternative methods of contraception were used were available for the efficacy analysis. One pregnancy was reported. This represents an overall user efficacy (typical user efficacy) pregnancy rate of 0.32 per 100 woman years (over 99% effective at preventing pregnancy). This rate includes patients who missed up to 3 tablets per cycle. The overall compliance (no missed tablets) was between 94.6% and 98.4% over the course of the study. Published data from a larger study with a similar preparation containing the same dosage of active ingredients in 1447 women, with 7720 cycles of exposure, report 5 pregnancies and an overall user efficacy pregnancy rate of 0.84 per 100 woman years, in women who missed up to 3 tablets consecutively per cycle or 5 nonconsecutive tablets per cycle.
The overall user efficacy pregnancy rates for Microgynon 20 and other forms of contraception from a number of noncomparative trials based on historical data are given in Table 3.
Whilst the contraceptive efficacy of Microgynon 20 was 99.68% in a single study, the contraceptive efficacy of the levonorgestrel 100 microgram/ ethinylestradiol 20 microgram formulations ranges from 99.16-99.68%, compared historically with the contraceptive efficacy of 99.7% for 150 microgram levonorgestrel/30 microgram ethinylestradiol tablets, this represents a similar up to 2-fold increase in the risk of pregnancy.
Cycle control was also evaluated by analysing cycle characteristics such as duration and intensity of withdrawal bleeding and the incidence of breakthrough bleeding and amenorrhoea. A total of 4400 cycles were valid for cycle control analysis; the overall incidence of intermenstrual bleeding was low. Although there was no comparative study of the cycle control of Microgynon 20 compared with higher dosage oral contraceptives, cycle control data from historical studies with oral contraceptives containing higher doses of ethinylestradiol and levonorgestrel are given in Table 4.
The length of withdrawal bleeding was 3-5 days for most patients (70%) (mean 4.7 days) and the intensity was scanty or normal for most subjects. Cycle length was between 26 and 30 days for most patients (up to 80%) with a tendency to be slightly shorter during the early cycles.

5.2 Pharmacokinetic Properties

A bioavailability study comparing Microgynon 20 to a microcrystalline solution was conducted. However, as this study employed doses equivalent to three tablets instead of single tablet dosing for technical reasons, the pharmacokinetic information provided is derived from a single tablet pharmacokinetic study conducted in 20 women.

Ethinylestradiol.

Absorption.

Orally administered ethinylestradiol is absorbed quickly and almost completely from the gastrointestinal tract but due to first pass metabolism in gut mucosa and liver, the absolute bioavailability of ethinylestradiol is subject to considerable interindividual variations. After oral ingestion, it amounts to around 40-60% of the dose.
Ingestion of Microgynon 20 ED leads to maximum plasma levels of approximately 50 picogram/mL after 1-2 hours. The substance concentration then falls in at least 2 disposition phases with a terminal half-life of around 24 hours. For technical reasons, these data can only be calculated at higher dosages.

Distribution.

Ethinylestradiol is bound nonspecifically to serum albumin to about 98%. Ethinylestradiol does not bind to SHBG but induces SHBG synthesis.

Metabolism.

Cytochrome P450 enzymes (CYP3A4) in the liver are responsible for the 2-hydroxylation that is the major oxidative reaction. The 2-hydroxy metabolite is further transformed by methylation and glucuronidation prior to urinary and faecal excretion. Levels of CYP3A4 vary widely amongst individuals and may explain the variations in rates of ethinylestradiol 2-hydroxylation. Ethinylestradiol is excreted in the urine and faeces as glucuronide and sulphate conjugates, and undergoes enterohepatic circulation.

Excretion.

Ethinylestradiol is eliminated not in unchanged form, but in the form of metabolites with a half-life of around 18 ± 4.7 hours at steady state. The excretion ratio is 40 (urine): 60 (bile).

Steady-state conditions.

