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DEPO-PROVERA 150MG/ML

Active substance(s): MEDROXYPROGESTERONE ACETATE

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Page 1

Page 4

Possible risk of weight gain:
Some women gained weight while using
Depo-Provera. Studies show that over the
first 1-2 years of use, the average weight
gain was 5-8 lbs. Women completing 4-6
years of therapy gained an average of
14-16.5 lbs.
Reporting of side effects
If you get any side effects, talk to your
doctor or pharmacist. This includes any
possible side effects not listed in this
leaflet. You can also report side effects
directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard. By reporting
side effects you can help provide more
information on the safety of this medicine.
5. How to store Depo-Provera

Manufacturer and Product Licence
Holder
This product is manufactured by Pfizer
Manufacturing
Belgium
N.V./S.A.,
Rijksweg 12, B-2870 Puurs, Belgium.
It is procured from within the EU by the
Product Licence Holder Swinghope Ltd.,
Brandon House, Marlowe Way, Croydon
CR0 4XS and repackaged by Interport
Ltd., Brandon House, Marlowe Way,
Croydon CR0 4XS.
POM

T05214

DEPO-PROVERA® 150 mg/ml
medroxyprogesterone acetate
Patient Information Leaflet

Please read all of this leaflet carefully
before you start using this medicine
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, pharmacist or nurse.
• This medicine has been prescribed for
you only. Do not pass it on to others. It
may harm them, even if their signs of
illness are the same as yours.
• If you get any of the side effects, talk to
your doctor, nurse or healthcare provider.
This includes any possible side effects
not listed in this leaflet. See section 4.

PL No: 10380/0981

Leaflet revision date: 22/10/2014
Depo-Provera is a registered trademark of
Pharmacia Limited, UK

• Keep out of sight and reach of children.
• Depo-Provera will be carefully stored at
your doctor’s surgery, local pharmacy
or your clinic.
• Your doctor or pharmacist will ensure
that the vial is not stored above 25ºC
and not allowed to freeze.
• It should not be used after the expiry
date printed on the label and carton.

IMPORTANT
INFORMATION
YOU
SHOULD KNOW ABOUT DEPO-PROVERA
Depo-Provera is a very effective
injectable contraceptive which gives 12
weeks continuous contraception with
each injection. The effect is not
reversible once the injection is given.
• You must have injections of this
contraceptive regularly every 12 weeks;
otherwise you may risk becoming
pregnant (see section 3).
• Depo-Provera may not be suitable for
every woman. You will need to discuss
with
your
doctor
or
healthcare
professional providing your contraception
on whether it is suitable for you,
especially if you wish to use it for more
than 2 years (See section 1).
• Depo-Provera may not be suitable for you
if you have a history of certain medical
conditions (see section 2) or if you are
taking
a
medicine
called
aminoglutethiamide that thins the blood
(see section 2). Your doctor or nurse
should take a full medical history before
prescribing Depo-Provera.
• Regular use of Depo-Provera causes a
gradual loss of bone mineral density (see
section 4). For a small number of patients
that were followed-up, the average bone
mineral density returned to average 1-3
years after they stopped using
Depo-Provera.
Teenagers who are rapidly developing
their bones may be at particular risk and
should only use Depo-Provera if other
methods of contraception have been
discussed and considered unsuitable or
unacceptable.
• Your doctor may plan to conduct a
general medical as well as a
gynaecological examination before they
decide to prescribe Depo-Provera for you
and may request you to visit the clinic for
similar examinations at appropriate
intervals thereafter.

6. Further information
What Depo-Provera contains:
methylparahydroxybenzoate,
macrogol,
polysorbate
80,
propylparahydroxybenzoate, sodium chloride and water for
injection. Hydrochloric acid or sodium
hydroxide may also be added when the
product is being made to adjust the acidity
or alkalinity of the product to the correct
level.
What Depo-Provera looks like and
contents of the pack:
Depo-Provera is a white, opaque
suspension for injection. Depo-Provera is
available in a clear, glass vial with a rubber
stopper that has an aluminium seal and a
purple protective cap. The vial contains 1
millilitre of suspension. Each 1 ml of
suspension
contains
150
mg
of
medroxyprogesterone acetate as the
active ingredient.

What is in this leaflet
1. What Depo-Provera is and what it is
used for
2. What you need to know before you
use Depo-Provera
3. How to use Depo-Provera
4. Possible side effects
5. How to store Depo-Provera
6. Contents of the pack and other
information
1. What Depo-Provera is and what it is
used for
Depo-Provera
is
a
long
acting
contraceptive. This medicine contains
medroxyprogesterone acetate (MPA),
which is one of a group of medicines called
‘Progestogens’. It is similar to (but not the
same
as)
the
natural
hormone,
progesterone that is produced in the
ovaries during the second half of your
menstrual cycle.

Fold

Depo-Provera acts by preventing an egg
from fully developing and being released
from the ovaries during your menstrual
cycle. If an egg is not released it cannot
become fertilised by sperm and result in
pregnancy. Depo-Provera also causes
changes in the lining of your womb that
makes it less likely for pregnancy to occur.
It also thickens the mucus at the entrance
of the womb, making it more difficult for
sperm to enter.

