Consumer medicine information

Seasonique

Levonorgestrel; Ethinylestradiol

BRAND INFORMATION

Brand name

Seasonique

Active ingredient

Levonorgestrel; Ethinylestradiol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Seasonique.

What is in this leaflet

This leaflet answers some common questions about Seasonique.

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 this medicine against the benefits they expect it will provide.

If you have any concerns about this medicine, ask your doctor or pharmacist.

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

What Seasonique is used for

Seasonique is used to prevent pregnancy.

Seasonique is a combined oral contraceptive (COC), commonly known as a 'birth control pill' or 'the Pill.' It is an extended-dosing cycle taken continuously for 91 days. This means whilst taking Seasonique you may not have your monthly periods for up to 3 months (equivalent to 1 period every 3 months).

When taken correctly Seasonique prevents pregnancy in several ways:

  • it inhibits the egg release by stopping it maturing
  • it changes the cervical mucus consistency making it difficult for the sperm to reach the egg
  • it changes the lining of the uterus making it less suitable for implantation

When the Pill is taken correctly by women under close observation in clinical trials, it is more than 99% effective in preventing pregnancy. However in real life the failure rate may increase if tablets are missed or taken incorrectly.

Like all other oral contraceptives Seasonique does not protect against HIV and other sexually transmitted infections (STIs). To protect yourself against STIs you need to use additional barrier contraceptives (e.g. condoms).

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 purpose.

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

Before you take Seasonique

When you must not take it

Do not take Seasonique if you have an allergy to:

  • any medicine containing ethinyloestradiol or levonorgestrel
  • any of the ingredients listed at the end of this leaflet
  • any other similar medicines (such as other oral contraceptives).

Some of the symptoms of an allergic reaction may include:

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

Do not take Seasonique if you have had or are at risk of having:

  • deep vein thrombosis (DVT) - a blood clot in the blood vessels of the leg
  • pulmonary embolism (PE) - a blood clot in the lungs
  • venous thromboembolism (VTE) - a blood clot in the veins and heart
  • arterial thromboembolism - (ATE) - a blood clot in the arteries
  • a blood clot in other parts of the body
  • heart valve or heart rhythm disorders that may be associated with the formation of blood clots
  • heart attack or stroke
  • chest pain (angina pectoris)
  • high blood pressure which is uncontrolled
  • some severe types of headache or migraine, including migraine accompanied by visual disturbances, weakness, speech disability or numbness in any part of your body
  • A tumour that may grow under the influence of sex hormones (e.g. of the breast or genital organs)
  • diabetes with blood vessel damage
  • breast cancer or cancer of the lining of the womb, cervix or vagina, or you think you have these conditions
  • unexplained vaginal bleeding
  • liver tumour or liver disease (e.g. hepatitis and/or elevated liver enzymes)
  • inflammation of the pancreas, which is associated with very high blood levels of triglycerides (fatty substances)
  • yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of an oral contraceptive
  • high blood levels of cholesterol or triglycerides
  • sickle cell anaemia
  • changes in vision, such as blurring.

If you are not certain whether these may apply to you, or you are worried by anything in this list, tell your doctor.

Do not take this medicine if you are pregnant or you think you are pregnant. Pregnancy must be excluded before you start taking Seasonique.

Do not take this medicine in association with herbal remedy St John's Wort.

Do not give this medicine to a child.

Do not take this medicine if you have already experienced menopause.

Do not take this medicine after the expiry date (EXP) printed on the pack or if the packaging is torn or shows signs of tampering. If it is expired or 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 Seasonique

You must have a thorough medical check-up, including a Pap smear, breast check, blood pressure check and urine test.

Tell your doctor if you are allergic to any foods, dyes, preservatives or any other medicines.

Tell your doctor if you smoke. Oral contraceptives increase your risk of having a stroke or heart attack. The risk of serious side effects on the heart and blood vessels is even greater if you smoke and take oral contraceptives. The risk increases with age and with heavy smoking (15 or more cigarettes per day), especially in women older than 35 years. If you take Seasonique, you should not smoke.

The use of any combined hormonal contraceptive (CHC) increases the risk of VTE compared with no use. The VTE risk is highest in the first ever year of use. There is some evidence that the risk is increased when a CHC is re-started after a break in use of four weeks or more.

Tell your doctor (or go to Accident and Emergency immediately) if VTE symptoms develop, Symptoms can include:

  • 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
  • sharp or sudden severe chest pain
  • severe light headedness or dizziness
  • sudden, severe or prolonged headache with no known cause
  • rapid or irregular heartbeat
  • sudden blurred vision or loss of sight in one or both eyes

There is some evidence that the use of CHCs may be associated with an increased risk of ATE.

Tell your doctor (or go to Accident and Emergency immediately) if ATE symptoms develop. Symptoms 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, trouble speaking or understanding
  • sudden blurred vision or loss of sight in one or both eyes
  • 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 or dizziness;
  • extreme weakness, anxiety, or shortness of breath;
  • rapid or irregular heartbeats.

Tell your doctor if you have any other health problems, especially:

  • breast lumps, abnormal breast X-ray or mammogram
  • diabetes
  • heart disease
  • high cholesterol or blood fats
  • high blood pressure, a history of high blood pressure or high blood pressure during pregnancy
  • migraine or other headaches
  • epilepsy
  • depression
  • gallbladder disease
  • fluid retention or kidney disease
  • asthma
  • fibroids
  • yellowing of the whites of the eyes or skin (jaundice) during pregnancy or during previous oral contraceptive use
  • hereditary angioedema (swelling of the face, lips, mouth, tongue or throat)
  • chloasma (yellowish-brown patches on the skin, particularly the face.
  • hepatitis or elevated liver enzymes

If you have any of these conditions you should have regular check-ups with your doctor to make sure that taking Seasonique is not making the conditions worse.

Tell your doctor if anyone in your family has had blood clots in the deep veins of the legs, a stroke or heart attack or you have any of the following conditions.

  • obesity
  • recent surgery or trauma
  • recently had a baby
  • lost a baby in the second trimester
  • confined to bed rest for long periods.

Some women have an increased chance of blood clots due to factors such as age, family history of VTE, high body weight and smoking. Women assessed by their doctor as being at increased risk of VTE should not use Seasonique.

The risk of developing blood clots in the deep veins of your legs, which can break away and block a blood vessel elsewhere in your body, are increased if you have any of these conditions and use an oral contraceptive. Blood clots are a rare occurrence and can develop whether or not you are taking an oral contraceptive. They can also happen during pregnancy. The risk of having a blood clot is higher in oral contraceptive users than in non-users, but not as high as during pregnancy or just after having a baby.

VTE with any combined hormonal method of contraception is much less common than VTE in pregnancy and the period immediately after having a baby.

Pills containing levonorgestrel (such as Seasonique) or norethisterone appear to have lower VTE risk.

The risk of VTE with the COC is greatest for products containing over 50 micrograms of ethinyloestradiol. There is less risk for products containing less than 35 micrograms of ethinyloestradiol such as Seasonique. It is not known how Seasonique, with its 91-day cycle, influences the occurrence of such events in comparison to other levonorgestrel containing COCs, which are based on a 28-day cycle.

If you are at risk of prolonged immobilisation, due to major surgery or, any surgery to the legs or pelvis or major trauma), you should discuss this with your doctor. It is recommended to discontinue the use of Seasonique and not resume until two weeks after complete remobilisation. Another method of contraception should be used during this time to avoid unintentional pregnancy.