According to the variable half-life of the terminal disposition phase from serum and the daily ingestion, steady-state serum levels of ethinylestradiol will be reached after about one week.

Levonorgestrel.

Absorption.

Levonorgestrel is absorbed quickly and completely. Maximum active substance levels of approximately 2.4 nanogram/mL were reached in serum approximately 1.0-1.3 hours after ingestion of Microgynon 20 ED. The absolute bioavailability of levonorgestrel amounts to almost 100%.

Distribution.

Levonorgestrel is bound to serum albumin and sex hormone binding globulin (SHBG). Only around 1.1% of the respective total concentration is present in unbound form, while approximately 65% is bound to SHBG. The relative proportions (free, albumin bound, SHBG bound) depend on the concentration of SHBG. After induction of the binding protein, the portion bound to SHBG increases to 75%, while the free portion and that bound to albumin decrease to around 0.8 and 25%, respectively.

Metabolism.

Levonorgestrel is extensively metabolised. The major metabolites in plasma are the unconjugated and conjugated forms of 3α, 5β-tetrahydrolevonorgestrel. Additionally, based on in vitro and in vivo studies, CYP3A4 is the main enzyme involved in the oxidative metabolism of levonorgestrel.
The metabolic clearance rate, including the bound component, from plasma is approximately 1.0 mL/min/kg.

Excretion.

The serum concentrations subsequently fall in at least 2 disposition phases with a terminal half-life of around 24 hours.
Levonorgestrel is eliminated not in unchanged form, but in the form of metabolites with a half-life of approximately 28 ± 7 hours and in almost equal proportions via the kidney and bile.

Steady-state conditions.

After daily repeated ingestion, levonorgestrel accumulates by about a factor of 3. A steady state is reached after approximately 11 days. The pharmacokinetics of levonorgestrel are nonlinear due to an increase in binding of levonorgestrel to SHBG which is attributed to increased SHBG levels that are induced by the daily administration of ethinylestradiol. The levonorgestrel serum levels do not change any further after 1-3 cycles of use because SHBG induction is concluded.

5.3 Preclinical Safety Data

Genotoxicity.

There is limited evidence available in the literature suggesting that estrogens may be weakly genotoxic at high doses. Ethinylestradiol was negative in studies for DNA adduct formation in cultured human liver slices and in assays for gene mutations (bacterial or mammalian cells in vitro) and gave equivocal results in assays for chromosomal damage (clastogenic effects were not consistently seen and occurred at high doses).
The genotoxic potential of levonorgestrel has not been fully investigated, although limited data available to date suggest that it does not appear to be genotoxic.

Carcinogenicity.

Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis and liver. A long-term study with levonorgestrel in dogs showed an increased incidence of mammary tumours, although a similar effect was not apparent in studies in mice, rats or monkeys. The occurrence of these mammary tumours in dogs may be due in part to a hormonal feedback mechanism. The clinical relevance of these findings is uncertain.
Numerous epidemiological studies have been conducted to determine the incidence of breast, endometrial, ovarian and cervical cancer in women taking COCs. Some of these studies have shown an increased relative risk of breast cancer in certain subgroups of COC users. Women with a strong family history of breast cancer or who have breast nodules, fibrocystic disease or abnormal mammograms should be monitored with particular care. Benign hepatic adenomas have been found to be associated with the use of oral contraceptives. Although benign, hepatic adenomas may rupture and cause death through intra-abdominal haemorrhage. Some epidemiological studies also suggest that COC use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women, although there continues to be controversy about the extent to which this finding is attributable to the confounding effects of sexual behaviour and other factors such as HPV. It must also be borne in mind that sexual steroids can promote the growth of certain hormone dependent tissues and tumours (also see Section 4.4 Special Warnings and Precautions for Use).

4 Clinical Particulars

4.1 Therapeutic Indications

Microgynon 20 ED is indicated for the prevention of pregnancy.