Depo-Provera can be used:
• For long-term contraception where you
and the person who provides your
contraception (e.g. your doctor or
healthcare professional) have decided
that this method is the most suitable for
you.
• If you wish to use Depo-Provera for more
than 2 years your doctor or healthcare
professional may wish to re-evaluate the
risks and benefits of using Depo-Provera
to make sure that it is still the best option
for you.
• In teenagers only after other methods of
contraception have been discussed with
the healthcare professional who provides
your contraception and considered to be
unsuitable or unacceptable.
• For just one or two occasions in the
following cases:
• if your partner is undergoing a
vasectomy, to give you protection until
the vasectomy becomes effective
• if you are being immunised against
rubella, to prevent pregnancy during
the period of activity of the virus
• if you are awaiting sterilisation.
2. What you need to know before you
use Depo-Provera
Do not use Depo-Provera:
• If you are allergic (hypersensitive) to the
active ingredient (MPA) or any of the
other ingredients (listed in section 6).
There is a small risk of a severe allergic
reaction to Depo-Provera that will require
emergency medical treatment.
• If you think you may be pregnant.
• If you have had, or think you may have,
hormone-dependent cancer of the breast
or reproductive organs.
• If you have unexplained bleeding from
the womb (uterus).
• If you have liver disease.
• If you have not yet started your periods.
Warnings and precautions
Talk to your doctor or healthcare
professional before using Depo-Provera.
Before your doctor or healthcare
professional prescribes Depo-Provera,
you may need to have a physical
examination. It is important to tell your
doctor or healthcare professional if you
have, or have had in the past, any of the
following conditions. Your doctor will then
discuss with you whether Depo-Provera is
suitable for you.
• Migraine headaches – if you develop
migraine you should consult your doctor
before receiving further injections of
Depo-Provera
• Diabetes or a family history of diabetes
• Severe pain or swelling in the calf
(indicating a possible clot in the leg,
which may be called phlebitis)
• Blood clotting disorders such as deep
vein thrombosis (blood clot in the legs),
pulmonary embolus (blood clot in the
lung) or a stroke you should not receive
further injections of Depo-Provera
• Problems with your eyesight while using
Depo-Provera; for example a sudden
partial or complete loss of vision or
double vision
• Past history of or current depression
• Problems with your liver or liver disease
• Problems with your kidneys or kidney
disease
• History of heart disease or cholesterol
problems including any family history
• If you have recently had a ‘hydatidiform
mole’ which is a type of abnormal
pregnancy
• Asthma
• Epilepsy
• If you are using certain medicines such
as high dose glucocorticoids (steroids),
antiepileptics, and thyroid hormones. Tell
the
person
who
provides
your
contraception if you are taking these or
any other medicines - they may
recommend a more suitable method of
contraception.

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Page 2

Protection against sexually transmitted
diseases:
Depo-Provera does not protect against
HIV infection (AIDS) and other sexually
transmitted diseases.
Other medicines and Depo-Provera:
• Tell your doctor or pharmacist if you are
taking, have recently taken or might take
any other medicines.
• Tell your doctor or healthcare professional
if you are taking a medicine called
aminoglutethiamide or other medicines
that thin your blood (anticoagulants) as
these may affect the way Depo-Provera
works.
• Always tell your doctor or healthcare
professional who treats you that you are
using Depo-Provera as a contraceptive if
you are taking or have recently taken any
other medicines, even those you bought
yourself without a prescription, because
medicines can sometimes interact with
each other.
Pregnancy:
• Your doctor will check that you are not
pregnant before giving you the first
injection and also if any following
injection is delayed beyond 89 days (12
weeks and 5 days).
• Depo-Provera must not be taken if you
are pregnant as hormonal medicines can
affect the developing baby.
• If you think you may have become
pregnant while using Depo-Provera for
contraception,
tell
your
doctor
immediately.
Effect on future fertility:
• Your usual level of fertility should return
when the effect of the injection has worn
off.
• This takes different amounts of time in
different women, and does not depend on
how long you have been using
Depo-Provera.
• In studies, over 80% of women trying to
get pregnant conceived within 15 months
of the last injection; however this varied
from 4 months after the last injection to
more than two years.
• Some women have got pregnant as early
as 14 weeks after their last injection.
If you are breast-feeding:
• Depo-Provera does not prevent the
breast from producing milk so nursing
mothers can use it; however, it is better
for the baby that for the first few weeks
after birth its mother’s milk contains no
traces of any medicines, including
Depo-Provera.
• Your doctor or healthcare professional
may advise that you wait until at least 6
weeks after your baby has been born
before you start using Depo-Provera for
contraception.
• If a baby is exposed to Depo-Provera in
the breast milk, no harmful effects have
been seen in babies and children.
Driving and using machines:
Depo-Provera may cause headaches and
dizziness. Therefore be careful until you
know whether this medicine affects your
ability to drive or use machines. If you have
any concerns discuss them with your
doctor.
Depo-Provera contains methylparaben
(E218), propylparaben (E216) and
sodium:
Methylparaben and propylparaben may
cause
allergic
reactions
(possibly
delayed),
and
exceptionally,
bronchospasm.
This medicinal product contains less than
1 mmol sodium (23 mg) per 150 mg/ml, i.e.
essentially ‘sodium free’.
3. How to use Depo-Provera
This medicine will be given to you by
your doctor or healthcare professional.
(The last section of this leaflet contains
instructions for your doctor or healthcare
professional on how they should do this.)

Depo-Provera is given every 12 weeks as
a single intramuscular injection of 1 ml
(150 mg medroxyprogesterone acetate)
into the buttock or upper arm. The injection
is given during the first 5 days after the
beginning of a normal menstrual period.

pelvic pain, hot flushes, acne, hair loss,
rash, weakness or tiredness, injection site
reactions, feeling of weakness, tingling or
numbness in the hands and feet,
depression,
nervousness,
insomnia
(difficulty sleeping), irritability, anorgasmia
(failure
to
climax
during
sexual
intercourse),
emotional
disturbance,
intermenstrual bleeding (bleeding between
periods), menorrhagia (heavy periods).

Following childbirth the first Depo-Provera
injection can be given within 5 days after
childbirth if you are not breast-feeding.
Provided that the injection is given at the
times stated above, then you are protected
from pregnancy straight away and there is
no need to take extra precautions.

