Consumer medicine information

NuvaRing

Ethinylestradiol; Etonogestrel

BRAND INFORMATION

Brand name

NuvaRing

Active ingredient

Ethinylestradiol; Etonogestrel

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using NuvaRing.

What NuvaRing contains:

Composition in Full

NuvaRing contains:

  • active substances: etonogestrel (11.7 mg) and ethinylestradiol (2.7 mg);
  • other substances: ethylene vinylacetate copolymer (a type of plastic that will not dissolve in the body), magnesium stearate.

Etonogestrel and ethinylestradiol are released from the ring at a rate of 0.120 mg/day and 0.015 mg/day respectively, each for 3 weeks.

1. WHAT NUVARING IS AND WHAT IT IS USED FOR

NuvaRing is a contraceptive vaginal ring used to prevent pregnancy. Each ring contains a small amount of two female sex hormones - etonogestrel and ethinylestradiol. The ring slowly releases these hormones into the blood circulation. Because of the low amount of hormones that is released, NuvaRing is considered a low-dose hormonal contraceptive. Since NuvaRing releases two different types of hormones it is a so-called combined hormonal contraceptive.

NuvaRing works just like a combined contraceptive pill (the Pill) but instead of taking a pill every day, the ring is used for 3 weeks in a row. NuvaRing releases two female sex hormones that prevent the release of an egg cell from the ovaries. If no egg is released you cannot become pregnant. An advantage of NuvaRing is that you do not have to remember to take a pill every day.

NuvaRing is very reliable, but as for all contraceptive methods, protection is never 100%. If NuvaRing is used according to the directions, your chance of getting pregnant is less than 0.7% per year. For comparison purposes, if combined oral contraceptives are used diligently, the chance of getting pregnant is expected to be about 0.1% and if progestogen only pills ("mini pills") are used about 0.3%. Your chance of getting pregnant increases if NuvaRing is not used exactly according to the directions.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE NUVARING

General notes

In this leaflet, several situations are described where you should stop using NuvaRing, or where NuvaRing may be less reliable. In such situations you should not have intercourse or you should take extra non-hormonal contraceptive precautions such as using a male condom or another barrier method. Do not use rhythm or temperature methods. These methods can be unreliable because NuvaRing alters the monthly changes of the body temperature and of the cervical mucous.

NuvaRing, like other hormonal contraceptives, does not protect against HIV infection (AIDS) or any other sexually transmitted disease.

2.1 When you should not use NuvaRing

In some situations you should not use a combined hormonal contraceptive. Tell your doctor if any of the following conditions apply to you. Your doctor may then advise you to use a different (non-hormonal) method of birth control.

Do not use NuvaRing:

  • If you have, or have ever had a disorder affecting the blood vessels. In particular, this applies to conditions relating to thrombosis. Thrombosis is the formation of a blood clot. This may occur in the blood vessels of the legs (deep vein thrombosis), the lungs (pulmonary embolism), the heart (heart attack), the brain (stroke), or other parts of the body;
  • if you have ever had a heart attack, or a stroke, or if you have (or have ever had) a condition that may be a first sign of a heart attack (such as angina pectoris, or severe chest pain) or stroke (such as a transient ischaemic attack [a TIA - a slight temporary stroke]);
  • if you have a serious risk factor, or several risk factors for developing a blood clot - see also in section 2.2 'Blood clots (Thrombosis)';
  • if you have a disorder affecting the blood clotting, for instance protein C deficiency;
  • if you have major surgery (e.g., an operation) and your ability to move around is limited for a long period of time (see in section 2.2 'Blood clots (Thrombosis)').
  • if you have (had) a type of migraine called 'migraine with aura' Ask your doctor if you are unsure;
  • if you have diabetes with damaged blood vessels;
  • if you have (had) an inflammation of the pancreas (pancreatitis) associated with high levels of fat in your blood;
  • If you have jaundice (yellowing of the skin) or if you have or ever had severe liver disease and your liver is not yet working normally;
  • if you have any unexplained vaginal bleeding;
  • if you are allergic to ethinylestradiol or etonogestrel, or any of the other ingredients of NuvaRing;
  • If you have or have had cancer of the breast or the genital organs;
  • If you have or have had a benign or malignant tumour in the liver;
  • If you are pregnant or think you might be pregnant.

If any of these conditions appear for the first time while using NuvaRing, remove the ring immediately and contact your doctor. In the meantime, use non-hormonal contraceptive measures.

Do not use NuvaRing if you have hepatitis C and are taking the combination drug regimen ombitasvir/paritaprevir/ritonavir with or without dasabuvir (see in section 2.2 'Other medicines and NuvaRing').

For possible signs of a blood clot see in section 2.2 'Blood Clots (Thrombosis)'.

2.2 Warnings and precautions

In some situations you need to take special care while using a combined hormonal contraceptive.

Talk to your doctor before using NuvaRing if any of the following conditions apply to you. Also if the condition develops or gets worse while you are using NuvaRing you must tell your doctor.

  • if you breast-feed a baby. The use of a hormonal contraceptive containing an estrogen is generally not recommended until the nursing mother has completely weaned her child;
  • if you have diabetes;
  • if you are overweight;
  • if you have high blood pressure;
  • if you have a heart valve disorder or a certain heart rhythm disorder;
  • if you have an inflammation of your veins (superficial phlebitis);
  • if you have varicose veins;
  • if anyone in your immediate family has had a thrombosis, a heart attack or a stroke;
  • if you suffer from migraine;
  • if a close relative has or has ever had breast cancer;
  • if you have epilepsy (see in section 2.2 'Other Medicines and NuvaRing');
  • if you or someone in your immediate family has or had high blood levels of fatty substances (cholesterol or triglycerides);
  • if you have liver disease (for instance jaundice) or gallbladder disease (for instance gallstones);
  • if you have Crohn's disease or ulcerative colitis (chronic inflammatory bowel disease);
  • if you have SLE (systemic lupus erythematosus; a disease affecting your natural defence system);
  • if you have HUS (haemolytic uraemic syndrome; a disorder of blood clotting causing failure of the kidneys);
  • if you have sickle cell anaemia (an inherited disease of the red blood cells);
  • if you have elevated levels of fat in the blood (hypertriglyceridemia) or a positive family history for this condition. Hypertriglyceridemia has been associated with an increased risk of developing pancreatitis (inflammation of the pancreas) in women using hormonal contraceptives.
  • if you have an operation, or if your ability to move around is limited for a long time (see in section 2.2 'Blood Clots (Thrombosis)';
  • if you have a condition that occurred for the first time or worsened during pregnancy or previous use of sex hormones, e.g. hearing loss, porphyria (a disease of the blood), herpes gestationis [skin rash with vesicles during pregnancy], Sydenham's chorea [a disease of the nerves in which sudden movements of the body occur]); hereditary angioedema [you should see your doctor immediately if you experience symptoms of angioedema such as swollen face, tongue and/or throat and/or difficulty swallowing or hives, together with difficulty breathing].
  • if you have (or have ever had) chloasma [yellowish-brown pigment patches, so called 'pregnancy patches', particularly on the face]; if so, avoid too much exposure to the sun or ultraviolet light;
  • if you have a medical condition that makes it difficult to use NuvaRing - e.g. if you are constipated, have a prolapse of the uterine cervix or have pain during intercourse;
  • 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 NuvaRing (see in section 2.2 'Blood clots (Thrombosis)');
  • if you have (or have ever had) an allergic reaction while using NuvaRing, including swelling of the face, lips, tongue, and/or throat causing difficulty in breathing or swallowing (angioedema and/or anaphylaxis);
  • if you have a history of toxic shock syndrome (TSS).

Even if none of the conditions listed above applies to you, it is sensible to see your doctor regularly for a medical check-up, e.g. once every year.

Blood clots (Thrombosis)

Blood clots in a vein

A blood clot in a vein (known as a 'venous thrombosis') can block the vein. This can happen in veins in the leg, the lung (a lung embolus), or other organs.

Using combined hormonal contraceptives, including NuvaRing, increases a woman's risk of developing a venous thrombosis compared with a woman not using any combined hormonal contraceptive. The risk of developing a blood clot in a vein is highest during the first year of using a combined hormonal contraceptive for the first time. The risk is also higher if you restart using a combined hormonal contraceptive (the same product or a different product) after a break of 4 weeks or more. The risk is not as high as the risk of developing a blood clot during pregnancy. The risk of getting a blood clot with NuvaRing is similar to the risk contraceptive pills.