4.3 Contraindications

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 risk of venous thromboembolism (VTE) (see Section 4.4 Special Warnings and Precautions for Use):
current VTE (on anticoagulants) or history of deep venous thrombosis [DVT] or pulmonary embolism [PE];
known hereditary or acquired predisposition for venous thromboembolism, such as APC-resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency;
major surgery with prolonged immobilisation;
a high risk of venous thromboembolism due to the presence of multiple risk factors.
Presence or risk of arterial thromboembolism (ATE) (see Section 4.4 Special Warnings and Precautions for Use):
current ATE or history of ATE (e.g. myocardial infarction or stroke) or prodromal condition (e.g. angina pectoris or transient ischaemic attack [TIA]);
known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (e.g. Anticardiolipin antibodies and lupus anticoagulant);
history of migraine with focal neurological symptoms;
a high risk of arterial thromboembolism due to multiple risk factors or to the presence of one serious risk factor such as: diabetes mellitus with vascular symptoms, severe hypertension, severe dyslipoproteinaemia.
Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
Use of direct-acting antiviral (DAA) medicinal products containing ombitasvir, paritaprevir or dasabuvir and combinations of these (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
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 any of the ingredients contained in Microgynon 20 ED.

4.4 Special Warnings and Precautions for Use

If any of the conditions/risk factors mentioned below are present, the benefits of Microgynon 20 ED should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start taking it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her doctor. The doctor should then decide whether Microgynon 20 ED should be discontinued.

Circulatory disorders.

Epidemiological studies have suggested an association between the use of combined oral contraceptives (COCs) containing ethinylestradiol 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 in average-risk women.

Risk of venous thromboembolism (VTE).

The use of any combined hormonal contraceptive (CHC) increases the risk of VTE compared with no use. The woman should be advised that her VTE risk is highest in the first ever year of use and that there is some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more.
Data from a large, prospective 3-armed cohort study (EURAS1 and LASS2) suggest that this increased risk is mainly present during the first 3 months.
A large prospective 3-armed cohort study has shown that the frequency of VTE diagnosis range from 8 to 10 per 10,000 woman years (WY) in low estrogen dose (< 50 microgram ethinylestradiol) COC users. The most recent data suggest that the frequency of VTE diagnosis is approximately 4.4 per 10,000 WY in non-pregnant non-COC users and ranges from 20 to 30 per 10,000 WY in pregnancy or the post-partum period.
Overall the risk of VTE in users of low estrogen dose (< 50 microgram 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.
It is important that women understand that VTE associated with CHC use is rare in average-risk women. The risk in pregnancy (5-20 per 10,000 women over 9 months) and the risk in the post-partum period (45-65 per 10,000 women over 12 weeks) is higher than that associated with CHC use.
An additional increase in VTE risk for CHCs containing ≥ 50 microgram ethinylestradiol cannot be excluded.
The decision to use any product other than one with the lowest VTE risk should be taken only after a discussion with the woman to ensure she understands the risk of VTE with CHCs, and how her current risk factors influence this risk.
The increased risk of VTE during the postpartum period must be considered if re-starting Microgynon 20 ED. See Section 4.2 Dose and Method of Administration; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy, Use in lactation.
VTE may be life-threatening or may have a fatal outcome (in 1-2% of cases).
Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels, e.g. hepatic, mesenteric, renal or retinal veins and arteries.
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 list below).
Microgynon 20 ED is contraindicated if a woman has multiple risk factors that put her at high risk of venous thrombosis. 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.
When considering risk/benefit, the doctor should take into account that the adequate treatment of a condition may reduce the associated risk of thrombosis.

Risk factors for VTE.

