Consumer medicine information

Micronelle 20 ED

Levonorgestrel; Ethinylestradiol

BRAND INFORMATION

Brand name

Micronelle 20 ED

Active ingredient

Levonorgestrel; Ethinylestradiol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

SUMMARY CMI

MICRONELLE 20 ED

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using MICRONELLE 20 ED?

MICRONELLE 20 ED contains the active ingredients ethinylestradiol and levonorgestrel. MICRONELLE 20 ED is used to prevent pregnancy. For more information, see Section 1. Why am I using MICRONELLE 20 ED? in the full CMI.

2. What should I know before I use MICRONELLE 20 ED?

Do not use if you have ever had an allergic reaction to MICRONELLE 20 ED or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use MICRONELLE 20 ED? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with MICRONELLE 20 ED and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use MICRONELLE 20 ED?

  • Take one tablet daily at about the same time every day.
  • You must take MICRONELLE 20 ED every day regardless of how often you have sex.
  • Swallow the tablet whole with a full glass of water. It does not matter if you take it before or after food.

More instructions can be found in Section 4. How do I use MICRONELLE 20 ED? in the full CMI.

5. What should I know while using MICRONELLE 20 ED?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using MICRONELLE 20 ED.
  • 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.
Things you should not do
  • Do not take MICRONELLE 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 MICRONELLE 20 ED, or do not take a tablet every day.
Looking after your medicine
  • Keep your tablets in the blister pack until it is time to take them.
  • Keep your tablets in a cool dry place where the temperature stays below 25°C.

For more information, see Section 5. What should I know while using MICRONELLE 20 ED? in the full CMI.

6. Are there any side effects?

Common side effects: acne; nausea; stomach pain; changes in weight; headache, including migraines; mood changes, including depression; breast tenderness or pain; hair loss or hair growth.

Serious side effects: Blood clots, jaundice (yellowing skin or yellowing eyes), you cough up blood, unexplained vaginal bleeding and breast lumps.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

MICRONELLE 20 ED

Active ingredient(s): ethinylestradiol and levonorgestrel


Consumer Medicine Information (CMI)

This leaflet provides important information about using MICRONELLE 20 ED. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using MICRONELLE 20 ED.

Where to find information in this leaflet:

1. Why am I using MICRONELLE 20 ED?
2. What should I know before I use MICRONELLE 20 ED?
3. What if I am taking other medicines?
4. How do I use MICRONELLE 20 ED?
5. What should I know while using MICRONELLE 20 ED?
6. Are there any side effects?
7. Product details

1. Why am I using MICRONELLE 20 ED?

MICRONELLE 20 ED contains the active ingredient ethinylestradiol and levonorgestrel. MICRONELLE 20 ED is a combined oral contraceptive tablet, commonly known as a ‘birth control pill’ or ‘the Pill’.

MICRONELLE 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, MICRONELLE 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, MICRONELLE 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.

2. What should I know before I use MICRONELLE 20 ED?

Warnings

Do not use MICRONELLE 20 ED if:

  • you are allergic to ethinylestradiol or levonorgestrel, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can use this medicine.
  • 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.
  • 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.
  • 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.
  • you are taking any antiviral medicines which contain glecaprevir, pibrentasvir, sofosbuvir, velpatasvir, voxilaprevir, 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)).
  • 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.
  • you have, or have had 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).
  • you have, or have had major surgery after which you have not been able to move around for a period of time.
  • you have, or have had angina (chest pain).
  • you have, or have had a mini-stroke (also known as TIA or transient ischaemic attack).
  • you have, or have had a migraine, where you have also had problems with seeing, speaking or had or weakness or numbness in any part of your body.
  • you have, or have had 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.
  • you have, or have had pancreatitis (an inflammation of the pancreas) associated with high levels of fatty substances in your blood.
  • you have, or have had severe liver disease and your liver function has not returned to normal.
  • you have, or have had cancer that may grow under the influence of sex hormones (e.g. of the breast or the genital organs).
  • you have, or have had a benign or malignant liver tumour.
  • you have, or have had 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).

