Consumer medicine information

Valette

Ethinylestradiol; Dienogest

BRAND INFORMATION

Brand name

Valette

Active ingredient

Ethinylestradiol; Dienogest

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Valette.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Valette. 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 Valette 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 VALETTE IS USED FOR

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

Valette is used to prevent pregnancy.

It is also used to treat mild to moderate acne in women seeking oral contraception.

You may also experience the following benefits:

  • more regular and lighter periods potentially resulting in a decreased risk in anaemia (iron deficiency)
  • a decrease in period pain
  • reduction of greasiness in skin and hair

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

When taken correctly, it 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

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 be missed, or taken with medicines that may interfere with their effectiveness, or may not be absorbed due to vomiting and diarrhoea.

Like all oral contraceptives, Valette 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 VALETTE

When you must not take it

Do not take Valette if you have an allergy to:

  • dienogest and/or ethinylestradiol (the active ingredients in Valette)
  • 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 Valette if you are taking any of the following medicines:

  • antiviral medicines which contain glecaprevir, pibrentasvir, sofosbuvir, velpatasvir, voxilaprevir, ombitasvir, paritaprevir, or dasabuvir, and combinations of these. 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)

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

You are more at risk of having a blood clot when you take the Pill. But 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 Valette 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 Valette, especially if you are older than 35 years of age.

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

  • blood clots in your legs
  • 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)
  • mini-stroke (also known as TIA or transient ischaemic attack)
  • migraine, where you have also had problems with seeing, speaking or had 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 Valette, 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 Valette if you are pregnant or think you might be pregnant. The possibility of pregnancy should be ruled out before starting Valette.

Do not give Valette to a child.

Do not take Valette 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 Valette 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

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 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 gall bladder disease
  • 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, or recur or worsen while taking Valette, you should tell your doctor.

Tell your doctor if you are breastfeeding or planning to breastfeed. Valette is generally not recommended if you are breastfeeding.

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

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

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.

There are some medicines that you must not take with Valette - see "When you must not take it".

Some medicines/foods and Valette may interfere with each other. These include:

  • medicines used to treat tuberculosis, such as rifampicin, rifabutin
  • medicines used to treat epilepsy, such as phenytoin, primidone, barbiturates (e.g. phenobarbitone), carbamazepine, oxcarbazepine, topiramate, felbamate, lamotrigine
  • medicines used to treat HIV, such as ritonavir or nevirapine
  • some medicines used to treat hepatitis C virus (HCV), such as boceprevir, telaprevir, glecaprevir, pibrentasvir, ombitasvir, paritaprevir, dasabuvir
  • macrolide antibiotics (e.g. clarithromycin, erythromycin)
  • medicines used to treat fungal infections, such as ketoconazole, itraconazole, voriconazole, fluconazole and griseofulvin
  • medicines used to treat depression such as nefazodone, fluvoxamine
  • antacids such as cimetidine
  • blood pressure medication such as diltiazem, verapamil
  • etoricoxib, an anti-inflammatory medicine used to treat pain
  • tizanidine, melatonin or midazolam which are medicines that relax the body
  • theophylline, a medicine that helps with breathing
  • cyclosporin, an immunosuppressant medicine
  • herbal medicines containing St John’s Wort
  • grapefruit juice

These medicines/foods may be affected by Valette, 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 Valette 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 VALETTE

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 each day. You must take Valette 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 days of the week.

Take your first tablet from the green area on the blister pack corresponding to the day of the week.

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

A period should begin 2-3 days after starting to take the brown 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 Valette for the first time

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

You may also start on days 2-5 of your period, but in that case make sure you also use additional barrier contraceptive precautions (e.g. condom) for the first 7 days of tablet-taking.

Your doctor will advise you when to start if you:

  • are taking Valette after having a baby
  • have had a miscarriage or an abortion

Changing from another contraceptive

Changing from a combined oral contraceptive:
Start taking Valette 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 Valette.

You can also switch to Valette after taking one or more inactive tablets in your previous Pill pack, but no later than the day after taking the last inactive tablet.

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

Changing from a progestogen-only pill (‘minipill’):
Stop taking the minipill on any day and start taking Valette 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 7 days of tablet-taking when having intercourse.

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

You must also use additional barrier contraceptive precautions (e.g. condoms or a diaphragm) for the first 7 days of tablet-taking when having intercourse.

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

Stopping Valette

You can stop taking Valette 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 Valette 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.

If you forget to take Valette

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 Valette to be most effective, white active tablets need to be taken uninterrupted for 7 days.

If you have been taking the white active tablets for 7 uninterrupted days and miss a white active tablet, take the missed tablet as soon as you remember, then go back to taking your medicine as you would normally, even if this means taking two tablets in one day. You will not need to use additional barrier contraceptive precautions.

The chance of pregnancy after missing a white 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 white active tablets left in a row, you should finish the active tablets in your pack but skip the brown inactive tablets and start a new pack with the white active tablets 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 white active tablets of the second pack. You may have spotting or breakthrough bleeding on tablet-taking days.

