Consumer medicine information

Marvelon 28

Desogestrel; Ethinylestradiol

BRAND INFORMATION

Brand name

Marvelon 28

Active ingredient

Desogestrel; Ethinylestradiol

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Marvelon 28.

What is in this leaflet

  1. What Marvelon 28 is used for
  2. When you must not use Marvelon 28
  3. What you need to know before using Marvelon 28
  4. When should you contact your doctor?
  5. How to use Marvelon 28
  6. What to do if...
  7. Side effects
  8. After taking Marvelon 28
  9. Product description

This leaflet answers some common questions about Marvelon 28. 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 Marvelon 28 against the benefits they expect it will have for you.

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

Read this information carefully before you start taking Marvelon 28 tablets.

Keep this leaflet. You may need to read it again.

1. What Marvelon 28 is used for

Marvelon 28 is an oral contraceptive, commonly known as a "Birth Control Pill" or "The Pill" that has been prescribed to prevent you from getting pregnant.

Marvelon 28 prevents pregnancy in several ways:

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

Marvelon 28 consists of 21 large white tablets, each containing 2 active ingredients: 30 micrograms of ethinylestradiol (an estrogen) and 150 micrograms of desogestrel (a progestogen) and 7 small white inactive tablets (first row of the blister pack).

Because of the small amounts of different female hormones in the active tablets, Marvelon 28 is considered a low-dose combined oral contraceptive.

Oral contraceptives are a very effective method of birth control. When taken correctly (without missing tablets) the chance of becoming pregnant is very low.

The following non-contraceptive health benefits have been associated with the combined Pill:

  • Your periods may be lighter and shorter. As a result, the risk of anaemia may be lower.
  • Your period pains may become less severe or may completely disappear.
  • In addition, some serious disorders have been reported to occur less frequently in users of Pills containing 50 micrograms of ethinylestradiol ('high-dose Pills'). These are benign breast disease, ovarian cysts, pelvic infections (pelvic inflammatory disease), ectopic pregnancy (pregnancy in which the embryo implants outside of the womb) and cancer of the endometrium (lining of the womb) and ovaries. This may also be the case for low-dose Pills but so far this has only been confirmed for endometrial and ovarian cancer.

Marvelon 28 is available only with a doctor's prescription.

2. When you must not use Marvelon 28

Do not take Marvelon 28 if you have an allergy to:

  • any medicine containing (desogestrel or ethinylestradiol)
  • any ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

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

Do not use the combined Pill if you have or have had any of the conditions listed below. If any of these conditions apply to you, tell your doctor before starting to use Marvelon 28. Your doctor may advise you to use a different type of Pill or an entirely different (non-hormonal) method of birth control.

  • a blood clot in the blood vessels of the legs (deep vein thrombosis), the lungs (pulmonary embolism), the heart (heart attack) or other parts of the body (see also the section later in this leaflet called 'The Pill and Thrombosis')
  • a stroke (caused by a clot in or a rupture of a blood vessel in the brain)
  • a condition that may be the first sign of a heart attack (such as angina pectoris or chest pain) or stroke (such as transient ischaemic attack or small reversible stroke)
  • a serious risk factor or several risk factors for developing a blood clot
  • very high blood pressure
  • a very high level of fat in the blood (cholesterol or triglycerides)
  • if you have major surgery (e.g., an operation) and your ability to move around is limited for a long period of time (see also the section later in this leaflet called "The Pill and Thrombosis")
  • a disorder affecting your blood clotting - for instance Activated Protein C resistance, antithrombin-III, protein C or protein S deficiencies
  • a history of migraine accompanied by e.g. visual symptoms, speech disability, or weakness or numbness in any part of the body
  • diabetes mellitus with blood vessel damage
  • pancreatitis (an inflammation of the pancreas) associated with high levels of fatty substances in your blood
  • jaundice (yellowing of the skin) or severe liver disease and your liver is not yet working normally
  • a cancer that may grow under the influence of sex hormones (e.g. of the breast or of the genital organs)
  • a benign or malignant liver tumour
  • any unexplained vaginal bleeding
  • you are pregnant or think you might be pregnant.

If any of these conditions appear for the first time while using the Pill, stop taking it at once and tell your doctor. In the meantime use non-hormonal contraceptive measures. See also 'General Notes' in the next section.

Do not use Marvelon 28 if you have Hepatitis C and are taking the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (see "Taking Other Medicines").

Do not take Marvelon 28 if the expiry date printed on the pack has passed.

Do not take Marvelon 28 if the packaging is torn or shows signs of tampering.

3. What you need to know before using Marvelon 28

General notes

In this leaflet, several situations are described where you should stop taking the Pill, or where the reliability of the Pill may be decreased. In such situations you should not have sex or you should take extra non-hormonal contraceptive precautions, e.g. use a condom or another barrier method. Do not use rhythm or temperature methods. These methods can be unreliable because the Pill alters the usual changes in temperature and cervical mucus that occur during the menstrual cycle.

If you are concerned about contracting a sexually transmitted infection (STI), ask your partner to wear a condom when having sexual intercourse with you.

Marvelon 28 will not protect you from HIV (AIDS) or any other sexually transmitted infections. To help protect yourself from STIs, you need to use a barrier contraceptive such as a condom, but even barrier contraceptives may not protect you against human papilloma virus (HPV).

Before you start to use Marvelon 28

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

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

You must tell your doctor if you smoke. The risk of having a heart attack or stroke increases as you get older. It also increases the more you smoke. When using the Pill you should stop smoking, especially if you are older than about 35 years of age.