If you use a combined hormonal contraceptive your risk of venous thrombosis increases further:

  • the older you are;
  • if one of your close relatives has had a blood clot in the leg, lung or other organ at a young age;
  • if you are overweight;
  • if you must have an operation, or if your ability to move around is limited for a long period of time because of any injury or illness, or you have your leg in a plaster cast.
If this applies to you, it is important to tell your doctor that you are using NuvaRing, as the treatment may have to be stopped. Your doctor may tell you to stop using your hormonal contraception several weeks before surgery or while you are less mobile. Your doctor will also tell you when you can start using NuvaRing again after you are able to move around. See also section 2.1 'When should you not use NuvaRing'.
  • if you gave birth less than a few weeks ago.

Blood clots in an artery

A blood clot in an artery can cause serious problems. For example, a blood clot in an artery in the heart causes a heart attack, or in the brain causes a stroke. Extremely rarely blood clots can occur in the liver, gut, kidney or eye.

The use of a combined hormonal contraceptive has also been connected with an increased risk of clots in the arteries. This risk increases further:

  • the older you are;
  • if you smoke.
When using a combined hormonal contraceptive like NuvaRing you are strongly advised to stop smoking, especially if you are older than about 35 years;
  • if you are overweight;
  • if you have high blood pressure. If you develop high blood pressure while using NuvaRing, you may be told to stop using it;
  • if a close relative has had a heart attack or stroke at a young age;
  • if you have a high level of fat in your blood (cholesterol or triglycerides);
  • if you have diabetes;
  • if you get migraine;
  • if you have a problem with your heart (valve disorder , disturbance of the rhythm).

Symptoms of blood clots

Remove NuvaRing and contact your doctor immediately if you notice possible signs of a blood clot, such as:

  • unusual pain and/or swelling in one of your legs;
  • severe pain in the chest which may reach the left arm;
  • sudden breathlessness;
  • sudden cough without an obvious cause;
  • any unusual, severe or long-lasting headache or worsening of migraine;
  • partial or complete blindness or double vision;
  • difficulty in speaking or inability to speak;
  • giddiness or fainting;
  • weakness, strange feeling, or numbness in any part of your body.

Following a blood clot recovery is not always complete. Very occasionally serious permanent disabilities may occur or the blood clot may even be fatal.

Cancer

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 contraceptives, such as NuvaRing.

In studies with the combined pill, breast cancer has been found slightly more often in women using combined pills, but it is not known whether this is caused by the treatment. For example, it may be that tumours are found more in women on combined pills because they are examined by the doctor more often. The increased occurrence of breast cancer becomes gradually less after stopping the combined pill, so that 10 years after stopping the extra risk has gone.

In the additional study that included both oral and non-oral hormonal contraceptives, such as NuvaRing, 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 had 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 important to regularly check your breasts and you should contact your doctor if you feel any lump. You should also tell your doctor if a close relative has, or ever had breast cancer (see section 2.2 Warnings and precautions).

In rare cases benign liver tumours and in even fewer cases, malignant liver tumours have been reported in pill users. Contact your doctor if you have unusual severe abdominal pain.

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.

Other medicines and NuvaRing

Always tell the doctor who prescribes NuvaRing which medicines or herbal products you are already using, including medicines obtained without a prescription. Also tell any other doctor or dentist who prescribes another medicine (or the dispensing pharmacist) that you use NuvaRing.

Some medicines may cause particular problems when you are using combined hormonal contraceptives, such as NuvaRing.

  • There are medicines that can make NuvaRing less effective in preventing pregnancy, or can cause unexpected bleeding. These include medicines used to treat:
    - epilepsy (e.g. primidone, phenytoin, phenobarbital, carbamazepine, oxcarbamazepine, topiramate, felbamate);
    - tuberculosis (e.g. rifampicin);
    - HIV infection (e.g. ritonavir, nelfinavir, nevirapine, efavirenz);
    - Hepatitis C virus infection (e.g. boceprevir, telaprevir)
    - other infectious diseases (e.g. griseofulvin).
    - high blood pressure in the blood vessels of the lungs (bosentan).
  • The herbal product St. John's wort may also stop NuvaRing from working properly. If you want to use herbal products containing St. John's wort while you are already using NuvaRing you should consult your doctor first.
  • If you are taking medicines or herbal products that might make NuvaRing less effective, a barrier contraceptive method should also be used. Since the effect of another medicine on NuvaRing may last up to 28 days after stopping the medicine, it is necessary to use the additional barrier contraceptive method for that long. Note: Do not use NuvaRing with a diaphragm, cervical cap, or a female condom.
  • NuvaRing may also interfere with the working of other medicines - such as ciclosporin and the anti-epileptic lamotrigine.
  • Do not use NuvaRing 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). NuvaRing can be restarted approximately 2 weeks after completion of treatment with the combination drug regimen. See section 2.1 'When you should not use NuvaRing'.

You can use tampons while using NuvaRing. Insert NuvaRing before inserting a tampon. You should be careful when removing a tampon to be sure that the ring is not accidentally pulled out. If the ring does come out, simply rinse the ring in cool to lukewarm water (do not use hot water) and immediately reinsert it.

Ring breakage has occurred when also using a vaginal product such as a lubricant or treatment for infection (see section 3.4 'What to do if...Your ring breaks').

Using spermicides or vaginal yeast products will not reduce the contraceptive efficacy of NuvaRing.

Laboratory tests

If you are having any blood or urinary test, tell your health care professional that you are using NuvaRing as it may affect the results of some tests.

Pregnancy

NuvaRing must not be used by women, who are pregnant, or who think they may be pregnant.

If you get pregnant while using NuvaRing you should remove the ring and contact your doctor.

If you want to stop NuvaRing because you want to get pregnant, see section 3.4 'What to do if…You want to stop using NuvaRing'.

Breastfeeding

NuvaRing is not usually recommended for use during breast-feeding. If you wish to use NuvaRing while breastfeeding, please seek the advice of your doctor.

Driving and using machines

NuvaRing is unlikely to affect your ability to drive or use machines.

More about hormonal contraceptives

Combined hormonal contraceptives, like NuvaRing, may also have non-contraceptive health benefits. 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. Your period may be more confined to the ring-free period when you use NuvaRing.

Furthermore, the following serious disorders have been reported to occur less frequently in users of hormonal contraceptives with 50 micrograms of ethinylestradiol ('high-dosed' pills) than in non-users. This may also be the case for NuvaRing but this has not been confirmed.

  • Cancer of the endometrium (the lining of the womb)
  • Cancer of the ovaries
  • Benign breast disease
  • Ovarian cysts
  • Pelvic infections (pelvic inflammatory disease or PID)
  • Ectopic pregnancy (pregnancy in which the embryo implants outside of the uterus)

3. HOW TO USE NUVARING?

You can insert and remove NuvaRing yourself. Your doctor will tell you when to start using NuvaRing for the first time. The vaginal ring must be inserted on the correct day in your monthly cycle (see section 3.3 'When to start with the first ring') and left in place for 3 consecutive weeks. Regularly check that NuvaRing is still in your vagina (for example, before and after intercourse) to ensure that you are protected from pregnancy. After the third week, you take NuvaRing out and have a one week break. You will usually have your monthly period during this ring-free interval.

While using NuvaRing, you should not use certain female barrier contraceptive methods such as a vaginal diaphragm, cervical cap, or female condom as your back-up method of birth control because NuvaRing may interfere with the correct placement and position of a diaphragm, cervical cap, or female condom.

3.1 How to insert and remove NuvaRing

  1. Before inserting the ring, check it is not out of date (see section 6 'How to store NuvaRing').
  2. Wash your hands before inserting or removing the ring.
  3. See Figures 1 - 5 below for details

Figure 1: Take NuvaRing out of the sachet.

Figure 2: Hold the ring between your thumb and index finger, press the opposite sites together. Compress the ring.

Figure 3: Choose a comfortable position to insert the ring, like standing with one leg up, squatting, or lying down.

Figure 4a: Insert the ring into the vagina with one hand, if necessary the labia may be spread with the other.

Figure 4b: Push the ring into the vagina until the ring feels comfortable. When NuvaRing is in place you should not feel anything. If you feel uncomfortable, gently change the position of the NuvaRing (e.g, push the ring a bit further into the vagina) until it is comfortable. The exact position of the ring inside the vagina is not important.

Figure 4c: Leave the ring in place for 3 weeks.

Figure 5: After 3 weeks, remove NuvaRing from the vagina. NuvaRing can be removed by hooking the index finger under the ring or by grasping the ring between the index and middle finger and pulling it out.

  1. Dispose of the used ring with the normal household waste, preferably inside the resealable sachet. Do not flush NuvaRing down the toilet.