Uncommon (may affect up to 1 in 100
people)
Jaundice (this will cause yellowing of the
skin and the whites of the eyes),
hypertension,
varicose
veins,
thrombophlebitis (inflammation of part of a
vein), pulmonary embolism (blood clot in
the lungs which causes chest pain and
breathlessness), allergic reactions (such
as swelling on the face and throat),
abnormal liver enzymes (blood tests used
to measure liver function), feeling of
dizziness
or
‘spinning’,
abdominal
discomfort, change in weight, fluid
retention, joint pain, muscle cramps, pain
in
legs
and
arms,
somnolence
(sleepiness), migraine, convulsion (‘fit’),
vaginal dryness, painful periods, change in
breast size, painful intercourse, ovarian
cyst, premenstrual syndrome, infections of
the urinary tract or reproductive organs, an
increase in thickness of the lining of the
womb, dark patches on the skin, bruising,
excessive hair growth, itching, skin rash,
swelling, chest pain, fever, abnormal
cervical smear results, anxiety, difficulty
breathing.

Depo-Provera works as a contraceptive for
12 weeks in your body. There is no way of
reversing the injection once it is given.
For
effective
contraceptive
cover,
Depo-Provera MUST be given every 12
weeks. Make sure that you or your doctor
makes your next appointment for 12 weeks
time.
The risk of heavy or pro-longed vaginal
bleeding
may
be
increased
if
Depo-Provera is used immediately
following childbirth or termination of
pregnancy.
If you forget an injection of
Depo-Provera:
If you forget your injection or are late
getting your next injection (i.e. wait longer
than 12 weeks between injections), there
is a greater risk that you could become
pregnant. Ask your doctor or healthcare
professional to find out when you should
receive
your
next
injection
of
Depo-Provera and which type of
contraception should be used in the
meantime.

Rare (may affect up to 1 in 1,000 people)
Tachycardia (faster heart beat), breast
lumps
or
nipple
bleeding,
thirst,
hoarseness, rectal bleeding (bleeding from
the anus), paralysis, decreased glucose
tolerance (abnormal blood sugar levels),
breast cancer, anaemia (reduction in red
blood cells which can make the skin pale
and cause weakness or breathlessness).

Switching from other methods of
contraception:
When you switch from other contraceptive
methods, your doctor will make sure you
are not at risk of becoming pregnant by
giving you your first injection at the
appropriate time. If you switch from oral
contraceptives, you should have your first
injection of Depo-Provera within 7 days
after taking your last pill.

Not known (frequency cannot be
estimated from the available data):
Blood clotting disorders, deep vein
thrombosis (blood clots forming in the
veins, usually the legs), disturbed liver
function. osteoporosis (thinning of the
bones) including fractures, loss of bone
mineral density (a test to measure the
strength of bones), swelling of ankles or
wrists,
abnormal
uterine
bleeding
(irregular, increase, decrease), milky
discharge from breasts in women who are
not breastfeeding, vaginal cysts, milk
supply
stopping
(in
breastfeeding
mothers), feeling pregnant, delay in
becoming
pregnant
after
stopping
Depo-Provera,
scaling
of
skin,
scleroderma (a rare autoimmune disease
that affects the skin and other parts of the
body), weakness in the face muscles,
fainting, blood disorder, skin striae (stretch
marks).

If you have any further questions on the
use of this medicine, ask your doctor or
healthcare professional.
4. Possible side effects
Like all medicines, this medicine can
cause side effects although not everybody
gets them.
There is a low risk of anaphylactic
responses (serious allergic reactions
which may need urgent medical attention
or hospitalization). Possible symptoms
include: swelling of the face, lips, tongue or
throat, or difficulty breathing or swallowing,
skin rashes, shock or collapse.
Deep vein thrombosis (DVT) is a condition
in which a blood clot forms in one of your
deep veins, usually in your leg. Signs of
possible DVT include: swelling of the
affected leg, pain and tenderness in the
affected leg (you may also find it difficult to
stand properly with your full weight on the
affected leg), a change in the colour of your
skin, for example, redness or skin that
feels warm or hot to the touch.

Possible effect on your periods:
Depo-Provera will usually disturb the
pattern of a woman’s period.
After the first injection it is most likely that
you will have irregular, possibly lengthy
bleeding or spotting. This will continue in
some women. This is quite normal and
nothing to worry about.
One third of women will not have any
bleeding at all after the first injection. After
4 injections, most women find that their
periods have stopped completely. Not
having periods is nothing to worry about.

Women who use Depo-Provera tend to
have lower bone mineral density than
women of the same age who have never
used it. The effects of Depo-Provera are
greatest in the first 2-3 years of use.
Following this, bone mineral density tends
to stabilise and there appears to be some
recovery when Depo-Provera is stopped. It
is not yet possible to say whether DepoProvera increases the risk of osteoporosis
(weak bones) and fractures in later life.

If you experience very heavy or prolonged
bleeding you should talk to your doctor.
This happens rarely but can be treated.
When you stop taking Depo-Provera your
periods will return to normal in a few
months.

Tell your doctor immediately if you
experience any of the above symptoms.

Possible effects on your bones:
Depo-Provera works by lowering levels of
oestrogen and other hormones. However,
low oestrogen levels can cause bones to
become thinner (by reducing bone mineral
density). Women who use Depo-Provera
tend to have lower bone mineral density
than women of the same age who have
never used it. The effects of Depo-Provera
are greatest in the first 2-3 years of use.

The following other side effects may occur:
Common (may affect up to 1 in 10 people)
Abdominal pain or discomfort, bloating,
feeling sick, vaginal discharge or
inflammation, changes in appetite, back
pain, headaches, dizziness, irregular
periods, very light or no periods
(amenorrhoea), breast pain or tenderness,
Fold

Cervical smear testing:
The results of a cervical smear and some
laboratory tests could also be affected if
you are using Depo-Provera so it is
important that you tell your doctor.

