DEPO-PROVERA 150MG/ML STERILE SUSPENSION FOR INJECTION

Active substance: MEDROXYPROGESTERONE ACETATE

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Depo-Provera® 150mg/ml
Sterile Suspension for Injection
(medroxyprogesterone acetate)

Your medicine is available using the name Depo-Provera
150mg/ml Sterile Suspension for Injection but will be referred to
as Depo-Provera throughout this leaflet.

Please read all of this leaflet carefully before
you start using this method of contraception.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, nurse or
healthcare provider.
This medicine has been prescribed for you. Do not pass it on
to others. It may harm them, even if their symptoms are the
same as yours.
If any of the side effects get serious, or if you notice any
side effects not listed in this leaflet, please tell your doctor,
nurse or healthcare provider.

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 ‘How to use Depo-Provera’).
Depo-Provera may not be suitable for every woman.
You will need to discuss with your doctor or healthcare
professional providing your contraception whether it is
suitable for you, especially if you wish to use it for more
than 2 years (See Section 1 ‘What Depo-Provera is and what
it is used for’).
Depo-Provera may not be suitable for you if you have a
history of certain medical conditions (see Section 2 under
‘Before you use Depo-Provera’) or if you are taking a
medicine called aminoglutethiamide that thins the blood
(see Section 2 under ‘Taking other medicines’). 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 ‘Possible side effects’).
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.

In this leaflet:
1.
2.
3.
4.
5.
6.

What Depo-Provera is and what it is used for
Before you use Depo-Provera
How to use Depo-Provera
Possible side effects
How to store Depo-Provera
Further information

1. What Depo-Provera is and what it is used
for
Depo-Provera is a long acting contraceptive. The active ingredient
in Depo-Provera, medroxyprogesterone acetate (MPA), 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.
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. 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. 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, hormonedependent cancer of the breast or reproductive organs.
If you have unexplained vaginal bleeding.
If you have liver disease.
If you have never had a period.
If you are using certain medicines such as high dose
glucocorticoids (steroids), anti-epileptics, 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.

Take special care with 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
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.

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.

Protection against sexually transmitted diseases:

Depo-Provera does not protect against HIV infection (AIDS) and
other sexually transmitted diseases.

Taking 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:

Because Depo-Provera is such an effective contraceptive
method, the risk of accidental pregnancy for women who
have their injections regularly (every 12 weeks) is very low.
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 will 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 DepoProvera.
In most women the effect will have worn off 5 to 6 months
after the last injection.
Over 80% of women trying to get pregnant will conceive
within a year of the first missed injection.
Some women have got pregnant in the first month after
missing an injection.

Page 1 of 2

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.

Important information about some of the
ingredients of Depo-Provera:

The active ingredient in Depo-Provera is medroxyprogesterone
acetate (MPA).
Depo-Provera also contains polyethylene glycol, polysorbate 80,
sodium chloride, methyl parahydroxybenzoate (E218),
propyl parahydroxybenzoate (E216) and water for injection.
Warning: Contains Parahydroxybenzoate. May cause allergic
reactions (possibly delayed) and exceptionally bronchospasm.

3. How to use Depo-Provera
This medicine will be given to you by your doctor or
healthcare professional. (The other 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 1ml (150mg 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.
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.
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.

If you miss an injection of Depo-Provera:

If you miss 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.

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.
If you have any further questions on the use of this product ask
your doctor or healthcare professional.

4. Possible side effects
Like all medicines, Depo-Provera 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.

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 Depo-Provera
increases the risk of osteoporosis (weak bones) and fractures in
later life.
Tell your doctor immediately if you experience any of the above
symptoms.

Common side effects (occur in more than 10 out of every
1,000 patients)
These include:
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, 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).

Uncommon side effects (occurs in fewer than 10 out of
every 1,000 patients)

These include:
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.

Rare side effects (occurs in less than 1 out of every
1,000 patients)

These include:
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).

Other side effects that have been observed include:

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 any of the side effects get serious, or if you notice any side
effects not listed in this leaflet, please tell your doctor or
healthcare professional.

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.
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.

Possible effects on your bones:

Depo-Provera works by lowering levels of estrogen and other
hormones. However, low estrogen 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.
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 Depo-Provera 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.

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.

Page 2 of 2

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or
nurse. 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
Keep out of the sight and reach of children.
Do not use after the expiry date (Exp) stated on the outer carton
and the vial. The expiry date refers to the last day of that month.
Do not store above 25°C.
Do not freeze.
Single use only. Discard after use.
Do not mix with other agents.
Medicines should not be thrown away in waste water or in
household waste. Please ask your pharmacist how to throw away
any medicine you do not need anymore. If you do this you will
help protect the environment.

6. Further information
What Depo-Provera contains

Each 1ml vial contains 150mg of medroxyprogesterone acetate.
Also contains: polyethylene glycol, polysorbate 80,
sodium chloride, methyl parahydroxybenzoate (E218),
propyl parahydroxybenzoate (E216) and water for injection.

What Depo-Provera looks like and contents of the
pack

Depo-Provera is a white, sterile, aqueous suspension contained
in a clear glass vial with a rubber stopper, an aluminium seal and
a purple cap.
Depo-Provera is available in packs containing 1ml of suspension.