You must tell your doctor if you have any of the conditions listed below. You may need to be kept under close observation. Your doctor can explain this to you. Tell your doctor if:

  • you have diabetes
  • you are overweight
  • you have high blood pressure
  • you have a heart valve disorder or a certain heart rhythm disorder
  • you have an inflammation of your veins (superficial phlebitis)
  • you have varicose veins
  • anyone in your immediate family has had a thrombosis, a heart attack or a stroke
  • you suffer from migraine
  • you suffer from epilepsy
  • you or someone in your immediate family has or has had high levels of cholesterol or triglycerides (fatty substances) in the blood
  • anyone in your immediate family has had breast cancer
  • you have liver or gall bladder disease
  • you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease)
  • you have systemic lupus erythematosus (SLE, a disease affecting the skin all over the body)
  • you have haemolytic uraemic syndrome (HUS; a disorder of blood coagulation causing failure of the kidneys)
  • you have sickle cell disease
  • you have a condition that occurred for the first time or worsened during pregnancy or previous use of sex hormones (e.g. hearing loss, a metabolic disease called porphyria, a skin disease called herpes gestationis, a neurological disease called Sydenham's chorea)
  • you have or have had chloasma (yellow brownish pigmentation patches on the skin, particularly of the face); if so, avoid too much exposure to the sun or ultraviolet radiation.
  • You need an operation or if your ability to move around is limited for a long period of time. This includes travelling by plane for greater than 4 hours.
  • if you have recently given birth you are at an increased risk of blood clots. You should ask your doctor how soon after delivery you can start using Marvelon 28 (see also the section in this leaflet called 'The Pill and Thrombosis');
  • you are lactose intolerant.

Tell your doctor if any of the above conditions appear for the first time, recur or worsen while using the Pill.

The Pill and Thrombosis

A thrombosis is the formation of a blood clot which may block a blood vessel.

A thrombosis sometimes occurs in the deep veins of the legs (deep venous thrombosis). If this blood clot breaks away from the veins where it is formed, it may reach and block the arteries of the lungs, causing a so-called 'pulmonary embolism'. Deep venous thrombosis is a rare occurrence. It can develop whether or not you are taking the Pill. The risk is higher in Pill-users than in non-users. The chance of getting a thrombosis is highest during the first year after you start using the Pill for the very first time. The risk is also higher if you restart using the Pill (the same product or a different product) after a break of 4 weeks or more. Thrombosis can also happen if you become pregnant.

The risk of getting a blood clot in the deep veins of the legs for women using Pills with desogestrel (in Marvelon 28) may be slightly higher than for women using Pills with levonorgestrel, norgestimate or norethisterone. The absolute numbers remain very small.

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

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

If you develop high blood pressure while using the Pill, you may be told to stop using it.

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

If you notice possible signs of a thrombosis, stop taking the Pill and consult your doctor immediately (See also 'When should you contact your doctor?').

The Pill and Cancer

Regularly examine your breasts.

The information given below was obtained from studies of women who used combined oral hormonal contraceptives, such as the combined pill, and from an additional study that included both oral and non-oral hormonal contraceptive-users.

In studies with the combined Pill, breast cancer has been diagnosed slightly more often in women who use the Pill than in women of the same age who do not use the Pill. This slight increase in the numbers of breast cancer diagnoses gradually disappears during the course of the 10 years after stopping use of the Pill.

In the additional study that included both oral and non-oral hormonal contraceptive-users, the occurrence of breast cancer was reported to increase the longer the women used the contraceptive. The difference in the reported risk of breast cancer between women who have never used the contraceptive and those who had used the contraceptive was small: 13 additional cases of breast cancer per 100,000 women-years.

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

Tell your doctor immediately if you have severe pain in your stomach. 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.

Chronic infection with Human Papilloma Virus (HPV) is the single most important risk factor for cervical cancer. HPV is a sexually transmitted infection. In women who use combined oral contraceptives for a long time the chance of getting cervical cancer may be slightly higher. This finding may not be caused by the Pill itself but may be related to sexual behaviour and other factors.

The Pill and Pregnancy

Tell your doctor immediately if you are pregnant or think you are pregnant while you are using Marvelon 28. Like most medicines, Marvelon 28 must not be used during pregnancy.

The Pill and Breastfeeding

Marvelon 28 is generally not recommended for use during breastfeeding. If you wish to take the Pill while breastfeeding, please seek the advice of your doctor.

The Pill and Ability to Drive

There are no observed effects.

Taking Other Medicines

Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines or herbal products, even those not prescribed. Also tell any other doctor or dentist who prescribes another medicine (or your pharmacist) that you use Marvelon 28.

Some medicines may stop Marvelon 28 from working properly. These include :

  • medicines for epilepsy (such as phenytoin, primidone, phenobarbital, carbamazepine, oxcarbazepine, topiramate, felbamate)
  • medicines for tuberculosis (e.g. rifampicin and rifabutin)
  • medicines for HIV infections (e.g. ritonavir, nelfinavir, nevirapine, efavirenz)
  • medicines for Hepatitis C virus infection (e.g. boceprevir, telaprevir);
  • antifungals (e.g. griseofulvin)
  • medicines for high blood pressure in the blood vessels of the lungs (bosentan);
  • herbal medicines containing St. John's Wort primarily for the treatment of depressive moods

If you are taking medicines or herbal products that might make Marvelon 28 less effective, a barrier contraceptive method should also be used. Since the effect of another medicine on Marvelon 28 may last up to 28 days after stopping the medicine, it is necessary to use the additional barrier contraceptive method for that long.

Your doctor will tell you how long you need to take additional contraceptive precautions or whether you should use another contraceptive method altogether.

Marvelon 28 may also interfere with how other medicines work, causing either an increase in effect (e.g., ciclosporin) or a decrease in effect (e.g lamotrigine).

Do not use Marvelon 28 if you have Hepatitis C and are taking the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir as this may cause increases in liver function blood test results (increase in ALT liver enzyme). Marvelon 28 can be restarted approximately 2 weeks after completion of treatment with the combination drug regimen. (See "When you must not use Marvelon 28").

4. When should you contact your doctor?

Regular check-ups

When you are using the Pill, your doctor will tell you to return for regular check-ups. You should have a check-up at least once a year.

