United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)
15-06-2018
15-06-2018
Package leaflet: Information for the user
NuvaRing®, 0.120 mg/0.015 mg per 24 hours, vaginal delivery system
Etonogestrel/Ethinylestradiol
Important things to know about combined hormonal contraceptives (CHCs):
They are one of the most reliable reversible methods of contraception if used correctly.
They slightly increase the risk of having a blood clot in the veins and arteries, especially in the
first year or when restarting a combined hormonal contraceptive following a break of 4 or more
weeks.
Please be alert and see your doctor if you think you may have symptoms of a blood clot (see
section 2 “Blood clots”).
Read all of this leaflet carefully before you start using NuvaRing
because it contains important
information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others. It may harm them.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side
effects not listed in this leaflet. See section 4.
What is in this leaflet
What NuvaRing is and what it is used for
What you need to know before you use NuvaRing
When you should not use NuvaRing
Warnings and precautions
Blood clots
Cancer
Children and adolescents
Other medicines and NuvaRing
Laboratory tests
Pregnancy and breast-feeding
Driving and using machines
How to use NuvaRing
How to insert and remove NuvaRing
Three weeks in, one week out
When to start with the first ring
What to do if…
Your ring is accidentally expelled from the vagina
Your ring has temporarily been out of the vagina
Your ring breaks
You have inserted more than one ring
You have forgotten to insert a new ring after the ring-free interval
You have forgotten to remove the ring
You have missed a menstrual period
You have unexpected bleeding
You want to change the first day of your menstrual period
You want to delay your menstrual period
When you want to stop using NuvaRing
Possible side effects
How to store NuvaRing
Contents of the pack and other information
What NuvaRing contains
What NuvaRing looks like and contents of the pack
Marketing Authorisation Holder and Manufacturer
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 cell is released you cannot become pregnant.
2.
What you need to know before you use NuvaRing
General notes
Before you start using NuvaRing you should read the information on blood clots in section 2. It is
particularly important to read the symptoms of a blood clot – see section 2 “Blood clots”.
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 mucus.
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
You should not use NuvaRing if you have any of the conditions listed below. If you do have any of
the conditions listed below, you must tell your doctor. Your doctor will discuss with you what other
form of birth control would be more appropriate.
if you have (or have ever had) a blood clot in a blood vessel of your legs (deep vein thrombosis,
DVT), your lungs (pulmonary embolus, PE) or other organs;
if you know you have a disorder affecting your blood clotting - for instance, protein C deficiency,
protein S deficiency, antithrombin – III deficiency, Factor V Leiden or antiphospholipid
antibodies;
if you need an operation or if you are off your feet for a long time (see section ‘Blood clots’);
if you have ever had a heart attack, or a stroke;
if you have (or have ever had) angina pectoris (a condition that causes severe chest pain and may
be a first sign of a heart attack) or transient ischaemic attack (TIA – temporary stroke symptoms);
if you have any of the following diseases that may increase your risk of a clot in the arteries:
severe diabetes with blood vessel damage
very high blood pressure
a very high level of fat in the blood (cholesterol or triglycerides)
a condition known as hyperhomocysteinaemia
if you have (or have ever had) a type of migraine called ‘migraine with aura’;
if you have (had) inflammation of the pancreas (pancreatitis) associated with high levels of fat in
your blood;
if you have (had) severe liver disease and your liver is not yet working normally;
if you have (had) a benign or malignant tumour in the liver;
if you have (had), or if you may have, cancer of the breast or the genital organs;
if you have any unexplained vaginal bleeding;
if you are allergic to ethinylestradiol or etonogestrel, or any of the other ingredients of this
medicine (listed in section 6).
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 medicinal products containing
ombitasvir/paritaprevir/ritonavir and dasabuvir (see also section 2.4 ‘
Other medicines and
NuvaRing
’).
2.2
Warnings and precautions
Tell your doctor if any of the following conditions apply to you.
If the condition develops, or gets worse while you are using NuvaRing, you should also tell your
doctor.
if a close relative has or has ever had breast cancer;
if you have epilepsy (see section 2.4: ‘
Other medicines and NuvaRing’
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 systemic lupus erythematosus (SLE - a disease affecting your natural defence
system);
if you have haemolytic uraemic syndrome (HUS - 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 (hypertriglyceridaemia) or a positive family
history for this condition. Hypertriglyceridaemia has been associated with an increased risk of
developing pancreatitis (inflammation of the pancreas);
if you need an operation, or you are off your feet for a long time (see in section 2 ‘Blood
clots’);
if you have just 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;
if you have an inflammation in the veins under the skin (superficial thrombophlebitis);
if you have varicose veins;
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 [y
ou 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;
When should you contact your doctor?
Seek urgent medical attention
if you notice possible signs of a blood clot that may mean you are suffering from a
blood clot in the leg (i.e. deep vein thrombosis), a blood clot in the lung (i.e.
pulmonary embolism), a heart attack or a stroke (see ‘Blood clots’ section below).
For a description of the symptoms of these serious side effects please go to “How to
recognise a blood clot”.
if you have a medical condition that makes it difficult to use NuvaRing – for example, if you
are constipated, have a prolapse of the uterine cervix or have pain during intercourse;
if 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.
BLOOD CLOTS
Using a combined hormonal contraceptive such as NuvaRing increases your risk of developing a
blood clot compared with not using one. In rare cases a blood clot can block blood vessels and cause
serious problems.
Blood clots can develop
in veins (referred to as a ‘venous thrombosis’, ‘venous thromboembolism’ or VTE);
in the arteries (referred to as an ‘arterial thrombosis’, ‘arterial thromboembolism’ or ATE).
Recovery from blood clots is not always complete. Rarely, there may be serious lasting effects or,
very rarely, they may be fatal.
It is important to remember that the overall risk of a harmful blood clot due to NuvaRing is
small.
HOW TO RECOGNISE A BLOOD CLOT
Seek urgent medical attention if you notice any of the following signs or symptoms.
Are you experiencing any of these signs?
What are you possibly
suffering from?
swelling of one leg or along a vein in the leg or foot especially when
accompanied by:
pain or tenderness in the leg which may be felt only when
standing or walking
increased warmth in the affected leg
change in colour of the skin on the leg e.g. turning pale, red or
blue
Deep vein thrombosis
sudden unexplained breathlessness or rapid breathing;
sudden cough without an obvious cause, which may bring up blood;
sharp chest pain which may increase with deep breathing;
severe light headedness or dizziness;
rapid or irregular heartbeat;
severe pain in your stomach;
If you are unsure, talk to a doctor as some of these symptoms such as
coughing or being short of breath may be mistaken for a milder condition
such as a respiratory tract infection (e.g. a ‘common cold’).
Pulmonary embolism
Symptoms most commonly occur in one eye:
immediate loss of vision or
painless blurring of vision which can progress to loss of vision
Retinal vein thrombosis
(blood clot in the eye)
chest pain, discomfort, pressure, heaviness
sensation of squeezing or fullness in the chest, arm or below the
Heart attack
breastbone;
fullness, indigestion or choking feeling;
upper body discomfort radiating to the back, jaw, throat, arm and
stomach;
sweating, nausea, vomiting or dizziness;
extreme weakness, anxiety, or shortness of breath;
rapid or irregular heartbeats
sudden weakness or numbness of the face, arm or leg, especially on
one side of the body;
sudden confusion, trouble speaking or understanding;
sudden trouble seeing in one or both eyes;
sudden trouble walking, dizziness, loss of balance or coordination;
sudden, severe or prolonged headache with no known cause;
loss of consciousness or fainting with or without seizure.