You should discuss this with your doctor before discontinuing the use of Seasonique.

Tell your doctor if you plan to become pregnant or are breast-feeding. Your doctor can discuss the risks and benefits involved with you.

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

Taking other medicines

Tell your doctor if you are taking any other medicines, including:

  • all prescription medicines
  • all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines may be affected by Seasonique or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor will advise you.

Tell your doctor or pharmacist if you are taking any of the following:

  • rifampicin and rifabutin for the treatment of tuberculosis
  • antibiotics such as ampicillin, other penicillins and tetracyclines
  • anti-fungal agents such as griseofulvin
  • medicines for epilepsy (such as phenytoin, primidone, carbamazepine and topiramate, phenobarbitone)
  • ritonavir for the treatment of HIV infection.
  • products used to treat hepatitis such as those containing ombitasvir, paritaprevir or dasabuvir
  • modafinil used to treat excessive daytime sleepiness
  • St. John's Wort, an ingredient in many medicines you can buy without a prescription from a pharmacy, health food shop or supermarket
  • corticosteroids such as dexamethasone.

While you are taking any of these medicines and for the next 7 days after stopping them, you must also use an additional non-hormonal method of contraception (such as condoms or a diaphragm, but not the rhythm or temperature methods).

If you take rifampicin and some other medicines, you may need to use additional non-hormonal contraception for four weeks after finishing the course of treatment.

Concomitant use with products containing ombitasvir, paritaprevir, ritonavir or dasabuvir with or without ribavirin may increase liver enzymes.

If you are taking or begin taking these medicines while taking Seasonique, you must switch to an alternative method of contraception (e.g. progestogen-only contraception or non-hormonal methods) prior to commencing therapy.

Seasonique can be restarted 2 weeks following completion of treatment with this combination regimen.

Ask your doctor or pharmacist about how long you need to use additional non-hormonal contraception.

Tell your doctor or pharmacist if you are taking any of the following.

  • atorvastatin used to treat high cholesterol
  • indinavir for the treatment of HIV infection
  • anti-fungal agents such as itraconazole and fluconazole
  • paracetamol and ascorbic acid (Vitamin C).
  • cyclosporin used to prevent organ rejection
  • theophyllines used for asthma and other breathing difficulties
  • corticosteroids
  • lamotrigine used for seizures

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Seasonique. Your doctor and pharmacist have more information on medicines to be careful with or avoid while you are taking this medicine.

How to take Seasonique

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

Seasonique pack consists of 84 pink tablets of 150 micrograms levonorgestrel and 30 micrograms ethinyloestradiol and 7 white tablets containing 10 micrograms of ethinyloestradiol

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

How to take it

The daily dosing regimen should start with the first tablet (#1) of Month 1 blister.

Take one tablet about the same time every day. Tablet taking is continuous for 91 days. You may take the tablets with or without food, and if necessary with a little liquid in the order shown at the blister pack.

Preparation of the pack
To help you keep track, there are 7 weekday sticker strips marked with the 7 days of the week. Choose the week sticker that starts with the day you begin taking the tablets. For example, if you start on a Wednesday, use the week sticker that starts with "WED". Stick the week sticker along the top of the Seasonique pack where it reads "Place week sticker here", so that the first day is above the tablet marked "1". There is now a day indicated above every tablet and you can see whether you have taken a certain pill. The arrows show the order you are to take the pills. Usually, so-called withdrawal bleeding starts when you are taking white tablets. Once you have taken the last white tablet, you should start with the following Seasonique pack, whether your bleeding has stopped or not. This means that you should start every pack on the same day of the week, and that the withdrawal bleed should occur on the same days each time. If you use Seasonique in this manner, you are protected against pregnancy during the whole 91 days. For continued protection against pregnancy make sure you have a new pack of Seasonique ready to start.

Do not confuse the tablets. One pink tablet containing levonorgestrel and ethinyloestradiol is taken daily for 84 consecutive days, followed by one white ethinyloestradiol tablet for 7 days.

When to take Seasonique

You must take Seasonique every day, regardless of how often you have sex.

The tablets must be taken every day at about the same time, if necessary with a little liquid, in the order shown on the blister pack. One tablet is to be taken daily for 91 consecutive days.

If you are concerned about this, please speak to your doctor or pharmacist.

Starting a hormonal contraceptive for the first time

To start taking Seasonique follow these steps:

  1. On the first day of your menstrual bleed, take a pink tablet containing levonorgestrel and ethinyloestradiol.
You may also begin on day 2-5 of the cycle, but then you must use extra protective measures (for example, a condom) for the first 7 days.
  1. One pink tablet should be taken daily for 84 consecutive days.
  2. One white tablet is taken for 7 consecutive days.
  3. A scheduled 'withdrawal' bleed should occur during the 7 days that the white tablets are taken.

Going on to further blister packs

Each subsequent 91-day cycle should be started without interruption on the same day of the week as you began your first dose of Seasonique, following the same schedule.

Switching from a different combined oral contraceptive, vaginal ring or transdermal patch

Follow the instructions below carefully.

When changing from a different combined oral contraceptive:

Follow the advice of your doctor. You should start with Seasonique on the day after the last active tablet (the last tablet containing the active substances) of your previous COC.

When changing from a vaginal ring or transdermal patch to Seasonique.

Follow the advice of your doctor. You should start using Seasonique on the day of removal but at the latest when the next application would have been due.

Switching from a progestogen-only contraceptive

You may switch any day from the progestogen-only pill (from an implant or the IUD on the day of its removal, from an injectable when the next injection would be due). In all of these cases you must use a barrier method of contraception (e.g. a condom) for the first 7 days of tablet-taking.

After having a miscarriage or abortion

Follow the advice of your doctor.

After having a baby

If you have just had a baby, talk to your doctor before you start taking Seasonique.

How long to take Seasonique

Continue taking your medicine for as long as your doctor tells you.

Your doctor may prescribe Seasonique for long periods, until you no longer need or want contraception.

If you are not sure how long you should be taking Seasonique, ask your doctor.

If you forget to take your tabets

White tablets: If you forget any of the white tablets (last 7 tablets in the pack), this has no effect on the reliability of Seasonique. Do not take the forgotten white tablet(s) and continue with the next tablet at the usual time.

Pink tablets: If you miss a pink tablet, depending on the day of the cycle on which the tablet has been missed, you may need to take additional contraceptive precautions, for example a barrier method such as a condom.

Take the pink tablets according to the following principles:

  • If you are less than 12 hours late when taking a tablet, the protection against pregnancy is not reduced. Take the tablet as soon as you remember and then continue taking the tablets again at the usual time.
  • If you are more than 12 hours late taking a tablet, the protection against pregnancy may be reduced. The greater the number of tablets you have forgotten the greater is the risk of becoming pregnant. There is a particularly high risk of becoming pregnant if you miss pink tablets at the beginning of the pack. Therefore you should follow the rules given below.

One pink tablet forgotten

One pink tablet forgotten between days 1-7

Take the tablet as soon as you remember even if this means taking two tablets at the same time. Continue taking the following tablets at the usual time. Use additional contraceptive precautions for the following 7 days e.g. a barrier method such as a condom. If you have had sex in the week before forgetting the tablet there is a possibility of pregnancy. So contact your doctor immediately.