Following this, bone mineral density tends
to stabilise and there appears to be some
recovery when Depo-Provera is stopped. It
is not yet possible to say whether DepoProvera increases the risk of osteoporosis
(weak bones) and fractures in later life.
The following are risk factors in the
development of osteoporosis in later life.
You should discuss with your doctor before
starting treatment if you have any of the
following as an alternative contraceptive
may be more suitable to your needs;
· Chronic alcohol and/or tobacco use
· Chronic use of drugs that can reduce
bone mass, e.g. epilepsy medication or
steroids
· Low body mass index or eating disorder,
e.g. anorexia nervosa or bulimia
· Previous low trauma fracture that was not
caused by a fall
· Strong family history of osteoporosis
Teenagers (up to 18 years): Normally, the
bones of teenagers are rapidly growing
and increasing in strength. The stronger
the bones are when adulthood is reached,
the greater the protection against
osteoporosis
in
later
life.
Since
Depo-Provera may cause teenage bones
to become thinner at a time when they
should be growing, its effect may be
particularly important in this age group.
Bones start to recover when Depo-Provera
is stopped, but it is not yet known whether
the bone mineral density reaches the
same levels as it would have if
Depo-Provera had never been used. You
should therefore discuss whether
another form of contraception might be
more suitable for you with the person
who provides your contraception
before starting Depo-Provera.
If you use Depo-Provera, it may help your
bones if you take regular weight-bearing
exercise and have a healthy diet, including
an adequate intake of calcium (e.g. in dairy
products) and vitamin D (e.g. in oily fish).
Possible risk of cancer:
Studies of women who have used different
forms of contraception found that women
who used Depo-Provera for contraception
had no increase in overall risk of
developing cancer of the ovary, womb,
cervix or liver.
Possible risk of breast cancer
Breast cancer is rare among women under
40 years of age whether or not they use
hormonal contraceptives. Depo-Provera
may increase the risk of breast cancer
slightly compared with women who have
never used it. However, any excess risk is
small in relation to the overall risk of breast
cancer, particularly in young women.
Older women have a higher baseline risk
of breast cancer and therefore the
increase in the number of cases due to
Depo-Provera is greater in older women
than in younger women.
In absolute terms this means that:
A 15 year old who uses Depo-Provera for 5
years increases her chance of developing
breast cancer by a negligible amount by
the age of 30.
A 25 year old who uses Depo-Provera for 5
years increases her chance of developing
breast cancer by the age of 40 from 44
cases per 10,000 women (without
Depo-Provera use) to up to 47 cases per
10,000 women i.e. an extra 3
cases/10,000.
A 35 year old who uses Depo-Provera for 5
years increases her chance of developing
breast cancer by the age of 50 from 160
cases per 10,000 women (without
Depo-Provera use) to 170 cases per
10,000 women i.e. an extra 10
cases/10,000.
Possible risk of forming an abscess at
the injection site:
As with any intramuscular injection, there
is a risk of an abscess forming at the site of
injection. This may require medical or
surgical attention.