Sometimes the symptoms of stroke can be brief with an almost immediate
and full recovery, but you should still seek urgent medical attention as you
may be at risk of another stroke.
Stroke
swelling and slight blue discolouration of an extremity;
severe pain in your stomach (acute abdomen).
Blood clots blocking
other blood vessels
BLOOD CLOTS IN A VEIN
What can happen if a blood clot forms in a vein?
The use of combined hormonal contraceptives has been connected with an increase in the risk
of blood clots in the vein (venous thrombosis). However, these side effects are rare. Most
frequently, they occur in the first year of use of a combined hormonal contraceptive.
If a blood clot forms in a vein in the leg or foot it can cause a deep vein thrombosis (DVT).
If a blood clot travels from the leg and lodges in the lung it can cause a pulmonary embolism.
Very rarely a clot may form in a vein in another organ such as the eye (retinal vein thrombosis).
When is the risk of developing a blood clot in a vein highest?
The risk of developing a blood clot in a vein is highest during the first year of taking a combined
hormonal contraceptive for the first time. The risk may also be higher if you restart taking a combined
hormonal contraceptive (the same product or a different product) after a break of 4 weeks or more.
After the first year, the risk gets smaller but is always slightly higher than if you were not using a
combined hormonal contraceptive.
When you stop using NuvaRing your risk of a blood clot returns to normal within a few weeks.
What is the risk of developing a blood clot?
The risk depends on your natural risk of VTE and the type of combined hormonal contraceptive you
are taking.
The overall risk of a blood clot in the leg or lung (DVT or PE) with NuvaRing is small.
Out of 10,000 women who are not using any combined hormonal contraceptive and are not
pregnant, about 2 will develop a blood clot in a year.
Out of 10,000 women who are using a combined hormonal contraceptive that contains
levonorgestrel, norethisterone, or norgestimate, about 5-7 will develop a blood clot in a year.
Out of 10,000 women who are using a combined hormonal contraceptive that contains
norelgestromin, or etonogestrel such as NuvaRing, between about 6 and 12 women will develop
a blood clot in a year.
The risk of having a blood clot will vary according to your personal medical history (see
“Factors that increase your risk of a blood clot” below).
Risk of developing a blood clot
in a year
Women who are
not using
a combined hormonal pill/patch/ring
and are not pregnant
About 2 out of 10,000 women
Women using a combined hormonal contraceptive pill containing
levonorgestrel, norethisterone or
norgestimate
About 5-7 out of 10,000 women
Women using NuvaRing
About 6-12 out of 10,000
women
Factors that increase your risk of a blood clot in a vein
The risk of a blood clot with NuvaRing is small but some conditions will increase the risk. Your risk
is higher:
if you are very overweight (body mass index or BMI over 30 kg/m
if one of your immediate family has had a blood clot in the leg, lung or other organ at a young
age (e.g. below the age of about 50). In this case you could have a hereditary blood clotting
disorder;
if you need to have an operation, or if you are off your feet for a long time because of an injury
or illness, or you have your leg in a cast. The use of NuvaRing may need to be stopped several
weeks before surgery or while you are less mobile. If you need to stop using NuvaRing ask your
doctor when you can start using it again;
as you get older (particularly above about 35 years);
if you gave birth less than a few weeks ago.
The risk of developing a blood clot increases the more conditions you have.
Air travel (>4 hours) may temporarily increase your risk of a blood clot, particularly if you have some
of the other factors listed.
It is important to tell your doctor if any of these conditions apply to you, even if you are unsure. Your
doctor may decide that NuvaRing needs to be stopped.
If any of the above conditions change while you are using NuvaRing, for example a close family
member experiences a thrombosis for no known reason, or you gain a lot of weight, tell your doctor.
BLOOD CLOTS IN AN ARTERY
What can happen if a blood clot forms in an artery?
Like a blood clot in a vein, a clot in an artery can cause serious problems. For example, it can cause a
heart attack or a stroke.
Factors that increase your risk of a blood clot in an artery
It is important to note that the risk of a heart attack or stroke from using NuvaRing is very small but
can increase:
with increasing age (beyond about 35 years);
if you smoke.
When using a combined hormonal contraceptive like NuvaRing you are advised
to stop smoking. If you are unable to stop smoking and are older than 35 your doctor may
advise you to use a different type of contraceptive;
if you are overweight;
if you have high blood pressure;
if a member of your immediate family has had a heart attack or stroke at a young age (less than
about 50). In this case you could also have a higher risk of having a heart attack or stroke;
if you, or someone in your immediate family, have a high level of fat in the blood (cholesterol
or triglycerides);
if you get migraines, especially migraines with aura;
if you have a problem with your heart (valve disorder, disturbance of the rhythm called atrial
fibrillation);
if you have diabetes.
If you have more than one of these conditions or if any of them are particularly severe, the risk of
developing a blood clot may be increased even more.
If any of the above conditions change while you are using NuvaRing, for example, you start smoking,
a close family member experiences a thrombosis for no known reason, or you gain a lot of weight, tell
your doctor.
Cancer
The information given below was obtained in studies with combined oral contraceptives and it may
also apply to NuvaRing. Information about vaginal administration of contraceptive hormones (as in
NuvaRing) is not available.
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.
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.
For users of the combined Pill it has been reported that cancer of the endometrium (the lining of the
womb) and cancer of the ovaries occur less frequently. This may also be the case for NuvaRing but
this has not been confirmed.
2.3
Children and adolescents
The safety and efficacy of NuvaRing in adolescents under the age of 18 have not been studied.
2.4
Other medicines and NuvaRing
Always tell your doctor which medicines or herbal products you are already using. Also tell any other
doctor or dentist (or the pharmacist) who prescribes another medicine that you use NuvaRing. They
can tell you if you need to take additional contraceptive precautions (for example, male condoms) and
if so, for how long, or, whether the use of another medicine you need must be changed.
Some medicines
can have an influence on the blood levels of NuvaRing;
can make it
less effective in preventing pregnancy
can cause unexpected bleeding.
These include medicines used for the treatment of:
epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine,
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);
depressive moods (the herbal remedy St. John’s wort (Hypericum perforatum)).
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 female condom.
NuvaRing may influence the effect of other medicines, e.g.
- medicines containing ciclosporin
- the anti-epileptic lamotrigine (this could lead to an increased frequency of seizures)
Do not use NuvaRing if you have Hepatitis C and are taking medicinal products containing
ombitasvir/paritaprevir/ritonavir and dasabuvir as this may cause increases in liver function blood test
results (increase in ALT liver enzyme).
Your doctor will prescribe another type of contraceptive prior to the start of treatment with these
medicinal products.
NuvaRing can be restarted approximately 2 weeks after completion of this treatment. See section 2.1
When you should not use NuvaRing’
Ask your doctor or pharmacist for advice before taking any medicine.
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 and immediately reinsert it.
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.
2.5
Pregnancy and breast-feeding
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 3.5 ‘
When you want to
stop using NuvaRing’.