Obesity (body mass index over 30 kg/m2). Risk increases substantially as BMI rises.
Prolonged immobilisation, major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma.
Temporary immobilisation including air travel > 4 hours can also be a risk factor for VTE, particularly in women with other risk factors.
Positive family history (venous thromboembolism ever in a sibling or parent especially at a relatively early age e.g. before 50).
Biochemical factors that may be indicative of hereditary or acquired predisposition for VTE include Activated Protein C (APC) resistance (including Factor V Leiden), antithrombin-III deficiency, protein C deficiency, protein S deficiency.
Other medical conditions associated with VTE include: cancer, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis), sickle cell disease.
Increasing age, particularly above 35 years.
Smoking.
In women at risk of prolonged immobilisation (including major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma), it is advisable to discontinue use of Microgynon 20 ED (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 Microgynon 20 ED has not been discontinued in advance.
If a hereditary predisposition to VTE is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use.
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.

Symptoms of VTE (deep vein thrombosis and pulmonary embolism).

Women should be informed of the symptoms of VTE and be advised to seek urgent medical attention if VTE symptoms develop 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 or sudden severe pain in the chest which may increase with deep breathing;
severe light headedness or dizziness;
rapid or irregular heartbeat.
Some of these symptoms (e.g. "shortness of breath", "coughing") are nonspecific 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 (e.g. myocardial infarction, angina pectoris, stroke or TIA). Arterial thromboembolic events may be fatal.
The risk of arterial thromboembolic complications in CHC users increases in women with risk factors. Microgynon 20 ED is contraindicated if a woman has one serious or multiple risk factors for ATE that puts her at high risk of arterial thrombosis. 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.

Risk factors for ATE.

Increasing age, particularly above 35 years.
Smoking.
Hypertension.
Obesity.
Positive family history (arterial thromboembolism ever in a sibling or parent especially at relatively early age e.g. below 50).
Biochemical factors that may be indicative of hereditary or acquired predisposition for ATE include: hyperhomocysteinaemia and antiphospholipid antibodies (e.g. anticardiolipin antibodies, and lupus anticoagulant).
Migraine.
Other medical conditions associated with adverse vascular events: diabetes mellitus, hyperhomocysteinaemia, valvular heart disease, atrial fibrillation, dyslipoproteinaemia, systemic lupus erythematosus.
Women should be advised not to smoke if they wish to use a CHC. Women over 35 years who continue to smoke should be strongly advised to use a different method of contraception.
If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use.
An increase in frequency or severity of migraine during CHC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation.

Symptoms of ATE.

Women should be informed of the symptoms of ATE and be advised to seek urgent medical attention if ATE symptoms develop and to inform the healthcare professional that she is taking a CHC.
Symptoms of a stroke 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, slurred speech or aphasia;
sudden partial or complete loss of vision; diplopia;
sudden, severe or prolonged headache with no known cause;
loss of consciousness or fainting with or without seizure.
Temporary symptoms suggest the event is a transient ischaemic attack (TIA).
Symptoms of myocardial infarction (MI) can include:
pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or below the breastbone;
discomfort radiating to the back, jaw, throat, arm, stomach;
feeling of being full, having indigestion or choking;
sweating, nausea, vomiting or dizziness;
extreme weakness, anxiety, or shortness of breath;
rapid or irregular heartbeats.

Tumours.

The most important risk factor for cervical cancer is persistent human papilloma virus (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 taking 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.
Malignancies may be life threatening or may have a fatal outcome.

Other conditions.

Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when taking 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, it is prudent for the doctor to withdraw the COC and treat the hypertension. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis related hearing loss.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.
Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal. Recurrence of cholestatic jaundice which occurred first during pregnancy or 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 women with diabetes taking low dose COCs (containing < 50 microgram ethinylestradiol). However, women with diabetes 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 whilst taking COCs.
Each pink active tablet contains 33 mg of lactose monohydrate and each white placebo tablet contains 34 mg of lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption who are on a lactose free diet should take this amount into consideration.

Medical examination/ consultation.

A complete medical history and physical examination should be taken prior to the initiation or reinstitution of COC use, guided by (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use), and should be repeated periodically during the use of COCs. In general, an annual examination is recommended. 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 and relevant laboratory tests.