T05214

FRONT PAGE

T05215

Depo-Provera® 150 mg/ml
Medroxyprogesterone

INFORMATION FOR DOCTORS AND PHARMICISTS
The following information is intended for medical or healthcare professionals only:
(For further information, consult the Summary of Product Characteristics.)
Description
Depo-Provera is a white, opaque suspension for injection. Each 1 ml of suspension contains
150 mg medroxyprogesterone acetate Ph. Eur. Excipients are methyl parahydroxybenzoate,
macrogol, polysorbate 80, propyl parahydroxybenzoate, sodium chloride, water for injection.
Hydrochloric acid or sodium hydroxide may be present as pH adjusters.
Uses
Depo-Provera is a long-term contraceptive agent suitable for use in women who have been
appropriately counselled concerning the likelihood of menstrual disturbance and the potential
for a delay in return to full fertility.
Depo-Provera may also be used for short-term contraception in the following circumstances:
(i) For partners of men undergoing vasectomy, for protection until the vasectomy becomes
effective.
(ii) In women who are being immunised against rubella, to prevent pregnancy during the
period of activity of the virus.
(iii) In women awaiting sterilisation.
Since loss of bone mineral density (BMD) may occur in females of all ages who use DepoProvera injection long-term, a risk/benefit assessment, which also takes into consideration
the decrease in BMD that occurs during pregnancy and/or lactation, should be considered.
Use in adolescents (12 – 18 years)
In adolescents, Depo-Provera may be used, but only after other methods of contraception
have been discussed with the patient and considered unsuitable or unacceptable.
It is of the greatest importance that adequate explanations of the long-term nature of the
product, of its possible side-effects and of the impossibility of immediately reversing the
effects of each injection are given to potential users and that every effort is made to ensure
that each patient receives such counselling as to enable her to fully understand these
explanations. Patient information leaflets are supplied by the manufacturer. It is
recommended that the doctor uses these leaflets to aid counselling of the patient before
giving the injection of Depo-Provera.
Consistent with good clinical practice, a general medical as well as a gynaecological
examination should be undertaken before administration of Depo-Provera and at appropriate
intervals thereafter.
Dosage
Each ml of suspension contains 150 mg medroxyprogesterone acetate. The sterile aqueous
suspension of Depo-Provera should be vigorously shaken just before use to ensure that the
dose being given represents a uniform suspension of Depo-Provera. Doses should be given
by deep intramuscular injection into the buttock or arm.
Care should be taken to ensure that the depot injection is given into the muscle tissue,
preferably the gluteus maximus, but other muscle tissue such as the deltoid may be used and
the site of injection should be cleansed using standard methods prior to administration of the
injection.
Assembly of syringe for single use:
1. Remove tip cap.
2. Position needle using aseptic technique.
3. Remove needle shield. The syringe is now ready for use.
Administration
Adults
First injection: To provide contraceptive cover in the first cycle of use, an injection of 150 mg
i.m. should be given during the first five days of a normal menstrual cycle. If the injection is
carried out according to these instructions, no additional contraceptive cover is required.
Postpartum: To increase assurance that the patient is not pregnant at the time of first
administration, this injection should be given within 5 days postpartum if not breast-feeding.
There is evidence that women prescribed Depo-Provera in the immediate puerperium can
experience prolonged and heavy bleeding. Because of this, the drug should be used with
caution in the puerperium. Women who are considering use of the product immediately
following delivery or termination should be advised that the risk of heavy or prolonged
bleeding may be increased.
Doctors are reminded that in the non breast-feeding postpartum patient, ovulation may occur
as early as week 4. If the puerperal woman will be breast-feeding, the initial injection should
be given no sooner than six weeks postpartum, when the infant’s enzyme system is more
fully developed. Further injections should be given at 12 week intervals.
Further doses: These should be given at 12 week intervals, however, as long as the injection
is given no later than five days after this time, no additional contraceptive measures (e.g.
barrier) are required.
(NB For partners of men undergoing vasectomy a second injection of 150 mg i.m. 12 weeks
after the first may be necessary in a small proportion of patients where the partner’s sperm
count has not fallen to zero.) If the interval from the preceding injection is greater than 89
days (12 weeks and five days) for any reason, then pregnancy should be excluded before the
next injection is given and the patient should use additional contraceptive measures (e.g.
barrier) for fourteen days after this subsequent injection.
Paediatric population (12-18 years): Depo-Provera is not indicated before menarche. Data in
adolescent females (12-18 years) is available. Other than concerns about loss of BMD, the
safety and effectiveness of Depo-Provera is expected to be the same for adolescents after
menarche and adult females.
Switching from other Methods of Contraception: Depo-Provera should be given in a manner
that ensures continuous contraceptive coverage. This should be based upon the mechanism
of action of other methods (e.g. patients switching from oral contraceptives should have their
first injection of Depo-Provera within 7 days of taking their last active pill).
Hepatic Insufficiency: The effect of hepatic disease on the pharmacokinetics of
Depo-Provera
is unknown. As Depo-Provera largely undergoes hepatic elimination it may be poorly
metabolised in patients with severe liver insufficiency (see Contraindications).
Renal Insufficiency: The effect of renal disease on the pharmacokinetics of Depo-Provera is
unknown. No dosage adjustment should be necessary in women with renal insufficiency,
since Depo-Provera is almost exclusively eliminated by hepatic metabolism.
Contraindications
Depo-Provera is contraindicated in patients with a known sensitivity to medroxyprogesterone
acetate or any ingredient of this medicine.
Depo-Provera should not be used during pregnancy, either for diagnosis or therapy.
Depo-Provera is contraindicated as a contraceptive at the above dosage in known or
suspected hormone-dependent malignancy of breast or genital organs.
Depo-Provera is contraindicated in patients with the presence or history of severe hepatic
disease whose liver function tests have not returned to normal.
Whether administered alone or in combination with oestrogen, Depo-Provera should not be
employed in patients with abnormal uterine bleeding until a definite diagnosis has been
established and the possibility of genital tract malignancy eliminated.

Special warnings and precautions for use
Warnings:
Loss of Bone Mineral Density:
Use of Depo-Provera reduces serum oestrogen levels and is associated with significant loss
of BMD due to the known effect of oestrogen deficiency on the bone remodelling system.
Bone loss is greater with increasing duration of use; however BMD appears to increase after
Depo-Provera is discontinued and ovarian oestrogen production increases. This loss of BMD
is of particular concern during adolescence and early adulthood, a critical period of bone
accretion. It is unknown if use of Depo-Provera by younger women will reduce peak bone
mass and increase the risk for fracture in later life.
A study to assess the BMD effects of medroxyprogesterone acetate IM (Depo-Provera,
DMPA) in adolescent females showed that its use was associated with a significant decline
in BMD from baseline. In the small number of women who were followed-up, mean BMD
recovered to around baseline values by 1- 3 years after discontinuing treatment. In
adolescents, Depo-Provera may be used, but only after other methods of contraception have
been discussed with the patients and considered to be unsuitable or unacceptable. In women
of all ages, careful re-evaluation of the risks and benefits of treatment should be carried out
in those who wish to continue use for more than 2 years. In particular, in women with
significant lifestyle and/or medical risk factors for osteoporosis, other methods of
contraception should be considered prior to use of Depo-Provera.
Significant risk factors for osteoporosis include:
• Alcohol abuse and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g., anticonvulsants or corticosteroids
• Low body mass index or eating disorder, e.g., anorexia nervosa or bulimia
• Previous low trauma fracture
• Family history of osteoporosis
A retrospective cohort study using data from the General Practice Research Database
(GPRD) reported that women using MPA injections (DMPA), have a higher risk of fracture
compared with contraceptive users with no recorded use of DMPA (incident rate ratio 1.41,
95% CI 1.35-1.47 for the five year follow-up period); it is not known if this is due to DMPA, or
to other related lifestyle factors which have a bearing on fracture rate. By contrast, in women
using DMPA, the fracture risk before and after starting DMPA was not increased (relative risk
1.08, 95% CI 0.92-1.26). Importantly, this study could not determine whether use of DMPA
has an effect on fracture rate later in life.
For further information on BMD changes in both adult and adolescent females, as reported
in recent clinical studies, refer to section 5.1 of the SPC. Adequate intake of calcium and
Vitamin D whether from the diet or from supplements is important for bone health in women
of all ages.
Menstrual Irregularity: The administration of Depo-Provera usually causes disruption of the
normal menstrual cycle. Bleeding patterns include amenorrhoea (present in up to 30% of
women during the first 3 months and increasing to 55% by month 12 and 68% by month 24);
irregular bleeding and spotting; prolonged (>10 days) episodes of bleeding (up to 33% of
women in the first 3 months of use decreasing to 12% by month 12). Rarely, heavy prolonged
bleeding may occur. Evidence suggests that prolonged or heavy bleeding requiring treatment
may occur in 0.5-4 occasions per 100 women years of use. If abnormal bleeding persists or
is severe, appropriate investigation should take place to rule out the possibility of organic
pathology and appropriate treatment should be instituted when necessary. Excessive or
prolonged bleeding can be controlled by the co-administration of oestrogen. This may be
delivered either in the form of a low dose (30 micrograms oestrogen) combined oral
contraceptive pill or in the form of oestrogen replacement therapy such as conjugated equine
oestrogen (0.625-1.25 mg daily). Oestrogen therapy may need to be repeated for 1-2 cycles.
Long-term co-administration of oestrogen is not recommended.
Return to Fertility: There is no evidence that Depo-Provera causes permanent infertility.
Pregnancies have occurred as early as 14 weeks after a preceding injection, however, in
clinical trials, the mean time to return of ovulation was 5.3 months following the preceding
injection. Women should be counselled that there is a potential for delay in return to full
fertility following use of the method, regardless of the duration of use, however, 83% of
women may be expected to conceive within 12 months of the first "missed" injection (i.e. 15
months after the last injection administered). The median time to conception was 10 months
(range 4-31) after the last injection.
Cancer Risks: Long-term case-controlled surveillance of Depo-Provera users found no
overall increased risk of ovarian, liver, or cervical cancer and a prolonged, protective effect of
reducing the risk of endometrial cancer in the population of users.
Breast cancer is rare among women under 40 years of age whether or not they use hormonal
contraceptives.
Results from some epidemiological studies suggest a small difference in risk of the disease
in current and recent users compared with never-users. Any excess risk in current and recent
DMPA users is small in relation to the overall risk of breast cancer, particularly in young
women (see below), and is not apparent after 10 years since last use. Duration of use does
not seem to be important.
Possible number of additional cases of breast cancer diagnosed up to 10 years after
stopping injectable progestogens*
Age at last use of DMPA
20
30
40
*based on use for 5 years