One pink tablet forgotten between days 8-84

Take the tablet as soon as you remember even if this means taking two tablets at the same time. Continue taking the following tablets at the usual time. The protection against pregnancy is not reduced and you do not need to take extra contraceptive precautions.

More than one pink tablet forgotten in this pack

Days 1-7

If two pink tablets are missed, take two tablets as soon as you remember and additional two on the next day. Continue taking the following tablets at the usual time.

If 3 or more pink tablets are missed, do not take the forgotten tablets and continue taking the following tablets at the usual time. You may experience bleeding during the week following the missed tablets.

In any case use additional contraceptive precautions for the following 7 days e.g. a barrier method such as a condom. If you have had sex in the week before forgetting tablets there is a possibility of pregnancy. So contact your doctor immediately.

Days 8-84

If two pink tablets are missed, take two tablets as soon as you remember and additional two on the next day. Continue taking the following tablets at the usual time. Use additional contraceptive precautions for the following 7 days e.g. a barrier method such as a condom.

If 3 or more pink tablets are missed, do not take the forgotten tablets and continue taking the following tablets at the usual time. You may experience bleeding during the week following the missed tablets. Use additional contraceptive precautions for the following 7 days e.g. a barrier method such as a condom. If you have had sex during the days of missed tablets there is a possibility of pregnancy. So contact your doctor immediately.

If you have forgotten any of the pink tablets, and you have no bleeding during the week 13, you may be pregnant. Contact your doctor before you start the next pack.

If you vomit or have diarrhoea after taking Seasonique

If you vomit within 3-4 hours of taking a tablet or you have severe diarrhoea, there is a risk that the active substances in the pill are not fully absorbed into your body. The situation is similar to if you forget a tablet. After vomiting or diarrhoea, you must take another tablet as soon as possible. The advice given under "If you forget to take your tablets" should be followed.

If you don't want to change your normal tablet-taking pattern take the extra pink tablet from the last row in the pack.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Seasonique.

Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include:

  • feeling sick or vomiting
  • dizziness
  • feeling sleepy or tired
  • women may also experience
  • menstrual bleeding.

While you are taking Seasonique

Things you must do

Tell any other doctors, dentists and pharmacists who are treating you that you are taking Seasonique.

If you are about to start taking any new medicines, tell the doctor or pharmacist that you are taking Seasonique.

If you become pregnant while taking Seasonique, see your doctor immediately.

Use of Seasonique is generally not advisable when a woman is breast-feeding. If you want to take the pill while you are breast-feeding you should contact your doctor.

If you are about to have any blood tests, tell your doctor you are taking Seasonique.

Have regular check ups from your doctor, including a Pap smear. Oral contraceptives should not be prescribed for longer than one year without your doctor carrying out a check-up. Your doctor will advise you how often you need a Pap smear. A Pap smear can detect abnormal cells lining the cervix. Sometimes abnormal cells can progress to cervical cancer. The most important risk factor for cervical cancer is persistent human papillomavirus (HPV) infection. However, cervical cancer has been reported to occur more often in women using an oral contraceptive for a long time. This finding may not be caused by the oral contraceptive, but may be related to sexual behaviour and other reasons.

Perform regular breast self-examination. Risk factors for the development of breast cancer include increasing age, family history, obesity, never having had a baby, and late age for first full term pregnancy. Breast cancer has also been found slightly more often in women who use oral contraceptives than in women of the same age who do not use them. This slight increase in the number of breast cancer cases gradually disappears during the course of the 10 years after stopping use of oral contraceptives. It is not known whether the oral contraceptive causes the difference. It may be that the women were examined more often, so that the breast cancer was noticed earlier.

If you are concerned about contracting a sexually transmitted disease (STD), ask your partner to wear a condom when having sexual intercourse with you. Seasonique will not protect you from HIV-AIDS or any other sexually transmitted diseases (STDs) such as chlamydia, genital herpes, genital warts, gonorrhoea, hepatitis B, human papilloma virus and syphilis. To help protect yourself from STDs, you need to use a barrier contraceptive such as a condom.

Tell your doctor you are using Seasonique at least 4 weeks before any planned hospitalisation or surgery. Your doctor may tell you to stop taking Seasonique several weeks before surgery or at the time of immobilisation. Your doctor will tell you when you can start taking Seasonique after you are back on your feet.

To avoid pregnancy during this time you must use a non-hormonal method of contraception such as condoms or a diaphragm.

Bleeding between periods
When you take Seasonique, which has a 91-day extended dosing cycle, you should expect to have 4 scheduled periods per year (bleeding when you are taking the 7 white pills). Each period is likely to last about 3 days.

During the first few months that you are taking Seasonique, you may have unexpected bleeding. This bleeding or spotting tends to decrease with time. Do not stop taking Seasonique because of this bleeding or spotting. If the spotting continues for more than 7 consecutive days or if the bleeding is heavy, contact your doctor.

Things you must not do

Do not take Seasonique to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else even if they have the same condition as you.

Do not stop taking Seasonique without checking with your doctor. If you stop taking Seasonique or do not take a tablet every day, without using another form of contraception, you may become pregnant.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Seasonique.

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

It can be difficult to tell whether side effects are the result of taking Seasonique or are side effects of another medicine you are taking.

Do not be alarmed by the list of possible side effects. You may not experience any of them.

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

Tell your doctor if....

Tell your doctor if you notice any of the following side effects and they worry you:

  • changes in bleeding patterns, including breakthrough bleeding/spotting
  • Painful periods
  • missed periods, but if you have not taken Seasonique as directed you should check whether you are pregnant
  • changes in mucus from the vagina
  • changes in the cervix
  • vaginal thrush (candida)
  • breast pain, tenderness, enlargement, possible milk secretion
  • changes in sex drive
  • nausea or vomiting
  • abdominal pain, cramps or bloating
  • mood changes, including depression and/or worsening of existing depression
  • headache, including migraines
  • nervousness
  • dizziness
  • contact lenses becoming uncomfortable to wear
  • weight change (increase or decrease)
  • changes in appetite
  • swelling of the hands, ankles or feet
  • acne
  • rash
  • darkening of the skin, which may persist after stopping your medicine
  • loss of scalp hair
  • increase in body hair

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

Tell your doctor as soon as possible if....

Tell your doctor as soon as possible if you notice any worsening of conditions that you may already have such as:

  • chorea (involuntary muscle spasm)
  • porphyria
  • systemic lupus erythematosus (Lupus)
  • varicose veins
  • gallbladder disease
  • hereditary angioedema (swelling of the face, lips, mouth, tongue or throat).

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

Go to hospital if....

Tell your doctor immediately, or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • sharp chest pain, coughing of blood, or sudden shortness of breath
  • pain in the calf muscle area
  • severe pain or swelling in one leg
  • crushing chest pain or heaviness in the chest
  • sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg
  • sudden changes or loss of vision
  • breast lumps
  • severe pain or tenderness in the stomach area
  • jaundice or a yellowing of the skin or eyeballs, often with fever, fatigue, loss of appetite, dark coloured urine or light coloured bowel movements. Taking oral contraceptives has been associated with an increased risk of having a benign liver tumour and, in very rare cases, liver cancer. The risk appears to increase the longer oral contraceptives are taken
  • migraine headaches for the first time
  • more frequent migraines if you already suffer from them
  • itchy rash
  • you are an epileptic and your fits become more frequent
  • rise in blood pressure. You may experience headache, blurred vision or palpitations. Sometimes your blood pressure may rise without you experiencing any of these symptoms. It is important to keep your routine doctor's appointments so that your blood pressure can be checked
  • swelling around the eyes or mouth
  • bloody diarrhoea, abdominal pain or tenderness, fever, nausea or vomiting.