3.2 Three weeks in, one week out

  1. Starting with the day you put it in, the vaginal ring must be left in place without interruption for 3 weeks.
  2. After 3 weeks you remove the ring on the same day of the week and at approximately the same time as it was put in. For example, if you put NuvaRing in on a Wednesday at about 22.00 h, you should remove the ring 3 weeks later, on Wednesday, at about 22.00 h.
  3. After you have removed the ring, you do not use a ring for 1 week. During this week a vaginal bleed should occur. Usually this starts 2-3 days after removal of NuvaRing.
  4. Start a new ring exactly after the 1 week interval (again on the same day of the week and approximately the same time), even if you have not stopped bleeding. If the new ring is inserted more than 3 hours too late, the protection from pregnancy may be reduced. Follow the instructions in section 3.4 'What to do if... You have forgotten to insert a new ring after the ring-free interval'.

If you use NuvaRing as described above, your vaginal bleed will take place every month on roughly the same days.

3.3 When to start with the first ring

  • You have not used a hormonal contraceptive during the last month.
Insert the first NuvaRing on the first day of your natural cycle (i.e. the first day of your menstrual period). NuvaRing starts working straight away. You don't need to take any other contraceptive precautions.
You can also start NuvaRing between day 2 and day 5 of your cycle, but if you have sexual intercourse during the first 7 days of NuvaRing use make sure that you also use an additional contraceptive method (such as a male condom). You only have to follow this advice when you use NuvaRing for the first time.
  • You have used a combined Pill during the last month.
Start using NuvaRing at the latest the day following the tablet-free period of your present Pill. If your Pill pack also contains inactive tablets, start NuvaRing at the latest on the day after the last inactive tablet. If you are not sure which tablet this is, ask your doctor or pharmacist. Never extend the hormone-free interval of your current Pill pack beyond its recommended length.
If you have used the Pill consistently and correctly and if you are sure that you are not pregnant, you can also stop taking the Pill on any day of your current Pill pack and start using NuvaRing immediately.
  • You have used a transdermal patch during the last month.
Start using NuvaRing at the latest the day following your usual patch-free break. Never extend the patch-free break beyond its recommended length.
If you have used the patch consistently and correctly and if you are sure that you are not pregnant, you can also stop using the patch on any day and start using NuvaRing immediately.
  • You have used a minipill (progestagen-only pill) during the last month.
You can stop taking the minipill any day and start NuvaRing the next day, at the same time you would have normally taken your pill. But make sure you also use an additional contraceptive method (such as a male condom) for the first 7 days of ring use.
  • You have used an injectable or an implant or a progestagen-releasing intrauterine device (IUD) during the last month.
Start using NuvaRing when your next injection is due or on the day that your implant or your progestagen-releasing IUD is removed. But make sure you also use an additional contraceptive method (such as a male condom) for the first 7 days of ring use.
  • 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 using NuvaRing. Sometimes it is possible to start sooner.Your doctor will advise you. If you are breast-feeding and want to use NuvaRing, you should discuss this first with your doctor.
  • After a miscarriage or an abortion.
Your doctor will advise you.
  • When you have had irregular cycles or no bleeding
Your doctor will advise you.

3.4 What to do if…

You ring is accidentally expelled from the vagina

NuvaRing may accidentally be expelled from the vagina for example, if it has not been inserted properly, while removing a tampon, during sexual intercourse, during constipation, or if you have a prolapse of the womb. Therefore, it is a good habit to regularly check whether the ring is still in your vagina (for example, before and after intercourse).

Your ring has temporarily been out of the vagina

NuvaRing might still protect you from getting pregnant depending on how long it has been out of your vagina.

If the ring has been out of your vagina for:

  • Less than 3 hours,
    it will still protect you from pregnancy. You should rinse the ring with cold to lukewarm water (do not use hot water) and put the ring back in as soon as possible but only if the ring has been out of the vagina for less than 3 hours.
  • More than 3 hours during the 1st and 2nd week,
    it may not protect you from pregnancy. You should rinse the ring with cold to lukewarm water (do not use hot water) and put the ring back in the vagina as soon as you remember, and leave the ring in place without interruption for at least 7 days. Use a male condom if you have sexual intercourse during these 7 days. If you are in your 1st week, and you had sexual intercourse during the past 7 days, there is a possibility you may be pregnant. In that case contact your doctor.
  • More than 3 hours in the 3rd week,
    it may not protect you from pregnancy. You should discard that ring and choose between one of the following two options:
  1. Insert a new ring immediately:
This will start the next 3-week use period. You may not have your period, but breakthrough bleeding and spotting may occur.
  1. Do not insert the ring again.
Have your period first and insert a new ring no later than 7 days from the time the previous ring was removed or fell out. You should only choose this option if you have used NuvaRing continuously during the previous 7 days.
  • An unknown amount of time, you may not be protected from pregnancy. Perform a pregnancy test and consult your doctor prior to inserting a new ring.

Your ring breaks

Very rarely NuvaRing may break. A broken ring is unlikely to cause an overdose because the ring will not release a higher amount of contraceptive hormones. Vaginal injury associated with ring breakage has been reported.

If NuvaRing breaks, expulsion of the ring is likely to occur (see section 3.4 'What to do if…Your ring has temporarily been out of the vagina'). Therefore, if you notice that your NuvaRing has broken, discard that ring and replace it with a new ring as soon as possible.

You have inserted more than one ring/Overdose

There have been no reports of serious harmful effects due to an overdose of the hormones in NuvaRing. If you have accidentally inserted more than one ring, you may feel sick (nausea), or have vomiting or vaginal bleeding. Remove excess rings and contact your doctor if these symptoms persist.

You have forgotten to insert a new ring after the ring-free interval

If your ring-free interval was longer than 7 days, put a new ring in as soon as you remember. Use extra contraceptive precautions (such as a male condom) if you have sexual intercourse during the next 7 days. If you had sexual intercourse in the ring-free interval, there is a possibility you may be pregnant. In that case contact your doctor immediately. The longer the ring-free interval, the higher the risk that you have become pregnant.

You have forgotten to remove the ring

  • If your ring has been left in place for between 3 and 4 weeks, it will still protect you from pregnancy. Have your regular ring-free interval of one week and subsequently insert a new ring.
  • If your ring has been left in place for more than 4 weeks there is a possibility of becoming pregnant. Contact your doctor before you start with a new ring.

You have missed a menstrual period

  • You have followed the instructions for NuvaRing
If you have missed a menstrual period but you followed the instructions for NuvaRing, and have not used other medicines it is very unlikely that you are pregnant. Continue to use NuvaRing as usual. If you miss your menstrual period twice in a row, however, you may be pregnant. Tell your doctor immediately. Do not start the next NuvaRing until your doctor has checked you are not pregnant.
  • If you have not followed the instructions for NuvaRing
If you have missed a menstrual period and you did not follow the instructions, and you do not have your expected period in the first normal ring-free interval, you may be pregnant. Contact your doctor before you start with a new NuvaRing.

You have unexpected bleeding

While using NuvaRing, some women have unexpected vaginal bleeding between menstrual periods. You may need to use sanitary protection. In any case, leave the ring in the vagina and continue to use the ring as normal. If the irregular bleeding continues becomes heavy or starts again, tell your doctor.

You want to change the first day of your menstrual period

If you follow the instructions for NuvaRing, your menstrual period (withdrawal bleed) will begin in the ring-free interval. If you want to change the day it starts, you can make the ring-free interval shorter (but never longer!). For example, if your ring-free interval begins on a Friday, you can change this to a Tuesday (3 days earlier). Simply insert your next ring 3 days earlier than usual.

If you make your ring-free interval very short (e.g. 3 days or less), you may not have your usual bleeding. You may have spotting (drops or flecks of blood) or breakthrough bleeding while using the next ring.

You want to delay your menstrual period

Delay of your menstrual period (withdrawal bleed) is possible by inserting a new ring immediately after removing the current ring, with no ring-free interval between rings.You can leave the new ring inserted for up to a maximum of 3 weeks. You may experience spotting (drops or flecks of blood) or breakthrough bleeding while using this new ring. When you want your period to begin, just remove the ring. Have your regular ring-free interval of one week and subsequently insert a new ring.

You want to stop using NuvaRing

You can stop using NuvaRing any time you want.

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

If you stop using NuvaRing because you want to get pregnant, you should wait until you have had a natural period before trying to conceive. This helps you calculate when the baby will be due.