No of cases per 10,000
women who are never-users
Less than 1
44
160

Possible additional cases
per 10,000 DMPA users
Much less than 1
2-3
10

Weight Gain: There is a tendency for women to gain weight while on Depo-Provera therapy.
Studies indicate that over the first 1-2 years of use, average weight gain was 5-8 lbs. Women
completing 4-6 years of therapy gained an average of 14-16.5 lbs. There is evidence that
weight is gained as a result of increased fat and is not secondary to an anabolic effect or fluid
retention.
Anaphylaxis: Reports of anaphylactic responses (anaphylactic reactions, anaphylactic
shock, anaphylactoid reactions) have been received.
Thromboembolic Disorders: Should the patient experience pulmonary embolism,
cerebrovascular disease or retinal thrombosis while receiving Depo-Provera, the drug should
not be readministered.
Psychiatric Disorders: Patients with a history of endogenous depression should be carefully
monitored. Some patients may complain of premenstrual-type depression while on
Depo-Provera therapy.
Abscess formation: As with any intramuscular injection, especially if not administered
correctly, there is a risk of abscess formation at the site of injection, which may require
medical and/or surgical intervention.
Precautions:
History or emergence of the following conditions requires careful consideration and
appropriate investigation: migraine or unusually severe headaches, acute visual
disturbances of any kind, pathological changes in liver function and hormone levels. Patients
with thromboembolic or coronary vascular disease should be carefully evaluated before
using Depo-Provera.

BACK PAGE

A decrease in glucose tolerance has been observed in some patients treated with
progestogens. The mechanism for this decrease is obscure. For this reason, diabetic
patients should be carefully monitored while receiving progestogen therapy.
Rare cases of thromboembolism have been reported with use of Depo-Provera, but causality
has not been established.
The effects of medroxyprogesterone acetate on lipid metabolism have been studied with no
clear impact demonstrated. Both increases and decreases in total cholesterol, triglycerides
and low-density lipoprotein (LDL) cholesterol have been observed in studies. The use of
Depo-Provera appears to be associated with a 15-20 % reduction in serum high density
lipoprotein (HDL) cholesterol levels which may protect women from cardiovascular disease.
The clinical consequences of this observation are unknown.
The potential for an increased risk of coronary disease should be considered prior to use.
Doctors should carefully consider the use of Depo-Provera in patients with recent
trophoblastic disease before levels of human chorionic gonadotrophin have returned to
normal.
Physicians should be aware that pathologists should be informed of the patient’s use of
Depo-Provera if endometrial or endocervical tissue is submitted for examination.
The results of certain laboratory tests may be affected by the use of Depo-Provera. These
include gonadotrophin levels (decreased), plasma progesterone levels (decreased), urinary
pregnanediol levels (decreased), plasma oestrogen levels (decreased), plasma cortisol
levels (decreased), glucose tolerance test, metyrapone test, liver function tests (may
increase), thyroid function tests (protein bound iodine levels may increase and T3 uptake
levels may decrease). Coagulation test values for prothrombin (Factor II), and Factors VII,
VIII, IX and X may increase.
Interaction with other medicinal products and other forms of interaction
Aminoglutethimide administered concurrently with Depo-Provera may significantly depress
the bioavailability of Depo-Provera.
Interactions with other medicinal treatments (including oral anticoagulants) have rarely been
reported, but causality has not been determined. The possibility of interaction should be
borne in mind in patients receiving concurrent treatment with other drugs.
The clearance of medroxyprogesterone acetate is approximately equal to the rate of hepatic
blood flow. Because of this fact, it is unlikely that drugs which induce hepatic enzymes will
significantly affect the kinetics of medroxyprogesterone acetate. Therefore, no dose
adjustment is recommended in patients receiving drugs known to affect hepatic metabolising
enzymes.
Medroxyprogesterone acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the
CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects with CYP3A4
inducers or inhibitors on MPA have not been conducted and therefore the clinical effects of
CYP3A4 inducers or inhibitors are unknown.
Fertility, pregnancy and lactation
Doctors should check that patients are not pregnant before the initial injection of
Depo-Provera, and also if administration of any subsequent injection is delayed beyond 89
days (12 weeks and five days).
Infants from accidental pregnancies that occur 1-2 months after injection of Depo-Provera
may be at an increased risk of low birth weight, which in turn is associated with an increased
risk of neonatal death. The attributable risk is low because such pregnancies are uncommon.
Children exposed to medroxyprogesterone acetate in utero and followed to adolescence,
showed no evidence of any adverse effects on their health including their physical,
intellectual, sexual or social development.
Medroxyprogesterone acetate and/or its metabolites are secreted in breast milk, but there is
no evidence to suggest that this presents any hazard to the child. Infants exposed to
medroxyprogesterone acetate via breast milk have been studied for developmental and
behavioural effects to puberty. No adverse effects have been noted.
Effects on ability to drive and use machines
Depo-Provera may cause headaches and dizziness. Patients should be advised not to drive
or operate machinery if affected.
Undesirable effects
In a large clinical trial of over 3900 women, who were treated with Depo-Provera for up to 7
years, the following adverse events were reported.
The following adverse events were commonly (by more than 5% of subjects) reported:
menstrual irregularities (bleeding and/or amenorrhoea), weight changes, headache,
nervousness, abdominal pain or discomfort, dizziness, asthenia (weakness or fatigue).
Adverse events reported by 1% to 5% of subjects using Depo-Provera were: decreased
libido or anorgasmia, backache, leg cramps, depression, nausea, insomnia, leucorrhoea,
acne, vaginitis, pelvic pain, breast pain, no hair growth or alopecia, bloating, rash, oedema,
hot flushes.
Adverse reactions are listed according to the following categories:
Very Common >10%, Common ≥1% and < 10%, Uncommon >0.1% and <1%, Rare < 0.1%,
Not known (frequency cannot be estimated from the available data)
Ear and Labyrinth Disorders: Uncommon: Vertigo.
Gastrointestinal Disorders: Very common: Abdominal pain or discomfort. Common: Bloating,
nausea. Uncommon: Abdominal distension, gastrointestinal disturbances. Rare: Rectal
bleeding.
Infection & Infestations: Common: Vaginitis.
Metabolism & Nutrition Disorders: Common: Appetite decrease, appetite increase
Uncommon: Weight increase, weight decrease, fluid retention.
Musculoskeletal, Connective Tissue & Bone Disorders: Common: Back pain. Uncommon:
Arthralgia, muscle cramps, pain in limbs. Not known: Osteoporosis including osteoporotic
fractures, loss of bone mineral density, axillary swelling.
Nervous System Disorders: Very common: Headaches. Common: Dizziness. Uncommon:
Somnolence, migraine, convulsions. Rare: Paralysis. Not known: Syncope.
Reproductive System & Breast Disorders: Common: Amenorrhea, breast pain/tenderness,
intermenstrual bleeding, menometrorrhagia, menorrhagia, pelvic pain, leucorrhoea.
Uncommon: Vaginal discharge, vulvovaginal dryness, dysmenorrhea, change in breast size,
dyspareunia, ovarian cyst, premenstrual syndrome, genitourinary infection, uterine
hyperplasia. Rare: Breast lumps or nipple bleeding. Not known: Abnormal uterine bleeding
(irregular, increase, decrease), galactorrhea, vaginal cysts, prevention of lactation, sensation
of pregnancy, lack of return to fertility.
Vascular Disorders: Common: Hot flushes. Uncommon: Hypertension, varicose veins,
thrombophlebitis, pulmonary embolism. Not known: Thromboembolic disorders, deep vein
thrombosis.
Cardiovascular Disorders: Rare: Tachycardia.
Immune System Disorders: Uncommon: Hypersensitivity reactions (e.g. anaphylaxis &
anaphylactoid reactions, angioedema).
Hepato-biliary disorders: Uncommon: Abnormal liver enzymes, jaundice. Not known:
Disturbed liver function.
Skin & Subcutaneous Tissue Disorders: Common: Acne, alopecia, rash. Uncommon:
Chloasma, dermatitis, ecchymosis, hirsutism, pruritus, melasma, urticaria, oedema. Not
known: Skin striae, scleroderma.
General Disorders and Administration Site Conditions: Common: Fatigue, injection site
reactions (such as pain or abscess), asthenia, paraesthesia. Uncommon: Chest pain,
pyrexia. Rare: Thirst, hoarseness, paralysis. Not known: Facial palsy.
Investigations: Uncommon: Cervical smear abnormal. Rare: Decreased glucose tolerance.
Psychiatric Disorders: Common: Anorgasmia, depression, nervousness, emotional
disturbance, libido decreased, mood disorder, irritability, insomnia. Uncommon: Anxiety.
Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps): Rare: Breast
cancer.

