Consumer medicine information

Femme-Tab ED 20/100

Ethinyloestradiol; Levonorgestrel

BRAND INFORMATION

Brand name

Femme-Tab ED 20/100 Tablets

Active ingredient

Ethinyloestradiol; Levonorgestrel

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Femme-Tab ED 20/100.

What is in this leaflet

Please read this leaflet carefully before you start using Femme-Tab ED 20/100. It will advise you about how to take Femme-Tab ED 20/100 properly and when to tell your doctor about health-related conditions. If you have any questions or need more advice, ask your doctor, professional health care provider or pharmacist.

What is Femme-Tab ED 20/100 used for and how does it work

Femme-Tab ED 20/100 is a combined oral contraceptive (often called "the Pill") consisting of 21 white to off white active tablets and 7 red-brown inactive (placebo) tablets. Each white to off white round film-coated tablet contains a small amount of two different female hormones. These are levonorgestrel (a progestogen) and ethinyloestradiol (an oestrogen). Because of the small amount of hormones, Femme-Tab ED 20/100 is considered to be a low-dose combined oral contraceptive preparation. The red-brown inactive tablets do not contain any active ingredients.

How does Femme-Tab ED 20/100 work?

Combined oral contraceptive Pills, such as Femme-Tab ED 20/100, provide one of the most effective reversible methods of contraception known. Usually, when Femme-Tab ED 20/100 is taken according to the instructions, the egg cells (normally released by the ovary each month) are prevented from maturing to the point where they can be fertilised. In addition, the cervical mucus remains thick, so it is more difficult for a man's sperm to enter the womb. Also, the lining of the womb is not prepared sufficiently for a fertilised egg to grow in.

What is Femme-Tab ED 20/100 used for?

Femme-Tab ED 20/100 is used to prevent pregnancy. Combined oral contraceptives are a very effective method of birth control. When taken correctly (without missing tablets) the chance of becoming pregnant is very low (approximately 1% per year). The failure rate may increase when tablets are missed or taken incorrectly.

Like other combined oral contraceptive pills, Femme-Tab ED 20/100 may also have non-contraceptive health benefits.

  • Your period may be lighter and shorter. As a result, the risk of anemia may be lower. Your period pains may become less severe or may completely disappear.
  • Some serious disorders have been reported to occur less frequently in users of "high-dose" oral contraceptive pills. These are benign breast disease, ovarian cysts, pelvic infections (pelvic inflammatory disease or PID), ectopic pregnancy (pregnancy in which the embryo implants outside of the womb) and cancer of the endometrium (lining of the womb) and ovaries. This may also be the case for "low-dose" pills such as Femme-Tab ED 20/100, but so far this has only been confirmed for endometrial and ovarian cancer.

Before you use Femme-Tab ED 20/100

Do not use Femme-Tab ED 20/100 if you have any of the conditions listed below. If any of these apply to you, tell your doctor before starting to use Femme-Tab ED 20/100. Your doctor may advise you to use a different type of hormonal contraception or an entirely different (non-hormonal) method of birth control.

You must not use Femme-Tab ED 20/100 if:

  • you have, or have ever had a disorder affecting the blood circulation. In particular, those conditions relating to thrombosis. Thrombosis is the formation of a blood clot. This may occur in the blood vessels of the legs (deep vein thrombosis), the lungs (pulmonary embolism), the heart (heart attack), the brain (stroke), or other parts of the body. (See also the section later in this leaflet called "Femme-Tab ED 20/100 and thrombosis").
  • you have or have ever had a stroke caused by a rupture of a blood vessel in the brain
  • you have or have ever had a condition that may be a first sign of a heart attack (such as angina pectoris or chest pain) or stroke (such as transient ischemic attack or small reversible stroke)
  • you have a history of migraine accompanied by visual symptoms or speech disability or weakness or numbness in any part of your body
  • you have diabetes mellitus with blood vessel damage
  • you or someone in your immediate family has or has had high blood levels of cholesterol or triglycerides (fatty substances)
  • you have or have had pancreatitis (an inflammation of the pancreas) associated with high levels of fatty substances in your blood
  • you have jaundice (yellowing of the skin) or severe liver disease, as long as liver function test results have not returned to normal
  • you have or have had a cancer that may grow under the influence of sex hormones (e.g. cancer of the breast or the genital organs)
  • you have or have had a benign or malignant liver tumour
  • you have any unexplained vaginal bleeding
  • you are pregnant or think you might be pregnant
  • you are allergic (hypersensitive) to any of the ingredients of Femme-Tab ED 20/100

If any of these conditions appear for the first time while using Femme-Tab ED 20/100, stop taking it at once and consult your doctor. In the meantime, use non-hormonal contraceptive measures.

Tell your doctor if:

If Femme-Tab ED 20/100 is used in the presence of any of the conditions listed below or they appear for the first time, recur or worsen during treatment, you may need to be kept under close observation. Your doctor can explain this to you. You should tell your doctor if:

  • you smoke
  • you have diabetes
  • you are overweight
  • you have high blood pressure
  • you have a heart valve disorder or a certain heart rhythm disorder
  • you have an inflammation of your veins (superficial phlebitis)
  • you have varicose veins
  • anyone in your immediate family has had thrombosis, a heart attack or a stroke
  • you suffer from headaches
  • you suffer from epilepsy
  • anyone in your immediate family has had breast cancer
  • you have liver, kidney or gallbladder disease
  • you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease)
  • you have systemic lupus erythematosus (SLE; a disease affecting the skin all over the body)
  • you have haemolytic uremic syndrome (HUS; a blood clotting disorder causing failure of the kidneys)
  • you have sickle cell disease
  • you 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)
  • you have or have had chloasma (yellowish-brown pigmentation patches on the skin, particularly of the face); if so, avoid too much exposure to the sun or ultraviolet radiation
  • you have hereditary angioedema; taking estrogens may induce or exacerbate symptoms of angioedema. You should see your doctor immediately if you experience symptoms of angioedema such as swollen face, tongue and/or throat and/or difficulty swallowing or hives together with difficulty breathing.