Check with your doctor if you:

  • have any other medical conditions
  • take any medicines for any other condition
  • smoke
  • 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
  • have, or have had diabetes
  • have, or have had high blood pressure
  • have, or have had heart valve disorders or certain heart rhythm disorders
  • have, or have had migraine
  • have, or have had cancer
  • have, or have had hyperhomocysteinaemia, a condition characterised by high levels of the amino acid homocysteine in the blood.
  • have, or have had high or low level of fats in your blood
  • 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.
  • you have an intolerance to some sugars.
    MICRONELLE 20 ED contains lactose.

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

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

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

Talk to your doctor if you are breastfeeding or intend to breastfeed. MICRONELLE 20 ED is generally not recommended if you are breastfeeding.

Children under 18 years old

Do not give this medicine to a child.

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

3. What if I am taking other medicines?

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

Some medicines may interfere with MICRONELLE 20 ED and affect how it works.

  • 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, glecaprevir, pibrentasvir, 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 MICRONELLE 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 MICRONELLE 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.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect MICRONELLE 20 ED.

4. How do I use MICRONELLE 20 ED?

How much to take / use

  • Take one tablet daily at about the same time every day. You must take MICRONELLE 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.
  • Follow the instructions provided and use MICRONELLE 20 ED until your doctor tells you to stop.

When to take / use MICRONELLE 20 ED

Taking MICRONELLE 20 ED for the first time

  • If you are starting MICRONELLE 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 MICRONELLE 20 ED after having a baby
    - have had a miscarriage or an abortion.

Changing from a combined oral contraceptive

  • Start taking MICRONELLE 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 MICRONELLE 20 ED.
  • You can also switch to MICRONELLE 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 MICRONELLE 20 ED.

Changing from a vaginal ring

Start taking MICRONELLE 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 (‘mini-pill’)

  • Stop taking the mini-pill on any day and start taking MICRONELLE 20 ED at the same time the day after your last mini-pill.
  • 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 MICRONELLE 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 MICRONELLE 20 ED

You can stop taking MICRONELLE 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 MICRONELLE 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 use MICRONELLE 20 ED

MICRONELLE 20 ED should be used regularly at the same time each day. If you miss your dose at the usual time, 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 MICRONELLE 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 use too much MICRONELLE 20 ED

If you think that you have used too much MICRONELLE 20 ED, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using MICRONELLE® 20 ED?

Things you should do

  • 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 MICRONELLE 20 ED.

Stop taking this medicine and call your doctor straight away if you notice:

  • 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

Remind any doctor, dentist or pharmacist you visit that you are using MICRONELLE 20 ED.

Surgery and prolonged immobilisation

If you are going to have surgery, tell the surgeon or anaesthetist beforehand that you are taking MICRONELLE 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 MICRONELLE 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 MICRONELLE 20 ED has not been discontinued in advance.

Temporary immobilisation

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.

High blood pressure

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

Pregnancy

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

Vomiting

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.

Unexpected bleeding

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.

Period

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 MICRONELLE 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 MICRONELLE 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.

Sexually transmitted infections (STIs)

MICRONELLE 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 should not do

  • Do not take MICRONELLE 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 MICRONELLE 20 ED, or do not take a tablet every day.

Looking after your medicine

  • 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 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.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Skin-related:
  • acne
  • hair loss or hair growth
Gastrointestinal-related:
  • nausea
  • stomach pain
Metabolic:
  • changes in weight
Neurological:
  • headache, including migraines
  • mood changes, including depression
Breast-related:
  • breast tenderness or pain
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Blood clot-related:
  • 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
Liver-related:
  • jaundice (yellowing skin or yellowing eyes)
Bleeding-related:
  • you cough up blood
Reproductive and breast-related:
  • unexplained vaginal bleeding
  • breast lumps
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