NuvaRing is not usually recommended for use during breast-feeding. If you wish to use NuvaRing
while breast-feeding, please seek the advice of your doctor.
2.6
Driving and using machines
NuvaRing is unlikely to affect your ability to drive or use machines.
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 put in 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 weeks in a row. Regularly
check that NuvaRing is 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. These contraceptive barrier methods should not
be used 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
Before inserting the ring, check that it is not out of date (see section 5 ‘
How to store
NuvaRing’
Wash your hands before inserting or removing the ring.
Choose the position for inserting that is most comfortable to you, like standing with one leg up,
squatting, or lying down.
Remove NuvaRing from its sachet.
Hold the ring between your thumb and index finger, press the opposite sides together and insert
the ring into the vagina (see Figures 1– 4). Alternatively, you may choose to use the NuvaRing
Applicator (not included with NuvaRing) to help you insert the ring. The NuvaRing Applicator
may not be available in all countries. When NuvaRing is in place you should not feel anything.
If you feel uncomfortable, gently push NuvaRing a bit farther into the vagina. The exact
position of the ring inside the vagina is not important.
After 3 weeks you remove NuvaRing from the vagina. You can do this by hooking your index
finger under the front rim of the ring or by grasping the rim and pulling it out (see Figure 5). If
you locate the ring in your vagina, but are unable to remove it, you should contact your doctor.
Dispose of the used ring with the normal household waste, preferably inside the reclosable
sachet. Do not flush NuvaRing down the toilet.
Figure 1
Take NuvaRing out of the
sachet
Figure 2
Compress the ring
Figure 3
Choose a comfortable position to insert the ring
Figure 4A
Figure 4B
Figure 4C
Insert the ring into the vagina with one hand (Figure 4A), if necessary the labia may be spread
with the other. Push the ring into the vagina until the ring feels comfortable (Figure 4B). Leave
the ring in place for 3 weeks (Figure 4C).
Figure 5
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.
3.2
Three weeks in, one week out
Starting with the day you put it in, the vaginal ring must be left in place
without interruption
for 3 weeks.
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.
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.
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 normally have 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 implant or a progestagen-releasing 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.
3.4
What to do if…
Your 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, you should regularly check whether the ring is still in your vagina
(for example, before and after intercourse).
If the ring is out for less than 3 hours it will still protect you from pregnancy. You can rinse the ring
with cold to lukewarm water (do not use hot water) and put it back in. If the ring is out for more than
3 hours, it may not protect you from pregnancy, see the advice in section 3.4 ‘
What to do if… Your
ring has temporarily been out of the vagina
’.
Your ring has temporarily been out of the vagina
When it is in the vagina, NuvaRing slowly releases hormones into the body to prevent pregnancy. If
the ring has been out of the vagina for more than 3 hours, it may not protect you from pregnancy. So,
the ring must not be outside the vagina for longer than 3 hours in every twenty-four hour period.
If the ring has been out of the vagina for
less than 3 hours
, it will still protect you from
pregnancy. You should put the ring back in as soon as possible but at the latest within 3 hours.
If the ring has been out of the vagina, or you suspect that the ring has been out of the vagina, for
more than 3 hours during the 1st and 2
nd
week
, it may not protect you from pregnancy. 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 1
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.
If the ring has been out of the vagina, or you suspect that the ring has been out of the vagina, for
more than 3 hours in the 3
rd
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 three-week use period. You may not have your period, but breakthrough
bleeding and spotting may occur.
2 – 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.
If NuvaRing was out of the vagina for 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. If you notice that your NuvaRing has broken, discard it and start
with a new ring as soon as possible. Use extra contraceptive precautions (e.g. a male condom) during
the next 7 days. If you had sexual intercourse before you noticed the ring breakage, please contact
your doctor.
You have inserted more than one ring
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
longer than 7 days
, put a new ring 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 period usually begins on a Friday, you can change this to a Tuesday (3 days
earlier) from next month onwards. Simply insert your next ring 3 days earlier than usual.
If you make your ring-free interval very short (for example, 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.
If you are not sure how to proceed, contact your doctor for advice.
You want to delay your menstrual period
Although it is not the recommended regimen, 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 can ask your doctor for advice before deciding to delay your menstrual period.
3.5
When 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.
Possible side effects
Like all medicines, NuvaRing can cause side effects, although not everybody gets them. If you get any
side effect, particularly if severe or persistent, or have any change to your health that you think may
be due to NuvaRing, please talk to your doctor.
An increased risk of blood clots in your veins (venous thromboembolism (VTE)) or blood clots in
your arteries (arterial thromboembolism (ATE)) is present for all women taking combined hormonal
contraceptives. For more detailed information on the different risks from taking combined hormonal
contraceptives, please see section 2, “What you need to know before you use NuvaRing”.
If you are allergic to one of the ingredients of Nuvaring (hypersensitivity) you may experience the
following symptoms (frequency unknown): angioedema [swollen face, tongue and/or throat and/or
difficulty swallowing] or hives together with difficulty breathing. If this happens, remove NuvaRing
and contact your doctor immediately.
Users of NuvaRing have reported the following side effects.
Common: may affect up to 1 in 10 women
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; pelvic pain; painful menstrual periods
acne
weight gain
the ring falling out
Uncommon: may affect up to 1 in 100 women
disturbed vision; dizziness
swollen abdomen; vomiting, diarrhoea or constipation
feeling tired, unwell or irritable; mood changes; mood swings
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 in 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 (growths in the cervix); rolling outward of the
margin of the cervix (ectropion)
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 (fungal and bacterial); burning feeling, smell, pain, discomfort or dryness in
the vagina or vulva
hair loss, eczema, itching, rash or hot flushes
ring breakage
Rare: may affect up to 1 in 1,000 women
harmful blood clots in a vein or artery, for example:
in a leg or foot (i.e. DVT)
in a lung (i.e. PE)
heart attack
stroke
mini-stroke or temporary stroke-like symptoms, known as a transient ischaemic attack
(TIA)
blood clots in the liver, stomach/intestine, kidneys or eye.
The chance of having a blood clot may be higher if you have any other conditions that increase this
risk. (See section 2 for more information on the conditions that increase risk for blood clots and the
symptoms of a blood clot.)
breast discharge
Not known (cannot be estimated from the available data)
chloasma (yellowish-brown pigmentation patches on the skin, particularly of the face)
penis discomfort of the partner (such as irritation, rash, itching)
inability to remove ring without medical assistance (e.g., because of adherence to vaginal wall)
Breast cancer and liver tumours have been reported in users of combined hormonal contraceptives.
For more information, see section 2.2
Warnings and precautions, Cancer
Reporting of side effects
If you get any side effects, talk to your doctor, nurse or pharmacist. This includes any possible side
effects not listed in this leaflet.
You can also report side effects directly (see details below). By reporting side effects, you can help
provide more information on the safety of this medicine.
United Kingdom:
Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA
Yellow Card in the Google Play or Apple App Store
Ireland:
HPRA Pharmacovigilance Earlsfort Terrace, IRL - Dublin 2 Tel: +353 1 6764971, Fax:
+353 1 6762517, Website: www.hpra.ie; e-mail: medsafety@hpra.ie.
Malta:
ADR Reporting at: www.medicinesauthority.gov.mt/adrportal
5.