Whilst these side effects are rare, they are serious. You may need urgent medical attention or hospitalisation.

Other side effects not listed above may also occur in some patients.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

After taking Seasonique

Storage

Keep your tablets in the blister pack until it is time to take them. Once opened, the product should be stored in the original packaging inside the inner carton. If you take the tablets out of the blister pack they may not keep well.

Keep your tablets in a cool, dry place where the temperature stays below 30°C and is away from light. Do not store Seasonique or any other medicine, in a bathroom or near a sink. Do not leave Seasonique in the car on hot days or on window sills. Heat and dampness can destroy some medicines. Keep it 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 Seasonique or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product Description

What it looks like

Seasonique pack contains 3 blisters in total: 2 blisters each holding 28 pink tablets and 1 blister holding 35 tablets in total- 28 pink tablets and 7 white tablets.

The pink tablets contain 150 micrograms levonorgestrel and 30 micrograms ethinyloestradiol. The white tablets contain 10 micrograms ethinyloestradiol.

The pink tablet is round, biconvex tablet, around 5.7 mm in diameter, embossed "172" on one side and "T" on the other side.

The white tablet is round, biconvex tablet, around 5.7 mm in diameter, embossed "173" on one side and "T" on the other side

Ingredients

Each pink film-coated tablet contains 150 micrograms of levonorgestrel and 30 micrograms ethinyloestradiol.

Each white tablet contains 10 micrograms ethinyloestradiol.

The pink tablets contain the following inactive ingredients:

  • lactose anhydrous
  • hypromellose
  • microcrystalline cellulose
  • magnesium stearate
  • titanium dioxide (E171)
  • Macrogol 400
  • Polysorbate 80

The pink tablets contain the colouring agents:

  • Allura Red AC (E129)
  • Brilliant Blue FCF (E133)

The white tablets contain the following inactive ingredients:

  • lactose anhydrous
  • Polacrilin potassium
  • microcrystalline cellulose
  • magnesium stearate
  • titanium dioxide (E171)
  • Polydextrose
  • hypromellose
  • glycerol triacetate
  • Macrogol 8000

Seasonique does not contain gluten or tartrazine.

Supplier

Seasonique is supplied in Australia by:

Theramex Australia Pty Ltd
Level 34, 60 Margaret Street,
Sydney NSW 2000
1800 THERAMEX or 1800 843 726

Australian Registration Number.

AUST R 238384

This leaflet was prepared in February 2019

® Registered Trade Mark

Published by MIMS May 2019

BRAND INFORMATION

Brand name

Seasonique

Active ingredient

Levonorgestrel; Ethinylestradiol

Schedule

S4

 

Name of the medicine

Levonorgestrel 150 microgram, ethinyloestradiol 30 microgram (pink tablets) + ethinyloestradiol 10 microgram (white tablets).

Excipients.

Pink tablets.

Lactose anhydrous, hypromellose, microcrystalline cellulose, magnesium stearate, titanium dioxide (E171), macrogol 400, allura red AC (E129), polysorbate 80, brilliant blue FCF (E133).

White tablets.

Lactose anhydrous, polacrilin potassium, microcrystalline cellulose, magnesium stearate, titanium dioxide (E171), polydextrose, hypromellose, glycerol triacetate, macrogol 8000.

Description

Seasonique is a 91-day extended-regimen oral contraceptive (OC) tablet containing a combination of 150 microgram of levonorgestrel and 30 microgram ethinyloestradiol for 84 days followed by 10 microgram ethinyloestradiol tablets for 7 days.

Levonorgestrel.

Chemical name: (-)-13-ethyl-17-hydroxy-18, 19-dinor-17α-pregn-4- en-20-yn-3-one. Molecular formula: C21H28O2. Molecular weight: 312.45. CAS number: 797-63-7.

Ethinyloestradiol.

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: 57-63-6.
Levonorgestrel is a white crystalline powder. It is practically insoluble in water, soluble in chloroform, sparingly soluble in ethanol and methylene chloride.
Ethinyloestradiol is a white to cream crystalline powder. It is insoluble in water, soluble in alcohol, ethanol, chloroform, ether, vegetable oil, and solutions of fixed alkali hydroxides.
Each Seasonique package contains 84 combination tablets of 150 microgram levonorgestrel and 30 microgram ethinyloestradiol and 7 tablets of 10 microgram ethinyloestradiol.
Each pink film-coated levonorgestrel and ethinyloestradiol tablet contains lactose anhydrous, hypromellose, microcrystalline cellulose, magnesium stearate, titanium dioxide (E171), macrogol 400, Allura Red AC (E129), Polysorbate 80, Brilliant Blue FCF (E133).
Each white ethinyloestradiol tablet contains lactose anhydrous, polacrilin potassium, microcrystalline cellulose, magnesium stearate, titanium dioxide (E171), polydextrose, hypromellose, glycerol triacetate, Macrogol 8000.

Pharmacology

Pharmacodynamic properties.

Levonorgestrel is a synthetic progestogen and ethinyloestradiol is a synthetic oestrogen. These hormonal components act to inhibit ovulation by supressing gonadotrophin release from the pituitary gland. This results in suppressed levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) with consequent inhibition of follicle development and ovulation. In addition, there are also other factors, such as changes in the endometrium, implantation, cervical mucus and ovum transport that can contribute to the efficacy of oral contraceptives in preventing pregnancy. While each hormonal component alone can be shown to exert these effects in certain circumstances, the combination synergistically decreases plasma gonadotrophin levels and suppresses ovulation more consistently than each substance alone.

Pharmacokinetics.

Absorption.

Ethinyloestradiol and levonorgestrel are absorbed with maximum plasma concentrations occurring within 2 hours after oral administration. Levonorgestrel is completely absorbed after oral administration (bioavailability nearly 100%) and is not subject to first-pass metabolism. Ethinyloestradiol is absorbed from the gastrointestinal tract but, due to first-pass metabolism in gut mucosa and liver, its bioavailability is approximately 43%.
The mean plasma pharmacokinetic parameters, including area under the curve (AUC), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and half-life (t1/2), of Seasonique following a single dose of two levonorgestrel/ ethinyloestradiol combination tablets used in Seasonique clinical studies in healthy women under fasting conditions are presented in Table 1.

Steady state.

During the continuous use of Seasonique serum levonorgestrel levels increase about 3-fold and ethinyloestradiol levels about 1.6-fold at day 21 compared to day 1 of the treatment.
The daily exposure to levonorgestrel and ethinyloestradiol on day 21, corresponding to the end of a typical 3 week contraceptive regimen, and on day 84, at the end of an extended regimen, were similar without any further accumulation of drug.

Distribution.

Levonorgestrel is highly protein bound, principally to sex hormone binding globulin (SHBG) and serum albumin. Only 1.3% or the total serum drug concentration is present as free steroid, approximately 64% is specifically bound to SHBG and about 35% is nonspecifically bound to albumin. Ethinyloestradiol is highly (about 95%-98.5%), but nonspecifically bound to serum albumin. Ethinyloestradiol does not bind to SHBG, but induces an increase in the serum concentrations of SHBG, influencing the relative distribution of levonorgestrel into different protein fractions (increase in SHBG bound fraction and decrease in albumin bound fraction).