4. WHEN SHOULD YOU CONTACT YOUR DOCTOR

Regular check-ups

When you are using NuvaRing, your doctor may tell you to return for regular check-ups. In general, you should have a check-up every 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 section 2.1 'When you should not use NuvaRing' and section 2.2 'Warnings and precautions'.
  • Your ability to move around is limited for a long period of time or you are to have surgery. Tell your doctor at least four weeks in advance (see also section 2.2 'Blood clots (Thrombosis)').
  • You feel a lump in your breast. This symptom may indicate breast cancer (see also section 2.2 'Cancer').
  • You experience an allergic reaction, including hives, swelling of the face, lips, tongue, and/or throat causing difficulty in breathing or swallowing (angioedema and/or anaphylaxis).
  • You have severe pain in your abdomen.
  • You have unusual, heavy vaginal bleeding. This symptom may indicate cervical cancer.
  • You are going to use other medications (see also in section 2.2 'Other medicines and NuvaRing').
  • The ring was out of the vagina for longer than 3 hours in the first week of use and you had intercourse in the 7 days before.
  • You have forgotten to insert a new ring after the ring-free interval of 7 days.
  • You left NuvaRing in place for more than 4 weeks. Do not start the next ring until your doctor tells you.
  • You missed your period twice in a row or suspect you are pregnant. Do not start the next ring until your doctor tells you.
  • You have an urgent frequent burning, and/or painful urination, and cannot locate the ring in the vagina. These symptoms may indicate accidental placement of NuvaRing into the urinary bladder.
  • If you locate the ring in your vagina, but are unable to remove it.

Remove NuvaRing and contact your doctor immediately if you notice possible signs of a blood clot. The symptoms are described in section 2.2 'Blood clots (Thrombosis) '.

5. POSSIBLE SIDE EFFECTS

Like all medicines, NuvaRing can cause side effects, although not everybody gets them.

Serious reactions seen with NuvaRing, as well as the related symptoms, are described in sections 2.2 'Blood clots (Thrombosis) ' and 'Cancer'. Please read these sections for additional information and consult your doctor if you suffer from any of these conditions or symptoms.

Users of NuvaRing have reported the following Common (affecting more than 1 in 100, but less than 1 in 10 women);and Uncommon (affecting more than 1 in 1000, but less than 1 in 100 women) side effects:

  • abdominal pain, feeling sick (nausea)
  • yeast infection of the vagina (such as 'thrush'); discomfort in the vagina due to the ring; genital itching; secretion from the vagina
  • headache or migraine; depressive moods; lower sex drive
  • breast pain; painful menstrual periods
  • acne
  • weight gain
  • the ring falling out
  • disturbed vision; dizziness
  • swollen abdomen; vomiting, diarrhoea or constipation
  • feeling tired, unwell or irritable; mood changes
  • extra fluid in the body (oedema)
  • bladder or urinary tract infection
  • difficulty or pain when passing urine; strong desire or need to pass urine; passing urine more often
  • problems during intercourse, including pain, bleeding or partner feeling the ring
  • increased blood pressure
  • increased appetite
  • back pain; muscle spasms; pain on legs or arms
  • less sensitive skin
  • sore or larger breasts; fibrocystic breast disease (cysts in the breasts which may become swollen or painful)
  • inflammation of the cervix; cervical polyps (growth in the cervix); rolling outward of the margin of the cervix (ectropion)
  • genital secretion; changes to menstrual periods (e.g. periods can be heavy, long, irregular or stop altogether); pelvic discomfort; premenstrual syndrome; spasm of the uterus
  • vaginal infection; burning feeling, smell, pain, discomfort or dryness in the vagina or vulva
  • hair loss, eczema, itching, rash or hot flushes
  • ring breakage.

Rare side effects

(affecting more than 1 in 10 000, but less than 1 in 1000 women)

  • blood clot in a vein
  • blood clot in an artery.

The following rare side effects have been reported in users of NuvaRing, but the frequency cannot be estimated from the available data: allergic reactions (hypersensitivity), including hives, swelling of the face, lips, tongue, and/or throat causing difficulty in breathing or swallowing (angioedema and/or anaphylaxis); vaginal injury associated with ring breakage; breast discharge; and penis discomfort of the partner (such as irritation, rash, itching).

If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet.

6. PHARMACEUTICAL PARTICULARS OF NUVARING

Storage Instructions

Store your NuvaRing in the original sachet below 30°C.

Protect from light and freezing.

Do not use a NuvaRing if it was dispensed to you more than 4 months ago. The dispensing date is shown on the carton and sachet.

Do not use NuvaRing after the expiry date which is shown on the carton and sachet.

Do not use NuvaRing if you notice a colour change in the ring or any visible signs of deterioration.

Keep NuvaRing out of the reach and sight of children. If you discover that a child has been exposed to the hormones from NuvaRing, ask your doctor for advice.

What NuvaRing looks like and contents of the pack

NuvaRing is flexible, transparent, colourless to almost colourless and 54 mm wide.

Each ring is packed in a resealable sachet that is made of aluminium foil. The sachet is packed in a cardboard box together with this package leaflet. Each box contains 1 or 3 rings.

IF YOU HAVE ANY FURTHER QUESTIONS, PLEASE CONSULT YOUR DOCTOR OR PHARMACIST.

Sponsors

Merck Sharp & Dohme (Australia) Pty Limited
Level 1, Building A, 26 Talavera Road,
Macquarie Park NSW 2113
Australia

Date of Preparation

March 2020

AUST R 96229

S-CCPPI-MK8342A-RNG-112018

Published by MIMS May 2020

BRAND INFORMATION

Brand name

NuvaRing

Active ingredient

Ethinylestradiol; Etonogestrel

Schedule

S4

 

1 Name of Medicine

Etonogestrel and ethinylestradiol.

6.7 Physicochemical Properties

Chemical structure.

Ethinylestradiol.


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

Etonogestrel.


Chemical name: (17α)-13-ethyl-17- hydroxy-11-methylene-18,19 dinorpregn-4-en-20-yn-3-one.
Molecular formula: C22H28O2.
Molecular mass: 324.44.

CAS number.

Ethinylestradiol.

57-63-6.

Etonogestrel.

54048-10-1.

2 Qualitative and Quantitative Composition

Controlled-release contraceptive ring for vaginal use. NuvaRing releases etonogestrel and ethinylestradiol at an average amount of 120 microgram and 15 microgram, respectively, per 24 hours, over a period of 3 weeks. The ring contains 11.7 mg etonogestrel and 2.7 mg ethinylestradiol.
For full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Vaginal drug delivery system.
NuvaRing is a flexible, transparent, colourless to almost colourless ring, with an outer diameter of 54 mm and a cross-sectional diameter of 4 mm.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

NuvaRing contains etonogestrel and ethinylestradiol. Etonogestrel is the biologically active metabolite of desogestrel, a progestogen widely used in oral contraceptives. It binds with high affinity to progesterone receptors in the target organs. Ethinylestradiol is an estrogen also widely used in contraceptive products. The contraceptive effect of NuvaRing is achieved primarily by inhibition of ovulation.

Clinical trials.

Six efficacy and safety studies were performed in healthy, fertile and sexually active women aged 18-40 years. The endpoints included contraceptive efficacy, cycle control parameters, safety, laboratory variables and acceptability parameters. In these studies a total number of 2501 subjects using NuvaRing and 126 subjects using a comparator combined oral contraceptive (30 microgram ethinylestradiol/150 microgram levonorgestrel) were studied. Total NuvaRing exposure was 24,519.9 treatment cycles (1879.34 women-years). See Table 3.

Contraceptive efficacy.

The two large efficacy and safety trials had the objective to collect at least 10,000 cycles of treatment each. In these two trials, a total of 21 in-treatment pregnancies were reported: 11 subjects did not comply with the protocol in the cycle of conception or the preceding cycle. The in-treatment pregnancies of the remaining 10 subjects were considered to be Per Protocol pregnancies representing method-failure during "perfect use". This results in a Pearl Index of 0.765 (95% confidence interval 0.367 - 1.407). The Pearl Index was higher in the US study (068003) than in the European study (34219). Compliance with the recommended ring/ring-free regimen was lower, and the occurrence of temporary removals higher, in the US study than the European study, which may have contributed to the difference in Pearl Index. The difference in compliance between the US and Europe has previously been reported in literature for other contraceptives. These findings indicate that the instructions for use as described in the Product Information should be followed. Contraceptive efficacy is satisfactory and the data demonstrate that NuvaRing is an efficacious contraceptive product when used in accordance with the use instructions. There are insufficient evaluated data to make direct comparisons concerning the efficacy of NuvaRing relative to other methods. These two studies permitted the occasional use of condoms to prevent the transmission of sexually transmitted diseases. See Table 4.