If you have been taking the white active tablets for less than 7 days and miss a white active tablet, take the missed tablet as soon as you remember, then go back to taking your medicine as you would normally, even if this means taking two tablets in one day. 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 during that time, there is a possibility of pregnancy and you may need emergency contraception.

If you forget to take more than one white 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 forget to take a brown inactive tablet, take it as soon as you remember and take the next tablet at the usual time. You should still be protected against pregnancy because the brown tablets do not contain any active ingredients.

Please see the diagram at the end of this leaflet for “Summary of advice if you missed an 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 Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Valette.

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

If you take several white active tablets at once, you may feel sick or vomit or may bleed from the vagina. Even girls who have not yet started to menstruate but have accidentally taken this medicine may experience such bleeding.

WHILE YOU ARE TAKING VALETTE

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 Valette, 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 Valette.

Stop taking Valette 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 Valette. 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 Valette, 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 Valette 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 Valette – you may be told to stop taking it.

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

If you vomit within 3-4 hours or have severe diarrhoea after taking a white 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 these tablets for the first few months, you can have irregular vaginal bleeding (spotting or breakthrough bleeding) between your periods. You may need to use sanitary products, but continue to take your tablets as normal. Irregular vaginal bleeding usually stops once your body has adjusted to Valette, usually after about 3 months.

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

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

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

Valette 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 papilloma virus 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 Valette 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 Valette, 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 Valette.

This medicine helps most women but it may have unwanted side effects in some women.

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

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

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

The following list includes the more common side effects of your Pill. These are usually mild and short-lived.

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

  • nausea, vomiting or diarrhoea
  • stomach pain (including stomach discomfort / swelling)
  • changes in weight
  • headache, including migraines
  • acne
  • hair loss
  • mood changes, including depression
  • changes in blood pressure
  • breast pain (including breast discomfort and breast tenderness), breast enlargement, breast swelling
  • unusual discharge from the vagina
  • abnormal vaginal bleeding or irregular bleeding between periods
  • fungal or yeast infection
  • discharge and itching in the vagina or genitals due to infection (genital inflammation)
  • vaginal thrush or other fungal infections of the genitals
  • increased appetite
  • rash (including patchy rash)
  • itching (sometimes all over your body)
  • abnormal periods or painful periods
  • pelvic pain
  • ovarian cysts
  • fatigue (including weakness and tiredness)

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

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

  • pain in the chest, arm or below the breastbone
  • pain or discomfort that goes to your back
  • breathlessness and/or difficulty breathing
  • swelling, pain or tenderness of one leg or along a vein in the leg
  • sudden weakness, numbness or bad ‘pins and needles’ of the face, arm or leg, especially on one side of the body
  • sudden trouble walking, dizziness, loss of balance or coordination
  • severe, sudden stomach pains
  • a fainting attack, or you collapse
  • unusual headaches or migraines that are worse than usual
  • sudden problems with speech, understanding or eyesight

The side effects listed above are possible signs of a blood clot (thrombosis).

  • allergic reaction
  • rapid heartbeat
  • darkening of the skin or pigment patches on the skin, particularly of the face
  • breast lumps

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed 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 (DVT). 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 (PE).

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

Blood clots are a rare occurrence and can develop whether or not you are taking the Pill. They can also happen during pregnancy. The risk of having blood clots is higher in the 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 Valette for the first time, or after having a break from Valette for 4 weeks or more.

If you notice possible signs of a blood clot, stop taking Valette 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 Valette, 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 VALETTE

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.

Keep the blister in the Outer Carton. Protect from light.

Do not store it or any other medicine in the bathroom, near a sink, or on a window-sill. Do not leave medication the car. Heat and damp can destroy some medicines.

Keep Valette where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

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

Return any unused medicine to your pharmacist.

PRODUCT DESCRIPTION

What it looks like

Valette comes in a box containing either 1 or 3 blister packs. Each blister pack contains 21 white active tablets and 7 brown inactive tablets.

The blister pack is marked with days of the week next to each tablet.

Ingredients

Each Valette white active tablet contains:

Active ingredients:

  • 2 milligrams of dienogest
  • 30 micrograms of ethinylestradiol

Inactive ingredients:

  • lactose monohydrate
  • maize starch
  • maltodextrin
  • sucrose
  • liquid glucose
  • calcium carbonate
  • povidone
  • macrogol 35000
  • carnauba wax
  • magnesium stearate
  • titanium dioxide

Each brown inactive tablet contains:

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

Valette tablets do not contain gluten, tartrazine or azo dyes.

Supplier

Made in Germany for:

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

Australian Registration Number

Valette - AUST R 122788

Date of Preparation

11 Apr 2023

See Bayer Australia website (www.bayer.com.au) for latest Australian Consumer Medicine Information.

Missed taking Valette?

See the end of this leaflet

® Registered Trademark of Bayer AG, Germany

© Bayer Australia Ltd

All rights reserved.