What else you should know

Femme-Tab ED 20/100 does not protect against HIV infection (AIDS) or any other sexually transmitted disease.
In this leaflet, several situations are described where you should stop taking Femme-Tab ED 20/100, or where the reliability of Femme-Tab ED 20/100 may be decreased. In such situations you should not have sex or you should take extra non-hormonal contraceptive precautions, e.g. use a condom or another barrier method. Do not use rhythm or temperature methods. These methods can be unreliable because Femme-Tab ED 20/100 alters the usual changes in temperature and cervical mucus that occur during the menstrual cycle.

Femme-Tab ED 20/100 and thrombosis
Thrombosis is the formation of a blood clot which may block a blood vessel.

Thrombosis sometimes occurs in the deep veins of the legs (deep venous thrombosis). If this blood clot breaks away from the veins where it is formed, it may reach and block the arteries of the lungs, causing a so-called "pulmonary embolism". Deep venous thrombosis is a rare occurrence. The risk is highest during the first year a woman ever uses the Pill.

Venous thrombosis can develop whether or not you are taking the Pill. It can also happen if you become pregnant. The risk is higher in Pill users than in non-users, but not as high as during pregnancy.

Blood clots can also occur very rarely in the blood vessels of the heart (causing a heart attack) or the brain (causing a stroke). Extremely rarely, blood clots can occur in the liver, gut, kidney or eye.

Very occasionally a thrombosis may cause serious permanent disabilities or may even be fatal.

The risk of having a heart attack or stroke increases as you get older. It also increases the more you smoke.

When using Femme-Tab ED 20/100 you should stop smoking, especially if you are older than about 35 years of age.

If you develop high blood pressure while using Femme-Tab ED 20/100, you may be told to stop using it.

The risk of having deep venous thrombosis is temporarily increased as a result of an operation or immobilization (for example, when you have your leg or legs in plaster or splints). In women who use the Pill (such as Femme-Tab ED 20/100) the risk may be even higher. Tell your doctor you are using Femme-Tab ED 20/100 well in advance of any expected hospitalization or surgery. Your doctor may tell you to stop taking Femme-Tab ED 20/100 several weeks before surgery or at the time of immobilization. Your doctor will also tell you when you can start taking Femme-Tab ED 20/100 again after you are back on your feet.

If you notice possible signs of thrombosis, stop taking the Pill and consult your doctor immediately. (See also the section called "Stop taking Femme-Tab ED 20/100 and see your doctor immediately ")

Femme-Tab ED 20/100 and cancer
Breast cancer has been diagnosed slightly more often in women who use the Pill than in women of the same age who do not use the Pill. This slight increase in the numbers of breast cancer diagnoses gradually disappears during the course of the ten years after stopping use of the Pill. It is not known whether the difference is caused by the Pill. It may be that the women were examined more often, so that the breast cancer was noticed earlier.

In rare cases, benign, 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.

The most important risk factor for cervical cancer is persistent human papilloma virus (HPV) infection. Some studies have indicated that long-term use of the Pill may further contribute to this increased risk, but there continues to be controversy about the extent to which this finding is attributable to other factors, e.g. cervical screening and sexual behaviour including use of barrier contraceptives.

Femme-Tab ED 20/100 and other medicines
Some medicines may stop Femme-Tab ED 20/100 from working properly. These include medicines used for the treatment of epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine, topiramate and felbamate); tuberculosis (e.g. rifampicin and rifabutin) and HIV infections (e.g. ritonavir and nevirapine); antibiotics (e.g. penicillins, tetracyclines and griseofulvin) for some other infectious diseases; and the herbal remedy St. John's wort (primarily used for the treatment of depressive moods).

The Pill may also interfere with the working of other medicines (e.g. medicines containing cyclosporin or the anti-epileptic lamotrigine).

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines or herbal products, even those not prescribed.

Always tell the doctor who prescribes Femme-Tab ED 20/100 which medicines you are already using. Also tell any other doctor or dentist who prescribes another medicine (or the dispensing pharmacist) that you use Femme-Tab ED 20/100. They can tell you if you need to take additional contraceptive precautions and if so, for how long.

Femme-Tab ED 20/100 and breast-feeding
Femme-Tab ED 20/100 is generally not recommended for use during breast-feeding. If you wish to take the Pill while breast-feeding, please seek the advice of your doctor.

Femme-Tab ED 20/100 and pregnancy
Femme-Tab ED 20/100 must not be used by women who are pregnant, or who think they may be pregnant. If you suspect that you are pregnant while you are using Femme-Tab ED 20/100 you should see your doctor as soon as possible.

How to use Femme-Tab ED 20/100 properly

Follow all directions given to you by your doctor or pharmacist carefully.

They may differ from the information in this leaflet.

When you follow the directions correctly, the contraceptive protection provided by Femme-Tab ED 20/100 is continuous. This includes the week when you take the inactive tablets.

Additional contraceptive precautions are only required when special circumstances (e.g. forgetting tablets) reduce the reliability of the preparation.

Remember that Femme-Tab ED 20/100 has been prescribed for you personally. Do not share it with others.

When and how to take the tablets

The Femme-Tab ED 20/100 pack contains 21 round white to off-white active tablets and 7 red-brown inactive tablets. On the pack each tablet is marked with the day of the week on which it is to be taken. Take your tablet at about the same time each day, with some water if necessary. Follow the direction of the arrows until all 28 tablets have been taken. A period (the withdrawal bleed) should begin during the 7 days of taking the red-brown inactive tablets. Start taking your next pack on the very next day after you have completed your last pack even if your period continues. This means that you will always start new packs on the same day of the week, and also that you will have your withdrawal bleed on or about the same day each month.

Starting your first pack of Femme-Tab ED 20/100

When no hormonal contraceptive has been used in the past month
Start taking Femme-Tab ED 20/100 on the first day of your cycle, i.e. the first day of menstrual bleeding. Take your first tablet from the red section marked with that day of the week. For example, if your period starts on a Monday, take the tablet marked Monday from the red section of the pack. Then follow the days in order of the directional arrows. When you start taking Femme-Tab ED 20/100 your very first cycle may be shorter than usual. Femme-Tab ED 20/100 will work immediately, it is not necessary to use an additional contraceptive method.

When changing from a combined Pill, or vaginal ring
You start taking Femme-Tab ED 20/100 the day after you take the last active tablet from your present Pill pack (this means no tablet-free break or taking of the inactive tablets). Take your first tablet from the red section marked with that day of the week. If you are not sure which are the active tablets in your present Pill pack, ask your doctor or pharmacist.

Where you have used a vaginal ring, you should start using Femme-Tab ED 20/100 on the day of removal. If you follow these instructions, it is not necessary to use an additional contraceptive method.

When changing from a progestogen-only Pill (minipill)
You can stop taking the minipill any day and start taking Femme-Tab ED 20/100 the next day, at the usual time. Take your first tablet from the red section marked with that day of the week. Make sure you also use an additional barrier contraceptive method for the first 7 days of tablet-taking when having intercourse.

When changing from an injectable, an implant or a progestogen-releasing intrauterine system (IUS)
Start using Femme-Tab ED 20/100 when your next injection is due or on the day that your implant or IUS is removed. Take your first tablet from the red section marked with that day of the week. Make sure you also use an additional barrier contraceptive method for the first 7 days of tablet-taking when having intercourse.

After having a baby
If you have just had a baby, your doctor may tell you to wait until after your first normal period before you start taking Femme-Tab ED 20/100. Sometimes it is possible to start sooner. Your doctor will advise you. If you are breast-feeding and want to take Femme-Tab ED 20/100, you should discuss this first with your doctor.

After a miscarriage or an abortion
Your doctor will advise you.

Special circumstances

The following describes special circumstances that could alter the way you take Femme-Tab ED 20/100. In all situations where the reliability of Femme-Tab ED 20/100 is reduced (such as missing tablets) additional contraceptive precautions are required following the advice given below. This advice should also be followed in situations where other medicines may stop Femme-Tab ED 20/100 from working properly and in the case of vomiting or severe diarrhoea after taking Femme-Tab ED 20/100.

If you forget to take your tablets
If you forget to take a red-brown inactive tablet, take it as soon as you remember and continue to take the medicine as usual. As the inactive tables do not contain any active ingredients, you are still protected against pregnancy.

If you missed a white to off-white active tablet and remembered to take the missed tablet within 12 hours, you will be protected against pregnancy.

If you missed a white to off-white tablet for more than 12 hours, follow the detailed instructions below:

If you have been taking the white to off-white active tablets for 7 uninterrupted days before your missed tablet:

Take the missed tablet as soon as you remember and continue to take the medicine as usually, even if this means taking 2 tablets in one day.

After missing a white to off-white active tablet, the chance of pregnancy depends on when you missed the tablet. The risk of pregnancy is higher if you missed a tablet at the beginning or end of a pack.

If after taking your missed tablet you have less than 7 white to off-white tablets left in the blister pack, you should continue to finish the white to off-white tablets in that blister but skip the red-brown inactive tablets and start to take the white to off-white active tablets from the next pack corresponding to the correct day of the week.

This is the best way to maintain protection against pregnancy. You may not have a period until the end of the white to off-white tablets in the second blister pack. You may have spotting or breakthrough bleeding during the days of taking the active tablets.

If you have been taking the white to off-white active tablets for less than 7 uninterrupted days before your missed tablet:

Take the missed tablet as soon as you remember and continue to take the medicine as usually, even if this means taking 2 tablets in one day. You should also use additional barrier contraceptive precautions for the next 7 days:
Either don’t have sex or use a cap plus spermicide or a condom. Do not use the rhythm or temperature methods as extra contraceptive precautions. This is because oral contraceptives alter the usual menstrual cycle changes, such as changes in temperature and cervical mucus. If you have sex during that time, it is possible to get pregnant and you may need emergency contraception.

If you have had sex in the week before the missed tablet, it is possible to get pregnant. See your doctor or pharmacist for advice.

If you forget to take more than one white to off-white active tablet, see your doctor or pharmacist for advice.

If you vomit or have severe diarrhoea after taking Femme-Tab ED 20/100
If you vomit or have severe diarrhoea within 3 to 4 hours after taking your Femme-Tab ED 20/100 active tablets, the active ingredients may not have been completely absorbed. This is like missing a tablet. Therefore, follow the advice for missed tablets. If vomiting or diarrhoea occurs while taking the inactive tablets, this does not have any influence on the contraceptive reliability.

If you are taking medicines that affect Femme-Tab ED 20/100
Some medicines may stop Femme-Tab ED 20/100 from working properly. These medicines are listed in an earlier section. For the time that you are taking the medicine and for the next 7 days follow the advice for missed tablets. If you are taking rifampicin, or you are taking these medicines continuously, your doctor will advise you on the length of time you need to take extra contraceptive precautions.

If you want to delay a period
You can delay your period if you miss out the red-brown inactive tablets and go straight to the white to off-white active tablets in the red section of your next blister pack. Continue with this pack until this pack is empty. Your period will start while you are taking the red-brown inactive tablets in the next pack. You may have some breakthrough bleeding or spotting while you are taking the white to off-white active tablets.

If you want to change the starting day of your period
If you take your tablets as directed, you will have your period on about the same day every 4 weeks. If you want to change this, just shorten (never lengthen) the duration of taking the red-brown inactive tablets. For example, if your period usually starts on a Friday and in future you want it to start on Tuesday (3 days earlier) you should start your next pack 3 days sooner than you usually do, discard the 3 remaining red-brown tablets of your previous pack and then continue with the next pack without having a break between the packs. If you make the duration of taking the inactive tablets very short (e.g. 3 days or less), you may not have bleeding during the break. You may have some breakthrough bleeding or spotting during the use of the next pack.

If you have unexpected bleeding
As with other Pills, for the first few months, you can have irregular vaginal bleeding (spotting or breakthrough bleeding) with Femme-Tab ED 20/100 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 Femme-Tab ED 20/100 (usually after about 3 tablet-taking cycles). If it continues, becomes heavy or starts again, tell your doctor.

If you have missed a period
If you have taken all of your tablets at the right time, and you have not vomited, had severe diarrhoea or used other medicines, then you are very unlikely to be pregnant. Continue to take Femme-Tab ED 20/100 as usual.

If you miss your period twice in a row, you may be pregnant. Tell your doctor immediately. Do not start the next pack of Femme-Tab ED 20/100 until your doctor has checked that you are not pregnant.

When you want to stop taking Femme-Tab ED 20/100
You can stop taking Femme-Tab ED 20/100 at any time you want. If you stop because you want to get pregnant, it is generally recommended that you wait until you have had a natural period before trying to conceive. This helps you to work out when the baby will be due.

If you do not want to become pregnant, ask your doctor about other methods of birth control.

Overdosage

There have been no reports of serious harmful effects from taking too many Femme-Tab ED 20/100 tablets at one time. If you think that you or anyone else may have taken too much Femme-Tab ED 20/100, telephone your doctor or the Poisons Information Centre (13 11 26 in Australia) for advice, or go to the Emergency Department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need medical attention.

While using Femme-Tab ED 20/100

Things you must do:

If you vomit within 3 to 4 hours or have severe diarrhoea after taking a white to off-white active tablet, the active ingredients may not have been completely absorbed. This should be treated as missing a tablet. Follow the advice above for missed tablets.

Femme-Tab ED 20/100 does not protect you from sexually transmitted diseases (STDs), such as HIV-AIDS, Chlamydia, genital herpes, genital warts, gonorrhoea, hepatitis B, human papilloma virus and syphilis.

You will need additional barrier contraceptives (e.g. condoms) to protect yourself from STDs.

Have regular check-ups with your doctor.

When you are using Femme-Tab ED 20/100, your doctor will tell you to return for regular check-ups, including a pap smear test. Your doctor will advise how often you need to take the test.

Stop taking Femme-Tab ED 20/100 and see your doctor immediately:

  • if you get a blood clot, heart attack or stroke. Warning signs for a blood clot, heart attack or stroke to look out for are:
    - an unusual cough
    - severe pain in the chest which may reach the left arm
    - 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 or swelling in either of your legs
  • if you become pregnant while taking the medicine
  • if you miss your period twice in a row. You may be pregnant. Do not start the next pack of Femme-Tab ED 20/100 until your doctor has checked that you are not pregnant

Tell your doctor:

  • if you develop high blood pressure while taking the medicine. You may be advised to stop taking it.
  • if you have unexpected bleeding and it continues, becomes heavy, or occurs again. 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 protection, but continue to take your tablets as usual. Irregular vaginal bleeding usually stops once your body has adjusted to the Pill, usually after about 3 months.
  • if you have any concerns for a missed period. It is very unlikely to be pregnant if you have been taking the medicine correctly, provided that you have taken the white to off-white active tablets at the right time, you have not been taking any other medicines that may interfere with Femme-Tab ED 20/100, and you have not vomited or had severe diarrhoea during the cycle.

Tell your doctors, pharmacists, dentists, surgeons or anaesthetists that you are taking Femme-Tab ED 20/100:

  • Before you have any treatments or tests
  • Before you start any new medicines
  • Before any surgeries. The risk of having deep venous thrombosis is temporarily increased as a result of an operation or immobilisation (for example, when you have your leg or legs in plaster or splints). The excess risk of thrombosis is highest during the first year a woman takes a combined oral contraceptive. Your doctor may tell you to stop taking the medicine several weeks before surgery, or at the time of immobilisation, and when you can start taking the medicine again.

Things you must not do:

  • Do not use Femme-Tab ED 20/100 for other purposes unless advised by your doctor
  • 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 Femme-Tab ED 20/100, or do not take a tablet every day.

Side effects

Tell your doctor if you notice any unwanted side effects, especially if severe or persistent, or if there is a change in your health that you think might be caused by Femme-Tab ED 20/100.

All medicines can have side effects. Some are serious, most of them are not. Do not be alarmed by the following lists of the side effects. You may not experience any of them.

More common side effects

These are usually mild and lessen with time.

If you notice any of the following side effects and have concerns or questions, tell your doctor or pharmacist:

  • nausea
  • stomach pain
  • changes in weight
  • headache, including migraine
  • mood changes, including depression
  • breast tenderness or pain

Very serious but rare side effects

If you experience any of the following tell your doctor immediately, or go to the Emergency Department at your nearest hospital. You may need urgent medical attention or hospitalisation.

  • possible signs of a thrombosis:
    - chest pain
    - breathlessness and/or difficulty breathing
    - painful swelling in your leg(s)
    - weakness, numbness or bad ‘pins and needles’ of an arm or leg
    - severe, sudden stomach pains
    - a bad fainting attack or you collapse
    - unusual headaches or migraines that are worse than usual
    - sudden problems with your speech or eyesight
  • jaundice (yellowing skin or yellowing eyes)
  • you cough up blood
  • breast lumps
  • unexplained vaginal bleeding.

After taking Femme-Tab ED 20/100

Storage

Do not use after the expiry date stated on the package.

Store all medicines properly and keep them out of reach of children.

Keep the medicine in the original packaging in a cool and dry place below 25 °C

Do not take the tablets out from the blister until it is time to take them.

Do not store the medicine in the bathroom, near a sink or on a window sill.

Do not leave the medicine in the car.

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.

Further information

Femme-Tab ED 20/100 comes in a box containing 1, 3 or 4 blister packs. AUST R 170389

Each blister pack contains 21 white to off-white active tablets and 7 red-brown inactive tablets.

The blister is marked with the days of the week for each tablet.

Ingredients

Active substances
Levonorgestrel 100 μg
Ethinyloestradiol 20 μg

Tablets also contain:

Each white to off-white active tablet also contains:

Lactose monohydrate, maize starch, gelatine, magnesium stearate, hypromellose (3cps), macrogol 4000 and titanium dioxide (E171).

Each red-brown inactive tablet contains:

Lactose monohydrate, maize starch, gelatine, magnesium stearate, hypromellose (3cps), macrogol 4000, titanium dioxide (E171), and iron oxide red (E172)

Supplier

AFT Pharmaceuticals Pty. Ltd.
113 Wicks Road
North Ryde
NSW 2113

Date of Preparation

13 August 2015

BRAND INFORMATION

Brand name

Femme-Tab ED 20/100 Tablets

Active ingredient

Ethinyloestradiol; Levonorgestrel

Schedule

S4

 

1 Name of Medicine

Levonorgestrel and ethinylestradiol.

2 Qualitative and Quantitative Composition

Femme-Tab ED 20/100 is a combined oral contraceptive (COC) tablet containing the synthetic progestogen, levonorgestrel, and the synthetic estrogen, ethinylestradiol.
Each round white to off-white active tablet contains ethinylestradiol 20 microgram and levonorgestrel 100 microgram.
Excipients with known effect: lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Film-coated tablet.
Femme-Tab ED 20/100 tablets are available in blister packs. Each blister contains 28 tablets consisting of 21 white to off-white round convex active tablets, followed by 7 red-brown round convex placebo tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

Femme-Tab ED 20/100 is used for oral contraception.

4.2 Dose and Method of Administration

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

How to take Femme-Tab ED 20/100.

One tablet is to be taken daily. Tablets must be taken in the order directed on the package every day at about the same time with some liquid as needed. Daily tablet taking should be continuous for 28 consecutive days, starting with a white to off white active tablet marked with the corresponding day of the week from the red area of the Femme-Tab ED 20/100 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 red brown placebo tablets and may not have finished before the next pack is started.

How to start Femme-Tab ED 20/100.

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 methods of contraception are required. Starting on days 2-5 of the menstrual cycle is allowed, but during the first cycle an additional barrier contraceptive method is recommended for the first 7 days of tablet taking.

When changing pills.

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

The woman should start with Femme-Tab ED 20/100 preferably on the day after the last active hormonal tablet of her previous COC, but at the latest on the day following the usual tablet free or placebo (nonhormonal) tablet interval of her previous COC.
Where a vaginal ring or has been used, the woman should start using Femme-Tab ED 20/100 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 progestogen releasing intrauterine system (IUS).

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

Following first trimester abortion.

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

Following delivery or second trimester abortion.

The woman should be advised to start at day 21 to 28 after delivery or second trimester abortion. When starting later than this, the woman should be advised to additionally use a barrier contraceptive method for the first 7 days of tablet taking. However, if intercourse has already occurred, pregnancy should be excluded before starting Femme-Tab ED 20/100 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 combined oral contraceptive 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 Femme-Tab ED 20/100 by missing the red brown placebo tablets from her current pack, and starting with the white to off white active tablets from the next pack as soon as the white to off white active tablets from the current pack are finished. 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 Femme-Tab ED 20/100 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 Femme-Tab ED 20/100 is taken according to the directions for use, the occurrence of pregnancy is highly unlikely. However, the reliability of combined oral contraceptives may be reduced under the following circumstances:

Management of missed tablets.

Missed placebo tablets can be disregarded. However, they should be discarded to avoid unintentionally prolonging the placebo tablet phase. The following advice only refers to missed white to off white active tablets:
If the user is less than 12 hours late in taking any white to off white active tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take subsequent tablets at the usual time.
If the user is more than 12 hours late in taking any white to off white active tablet, contraceptive protection may be reduced.
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.
These rules form the basis of the instructions to patients provided in the package insert.
Accordingly the following advice can be given in daily practice:

Week 1.

The user should take the last missed white to off white active tablet as soon as she remembers, even if this means taking two white to off white 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. The more white to off white active tablets missed and the closer they are to the red brown placebo tablet phase the higher the risk of a pregnancy.

Week 2.

The user should take the last missed white to off white active tablet as soon as she remembers, even if this means taking two white to off white 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 white to off white 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 white to off white active tablet, the woman should be advised to use extra precautions for 7 days.

Week 3.

The risk of reduced reliability is imminent because of the forthcoming 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 white to off white active tablet the user has taken all tablets correctly. If this is not the case, the user should be advised to follow the first of these two options and to use extra precautions for the next 7 days as well.
1. The user should take the last missed white to off white active tablet as soon as she remembers, even if this means taking two white to off white active tablets at the same time. She then continues to take tablets at her usual time until all the white to off white active tablets are taken. The 7 red brown placebo tablets must be discarded. The next pack must be started right away. The user is unlikely to have a withdrawal bleed until the end of the active tablets of the second pack, but she may experience spotting or breakthrough bleeding on tablet taking days.
2. The user may also be advised to discontinue tablet taking from the current pack. She should then have a tablet free interval of up to 7 days, including the days she missed tablets, and subsequently continue with the next pack.
If the woman missed tablets and subsequently has no withdrawal bleed in the first placebo tablet interval, 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 management of missed tablets is applicable. If the woman does not want to change her normal tablet taking schedule, she has to take the extra tablet(s) needed from another pack.

4.3 Contraindications

COCs should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during COC use, the product should be stopped immediately.
Presence or risk of venous thromboembolism (VTE) (see Section 4.4 Special Warnings and Precautions for Use):
current VTE (on anticoagulants) or history of deep venous thrombosis [DVT] or pulmonary embolism [PE];
known hereditary or acquired predisposition for venous thromboembolism, such as APC-resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency;
major surgery with prolonged immobilisation;
a high risk of venous thromboembolism due to the presence of multiple risk factors.
Presence or risk of arterial thromboembolism (ATE) (see Section 4.4 Special Warnings and Precautions for Use):
current ATE or history of ATE (e.g. myocardial infarction or stroke) or prodromal condition (e.g. angina pectoris or transient ischaemic attack [TIA]);
known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (e.g. anticardiolipin-antibodies and lupus anticoagulant);
history of migraine with focal neurological symptoms;
a high risk of arterial thromboembolism due to multiple risk factors or to the presence of one serious risk factor such as: diabetes mellitus with vascular symptoms, severe hypertension, severe dyslipoproteinaemia.
Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
Presence or history of liver tumours (benign or malignant).
Known or suspected sex steroid-influenced malignancies (e.g. of the genital organs or the breasts).
Undiagnosed vaginal bleeding.
Known or suspected pregnancy.
Hypersensitivity to any of the ingredients contained in Femme-Tab ED 20/100.

4.4 Special Warnings and Precautions for Use

If any of the conditions/risk factors mentioned below are present, the benefits of Femme-Tab ED 20/100 should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start taking it. In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her doctor. The doctor should then decide whether Femme-Tab ED 20/100 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 disease such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism. These events occur rarely in average-risk women.

Risk of venous thromboembolism (VTE).

The use of any combined hormonal contraceptive (CHC) increases the risk of VTE compared with no use. The woman should be advised that her VTE risk is highest in the first ever year of use and that there is some evidence that the risk is increased when a CHC is re-started after a break in use of 4 weeks or more.
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 post-partum period (45-65 per 10,000 women over 12 weeks) is higher than that associated with CHC use.
Combined hormonal contraceptive (CHC) in the table below 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 use and how her current risk factors influence this risk.
Products that contain the progestogens levonorgestrel, such as Femme-Tab ED 20/100, norgestimate or noresthisterone are associated with the lowest risk of VTE.
The increased risk of VTE during the postpartum period must be considered if restarting Femme-Tab ED 20/100 (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).
Femme-Tab ED 20/100 is contraindicated if a woman has multiple risk factors that put her at high risk of venous thrombosis. If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in this case her total risk of VTE should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed.
When considering risk/benefit, the doctor should take into account that the adequate treatment of a condition may reduce the associated risk of thrombosis.

Risk factors for VTE.

Obesity (body mass index over 30 kg/m2). Risk increases substantially as BMI rises.
Prolonged immobilisation, major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma.
Temporary immobilisation, including air travel > 4 hours can also be a risk factor for VTE, particularly in women with other risk factors.
Positive family history (venous thromboembolism ever in a sibling or parent especially at a relatively early age e.g. before 50).
Biochemical factors that may be indicative of hereditary or acquired predisposition for VTE include Activated Protein C (APC) resistance (including Factor V Leiden), antithrombin-III deficiency, protein C deficiency, protein S deficiency.
Other medical conditions associated with VTE: 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 Femme-Tab ED 20/100 (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 Femme-Tab ED 20/100 has not been discontinued in advance.
If a hereditary predisposition to VTE is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use.
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism.

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

Women should be informed of the symptoms of VTE and be advised to seek urgent medical attention if VTE symptoms develop and to inform the healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include:
unilateral swelling of the leg and/or foot or along a vein in the leg;
pain or tenderness in the leg which may be felt only when standing or walking;
increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include:
sudden onset of unexplained shortness of breath or rapid breathing;
sudden coughing which may be associated with haemoptysis;
sharp chest pain or sudden severe pain in the chest which may increase with deep breathing;
severe lightheadedness 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 discolouration 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.

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. Femme-Tab ED 20/100 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 a 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 HPV infection. Some epidemiological studies have indicated that long-term use of COCs may further contribute to this increased risk but there continues to be controversy about the extent to which this finding is attributable to confounding effects, e.g. cervical screening and sexual behaviour including use of barrier contraceptives.
A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using COCs. The excess risk gradually disappears during the course of the 10 years after cessation of COC use. Because breast cancer is rare in women under 40 years of age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer. These studies do not provide evidence for causation. The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. The breast cancers diagnosed in ever users tend to be less advanced clinically than the cancers diagnosed in never users.
In rare cases, benign liver tumours, and even more rarely, malignant liver tumours have been reported in users of COCs. In isolated cases, these tumours have led to life threatening intra-abdominal haemorrhages. A liver tumour should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage occur in women taking COCs.

Other conditions.

Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.
Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. However, if a sustained clinically significant hypertension develops during the use of a COC, then it is prudent for the physician to withdraw the COC and treat the hypertension. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uremic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis related hearing loss.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.
Acute or chronic disturbances of liver or kidney function may necessitate the discontinuation of COC use until markers of liver or kidney 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 diabetics using low dose COCs (containing < 50 microgram ethinylestradiol). However, diabetic women should be carefully observed while taking COCs.
Crohn's disease and ulcerative colitis have been associated with COC use.
Each white to off white active tablet contains 36.56 mg of lactose and each red brown placebo tablet contains 74.71 mg of lactose. 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 Femme-Tab ED 20/100 use, guided, see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use. This should be repeated periodically during the use of Femme-Tab ED 20/100. In general, an annual examination is recommended. Periodic medical assessment is also of importance because contraindications (e.g. a transient ischemic 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 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 diseases including HIV infections and AIDS.

Femme-Tab ED 20/100 is intended to prevent pregnancy. It does not protect against sexually transmitted diseases (STDs), including HIV infections (AIDS). The woman should be advised that additional barrier contraceptive measures are needed to prevent transmission of STDs.

Reduced efficacy.

The efficacy of Femme-Tab ED 20/100 may be reduced in the event of missed white to off white tablets, vomiting or diarrhoea during tablet taking or concomitant medication (see Section 4.2 Dose and Method of Administration).

Reduced cycle control.

With all COCs, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first months of use. Therefore, the evaluation of any irregular bleeding is only meaningful after an adaptation interval of about three cycles.
If bleeding irregularities persist or occur after previously regular cycles, then nonhormonal causes should be considered and adequate diagnostic measures are indicated to exclude malignancy or pregnancy. These may include curettage.
In some women withdrawal bleeding may not occur during the placebo tablet interval. If Femme-Tab ED 20/100 has been taken according to the directions described, see Section 4.2 Dose and Method of Administration, it is unlikely that the woman is pregnant. However, if Femme-Tab ED 20/100 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 Femme-Tab ED 20/100 use is continued.

Use in hepatic impairment.

Femme-Tab ED 20/100 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.

Femme-Tab ED 20/100 has not been specifically studied in renally impaired patients.

Use in elderly.

Femme-Tab ED 20/100 is not indicated after menopause.

Paediatric use.

Femme-Tab ED 20/100 is only indicated after menarche.

Effects on laboratory tests.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

Interactions between oral contraceptives and other medicines may lead to breakthrough bleeding and/or oral contraceptive failure.

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

Enzyme induction (increase of hepatic metabolism).

Interactions can occur with medicines that induce microsomal enzymes which can result in increased clearance of sex hormones (e.g. cytochrome P450 enzymes, CYP34A, phenytoin, barbiturates, primidone, carbamazepine, rifampicin and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and herbal medicines containing St. John's wort (Hypericum perforatum)).
HIV protease (e.g. ritonavir) and the non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and combinations of them, have been reported to potentially affect hepatic metabolism.
Women prescribed any of these medicines should temporarily use a barrier method in addition to Femme-Tab ED 20/100 or choose another method of contraception. With microsomal enzyme inducing medicines, the barrier method should be used during the time of concomitant medicine administration and for 28 days after their discontinuation.

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 and tetracyclines).
Women prescribed antibiotics (except rifampicin and griseofulvin) should use a barrier method until 7 days after completing a course of antibiotics. If the period during which the barrier method is used runs beyond the end of the hormonal tablets in the Femme-Tab ED 20/100 pack, the red brown placebo tablets should be omitted and the next Femme-Tab ED 20/100 pack started.
Women taking interacting medications on a chronic basis should consider another method of contraception.

Influence of Femme-Tab ED 20/100 on other medication.

Oral contraceptives may interfere with the metabolism of other medicines. Accordingly, plasma and tissue concentrations may either increase (e.g. cyclosporin) or decrease (e.g. lamotrigine). The prescribing information of concomitant medications should be consulted to identify potential interactions.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
The administration of Femme-Tab ED 20/100 is contraindicated during pregnancy. If pregnancy occurs during treatment with Femme-Tab ED 20/100, further intake should 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. See Section 4.3 Contraindications.
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 Femme-Tab ED 20/100 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 this medicine 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. Serious adverse reactions are arterial and venous thromboembolism.
The most serious adverse reactions associated with the use of oral contraceptives are discussed, see Section 4.4 Special Warnings and Precautions for Use.
In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her doctor. The doctor should then decide on whether Femme-Tab ED 20/100 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 formulation, 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 the COC therapy due to the adverse events. Intermenstrual bleeding and metrorrhagia (4%) were the study events most frequently reported as the reason for discontinuing the COC therapy. All other events that resulted in discontinuation were reported by less than 1% of the women.
A bioavailability study (n = 22) reported the following adverse events with a frequency of > 1%; intermenstrual bleeding 45%, headache/migraine 27%, dysmenorrhoea 23%, flu syndrome 18%, nausea 14%. A pharmacokinetic study (n = 18) reported the following adverse events with a frequency of > 1%; headache 78%, dysmenorrhoea 61%, flu syndrome 33%, common cold 28%, breast pain 17%.

Post-marketing data.

The following adverse events have been reported in users of low dose oral contraceptives and have observed at the frequencies listed in Table 3, 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 1000 and < 1 in 100 (between 0.1% and 1%); rare: > 1 in 10,000 and < 1 in 1000 (between 0.01% and 0.1%); very rare: < 1 in 10,000 (< 0.01%).
'Venous and arterial thromboembolic events' summarises the following medical entities: peripheral deep venous occlusion, thrombosis and embolism/pulmonary vascular occlusion, thrombosis, embolism and infarction/myocardial infarction/cerebral infarction and stroke not specified as haemorrhagic.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There have been no reports of serious deleterious effects from overdose.

Symptoms and signs.

Symptoms that may occur in case of taking an overdose of 'active tablets' are: nausea, vomiting and, in young girls, slight vaginal bleeding.

Management.

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.

The hormonal components of Femme-Tab ED 20/100 inhibit ovulation by suppressing gonadotrophin release. Secondary mechanisms which may contribute to the effectiveness of Femme-Tab ED 20/100 as a contraceptive include changes in the cervical mucus (which increase the difficulty of sperm penetration) and changes in the endometrium (which reduce the likelihood of implantation).

Clinical trials.

An open label, noncomparative multicentre phase III clinical study was conducted in 820 women receiving COC tablets containing ethinylestradiol 20 microgram and levonorgestrel 100 microgram for a planned individual maximum of 6 cycles (study 1). 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, reports 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 nonconsecutive tablets per cycle.
The overall user efficacy pregnancy rates for COC tablets containing ethinylestradiol 20 microgram and levonorgestrel 100 microgram and other forms of contraception from a number of noncomparative trials based on historical data are given in Table 4.
The contraceptive efficacy of the levonorgestrel 100 microgram/ethinylestradiol 20 microgram formulations ranges from 99.16-99.68%. Compared historically with the contraceptive efficacy of 99.7% for 150 microgram levonorgestrel/30 microgram ethinylestradiol tablets, this represents a similar up to 2-fold increase in the risk of pregnancy.
Cycle control was also evaluated by analysing cycle characteristics such as duration and intensity of withdrawal bleeding and the incidence of breakthrough bleeding and amenorrhoea. A total of 4400 cycles were valid for cycle control analysis; the overall incidence of intermenstrual bleeding was low. Although there was no comparative study of the cycle control of the lower dose COCs, compared with higher dosage COCs, 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 pharmacokinetic study using a single tablet containing ethinylestradiol 20 microgram and levonorgestrel 100 microgram conducted in 20 women.

Levonorgestrel.

Absorption.

Levonorgestrel is absorbed quickly and completely. Maximum active substance levels of approx. 2.4 nanogram/mL were reached in serum approximately 1.0-1.3 hours after ingestion of one tablet containing ethinylestradiol 20 microgram and levonorgestrel 100 microgram. The serum concentrations subsequently fall in at least 2 disposition phases with a terminal half-life of around 24 hours. The metabolic clearance rate, including the bound component, from plasma is approx. 1.0 mL/min/kg.

Distribution.

Levonorgestrel is bound to serum albumin and sex hormone binding globulin (SHBG). Only around 1.1% of the total serum medicine concentrations are present as free steroid, approximately 65% are specifically 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.
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 nonlinear due to an increase in binding of levonorgestrel to SHBG which is attributed to increased SHBG levels that are induced by the daily administration of ethinylestradiol. The levonorgestrel serum levels do not change any further after 1-3 cycles of use because SHBG induction is concluded. The absolute bioavailability of levonorgestrel amounts to almost 100%.

Metabolism.

Extensive reduction of the α, β-unsaturated ketone in ring A occurs, in addition to hydroxylation at carbons 2 and 16 to form dihydro and tetrahydro reduced products. Metabolites may circulate as sulfates or glucuronides, however most of the metabolites that circulate in the blood are sulfates of 3α, 5β-tetrahydro-levonorgestrel. There are also large amounts of unconjugated levonorgestrel in the circulation with small amounts of unconjugated and/or conjugated forms of 3α, 5β-tetrahydrolevonorgestrel and 16β-hydroxylevonorgestrel. Excretion occurs predominantly in the form of glucuronides.

Excretion.

Levonorgestrel is eliminated in the form of metabolites with a half-life of approximately 28 ± 7 hours and in almost equal proportions via the kidney and bile.

Ethinylestradiol.

Absorption.

Orally administered ethinylestradiol is absorbed quickly and almost completely from the gastrointestinal tract but due to first pass metabolism in gut mucosa and liver, the absolute bioavailability of ethinylestradiol is subject to considerable interindividual variations. After oral ingestion, it amounts to around 40-60% of the dose.
Ingestion of tablets containing ethinylestradiol 20 microgram and levonorgestrel 100 microgram leads to maximum plasma levels of approx. 50 picogram/mL after 1-2 hours. The substance concentration then falls in at least 2 disposition phases with a terminal half-life of around 24 hours. For technical reasons, these data can only be calculated at higher dosages.

Distribution.

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

Metabolism.

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

Excretion.

Ethinylestradiol is eliminated 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).

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 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. 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

Each white to off white active tablet contains the excipients: lactose monohydrate, maize starch, gelatin, magnesium stearate, hypromellose, macrogol 4000, and titanium dioxide.
Each red-brown placebo tablet contains lactose monohydrate, maize starch, gelatin, magnesium stearate, hypromellose, macrogol 4000, titanium dioxide, and iron oxide red.

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. Protect from light and moisture. Keep in the original packaging.
Store all medicines properly and keep them out of reach of children.

6.5 Nature and Contents of Container

Femme-Tab ED 20/100 tablets are available in PVC/PVDC/Al blister packs. Each blister contains 28 tablets and are supplied in packs of 1 (sample pack), 3 and 4 blister packs.

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

Levonorgestrel is a white or almost white, odourless or almost odourless, crystalline powder. Practically insoluble in water; slightly soluble in alcohol, in acetone, and in ether; soluble in chloroform; 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.

Schematic structure.
Chemical name: 13β-ethyl-17β-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one.
Molecular formula: C21H28O2.
Molecular weight: 312.5.

Ethinylestradiol.

Schematic structure.
Chemical name: 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol.
Molecular formula: C20H24O2.
Molecular weight: 296.4.

CAS number.

Levonorgestrel.

797-63-7.

Ethinylestradiol.

57-63-6.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription only medicine.

Summary Table of Changes