Contact your doctor as soon as possible if:

  • you notice any changes in your own health, especially involving any of the items mentioned in this leaflet (see also 'When you must not use Marvelon 28?' and 'Before you start to use Marvelon 28'); do not forget about the items related to your immediate family
  • you feel a lump in your breast
  • you are going to use other medicines (see also Taking Other Medicines)
  • your ability to move around is limited for a long period of time or you are to have surgery (consult your doctor at least 4 weeks in advance)
  • you have unusual, heavy vaginal bleeding
  • you forgot tablets in the first week of the pack and had intercourse in the seven days before
  • you have severe diarrhoea
  • you miss your period twice in a row or suspect you are pregnant. Do not start the next pack until told to by your doctor.

Stop taking tablets and see your doctor immediately if you notice possible signs of thrombosis, myocardial infarction or a stroke such as:

  • an unusual cough
  • severe pain in the chest which may reach the left arm - this discomfort may include the back, jaw, throat, arm, stomach
  • feeling of being full, having indigestion or choking
  • sweating, nausea, vomiting, anxiety
  • breathlessness or rapid breathing
  • any unusual, sudden, severe or prolonged headache or migraine attack
  • partial or complete loss of vision, or double vision
  • confusion, slurring or speech disability
  • sudden changes to your hearing, sense of smell or taste
  • dizziness or fainting
  • fast or irregular heartbeat
  • weakness or numbness in any part of your body
  • severe pain in your stomach
  • severe pain or swelling in either of your legs
  • pain or tenderness in the leg which may be felt only when standing or walking
  • warmth, red or discoloured skin on the leg
  • sudden pain, swelling and slight blue discoloration of an extremity
  • sudden trouble walking, loss of balance or coordination

The situations and symptoms mentioned above are described and explained in more detail in the following section 'What do you need to know before using Marvelon 28'.

5. How to use Marvelon 28

Marvelon 28 pack contains 28 tablets: 21 large white tablets with active substances and 7 small tablets that do not contain active substances. On the blister each tablet is marked with the day of the week on which it is to be taken. Take your tablet about the same time each day, with some liquid if necessary. Follow the direction of the arrows on the pack until all 28 tablets have been taken. A period should begin during the 7 days that you use the inactive tablets (the withdrawal bleed). Usually it will start on day 2-3 after the last large tablet.

Start taking your next pack immediately after the last small inactive tablet, even if your period continues. This means you will always start new packs on the same day of the week, and also means that you have your period on about the same days, each month.

When no hormonal contraception has been used in the past month

Start taking Marvelon 28 on the first day of your cycle, i.e. the first day of menstrual bleeding. Take a tablet from the green section marked with that day of the week. For example, if your period starts on a Friday, then take a tablet marked Friday. Then follow the days in order. Marvelon 28 will work immediately, it is not necessary to use an additional contraceptive method.

You may also start on days 2-5 of your cycle, but in that case make sure you also use an additional contraceptive method (barrier method) for the first 7 days of tablet-taking in the 1st cycle.

When changing from another combined hormonal contraceptive (combined oral contraceptive (COC), vaginal ring, or transdermal patch)

You can start taking Marvelon 28 the day after you take the last tablet from your present Pill pack. If your present Pill pack contains inactive tablets (placebo) tablets you can start Marvelon 28 on the day after taking the last active tablet (if you are not sure which this is, ask your doctor or pharmacist). You can also start later, but never later than the day following the tablet-free break of the present Pill (or the day after the last inactive tablet of your present Pill).

In case you use a vaginal ring or transdermal patch, you should start using Marvelon 28 preferably on the day of removal, but at latest when the next ring or patch would have been applied.

When changing from a progestogen-only method (minipill)

You can stop taking the minipill any day and start taking Marvelon 28 the next day, at the same time. But make sure you also use an additional contraceptive method (a barrier method) for the first 7 days of tablet-taking.

When changing from an injectable, an implant or a progestogen-releasing intrauterine device (IUD)

Start using Marvelon 28 when your next injection is due or on the day that your implant or your IUD is removed. Make sure you also use an additional contraceptive method (a barrier method) for the first 7 days of tablet-taking.

After having a baby

If you have just had a baby, your doctor may tell you to wait until after your first normal period before you start taking Marvelon 28. Sometimes it is possible to start sooner. Your doctor will advise you. If you are breast-feeding and want to take Marvelon 28, you should discuss this first with your doctor.

After a miscarriage or abortion

Your doctor will advise you.

Additional contraceptive precautions

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

6. What to do if...

You forget to take your tablets

  • If you are less than 12 hours late in taking any tablet, take the tablet as soon as you remember and take further tablets at the usual time.
  • If you are more than 12 hours late in taking a large (active) tablet, the reliability of the Pill may be reduced. The more consecutive tablets you have missed, the higher the risk that the contraceptive efficacy is decreased. There is a particularly high risk of becoming pregnant if you miss large (active) tablets at the beginning of the pack or in the 3rd week (the week before you start taking the small tablets). Therefore you should follow the rules given below.

More than one tablet forgotten in a pack
Ask your doctor for advice.

One tablet missed in week 1
Take the missed tablet as soon as you remember (even if this means taking two tablets at the same time) and take the next tablets at the usual time. Use extra contraceptive precautions (barrier method) for the next 7 days. If you had sexual intercourse in the week before missing the tablets, there is a possibility of becoming pregnant. So tell your doctor immediately.

One tablet missed in week 2
Take the missed tablet as soon as you remember (even if this means taking two tablets at the same time) and take the next tablets at the usual time. The reliability of the Pill is maintained. You need not use extra contraceptive precautions.

One tablet missed in week 3
You may choose either of the following options, without the need for extra contraceptive precautions.