How to store NuvaRing
Keep NuvaRing out of the sight and reach of children.
If you discover that a child has been exposed to the hormones from NuvaRing, ask your doctor for
advice.
Store below 30
C. Store in the original package in order to protect from light and moisture.
Do not use a NuvaRing if it was dispensed to you more than 4 months ago. The dispensing date is
stated on the carton and sachet.
Do not use NuvaRing after the expiry date which is stated on the carton and sachet.
Do not use NuvaRing if you notice a colour change in the ring or any visible signs of deterioration.
Dispose of the used ring with the normal household waste, preferably inside the reclosable sachet. Do
not flush NuvaRing down the toilet. As with other medicines, do not throw away unused or outdated
rings via wastewater or household waste. Ask your pharmacist how to throw away any unused rings
no longer required. These measures will help protect the environment.
6.
Contents of the pack and other information
What NuvaRing contains
The active substances are: etonogestrel (11.7 mg) and ethinylestradiol (2.7 mg)
The other ingredients are: ethylene vinylacetate copolymers (28% and 9% vinylacetate) (a type
of plastic that will not dissolve in the body) and magnesium stearate.
Etonogestrel and ethinylestradiol are released from the ring at a rate of 0.120 mg/day and
0.015 mg/day, each for 3 weeks.
What NuvaRing looks like and contents of the pack
NuvaRing is a flexible, transparent, colourless to almost colourless ring, 54 mm wide.
Each ring is packed in a reclosable foil sachet. The sachet is packed in a cardboard box together with
this package leaflet. Each box contains 1 or 3 rings.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holders
The Marketing Authorisation Holder
in the UK and Malta is Merck Sharp & Dohme Ltd, Hertford
Road, Hoddesdon, Hertfordshire, EN11 9BU, UK.
The Marketing Authorisation Holder
in Ireland is Merck Sharp & Dohme Ireland (Human Health)
Ltd, Red Oak North, South County Business Park, Leopardstown, Dublin 18, Ireland.
Manufacturer:
N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands.
This medicinal product is authorised in the Member States of the EEA under the following
name:
NuvaRing
0.120 mg/0.015 mg per 24 hours, vaginal delivery system
Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany,
Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, The Netherlands,
Norway, Romania, Poland, Portugal, Slovak Republic, Slovenia, Spain, Sweden, United Kingdom.
This leaflet was last revised in July 2017.
© Merck Sharp & Dohme Limited, 2017. All rights reserved.
PIL.NVRNG.17.UK.5034.WS 232
Object 1
Nuvaring
Summary of Product Characteristics Updated 17-Jan-2018 | Merck Sharp & Dohme Limited
1. Name of the medicinal product
NuvaRing®, 0.120 mg/0.015 mg per 24 hours, vaginal delivery system
2. Qualitative and quantitative composition
NuvaRing contains 11.7 mg etonogestrel and 2.7 mg ethinylestradiol. The ring releases etonogestrel and
ethinylestradiol at an average amount of 0.120 mg and 0.015 mg respectively per 24 hours, over a period
of 3 weeks.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Vaginal delivery system.
NuvaRing is flexible, transparent, and colourless to almost colourless ring, with an outer diameter of 54
mm and a cross-sectional diameter of 4 mm.
4. Clinical particulars
4.1 Therapeutic indications
Contraception.
NuvaRing is intended for women of fertile age. The safety and efficacy have been established in women
aged 18 to 40 years.
The decision to prescribe NuvaRing should take into consideration the individual woman's current risk
factors, particularly those for venous thromboembolism (VTE), and how the risk of VTE with NuvaRing
compares with other combined hormonal contraceptives (CHCs) (see sections 4.3 and 4.4).
4.2 Posology and method of administration
Posology
To achieve contraceptive effectiveness, NuvaRing must be used as directed (see 'How to use NuvaRing'
and 'How to start NuvaRing').
Paediatric population
The safety and efficacy of NuvaRing in adolescents under the age of 18 have not been studied.
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. An optional alternative is to insert the ring using the
NuvaRing Applicator which is distributed separately or is included in the package. The NuvaRing
Applicator may not be available in all countries. The exact position of NuvaRing in the vagina is not
critical for the contraceptive effect of the ring (see Figures 1-4).
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, the woman should follow the instructions
given in section 4.2, 'What to do if the ring is temporarily outside the vagina' (for more information, see
also section 4.4, '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 22.00 h the ring should be removed again on the
Wednesday 3 weeks later at about 22.00 h. 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 (Figure 5). The used ring should be placed in the sachet (keep
out of the reach of children and pets) and discarded as described in section 6.6. 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 female vaginal barrier methods
NuvaRing may interfere with the correct placement and position of certain female barrier methods, such
as a diaphragm, cervical cap, or female condom. These contraceptive methods should not be used as
back-up methods with NuvaRing.
How to insert NuvaRing with fingers only:
Figure 1
Take NuvaRing out of the sachet
Figure 3
Choose a comfortable position to insert the ring
Figure 2
Compress the ring
Insert the ring into the vagina with one hand (Figure 4A), if necessary the labia may be spread with the
other. Push the ring into the vagina until the ring feels comfortable (Figure 4B). Leave the ring in place
for 3 weeks (Figure 4C).
Figure 5:
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.
How to insert NuvaRing with the applicator:
1: Prepare
Wash your hands before opening the package. Open ONLY
immediately before use. DO NOT use if the contents or packaging are
visibly damaged.
The applicator is for use with the NuvaRing ring ONLY, not with other
products.
Review the picture of the applicator to familiarise yourself with the
parts of the applicator.
A. Plunger
B. Finger Grip
C. Barrel
D. Barrel Opening
E. NuvaRing
2: Load & Position
Pull the plunger back gently until it stops.
Squeeze opposite sides of the ring together and insert the ring into the
barrel opening.
Gently push the ring into the barrel. The tip of the ring should stick out
slightly from the barrel opening.
Choose the position for inserting the ring that is most comfortable for
you, like lying down, squatting, or standing with one leg up.
3: Insert & Dispose
Place your thumb and middle finger on the finger grip.
Gently insert the barrel into the vagina until your fingers (on the finger
grip) touch your body.
Then use your index finger to gently push the plunger entirely into the
barrel.
Some women have experienced a brief mild pinching sensation when
using the applicator.
The ring is pushed out of the applicator. Gently remove the applicator.
Confirm that the ring is NOT in the applicator. Dispose of the used
applicator with the normal household waste. DO NOT flush the
applicator down the toilet. DO NOT reuse the applicator.
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 is
recommended in addition for the first 7 days of NuvaRing use.
Changing from a combined hormonal contraceptive
The woman should insert NuvaRing at the latest on the day following the usual tablet-free, patch-free or
placebo tablet interval of her previous combined hormonal contraceptive.
If the woman has been using her previous method consistently and correctly and if it is reasonably certain
that she is not pregnant she may also switch from her previous combined hormonal contraceptive on any
day of the cycle.
The hormone-free interval of the previous method should never be extended beyond its recommended
length.
Changing from a progestagen-only method (minipill, implant, or injection), or from a progestagen-
releasing intrauterine system [IUS].
The woman may switch on any day from the minipill (from an implant, or the IUS on the day of its
removal, from an injectable when the next injection would be due) but should in all of these cases use an
additional barrier method for the first 7 days of NuvaRing use.