Manufacturer

Manufactured by: Pfizer Manufacturing Belgium N.V./S.A.,
Rijksweg 12, 2870 Puurs, Belgium.
Procured from within the EU and repackaged by: Doncaster
Pharmaceuticals Group Ltd., Kirk Sandall, Doncaster, DN3 1QR.
Product Licence holder: Landmark Pharma Ltd., 7 Regents Drive,
Prudhoe, Northumberland, NE42 6PX.
PL No: 21828/0590

POM

Depo-Provera® is a registered trademark of Pharmacia Limited.
Leaflet revision date: 28.04.14

Depo-Provera® 150mg/ml
Sterile Suspension for Injection
(medroxyprogesterone acetate)

INFORMATION FOR DOCTORS AND PHARMACISTS
For further information, consult the Summary of Product
Characteristics.
This medicine is available using the name Depo-Provera
150mg/ml Sterile Suspension for Injection but will be referred to
as Depo-Provera throughout this leaflet.

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 150mg 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.

Depo-Provera is a white, sterile, aqueous suspension contained in
a clear glass vial with a rubber stopper, an aluminium seal and a
purple cap.

Children: 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.

Each 1ml vial contains 150mg of medroxyprogesterone acetate.

Switching from other Methods of Contraception:

Description

Also contains: polyethylene glycol, polysorbate 80,
sodium chloride, methyl parahydroxybenzoate (E218),
propyl parahydroxybenzoate (E216) and water for injection.

Uses

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).

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.

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).

Since loss of bone mineral density (BMD) may occur in females of
all ages who use Depo-Provera 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. 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.

Contra-indications

Dosage

Each ml of suspension contains 150mg medroxyprogesterone
acetate Ph. Eur. 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, both
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

First injection: To provide contraceptive cover in the first cycle of
use, an injection of 150mg 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.

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.

Depo-Provera is contra-indicated in patients with a known
sensitivity to medroxyprogesterone acetate or any ingredient of
the vehicle.
Depo-Provera should not be used during pregnancy, either for
diagnosis or therapy.
Depo-Provera is contra-indicated as a contraceptive at the above
dosage in known or suspected hormone-dependent malignancy of
breast or genital organs.
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 estrogen levels and is
associated with significant loss of BMD due to the known effect of
estrogen 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 estrogen
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.
Page 1 of 2

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 (0.625-1.25mg 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
No of cases per 10,000
Possible additional
of DMPA
cases per
women who are
10,000 DMPA users
never-users
20
30
40
*based on use for

Less than 1
44
160
5 years

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.
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 lowdensity 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 Medicaments 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.

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 via breast milk have been studied for
developmental and behavioural effects to puberty. No adverse
effects have been noted.

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%,
Unknown (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. Frequency 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. Unknown: 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.
Frequency 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. Frequency 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. Frequency not known: Disturbed liver function.
Skin & Subcutaneous Tissue Disorders: Common: Acne, alopecia,
rash. Uncommon: Chloasma, dermatitis, ecchymosis, hirsutism,
pruritus, melasma, urticaria, oedema.
Frequency 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. Frequency 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.
Frequency unknown: Blood dyscrasia.
Respiratory, thoracic, and mediastinal disorders:
Uncommon: Dyspnoea.

Overdose

No positive action is required other than cessation of therapy.

Pharmacodynamic Properties

Medroxyprogesterone acetate exerts anti-oestrogenic,
anti-androgenic and antigonadotrophic effects.
BMD Changes in Adult Women: A study comparing changes in
BMD in women using Depo-Provera with women using
medroxyprogesterone acetate injection (150mg 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
Lumbar Spine
Total Hip
Femoral Neck
Time on
N
Mean %
N
Mean %
N
Mean %
Treatment
Change
Change
Change
(95% CI)
(95% CI)
(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 years

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 (150mg 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 (150mg IM), BMD
increased towards baseline values during the post-therapy period.
Page 2 of 2

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 150mg IM and after 2 Years
Post-Therapy or 7 Years of Observation (Control)
Time in
Spine
Total Hip
Femoral Neck
Study
Medroxypro Control
gesterone
acetate

Medroxypro Control
gesterone
acetate

Medroxypro Control
gesterone
acetate

5 years*

n=33
-5.38%

n=105
0.43%

n=21
-5.16%

n=65
0.19%

n=34
-6.12%

n=106
-0.27%

7
years**

n=12
-3.13%

n=60
0.53%

n=7
-1.34%

n=39
0.94%

n=13
-5.38%

n=63
-0.11%

*The treatment group consisted of women who received
medroxyprogesterone acetate injection (150mg 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 (150mg 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 (150mg 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 150mg/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

Do not use after the expiry date (Exp) stated on the outer carton
and the vial. The expiry date refers to the last day of that month.

Storage of the product

Do not store above 25°C.
Do not freeze.
Single use only. Discard after use.
Do not mix with other agents.

Name and address of the manufacturer

Manufactured by: Pfizer Manufacturing Belgium N.V./S.A.,
Rijksweg 12, 2870 Puurs, Belgium.
Procured from within the EU and repackaged: by Doncaster
Pharmaceuticals Group Ltd., Kirk Sandall, Doncaster, DN3 1QR.
Product Licence holder: Landmark Pharma Ltd., 7 Regents Drive,
Prudhoe, Northumberland, NE42 6PX.
PL No: 21828/0590

POM

®

Depo-Provera is a registered trademark of Pharmacia Limited.
Leaflet revision date: 28.04.14

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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