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 MICRONELLE 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 MICRONELLE 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.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What MICRONELLE 20 ED contains

Each pink active tablet contains:
Active ingredients
(main ingredients)
  • 20 micrograms of ethinylestradiol
  • 100 micrograms of levonorgestrel
Other ingredients
(inactive ingredients)
  • lactose monohydrate
  • povidone
  • crospovidone
  • magnesium stearate
  • OPADRY II complete film coating system 85F34610 Pink (ARTG ID 108065).
Potential allergensLactose monohydrate
Each white inactive tablet contains:
Other ingredients
(inactive ingredients)
  • lactose
  • povidone
  • magnesium stearate
  • OPADRY II complete film coating system 85F18422 White (ARTG ID 11376).
Potential allergensLactose

Do not take this medicine if you are allergic to any of these ingredients.

Tablets do not contain gluten.

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

What MICRONELLE 20 ED looks like

  • MICRONELLE 20 ED active tablets are plain, pink and round.
  • MICRONELLE 20 ED inactive tablets are plain, white and round.
  • MICRONELLE 20 ED comes in a box containing 1, 2, 3 or 4 blister packs (AUST R 211154).
  • Not all pack sizes may be marketed.
  • Each blister pack contains 21 pink active tablets and 7 white inactive tablets.

Who distributes MICRONELLE 20 ED

Arrotex Pharmaceuticals
15-17 Chapel St
Cremorne VIC 3121

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

This leaflet was prepared in July 2023.

SUMMARY OF ADVICE IF YOU MISSED A PINK ACTIVE TABLET MORE THAN 12 HOURS AGO

Before missing your tablet, did you take pink active tablets for the previous 7 days?NoDid you have sex in the 7 days before missing the tablet?No
Take the tablet missed AND use extra barrier precaution for 7 days. If there are fewer than 7 pink active tablets left in the pack, finish the pink active tablets and go straight to the pink active tablets of the next pack. This means you skip the white inactive tablets.

Yes
See your Doctor or Pharmacist for advice.
YesDoes your pack still have 7 pink active tablets in a row to follow?No
Take the tablet you missed AND complete taking the pink active tablets. Skip the white inactive tablets. Start your next pack with pink active tablets.

Yes
Take the tablet you missed AND complete the pack as normal.

Published by MIMS August 2023

BRAND INFORMATION

Brand name

Micronelle 20 ED

Active ingredient

Levonorgestrel; Ethinylestradiol

Schedule

S4

 

1 Name of Medicine

Levonorgestrel and ethinylestradiol.

2 Qualitative and Quantitative Composition

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

Excipients with known effect.

Pink active tablet in Micronelle 20 ED: Lactose monohydrate.
White placebo tablet in Micronelle 20 ED: Lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Active tablet.

Plain, round, pink film-coated tablet.

Placebo tablet.

Plain, round, white film-coated tablet.

4 Clinical Particulars

4.1 Therapeutic Indications

Oral contraception.

4.2 Dose and Method of Administration

Micronelle 20 ED tablets are intended for oral administration.

Dosage. How to take Micronelle.

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 Micronelle 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 Micronelle.

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 COC or vaginal ring.

The woman should start Micronelle 20 ED 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 has been used, the woman should start taking Micronelle 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 the minipill on any day; an implant or IUS on the day of removal; when the next injection would be due for an injectable; but in all of these cases she 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 Micronelle 20 ED by missing the white placebo tablets (last row) from the 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 Micronelle 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 COCs are 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 user 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 pink 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 above, 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

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 hypertriglyceridaemia.
Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
Micronelle 20 is contraindicated for concomitant use with the medicinal products glecaprevir, pibrentasvir, sofosbuvir, velpatasvir, voxilaprevir, ombitasvir, paritaprevir or dasabuvir and combinations of these (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Presence or history of liver tumours (benign or malignant).
Known or suspected malignant conditions of the genital organs, the breasts, or other organs, if sex steroid-influenced.
Undiagnosed vaginal bleeding.
Known or suspected pregnancy.
Hypersensitivity to any of the ingredients contained in Micronelle 20 ED tablets.