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 mean time, she should be advised to use
an alternative contraceptive method.
Following delivery or second-trimester abortion
For breast-feeding women, see section 4.6.
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.
DEVIATIONS FROM THE RECOMMENDED REGIMEN
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 in case of a lengthened ring-free interval
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 the ring was temporarily outside the vagina
NuvaRing should be left in the vagina for a continuous period of 3 weeks. If the ring is accidentally
expelled, it can be rinsed with cool to lukewarm (not hot) water and should be reinserted immediately.
If NuvaRing has been out 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, or is suspected to have been out of the vagina for more than 3
hours during the 1
st
or 2
nd
week of use, 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 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, or is suspected to have been out of the vagina for more than 3
hours during the 3
rd
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 bleeding and insert a new ring no later than 7 days (7x24 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 in case of lengthened ring-use
Although this is not the recommended regimen, as long as NuvaRing has been used for maximally 4
weeks, contraceptive efficacy is still adequate. 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
If in exceptional cases a period needs to be delayed, 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.
4.3 Contraindications
CHCs should not be used in the following conditions. Should any of the conditions appear for the first
time during the use of NuvaRing, it should be removed immediately.
Presence or risk of venous thromboembolism (VTE)
o Venous thromboembolism - current VTE (on anticoagulants) or history of (e.g. deep venous thrombosis
[DVT] or pulmonary embolism [PE]).
o Known hereditary or acquired predisposition for venous thromboembolism, such as APC-resistance
(including Factor V Leiden), antithrombin-III-deficiency, protein C deficiency, protein S deficiency.
o Major surgery with prolonged immobilisation (see section 4.4).
o A high risk of venous thromboembolism due to the presence of multiple risk factors (see section 4.4).
Presence or risk of arterial thromboembolism (ATE)
o Arterial thromboembolism - current arterial thromboembolism, history of arterial thromboembolism
(e.g. myocardial infarction) or prodromal condition (e.g. angina pectoris).
o Cerebrovascular disease – current stroke, history of stroke or prodromal condition (e.g.
transient ischaemic attack, TIA).
o Known hereditary or acquired predisposition for arterial thromboembolism, such as
hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus
anticoagulant).
o History of migraine with focal neurological symptoms.
o A high risk of arterial thromboembolism due to multiple risk factors (see section 4.4) or to the presence
of one serious risk factor such as:
diabetes mellitus with vascular symptoms
severe hypertension
severe dyslipoproteinaemia.
Pancreatitis or a history thereof if associated with severe hypertriglyceridemia.
Presence or history of severe hepatic disease as long as liver function values have not returned to
normal.
Presence or history of liver tumours (benign or malignant).
Known or suspected malignant conditions of the genital organs or the breasts, if sex steroid-influenced.
Undiagnosed vaginal bleeding.
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 of NuvaRing
NuvaRing is contraindicated for concomitant use with medicinal products containing
ombitasvir/paritaprevir/ritonavir and dasabuvir (see sections 4.4 and section 4.5).
4.4 Special warnings and precautions for use
WARNINGS
If any of the conditions or risk factors mentioned below is present, the suitability of NuvaRing should be
discussed with the woman.
In the event of aggravation, or first appearance of any of these conditions or risk factors, the woman
should be advised to contact her doctor to determine whether the use of NuvaRing should be
discontinued.
1. Circulatory Disorders
Risk of venous thromboembolism (VTE)
The use of any combined hormonal contraceptive (CHC) increases the risk of venous thromboembolism
(VTE) compared with no use. Products that contain levonorgestrel, norgestimate or norethisterone
are associated with the lowest risk of VTE. Other products such as NuvaRing may have up to twice
this level of risk. The decision to use any product other than one with the lowest VTE risk should be
taken only after a discussion with the woman to ensure she understands the risk of VTE with
NuvaRing, how her current risk factors influence this risk, and that her VTE risk is highest in the
first ever year of use. There is also some evidence that the risk is increased when a CHC is re-
started after a break in use of 4 weeks or more.
In women who do not use a CHC and are not pregnant about 2 out of 10,000 will develop a VTE over
the period of one year. However, in any individual woman, the risk may be far higher, depending on her
underlying risk factors (see below).
It is estimated that out of 10,000 women who use a low dose CHC that contains levonorgestrel, about 6
will develop a VTE in one year. Inconsistent results on the risk of VTE with NuvaRing compared with
CHCs that contain levonorgestrel have been found (with relative risk estimates ranging from no increase,
RR=0.96, to an almost 2-fold increase, RR=1.90). This corresponds to between about 6 and 12 VTEs in a
year out of 10,000 women who use NuvaRing.
In both cases, the number of VTEs per year is fewer than the number expected in women during
pregnancy or in the postpartum period.
VTE may be fatal in 1-2 % of the cases.
Number of VTE events per 10,000 women in one year
Extremely rarely, thrombosis has been reported to occur in CHC users in other blood vessels, e.g.
hepatic, mesenteric, renal, or retinal veins and arteries.
Risk factors for VTE
The risk for venous thromboembolic complications in CHC users may increase substantially in a woman
with additional risk factors, particularly if there are multiple risk factors (see table).
NuvaRing is contraindicated if a woman has multiple risk factors that put her at high risk of venous
thrombosis (see section 4.3). If a woman has more than one risk factor, it is possible that the increase in
risk is greater than the sum of the individual factors – in this case her total risk of VTE should be
considered. If the balance of benefits and risks is considered to be negative, a CHC should not be
prescribed (see section 4.3).
Table: Risk factors for VTE
Risk factor
Comment
Obesity (body mass index over 30 kg/m
Risk increases substantially as BMI rises.
Particularly important to consider if other risk
factors also present.
Prolonged immobilisation, major surgery, any
surgery to the legs or pelvis, neurosurgery, or major
trauma
Note: Temporary immobilisation including air travel
> 4 hours can also be a risk factor for VTE,
particularly in women with other risk factors.
In these situations it is advisable to discontinue use
of the patch/pill/ring (in the case of elective surgery
at least four weeks in advance) and not resume until
two weeks after complete remobilisation. Another
method of contraception should be used to avoid
unintentional pregnancy.
Antithrombotic treatment should be considered if
NuvaRing has not been discontinued in advance.
Positive family history (venous thromboembolism
ever in a sibling or parent especially at a relatively
early age, e.g. before 50)
If a hereditary predisposition is suspected, the
woman should be referred to a specialist for advice
before deciding about any CHC use.
Other medical conditions associated with VTE
Cancer, systemic lupus erythematosus, haemolytic
uraemic syndrome, chronic inflammatory bowel
disease (Crohn's disease or ulcerative colitis) and
sickle cell disease
Increasing age
Particularly above 35 years
There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in the
onset or progression of venous thrombosis.
The increased risk of thromboembolism in pregnancy, and particularly the 6-week period of the
puerperium, must be considered (for information on "Pregnancy and lactation" see section 4.6).
Symptoms of VTE (deep vein thrombosis and pulmonary embolism)
In the event of symptoms women should be advised to seek urgent medical attention and to inform the
healthcare professional that she is taking a CHC.
Symptoms of deep vein thrombosis (DVT) can include:
- unilateral swelling of the leg and/or foot or along a vein in the leg;
- pain or tenderness in the leg which may be felt only when standing or walking;
- increased warmth in the affected leg; red or discoloured skin on the leg.