Blood and lymphatic system disorders: Rare: Anaemia. Not known: Blood dyscrasia.
Respiratory, thoracic, and mediastinal disorders: Uncommon: Dyspnoea.
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
Overdose
No positive action is required other than cessation of therapy.
Pharmacodynamic properties
Pharmacotherapeutic group: Progestogens, ATC code: G03AC06
Medroxyprogesterone
acetate
exerts
anti-oestrogenic,
antigonadotrophic effects.

anti-androgenic

and

BMD Changes in Adult Women: A study comparing changes in BMD in women using
Depo-Provera with women using medroxyprogesterone acetate injection (150 mg IM)
showed no significant differences in BMD loss between the two groups after two years of
treatment. Mean percent changes in BMD in the Depo-Provera group are listed in Table 1
Table 1. Mean Percent Change from Baseline in BMD in Women Using DEPO-PROVERA by
Skeletal Site
Time on
Treatment

Lumbar Spine

Total Hip

Femoral Neck

N

Mean % Change N
(95% CI)

Mean % Change N
(95% CI)

Mean % Change
(95% CI)

1 year

166

-2.7
(-3.1 to -2.3)

166

-1.7
(-2.1 to -1.3)

166

-1.9
(-2.5 to -1.4)

2 year

106

-4.1
(-4.6 to -3.5)

106

-3.5
(-4.2 to -2.7)

106 -3.5
(-4.3 to -2.6)

In another controlled, clinical study adult women using medroxyprogesterone acetate
injection (150 mg IM) for up to 5 years showed spine and hip mean BMD decreases of 5-6%,
compared to no significant change in BMD in the control group. The decline in BMD was
more pronounced during the first two years of use, with smaller declines in subsequent
years. Mean changes in lumbar spine BMD of –2.86%, -4.11%, -4.89%, -4.93% and –5.38%
after 1, 2, 3, 4 and 5 years, respectively, were observed. Mean decreases in BMD of the total
hip and femoral neck were similar. Please refer to Table 2 below for further details. After
stopping use of medroxyprogesterone acetate injection (150 mg IM), BMD increased
towards baseline values during the post-therapy period. A longer duration of treatment was
associated with a slower rate of BMD recovery.
Table 2. Mean Percent Change from Baseline in BMD in Adults by Skeletal Site and Cohort
after 5 Years of Therapy with medroxyprogesterone acetate 150 mg IM and after 2 Years
Post-Therapy or 7 Years of Observation (Control)
Time in Study Spine
Medroxypro
gesterone
acetate
n=33
5 years*
-5.38%
7 years**
n=12
-3.13%

Total Hip
Control Medroxypro
gesterone
acetate
n=105 n=21
0.43% -5.16%
n=60
n=7
0.53% -1.34%

Control
n=65
0.19%
n=39
0.94%

Femoral Neck
Medroxypro Control
gesterone
acetate
n=34
n=106
-6.12%
-0.27%
n=13
n=63
-5.38%
-0.11%

*The treatment group consisted of women who received medroxyprogesterone acetate
injection (150 mg IM) for 5 years and the control group consisted of women who did not use
hormonal contraception for this time period.
** The treatment group consisted of women who received medroxyprogesterone acetate
Injection (150 mg IM) for 5 years and were then followed up for 2 years post-use and the
control group consisted of women who did not use hormonal contraceptive for 7 years.
BMD Changes in Adolescent Females (12-18 years)
Results from an open-label, non-randomised, clinical study of medroxyprogesterone acetate
Injection (150 mg IM every 12 weeks for up to 240 weeks (4.6 years), followed by post–
treatment measurements) in adolescent females (12-18 years) also showed that
medroxyprogesterone acetate IM use was associated with a significant decline in BMD from
baseline. Among subjects who received ≥ 4 injections/60-week period, the mean decrease in
lumbar spine BMD was - 2.1 % after 240 weeks (4.6 years); mean decreases for the total hip
and femoral neck were -6.4 % and -5.4 %, respectively. Post-treatment follow-up showed
that, based on mean values, lumbar spine BMD recovered to baseline levels approximately
1 year after treatment was discontinued and that hip BMD recovered to baseline levels
approximately 3 years after treatment was discontinued. However, it is important to note that
a large number of subjects discontinued from the study, therefore these results are based on
a small number of subjects (n=71 at 60 weeks and n=25 at 240 weeks after treatment
discontinuation). In contrast, a non-comparable cohort of unmatched, untreated subjects,
with different baseline bone parameters from the DMPA users, showed mean BMD increases
at 240 weeks of 6.4%, 1.7% and 1.9% for lumbar spine, total hip and femoral neck,
respectively.
Pharmacokinetic properties
Parenteral medroxyprogesterone acetate (MPA) is a long acting progestational steroid. The
long duration of action results from its slow absorption from the injection site. Immediately
after injection of 150 mg/ml MPA, plasma levels were 1.7 ± 0.3 nmol/l. Two weeks later, levels
were 6.8 ± 0.8 nmol/l. Concentrations fell to the initial levels by the end of 12 weeks. At lower
doses, plasma levels of MPA appear directly related to the dose administered. Serum
accumulation over time was not demonstrated. MPA is eliminated via faecal and urinary
excretion. Plasma half-life is about six weeks after a single intramuscular injection. At least
11 metabolites have been reported. All are excreted in the urine, some, but not all,
conjugated.
Shelf-life
The shelf-life is printed on labels and cartons. Do not use Depo-Provera after this date.
Storage of the product
Do not store above 25ºC. Do not freeze. Do not mix with other agents. Discard any remaining
contents after use.
Manufacturer and Product Licence Holder
This product is manufactured by Pharmacia N.V./S.A., Rijksweg 12, B-2870 Puurs, Belgium.
It is procured from within the EU by the Product Licence Holder Swinghope Ltd., Brandon
House, Marlowe Way, Croydon CR0 4XS and repackaged by Interport Ltd., Brandon House,
Marlowe Way, Croydon CR0 4XS.
POM

PL No: 10380/0981

Leaflet revision date: 22/10/2014
Depo-Provera® is a registered trademark of Pharmacia Limited, UK.
T05215

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Source: Medicines and Healthcare Products Regulatory Agency

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