4.4 Special Warnings and Precautions for Use

If any of the conditions/ risk factors mentioned below are present, the benefits of Micronelle 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 on whether Micronelle 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, cerebrovascular accidents, deep venous thrombosis (DVT) and pulmonary embolism (PE). These events occur rarely in average-risk woman.
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.
It is important that women understand that VTE associated with CHC use is rare in average risk women (see Table 1). The risk in pregnancy (5 - 20 per 10,000 women over 9 months) and the risk in the postpartum period (45-65 per 10,000 women over 12 weeks) is higher than that associated with CHC use.
Combined hormonal contraceptive (CHC) in Table 1 refers to oral contraceptives with a low estrogen dose (< 50 microgram ethinylestradiol). 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.
Products that contain the progestogens levonorgestrel, such as Micronelle 20 ED, norgestimate or norethisterone are associated with the lowest risk of VTE.
The increased risk of VTE during the postpartum period must be considered if restarting Micronelle 20 ED (see Section 4.2 Dose and Method of Administration; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
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, cerebral 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).
Micronelle 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 (i.e. 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 Micronelle (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 Micronelle 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 VTE.

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 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 (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. Micronelle 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 as 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, then 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; and 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 84.38 mg lactose and each white placebo tablet contains 89.50 mg lactose anhydrous. 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 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.

Micronelle 20 ED is intended to prevent pregnancy. It does not protect against sexually transmitted infections (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 tablet 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 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 placebo tablet interval. If the COC has been taken according to the directions described in 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.

Alanine transaminase (ALT) elevations.

In patients treated with hepatitis C antiviral medications including glecaprevir, pibrentasvir, ombitasvir, paritaprevir or dasabuvir, ALT elevations may occur in women using ethinylestradiol-containing medications such as CHCs. Prescribers should consult the relevant antiviral medicine product safety information. Patients taking a CHC should therefore be switched to an alternative method of contraception (e.g. progestogen-only contraception or non-hormonal methods) prior to starting therapy.

Use in renal impairment.

No data available.

Use in hepatic impairment.

COCs are 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 the elderly.

COCs are not indicated after menopause.

Paediatric use.

COCs are 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 Micronelle 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 during 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 be started.
Women taking interacting medications on a chronic basis should consider another method of contraception.

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).
Women prescribed antibiotics (except rifampicin and griseofulvin) should use the barrier method until 7 days after completing a course of antibiotics. If the period in which the barrier method is used runs beyond the end of the active tablets in the COC pack, the white placebo tablets should be omitted and the next COC pack started.

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, e.g.

When co-administered with COCs, many human immunodeficiency virus (HIV)/ hepatitis C virus (HCV) protease inhibitors (e.g. ritonavir), non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) can increase or decrease plasma concentration of estrogen or progestogen. These changes may be clinically relevant in some cases and combinations of them have been reported to potentially affect hepatic metabolism.

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 levonorgestrel/ ethinylestradiol on other medicines.

Oral contraceptives may affect the metabolism of other medicines. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) 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; Section 4.4 Special Warnings and Precautions for Use). ALT elevations have also been observed with HCV anti-viral medicinal products including glecaprevir/pibrentasvir. Patients taking a CHC should therefore be switched to an alternative method of contraception (e.g. progestogen-only contraception or non-hormonal methods) prior to starting therapy.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
COCs are contraindicated during pregnancy. If pregnancy occurs during treatment, 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.

4.7 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. However adverse effects of Micronelle 20 ED include dizziness which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Various adverse reactions have been associated with oral contraceptive use. The most commonly reported adverse reactions with levonorgestrel/ ethinylestradiol 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 under 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 2 displays the adverse events reported amongst patients in a clinical trial of levonorgestrel 100 microgram/ ethinylestradiol 20 microgram 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 levonorgestrel 100 microgram/ ethinylestradiol 20 microgram therapy due to the adverse events. Intermenstrual bleeding and metrorrhagia (4%) were the study events most frequently reported as the reason for discontinuing levonorgestrel 100 microgram/ ethinylestradiol 20 microgram 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%: inter-menstrual 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:
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%). (See Table 3.)
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 and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

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 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Levonorgestrel/ ethinylestradiol inhibit ovulation by suppressing gonadotrophin release. Secondary mechanisms which may contribute to the effectiveness of levonorgestrel/ ethinylestradiol 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, non-comparative, multi-centre, phase III clinical study was conducted in 820 women receiving levonorgestrel 100 microgram/ ethinylestradiol 20 microgram 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 women 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 women years, in women who missed up to 3 tablets consecutively per cycle or 5 non-consecutive tablets per cycle.
The overall user efficacy pregnancy rates for levonorgestrel 100 microgram/ ethinylestradiol 20 microgram and other forms of contraception from a number of non-comparative trials based on historical data are given in Table 4.
Whilst the contraceptive efficacy of levonorgestrel 100 microgram/ ethinylestradiol 20 microgram 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 levonorgestrel 150 microgram/ ethinylestradiol 30 microgram 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 4,400 cycles were valid for cycle control analysis; the overall incidence of inter-menstrual bleeding was low. Although there was no comparative study of the cycle control of levonorgestrel 100 microgram/ ethinylestradiol 20 microgram, 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 5.
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

The pharmacokinetic information provided is derived from a single tablet (levonorgestrel 100 microgram/ ethinylestradiol 20 microgram) pharmacokinetic study conducted in 20 women.

Levonorgestrel.

Absorption.

Levonorgestrel is absorbed quickly and completely. Maximum active substance levels of ~ 2.4 nanogram/mL were reached in serum approximately 1.0 - 1.3 hours after ingestion of one tablet containing levonorgestrel 100 microgram/ ethinylestradiol 20 microgram. 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 ~ 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 the factor of 3. A steady state is reached after approximately 11 days. The pharmacokinetics of levonorgestrel are non-linear 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. The absolute bioavailability of levonorgestrel amounts to almost 100%.

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 inter-individual variations. After oral ingestion, it amounts to around 40 - 60% of the dose.
Ingestion of Micronelle 20 ED leads to maximum plasma levels of ~ 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 non-specifically 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 sulfate 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.

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 did 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 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).

6 Pharmaceutical Particulars

6.1 List of Excipients

Each pink active tablet contains the following inactive ingredients: Lactose monohydrate, povidone, crospovidone, magnesium stearate, Opadry II complete film coating system 85F34610 Pink.
Each white placebo tablet in Micronelle 20 ED contains lactose, povidone, magnesium stearate, Opadry II complete film coating system 85F18422 White.

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

Each blister platform (PVC/PVdC/Al) contains 21 active tablets and 7 placebo tablets (28 tablets). Blister platforms are packed within a carton.
Each carton contains 1 x 28, 3 x 28 or 4 x 28 tablets.
AUST R 211154.
Micronelle is a registered trade mark of Apotex Pty Ltd.
Not all pack sizes may be available.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Levonorgestrel is a white or almost white, odourless or almost odourless, crystalline powder. It is practically insoluble in water; slightly soluble in alcohol, acetone, and ether; soluble in chloroform; and sparingly soluble in methylene chloride.
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.

Chemical structure.

Levonorgestrel.


Chemical Name: 13β-ethyl-17β-hydroxy-18,19-dinor- 17α-pregn-4-en-20-yn-3-one.
Molecular Formula: C21H28O2.
Molecular Weight: 312.45.

Ethinylestradiol.


Chemical Name: 19-nor-17α-pregna-1,3,5(10)-trien- 20-yne-3,17β-diol.
Molecular Formula: C20H24O2.
Molecular Weight: 296.41.

CAS number.

Levonorgestrel.

797-63-7.

Ethinylestradiol.

57-63-6.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes