Consumer medicine information

Microlut

Levonorgestrel

BRAND INFORMATION

Brand name

Microlut

Active ingredient

Levonorgestrel

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Microlut.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Microlut. 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 Microlut 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 MICROLUT IS USED FOR

Microlut is an oral progestogen-only contraceptive, commonly known as the ‘Mini-pill’.

Microlut is used to prevent pregnancy.

When taken correctly, it prevents you from becoming pregnant in several ways, including:

  • 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
  • impairing mid-cycle functions, which may contribute to contraceptive action.

Like all oral contraceptives (OC), Microlut 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 MICROLUT

When you must not take it

Do not take Microlut if you have an allergy to:

  • levonorgestrel the active ingredient in Microlut
  • 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 Microlut 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 Microlut if you 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 Mini-pill. However, the risk of having a blood clot when taking the Mini-pill is less than the risk of having a blood clot during pregnancy.

Do not take Microlut 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 Mini-pill, especially if you are older than 35 years of age.

Do not take Microlut if you have, or have had:

  • diabetes mellitus with blood vessel damage
  • 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)
  • benign or malignant liver tumour
  • unexplained vaginal bleeding.

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

Do not give this medicine to a child. Microlut 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 have abdominal pain with infrequent and/ or irregular periods
  • you have ever had an extra uterine/ectopic pregnancy (where an embryo has developed outside the womb) or an impairment in your fallopian tube function (e.g. caused by inflammation).
  • 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
  • kidney or heart problems
  • migraine
  • asthma
  • epilepsy
  • depression

Ask your doctor to check if you:

  • are overweight
  • have high cholesterol or triglycerides
  • have liver disease
  • have gall bladder disease
  • have a condition that occurred for the first time, or worsened during pregnancy or previous use of sex hormones (e.g. cholestatic jaundice and/or pruritis (itching)
  • have chloasma (yellowish-brown pigmentation patches on the skin, particularly of the face)
    – if so, avoid exposure to the sun or ultraviolet radiation.

If any of the above conditions appear for the first time, recur or worsen while taking Microlut, you should contact your doctor.

Microlut contains lactose. If you have an intolerance to some sugars, contact your doctor before you start taking Microlut.

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

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 Microlut 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 Hepatitis C Virus (HCV), such as boceprevir, telaprevir
  • medicines used to treat epilepsy such as phenytoin, primidone, barbiturates (e.g. phenobarbitone), carbamazepine, oxcarbazepine, topiramate, felbamate, lamotrigine
  • antibiotics (e.g. penicillins, nitrofurantoin, tetracycline)
  • cyclosporin, an immunosuppressant medicine
  • 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 Microlut, 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 and for some time after stopping them. Your doctor will be able to advise you on 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 MICROLUT

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, on the pharmacist label or in this leaflet, ask your doctor or pharmacist for help.

How to take it

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

An interval of exactly 24 hours should be maintained between tablets. This interval must not be exceeded by more than 3 hours.

Even if one tablet is taken late (i.e. more than 3 hours later than when it should have been taken) or if one tablet is missed altogether, protection against pregnancy may be impaired.

Swallow the tablet whole with 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 tablet from 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. Each blister pack is marked with the day of the week.

Tablets must be taken for 28 consecutive days. There is no break between packs. This means that when the first pack is finished the next should be started without interruption.

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

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

Taking Microlut for the first time

If you are starting Microlut 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. on the first day of your menstrual bleeding.

Your doctor will advise you when to start if you:

  • are taking Microlut after having a baby
  • are breast-feeding
  • have had a miscarriage or an abortion.

Changing from another contraceptive

Changing from a combined oral contraceptive:
Start taking Microlut on the day after taking the last active tablet in your previous pill pack. Do not take the inactive (sugar) tablets of your previous pack.

If you are not sure which were 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 Microlut.

Changing from a progestogen-only pill (‘minipill’):
Stop taking the previous Mini-pill on any day and start taking Microlut at the same time the next day, with out any break between Mini-pills.

Changing from a progesterone only injection or implant:
Start taking Microlut when your next injection is due, or on the day that your implant 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 Microlut

You can stop taking Microlut 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 Microlut and not stop until your doctor advises this. Seek advice from 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 Microlut disrupts the cyclical changes associated with the natural menstrual cycle e.g. changes in temperature and cervical mucus.

If you forget to take it

If you miss a tablet, take the missed tablet as soon as you remember, even if this means taking two tablets at the same time. Then continue to take your tablets at the usual time. In addition, you should 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 week before, taking your tablet(s) late or missed a tablet(s), there is a high possibility of becoming pregnant. Seek advice from your doctor or pharmacist about what to do.

Please refer to the table at the end of this leaflet “Summary of advice when late taking or missing a Mini-pill”.

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 (Australia: 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 Microlut. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

WHILE YOU ARE TAKING MICROLUT

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 Microlut, your doctor will tell you to return for regular check ups, including getting a Pap smear test. Your doctor will advise how often you need a Pap smear test. A Pap smear 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 Microlut.

Stop taking Microlut and see your doctor immediately if you notice possible signs of thrombosis. These include:

  • an unusual cough
  • severe pain or heaviness in the chest
  • breathlessness
  • any unusual, severe, or prolonged headache or migraine attack
  • partial or complete loss of vision, or double vision
  • slurring or speech disability
  • sudden changes to your hearing, sense of smell, or taste
  • dizziness or fainting
  • weakness or numbness in any part of your body
  • severe pain in your abdomen
  • severe pain, swelling or discolouration in either of your legs.

If you are going to have surgery, tell the surgeon or anaesthetist beforehand that you are taking Microlut. The risk of having DVT is temporarily increased as a result of an operation or immobilisation (for example, when you have your leg(s) in plaster/splints). In women who take the Mini-pill, the risk may be higher.

Your doctor may tell you to stop taking the Mini-pill several weeks before surgery, or at the time of immobilisation, and when you can start taking the Mini-pill again. If you notice possible signs of a thrombosis, stop taking the Mini-pill and consult your doctor immediately.

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

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

If you vomit within 3-4 hours or have severe diarrhoea after taking a 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 these tablets for the first few months, you can have irregular vaginal bleeding (spotting or breakthrough bleeding) between your periods. You may need to use sanitary protection, but continue to take your tablets as normal. Irregular vaginal bleeding usually stops once your body has adjusted to the Mini-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 tablets at the right time
  • you have not been taking a medicine(s) that may interfere with your Mini-pill
  • you have not vomited or had severe diarrhoea during this cycle.

If this is so, continue to take Microlut 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 Microlut correctly. Stop taking Microlut 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.

Microlut will not protect you from HIV-AIDS or any other sexually transmitted infection (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 Microlut 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 Microlut, 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 Microlut.

This medicine 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. Tell your doctor or pharmacist if you feel unwell.

Other side effects not listed on the following pages may also occur in some people.

The following list includes the more common side effects of your medicine. 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:

  • nausea, vomiting
  • stomach pain together with bleeding irregularities including more frequent, less frequent or no bleeding
  • headache, including migraines
  • dizziness
  • mood changes, including depression
  • breast tenderness or pain.

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 Emergency Department at your nearest hospital:

  • pain in the chest, arm or below the breastbone
  • discomfort radiating to the back
  • breathlessness and/or difficulty breathing
  • swelling, pain or tenderness in 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 speech, understanding or eyesight

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 lower abdominal pain, including loss of periods or heavy bleeding. In rare cases pregnancies may occur during use of the mini-pill. These pregnancies are more likely to be extrauterine/ectopic (where the embryo grows outside of the womb)
  • 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.

Thrombosis and the Mini-pill

Thrombosis is the formation of a blood clot that may block a blood vessel.

Thrombosis sometimes occurs in the deep veins of the legs (DVT). If a blood clot breaks away from the veins where it has formed, it may reach and block the arteries of the lungs, causing pulmonary embolism (PE).

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 Mini-pill. They can also happen during pregnancy. The risk of having blood clots is higher in Mini-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 Mini-pill for the first time, or after having a break from the Mini-pill for 4 weeks or more.

If you notice possible signs of a blood clot, stop taking Microlut and consult your doctor immediately.

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

Cancer and the Mini-pill

Breast cancer has been diagnosed slightly more often in women who use oral contraception than in women of the same age who do not. This slight increase in the numbers of breast cancer diagnoses gradually disappears during the course of the 10 years after women stop taking the Mini-pill.

It is not known whether the difference is caused by the Mini-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 lump. In rare cases benign liver tumours and, even more rarely, malignant liver tumours have been reported in users of the Mini-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 Mini-pill for a long time. This finding may not be caused by the Mini-pill, but may be related to sexual behaviour and other factors.

AFTER TAKING MICROLUT

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 30°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 Microlut 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 it looks like

Microlut comes in a box containing 1 or 4 blister packs. Each blister pack contains 28 white active tablets. Not all pack sizes may be marketed.

Ingredients

Active ingredients:

  • Microlut – 30 microgram of levonorgestrel per tablet

Each tablet also 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

Microlut - AUST R 10696

Date of Preparation

February 2017

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

® Registered Trademark of the Bayer Group, Germany

© Bayer Australia Ltd
All rights reserved.

Published by MIMS July 2017

BRAND INFORMATION

Brand name

Microlut

Active ingredient

Levonorgestrel

Schedule

S4

 

1 Name of Medicine

Levonorgestrel.

2 Qualitative and Quantitative Composition

Each Microlut tablet contains 0.03 mg levonorgestrel.

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.
Each blister contains 28 small white tablets, each containing levonorgestrel 0.03 mg.

4 Clinical Particulars

4.1 Therapeutic Indications

Oral contraception.

4.2 Dose and Method of Administration

The dosage of Microlut is one tablet daily without any break, taken at the same time each day with some liquid as needed. Tablets must be taken in the order directed on the package throughout the 28 days without regard to bleeding. This means that after the first pack has been finished the next should be started without interruption. The number of 28 tablets per pack is not related to the menstrual cycle. The days of the week printed on the pack provide easy control of Microlut tablet taking.
The attempt should always be made to maintain an interval of exactly 24 hours between tablets. This interval should by no means be exceeded by more than 3 hours.
If, for example, the patient chooses 7 a.m. as the time for taking her tablets, she should try to always take them at this time. Whenever this is impossible, the tablet must be taken by 10 a.m. at the very latest, otherwise protection against conception may decline. The greatest possible reliability of Microlut can be assured only by adhering as closely as possible to the 24 hour intervals.

How to start Microlut.

No preceding hormonal contraceptive use (in the past month).

Tablet taking has to start on the first day of the menstrual bleeding.

Changing from a combined oral contraceptive (COC).

The woman should start with Microlut immediately on the day after the last active tablet of her previous COC and omit the pill-free interval of this COC.

Changing from another progestogen-only pill.

When switching from another progestogen-only pill, the woman may start with Microlut on any day, without any break between the tablets.

Changing from a non-oral progestogen-only method (injection, implant).

The woman may switch from an implant on the day of its removal, from an injectable when the next injection would be due, but should in all of these cases be advised to additionally use a barrier method for the first 7 days of tablet taking.

Following abortion.

The woman may start immediately after abortion.

Following delivery.

For breastfeeding women see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.
Non-breastfeeding women should be advised to start in the fourth week after delivery. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days of tablet taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of Microlut use or the woman has to wait for her first menstrual period.

Management of missed tablets.

If even 1 tablet is taken late (i.e. if it is more than 27 hours since the last tablet was taken, i.e. more than three hours later than it should have been taken) or if even 1 tablet is missed, protection against conception may be impaired. The user should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. In addition, a barrier method should be used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered. The more tablets are missed, the higher the risk of a pregnancy.

Advice in case of vomiting or diarrhoea.

If vomiting and/or diarrhoea occur within 3-4 hours after tablet taking, absorption may not be complete and additional contraceptive measures should be taken. In such an event, the advice concerning missed tablets, as given in the section "Management of missed tablets" above, is applicable. The last tablet(s) in the pack should be used for the replacement tablet.

4.3 Contraindications

Microlut should not be used in the presence of any of the conditions listed below. Should any of the conditions appear during the use of Microlut, the use of the preparation must be discontinued immediately.
Known or suspected pregnancy.
Active venous thromboembolic disorder.
Arterial and cardiovascular disease present or in history (e.g. myocardial infarction, cerebrovascular accident, ischaemic heart disease).
Diabetes mellitus with vascular involvement.
Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
Presence or history of liver tumours (benign or malignant).
Known or suspected sex hormone-dependent malignancies, e.g. of the breast.
Undiagnosed vaginal bleeding.
Known hypersensitivity to any of the components of Microlut.

4.4 Special Warnings and Precautions for Use

Medical examination/consultation.

A complete medical history should be taken and a physical and gynaecological examination should be performed prior to the initiation or reinstitution of the use of Microlut, guided by the Contraindications and Precautions, and these should be repeated at least annually during the use of Microlut. The frequency and nature of these assessments should be based on established practice guidelines and adapted to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, and should also include cervical cytology.
Women should be advised that oral contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted diseases.
If any of the conditions/risk factors mentioned below is present, the benefits of using Microlut should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether Microlut should be discontinued.

Circulatory disorders.

An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Increased risks of thrombotic and thromboembolic events, including cerebrovascular events and myocardial infarction, have been associated with the use of combined oral contraceptives. The available literature, which is limited because of infrequent use of progestogen only contraceptives, does not suggest an increased risk of these conditions. However, there have been reports of these conditions coincident with the use of progestogen only contraceptives. Therefore, the possibility of thrombosis should be considered. The doctor should be alert to the earliest manifestations of these disorders (e.g. thrombophlebitis, pulmonary embolism, cerebrovascular insufficiency, cerebral haemorrhage, cerebral thrombosis, coronary occlusion, retinal thrombosis, mesenteric thrombosis). Should any of these occur or be suspected, the drug should be discontinued immediately.
A fourfold to six fold increased risk of thromboembolic complications following surgery has been reported in users of combined oral contraceptives. If feasible, oral contraceptives should be discontinued at least four weeks before surgery associated with an increased risk of thromboembolism or prolonged immobilisation.

Myocardial infarction and coronary artery disease.

An increased risk of myocardial infarction associated with the use of oral contraceptives has been reported. Studies found that the greater the number of underlying risk factors for coronary artery disease (cigarette smoking, hypertension, hypercholesterolaemia, obesity, diabetes, history of pre-eclamptic toxaemia) the higher the risk of developing myocardial infarction, regardless of whether or not the patient used an oral contraceptive. Oral contraceptives, however, were found to be a clear additional factor.
The increased risk of thromboembolism in the puerperium must be considered.
Treatment should be stopped at once if there are symptoms of an arterial or venous thrombotic event or suspicion thereof.

Neoplasms.

A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using combined oral contraceptives (COCs), mainly using estrogen-progestogen preparations. 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. The risk of having breast cancer diagnosed in progestogen-only pill users is possibly of similar magnitude to that associated with COC. However, for progestogen-only preparations, the evidence is based on much smaller populations of users and so is less conclusive than that for COCs. 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 OC users, the biological effects of OCs 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 oral contraceptives. In isolated cases, these tumours have led to life threatening intra-abdominal haemorrhages. A hepatic tumour should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage occur in women taking Microlut.
Some epidemiological studies also suggest that combination oral contraceptive 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 human papilloma virus (HPV).

Other conditions.

Progestogen-only pills generally do not appear to affect blood pressure in normotensive women. However, if a sustained clinically significant hypertension develops during the use of Microlut, it is advisable to withdraw Microlut and treat the hypertension.
Recurrence of cholestatic jaundice and/or pruritus which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of Microlut.
Although Microlut may have a slight effect on peripheral insulin resistance and glucose tolerance, there is generally no need to alter the therapeutic regimen in diabetics using progestogen-only pills. However, diabetic women, also those with a history of gestational diabetes mellitus, should be carefully observed while taking Microlut.
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 Microlut.
Pregnancies that occur among users of progestogen-only pill are more likely to be ectopic than are pregnancies among users of combined oral contraceptives. Therefore, in women with a history of extrauterine pregnancy or an impairment of tube function, the use of Microlut should be decided on only after carefully weighing the benefits against the risks.
If lower abdominal complaints occur together with an irregular cycle pattern (amenorrhea or amenorrhea followed by persistent bleeding), an extrauterine pregnancy must be considered.
Persistent ovarian follicles (often referred to as functional ovarian cysts) may occur during the use of Microlut. Most of these follicles are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia. In most cases, the enlarged follicles disappear spontaneously during two to three months of observation.
Oral contraceptives may cause mental depression. Patients with a history of mental depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.
These agents may cause some degree of fluid retention. Women with cardiac or renal dysfunction, convulsive disorders, migraine, or asthma require careful observation since these conditions may be exacerbated by the fluid retention which may occur in users of oral contraceptives.
Steroid hormones may be poorly metabolised in patients with impaired liver function and should be administered with caution to such patients.
Users of oral contraceptives may have disturbances in normal tryptophan metabolism which may result in a relative pyridoxine deficiency. The clinical significance of this is yet to be determined.
Serum folate levels may be depressed by oral contraceptive use. Women who became pregnant shortly after discontinuing these drugs may have a greater chance of developing folate deficiency and its complications.

Ocular lesions.

Discontinue oral contraceptives and institute appropriate diagnostic and therapeutic measures if there is unexplained, gradual or sudden, partial or complete loss of vision; proptosis or diplopia; papilloedema; or any evidence of retinal vascular lesions or optic neuritis.

Elevated blood pressure.

An increase in blood pressure has been reported in patients receiving oral contraceptives. In some women, hypertension may occur within a few months of beginning use. In the first year of use, the prevalence of women with hypertension is low but the incidence increases with increasing exposure. Age is also strongly correlated with the development of hypertension in oral contraceptive users. Women who previously have had hypertension during pregnancy may be more likely to develop an elevation of blood pressure when given oral contraceptives. If blood pressure rises markedly, the drug should be discontinued. Hypertension that develops as a result of taking oral contraceptives usually returns to normal after discontinuing the drug.

Gall bladder disease.

Studies report an increased risk of surgically confirmed gall bladder disease in users of oral contraceptives.

Headache.

The onset or exacerbation of migraine or development of headache of a new pattern which is recurrent, persistent or severe requires discontinuation of the drug and evaluation of the cause.

Carbohydrate and lipid metabolic effects.

An increase in triglycerides and total phospholipids has been observed in patients receiving oral contraceptives.

Bleeding irregularities.

Breakthrough bleeding, spotting and amenorrhoea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases or irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, appropriate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem. Changing from a progestin only oral contraceptive to an estrogen-progestin oral contraceptive, whilst potentially useful in minimising menstrual irregularity, should be done only if necessary, since this may increase the risk of thromboembolic disease.
An alteration in menstrual patterns is likely to occur in women using progestin only oral contraceptives. The amount and duration of flow, cycle length, breakthrough bleeding, spotting and amenorrhoea will probably be quite variable. Bleeding irregularities occur more frequently with the use of progestin only oral contraceptives than with estrogen-progestin oral contraceptives.
Women with a history of oligomenorrhoea or secondary amenorrhoea or young women without regular cycles may have a tendency to remain anovulatory or to become amenorrhoeic after discontinuation of oral contraceptives. Women with these pre-existing problems should be advised of this possibility and encouraged to use another method of contraception. Post-use anovulation, possibly prolonged, may also occur in women without previous irregularities.

Reduced efficacy.

The efficacy of Microlut may be reduced in the event of missed tablets (see Section 4.2 Dose and Method of Administration, Management of missed tablets), vomiting and/or diarrhoea (see Section 4.2 Dose and Method of Administration, Advice in case of vomiting or diarrhoea) or concomitant medication (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Reduced cycle control.

Menstrual bleeding.

Menstrual bleeding occurs at normal intervals and is of normal duration and intensity in the majority of cases. However, both shortened and lengthened intervals are observed.
For this reason the possibility of such changes in menstrual rhythm should, as a precaution, be pointed out to the patient before the start of tablet taking. The changes occur mainly during the first few months of use, but with continuing treatment the cycle pattern tends to stabilize, and in most cases an individual pattern is established. The patient should be encouraged to keep a record of bleeding on the calendar contained in each pack.

Procedure in the event of intermenstrual bleeding.

Intermenstrual bleeding of varying intensity may occur, particularly during the first few months. It is not a medical reason to stop tablet taking, as long as organic causes for such bleeding can be ruled out by means of adequate diagnostic measures.
It is inadvisable to attempt to influence cycle disturbances by the additional administration of an estrogen. This would only serve to reverse the changes brought about by Microlut in the cervical mucus, thereby considerably jeopardizing the contraceptive effect.

Absence of withdrawal bleeding.

Amenorrhea may occur in some women, in most cases only for one or two menstrual periods. In rare cases bleeding may fail to occur at longer intervals.
If no menstrual bleeding has occurred within 6 weeks after the last menstrual bleeding, pregnancy must be excluded before tablet taking is continued.

Use in hepatic impairment.

Microlut 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.

Microlut has not been specifically studied in renally impaired patients.

Use in the elderly.

Microlut is not indicated after menopause.

Paediatric use.

Microlut is only indicated after menarche.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Note.

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

Effects of other medicinal products on Microlut.

Interactions can occur with drugs that induce microsomal enzymes, which can result in increased clearance of sex hormones which may lead to changes in the uterine bleeding profile and/or contraceptive failure.
Women on treatment with any of these drugs should temporarily use a barrier method in addition to Microlut or choose another method of contraception. The barrier method should be used during the time of concomitant drug administration and for 28 days after their discontinuation.

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

Phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, rifabutin, griseofulvin and products containing St John's Wort (Hypericum perforatum).
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.
For women on rifampicin a barrier method should be used in addition to the POP during the time of rifampicin administration and for 28 days after its discontinuation.

Substances with variable effects on the clearance of levonorgestrel.

When co-administered with sex hormones, many HIV/HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors can increase or decrease plasma concentrations of the progestin. These changes may be clinically relevant in some cases.

Substances decreasing the clearance of levonorgestrel (enzyme inhibitors).

Strong and moderate CYP3A4 inhibitors such as azole antifungals (e.g. fluconazole, itraconazole, ketoconazole, voriconazole), verapamil, macrolides (e.g. clarithromycin, erythromycin), diltiazem and grapefruit juice can increase plasma concentrations of the progestin.
Increased intermenstrual bleeding and occasional pregnancies have been reported during concomitant administration of oral contraceptives and ampicillin, sulfamethoxypyridazine, chloramphenicol, nitrofurantoin, phenoxymethylpenicillin and neomycin. The mechanism appears to be reduced enterohepatic circulation of sex steroid due to change in bowel flora. It may be prudent for women to use supplemental forms of contraception during therapy with these antibiotics.
Combination oral contraceptives have been reported to antagonise the effectiveness of oral anticoagulants, antihypertensive agents, anticonvulsants, and hypoglycaemic agents. Patients should be carefully monitored for a decreased response to these drugs.
Combination oral contraceptives may interfere with the oxidative metabolism of diazepam and chlordiazepoxide, resulting in plasma accumulation of the parent compound. Patients receiving these benzodiazepines on a long-term basis should be monitored for increased sedative effects.
The effects of benzodiazepines on oral contraceptive metabolism have not been determined.

Effects of Microlut on other medicinal products.

Oral contraceptives may affect the metabolism of certain other drugs. Accordingly, plasma and tissue concentrations may be affected (e.g. cyclosporin).

Other forms of interaction.

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.
Papanicolaou smears should be performed before prescribing these drugs and periodically during their administration.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Microlut is not indicated during pregnancy. If pregnancy occurs during treatment with Microlut, further intake must be stopped. However, extensive epidemiological studies have revealed no significant effects on foetal development associated with the use of combined oral contraceptives before pregnancy or taken inadvertently during early pregnancy. There have been an insufficient number of pregnancies in patients using levonorgestrel only oral contraceptives to rigorously evaluate the potential for developmental toxicity; however, based on the experience with combined oral contraceptives, an increase in foetal abnormalities is not expected.
 Progestogens do not appear to affect the quantity or quality of breast milk. However, levonorgestrel is secreted into the breast milk following oral administration to lactating women. Very rarely, adverse effects on the child have been reported, including jaundice.

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.

4.8 Adverse Effects (Undesirable Effects)

In addition to the adverse effects listed (see Section 4.4 Special Warnings and Precautions for Use), the following undesirable effects have been reported in users of progestogen-only pills, although a causal relationship with progestogen only pills could not always be confirmed.
A review (McCann MF and Poter LS Contraception 1994; 50(Supp 1) S9-S198) provided estimates of adverse effects from several studies that included levonorgestrel only oral contraceptive use in women who were not breastfeeding. Approximate incidence levels associated with these studies were as follows, see Table 1:
The following reactions, as a general rule, are seen much less frequently or only occasionally in users of progestogen-only pills, however, that does not necessarily mean that these reactions have been reported in association with Microlut: gastrointestinal disturbances such as bloating and abdominal cramps, chloasma or melasma which may be persistent, breast enlargement, and secretion, change in cervical erosion or cervical secretion, rash (allergic), vaginal candidiasis.
The following adverse reactions have been reported in users of combined oral contraceptives, but the association has been neither confirmed nor refuted: premenstrual-like syndrome, changes in appetite, cystitis-like syndrome, nervousness, loss of scalp hair, erythema multiforme, erythema nodosum, haemorrhagic eruption, vaginitis, oedema.
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: chorea, porphyria, haemolytic uraemic syndrome.
The following adverse effects have been reported with users of POP pills, however, their frequency is unknown:
Contact lens intolerance, hypersensitivity, changes in libido, various skin disorders.

Postmarketing information.

The following postmarketing events have been reported for Microlut with a low frequency and causality has not been determined:
Skin disorders including acne, dermatitis acneform, chloasma, rash and skin desquamation, visual disturbance, abdominal pain, diarrhoea, migraine, alopecia.

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.

4.9 Overdose

There have been no reports of serious deleterious effects from overdose. Symptoms that may occur in this case are: nausea, vomiting and slight vaginal bleeding. 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).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Pharmacological actions.

Microlut contains the oral progestogen levonorgestrel in a very low dose. The continuous daily ingestion of 0.03 mg levonorgestrel prevents conception in several independent ways. Mainly, there are changes in the cervical mucus which make the migration and ascent of sperm difficult or block this. Furthermore, changes in the endometrium throughout the cycle can be considered as having the effect of rendering nidation difficult. Ovulation is not inhibited in the majority of women, but Microlut can impair the midcycle gonadotropin peaks and the corpus luteum function which may contribute to the contraceptive action.
The pregnancy rates of oral progestogen only contraceptives are slightly higher than that of combined progestogen-estrogen oral contraceptives. However, when taken correctly (without missing tablets), the chance of becoming pregnant is very low.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Orally administered levonorgestrel is rapidly and completely absorbed. Peak serum concentrations of 0.8 nanogram/mL are reached at about 1 hour after single ingestion of Microlut. In a study of 18 healthy women the absolute bioavailability of levonorgestrel from Microlut was found to be 82% ± 16. The mean volume of distribution of levonorgestrel was 106 L ± 37.5.

Distribution.

Levonorgestrel is bound to serum albumin and to sex hormone-binding globulin (SHBG). Only about 1.5% of the total serum drug concentrations are present as free steroid and about 65% are specifically bound to SHBG. The relative distribution of levonorgestrel in serum (free, albumin-bound, SHBG-bound) depends on the actual SHBG concentrations (see Section 5.2 Pharmacokinetic Properties, Steady-state conditions). The apparent volume of distribution of levonorgestrel is about 106 L.
Levonorgestrel distributes into mother's milk and about 0.1% of the maternal dose can be transferred to the breast-fed infant.

Metabolism.

Levonorgestrel is completely metabolized by the known pathways of steroid metabolism. The metabolic clearance rate from serum is between 1 and 1.5 mL/min/kg.

Excretion.

Levonorgestrel serum levels decrease in two phases which are characterized by half-lives of about 1 hour and about 20 hours, respectively. Levonorgestrel is not excreted in unchanged form. Its metabolites are excreted at about equal parts via urine and faeces. The half-life of metabolite excretion is about 1 day.

Steady-state conditions.

Following daily repeated administration of levonorgestrel, drug serum levels reach steady-state after about 2-3 weeks, when SHBG levels achieve steady-state. The pharmacokinetics of levonorgestrel is influenced by serum levels of SHBG. In a study of 12 healthy women administered 0.150 mg for 28 days, there was a 50% decrease in SHBG serum levels and thus, a 40% reduction in levonorgestrel trough levels after 2-3 weeks. The extent of the effect of Microlut on these binding proteins is not known.

5.3 Preclinical Safety Data

Genotoxicity.

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.

A long-term study in dogs showed that levonorgestrel was associated with an increased incidence of mammary tumours, although similar findings were 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 feed-back mechanism. The clinical relevance of this finding to humans remains largely unknown. Numerous epidemiological studies have been conducted to determine the incidence of breast, endometrial, ovarian and cervical cancer in women using combination oral contraceptives. Some of these studies have shown an increased relative risk of breast cancer in certain subgroups of combination oral contraceptive 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 containing sex hormones such as levonorgestrel. Although benign, hepatic adenomas may rupture and cause death through intra-abdominal haemorrhage. Some epidemiological studies also suggest that combination oral contraceptive 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 human papilloma virus (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

Microlut also contains the inactive excipients calcium carbonate, glycol montanate, lactose monohydrate, macrogol, magnesium stearate, maize starch, povidone, sucrose and talc.
See Section 2 Qualitative and Quantitative Composition.

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 30°C. Storage conditions and expiry date are printed on the pack.

6.5 Nature and Contents of Container

Carton containing blister packs of 1 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 in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

The chemical name for levonorgestrel is 13β-ethyl-17β-hydroxy-18, 19-dinor-17α-pregn-4 -en-20-yn-3-one. Levonorgestrel is a white or almost white, odourless or almost odourless, crystalline powder. It is insoluble in water or hexane, slightly soluble in ethanol or acetone, and sparingly soluble in methylene chloride.
Chemical formula: C21H28O2.
Molecular weight: 312.45.
Melting point: 232-239°C.

CAS number.

797-63-7.

7 Medicine Schedule (Poisons Standard)

S4, Prescription Only Medicine.

Summary Table of Changes