  1. Take the missed tablet as soon as you remember (even if this means taking two tablets at the same time) and take the next tablets at the usual time. Start the next pack as soon as the large (active) tablets in the current pack are finished, so skip the smaller placebo tablets. You may not have a withdrawal bleed until you take the placebo tablets at the end of the second pack but you may have spotting or breakthrough bleeding on active tablet-taking days.
    Or
  2. Stop taking the large (active) tablets from your current pack and immediately continue with the smaller placebo tablets (a maximum of 6 days, the total number of placebo plus missed tablets may not be more than 7). Then continue with the next pack. When following this method, you can always start your next pack on the same day of the week as you usually do.

One tablet missed in week 4
The reliability of the Pill is maintained. Take the tablet as soon as you remember and take the next tablets at the usual times.

If you have forgotten tablets in a pack and you do not have the expected period in the first normal placebo tablet interval, you may be pregnant. Consult your doctor before you start with the next pack.

You want to delay your period

You can delay your period if you continue with the large (active) tablets in your next pack of Marvelon 28 immediately after finishing the large tablets in your current pack. You can continue with this pack for as long as you wish, until this pack is empty. When you wish your period to begin, just stop tablet-taking. While using the second pack you may have some breakthrough bleeding or spotting on active tablet-taking days. Start your next pack after the usual 7 day inactive tablet interval.

You want to change the starting day of your period

If you take your tablets as directed, you will have your period on about the same day every 4 weeks. If you want to change this, just shorten (never lengthen) the next placebo tablet interval. For example, if your period usually starts on a Friday and in future you want it to start on Tuesday (3 days earlier) you should now start your next pack 3 days sooner than you usually do. If you make your placebo tablet interval very short (e.g. 3 days or less), you may not have a bleeding during the interval. You may have some breakthrough bleeding or spotting during the use of the large tablets in the next pack.

If you vomit or have diarrhoea

If you vomit, or have severe diarrhoea, the active ingredients of your Marvelon 28 tablet may not have been completely absorbed. If you vomit within 3 to 4 hours after taking your tablet, this is like missing a tablet. Therefore, follow the advice for missed tablets. If you have severe diarrhoea, please contact your doctor.

If you have unexpected bleeding

With all Pills, for the first few months, you can have irregular vaginal bleeding (spotting or breakthrough bleeding) between your periods. You may need to use sanitary protection, but continue to take your tablets as normal. Irregular vaginal bleeding usually stops once your body clock has adjusted to the Pill (usually after about 3 tablet-taking cycles). Tell your doctor if it continues, becomes heavy or starts again.

If you have missed a period

If you have taken all of your tablets at the right time, and you have not vomited, or had severe diarrhoea or used other medicines then you are very unlikely to be pregnant. Continue to take Marvelon 28 as usual.

If you miss your period twice in a row, you may be pregnant. Do not start the next pack of Marvelon 28 until your doctor has checked you are not pregnant.

If you take too much (overdose)

There have been no reports of serious harmful effects from taking too many Marvelon 28 tablets at one time. If you take too much Marvelon 28 you may feel sick, vomit or have vaginal bleeding.

If you discover a child has taken Marvelon 28, ask your doctor for advice.

If you are not sure what to do, telephone your doctor or the Poisons Information Centre on 13 11 26 for advice.

7. Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while taking Marvelon 28.

Like all medicines, Marvelon 28 can have side effects. Sometimes they are serious, most of the time they are not.

Serious side effects
Serious reactions associated with the use of the Pill, as well as the related symptoms, are described in the following sections: 'The Pill and Thrombosis/ The Pill and Cancer'. Please read these sections for additional information and consult your doctor at once where appropriate.

Other possible side effects
The following side effects have been reported by users of the Pill, although they may not be caused by the Pill. These side effects may occur in the first few months that you are using the Pill and usually lessen with time.

Common/uncommon (occurring in more than one per 1000 users):

  • nausea, vomiting, abdominal pain, diarrhoea
  • increase in body weight, fluid retention
  • headache, migraine
  • decreased sexual drive, depressed mood, mood changes
  • breast pain, breast tenderness, breast enlargement
  • rash, hives.

Rare (occurring in less than one per 1000 users):

  • contact lens intolerance
  • hypersensitivity reactions
  • decrease in body weight
  • increased sexual drive
  • breast secretion
  • vaginal secretion
  • acne
  • erythema nodosum, erythema multiforme (these are skin conditions)
  • hair loss
  • excessive hair growth

You should stop taking Marvelon if you experience any signs of thrombosis (headache or pain elsewhere in your body, dizziness, fainting, disturbances in vision, swollen ankles), or jaundice (yellowing of the eyes or skin).

Tell your doctor or pharmacist if you notice any side effects not mentioned in this leaflet.

8. After taking Marvelon 28

If you want to stop taking Marvelon 28

You can stop taking Marvelon 28 any time you want to.

If you do not want to get pregnant, use another reliable birth control method after stopping Marvelon 28. Ask your doctor for advice.

If you stop because you want to get pregnant, it is generally recommended that you wait until you have had natural period before trying to conceive. This helps you to work out when the baby will be due.

Ask your doctor or pharmacist for advice about taking folate if you plan to become pregnant.

Storage

Do not use after the expiry date stated on the blister and outer box.

Store your tablets below 30°C in a dry place and protect them from light.

Do not store Marvelon 28 or any other medicine in the bathroom or near a sink. Do not leave it in the car or on a window sill. Heat and dampness can destroy some medicines.

Do not use the product if you notice, for example, colour change in the tablet, crumbling of the tablet or any other visible signs of deterioration.

Keep it where children cannot reach it. A locked cupboard at least 1.5 meters above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using Marvelon 28 or the tablets have passed their expiry date, ask your pharmacist what to do with any left over.

9. Product description

What it looks like

Marvelon 28 is presented in a PVC/Aluminium backed blister containing 28 tablets (21 active tablets) and 7 smaller (inactive) tablets packed in a sealed sachet. The sachet is packed in a carton together with the package leaflet.

Active Substance
In the large tablets:

  • ethinylestradiol 30 micrograms
  • desogestrel 150 micrograms

In the smaller (inactive) tablets:

  • no active ingredients

Other ingredients
In the large tablets:

  • colloidal anhydrous silica; lactose monohydrate; potato starch; povidone; stearic acid; dl-alpha-tocopherol.

In the smaller (inactive) tablets:

  • lactose monohydrate; potato starch; magnesium stearate

Supplier

Organon Pharma Pty Limited
Building A, 26 Talavera Road,
Macquarie Park, NSW 2113
Australia

The leaflet was prepared in February 2021

AUST R 42894

S-CCPPI-MK8276A-TB-112018

Published by MIMS April 2021

BRAND INFORMATION

Brand name

Marvelon 28

Active ingredient

Desogestrel; Ethinylestradiol

Schedule

S4

 

1 Name of Medicine

Desogestrel and ethinylestradiol.

2 Qualitative and Quantitative Composition

Each pack contains 21 active tablets each containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol and 7 inert (placebo) tablets.

Excipients with known effect.

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

3 Pharmaceutical Form

Marvelon 28 has:
21 large, white, round, biconvex tablets coded TR5 on one side, and Organon and a star on the other; and
7 small, white, round, biconvex tablets coded KH2 on one side and a square on the other. These tablets do not contain active ingredients.

4 Clinical Particulars

4.1 Therapeutic Indications

Oral contraception.

4.2 Dose and Method of Administration

How to take Marvelon 28.

One tablet is to be taken daily. The tablets must be taken in the order directed on the package at about the same time each day, with some liquid as needed. Daily tablet taking should be continuous, starting with the tablet marked with the corresponding day from the green zone. Each subsequent pack is to be started immediately following the last placebo (small) tablet. During the placebo days a withdrawal bleed usually occurs. This usually starts on day 2-3 after the last active (large) tablet and may not have finished before the next pack is started.

How to start taking Marvelon 28.

The tablets are taken starting with the tablet marked with the corresponding day from the green zone of the pack. This way, the woman will virtually always have a menstruation free weekend.

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

Tablet taking has to start on day 1 of the woman's natural cycle (i.e. the first day of her menstrual bleeding). If the woman starts on a Thursday or Friday (although these tablets are in the green zone, they are inactive tablets), additional contraceptive precautions are necessary for the first 7 days of active tablet taking.

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

The woman should start with Marvelon 28 preferably on the day after the last active tablet (the last tablet containing the active substances) of her previous COC, but at the latest on the day following the usual tablet free interval or following the last placebo tablet of her previous COC. In case a vaginal ring or transdermal patch has been used, the woman should start using Marvelon 28 preferably on the day of removal, but at the latest when the next application would have been due.
The hormone free interval of the previous method should never be extended beyond its recommended length.

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

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

Following a first trimester abortion.

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

After childbirth or a second or third trimester abortion.

For breastfeeding women see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.
Women should be advised to start 21 to 28 days after delivery or second trimester abortion (no later than day 26 if starting on a Thursday or day 27 if starting on a Friday). When starting later than day 28, the woman should be advised to additionally use a barrier method for the first 7 days of active 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. The increased risk of VTE during the postpartum period should be considered when restarting Marvelon 28 (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

Management of missed tablets.

When Marvelon is taken according to the directions for use, the occurrence of pregnancy is highly unlikely. However, the reliability of oral contraceptives may be reduced under the following circumstances.
If the user 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 active tablet, contraceptive protection may be reduced. The management of missed tablets can be guided by the following two basic rules:
1.'active tablet' taking must never be discontinued for longer than 7 days.
2. 7 days of uninterrupted 'active tablet' taking are required to attain adequate suppression of the hypothalamic pituitary ovarian axis.
Accordingly the following advice can be given in daily practice.
If the user is more than 12 hours late in taking any large tablet (or several large tablets) from the pack, she should take the last forgotten tablet, even if this means taking two tablets in one day, and then continue to take tablets at the normal time. Additional contraceptive precautions should be taken for the next 7 days.
If these 7 days would usually include the taking of small (inert) tablets, the large (active) tablets of the next pack should be started as soon as the large tablets from the current pack are finished. This prevents an extended break in taking active tablets, which may increase the risk of the ovaries releasing an egg and thus reducing contraceptive protection. The woman will not have a period until the end of the second pack of tablets, but this is not harmful, nor does it matter if she experiences some bleeding on the days she is taking Marvelon.
Whenever large tablets are missed at the beginning of the pack (that is, missing one or more of the first 7 large tablets) and sexual intercourse has taken place, the possibility of pregnancy should be considered.

Advice in case of gastrointestinal disturbances.

In case of severe gastrointestinal disturbance, absorption may not be complete and additional contraceptive measures should be taken.
If vomiting occurs within 3-4 hours after tablet taking, the advice concerning missed tablets, as given previously, 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.

Additional contraceptive precautions.

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

How to shift periods or how to delay a period.

To delay a period the woman should continue with another pack of Marvelon 28 without having a placebo tablet interval. The extension can be carried on for as long as wished until the end of the second pack. During the extension the woman may experience breakthrough bleeding or spotting. Regular intake of Marvelon 28 is then resumed after the usual 7 day placebo tablet interval.
To shift her period to another day of the week than the woman is used to with her current scheme, she can be advised to shorten her forthcoming placebo tablet interval by as many days as she likes. The shorter the interval, the higher the risk that she does not have a withdrawal bleed and will experience breakthrough bleeding and spotting during the second pack (just as when delaying a period).

4.3 Contraindications

Combined oral contraceptives (COCs) should not be used in the presence of any of the conditions listed below. Should any of the conditions appear for the first time during the use of Marvelon, 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, hyperhomocysteinaemia and antiphospholipid antibodies;
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), APC resistance (including factor V Leiden), antithrombin III deficiency, protein C deficiency, protein S deficiency;
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 hypertriglyceridaemia.
Presence or history of severe hepatic disease as long as liver function have not returned to normal.
Presence or history of liver tumours (benign or malignant).
Known or suspected sex steroid influenced malignancies (e.g. of the genital organs or the breasts).
Undiagnosed vaginal bleeding.
Known or suspected pregnancy.
Hypersensitivity to any of the ingredients contained in Marvelon.
Marvelon 28 is contraindicated for use with the hepatitis C virus combination drug regimen ombitasvir/ paritaprevir/ ritonavir with or without dasabuvir (see Section 4.4 Special Warnings and Precautions for Use).

4.4 Special Warnings and Precautions for Use

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

1. Circulatory disorders.

Risk of venous thromboembolism (VTE).

Epidemiological studies have shown an association between the use of combined oral contraceptives (COCs) containing ethinylestradiol and an increased risk of venous thrombotic and thromboembolic diseases such as deep venous thrombosis and pulmonary embolism. These events occur rarely in average risk women.
The use of any ethinylestradiol containing COC is associated with an increased risk of venous thromboembolism (VTE) compared with no use. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive. The risk is also increased after initially starting a COC or restarting the same or different COC after a break in use of 4 weeks or more. This increased risk is less than the risk of VTE associated with pregnancy, which is estimated as 5 to 20 per 10,000 pregnant woman years. This compares with 1 to 5 cases per 10,000 woman years for nonusers. VTE is fatal in 1%-2% of cases.
Extremely rarely, thrombosis has been reported to occur in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.
The use of any CHC increases the risk of VTE compared with no use.
The risk of VTE with the COC is greatest for products containing over 50 microgram of ethinylestradiol. There is less risk for products containing less than 35 microgram ethinylestradiol. Marvelon contains the progestogen desogestrel which has an increased risk of VTE compared to other progestogens such as levonorgestrel, norgestimate or norethisterone which are associated with the lowest risk of VTE (see Table 1).
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 1.
The increased risk of VTE during the postpartum period should be considered if restarting Marvelon (see Section 4.2 Dose and Method of Administration).
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 below).
Marvelon 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.

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, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
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 Marvelon (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 Marvelon 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.
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 discoloration of an extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can progress to loss of vision. Sometimes loss of vision can occur almost immediately.

Risk of arterial thromboembolism (ATE).

Epidemiological studies have associated the use of COCs 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 COC users increases in women with risk factors. Marvelon 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.

Risk factors for ATE.

Increasing age, particularly above 35 years.
Smoking.
Hypertension.
Obesity (BMI 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), activated protein C (APC) resistance (including factor V Leiden), antithrombin III deficiency, protein C deficiency, protein S deficiency.
Migraine.
Other medical conditions associated with adverse vascular events: diabetes mellitus, valvular heart disease, atrial fibrillation, dyslipoproteinaemia, systemic lupus erythematosus.
Women should be 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.

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;
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.

2. Neoplasms.

Several epidemiological studies suggest that use of combined oral contraceptives, in particular if used for 5 years or longer, has been associated with an increased risk of cervical intraepithelial neoplasia or invasive cervical cancer. After cessation of use of oral contraceptives the risk gradually decreases over time to that of nonusers in about 8 years. Human papilloma virus is believed to be the most important cause of cervical cancer, but the independent association with the use of hormonal contraceptives suggests a contributing effect. These findings must be balanced against evidence of significant effects attributable to sexual behaviour, smoking, parity and other factors. See Section 4.4 Special Warnings and Precautions for Use, Medical examination/ consultation.
An increased risk of cervical cancer in long-term users of COCs 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).
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. The breast cancers diagnosed in ever-users tend to be less advanced clinically than the cancers diagnosed in never-users.
In another epidemiological study of 1.8 million Danish women followed an average of 10.9 years, the reported RR of breast cancer among COC users increased with longer duration of use compared with women who never used COCs (overall RR = 1.19; RR ranged from 1.17 for 1 to less than 5 years of use to 1.46 after more than 10 years of use). The reported absolute risk difference (number of breast cancer cases between never-users compared with current and recent COC users) was small: 13 per 100,000 woman-years.
Epidemiological 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.
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.
(Also see Section 5.3 Preclinical Safety Data, Genotoxicity, Carcinogenicity.)

3. Hepatitis C.

During clinical trials with the HCV combination drug regimen ombitasvir/ paritaprevir/ ritonavir with and without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN) were significantly more frequent in women using ethinylestradiol containing medications such as CHCs. Marvelon 28 must be discontinued prior to starting therapy with the combination drug regimen ombitasvir/ paritaprevir/ ritonavir with or without dasabuvir (see Section 4.3 Contraindications; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Marvelon 28 can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.

4. Other conditions.

Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.
Although small increases in blood pressure have been reported in many women taking COCs, clinically relevant increases are rare. However, if a sustained clinically significant hypertension develops during the use of a COC then it is prudent for the physician to withdraw the COC and treat the hypertension. Where considered appropriate, COC use may be resumed if normotensive values can be achieved with antihypertensive therapy.
The following conditions have been reported to occur or deteriorate with both pregnancy and COC use, but the evidence of an association with COC use is inconclusive: jaundice and/or pruritus related to cholestasis; gallstone formation; porphyria; systemic lupus erythematosus; haemolytic uraemic syndrome; Sydenham's chorea; herpes gestationis; otosclerosis related hearing loss; (hereditary) angioedema.
Although COCs may have an effect on peripheral insulin resistance and glucose tolerance, there is no evidence for a need to alter the therapeutic regimen in diabetics using low dose COCs (containing < 50 microgram ethinylestradiol). However, diabetic women should be carefully observed while taking COCs.
Crohn's disease and ulcerative colitis have been associated with COC use.
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.
Marvelon 28 contains < 80 mg lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption who are on lactose free diet should take this amount into consideration.
When counselling the choice of contraceptive method(s), all the above information should be taken into account.

Medical examination/ consultation.

A complete medical history and physical examination should be taken prior to the initiation or reinstitution of COC use, see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, and should be repeated periodically during the use of COCs. In general, an annual examination is recommended. Periodic medical assessment is also of importance because contraindications (e.g. a transient ischaemic attack, etc.) or risk factors (e.g. a family history of venous or arterial thrombosis) may appear for the first time during the use of a COC. The frequency and nature of these assessments should be based on established guidelines and be adapted to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology. Women who have ever been sexually active, including current and past users of hormonal contraceptives, should have scheduled Pap smear examinations in accordance with current public health guidelines.
Women should be advised that Marvelon does not protect against sexually transmitted diseases (STDs), including HIV infections (AIDS) and human papilloma virus (HPV). The woman should be advised that additional barrier contraceptive measures are needed to prevent transmission of STDs, but that even barrier contraceptives may not protect against HPV.

Reduced efficacy.

The efficacy of Marvelon 28 may be reduced in the event of missed active tablets, gastrointestinal disturbances during active tablet taking or concomitant medications that decrease the plasma concentration of etonogestrel, the active metabolite of desogestrel.

Reduced cycle control.

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

Use in hepatic impairment.

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.
See Section 4.3 Contraindications.

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Effects on laboratory tests

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

Hepatic metabolism.

Interactions can occur with medicinal or herbal products that induce microsomal enzymes, specifically cytochrome P450 enzymes (CYP), which can result in increased clearance reducing plasma concentrations of sex hormones and may decrease the effectiveness of combined oral contraceptives, including Marvelon 28. These products include phenytoin, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, rifabutin and possibly also oxycarbazepine, topiramate, felbamate, griseofulvin, some HIV protease inhibitors (e.g. ritonavir) and non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz) and products containing the herbal remedy St John's wort.
Enzyme induction can occur after a few days of treatment. Maximum enzyme induction is generally observed within a few weeks. After drug therapy is discontinued enzyme induction can last for about 28 days.
When coadministered with hormonal contraceptives, many combinations of HIV protease inhibitors (e.g. nelfinavir) and non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine), and/or combinations with hepatitis C virus (HCV) medicinal products (e.g. boceprevir, telaprevir), can increase or decrease plasma concentrations of progestins, including etonogestrel, the active metabolite of desogestrel, or estrogens. The net effect of these changes may be clinically relevant in some cases.
Women receiving any of the above mentioned hepatic enzyme inducing medicinal or herbal products should be advised that the efficacy of Marvelon 28 may be reduced. A barrier contraceptive method should be used in addition to Marvelon 28 during administration of the hepatic enzyme inducing medicinal product, and for 28 days after discontinuation of the hepatic enzyme inducing medicinal product.
If concomitant drug administration runs beyond the end of the active tablets in the current COC pack, the next COC pack should be started right away without the usual placebo tablet interval.
For women on long-term therapy with enzyme inducing medicinal products an alternative method of contraception unaffected by enzyme inducing medicinal products should be considered.
Concomitant administration of strong (e.g. ketoconazole, itraconazole, clarithromycin) or moderate (e.g. fluconazole, diltiazem, erythromycin) CYP3A4 inhibitors may increase the serum concentrations of estrogens or progestins, including etonogestrel, the active metabolite of desogestrel.
Oral contraceptives may affect the metabolism of other drugs. Accordingly, plasma and tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).
During clinical trials with the HCV combination drug regimen ombitasvir/ paritaprevir/ ritonavir with and without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN) were significantly more frequent in women using ethinylestradiol containing medications such as CHCs. Marvelon 28 must be discontinued prior to starting therapy with the combination drug regimen ombitasvir/ paritaprevir/ ritonavir with or without dasabuvir (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use). Marvelon 28 can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.

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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

See Section 5.1 Pharmacodynamic Properties.
(Category B3)
Marvelon is contraindicated during pregnancy. If pregnancy occurs during treatment with Marvelon, further intake should be stopped. However, 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.
In animal studies, maternal administration of high doses of estrogens has produced urogenital malformations in the offspring. The relevance of the animal findings for the clinical use of ethinylestradiol is not certain. However, there was no evidence for teratogenic activity when ethinylestradiol/ desogestrel was given orally to pregnant rats (up to 0.2/0.5 mg/kg) or rabbits (0.04/0.1 mg/kg) during organogenesis. These doses correspond to exposure levels (based on body surface area) 15 to 60 times human exposure at the maximum recommended dose. The combination had no adverse peri/post natal effects in rats at similarly high exposure levels.
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 nursing mother has completely weaned her child. Small amounts of the contraceptive steroids and/or their metabolites may be excreted with the milk but there is no evidence that this adversely affects infant health.

4.7 Effects on Ability to Drive and Use Machines

No effects on ability to drive and use machines have been observed.

4.8 Adverse Effects (Undesirable Effects)

Various adverse reactions have been associated with oral contraceptive use. The most serious reactions associated with the use of oral contraceptives are dealt with (see Section 4.4 Special Warnings and Precautions for Use; Section 4.3 Contraindications).
In the event of aggravation, exacerbation or first appearance of any of these conditions or risk factors, the woman should contact her physician. The physician should then decide on whether its use should be discontinued.
Possibly related undesirable effects that have been reported in clinical trials or observational studies with Marvelon 28 or CHC users in general are listed in Table 2:
The most appropriate MedDRA term (version 11.0) to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well.
A number of undesirable effects have been reported in women using combined oral contraceptives, which are discussed in more detail (see Section 4.4 Special Warnings and Precautions for Use). These include: venous thromboembolic disorders; arterial thromboembolic disorders; hypertension; hormone dependent tumours (e.g. liver tumours, breast cancer); chloasma.

Reporting suspected adverse effects.

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

4.9 Overdose

There have been no reports of serious deleterious effects from overdose. Symptoms that may occur in this case are nausea, vomiting and, in young girls, slight vaginal bleeding. There are no antidotes and further treatment should be symptomatic.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The contraceptive effect of COCs is based on the interaction of various factors. The primary mechanisms are inhibition of ovulation (by suppression of gonadotropins) and changes in the cervical secretion (blocking the entry of sperm into the uterus). Besides protection against pregnancy, COCs have several positive properties which, next to the negative properties (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)), can be useful in deciding on the method of birth control. For the majority of users, the cycle is more regular, the menstruation is often less painful and bleeding is lighter. The latter may result in a decrease in the occurrence of iron deficiency. Apart from this, there is evidence of a reduced risk of endometrial cancer and ovarian cancer. Furthermore, the higher dosed (0.050 mg ethinylestradiol) COCs have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Whether this also applies to lower dosed COCs remains to be confirmed.
Receptor binding studies as well as studies in animals and humans have shown that etonogestrel, the biologically active metabolite of desogestrel, combines high progestational activity with low intrinsic androgenicity. As a result, desogestrel in Marvelon does not counteract the estrogen induced increase in SHBG, resulting in lower serum levels of free testosterone.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Desogestrel.

Absorption.

After oral dosing of Marvelon, desogestrel is rapidly absorbed and converted to 3-keto-desogestrel (etonogestrel). Peak serum concentrations of approximately 2 nanogram/mL are reached after 1.5 h after single ingestion and absolute bioavailability is 62-81%.

Distribution.

Etonogestrel is bound to serum albumin and to sex hormone binding globulin (SHBG). Only 2-4% of the total serum drug concentrations are present as free steroid, 40-70% are specifically bound to SHBG. The ethinylestradiol induced increase in SHBG influences the distribution over the serum proteins, causing an increase of the SHBG bound fraction and a decrease of the albumin bound fraction. The apparent volume of distribution of desogestrel is 1.5 L/kg.

Metabolism.

Etonogestrel is completely metabolised by the known pathways of steroid metabolism. The metabolic clearance rate from serum is about 2 mL/min/kg. No interaction was found when coadministered with ethinylestradiol.

Excretion.

Etonogestrel serum levels decrease in two phases. The terminal disposition phase is characterised by a half-life of approximately 30 hours. Desogestrel and its metabolites are excreted at a urinary to biliary ratio of about 6:4.

Steady-state conditions.

Etonogestrel pharmacokinetics are influenced by SHBG levels, which are increased threefold by ethinylestradiol. Following daily ingestion, drug serum levels increase about two to threefold, reaching steady-state conditions during the second half of the treatment cycle.

Ethinylestradiol.

Absorption.

Orally administered ethinylestradiol is rapidly and almost completely absorbed. Peak serum concentrations of about 80 picogram/mL are reached within 1-2 hours. Absolute bioavailability, as a result of presystemic conjugation and first-pass metabolism, is approximately 60%.

Distribution.

Ethinylestradiol is highly but not specifically bound to serum albumin (approximately 98.5%) and induces an increase in the serum concentrations of SHBG. An apparent volume of distribution of about 5 L/kg was determined.

Metabolism.

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

Excretion.

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

Steady-state conditions.

Steady-state concentrations are reached after 3-4 days when serum drug levels are higher by 30-40% as compared to single dose.

5.3 Preclinical Safety Data

Genotoxicity.

Assays for gene mutations (S. typhimurium) and chromosomal damage (in vivo mouse micronucleus test) performed with desogestrel or the combination did not provide any evidence of a genotoxic potential.

Carcinogenicity.

Carcinogenicity studies for human risk estimation were performed for both components of the preparation, ethinylestradiol and desogestrel, and the combination.
Long-term studies with ethinylestradiol/desogestrel in rats and mice at oral doses up to 0.2/0.5 mg/kg elicited an increased incidence of pituitary and mammary gland tumours. The tumours occurred at exposure levels (based on body surface area) 30 to 60 times human exposure at the maximum recommended dose. The mechanism involved estrogen- and prolactin-sensitive pathways in rodents. These pathways have no direct counterpart in humans, therefore the clinical significance of these findings is uncertain.

6 Pharmaceutical Particulars

6.1 List of Excipients

Active tablets: potato starch, povidone, stearic acid, colloidal anhydrous silica, dl-alpha-tocopherol, lactose monohydrate.
Inert tablets: potato starch, magnesium stearate and lactose monohydrate.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 30°C and protect from light.

6.5 Nature and Contents of Container

Each pack of Marvelon (28 day pack), AUST R42894, consists of push-through strips with:
21 large, white, round, biconvex tablets and 7 small, white, round, biconvex tablets.

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

Marvelon is a combined oral contraceptive (COC) preparation containing the estrogen ethinylestradiol and the progestagen desogestrel as the active substances.

Chemical structure.

Ethinylestradiol.


Chemical Name: 19-nor-17a-pregna-1,3,5,(10)-triene-20-yne-3,17b-diol.
Molecular Formula: C20H24O2. Molecular mass: 296.4.
Ethinylestradiol: a white or slightly yellowish white crystalline powder. Melting Point: 181-185°C. It is practically insoluble in water, freely soluble in ethanol (96%) and in ether, sparingly soluble in chloroform. It dissolves in dilute alkaline solutions.

Desogestrel.


Chemical name: 13β-Ethyl-11-methylene-18, 19-dinor-17α-pregn-4-en-20-yn-17β-ol.
Molecular Formula: C22H30O. Molecular mass: 310.5.
Desogestrel: a crystalline powder, it is a progestogen, semi synthetically produced from naturally occurring plant steroids. It is optically pure, is practically insoluble in water, and slightly soluble in ethanol and ethylacetate.

CAS number.

Ethinylestradiol: 57-63-6.
Desogestrel: 54024-22-5.

7 Medicine Schedule (Poisons Standard)

Schedule 4.

Summary Table of Changes