Sexually transmitted infections (STIs) including human immunodeficiency virus (HIV) infections and AIDS.

Microgynon 20 ED is intended to prevent pregnancy. It does not protect against STIs, including HIV infections (AIDS). The woman should be advised that additional barrier contraceptive measures are needed to prevent transmission of STIs.

Reduced efficacy.

The efficacy of COCs may be reduced in the event of missed pink active tablets, vomiting or diarrhoea during active taking (see Section 4.2 Dose and Method of Administration) or concomitant medication (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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 nonhormonal causes should be considered and adequate diagnostic measures are indicated to exclude malignancy or pregnancy. These may include curettage.
In some women withdrawal bleeding may not occur during the placebo tablet interval. If the COC has been taken according to the directions described (see Section 4.2 Dose and Method of Administration), 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.

Use in hepatic impairment.

Microgynon 20 ED is contraindicated in women with severe hepatic disease as long as liver function values have not returned to normal (see Section 4.3 Contraindications).

Use in renal impairment.

Microgynon 20 ED has not been specifically studied in renally impaired patients.

Use in the elderly.

Microgynon 20 ED is not indicated after menopause.

Paediatric use.

Microgynon 20 ED is only indicated after menarche.

Effects on laboratory tests.

The use of contraceptive steroids may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of carrier proteins, e.g. corticosteroid binding globulin and lipid/ lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis. Changes generally remain within the normal laboratory range.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Note.

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

Effects of other medicines on Microgynon 20 ED.

Interactions can occur with medicines that induce microsomal enzymes (e.g. cytochrome P450 enzymes, CYP3A4), which can result in increased clearance of sex hormones and may lead to breakthrough bleeding and/or oral contraceptive failure.
Enzyme induction can already be observed after a few days of treatment. Maximal enzyme induction is generally seen within a few weeks. After the cessation of drug therapy enzyme induction may be sustained for about 4 weeks.
Women prescribed any of these medicines should temporarily use a barrier method in addition to the COC or choose another method of contraception. The barrier method should be used during the time of concomitant medicine administration and for 28 days after their discontinuation. If the period in which the barrier method is used runs beyond the end of the pink active tablets in the COC pack, the white placebo tablets should be omitted and the next COC pack started.
Women taking interacting medications on a chronic basis should consider another method of contraception.

Substances increasing the clearance of COCs (diminished efficacy of COCs by enzyme induction), e.g.

Phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and herbal medicines containing St John's wort (Hypericum perforatum).

Substances with variable effects on the clearance of COCs.

When co-administered with COCs, many human immunodeficiency virus (HIV)/ hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors can increase or decrease plasma concentration of estrogen or progestogen. These changes may be clinically relevant in some cases.

Substances decreasing the clearance of COCs (enzyme inhibitors).

Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g. clarithromycin, erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of the estrogen or the progestin or both.
Etoricoxib doses of 60 to 120 mg/day have been shown to increase plasma concentrations of ethinylestradiol 1.4 to 1.6-fold, respectively when taken concomitantly with a combined hormonal contraceptive containing 0.035 mg ethinylestradiol.

Influence of Microgynon 20 ED on other medicines.

Oral contraceptives may affect the metabolism of certain other medicines. Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).
In vitro, ethinylestradiol is a reversible inhibitor of CYP2C19, CYP1A1 and CYP1A2 as well as a mechanism based inhibitor of CYP3A4/5, CYP2C8, and CYP2J2. In clinical studies, administration of a hormonal contraceptive containing ethinylestradiol lead to no, or a weak increase in CYP3A4 substrates (e.g. midazolam) and a weak (e.g. theophylline) to moderate (e.g. melatonin, tizanidine) increase of CYP1A2 substrates.

Pharmacodynamic interactions.

Co-administration of ethinylestradiol-containing medicinal products with direct-acting antiviral (DAA) medicinal products containing ombitasvir, paritaprevir, or dasabuvir, and combinations of these has been shown to be associated with increases in alanine aminotransferase (ALT) levels to greater than 20 times the upper limit of normal in healthy female subjects and HCV infected women (see Section 4.3 Contraindications).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Microgynon 20 ED is contraindicated during pregnancy. If pregnancy occurs during treatment with Microgynon 20 ED, further intake must be stopped immediately.
Epidemiological studies have found no significant effects on foetal development 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. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk. Therefore, the use of COCs should generally not be recommended until the nursing mother has completely weaned her child.

4.8 Adverse Effects (Undesirable Effects)

Various adverse reactions have been associated with oral contraceptive use. The most commonly reported adverse reactions with Microgynon 20 ED are nausea, abdominal pain, increased weight, headache, depressed mood, altered mood, breast pain and breast tenderness. They occur in ≥ 1% of users.
Serious adverse reactions are arterial and venous thromboembolism.
The most serious reactions associated with the use of oral contraceptives are discussed (see Section 4.4 Special Warnings and Precautions for Use).
In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her doctor. The doctor should then decide on whether COC use should be discontinued.

Clinical trial data.

Table 1 displays the adverse events reported amongst patients in a clinical trial of Microgynon 20, for contraception (n = 805). It includes all adverse events reported with an incidence of 1% or greater. A total of 8.4% of women discontinued Microgynon 20 therapy due to the adverse events. Intermenstrual bleeding and metrorrhagia (4%) were the study events most frequently reported as the reason for discontinuing Microgynon 20 therapy. All other events that resulted in discontinuation were reported by less than 1% of the women.
A bioavailability study (n = 22) reported the following adverse events with a frequency of > 1%: intermenstrual bleeding 45%, headache/ migraine 27%, dysmenorrhoea 23%, flu syndrome 18%, nausea 14%. A pharmacokinetic study (n = 18) reported the following adverse events with a frequency of > 1%: headache 78%, dysmenorrhoea 61%, flu syndrome 33%, common cold 28%, breast pain 17%.

Post-marketing data.

The following adverse events have been reported in users of low dose oral contraceptives and have been observed at the frequencies listed below, but an association has neither been confirmed nor totally refuted. See Table 2.
Very common: ≥ 1 in 10 (≥ 10%).
Common: ≥ 1 in 100 and < 1 in 10 (between 1% and 10%).
Uncommon: ≥ 1 in 1,000 and < 1 in 100 (between 0.1% and 1%).
Rare: ≥ 1 in 10,000 and < 1 in 1,000 (between 0.01% and 0.1%).
Very rare: < 1 in 10,000 (< 0.01%).
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

How to take Microgynon 20 ED.

COCs, when taken correctly, have a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly.
One tablet is to be taken daily. The tablets must be taken in the order directed on the package at about the same time each day, with some liquid as needed. Daily tablet taking should be continuous for 28 consecutive days, starting with a pink active tablet marked with the corresponding day of the week from the green area of the Microgynon 20 ED pack. Each subsequent pack is to be started the day after the last tablet of the previous pack. A withdrawal bleed usually starts on day 2 to 3 after starting the white placebo tablets (last row) and may not have finished before the next pack is started.

How to start Microgynon 20 ED.

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). If started on day 1 in this way, protection against pregnancy is immediate and no additional method of contraception is required. Starting on day 2-5 of the menstrual cycle is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet taking.

When changing pills.

Changing from a combined hormonal contraceptive (COC) or vaginal ring.

The woman should start with Microgynon 20 ED preferably on the day after her 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 has been used, the woman should start taking Microgynon 20 ED 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 from a minipill on any day; an implant or IUS, on the day of its removal; or an injectable, when the next injection would be due. In all of these cases the woman should be advised to additionally use a barrier method for the first 7 days of tablet taking.

Following first trimester abortion.

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

Following delivery or second trimester abortion.