Published by MIMS May 2023

BRAND INFORMATION

Brand name

Valette

Active ingredient

Ethinylestradiol; Dienogest

Schedule

S4

 

1 Name of Medicine

Valette (dienogest and ethinylestradiol).

2 Qualitative and Quantitative Composition

Valette is a combined oral contraceptive (COC) preparation containing the synthetic progestogen, dienogest and the synthetic estrogen, ethinylestradiol as the active substances.
Valette tablets are contained in blister packs. Each blister contains 21 white active tablets containing dienogest 2 mg and ethinylestradiol 30 microgram, followed by 7 brown placebo tablets.

Excipients with known effect.

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

3 Pharmaceutical Form

The small active tablets are small round white glossy coated tablets.
The inactive tablets are large round brown coated tablets.

4 Clinical Particulars

4.1 Therapeutic Indications

Valette is indicated for use as an oral contraceptive and in the treatment of mild to moderate acne in women who seek oral contraception.

4.2 Dose and Method of Administration

Combined oral contraceptives, when taken correctly, have a failure rate of approximately 1% per year. The failure rate may increase when pills are missed or taken incorrectly.
Tablets must be taken in the order directed on the package every day at about the same time with some liquid as needed. Tablet taking is continuous. One tablet is to be taken continuously for 28 consecutive days. Each subsequent pack is started the day after the last tablet of the previous pack. Withdrawal bleeding usually starts on day 2-3 after starting the brown placebo tablets (last row) and may not have finished before the next pack is started.

How to start Valette.

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 should be instructed to take a white active tablet from the green section of the pack, corresponding to that day of the week. If Valette is started as described above, there is no need to employ an additional barrier method of contraception during the first cycle.
Starting on day 2-5 of menstrual bleeding is allowed, but during the first cycle a barrier method is recommended in addition for the first 7 days of tablet taking.

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

The woman should start with Valette preferably on the day after the last active tablet of her previous COC, but at the latest on the day following the usual tablet free or placebo tablet interval of her previous COC.
In case a vaginal ring has been used, the woman should start taking Valette preferably on the day of removal of the ring, but at the latest when the next application would have been due. Valette should be started by taking a white active tablet from the green section of the pack.

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

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

Following first trimester abortion.

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

Following delivery or second trimester abortion.

For breastfeeding women see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.
Women should be advised to start on 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 of tablet taking. However, if intercourse has already occurred, pregnancy should be excluded before the actual start of COC use or the woman has to wait for her first menstrual period.

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 white active tablets (rows 1-3 of the blister).
If the woman is less than 12 hours late in taking any 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 she is more than 12 hours late in taking any tablet, 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.
The following advice can be given in daily practice.

Week 1.

The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. In addition, a barrier method such as a condom should be used for the next 7 days. If intercourse took place in the preceding 7 days, the possibility of a pregnancy should be considered. The more tablets are missed and the closer they are to the placebo tablet phase the higher the risk of a pregnancy.

Week 2.

The woman should take the last missed tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time. Provided that the woman has taken her tablets correctly in the 7 days preceding the first missed tablet, there is no need to use extra contraceptive precautions. However, if this is not the case, or if she missed more than 1 tablet, the woman should be advised to use extra precautions for 7 days.

Week 3.

The risk of reduced reliability is imminent because of the forthcoming placebo tablet phase. However, by adjusting the tablet intake schedule, reduced contraceptive protection can still be prevented. By adhering to either of the following two options, there is therefore no need to use extra contraceptive precautions, provided that in the 7 days preceding the first missed 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 tablet as soon as she remembers, even if this means taking two tablets at the same time. She then continues to take tablets at her usual time until all the active tablets are used up. The 7 tablets from the last row (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 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 placebo tablet interval, the possibility of a pregnancy should be considered.

Advice in case of gastrointestinal disturbances.

In case of severe gastrointestinal disturbances, absorption may not be complete and additional contraceptive measures should be taken.
If vomiting occurs within 3-4 hours after tablet-taking, absorption may not be complete. In such an event, the advice concerning missed tablets (see above) is applicable. If the woman does not want to change her normal tablet-taking schedule, she has to take the extra tablet(s) needed from another pack.

How to delay a period.

To delay a period the woman should continue with another pack of Valette without taking the brown placebo tablets from her current pack. The extension can be carried on for as long as wished until the end of the active tablets in the second pack. During the extension the woman may experience breakthrough bleeding or spotting. Regular intake of Valette is then resumed with the next pack.

4.3 Contraindications

Combined oral contraceptive (COCs) including Valette, should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during COC use, the product should be stopped immediately.
Presence or risk of venous thromboembolism (VTE) (see Section 4.4 Special Warnings and Precautions for Use):
current VTE (on anticoagulants) or history of deep venous thrombosis [DVT] or pulmonary embolism [PE];
known hereditary or acquired predisposition for venous thromboembolism, such as APC-resistance (including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency;
major surgery with prolonged immobilisation;
a high risk of venous thromboembolism due to the presence of multiple risk factors.
Presence or risk of arterial thromboembolism (ATE) (see Section 4.4 Special Warnings and Precautions for Use):
current ATE or history of ATE (e.g. myocardial infarction or stroke) or prodromal condition (e.g. angina pectoris or transient ischaemic attack [TIA]);
known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (e.g. anticardiolipin-antibodies and lupus anticoagulant);
history of migraine with focal neurological symptoms;
a high risk of arterial thromboembolism due to multiple risk factors or to the presence of one serious risk factor such as: diabetes mellitus with vascular symptoms, severe hypertension, severe dyslipoproteinaemia.
Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
Valette is contraindicated for concomitant use with the medicinal products glecaprevir, pibrentasvir, sofosbuvir, velpatasvir, voxilaprevir, ombitasvir, paritaprevir or dasabuvir and combinations of these (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Presence or history of liver tumours (benign or malignant).
Known or suspected 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 Valette.

4.4 Special Warnings and Precautions for Use

If any of the conditions/ risk factors mentioned below are present, the benefits of Valette 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 Valette 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 (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 study1 suggest that this increased risk is mainly present during the first 3 months.
A recently conducted, large (approximately 140,000 women years (WY) of observation), prospective, multinational, cohort study on the safety of OC use, the EURAS study1 found that the VTE incidence in women with or without other risk factors for VTE who used COCs was in the range of 8-9.9 VTE per 10,000 WY. The study did not analyse incidence of VTE in Valette users separately.
The overall incidence rate for past OC users was 4.7 VTE/10,000 WY, which was further specified to 19.4 VTE/10,000 WY for pregnant past OC users and 2.3 VTE/10,000 WY for non pregnant past OC users.
Another recently conducted large population based study2 found an incidence rate of 20 VTE/10,000 WY in pregnant or postpartal women and 4.6 in non pregnant women of reproductive age. These rates tend to be higher than those reported in the past.
Based on the new data it can be assumed that the VTE risk in OC users is roughly twice as high as for non pregnant non OC users. The absolute attributable risk (approximately 4 VTEs per 10,000 WY of use) was found to be slightly higher in these studies than reported in the past. Nevertheless the risk in OC users remains lower than the VTE risk associated with pregnancy and the first weeks following 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 what is associated with CHC use.
Epidemiological studies, that compared the risk of VTE associated with use of dienogest/ethinylestradiol to the risk with use of COCs containing levonorgestrel/ ethinylestradiol, reported differing results ranging from no difference in risk to a three-fold increase in risk.
Meta-analysis of four large prospective cohort studies yielded an adjusted Hazard Ratio of 1.57 (95% Confidence Interval, 1.07 - 2.30) for VTE risk with Valette compared to COCs containing levonorgestrel/30 microgram ethinylestradiol. These studies cover 38,708 women-years of exposure to Valette.
An additional increase in VTE risk for CHCs containing ≥ 50 microgram ethinyloestradiol 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 Valette (see Section 4.2 Dose and Method of Administration; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy, 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, cerebral or retinal veins and arteries.
The risk for venous thromboembolic complications in CHC users may increase substantially in a woman with additional risk factors, particularly if there are multiple risk factors (see list below).
Valette is contraindicated if a woman has multiple risk factors that put her at high risk of venous thrombosis. If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in this case her total risk of VTE should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed.
When considering risk/benefit, the doctor should take into account that the adequate treatment of a condition may reduce the associated risk of thrombosis.

Risk factors for VTE.

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

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

Women should be informed of the symptoms of VTE and be advised to seek urgent medical attention if VTE symptoms develop and to inform the healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include:
unilateral swelling of the leg and/or foot or along a vein in the leg;
pain or tenderness in the leg which may be felt only when standing or walking;
increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include:
sudden onset of unexplained shortness of breath or rapid breathing;
sudden coughing which may be associated with haemoptysis;
sharp chest pain or sudden severe pain in the chest which may increase with deep breathing;
severe 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 discolouration of an extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision. Sometimes loss of vision can occur almost immediately.
Risk of arterial thromboembolism (ATE). Epidemiological studies have associated the use of CHCs with an increased risk for arterial thromboembolism (e.g. myocardial infarction, angina pectoris, stroke or TIA).
Arterial thromboembolic events may be fatal.
The risk of arterial thromboembolic complications in CHC users increases in women with risk factors. Valette is contraindicated if a woman has one serious or multiple risk factors for ATE that puts her at high risk of arterial thrombosis. If a woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the individual factors - in this case her total risk should be considered. If the balance of benefits and risks is considered to be negative a CHC should not be prescribed.

Risk factors for ATE.

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

Symptoms of ATE.

Women should be informed of the symptoms of ATE and be advised to seek urgent medical attention if ATE symptoms develop and to inform the healthcare professional that she is taking a CHC.
Symptoms of a stroke can include:
sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
sudden trouble walking, dizziness, loss of balance or coordination;
sudden confusion, slurred speech or aphasia;
sudden partial or complete loss of vision; diplopia;
sudden, severe or prolonged headache with no known cause;
loss of consciousness or fainting with or without seizure.
Temporary symptoms suggest the event is a transient ischaemic attack (TIA).
Symptoms of myocardial infarction 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 papillomavirus (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 fatal outcomes.

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 physician to withdraw the COC and treat the hypertension. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic 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 white active tablet contains 28.72 mg of lactose monohydrate and each brown 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, guided by the contraindications and warnings, 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 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.

Valette 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 tablets (see Section 4.2 Dose and Method of Administration, Management of missed tablets), vomiting, diarrhoea (see Section 4.2 Dose and Method of Administration, Advice in case of gastrointestinal disturbances) or concomitant medication (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Reduced cycle control.

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

Alanine transaminase (ALT) elevations.

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

Use in hepatic impairment.

Valette is contraindicated in women with severe hepatic diseases whilst liver function values have not returned to normal.

Use in renal impairment.

Valette has not been specifically studied in renally impaired patients.

Use in the elderly.

Valette is not indicated after menopause.

Paediatric use.

Valette 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.

Effect of other medicines on Valette.

Interactions can occur with medicines that induce microsomal enzymes which can result in increased clearance of sex hormones and which may lead to breakthrough bleeding and/or 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 drug administration and for 28 days after their discontinuation. If the period during which the barrier method is used runs beyond the end of the white active tablets, the brown placebo tablets should be omitted and the next COC pack should be started with the white active tablet in the green section of the corresponding day.

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

Phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin and products containing St. John's Wort.

Substances with variable effects on the clearance of COCs.

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

Substances decreasing the clearance of COCs (enzyme inhibitors).

Dienogest is a substrate of cytochrome P450 (CYP) 3A4.
Strong and moderate CYP3A4 inhibitors like azole antifungals (e.g. ketoconazole, itraconazole, voriconazole, fluconazole), cimetidine, verapamil, macrolides (e.g. clarithromycin, erythromycin), diltiazem, antidepressants and grapefruit juice may increase plasma levels of the estrogen or progestogen or both.
Etoricoxib doses of 60 to 120 mg/day have been shown to increase plasma concentrations of ethinylestradiol by 1.4 to 1.6-fold respectively, when taken concomitantly with a COC containing 35 microgram ethinylestradiol.

Effects of Valette on other medication.

Oral contraceptives may affect the metabolism of certain other medicines. Accordingly, plasma and tissue concentrations may increase (e.g. cyclosporin) or decrease (e.g. lamotrigine).
In clinical studies, administration of a hormonal contraceptive containing ethinylestradiol lead to no, or a weak increase in CYP3A4 substrates (e.g. midazolam) and a weak (e.g. theophylline) to moderate (e.g. melatonin, tizanidine) increase of CYP1A2 substrates.

Pharmacodynamic interactions.

Co-administration of ethinylestradiol-containing medicinal products with direct-acting antiviral (DAA) medicinal products containing ombitasvir, paritaprevir or dasabuvir and combinations of these has been shown to be associated with increases in alanine aminotransferase (ALT) levels to greater than 20 times the upper limit of normal in healthy female subjects and HCV infected women (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use). ALT elevations have also been observed with HCV anti-viral medicinal products including glecaprevir/ pibrentasvir. Patients taking a CHC should therefore be switched to an alternative method of contraception (e.g. progestogen-only contraception or non-hormonal methods) prior to starting therapy.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.
The reproductive toxicity of Valette has not been assessed in animals. Oral treatment of rats or rabbits with dienogest (the progestogen component) during organogenesis caused up to 12% increase in post-implantation loss at systemic exposure levels (based on AUC) similar to that anticipated clinically. No teratogenicity was evident in either species at systemic exposure levels up to ten-fold higher than that expected in humans at the clinical dose, based on AUC.
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 early pregnancy.
Valette is contraindicated during pregnancy. Pregnancy should be ruled out before the start of therapy. Should pregnancy occur during the use of Valette, Valette must be discontinued immediately.
 Dienogest is excreted into rat milk. Impaired reproductive function was seen in female rat pups of dams administered dienogest in the peri/ postnatal period at a systemic exposure level approximately one-third of that anticipated clinically, based on AUC. Based on animal data, there is some concern for an infant exposed to dienogest.
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 metabolites may be excreted with the milk. Therefore, the use of COCs should generally not be recommended until the nursing mother has completely weaned her child.

4.7 Effects on Ability to Drive and Use Machines

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

4.8 Adverse Effects (Undesirable Effects)

Various adverse effects have been associated with oral contraceptive use. The most serious adverse effects associated with the use of oral contraceptives are dealt with under Section 4.4 Special Warnings and Precautions for Use.
In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her doctor. The doctor should then decide on whether its use should be discontinued.

Clinical trial data.

The incidence of adverse events was derived from the phase III contraception study involving 2,290 women for a total of 28,183 cycles. Table 1 lists the adverse events (whether attributable to the medication or not) reported at a frequency of ≥ 1% of the events that occurred in this study.
In acne study 28501, which included patients with mild to moderate acne, the frequency of adverse events in the Valette group (n = 525) compared to the placebo group (n = 264) was as shown in Table 2 (for events affecting ≥ 1% of the Valette patients, i.e. at least 6 of 525), whether attributable to the medication or not.
Other adverse drug reactions reported in clinical trials with Valette, as oral contraceptive and in the treatment of mild to moderate acne in women who seek oral contraception, includes:

Infections and infestations.

Vulvovaginitis, vaginal candidiasis or other fungal vulvovaginal infections, salpingo-oophoritis, mastitis, cervicitis, candidiasis, oral herpes, upper respiratory infections, viral infection.

Neoplasms benign, malignant and unspecified (incl. cysts and polyps).

Uterine leiomyoma, lipoma of breast.

Blood and lymphatic system disorders.

Anaemia.

Endocrine disorders.

Virilism.

Metabolism and nutrition disorders.

Increased appetite, anorexia.

Psychiatric disorders.

Depressed mood, mental disorder, insomnia, sleep disorder, aggression, libido decreased, libido increased.

Nervous system disorders.

Dizziness, ischaemic stroke, cerebrovascular disorder, dystonia.

Eye disorders.

Dry eye, eye irritation, oscillopsia, visual impairment.

Ear and labyrinth disorders.

Sudden hearing loss, tinnitus, vertigo, hearing impaired.

Cardiac disorders.

Cardiovascular disorder, tachycardia (including hear rate increased).

Vascular disorders.

Venous and arterial thromboembolic events, thrombophlebitis, diastolic hypertension, orthostatic circulatory dysregulation, hot flush, varicose veins, vein disorder, vein pain.

Respiratory thoracic and mediastinal disorders.

Hyperventilation.

Gastrointestinal disorders.

Gastritis, dyspepsia.

Skin and subcutaneous tissue disorders.

Rash (including rash macular), pruritus (including pruritus generalised), dermatitis allergic, dermatitis atopic/neurodermatitis, psoriasis, hyperhidrosis, pigmentation disorder, hyperpigmentation, seborrhoea, dandruff, hirsutism, skin disorder, skin reaction, peau d'orange, spider naevus.

Musculoskeletal and connective tissue disorders.

Musculoskeletal discomfort, myalgia.

Reproductive system and breast disorders.

Abnormal withdrawal bleeding (including menorrhagia, hypomenorrhoea, oligomenorrhoea, and amenorrhoea), breast enlargement (including breast engorgement and breast swelling), breast oedema, genital/vaginal discharge, pelvic pain, cervical dysplasia, adnexa uteri cyst, adnexa uteri pain, breast cyst, fibrocystic breast disease, dyspareunia.

General disorders and administration site conditions.

Fatigue (including asthenia and malaise), chest pain, oedema peripheral, inflammation, pyrexia, irritability.

Investigations.

Weight changes (including weight increase, decrease and fluctuation), blood triglycerides increased, hypercholesterolaemia.

Congenital familial and genetic disorders.

Manifestation of asymptomatic accessory breast.

Postmarketing data.

The following undesirable effects have been reported in users of Valette or other COCs and the association has been neither confirmed nor refuted.

Cardiovascular.

Deep venous thrombosis, pulmonary embolism, cerebral infarction, thrombosis, migraine, stroke, occlusion retinal artery, hepatic haemangioma, superficial thrombophlebitis, hypertension, peripheral vascular disease.

Genital tract.

Intermenstrual bleeding (consisting of vaginal haemorrhage and metrorrhagia), menstrual disorders, vaginal mycosis.

Digestive.

Nausea, vomiting, diarrhoea, cholelithiasis, liver neoplasm, fatty liver, pancreatitis, hepatitis, hepatic cyst, decreased cholinesterase, gingivitis and abdominal pain (including upper and lower abdominal pain, abdominal discomfort/ distention).

Nervous system.

Depression, mood altered, headache, migraine, galactorrhoea, paraesthesia and changes in libido.

Musculoskeletal.

Articular swelling.

Respiratory tract.

Voice alteration, dyspnoea, asthma.

Skin.

Dermatitis, rash, urticaria, erythema nodosum, erythema multiforme, atopic eczema (exacerbation), papulous exanthema, chloasma.

Eyes.

Contact lens intolerance, blurred vision.

Metabolic.

Hypertriglyceridaemia, oedema, change in weight, fluid retention.

Haemic and lymphatic.

Haemorrhagic purpura, leucopoenia.

Body as a whole.

Anaphylactic reaction, pain in extremities.

Breast disorders.

Breast pain (including breast discomfort and breast tenderness), breast hypertrophy and breast discharge.

Immune system disorders.

Hypersensitivity.

Special senses.

Acute deafness.
In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

Reporting suspected adverse effects.

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

4.9 Overdose

There have been no reports of serious deleterious effects from overdose. On the basis of general experience with COCs, symptoms that may occur in case of overdose of active tablets are: nausea, vomiting and withdrawal bleeding. There are no antidotes and further treatment should be symptomatic. The later may occur in girls before their menarche, if they have accidentally taken the product.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The contraceptive effect of combined oral contraceptives (COCs) is based on the interaction of various factors. The primary mechanisms are inhibition of ovulation (by suppression of gonadotrophins) and changes in the cervical secretion (blocking the entry of sperm into the uterus). As well as protection against pregnancy, combined oral contraceptives 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, the menstruation is often less painful and bleeding is lighter. The latter may result in a decrease in the occurrence of iron deficiency.
Dienogest has beneficial properties in addition to contraception. Dienogest exerts antiandrogenic activity leading to a positive effect on the skin and to a reduction in acne lesions and sebum production. In addition, with the higher-dosed COCs (50 microgram ethinylestradiol), there is evidence of a reduced risk of fibrocystic tumours of the breasts, ovarian cysts, pelvic inflammatory disease, ectopic pregnancy and endometrial and ovarian cancer. Whether this also applies to lower-dosed combined oral contraceptives such as Valette remains to be confirmed.

Clinical trials.

The contraceptive efficacy and safety of Valette was examined in two open phase III multicentre studies, the first of which involved 2,290 evaluable women over a period ranging from 1 to 22 cycles, with 1,612 women completing 12 cycles. The second study investigated 97 women up to 12 cycles. The total cycle numbers were 28,183 and 686, respectively. The unadjusted Pearl Index for the first study was 0.68; the adjusted Pearl index was 0.21. No pregnancies occurred in the second study. Data are also available from two large post-marketing surveillance studies involving 92,146 treatment cycles from 16,087 women and 63,474 treatment cycles in 10,718 women. In the first of these studies only 17 pregnancies occurred, 6 after discontinuation. The Pearl Index was therefore 0.14. During the second study only 3 unintended pregnancies occurred, corresponding to an unadjusted Pearl Index of 0.057.
The effects on cycle control displayed in the phase III trials were as expected for a low dose combined oral contraceptive preparation. Intermenstrual bleeding was highest in the first cycle, with cycle stabilisation occurring with treatment duration. In the largest study spotting and breakthrough bleeding had been reduced by 50% after one year of treatment (from 21.5% in cycle 1 to 6.8% by cycle 12). The duration of bleeding decreased over the study periods, from 4.7 days to 3.2 days and from 6.2 days to 4 days in the two studies. Dysmenorrhoea, which occurred frequently before treatment (approx. 29%) had decreased so that 93% of women were complaint free by cycle 6 and it occurred only rarely after 12 cycles. Bleeding intensity also decreased under treatment. Prior to treatment 17.4% reported scanty bleeding and 7.4% excessive bleeding. By the 6th cycle 47.2% had scanty bleeding and only 2% excessive bleeding.

Acne.

A phase III study (Clinical Research Report No. 28501) investigated the anti-acne effects of Valette versus both a placebo control arm and a comparator arm with Diane-35 (ethinylestradiol and cyproterone acetate). The primary efficacy variables were the percentage change from baseline to cycle 6 in inflammatory (papules, pustules, nodules) lesion count, the total lesion count and improvement in facial acne according to the investigator's global assessment (IGA). The hypothesis that Valette is superior to placebo and not inferior to Diane-35 would only be correct if all 3 variables met the criteria. The study included 525 women treated with Valette, 537 with Diane-35 and 246 with placebo over 6 treatment cycles of 28 days. During the study, subjects were required to refrain from other anti-acne treatments and acne causing medications and comedogenic preparations. The results for the primary efficacy variables (FAS - Full Analysis Set) are provided in Table 3.
The conclusion is that Valette is superior to placebo while similar results for all three variables were obtained for the Valette and Diane-35 groups leading to the conclusion that Valette is not inferior to Diane-35.

5.2 Pharmacokinetic Properties

Bioavailability studies have been conducted with Valette.

Dienogest.

Absorption.

After single oral administration of 2 mg dienogest in combination with 30 microgram ethinylestradiol, dienogest is absorbed rapidly and almost completely. Maximum plasma concentrations of 51.6 ± 9.5 nanogram/mL are reached in 2.4 ± 1.4 hours after single dose oral administration. A high absolute bioavailability of about 96% was demonstrated in a bioavailability study.

Distribution.

10% is present in plasma in free form, whilst approx. 90% is bound non-specifically to albumin. Unlike all other 19-norprogesterones, dienogest does not bind to the specific transport proteins, sex hormone binding globulin (SHBG) and corticosteroid-binding globulin (CBG). As there is therefore no possibility of testosterone being displaced from its SHBG binding or of cortisols being displaced from its CBG binding, an influence on the physiological transport processes for endogenous steroids is unlikely.
The half-life of dienogest is 9.3 ± 1.8 hours, which is relatively short compared to other progestogens. There is thus very little accumulation with daily administration.

Metabolism.

Dienogest is metabolised mainly by hydroxylation, but also by hydrogenation, conjugation and aromatisation, to endocrinologically largely inactive metabolites. The contribution of the metabolites to the pharmacological and toxicological effects of dienogest is insignificant.

Excretion.

After an oral dose of 0.1 mg/kg body weight, the ratio of renal to faecal excretion is 3.2. The total clearance is 3.66 ± 0.71 L/h after a single dose.

Steady state conditions.

The pharmacokinetics of dienogest is not influenced by SHBG levels. Following daily ingestion, drug serum levels increase about 1.5-fold reaching steady-state conditions after approximately 4 daily administrations.

Ethinylestradiol.

Absorption.

Orally administered ethinylestradiol is absorbed rapidly in the small intestine. 50-60% of it is converted primarily to sulphate metabolites in the wall of the small intestine and in the liver (first-pass effect). After administration of the ethinylestradiol-dienogest combination, the absolute bioavailability of ethinylestradiol is about 44%.
After a single administration of 30 microgram ethinylestradiol and 2 mg dienogest, maximum plasma concentrations are reached after 1.5 to 4 hours.

Distribution.

Serum ethinylestradiol levels decrease in two phases, with an elimination half-life of 11.7 ± 6.5 hours following single administration of 30 microgram ethinylestradiol and 2 mg dienogest. Ethinylestradiol is highly but non-specifically bound to serum albumin (approximately 98.5%) and induces an increase in the serum concentrations of SHBG.

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. These are present as free metabolites and as conjugates with glucuronides and sulphate. The metabolic clearance rate of ethinylestradiol is about 5 mL/min/kg.

Excretion.

Ethinylestradiol is not excreted in unchanged form to any significant extent. The metabolites of ethinylestradiol are excreted 30-50% via the kidneys, with 30-40% being excreted with the faeces.

Steady state conditions.

Steady-state conditions are reached during the second half of treatment cycle when serum drug levels are approximately two fold higher than that of a single dose of ethinylestradiol.

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).
Assays for gene mutations in bacteria and mammalian cells, clastogenicity both in vitro and in vivo and unscheduled DNA synthesis, did not provide any evidence of a genotoxic potential for dienogest.

Carcinogenicity.

No long-term animal studies of the carcinogenic potential of Valette have been performed. However, studies have been performed for both ethinylestradiol and dienogest, the individual components of Valette. Long-term studies in rats and mice with dienogest showed increased incidences of pituitary adenomas, fibroepithelial mammary tumours, stromal polyps of the uterus, and malignant lymphoma, at doses corresponding to exposure levels about 10 times that anticipated at the maximum recommended clinical dose, based on AUC. Similar tumours have been shown to develop with other estrogenic/ progestogenic compounds. The tumours are thought to result from marked species differences in the optimal estrogen:progestogen ratio for reproductive function. Dienogest showed no tumour promotion activity in the rat liver foci assay at exposure levels corresponding to > 100 times the estimated human exposure at the clinical dose, based on AUC.
Although long-term animal studies did not definitely indicate a tumourigenic potential for the clinical use of either dienogest or ethinylestradiol, it should be noted that the tumourigenic potential of a combination of ethinylestradiol and dienogest has not been specifically investigated. Also, it must be borne in mind that sex steroids can promote the growth of certain hormone dependent tumours.

6 Pharmaceutical Particulars

6.1 List of Excipients

Valette tablets contain the following excipients: lactose monohydrate, maize starch, magnesium stearate, sucrose, liquid glucose, calcium carbonate, povidone, macrogol 35000, carnauba wax, maltodextrin and titanium dioxide.
Each placebo tablet contains: lactose monohydrate, maize starch, purified talc, magnesium stearate, povidone, sucrose, macrogol 6000, calcium carbonate, titanium dioxide, glycerol, ferric oxide, glycol montanate.

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.
Keep the blister in the outer carton. Protect from light.

6.5 Nature and Contents of Container

Valette tablets are contained in blister packs. Each blister contains 21 white active tablets containing dienogest 2 mg and ethinylestradiol 30 microgram, followed by 7 brown placebo tablets.
Blister packs are PVC/Al blister pack.
Carton containing blister packs of 1 x 28, 2 x 28, 3 x 28 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.

6.7 Physicochemical Properties

Chemical structure.

Dienogest.

Dienogest is a progestogen. The chemical name for dienogest is 17α-cyanomethyl-17β-hydroxy- estra-4,9(10)-dien-3-one and has the following structural formula:
Chemical formula: C20H25NO2.
Molecular weight: 311.42.
Melting point: 210-218°C.
Dienogest is a white to pale yellow crystalline powder, odourless, practically insoluble in water, sparingly soluble in ethanol and acetone, soluble in chloroform.

CAS number.

65928-58-7.

Chemical structure.

Ethinylestradiol.

Ethinylestradiol is an estrogen. Chemically, 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.
Ethinylestradiol is a white to creamy white, odourless, crystalline powder. It is insoluble in water and soluble in alcohol, chloroform, ether, vegetable oils and aqueous solutions of alkali hydroxides.

CAS number.

57-63-6.

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. Heit JA, Kobbervig CE, James AH et al. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30 year population based study. Ann Intern Med. 2005; 143:697-706.

7 Medicine Schedule (Poisons Standard)

Prescription Medicine.

Summary Table of Changes