Symptoms of pulmonary embolism (PE) can include:
- sudden onset of unexplained shortness of breath or rapid breathing;
- sudden coughing which may be associated with haemoptysis;
- sharp chest pain;
- severe light headedness or dizziness;
- rapid or irregular heartbeat.
Some of these symptoms (e.g. “shortness of breath”, “coughing”) are non-specific and might be
misinterpreted as more common or less severe events (e.g. respiratory tract infections).
Other signs of vascular occlusion can include: sudden pain, swelling and slight blue discoloration of an
extremity.
If the occlusion occurs in the eye symptoms can range from painless blurring of vision which can
progress to loss of vision. Sometimes loss of vision can occur almost immediately.
Risk of arterial thromboembolism (ATE)
Epidemiological studies have associated the use of CHCs with an increased risk for arterial
thromboembolism (myocardial infarction) or for cerebrovascular accident (e.g. transient ischaemic attack,
stroke). Arterial thromboembolic events may be fatal.
Risk factors for ATE
The risk of arterial thromboembolic complications or of a cerebrovascular accident in CHC users
increases in women with risk factors (see table). NuvaRing is contraindicated if a woman has one serious
or multiple risk factors for ATE that puts her at high risk of arterial thrombosis (see section 4.3). If a
woman has more than one risk factor, it is possible that the increase in risk is greater than the sum of the
individual factors – in this case her total risk should be considered. If the balance of benefits and risks is
considered to be negative a CHC should not be prescribed (see section 4.3).
Table: Risk factors for ATE
Risk factor
Comment
Increasing age
Particularly above 35 years
Smoking
Women should be advised not to smoke if they wish
to use a CHC. Women over 35 who continue to
smoke should be strongly advised to use a different
method of contraception.
Hypertension
Obesity (body mass index over 30 kg/m
Risk increases substantially as BMI increases.
Particularly important in women with additional risk
factors
Positive family history (arterial thromboembolism
ever in a sibling or parent especially at relatively
early age, e.g. below 50)
If a hereditary predisposition is suspected, the
woman should be referred to a specialist for advice
before deciding about any CHC use.
Migraine
An increase in frequency or severity of migraine
during CHC use (which may be prodromal of a
cerebrovascular event) may be a reason for
immediate discontinuation.
Other medical conditions associated with adverse
vascular events
Diabetes mellitus, hyperhomocysteinaemia, valvular
heart disease and atrial fibrillation,
dyslipoproteinaemia and systemic lupus
erythematosus.
Symptoms of ATE
In the event of symptoms women should be advised to seek urgent medical attention and to inform the
healthcare professional that she is taking a CHC.
Symptoms of a cerebrovascular accident can include:
- sudden numbness or weakness of the face, arm or leg, especially on one side of the body;
- sudden trouble walking, dizziness, loss of balance or coordination;
- sudden confusion, trouble speaking or understanding;
- sudden trouble seeing in one or both eyes;
- sudden, severe or prolonged headache with no known cause;
- loss of consciousness or fainting with or without seizure.
Temporary symptoms suggest the event is a transient ischaemic attack (TIA).
Symptoms of a myocardial infarction (MI) can include:
- pain, discomfort, pressure, heaviness, sensation of squeezing or fullness in the chest, arm, or below the
breastbone;
- discomfort radiating to the back, jaw, throat, arm, stomach;
- feeling of being full, having indigestion or choking;
- sweating, nausea, vomiting or dizziness;
- extreme weakness, anxiety, or shortness of breath;
- rapid or irregular heartbeats.
In case of suspected or confirmed VTE or ATE, CHC use should be discontinued. Adequate
contraception should be initiated because of the teratogenicity of anti-coagulant therapy (coumarins).
2. Tumours
Epidemiological studies indicate that the long-term use of oral contraceptives displays a risk factor for
the development of cervical cancer in women infected with human papillomavirus (HPV). However, there
is still uncertainty about the extent to which this finding is influenced by confounding effects (e.g.
differences in number of sexual partners or in use of barrier contraceptives). No epidemiological data on
the risk of cervical cancer in users of NuvaRing are available (see 'medical examination/consultation').
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. 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 hemorrhages.
Therefore, a hepatic tumour should be considered in the differential diagnosis when severe upper
abdominal pain, liver enlargement or signs of intra-abdominal hemorrhage occur in women using
NuvaRing.
3. ALT elevations
During clinical trials with patients treated for hepatitis C virus infections (HCV) with medicinal
products containing ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin,
transaminase (ALT) elevations higher than 5 times the upper limit of normal (ULN) occurred
significantly more frequently in women using ethinylestradiol-containing medications such as combined
hormonal contraceptives (CHCs) (see sections 4.3 and 4.5).
4. Other conditions
Women with hypertriglyceridemia, 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. A definitive relationship between hormonal
contraceptive use and clinical hypertension has not been established. 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;
hemolytic 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 oestrogens and progestagens 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 hormonal
contraception. However, diabetic women should be carefully monitored while using NuvaRing especially
in the first months of use.
New onset or deterioration of Crohn's disease and ulcerative colitis has been reported to occur with the
use of hormonal contraceptives, but the evidence of an association with its use is inconclusive.
Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women
with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst 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.
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, or that the use of NuvaRing affects
the treatment of vaginitis (see section 4.5).
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.
MEDICAL EXAMINATION/CONSULTATION
Prior to the initiation or reinstitution of NuvaRing use a complete medical history (including family
history) should be taken and pregnancy must be ruled out. Blood pressure should be measured and a
physical examination should be performed, guided by the contraindications (see section 4.3) and warnings
(see section 4.4). It is important to draw a woman's attention to the information on venous and arterial
thrombosis, including the risk of NuvaRing compared with other CHCs, the symptoms of VTE and ATE,
the known risk factors and what to do in the event of a suspected thrombosis.
The woman should also be instructed to carefully read the user leaflet and to adhere to the advice given.
The frequency and nature of examinations should be based upon established practice guidelines and be
adapted to the individual woman.
Women should be advised that hormonal contraceptives do 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 (section 4.2), or when
concomitant medications that decrease the plasma concentration of ethinylestradiol and/or etonogestrel
are used (section 4.5).
REDUCED CYCLE CONTROL
Irregular bleeding (spotting or breakthrough bleeding) may occur during the use of NuvaRing. 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 in section 4.2, 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 very rare occasions NuvaRing has been reported to get disconnected during use (see section 4.5). The
woman is advised to remove the broken ring and reinsert a new ring as soon as possible and use a barrier
method such as a male condom in addition for the next 7 days. The possibility of a pregnancy should be
considered and the woman should contact her physician.
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. Prolonged
expulsion may lead to contraceptive failure and/or breakthrough bleeding. Therefore, to ensure efficacy
the woman should be advised to regularly verify the presence of NuvaRing (for example, before and after
intercourse).
If NuvaRing is accidentally expelled and is left outside of the vagina for less than 3 hours contraceptive
efficacy is not reduced. The woman should rinse the ring with cool to lukewarm (not hot) water and
reinsert it as soon as possible, but at the latest within 3 hours.
If NuvaRing has been out of the vagina, or is suspected to have been out of the vagina for more than 3
hours contraceptive efficacy may be reduced. In that case, the applicable advice given in section 4.2
'What to do if the ring was temporarily outside the vagina' should be followed.