Women should be advised to start on day 21 to 28 after delivery or second trimester abortion. When starting later than day 28, 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.
For breastfeeding women see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.

Additional contraceptive precautions.

When additional contraceptive precautions are required the woman should be advised either to abstain from sex, or to use a barrier method of contraception, such as a cap (or diaphragm) plus spermicide, or for her partner to use a condom. Rhythm methods should not be advised as the COC disrupts the cyclical changes associated with the natural menstrual cycle, e.g. changes in temperature and cervical mucus.

How to shift periods or how to delay a period.

To delay a period the woman should continue with another pack of Microgynon 20 ED by missing the white placebo tablets (last row) from her current pack. 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 Microgynon 20 ED is then resumed after the usual 7 day placebo tablet 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 placebo tablet 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).

How to manage reduced reliability.

When Microgynon 20 ED is taken according to the directions for use, the occurrence of pregnancy is highly unlikely. However, the reliability of COCs may be reduced under the following circumstances.

Management of missed tablets.

Missed pills from the last row of the blister are placebo tablets and thus can be disregarded. However they should be discarded to avoid unintentionally prolonging the placebo tablet phase. The following advice only refers to missed pink active tablets (rows 1-3 of the blister).
If the woman is less than 12 hours late in taking any pink active 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 the woman is more than 12 hours late in taking any pink active tablet, contraceptive protection may be reduced. The more pink active tablets missed and the closer they are to the white placebo tablet phase the higher the risk of a pregnancy. The management of missed tablets can be guided by the following two basic rules.
1. Active tablet taking must never be discontinued for longer than 7 days.
2. Seven days of uninterrupted active 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 of active tablets.

The woman should take the last missed pink active tablet as soon as she remembers, even if this means taking two pink active 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.

Week 2 of active tablets.

The woman should take the last missed pink active tablet as soon as she remembers, even if this means taking two pink active 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 pink active tablet, there is no need to use extra contraceptive precautions. However, if this is not the case, or if she missed more than one pink active tablet, the woman should be advised to use extra precautions for 7 days.

Week 3 of active tablets.

The risk of reduced reliability is imminent because of the forthcoming white placebo tablet phase. 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 pink active 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 woman should take the last missed pink active tablet as soon as she remembers, even if this means taking two pink active tablets at the same time. She then continues to take tablets at her usual time until all the pink active tablets are taken. The 7 white placebo tablets from the last row must be discarded. The next pack must be started right away. The woman is unlikely to have a withdrawal bleed until the end of the active tablets 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 hormone free white coated tablet phase, the possibility of a pregnancy should be considered.

Advice in case of gastrointestinal disturbances.

In case of severe gastrointestinal disturbances, 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 previously, 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.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

There have been no reports of serious deleterious effects from overdose. Symptoms that may occur in this case are: nausea, vomiting and withdrawal bleeding. The last may even occur in girls before their menarche, if they have accidentally taken the medicinal product. There are no antidotes and further treatment should be symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

References

1. Dinger JC, Heinemann LA, Kuhl-Habich D. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance study on Oral Contraceptives based on 142,475 women-years of observation. Contracept 2007; 75:344-54.
2. Long-term Active Surveillance Study for Oral contraceptives (LASS), 2nd update report based on study status. May 2009.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each pink active tablet also contains the following excipients: calcium carbonate, glycerol, glycol montanate, iron oxide red, iron oxide yellow, lactose monohydrate, macrogol 6000, magnesium stearate, maize starch, povidone, pregelatinised maize starch, purified talc, sucrose and titanium dioxide.
Each white placebo tablet contains calcium carbonate, glycol montanate, lactose monohydrate, macrogol 6000, magnesium stearate, maize starch, povidone, purified talc and sucrose.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Microgynon 20 ED tablets are available in PVC/Al blister packs and are supplied in cartons containing memo packs of 1 x 28 tablets, 2 x 28 tablets, 3 x 28 tablets or 4 x 28 tablets. Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes