Consumer medicine information

Levlen ED

Ethinylestradiol; Levonorgestrel

BRAND INFORMATION

Brand name

Levlen ED

Active ingredient

Ethinylestradiol; Levonorgestrel

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Levlen ED.

WHAT IS IN THIS LEAFLET

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

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

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

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

WHAT LEVLEN ED IS USED FOR

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

Levlen ED is used to prevent pregnancy.

You may also experience the following benefits:

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

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

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

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

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

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

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

BEFORE YOU TAKE LEVLEN ED

When you must not take it

Do not take Levlen ED if you have an allergy to:

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

Some of the symptoms of an allergic reaction may include:

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

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

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

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

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

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

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

Do not take Levlen ED if you have, or have had:

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

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

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

Do not give this medicine to a child. Levlen ED is not intended for use in females whose periods have not yet started.

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

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

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

Before you start to take it

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

Tell your doctor if:

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

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

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

Ask your doctor to check if you:

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

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

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

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

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

Taking other medicines

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

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

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

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

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

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

HOW TO TAKE LEVLEN ED

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

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

How to take it

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

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

Each blister pack is marked with the day of the week. Take your first tablet from the red area on the blister pack corresponding to the day of the week.

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

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

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

Taking Levlen ED for the first time

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

You must also use additional barrier contraceptive precautions (e.g. condoms or a cap or diaphragm with spermicide) for the first 14 days of tablet-taking when having intercourse.

Your doctor will advise you when to start if you:

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

Changing from another contraceptive

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

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

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

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

You must also use additional barrier contraceptive precautions (e.g. condoms or a diaphragm) for the first 14 days of tablet-taking when having intercourse.

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

You must also use additional barrier contraceptive precautions (e.g. condoms or a diaphragm) for the first 14 days of tablet-taking when having intercourse.

Stopping Levlen ED

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

Additional contraceptive precautions

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

If you forget to take Levlen ED

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

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

For Levlen ED to be most effective, beige active tablets need to be taken uninterrupted for 7 days.

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

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

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

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

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

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

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

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

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

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

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (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 Levlen ED. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

WHILE YOU ARE TAKING LEVLEN ED

Things you must do

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

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

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

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

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

  • one-sided swelling of the leg and/or foot or along a vein in the leg
  • pain or tenderness in the leg which may be felt only when standing or walking
  • increased warmth in the affected leg; red or discoloured skin on the leg
  • sudden onset of unexplained shortness of breath or rapid breathing
  • sudden coughing or coughing up of blood
  • sharp chest pain or sudden severe pain in the chest which may increase with deep breathing
  • severe light headedness or dizziness
  • rapid or irregular heartbeat
  • sudden pain, swelling and slight blue discoloration of an extremity
  • sudden numbness or weakness of the face, arm or leg, especially on one side of the body
  • sudden trouble walking, dizziness, loss of balance or coordination
  • sudden confusion, slurred speech or aphasia; sudden partial or complete loss of vision, double vision, painless blurring of vision which can progress to loss of vision
  • sudden, severe or prolonged headache with no known cause
  • loss of consciousness or fainting with or without seizure
  • pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest arm, or below the breastbone
  • discomfort radiating to the back, jaw, throat, arm, stomach
  • feeling of being full, having indigestion or choking
  • sweating, nausea, vomiting extreme weakness and anxiety.

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

In women at risk of prolonged immobilisation (including major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma), your doctor may tell you to stop taking (in the case of elective surgery at least four weeks in advance) and not resume until two weeks after complete remobilisation. Another method of contraception should be used to avoid unintentional pregnancy. Your doctor may prescribe other treatment (e.g. treatment for blood clots) if Levlen ED has not been discontinued in advance.

Other risk factors for blood clotting include temporary immobilisation including air travel of greater than 4 hours, particularly in women with other risk factors. Consult your doctor if you plan to air travel for greater than 4 hours. Consult your doctor if you develop high blood pressure while taking Levlen ED – you may be told to stop taking it.

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

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

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

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

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

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

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

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

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

Things you must not do

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

Do not give your medicine to anyone else.

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

SIDE EFFECTS

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

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

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

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

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

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

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

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

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

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

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

Blood clots and the Pill

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

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

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

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

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

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

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

Cancer and the Pill

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

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

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

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

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

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

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

AFTER TAKING LEVLEN ED

Storage

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

Keep your tablets in a cool dry place where the temperature stays below 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 Levlen ED where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

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

Return any unused medicine to your pharmacist.

PRODUCT DESCRIPTION

What Levlen ED looks like

Levlen ED active tablets are beige and round.

Levlen ED inactive tablets are white and round.

Levlen ED comes in a box containing 1 or 4 blister packs. Not all pack sizes may be marketed.

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

Ingredients

Each Levlen ED beige active tablet contains:

Active ingredients:

  • 30 microgram of ethinylestradiol
  • 150 microgram of levonorgestrel

Inactive ingredients:

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

Each white inactive tablet contains:

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

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

Supplier

Made in Germany for:

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

Australian Registration Number

Levlen ED - AUST R 40193

Date of Preparation

March 2020

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

Missed a pill?
See the end of this leaflet.

® Registered Trademark of the Bayer Group, Germany

© Bayer Australia Ltd

All rights reserved.

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Levlen ED

Active ingredient

Ethinylestradiol; Levonorgestrel

Schedule

S4

 

1 Name of Medicine

Ethinylestradiol and levonorgestrel.

6.7 Physicochemical Properties

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

Chemical structure.

Ethinylestradiol.

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

Levonorgestrel.

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

CAS number.

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

2 Qualitative and Quantitative Composition

Levlen ED is a combined oral contraceptive (COC) tablet containing the synthetic estrogen, ethinylestradiol and the synthetic progestogen, levonorgestrel.
Each beige active tablet contains ethinylestradiol 30 microgram and levonorgestrel 150 microgram.

Excipients with known effect.

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

3 Pharmaceutical Form

Tablet, sugar coated.
Levlen ED tablets are available in blister packs. Each blister pack contains 28 tablets consisting of 21 round beige active tablets followed by 7 round white placebo tablets.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The contraceptive effect of COCs is based on the interaction of various factors. The primary mechanisms are inhibition of ovulation (by suppression of gonadotropins) and changes in cervical secretion (blocking the entry of sperm into the uterus).
As well as protection against pregnancy, COCs have several positive properties which, next to the negative properties (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)), can be useful in deciding on the method of birth control. For the majority of users, the cycle is more regular, menstruation is often less painful and bleeding is lighter.
The latter may result in a decrease in the occurrence of iron deficiency. In addition, with the higher dosed COCs (> 35 microgram ethinylestradiol), there is evidence of a reduced risk of fibrocystic tumours of the breasts, ovarian cysts, pelvic inflammatory disease, ectopic pregnancy, endometrial and ovarian cancer and a decreased incidence and severity of acne. These additional benefits have only been established in case control and cohort studies. Results from randomised control trials are not available. Whether this also applies to lower dosed COCs remains to be confirmed.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Ethinyloestradiol.

Absorption.

Orally administered ethinylestradiol is rapidly and almost completely absorbed. Peak serum concentrations of about 95 picogram/mL are reached within 1-2 hours. Absolute bioavailability, as a result of presystemic conjugation and first pass metabolism, is approximately 60%.

Distribution.

Ethinylestradiol is highly but nonspecifically bound to serum albumin (approximately 98.5%), and induces an increase in the serum concentrations of sex hormone binding globulin (SHBG). An apparent volume of distribution of about 5 L/kg was reported.

Metabolism.

Ethinylestradiol is subject to presystemic conjugation in both small bowel mucosa and the liver. Ethinylestradiol is primarily metabolised by aromatic hydroxylation but a wide variety of hydroxylated and methylated metabolites are formed, and these are present as free metabolites and as conjugates with glucuronides and sulfate. The metabolic clearance rate is approximately 5 mL/min/kg.

Excretion.

Ethinylestradiol serum levels decrease in two phases, the terminal disposition phase is characterised by a half-life of approximately 24 hours. Ethinylestradiol is not excreted as unchanged drug. Ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 4:6. The half-life of metabolite excretion is approximately 1 day.

Steady-state conditions.

Ethinylestradiol serum concentrations increase slightly after daily oral administration of ethinylestradiol/ levonorgestrel tablets. The maximum concentrations are about 114 picogram/mL at the end of a treatment cycle. According to the variable half-life of the terminal disposition phase from serum and the daily ingestion, steady-state serum levels of ethinylestradiol will be reached after about one week.

Levonorgestrel.

Absorption.

Orally administered levonorgestrel is rapidly and completely absorbed. Peak serum concentrations of about 3-4 nanogram/mL are reached at about 1 hour after single ingestion. Levonorgestrel is almost completely bioavailable after oral administration. In a study comparing the AUC level following 0.09 mg levonorgestrel administration orally with same dose administered intravenously in 18 healthy women, the absolute bioavailability obtained was 82%.

Distribution.

Levonorgestrel is bound to serum albumin and to SHBG. Only 1.3% of the total serum drug concentrations are present as free steroid, approximately 64% are specifically bound to SHBG and about 35% are nonspecifically bound to albumin. The ethinylestradiol induced increase in SHBG influences the proportion of levonorgestrel bound to the serum proteins, causing an increase of the SHBG bound fraction and a decrease of the albumin bound fraction. The apparent volume of distribution of levonorgestrel is about 184 L after single administration.

Metabolism.

Levonorgestrel is extensively metabolised. The major metabolites in plasma are the unconjugated and conjugated forms of 3α, 5β-tetrahydrolevonorgestrel. Additionally, based on in vitro and in vivo studies, CYP3A4 is the main enzyme involved in the oxidative metabolism of levonorgestrel.
The clearance rate from serum is approximately 1.3-1.6 mL/min/kg.

Excretion.

Levonorgestrel serum levels decrease in two phases, which are characterised by half-lives of approximately 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 ingestion, drug serum levels increase about three to fourfold reaching steady-state conditions during the second half of a treatment cycle. Levonorgestrel pharmacokinetics are influenced by SHBG levels, which are increased about 1.7-fold after daily oral administration of ethinylestradiol/ levonorgestrel tablets. This effect leads to a reduction of the clearance rate to about 0.7 mL/min/kg at steady state.

5.3 Preclinical Safety Data

Genotoxicity.

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

Carcinogenicity.

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

4 Clinical Particulars

4.1 Therapeutic Indications

Oral contraception.

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 Warning 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 VTE, 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 VTE due to the presence of multiple risk factors.
Presence or risk of arterial thromboembolism (ATE) (see Section 4.4 Special Warning and Precautions for Use).
Current ATE or history of ATE (e.g. myocardial infarction [MI] or stroke) or prodromal condition (e.g. angina pectoris or transient ischaemic attack [TIA]).
Known hereditary or acquired predisposition for ATE, such as hyperhomocysteinaemia and antiphospholipid-antibodies (e.g. anticardiolipin-antibodies and lupus anticoagulant).
History of migraine with focal neurological symptoms.
A high risk of ATE due to multiple risk factors or to the presence of one serious risk factor such as: diabetes mellitus with vascular symptoms; severe hypertension; severe dyslipoproteinaemia.
Pancreatitis or a history thereof, if associated with severe hypertriglyceridaemia.
Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
Use of direct-acting antiviral (DAA) medicinal products containing ombitasvir, paritaprevir, or dasabuvir, and combinations of these (see Section 4.5 Interactions with Other Medicines and Other Form of Interactions).
Presence or history of liver tumours (benign or malignant).
Known or suspected sex steroid-influenced malignancies(e.g. of the genital organs or the breasts).
Undiagnosed vaginal bleeding.
Known or suspected pregnancy.
Hypersensitivity to any of the ingredients contained in Levlen ED.

4.4 Special Warnings and Precautions for Use

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

Circulatory disorders.

Epidemiological studies have suggested an association between the use of COCs containing ethinylestradiol and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as MI, stroke, DVT and PE. These events occur rarely in average-risk women.

Risk of venous thromboembolism (VTE).

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

Risk factors for VTE.

Obesity (body mass index over 30 kg/m2). Risk increases substantially as BMI rises.
Prolonged immobilisation, major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma.
Temporary immobilisation including air travel > 4 hours can also be a risk factor for VTE, particularly in women with other risk factors.
Positive family history (VTE ever in a sibling or parent especially at a relatively early age e.g. before 50).
Biochemical factors that may be indicative of hereditary or acquired predisposition for VTE include Activated Protein C (APC) resistance (including Factor V Leiden), antithrombin-III deficiency, protein C deficiency, protein S deficiency.
Other medical conditions associated with VTE include: Cancer; Systemic lupus erythematosus; Haemolytic uraemic syndrome; Chronic inflammatory bowel disease (e.g. Crohn’s disease or ulcerative colitis); Sickle cell disease.
Increasing age, particularly above 35 years.
Smoking.
In women at risk of prolonged immobilisation (including major surgery, any surgery to the legs or pelvis, neurosurgery, or major trauma), it is advisable to discontinue use of Levlen ED in the case of elective surgery at least four weeks in advance) and not resume until two weeks after complete remobilisation. Another method of contraception should be used to avoid unintentional pregnancy. Antithrombotic treatment should be considered if Levlen ED has not been discontinued in advance.
If a hereditary predisposition to VTE is suspected, the woman should be referred to a specialist for advice before deciding about any CHC use.
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in VTE.

Symptoms of VTE (DVT and PE).

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 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 PE can include: sudden onset of unexplained shortness of breath or rapid breathing; sudden coughing which may be associated with haemoptysis; sharp chest pain or sudden severe pain in the chest which may increase with deep breathing; severe light headedness or dizziness; rapid or irregular heartbeat.
Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific and might be misinterpreted as more common or less severe events (e.g. respiratory tract infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision. Sometimes loss of vision can occur almost immediately.

Risk of arterial thromboembolism (ATE).

Epidemiological studies have associated the use of CHCs with an increased risk for ATE (e.g. MI, 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. Levlen ED is contraindicated if a woman has one serious or multiple risk factors for ATE that puts her at high risk of arterial thrombosis. If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in this case her total risk should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed.

Risk factors for ATE.

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

Symptoms of ATE.

Women should be informed of the symptoms of ATE and be advised to seek urgent medical attention if ATE symptoms develop and to inform the healthcare professional that she is taking a CHC.
Symptoms of 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 MI can include: pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest arm, or below the breastbone; discomfort radiating to the back, jaw, throat, arm, stomach; feeling of being full, having indigestion or choking; sweating, nausea, vomiting or dizziness; extreme weakness, anxiety, or shortness of breath; rapid or irregular heartbeats.

Tumours.

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

Other conditions.

Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when taking COCs.
Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. However, if a sustained clinically significant hypertension develops during the use of a COC, it is prudent for the doctor to withdraw the COC and treat the hypertension. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis related hearing loss.
In women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.
Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal. Recurrence of cholestatic jaundice which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of COCs.
Although COCs may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in women with diabetes taking low dose COCs (containing < 50 microgram ethinylestradiol). However, women with diabetes should be carefully observed while taking COCs.
Crohn's disease and ulcerative colitis have been associated with COC use.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking COCs.
Each beige active tablet contains 32.97 mg of lactose monohydrate and each white placebo tablet contains 48.25 mg of lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption who are on a lactose free diet should take this amount into consideration.

Medical examination/ consultation.

A complete medical history and physical examination should be taken prior to the initiation or reinstitution of COC use, see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, and should be repeated periodically during the use of COCs. In general, an annual examination is recommended. Periodic medical assessment is also of importance because contraindications (e.g. a transient ischaemic attack, etc.) or risk factors (e.g. a family history of venous or arterial thrombosis) may appear for the first time during the use of a COC. The frequency and nature of these assessments should be based on established practice guidelines and be adapted to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology and relevant laboratory tests.

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

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

Reduced efficacy.

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

Reduced cycle control.

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

Use in hepatic impairment.

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

Use in renal impairment.

Levlen ED has not been specifically studied in renally impaired patients.

Use in the elderly.

Levlen ED is not indicated after menopause.

Paediatric use.

Levlen ED is only indicated after menarche.

Effects on laboratory tests.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

Note.

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

Effects of other medicines on Levlen ED.

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

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

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

Substances with variable effects on the clearance of COCs.

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

Substances decreasing the clearance of COCs (enzyme inhibitors).

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

Influence of Levlen ED on other medicines.

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

Pharmacodynamic interactions.

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

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Levlen ED is contraindicated during pregnancy. If pregnancy occurs during treatment with Levlen ED, further intake must be stopped immediately.
Epidemiological studies have found no significant effects on foetal development in children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during early pregnancy.
Lactation may be influenced by COCs as they may reduce the quantity and change the composition of breast milk. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk. Therefore, the use of COCs should generally not be recommended until the nursing mother has completely weaned her child.

4.8 Adverse Effects (Undesirable Effects)

Various adverse reactions have been associated with oral contraceptive use. The most commonly reported adverse reactions with Levlen ED are nausea, abdominal pain, increased weight, headache, depressed mood, altered mood, breast pain and breast tenderness. They occur in ≥ 1% of users.
Serious adverse reactions are arterial and venous thromboembolism.
The most serious reactions associated with the use of oral contraceptives are discussed see Section 4.4 Special Warnings and Precautions for Use.
In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her doctor. The doctor should then decide on whether COC use should be discontinued.
The following adverse reactions have been reported in users of COCs and the association has been neither confirmed nor refuted.

Genital tract.

Changes in vaginal discharge (e.g. due to vaginitis).

Breast.

Breast tenderness, breast pain, breast hypertrophy and breast discharge.

Gastrointestinal tract.

Nausea, diarrhoea, abdominal pain and vomiting.

Skin.

Various skin disorders (e.g. acne, hirsutism, alopecia, rash, urticaria, erythema nodosum, erythema multiforme).

Eyes.

Contact lens intolerance, cataract.

CNS.

Headache, migraine, depressive moods, mood altered and change in libido.

Metabolic.

Fluid retention, and change in bodyweight.

Body as a whole.

Hypersensitivity reaction.

Vascular disorders.

Venous and arterial thromboembolic events (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.
(Also see Section 4.4 Special Warnings and Precautions for Use, Effects on laboratory tests).

Reporting suspected adverse effects.

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

4.2 Dose and Method of Administration

How to take Levlen ED.

COCs, when taken correctly, have a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly.
One tablet is to be taken daily. The tablets must be taken in the order directed on the package at about the same time every day, with some liquid as needed. Daily tablet taking should be continuous for 28 consecutive days, starting with a tablet corresponding to that day of the week from the red section of the Levlen ED pack.
If a woman starts on a Monday, Tuesday, Wednesday, Thursday or Friday, her first tablet is a white placebo one, while if she starts on a Saturday or Sunday her first tablet will be a beige active one. Thereafter, one tablet is taken daily, following the arrows marked on the pack, until all tablets have been taken. Each subsequent pack is started the day after the last tablet of the previous pack. Withdrawal bleeding usually starts on day 2 to 3 after starting the white placebo tablets (last row) and may not have finished before the next pack is started.

How to start Levlen ED.

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

Tablet taking has to start on day 1 of the woman's natural cycle (i.e the first day of her menstrual bleeding), but during the first cycle additional nonhormonal contraceptive methods must be used for the first 14 days of tablet taking.

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

The woman should start with Levlen ED on the day after the last active tablet (the last tablet containing the active substances) of her previous COC.
In case a vaginal ring has been used, the woman should start taking Levlen ED on the day of removal.

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

The woman may switch from a minipill on any day; an implant, or IUS, on the day of its removal; or an injectable, when the next injection would be due. In all of these cases the woman should be advised to additionally use a barrier method for the first 14 days of tablet taking.

Following first trimester abortion.

The woman may start immediately. Additional nonhormonal contraceptive measures are necessary for the first 14 days of tablet taking.

Following delivery or second trimester abortion.

Women should be advised to start 21 to 28 days after delivery or second trimester abortion. Additional nonhormonal contraceptive methods are necessary for the next 14 days. If intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period.
For breastfeeding women see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.

Additional contraceptive precautions.

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

How to shift periods or how to delay a period.

To delay a period the woman should continue with another pack of Levlen ED by missing the white placebo tablets from the current pack, and starting with the beige active tablets from the next pack as soon as the beige 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 Levlen ED is then resumed after the white placebo tablet phase.
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 white placebo tablet phase 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 Levlen ED is taken according to the directions for use, the occurrence of pregnancy is highly unlikely. However, the reliability of COCs may be reduced under the following circumstances.

Management of missed tablets.

Missed pills from the last row of the blister are placebo tablets and thus can be disregarded. However they should be discarded to avoid unintentionally prolonging the placebo tablet phase. The following advice only refers to missed beige active tablets (rows 1-3 of the blister).
If the woman is less than 12 hours late in taking any beige active tablet, contraceptive protection is not reduced. The woman should take the tablet as soon as she remembers and should take further tablets at the usual time.
If the woman is more than 12 hours late in taking any beige active tablet, contraceptive protection may be reduced. The more tablets are missed and the closer they are to the white placebo tablet phase, the higher the risk of a pregnancy.
The management of missed tablets can be guided by the following two basic rules.
1. Active tablet taking must never be discontinued for longer than 7 days.
2. Seven days of uninterrupted active tablet taking are required to attain adequate suppression of the hypothalamic pituitary ovarian axis.

Accordingly, the following advice can be given in daily practice.

Week 1 of active tablets.

If the woman is more than 12 hours late in taking any beige active tablet (or several active tablets) from the pack, she should take the last missed beige active tablet as soon as she remembers, even if this means taking two tablets in one day at the same time, and then continue to take tablets at the normal time. Additional contraceptive precautions such as a condom should be used for the next 7 days.
If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered.

Week 2 of active tablets.

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

Week 3 of active tablets.

The risk of reduced reliability is imminent because of the forthcoming white placebo tablet interval. However, by adjusting the tablet intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the following two options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed beige active tablet the woman has taken all tablets correctly. If this is not the case, the woman should be advised to follow the first of these two options and to use extra precautions for the next 7 days as well.
1. The woman should take the last missed beige active tablet as soon as she remembers, even if this means taking two beige active tablets at the same time. She then continues to take tablets at her usual time until the beige active tablets are taken. The 7 white placebo tablets must be discarded. The next pack must be started right away. The woman is unlikely to have a withdrawal bleed until the end of the beige active tablets of the second pack, but she may experience spotting or breakthrough bleeding on tablet taking days.
2. The woman may also be advised to discontinue tablet taking from the current pack. She should then have a tablet-free interval of up to 7 days, including the days she missed tablets, and subsequently continue with the next pack.
If the woman missed tablets and subsequently has no withdrawal bleed in the hormone free white coated tablet phase, the possibility of a pregnancy should be considered.

Advice in case of gastrointestinal disturbances.

In case of severe gastrointestinal disturbances, absorption may not be complete and additional contraceptive measures should be taken.
If vomiting occurs within 3-4 hours after taking an active tablet, 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.

4.7 Effects on Ability to Drive and Use Machines

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

4.9 Overdose

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

7 Medicine Schedule (Poisons Standard)

S4.

References

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

6 Pharmaceutical Particulars

6.1 List of Excipients

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

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Levlen ED tablets are available in PVC/Al blister packs and are supplied in cartons containing memo 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 by taking to your local pharmacy.

Summary Table of Changes