Metabolism.

Following absorption, levonorgestrel is conjugated at the 17β-OH position to form sulfate and to a lesser extent, glucuronide conjugates in plasma.
First-pass metabolism of ethinyloestradiol involves formation of ethinylestradiol-3-sulfate in the gut wall, followed by 2-hydroxylation of a portion of the remaining untransformed ethinyloestradiol by hepatic cytochrome P450 3A4. The various hydroxylated metabolites are subject to further methylation and/or conjugation.

Excretion.

About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in faeces, mostly as glucuronide conjugates. The terminal elimination half-life for levonorgestrel after a single dose of Seasonique was about 34 hours.
Ethinyloestradiol is excreted in the urine and faeces as glucuronide and sulfate conjugates, and it undergoes enterohepatic recirculation. The terminal elimination half-life of ethinyloestradiol after a single dose of Seasonique was found to be about 18 hours.

Special populations.

Effect of hepatic impairment.

No formal studies to evaluate the effect of hepatic disease on the disposition of Seasonique have been conducted. However, steroid hormones may be poorly metabolized in patients with impaired liver function.

Effect of renal impairment.

No formal studies to evaluate the effect of renal disease on the disposition of Seasonique have been conducted. However, renal excretion is the principal route of elimination for ethinyloestradiol, and ethinyloestradiol clearance in renal failure patients was found to be decreased relative to normal healthy women.

Elderly.

Combined oral contraceptives are not indicated for use in postmenopausal women.

Gender.

Seasonique is an oral contraceptive and therefore is for use in women only.

Race.

Population pharmacokinetic analyses (including caucasians, African-American, Asian, hispanic and other) showed no effect of race on the pharmacokinetics of levonoregstrel or ethinyloestradiol.

Bodyweight.

There has been some concern that some hormonal contraceptives are not as effective in obese women, possibly due to an enhanced metabolic rate in obese women leading to more rapid drug metabolism and subsequent insufficient hormone levels. There were no pregnancies in women who weighed ≥ 90 kg and the efficacy of Seasonique does not appear to be reduced in obese women.

Clinical Trials

The clinical efficacy and safety of Seasonique (84 day 150 microgram levonorgestrel/ 30 microgram ethinyloestradiol + 7 day 10 microgram ethinyloestradiol (DP3-84/10)) was examined in two multicenter open trials, PSE-301 and PSE-302 and one long-term extension study (DR-PSE-304) for safety monitoring.
The contraceptive reliability was analysed in both studies using the Pearl Index (PI) and a life table analysis. Pearl Index (PI) calculations (for study PSE-301) using both 91 day and 28 day cycle equivalents were performed to retain relevant data and for comparison of Seasonique with currently available 28 day oral contraceptive regimens.

PSE-301.

The pivotal study, PSE-301 was a phase III, 12 month, multicenter, randomised, open label clinical trial conducted to evaluate the efficacy and safety of two 91 day extended regimens, Seasonique and DP3-84/30, (84 day 150 microgram levonorgestrel/ 30 microgram ethinyloestradiol + 7 day 30 microgram ethinyloestradiol). The mean age of the subjects was 27.4 years, mean weight was 69.6 kg and mean body mass index (BMI) 26.0 kg/m2. At enrolment in the study, most subjects (63.1%) were taking another oral contraceptive regimen and were then switched to the extended regimen. The racial demographic of those enrolled was: caucasian (80%), African-American (11%), hispanic (5%), Asian (2%), and other (2%). Almost 80% of the patients were nonsmokers.
Out of the 1006 women who received Seasonique, 799 had completed at least one complete cycle and 500 completed the study.
In the efficacy analysis, 1,578 91-day cycles (621 women), in which no other backup contraceptive method was used, were included yielding a PI of 0.76 (95% CI: 0.00-1.76), based on 3 pregnancies. When calculated on 6,814 28-day cycles (841 women), in which no other backup contraceptive method was used, a PI of 0.57 was calculated (95% CI: 0.00-1.33), based on 3 pregnancies.
In addition to the Pearl Index calculation, a life table approach was used to estimate the cumulative pregnancy rate on a cycle by cycle basis. The life table results for patients between the ages of 18 and 35 years who completed one cycle of treatment was calculated. The cumulative failure rate at the end of one year of treatment, estimated by the life table method was 0.61% (95% CI: 0.19%-1.90%) for Seasonique. Life table estimates of the cumulative pregnancy confirm that Seasonique is > 99% effective in preventing pregnancy and are comparable to the PI calculations.
As seen in PSE-301 and also confirmed by the formal ovarian inhibition studies (DR-PSE-310 and DR-PSE-312) the addition of EE 10 microgram during the standard hormone free interval (HFI) appears to better suppress ovarian function. Estradiol, FSH, and LH levels were lower during the Seasonique EE 10 microgram monotherapy interval compared with the HFIs of the 21/7 OC and the 84/7 day cycle OC. Seasonique suppresses ovarian function as assessed both by ovarian hormone levels and follicular growth.

PSE-302.

The second study PSE-302 was an open label, randomised clinical trial designed to assess endometrial biopsy results and included a limited number of cycles of exposure available for the PI evaluation. In addition to three test products, including Seasonique, a standard 28 day LNG/EE comparator was included. The majority of treated patients (n = 95) were caucasian (60%), 20% African-American, and 12% hispanic. Almost 80% of the patients were nonsmokers, and 60% were continuous users of oral contraceptives (28% prior users and 11% fresh starts). The median age was about 26 years, median weight was 66.2 kg, and the median BMI was 24.1 kg/m2. 95 subjects received Seasonique and 80 completed at least one complete cycle. Study participants completed 166 91-day cycles or 539.50 28-day patient cycles. The results show similar contraceptive efficacy as observed in the pivotal PSE-301 study.
Endometrial biopsy results showed no evidence of any pathologic changes; hyperplasia was not observed in any of the end of treatment biopsy samples. Other safety results for Seasonique were comparable to those for the 28 day comparator, including the incidence of serious adverse events, changes in vital signs, and changes in laboratory values from baseline to end of treatment; none were of any clinical significance.

Cycle control.

In study PSE-301, the median number of scheduled bleeding/ spotting was 3 days for all 4 cycles. The number of scheduled bleeding only days decreased from a median of 3 days during the first cycle to 2 days during the 3 subsequent cycles.
A reduction in the number of unscheduled bleeding/ spotting days and unscheduled bleeding only days was observed from the beginning at the second 91 day cycle of treatment, see Table 2.
The decrease in the unscheduled bleeding/ spotting over treatment cycles was confirmed in the comparative PSE-302 study. After one year of treatment, the total number of days of bleeding/ spotting was similar for Seasonique and the 28 day comparator.
Observations from a cross study analysis of clinical trials for the 84/7 EE Seasonique and 84/7 placebo regimen showed statistically significant reductions in bleeding and/or spotting at all four cycles during the 7 days of low dose EE (in the 84/7-EE Seasonique regimen) compared to the 7 days of placebo (in the 84/7 placebo regimen). The duration of the scheduled withdrawal bleeding episodes appeared to be shorter with the 84/7-EE Seasonique regimen than with 84/7 placebo (median of 3 days compared to a median of 4 days).

DR-PSE-304.

Study DR-PSE-304 was an open label, nonrandomised extension study of both PSE-301 and PSE-302, designed to evaluate Seasonique's safety profile when taken for up to an additional 5 consecutive years in a subset of patients who had successfully completed one year of therapy in either the pivotal PSE-301 study (either the Seasonique or the DP3 84/30 arm) or the endometrial biopsy study PSE-302.
The study demographic for DR-PSE-304 was 82% caucasian; about 12.5% African-American; Asian, hispanic the remainder were other ethnicities. About 84% of the patients were nonsmokers and about 70% were continuous users of OCs (21% prior user and 9% fresh starts). The median age of all treated patients was 27.5 years, median weight was 65.3 kg, and the median BMI was approximately 24.1 kg/m2.
The DR-PSE-304 study included exposure for a total of 1302 complete 91 day Seasonique cycles, corresponding to 4,411 28-day cycles. These cycles combined with the exposure observed in studies PSE-301 and PSE-302 result in over 25,000 28-day cycles of exposure among patients in the Seasonique clinical development program.
Overall rates of study discontinuation, the incidence of adverse events (including serious adverse events and adverse events leading to study discontinuation) are consistent with those observed in study PSE-301 and PSE-302 and support the long-term safety of the Seasonique 84/10 extended regimen oral contraceptive, (see Adverse Effects).

Indications

Seasonique is indicated for use as an oral contraceptive.

Contraindications

Seasonique should not be used in the presence of any of the conditions listed. Should any of the conditions appear for the first time during Seasonique use, the product should be stopped immediately.
Presence or risk of venous thromboembolism (VTE) (see Precautions): 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 severe or multiple risk factors.
Presence or risk of arterial thromboembolism (ATE) (see Precautions): 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.
In association with herbal remedy St. John's wort (Hypericum perforatum).
Hypersensitivity to any of the ingredients contained in Seasonique.
Concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir.

Precautions

If any of the conditions/ risk factors mentioned below are present, the benefits of Seasonique use 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 Seasonique should be discontinued. In the case of suspected or confirmed thrombosis, combined oral contraceptives (COC) use should be discontinued.

Circulatory disorders.

Epidemiological studies have suggested an association between the use of combined oral contraceptives (COCs) containing ethinyloestradiol and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism. These events occur rarely in average risk women.

Risk of venous thromboembolism.

The use of any COC increases the risk of VTE compared with no use. The women considering using Seasonique 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 COC is restarted after a break in use of 4 weeks or more.
The risk of VTE with the COC is greatest for products containing over 50 microgram of ethinyloestradiol. There is less risk for products such as Seasonique containing less than 35 microgram ethinyloestradiol. It is not known how Seasonique, with its 91 day regimen, influences the occurrence of such events in comparison to other levonorgestrel containing COCs, which have a 28 day regimen.
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 COCs, and how her current risk factors influence this risk. See Table 3.
It is important that women understand that VTE associated with COC use is rare. The risk in pregnancy (5-20 per 10,000 women over 9 months) and the risk in the postpartum period (45-65 per 10,000 women over 12 weeks) is higher than that as associated with COC use.
However VTE is a serious condition and may be fatal in 1-2% of cases. Extremely rarely, thrombosis has been reported to occur in COC users in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries.

Risk factors for VTE.

The risk for venous thromboembolic complications in COC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see List of risk factors for VTE).
Seasonique 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 COC should not be prescribed.

List of 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: 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 Seasonique (in the case of elective surgery at least six 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 Seasonique 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 COC use.
The possibility of anticoagulant therapy should also be taken into account. Adequate alternative contraception should be initiated because of the teratogenicity of anticoagulant therapy (coumarins).
The increased risk of thromboembolism in the puerperium must be considered (see Use in pregnancy).
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 COC.
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; severe light headedness or dizziness; rapid or irregular heartbeat.
Some of these symptoms (e.g. shortness of breath, coughing) are nonspecific and might be misinterpreted as more common or less severe events (e.g. respiratory tract infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discolouration of an extremity or an ‘acute’ abdomen.
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 (partial or complete) can occur almost immediately.

Risk of arterial thromboembolism (ATE).

Epidemiological studies have associated the use of COCs with an increased risk for arterial thromboembolism (e.g. myocardial infarction, angina pectoris, stroke or TIA). Arterial thromboembolic events may be fatal.

Risk factors for ATE.

The risk of arterial thromboembolic complications in COC users increases in women with risk factors. Seasonique 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 COC should not be prescribed.

List of risk factors for ATE.

Increasing age, particularly above 35 years; smoking; hypertension; obesity (body mass index over 30 kg/m2); positive family history (arterial thromboembolism ever in a sibling or parent especially at relatively early age e.g. below 50); biochemical factors: 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 strongly advised not to smoke if they wish to use a COC. 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 COC use.
An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation.
The possibility of anticoagulant therapy should also be taken into account. Adequate alternative contraception should be initiated because of the teratogenicity of anticoagulant therapy (coumarins).
The increased risk of thromboembolism in the puerperium must be considered (see Use in pregnancy).
When considering risk/ benefit, the doctor should take into account that the adequate treatment of a condition may reduce the associated risk of thrombosis.

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 COC.
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, trouble speaking or understanding; sudden trouble seeing in one or both eyes, including 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.

Carcinogenicity.

Sex steroids can promote the growth of certain hormone dependent tissues and tumours. Long-term continuous administration of natural and synthetic oestrogens 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.
Combined oestrogen progestogen oral contraceptives are classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC) reflecting sufficient evidence of carcinogenicity in humans based on findings of increased risk for cancer of the breast among current and recent user only, for cancer of the cervix and for cancer of the liver in populations that are at low risk of hepatitis B viral infection (see Tumours). However, there is also convincing evidence in humans that these agents confer a protective effect against cancer of the endometrium and ovary and that the protection lasts for up to 2 decades after stopping use.

Genotoxicity.

Oestrogenic and progestogenic hormones have been tested for genotoxicity in a number of in vitro and in vivo test systems with mixed results. The genotoxicity of levonorgestrel has not been fully investigated, although limited data available to date suggest that it does not appear to be genotoxic. In mutagenicity studies performed in different strains of Salmonella typhimurium with and without metabolic activation no mutagenic potential of levonorgestrel was detected.
There is limited evidence available in the literature suggesting that oestrogens may be weakly genotoxic at high doses. Ethinyloestradiol did not induce mutations in bacterial, yeast or mammalian cells or unscheduled DNA synthesis in rat hepatocytes or DNA adduct formation in cultured human liver slices in vitro. It also did not induce sex linked recessive lethal mutations in Drosophila. Ethinyloestradiol gave equivocal results in assays for chromosomal damage (clastogenic effects were not consistently seen and occurred at high doses).

Tumours.

Cervical cancer.

An increased risk of cervical cancer in long-term users of COCs (> 5 years) has been reported in some epidemiological studies, but 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).

Breast cancer.

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.

Hepatocellular carcinoma.

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 hepatic tumour should be considered in the differential diagnosis when severe upper abdominal pain, liver enlargement or signs of intra-abdominal haemorrhage occur in women taking COCs.
With the use of the higher dosed COCs (50 microgram ethinyloestradiol) the risk of endometrial and ovarian cancer is reduced. Whether this also applies to lower dosed COCs remains to be confirmed.