Mid-point range of 5-7 per 10,000 WY, based on a relative risk for CHCs containing levonorgestrel
versus non-use of approximately 2.3 to 3.6
4.5 Interaction with other medicinal products and other forms of interaction
INTERACTIONS WITH OTHER MEDICINAL PRODUCTS
Note: The prescribing information of concomitant medications should be consulted to identify potential
interactions.
Effects of other medicinal products on NuvaRing
Interactions can occur with drugs or herbal products that induce microsomal enzymes which can result in
increased clearance of sex hormones and which may lead to breakthrough bleeding and/or contraceptive
failure.
Management
Enzyme induction can already be observed after a few days of treatment. Maximum enzyme induction is
generally seen within a few weeks. After the cessation of drug therapy, enzyme induction may be
sustained for about 4 weeks.
Short-term treatment
Women on treatment with enzyme-inducing drugs or herbal products should temporarily use a barrier
method or another method of contraception in addition to NuvaRing. Note: NuvaRing should not be used
with a diaphragm, cervical cap, or female condom. The barrier method must be used during the whole
time of the concomitant drug therapy and for 28 days after its discontinuation. 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 interval.
Long-term treatment
In women on long-term treatment with hepatic enzyme-inducing active substances, another reliable, non-
hormonal method of contraception is recommended.
The following interactions have been reported in the literature.
Substances increasing the clearance of combined hormonal contraceptives
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, 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.
Substances with variable effects on the clearance of combined hormonal contraceptives
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
HCV medicinal products (e.g. boceprevir, telaprevir), can increase or decrease plasma concentrations of
progestagens, including etonogestrel, or estrogen. The net effect of these changes may be clinically
relevant in some cases.
Substances decreasing the clearance of combined hormonal contraceptives
The clinical relevance of potential interactions with enzyme inhibitors remains unknown.
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 progestogens, including etonogestrel.
Based on pharmacokinetic data, vaginally administered antimycotics and spermicides are unlikely to
affect the contraceptive efficacy and safety of NuvaRing. During concomitant use of antimycotic ovules
the chance of ring disconnection may be slightly higher (see section 4.4, 'Broken Rings').
Hormonal contraceptives may interfere with the metabolism of other drugs. Accordingly, plasma and
tissue concentrations may either increase (e.g. ciclosporin) or decrease (e.g. lamotrigine).
Pharmacodynamic interactions
Concomitant use with medicinal products containing ombitasvir/paritaprevir/ritonavir and dasabuvir, with
or without ribavirin, may increase the risk of ALT elevations (see sections 4.3 and 4.4). Therefore,
NuvaRing users must switch to an alternative method of contraception (e.g., progestagen-only
contraception or non-hormonal methods) prior to starting therapy with this combination drug regimen.
NuvaRing can be restarted 2 weeks following completion of treatment with this combination drug
regimen.
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.
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 advice for 'What to do if the ring was temporarily outside the vagina').
4.6 Fertility, pregnancy and lactation
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.
Pregnancy
NuvaRing is not indicated during pregnancy. If pregnancy occurs with NuvaRing in situ, the ring should
be removed. Extensive epidemiological studies have revealed neither an increased risk of birth defects in
children born to women who used COCs prior to pregnancy, nor a teratogenic effect when COCs were
used inadvertently during early pregnancy.
A clinical study in a small number of women showed that despite the intravaginal administration,
intrauterine concentrations of contraceptive steroids with NuvaRing are similar to the levels observed in
COC users (see section 5.2). Clinical experience of the outcomes of pregnancies exposed to NuvaRing
has not been reported.
The increased risk of VTE during the postpartum period should be considered when re-starting NuvaRing
(see sections 4.2 and 4.4).
Breastfeeding
Lactation may be influenced by oestrogens, 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. Small amounts of the contraceptive steroids and / or their
metabolites may be excreted with the milk but there is no evidence that this adversely affects the infant's
health.
4.7 Effects on ability to drive and use machines
On the basis of the pharmacodynamic profile, NuvaRing has no or negligible influence on the ability to
drive and use machines.
4.8 Undesirable effects
The most frequently reported undesirable effects in the clinical trials with NuvaRing were headache and
vaginal infections and vaginal discharge, each reported by 5-6% of the women.
Description of selected adverse reactions
An increased risk of arterial and venous thrombotic and thromboembolic events, including myocardial
infarction, stroke, transient ischaemic attacks, venous thrombosis and pulmonary embolism has been
observed in women using CHCs, which are discussed in more detail in section 4.4.
Also other undesirable effects have been reported in women using CHCs: these are discussed in more
detail in section 4.4.
Adverse drug reactions that have been reported in clinical trials, observational studies, or during
postmarketing use with NuvaRing are listed in the Table below. The most appropriate MedDRA term to
describe a certain adverse event 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).
System Organ
Class
Common
Uncommon
Rare
Not known
Infections and
infestations
Vaginal infection
Cervicitis, Cystitis,
Urinary tract
infection
Immune system
disorders
Hypersensitivity
Metabolism and
nutrition disorders
Increased appetite
Psychiatric
disorders
Depression, Libido
decreased
Affect lability,
Mood altered,
Mood swings
Nervous system
disorders
Headache, Migraine
Dizziness,
Hypoaesthesia
Eye disorders
Visual disturbance
Vascular disorders
Hot flush
Venous
thromboembolism
Arterial
thromboembolism
Gastrointestinal
disorders
Abdominal pain,
Nausea
Abdominal
distension,
Diarrhoea,
Vomiting,
Constipation
Skin and
subcutaneous
tissue disorders
Acne
Alopecia, Eczema,
Pruritus, Rash
Chloasma
Urticaria
Musculoskeletal
and connective
tissue disorders
Back pain, Muscle
spasms, Pain in
extremity
Renal and urinary
disorders
Dysuria,
Micturition
urgency,
Pollakiuria
Reproductive
system and breast
disorders
Breast tenderness,
Genital pruritus
female,
Dysmenorrhoea,
Pelvic pain, Vaginal
discharge
Amenorrhoea,
Breast discomfort,
Breast
enlargement,
Breast mass,
Cervical polyp,
Coital bleeding,
Dyspareunia,
Ectropion of
cervix, Fibrocystic
breast disease,
Menorrhagia,
Metrorrhagia,
Pelvic discomfort,
Premenstrual
syndrome, Uterine
spasm, Vaginal
burning sensation,
Vaginal odour,
Vaginal pain,
Vulvovaginal
discomfort,
Vulvovaginal
dryness
Galactorrhoea
Penis disorders
General disorders
and administration
site conditions
Fatigue, Irritability,
Malaise, Oedema,
Sensation of
foreign body
Vaginal ring site tissue
overgrowth
Investigations
Weight increased
Blood pressure
increased
Injury, poisoning
and procedural
complications
Medical device
discomfort, Vaginal
contraceptive device
expelled
Contraceptive
device
complication,
Device breakage
) Listing of adverse events based on spontaneous reporting.
Hormone-dependent tumours (e.g. liver tumours, breast cancer) have been reported in association with
CHC use. For further information see section 4.4.