Bleeding pattern.

Intended bleeding was defined as bleeding/spotting which occurs only during the ring-free period. The incidence of intended bleeding over cycles 1-12 ranged from 59.9% to 68.5% in the two large efficacy and safety studies. The incidence of other bleeding patterns was low and consistent over up to 13 cycles of NuvaRing use: breakthrough bleeding/spotting (5.1%-7.9%), absence of withdrawal bleeding (1.5-2.9%), early withdrawal bleeding (5.6-8.8%), withdrawal bleeding/spotting continuing beyond the ring-free period (mainly spotting days: 15.7-20.5%). The discontinuation rate due to bleeding irregularity was low (0.8%).
The bleeding characteristics of NuvaRing were compared to those of a 30 microgram EE/150 microgram LNG containing COC during 13 cycles in more than 1000 women. The results of this study show that the occurrence of breakthrough bleeding or spotting varied over the Cycles 2-13 from 2.0% to 6.4% in the NuvaRing group and from 3.5% to 12.6% in the LNG/EE OC group. Superiority for the NuvaRing group over the LNG/EE OC group was demonstrated, because a statistically significantly lower incidence was observed in cycles 2 and 9 of the 13 cycles. Cycle 1 was excluded from the analysis because the starting regimens were not comparable. Furthermore, the incidence of intended bleeding patterns was statistically significantly better in the NuvaRing group for each of the cycles 1-12; these occurred in 58.8% to 72.8% of the subjects in the NuvaRing group and in 43.3% to 57.9% of the subjects in the LNG/EE OC group.

Ovulation suppression and return.

In supportive studies the ovulation-inhibiting effect of NuvaRing appeared to be similar to that of a comparator combined oral contraceptive (30 microgram ethinylestradiol/150 microgram desogestrel). Even though NuvaRing was inserted on day 5 and the COC was started on day 1 the study data support inhibition of ovulation in the first cycle with both products. Return of ovulation was assessed by ultrasound measurements and hormone assessments. Return of ovulation is likely to occur after 12 days after ring removal (median 19 days). Return of ovulation implies restoration of fertility. This conclusion is indirectly supported by the return of menses in 90% of women by the 4th week after last NuvaRing removal and the occurrence of 27 post-treatment pregnancies after last ring removal in the two large efficacy and safety trials.

Effects on bone mineral density.

The effects of NuvaRing (n=76) on bone mineral density (BMD) were studied in comparison to a non-hormonal intrauterine device (IUD) (n=31) in women over a period of two years. The observed differences were not considered to be clinically relevant.

Other considerations.

Acceptability of NuvaRing was assessed in the two large efficacy and safety studies. The large majority of users felt that the ring could easily be inserted (97%) or removed (98%). In total, 35.4% of the subjects in these trials discontinued: 15.1% because of an adverse event/serious adverse event, 0.8% because of bleeding irregularity, 0.9% to become pregnant and 18.5% because of other reasons (mainly loss to follow-up, 2 women for unspecified reasons and 3 for "nonacceptance of NuvaRing concept"). Male discomfort during sexual intercourse was reported by 2% of clinical trial subjects.
Combined oral contraceptives (COCs) have, in addition to protection against pregnancy, several positive properties which, together with the negative properties (see Section 4.4 Special Warnings and Precautions for Use), can be useful in deciding on the method of birth control. The cycle is more regular and the menstruation is often less painful and bleeding is lighter. Apart from this, there is evidence of a reduced risk of endometrial cancer and ovarian cancer but it is not known whether these apply to NuvaRing. Furthermore, the higher-dosed COCs (50 microgram ethinylestradiol), have been shown to reduce the incidence of ovarian cysts, pelvic inflammatory disease, benign breast disease and ectopic pregnancy. Confirmation is required as to whether these benefits also apply to lower dosed COCs or NuvaRing.

5.2 Pharmacokinetic Properties

NuvaRing releases relatively low doses of hormones continuously, which are rapidly absorbed by the vaginal mucosa. With the vaginal route of administration, lower doses are administered to achieve effective plasma concentrations than with many current combined oral contraceptives since a "hepatic first-pass" effect is avoided. The maximum serum values for etonogestrel and ethinylestradiol are approximately 40% and 30%, respectively, as compared to those of a comparator combined oral contraceptive (30 microgram ethinylestradiol/150 microgram desogestrel) and occur only once per cycle. The mean etonogestrel serum levels are in the same order of magnitude as those obtained for this comparator, whereas the ethinylestradiol serum levels are approximately 50%.
NuvaRing is used continuously for three weeks. Daily variations in hormonal levels that occur during oral contraceptive use are not a feature with NuvaRing. Vaginal administration avoids daily peak concentrations. NuvaRing is not subject to factors that may affect oral contraceptive tablets' efficacy such as vomiting, food interactions and diarrhoea.

Etonogestrel.

Absorption.

Etonogestrel released by NuvaRing is rapidly absorbed by the vaginal mucosa. Maximum serum concentrations of etonogestrel of approximately 1700 picogram/mL are reached at about 1 week after insertion. Serum concentrations show small fluctuations and slowly decrease to approximately 1400 picogram/mL after 3 weeks of use. Absolute bioavailability is approximately 100%, compared to approximately 80% for the DSG/EE COC.

Distribution.

Etonogestrel is bound to serum albumin and to sex hormone binding globulin (SHBG). The apparent volume of distribution of etonogestrel is 2.3 L/kg.

Metabolism.

Etonogestrel is metabolised by the known pathways of steroid metabolism. The apparent clearance from serum is about 3.5 L/h. No direct interaction was found with the co-administered ethinylestradiol.

Excretion.

Etonogestrel serum levels decrease in two phases. The terminal elimination phase is characterised by a half-life of approximately 29 hours. Etonogestrel and its metabolites are excreted at a urinary to biliary ratio of about 1.7:1. The half-life of metabolite excretion is about 6 days.

Ethinylestradiol.

Absorption.

Ethinylestradiol released by NuvaRing is rapidly absorbed by the vaginal mucosa. Maximum serum concentrations of about 35 picogram/mL are reached 3 days after insertion and decrease to 18 picogram/mL after 3 weeks of use. Absolute bioavailability is approximately 56%, which is comparable with oral administration of ethinylestradiol.

Distribution.

Ethinylestradiol is highly but non-specifically bound to serum albumin. An apparent volume of distribution of about 15 L/kg was determined.

Metabolism.

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 sulphate and glucuronides conjugates. The apparent clearance is about 35 L/h.

Excretion.

Ethinylestradiol serum levels decrease in two phases. The terminal elimination phase is characterised by a large individual variation in half-life, resulting in a median half-life of approximately 34 hours. Unchanged ethinylestradiol is not excreted; ethinylestradiol metabolites are excreted at a urinary to biliary ratio of 1.3:1. The half-life of metabolite excretion is about 1.5 days.

5.3 Preclinical Safety Data

Genotoxicity.

Etonogestrel was negative in assays for reverse gene mutation in bacteria, chromosomal aberrations in mammalian cells, and micronuclei formation in mice. Data on the genotoxic potential of ethinylestradiol are currently limited, but there is some evidence available in the literature suggesting that estrogens may be weakly genotoxic at high doses. The genotoxic potential of the ethylene vinylacetate polymers has not been investigated.

Carcinogenicity.

No study has been conducted to investigate the carcinogenicity of NuvaRing. In a 24-month carcinogenicity study in rats with subdermal implants releasing 10 and 20 microgram etonogestrel per day, (approximately 0.3 and 0.6 times the systemic steady state exposure of women using NuvaRing), no drug-related increase in tumour incidence was observed. Studies with a combination of ethinylestradiol and desogestrel in rats and mice elicited an increased incidence of pituitary and mammary gland tumours. Long-term animal studies of natural and synthetic estrogens have also shown an increased incidence of carcinomas in the breast, uterus, cervix, vagina, testis and liver.
An increased risk of tumours in estrogen-sensitive target organs, such as uterus, breast and ovary, is associated with prolonged estrogen therapy in women. In rare cases, benign liver adenomas, and even more rarely, malignant liver tumours have been reported in users of combined oral contraceptives. Although benign, hepatic adenomas may rupture and cause death through intra-abdominal haemorrhage.

4 Clinical Particulars

4.1 Therapeutic Indications

For use for contraception.

4.3 Contraindications

NuvaRing 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 NuvaRing, it should be removed immediately.
Presence or history of venous thrombosis, with or without pulmonary embolism.
Presence or history of arterial thrombosis (e.g. cerebrovascular accident, myocardial infarction) or prodromi of a thrombosis (e.g. transient ischaemic attack or angina pectoris).
Known hereditary or acquired predisposition for venous or arterial thromboembolism, such as Activated Protein C (APC) resistance (including Factor V Leiden), antithrombin-III deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia and antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
Major surgery with prolonged immobilization (see Section 4.4 Special Warnings and Precautions for Use).
History of migraine with focal neurological symptoms.
Diabetes mellitus with vascular involvement.
The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis may also constitute a contraindication (see Section 4.4 Special Warnings and Precautions for Use).
Pancreatitis or a history thereof if associated with severe hypertriglyceridaemia.
Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
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 the active substances or to any of the excipients of NuvaRing.
NuvaRing is contraindicated for use with the hepatitis C virus (HCV) 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 NuvaRing should be weighed against the possible risks for each individual woman and discussed with the woman before she decides to start using it. 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 NuvaRing use should be discontinued.

1. Circulatory disorders.

The use of combined hormonal contraceptives (CHCs) has been associated with the occurrence of venous thrombosis (deep vein thrombosis and pulmonary embolism) and arterial thrombosis (such as myocardial infarction and stroke) and associated complications, sometimes with fatal consequences.
An increased risk of thromboembolic and thrombotic disease associated with the use of CHCs is well-established. Although the absolute VTE rates are increased for users of CHCs compared to non-users, the rates associated with pregnancy are even greater, especially during the post-partum period (see Figure 1).
The frequency of VTE in women using CHCs has been estimated to be 3 to 12 cases per 10,000 women-years.
The excess risk of VTE is highest during the first year of CHC use. The excess risk of VTE gradually disappears after use is discontinued. Data from a large, prospective cohort safety study of various COCs suggest that this increased risk, as compared to that in non-COC users, is greatest during the first 6 months of COC use and is present after initially starting a COC or restarting (following a 4 week or greater pill-free interval) the same or a different COC. This increased risk is less than the risk of VTE associated with pregnancy which is estimated as 5 to 20 cases per 10,000 women-year (WY). VTE is fatal in 1-2% of cases.
Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use CHCs, for women who use CHCs, for pregnant women, and for women in the postpartum period. To put the risk of developing a VTE into perspective: if 10,000 women who are not pregnant and do not use CHCs are followed for one year, between 1 and 5 of these women will develop a VTE.
Several epidemiology studies indicate that third generation oral contraceptives, including those containing desogestrel (etonogestrel, the progestin in NuvaRing, is the biologically active metabolite of desogestrel), are associated with a higher risk of venous thromboembolism than certain second generation oral contraceptives. In general, these studies indicate an approximate two-fold increased risk, which corresponds to an additional one to two cases of venous thromboembolism per 10,000 women-years of use. However, data from additional studies have not shown this two-fold increase in risk.
In studies required or sponsored by regulatory agencies, NuvaRing users had a risk of VTE similar to COC users (see Table 1 for adjusted hazard ratios). A large prospective, observational study, the Transatlantic Active Surveillance on Cardiovascular Safety of NuvaRing (TASC), investigated the risk of VTE for new users, switchers, and restarters of NuvaRing and COCs in a population that is representative of routine clinical users. The women were followed for 24 to 48 months. The results showed a similar risk of VTE among NuvaRing users (VTE incidence 8.3 per 10,000 WY; 95% CI: 5.0-12.9) and women using COCs (VTE incidence 9.2 per 10,000 WY; 95% CI: 6.0-13.5). For women using COCs, excluding desogestrel (DSG), gestodene (GSD) and drospirenone (DRSP), VTE incidence was 8.5 per 10,000 WY (95% CI: 4.5-14.6).
A retrospective cohort study using data from 4 health plans in the US ("FDA-funded study") showed a VTE incidence for new users of NuvaRing of 11.4 events per 10,000 WY and for new users of a levonorgestrel (LNG)-containing COC of 9.2 events per 10,000 WY.
Extremely rarely, thrombosis has been reported to occur in other blood vessels, e.g. hepatic, mesenteric, renal, cerebral or retinal veins and arteries, in CHC users.
Symptoms of venous or arterial thrombosis can include: unusual unilateral leg pain and/or swelling; sudden severe pain in the chest, whether or not it radiates to the left arm; sudden breathlessness; sudden onset of coughing; any unusual, severe, prolonged headache; sudden partial or complete loss of vision; diplopia; slurred speech or aphasia; vertigo; collapse with or without focal seizure; weakness or very marked numbness suddenly affecting one side or one part of the body; motor disturbances; 'acute' abdomen.
The risk of venous thromboembolism increases with:
increasing age;
a positive family history (i.e. venous thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any hormonal contraceptive use;
prolonged immobilisation, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilisation, also see Section 4.3 Contraindications;
obesity (body mass index over 30 kg/m2); and
possibly also with superficial thrombophlebitis and varicose veins. There is no consensus about the possible role of these conditions in the etiology of venous thrombosis.
The risk of arterial thromboembolic complications increases with: increasing age; smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age); dyslipoproteinaemia; obesity (body mass index over 30 kg/m2); hypertension; migraine; valvular heart disease; atrial fibrillation; a positive family history (arterial thrombosis ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any hormonal contraceptive use.
Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance (including Factor V Leiden), hyperhomocysteinaemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).
Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis), and sickle cell disease.
The increased risk of thromboembolism in the puerperium must be considered (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
An increase in frequency or severity of migraine during hormonal contraceptive use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the use of hormonal contraceptives.
When considering risk/benefit, the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with hormonal contraceptive use.
Women using combined hormonal contraceptives (CHCs) should be advised to contact their physician in case of possible symptoms of thrombosis. In case of suspected or confirmed thrombosis, CHC use should be discontinued. Adequate contraception should be initiated because of the teratogenicity of anti-coagulant therapy (coumarins).

2. Tumours.

The most important risk factor for cervical cancer is persistent human papilloma virus (HPV) infection. Epidemiological studies have indicated that long-term use of COCs contributes to this increased risk, but there continues to be uncertainty about the extent to which this finding is attributable to confounding effects, like increased cervical screening and difference in sexual behaviour including use of barrier contraceptives, or a causal association. It is unknown how this effect relates to NuvaRing.
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. Therefore, 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 using NuvaRing.

3. Hypersensitivity reactions.

Hypersensitivity reactions of angioedema and anaphylaxis have been reported during use of NuvaRing. If angioedema and/or anaphylaxis is suspected, NuvaRing should be discontinued and appropriate treatment administered.

4. 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. NuvaRing 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). NuvaRing can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.

5. Other conditions.

Women with hypertriglyceridaemia, or a family history thereof, may be at an increased risk of pancreatitis when using hormonal contraceptives.
Although small increases in blood pressure have been reported in many women using hormonal contraceptives, clinically relevant increases are rare. However, if a sustained clinically significant hypertension develops during the use of NuvaRing then it is prudent for the physician to suspend the use of the ring and treat the hypertension. Where considered appropriate, NuvaRing 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 during the use of hormonal contraceptives, but the evidence of an association with its 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.
Acute or chronic disturbances of liver function may necessitate the discontinuation of the use of NuvaRing until markers of liver function return to normal. Recurrence of cholestatic jaundice and/or pruritus related to cholestasis, which occurred first during pregnancy or previous use of sex steroids necessitates the discontinuation of the ring.
Although estrogens and progestogens 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 hormonal contraceptives (containing < 50 microgram ethinylestradiol). However, diabetic women should be carefully monitored while using NuvaRing especially in the first months of use.
Crohn's disease and ulcerative colitis have been reported in association with the use of hormonal contraceptives.
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 while using NuvaRing.
If a woman has any of the following conditions, she may not be able to insert NuvaRing correctly or may in fact lose the ring: prolapse of the uterine cervix, cystocele, and/or rectocele, severe or chronic constipation.
Very rarely it has been reported that NuvaRing is inadvertently inserted in the urethra and possibly ending up in the bladder. Therefore, incorrect positioning should be considered in the differential diagnosis in case of symptoms of cystitis.
As with other hormonal combination contraceptives there was a tendency in the clinical studies for some subjects to experience clinically significant weight changes. In US study 068003, 10.3% had a ≥ 7% weight loss while 18.1% experienced a ≥ 7% weight gain during therapy. In the European study 34219, 8.4% had a ≥ 7% weight loss while 10.2% experienced a ≥ 7% weight gain during therapy.
During the use of NuvaRing, women may occasionally experience vaginitis. There are no indications that the efficacy of NuvaRing is affected by the treatment of vaginitis, nor that the use of NuvaRing affects the treatment of vaginitis (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Very rarely it has been reported that the ring adhered to vaginal tissue, necessitating removal by a healthcare provider. In some cases when the tissue had grown over the ring, removal was achieved by cutting the ring without incising the overlying vaginal tissue.
Cases of toxic shock syndrome have been associated with tampons and certain barrier contraceptives. Very rare cases of TSS have been reported by NuvaRing users; in some cases the women were also using tampons. No causal relationship between the use of NuvaRing and TSS has been established. If a patient exhibits signs or symptoms of TSS, the possibility of this diagnosis should not be excluded and appropriate medical evaluation and treatment initiated.