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. Only in these rare cases an immediate discontinuation of COC use is justified. If, during the use of a COC in preexisting hypertension, constantly elevated blood pressure values or a significant increase in blood pressure do not respond adequately to antihypertensive treatment, the COC must be withdrawn. 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; gallstones; 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 function may necessitate the discontinuation of COC use until markers of liver function return to normal. Recurrence of cholestatic jaundice and/or cholestasis related pruritus which previously occurred during pregnancy or during 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 ethinyloestradiol). However, diabetic women should be carefully observed, particularly in the early stage of COC use.
Worsening of existing endogenous depression, of epilepsy, of Crohn's disease and of ulcerative colitis has been reported during 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.

Medical examination/ consultation.

A complete medical history and physical examination should be taken prior to the initiation or reinstitution of COC use, guided by the contraindications and precautions, and should be repeated periodically during the use of COCs. In general an annual examination is recommended. Pregnancy should be ruled out before the start of therapy. 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 COC use. The frequency and nature of examinations 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.
The woman should also be instructed to carefully read the user leaflet and to adhere to the advice given.

Sexually transmitted infections including human immunodeficiency virus (HIV) infections and (acquired immune deficiency syndrome) AIDS.

Women should be advised that oral contraceptives do not protect against HIV infections (AIDS) and other sexually transmitted infections (STIs). Women 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 active tablets, gastrointestinal disturbances or concomitant medication (see Dosage and Administration and Interactions with Other Medicines).

Reduced cycle control.

With all COCs, irregular bleeding (spotting or breakthrough bleeding) may occur, especially during the first 3 months of use. The evaluation of any irregular bleeding should be conducted if the bleeding persists.
In the Seasonique clinical trials scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with an average of 3 days of bleeding and/or spotting per each 91 day cycle. Unscheduled bleeding and unscheduled spotting decreased over successive 91 day cycles.
If unscheduled spotting or bleeding occurs, the woman should be instructed to continue on the same regimen. If the bleeding is persistent or prolonged, the woman should be advised to consult her doctor.

ALT elevations.

During clinical trials with patients treated for hepatitis C virus infections (HCV) with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin, transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred significantly more frequent in women using ethinylestradiol-containing medications such as combined hormonal contraceptives (CHCs).

Information for the patient.

A consumer medicine information leaflet is available. Please advise your patient to read this information carefully. Seasonique tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Seasonique pink tablets contain the azo colouring agents allura red AC aluminium lake (E129) and brilliant blue FCF (E133) that can cause allergic reactions.

Effects on fertility.

In studies PSE-301 and PSE-302 poststudy follow-up was planned for all patients after study completion or withdrawal for occurrence of pregnancy and/or until the menstrual cycle return to normal; subjects were followed for three months for return to fertility. Among the patients who reported pregnancies rapid return to fertility was noted with 9 of 18 reported pregnancies (on treatment or off treatment) occurred within three weeks of discontinuing or completing treatment with Seasonique and 15 out of 18 occurred within three months of the last dose. Overall, there was no suggestion of any impairment of fertility following cessation of the Seasonique in its clinical programme.

Use in pregnancy.

(Category B3)
Seasonique is contraindicated during pregnancy.
If pregnancy occurs during use of Seasonique, the treatment should be withdrawn immediately. Extensive epidemiological studies have revealed neither an increased risk of birth defects in children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs were taken inadvertently during pregnancy.
Animal studies have shown adverse effects during pregnancy and lactation. Based on these animal data, adverse effects due to hormonal action of the active compounds cannot be excluded.

Use in lactation.

Lactation may be influenced by COCs as they may reduce the quantity and change the composition of breast milk. Therefore, the use of COCs should generally not be recommended until the breastfeeding mother has completely weaned her child. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk during COC use. These amounts may affect the child.

Children and adolescents.

The efficacy and safety of Seasonique in women of reproductive age under 18 years have not been established.

Effects on ability to drive and use machines.

No studies on the effects on the ability to drive and use machines have been performed. No effects on ability to drive and use machines have been observed in users of COCs.

Interactions

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

Influence of other medicinal products on Seasonique.

Interactions between oral contraceptives and other medicinal products may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.

Hepatic metabolism.

Interactions can occur with drugs that induce hepatic enzymes which can result in increased clearance of sex hormones (e.g. phenytoin, barbiturates, primidone, carbamazepine, rifampicin, bosentan, vemurafenib and HIV medication (e.g. ritonavir, nevirapine) and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing the herbal remedy St. John's wort (Hypericum perforatum)). Maximal enzyme induction is generally seen in about 10 days but may then be sustained for at least 4 weeks after the cessation of drug therapy.

Management.

Women on short-term treatment with any of the above mentioned classes of medicinal products or individual active substances (hepatic enzyme inducing medicine) besides rifampicin should temporarily use a barrier method in addition to the COC, i.e. during the time of concomitant medicinal product administration and for 7 days after their discontinuation. For women on rifampicin a barrier method should be used in addition to the COC during the time of rifampicin administration and for 28 days after its discontinuation.
In women on long-term treatment with hepatic enzyme inducing active substances, another reliable, nonhormonal, method of contraception is recommended.

Influence of Seasonique on other medicinal products.

The concomitant use of COCs and lamotrigine has been shown to reduce lamotrigine levels by about 50%. This interaction may be due to the estrogen component since it does not occur with progestogens given alone. In a patient already treated with lamotrigine, close clinical monitoring and a possible dosage adjustment at the beginning and the end of the contraceptive may be necessary. Conversely, starting oral contraception during lamotrigine titration should be avoided.

Pharmacodynamic interactions.

Concomitant use with the medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin may increase the risk of ALT elevations. Therefore, patients on Seasonique must switch to an alternative method of contraception (e.g. progestogen-only contraception or non-hormonal methods) prior to starting therapy with this combination drug regimen.
Seasonique can be restarted 2 weeks following completion of treatment with this combination drug regimen.

Laboratory tests.

The use of COCs may change the results of some 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. The changes generally remain within the normal laboratory range.
Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid binding globulin increase with use of COCs.

Adverse Effects

The pivotal clinical trial that evaluated the safety and efficacy of Seasonique was a 12 month, randomised, multicenter, open label study, which enrolled women aged 18-40, of whom 1006 took at least one dose of Seasonique. The most commonly reported treatment emergent adverse reactions were irregular and/or heavy uterine bleeding, weight gain and acne. See Table 4.
The adverse events associated with bleeding were consistently slightly higher for DP3-84/30 compared to Seasonique. Intermenstrual bleeding was reported in 12.1% of the DP3-84/30 patients compared to 11.5% of the DP3-84/10 patients and menorrhagia was reported in 7.7% of patients on DP3-84/30 compared to 5.8% on DP3-84/10. See Tables 5 and 6.
The following serious adverse events have been reported in women using COCs, which are discussed in Contraindications and Precautions.
Venous thromboembolic disorders; arterial thromboembolic disorders; hypertension; liver tumours; depression; occurrence or deterioration of conditions for which association with COC use is not conclusive: Crohn's disease, ulcerative colitis, epilepsy, migraine, uterine myoma, porphyria, systemic lupus erythematosus, herpes gestationis, Sydenham's chorea, haemolytic uremic syndrome, cholestatic jaundice;
chloasma; acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal; in women with hereditary angioedema exogenous estrogens may induce or exacerbate symptoms of angioedema.

Other adverse reactions reported in the clinical trial and not already mentioned include.

Common: mood changes, abdominal pain.
Uncommon: insulin resistance, depressed mood, dizziness, vomiting, nausea aggravated, cholecystitis, cholelithiasis, peripheral swelling, muscle spasm, arthralgia, joint stiffness, myalgia, neck pain, chest pain, pain, malaise, lipids increased.

Postmarketing adverse reactions.

The most commonly reported adverse events were in the category of reproductive system and breast disorders, most commonly metrorrhagia (n = 159), vaginal haemorrhage (n = 58) and menorrhagia (n = 18).
Additional adverse reactions that have been identified during postmarketing experience with Seasonique include hypersensitivity reaction, loss of consciousness, thrombosis, pulmonary embolism, pulmonary thrombosis, alopecia and pain in extremity.

Dosage and Administration

Seasonique is an extended regimen oral contraceptive where tablets are taken continuously for 91 days. Each subsequent 91 day pack is started the day after the last tablet of the previous pack. Seasonique pack consists of 84 combination tablets of 150 microgram levonorgestrel and 30 microgram ethinyloestradiol and 7 tablets of 10 microgram ethinyloestradiol.

How to use Seasonique.

Tablet taking is continuous for 91 days. One tablet is to be taken by mouth at the same time every day in the order shown at the blister pack.
One pink tablet containing levonorgestrel and ethinyloestradiol is taken daily for 84 consecutive days, followed by one white ethinyloestradiol tablet for 7 days, during which time withdrawal bleeding usually occurs.

How to start Seasonique.

The daily dosing regime should start with the first tablet (#1) of month 1 blister, consistent with the packaging presentation. The tablets must be taken every day at about the same time, if necessary with a little liquid, in the order shown on the blister pack. One tablet is to be taken daily for 91 consecutive days. One pink tablet should be taken daily for 84 consecutive days, followed by one white tablet for 7 consecutive days. A scheduled withdrawal bleeding should occur during the 7 days that the white tablets are taken.
Each subsequent 91 day cycle is started without interruption on the same day of the week on which the patient began her first dose of Seasonique, following the same schedule.

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). The women may start Seasonique later (i.e. days 2-5 of the cycle), but should in this case be advised to additionally use a barrier method for the first 7 days of tablet taking.

Changing from a combined hormonal contraceptive (combined oral contraceptive (COC)), vaginal ring, or transdermal patch.

The woman should start with Seasonique on the day after the last active tablet (the last tablet containing the active substances) of her previous COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Seasonique on the day of removal but at the latest when the next application would have been due.

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

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

Following first trimester abortion.

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

Following delivery or second trimester abortion.

Women should be advised to start at day 21 to 28 after delivery or second trimester abortion. When starting later, the woman should be advised to additionally use a barrier method for the first 7 days. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period.
For breastfeeding women see Precautions, Use in lactation.

Management of missed tablets.

Contraceptive reliability may be reduced if taking the pink tablets is forgotten and particularly if one forgets to take the first tablets from the blister pack.
If it is found within 12 hours of the usual time of taking that one pink tablet has been forgotten, the tablet that was forgotten should be taken immediately, and the treatment should be continued normally by taking the next tablet at the usual time.
If it is found more than 12 hours after the normal time of taking that one or several pink tablets have been forgotten, contraceptive protection may be reduced. The management of missed tablets can be guided by the following two basic rules.
1. Tablet taking must never be discontinued for longer than 7 days.
2. 7 days of uninterrupted tablet taking are required to attain adequate suppression of the hypothalamic pituitary ovarian axis.
Accordingly the following advice can be given in daily practice.

Missed pink levonorgestrel/ ethinyloestradiol tablets.

During day 1 to day 7 (week 1).

If one or more tablets are missed during week 1, there is a higher risk of pregnancy because 7 days of uninterrupted tablet taking are required to attain suppression of the hypothalamic pituitary ovarian axis. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered. The more tablets are missed and the closer they are to the white tablet phase, the higher the risk of a pregnancy.
A single delayed pink tablet should be taken as soon as possible even if this means taking two tablets at the same time. Further tablets should be taken at the usual time.
If two pink tablets are missed, two tablets should be taken on the day woman remembers missing tablets and additional two on the next day. Further tablets should be taken at the usual time.
If three or more pink tablets are missed, the missed tablets should be omitted and further tablets continued at the usual time as indicated on the pack. Woman may experience bleeding during the week following the missed tablets.
In any case, backup contraception should be used for the next 7 days.

During day 8 to day 84 (week 2 to week 12).

A single delayed pink tablet should be taken as soon as possible even if this means taking two tablets at the same time. Further tablets should be taken at the usual time. No additional contraception precautions are required.
If two pink tablets are missed, two tablets should be taken on the day woman remembers missing tablets and additional two on the next day. Further tablets should be taken at the usual time. Additional nonhormonal methods of contraception should be used for the next 7 days after restarting tablets.
If three or more pink tablets are missed, the missed tablets should be omitted and further tablets continued at the usual time as indicated on the pack. Woman may experience bleeding during the week following the missed tablets. Additional nonhormonal methods of contraception should be used for the next 7 days after restarting tablets. If intercourse took place during the days of missed tablets, the possibility of a pregnancy should be considered. The more tablets are missed and the closer they are to the white tablet phase, the higher the risk of a pregnancy.

Missed white ethinyloestradiol tablets (week 13).

The missed tablets should be omitted and further tablets continued at the usual time until the pack is finished. No additional contraception precautions are required.
If the woman has no withdrawal bleeding during the week 13 (while taking the white ethinyloestradiol tablets), the possibility of pregnancy must be ruled out before a new 91 day cycle is started.

Advice in case of gastrointestinal disturbances.

In case of severe gastrointestinal disturbances (e.g. vomiting or diarrhoea), absorption may not be complete and additional contraceptive measures should be taken. If vomiting occurs within 3-4 hours after tablet taking, the women should apply the advice given for missed tablets. If the woman does not want to change her normal tablet taking schedule, she can take the extra pink tablet(s) from the last row (week 12).

Disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Overdosage

There have been no reports of serious adverse effects from overdose of oral contraceptives. On the basis of general experience with combined oral contraceptives, symptoms that may possibly occur in this case are: nausea, vomiting and, in young girls, slight vaginal bleeding. There are no antidotes and treatment should be symptomatic.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

Presentation

Each composite pack contains 84 round pink tablets each containing levonorgestrel 150 microgram/ethinyloestradiol 30 microgram tablets embossed "172" on one side and "T" on the other side and 7 round white film-coated tablets, each containing ethinyloestradiol 10 microgram embossed "173" on one side and "T" on the other side.
The carton contains three monthly blisters packaged inside an inner carton folder inside a nonresealable foil pouch:
Month 1 and Month 2 blisters contain 28 pink film-coated levonorgestrel 150 microgram/ethinyloestradiol 30 microgram tablets;
Month 3 blister contains 28 pink film-coated levonorgestrel 150 microgram/ethinyoestradiol 30 microgram tablets + 7 white film-coated ethinyloestradiol 10 microgram tablets.

Storage

Store below 25°C. Keep in original container in order to protect from light and humidity.
Once opened, the product should be stored in the original packaging inside the inner carton.

Poison Schedule

S4.