Interactions
Breakthrough bleeding and/or contraceptive failure may result from interactions of other drugs (enzyme
inducers) with hormonal contraceptives (see section 4.5).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
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.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other gynecologicals, Intravaginal contraceptives, vaginal ring with
progestagen and oestrogen, ATC code: G02BB01
Mechanism of action
NuvaRing contains etonogestrel and ethinylestradiol. Etonogestrel is a 19-nortestosterone-derived
progestagen and binds with high affinity to progesterone receptors in the target organs. Ethinylestradiol is
an oestrogen widely used in contraceptive products. The contraceptive effect of NuvaRing is based on
various mechanisms, the most important of which is the inhibition of ovulation.
Clinical efficacy and safety
Clinical studies were performed worldwide (US, EU, and Brazil) in women between the ages of 18 and
40 years. The contraceptive efficacy appeared to be at least comparable with that known for combined
oral contraceptives. The following table shows the Pearl Indices (number of pregnancies per 100 woman
years of use) found in the clinical studies with NuvaRing.
Analysis Method
Pearl Index
95 % CI
No of Cycles
ITT (user + method
failure)
0.96
0.64 – 1.39
37,977
PP (method failure)
0.64
0.35 – 1.07
28,723
With the use of higher-dosed COCs (0.05 mg ethinylestradiol) the risk of endometrial and ovarian cancer
is reduced. Whether this also applies to a lower-dosed contraceptive like NuvaRing remains to be
determined.
BLEEDING PATTERN
A large comparative study with 150/30 µg levonorgestrel/ethinylestradiol OC (n= 512 vs n= 518)
evaluating vaginal bleeding characteristics over 13 cycles showed low incidences of breakthrough
spotting or bleeding for NuvaRing (2.0-6.4%). Furthermore, vaginal bleeding was exclusively restricted
to the ring-free interval for most subjects (58.8-72.8 %).
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. No adverse effects on
bone mass have been observed.
Paediatric population
The safety and efficacy of NuvaRing in adolescents under the age of 18 have not been studied.
5.2 Pharmacokinetic properties
Etonogestrel
Absorption
Etonogestrel released by NuvaRing is rapidly absorbed by the vaginal mucosa. Maximum serum
concentrations of etonogestrel of approximately 1,700 pg/mL are reached at about 1 week after insertion.
Serum concentrations show small fluctuations and slowly decrease to approximately 1,600 pg/mL after 1
week, 1,500 pg/mL after 2 weeks and 1,400 pg/mL after 3 weeks of use. Absolute bioavailability is
approximately 100%, which is higher than after oral administration. Cervical and intrauterine etonogestrel
levels were measured in a small number of women using NuvaRing or an oral contraceptive containing
0.150 mg desogestrel and 0.020 mg ethinylestradiol. The observed levels were comparable.
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.
Biotransformation
Etonogestrel is metabolized 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.
Elimination
Etonogestrel serum levels decrease in two phases. The terminal elimination phase is characterized 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 pg/mL are reached 3 days after insertion and decrease to 19 pg/mL after 1
week, 18 pg/mL after 2 weeks and 18 pg/mL after 3 weeks of use. The monthly systemic ethinylestradiol
exposure (AUC
0-ω
) with NuvaRing is 10.9 ng.h/mL. Absolute bioavailability is approximately 56%,
which is comparable with oral administration of ethinylestradiol. Cervical and intrauterine
ethinylestradiol levels were measured in a small number of women using NuvaRing or an oral
contraceptive containing 0.150 mg desogestrel and 0.020 mg ethinylestradiol. The observed levels were
comparable.
Distribution
Ethinylestradiol is highly but non-specifically bound to serum albumin. An apparent volume of
distribution of about 15 L/kg was determined.
Biotransformation
Ethinylestradiol is primarily metabolized 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.
Elimination
Ethinylestradiol serum levels decrease in two phases. The terminal elimination phase is characterized 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.
Special populations
Paediatric population
The pharmacokinetics of NuvaRing in healthy postmenarcheal female adolescents under the age of 18
have not been studied.
Effect of renal impairment
No studies were performed to evaluate the effect of renal disease on the pharmacokinetics of NuvaRing.
Effect of hepatic impairment
No studies were conducted to evaluate the effect of hepatic disease on the pharmacokinetics of NuvaRing.
However, steroid hormones may be poorly metabolized in women with impaired liver function.
Ethnic groups
No formal studies were performed to assess pharmacokinetics in ethnic groups.
5.3 Preclinical safety data
Non-clinical data with ethinylestradiol and etonogestrel reveal no special hazard for humans based on
conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential,
and toxicity to reproduction, other than those already known for humans.
Environmental Risk Assessment (ERA)
Environmental risk assessment studies have shown that 17α-ethinylestradiol and etonogestrel may pose a
risk to surface water organisms (see section 6.6).
6. Pharmaceutical particulars
6.1 List of excipients
Ethylene vinylacetate copolymer, 28% vinylacetate;
ethylene vinylacetate copolymer, 9% vinylacetate;
magnesium stearate.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
40 months.
6.4 Special precautions for storage
Prior to dispensing:
3 years, store in a refrigerator (2 °C - 8 °C).
At the time of dispensing:
The dispenser places a date of dispensing on the packaging. The product should be inserted no later than 4
months from the date of dispensing, but in all cases prior to the expiry date, whichever comes first.
After dispensing:
4 months, store below 30°C.
Store in the original package in order to protect from light and moisture.
6.5 Nature and contents of container
NuvaRing
Sachet containing one NuvaRing. The sachet is made of aluminum foil with an inner layer of low-density
polyethylene and an outer layer of polyethylene terephthalate (PET). It is reclosable and waterproof. The
sachet is packed in a printed cardboard box together with the package leaflet.
NuvaRing Applicator
Distributed separately or included in the package. The NuvaRing Applicator may not be available in all
countries. The applicator is a plastic, non-sterile device made from a polypropylene polymer, containing a
friction reduction additive (comprising of less than 5%). It is intended for single use (i.e. disposable).
Each applicator is individually packed. The applicator has a CE marking which is embossed on the
device.
The product is supplied as:
- Pack of 1 ring
- Pack of 1 ring and 1 applicator
- Pack of 3 rings
- Pack of 3 rings and 3 applicators
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
NuvaRing
See section 4.2. The dispenser has to indicate the date of dispensing on the packaging. It is recommended
for the 3-rings presentation to indicate this date on the ply carton as well as on the sachet. NuvaRing
should be inserted no later than 4 months from the date of dispensing, but in all cases prior to the expiry
date, which ever comes first. 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. This
medicinal product may pose a risk to the environment (see section 5.3). NuvaRing should not be flushed
down the toilet. Any unused (expired) rings should be disposed of in accordance with local requirements.
NuvaRing Applicator
The NuvaRing Applicator must not be reused; it is designed for one time use. If the applicator is
accidently dropped, it should be washed with cool to lukewarm (NOT hot) water. The applicator should
be disposed of with the normal household waste immediately after use. It should not be flushed down the
toilet.
7. Marketing authorisation holder
Merck Sharp & Dohme Limited
Hertford Road
Hoddesdon
Hertfordshire
EN11 9BU
8. Marketing authorisation number(s)
PL 00025/0565
9. Date of first authorisation/renewal of the authorisation
05 June 2008/12 June 2011
10. Date of revision of the text
11 January 2018
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Prescription Only Medicine
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