Medical examination/consultation.

A complete medical history and physical examination should be taken prior to the initiation or reinstitution of NuvaRing use, see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, and should be repeated periodically. 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 hormonal contraceptive. The frequency and nature of these further periodic checks should be based upon established clinical practice guidelines and adapted to the individual woman but should generally include special reference to blood pressure, breasts, abdomen and pelvic organs, including routine cervical cytology.
Women should be advised that NuvaRing does not protect against HIV infections (AIDS) and other sexually transmitted diseases.

Reduced efficacy.

The efficacy of NuvaRing may be reduced in the event of non-compliance (see Section 4.2 Dose and Method of Administration, Deviations from the recommended regime) or when concomitant medications that decrease the plasma concentration of etonogestrel are used (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Ectopic as well as intrauterine pregnancy may occur in contraceptive failures.

Reduced cycle control.

Irregular bleeding (spotting or breakthrough bleeding) may occur during the use of NuvaRing (see Section 5.1 Pharmacodynamic Properties, Bleeding pattern). If bleeding irregularities occur after previously regular cycles while NuvaRing has been used according to the recommended regimen, 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, a withdrawal bleed may not occur during the ring-free interval. If NuvaRing has been used according to the instructions described (see Section 4.2 Dose and Method of Administration), it is unlikely that the woman is pregnant. However, if NuvaRing has not been used according to these instructions prior to the first missed withdrawal bleed or if two withdrawal bleeds are missed, pregnancy must be ruled out before use of NuvaRing is continued.

Male exposure to ethinylestradiol and etonogestrel.

The extent and possible pharmacological role of exposure of male sexual partners to ethinylestradiol and etonogestrel through absorption through the penis have not been examined.

Broken rings.

On rare occasions NuvaRing has been reported to get disconnected during use (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Since NuvaRing's core is solid, its contents will remain intact and release of hormones will not be significantly affected. Vaginal injury associated with ring breakage has been reported. In the event of disconnection of the ring, expulsion is likely to occur (see Section 4.2 Dose and Method of Administration, What to do if NuvaRing is removed or expelled from the vagina during the 3 weeks of ring use). If NuvaRing is broken, the woman should discard the ring and replace with a new ring.

Expulsion.

NuvaRing has been reported to get expelled, for example if the ring has not been inserted properly, while removing a tampon, during sexual intercourse, or in case of severe or chronic constipation. Therefore, it is good habit for the woman to regularly verify the presence of NuvaRing (for example, before and after intercourse). If NuvaRing is accidentally expelled, the woman should follow the instructions given (see Section 4.2 Dose and Method of Administration, What to do if NuvaRing is removed or expelled from the vagina during the 3 weeks of ring use).

Use in the elderly.

No data available.

Paediatric use.

The safety and efficacy of NuvaRing in adolescents under the age of 18 have not been studied.

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 sex hormone binding globulin), 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.
Interactions between hormonal contraceptives and other medicinal products may lead to breakthrough bleeding and/or contraceptive failure. The following interactions have been reported in the literature.

Hepatic metabolism.

Interactions can occur with 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 hormonal contraceptives, including NuvaRing. These products include phenytoin, phenobarbital, primidone, bosentan, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, chloramphenicol, neomycin, nitrofurantoin, tetracyclines, 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. Other enzyme inducers that may interact with hormonal contraceptives are: barbiturates.
Enzyme induction can occur after a few days of treatment. Maximal enzyme induction is generally observed within a few weeks. After drug therapy is discontinued, enzyme induction can last for about 28 days.
When co-administered 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, or estrogen. 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 NuvaRing may be reduced. A barrier contraceptive method should be used in addition to NuvaRing during administration of the hepatic enzyme-inducing medicinal product, and for 28 days after discontinuation of the hepatic enzyme-inducing medicinal product.

Note.

NuvaRing should not be used with a diaphragm, cervical cap, or female condom.
If concomitant drug administration runs beyond the 3 weeks of a ring-cycle, the next ring should be inserted immediately, without having the usual ring-free period.
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.
In a pharmacokinetic interaction study, oral administration of amoxicillin (875 mg, two times daily) or doxycycline (200 mg on day 1, followed by 100 mg per day for 10 days during use of NuvaRing), did not significantly affect pharmacokinetics of etonogestrel and ethinylestradiol (EE). The effects of other antibiotics on etonogestrel or ethinylestradiol concentrations have not been evaluated.
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.
Other medicines that have been reported but not yet confirmed to reduce contraceptive efficacy are phenylbutazone, sulfamethoxypyridazine, hydantoins.
A single-dose vaginal administration of 100 mg water-based nonoxynol-9 spermicide gel did not affect the serum concentrations of etonogestrel or ethinylestradiol. A single-dose vaginal administration of an oil-based 1200 mg miconazole nitrate capsule increased the serum concentrations of etonogestrel and ethinylestradiol by approximately 17% and 16%, respectively. Following multiple doses of 200 mg miconazole nitrate by vaginal suppository or vaginal cream, the mean serum concentrations of etonogestrel and ethinylestradiol increased by up to 40%. There have been reports of ring breakage during concomitant use of intravaginal preparations, including antimycotic, antibiotic and lubricant products (see Section 4.4 Special Warnings and Precautions for Use, Broken rings). However, based on pharmacokinetic data, vaginally administered antimycotics and spermicides are unlikely to affect the contraceptive efficacy and safety of NuvaRing.
Hormonal contraceptives may interfere with the metabolism or pharmacodynamics of other drugs. Accordingly, plasma and tissue concentrations or clinical effects may be affected. Some of these drugs include: anticoagulants, some anti-diabetic drugs, ciclosporin, theophylline, imipramine and lamotrigine. 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. NuvaRing 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). NuvaRing can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.

Interaction with tampons.

Pharmacokinetic data show that the use of tampons has no effect on the systemic absorption of the hormones released by NuvaRing. On rare occasions NuvaRing might be expelled while removing a tampon (see Section 4.2 Dose and Method of Administration, What to do if NuvaRing is removed or expelled from the vagina during the 3 weeks of ring use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

NuvaRing is indicated for the prevention of pregnancy. If the woman wants to stop using NuvaRing because she wants to get pregnant, she is advised to wait until she has a natural period before trying to conceive as this will help her calculate when the baby is due.
(Category B3)
NuvaRing is contraindicated in pregnancy. If pregnancy occurs with NuvaRing in situ, the ring should be removed.
In animal studies, maternal administration of high doses of estrogens has produced urogenital malformations in the offspring. Maternal administration of high doses of progestogens has also elicited masculinisation of the female fetus in animal studies. The clinical relevance of these animal findings is not certain. 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 used inadvertently during early pregnancy. Although this probably applies to all COCs it is not clear whether this is also the case for NuvaRing.
Due to the intravaginal administration, intrauterine concentrations of the contraceptive steroids in NuvaRing are likely to be higher than in COC users. An effect on the fetus can therefore not be excluded. Clinical experience of the outcomes of pregnancies exposed to NuvaRing have not been reported.
No postnatal toxicity data are currently available in animals or humans concerning the safety of the use of NuvaRing when breastfeeding. Contraceptive steroids and/or their metabolites are known to be excreted into the milk. Lactation may be influenced by estrogens, as they may reduce the quantity and change the composition of breast milk. Therefore, the use of NuvaRing should generally not be recommended until the nursing mother has completely weaned her child.

4.8 Adverse Effects (Undesirable Effects)

The most serious undesirable effects associated with the use of hormonal contraceptives are listed, see Section 4.4 Special Warnings and Precautions for Use.
Adverse effects that have been reported in users of NuvaRing are listed in Table 2. The most appropriate MedDRA term (version 11.0) to describe a certain adverse effect is listed.
All adverse reactions are listed by system organ class and frequency: common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), and not known (cannot be estimated from the available data).

Reporting suspected adverse effects.

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

4.2 Dose and Method of Administration

Dose.

To achieve contraceptive effectiveness, NuvaRing must be used as directed (see How to use NuvaRing, How to start NuvaRing).

Method of administration.

How to use NuvaRing.

The woman herself can insert NuvaRing in the vagina. The physician should advise the woman how to insert and remove NuvaRing. For insertion the woman should choose a position that is most comfortable for her, e.g. standing with one leg up, squatting, or lying down. NuvaRing should be compressed and inserted into the vagina until it feels comfortable. The exact position of NuvaRing in the vagina is not critical for the contraceptive effect of the ring (see illustrations on package insert). However, it must be inserted correctly to minimize the chance of expulsion.
1. Take NuvaRing out of the sachet.
2. Compress the ring.
3. Choose a comfortable position to insert the ring.
4. Insert the ring into the vagina with one hand, if necessary the labia may be spread with the other. Push the ring into the vagina until the ring feels comfortable. Leave the ring in place for 3 weeks.
Once NuvaRing has been inserted (see How to start NuvaRing) it is left in the vagina continuously for 3 weeks. Advise women to regularly check for the presence of NuvaRing in the vagina (for example, before and after intercourse). If NuvaRing is accidentally expelled (e.g. while removing a tampon), it can be rinsed with cool to lukewarm (not hot) water and should be reinserted immediately. In the unusual case of women whose partners object to the presence of the ring during sexual intercourse, the ring should not be temporarily removed; rather it is preferable to switch to another method of contraception. In the two major clinical studies 2.7% of women experienced ring expulsion. NuvaRing must be removed after 3 weeks of use on the same day of the week as the ring was inserted. After a ring-free interval of one week a new ring is inserted (e.g. when NuvaRing is inserted on a Wednesday at about 10 pm the ring should be removed again on the Wednesday 3 weeks later at about 10 pm. The following Wednesday a new ring should be inserted). NuvaRing can be removed by hooking the index finger under the ring or by grasping the ring between the index and middle finger and pulling it out. The used ring should be placed in the sachet (keep out of the reach of children and pets) and discarded as described (see Section 6.6 Special Precautions for Disposal). The withdrawal bleed usually starts 2-3 days after removal of NuvaRing and may not have finished completely before the next ring insertion is due.

Use with other vaginal products.

NuvaRing may interfere with the correct placement and position of certain female barrier methods such as a diaphragm, cervical cap, or female condom.
These methods should not be used as back-up methods with NuvaRing.

How to start NuvaRing.

No hormonal contraceptive use in the preceding cycle.

NuvaRing has to be inserted on the first day of the woman's natural cycle (i.e. the first day of her menstrual bleeding). Starting on days 2-5 is allowed, but during the first cycle a barrier method (such as male condoms or spermicide) should be used in addition for the first 7 days of NuvaRing use. See Section 5.1 Pharmacodynamic Properties, Clinical trials.

Changing from a combined hormonal contraceptive.

The woman should insert NuvaRing at the latest on the day following the usual tablet-free or placebo tablet interval of her previous COC.

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

The woman may switch on any day from the minipill. She should switch from an implant or the IUS on the day of its removal and from an injectable on the day when the next injection would be due. In all of these cases, the woman should use an additional barrier method for the first 7 days.

Following first-trimester abortion.

The woman may start immediately. When doing so, she needs not to take additional contraceptive measures. If an immediate switch is considered undesirable, the woman should follow the advice given for 'no hormonal contraceptive use in the preceding cycle'. In the meantime, she should be advised to use an alternative contraceptive method.

Following delivery or second-trimester abortion.

For breast-feeding women, see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation.
Women should be advised to start during the fourth week 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 NuvaRing use. However, if intercourse has already occurred, pregnancy should be excluded or the woman has to wait for her first menstrual period, before starting NuvaRing use.
The increased risk of VTE during the postpartum period should be considered when restarting NuvaRing (see Section 4.4 Special Warnings and Precautions for Use).

Following amenorrhoea or oligomenorrhoea.

Exclude the possibility of pregnancy and then start NuvaRing. The woman should be advised to additionally use a barrier contraceptive method for the first seven days of NuvaRing use. If unprotected intercourse has occurred consider the delay between conception and a positive pregnancy test.

Deviations from the recommended regime.

Contraceptive efficacy and cycle control may be compromised if the woman deviates from the recommended regimen. To avoid loss of contraceptive efficacy in case of a deviation, the following advice can be given:

What to do if the patient forgets to insert a new NuvaRing after the 7 day ring free period.

The woman should insert a new ring as soon as she remembers. A barrier method such as a male condom should be used in addition for the next 7 days. If intercourse took place during the ring-free interval, the possibility of a pregnancy should be considered. The longer the ring-free interval, the higher the risk of a pregnancy.

What to do if NuvaRing is removed or expelled from the vagina during the 3 weeks of ring use.

NuvaRing should be left in the vagina for a continuous period of 3 weeks. If the ring is accidentally expelled and is left outside of the vagina for less than 3 hours contraceptive efficacy is not reduced. The woman should reinsert the ring as soon as possible, but at the latest within 3 hours.
If NuvaRing has been out of the vagina for more than 3 hours during the 1st or 2nd week, contraceptive efficacy may be reduced. The woman should reinsert the ring as soon as she remembers. A barrier method such as a male condom should be used in addition to NuvaRing until NuvaRing has been in the vagina continuously for 7 days. The longer the time NuvaRing has been out of the vagina and the closer this is to the ring-free interval, the higher the risk of a pregnancy.
If NuvaRing has been out of the vagina for more than 3 hours during the 3rd week of the three-week use period, contraceptive efficacy may be reduced. The woman should discard that ring, and one of the following two options should be chosen:
1. Insert a new ring immediately.

Note.

Inserting a new ring will start the next three-week use period. The woman may not experience a withdrawal bleed from her previous cycle. However, breakthrough spotting or bleeding may occur.
2. Have a withdrawal bleed and insert a new ring no later than 7 days (7 x 24 hours) from the time the previous ring was removed or expelled.

Note.

This option should only be chosen if the ring was used continuously for the preceding 7 days.
If NuvaRing was out of the vagina for an unknown amount of time, the possibility of pregnancy should be considered. A pregnancy test should be performed prior to inserting a new ring.

What to do if NuvaRing is not removed after 3 weeks.

The contraceptive efficacy of NuvaRing is adequate for up to 4 weeks. In circumstances where the ring has been in use for between 3 and 4 weeks, the woman may maintain her one-week ring-free interval and subsequently insert a new ring. If NuvaRing has been left in place for more than 4 weeks, contraceptive efficacy may be reduced and pregnancy should be ruled out before inserting a new NuvaRing.
If the woman has not adhered to the recommended regimen and subsequently has no withdrawal bleed in the following ring-free interval, pregnancy should be ruled out before inserting a new NuvaRing.

How to shift periods or how to delay a period.

To delay a period the woman may insert a new ring without having a ring-free interval. The next ring can be used for up to 3 weeks again. The woman may experience bleeding or spotting. Regular use of NuvaRing is then resumed after the usual one week ring-free 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 ring-free interval by as many days as she likes. The shorter the ring-free interval, the higher the risk that she does not have a withdrawal bleed and will experience breakthrough bleeding and spotting during the use of the next ring.

4.7 Effects on Ability to Drive and Use Machines

On the basis of the pharmacodynamic profile, NuvaRing is expected to have no influence on the ability to drive and use machines.

4.9 Overdose

There have been no reports of serious deleterious effects from an overdose of hormonal contraceptives. 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).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Evatane (28-25) ARTG No. 12054, Evatane (1020 VN3) ARTG No. 12053, Magnesium stearate.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

The shelf life of NuvaRing is 40 months, if stored in accordance with prescribed storage instructions.
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

Prior to dispensing: 36 months, store in a refrigerator (2°C-8°C).
At the time of dispensing: The dispenser places a date of dispensing on the box and the sachet(s). The product should not be inserted after the expiry date or 4 months from the date of dispensing, whichever comes first.
After dispensing: 4 months; do not store above 30°C.
Store NuvaRing in the original package.
Protect from light and freezing.

6.5 Nature and Contents of Container

Sachet containing one NuvaRing. The sachet is made of aluminum foil with an inner layer of low-density polyethylene and an outer layer of polyester. It is reclosable and waterproof. The sachet is packed in a printed cardboard box together with the package leaflet. Each box contains 1 or 3 sachets.

6.6 Special Precautions for Disposal

See Section 4.2 Dose and Method of Administration. The dispenser has to indicate the date of dispensing and the date before which NuvaRing has to be used on the box. After removal, NuvaRing should be replaced in the reclosable sachet and disposed of with the normal household waste in a manner that avoids accidental contact with others. NuvaRing should not be flushed down the toilet.

Summary Table of Changes