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DEPO-PROVERA 150MG/ML STERILE SUSPENSION FOR INJECTION

Active substance(s): MEDROXYPROGESTERONE ACETATE / MEDROXYPROGESTERONE ACETATE / MEDROXYPROGESTERONE ACETATE

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PACKAGE LEAFLET:
INFORMATION FOR THE PATIENT

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 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.

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 aminoglutethimide 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.

What is in this leaflet
1.
2.
3.
4.
5.
6.

What Depo-Provera is and what it is used for
What you need to know before you use Depo-Provera
How to use Depo-Provera
Possible side effects
How to store Depo-Provera
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 the active substance 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.
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.






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), 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.

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







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 reevaluate 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.

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 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 breastfeeding.
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.
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.

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 medicine,
ask your doctor or healthcare professional.

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

4. Possible side effects

Other medicines and Depo-Provera

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






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 aminoglutethimide 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, breast-feeding and fertility





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.

Seek medical help immediately if you notice any of the
following side effects:

Hypersensitivity (allergic) reaction (it is not known how
frequently this occurs)
Symptoms include sudden skin rash, swelling of
the face, lips, tongue or throat, wheezing or difficulty in
breathing.

A blood clot in the lungs (this occurs rarely - may affect
up to 1 in 1000 people)
Symptoms include

Shortness of breath

Breath-related chest pains

Coughing up blood

A blood clot in the leg (this occurs rarely - may affect
up to 1 in 1000 people)
Deep vein thrombosis (DVT) is a condition in which a
blood clot forms in one of your deep veins, usually in
your leg.

These are symptoms of a deep-vein thrombosis
(DVT):


Effect on future fertility





Depo-Provera can be used:


If you have had, or think you may have, hormonedependent 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.



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’.
Page 1 of 2







You have pain, tenderness or swelling in your calf,
ankle or foot
You have painful or inflamed veins in your leg
You find it difficult to put full weight on the affected
leg
You have purple discolouration of the skin of the
leg or the skin becomes red and warm to touch.

Jaundice (yellowing of the skin or the whites of the
eyes).

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.

Other side-effects include:
Very common: may affect more than 1 in 10 people





nervousness
headache
stomach pain or discomfort
weight increase or decrease

Common: may affect up to 1 in 10 people















depression
libido decreased (reduced sex drive)
dizziness
feeling sick
feeling bloated
hair loss
acne
back pain
vaginal discharge
breast tenderness
difficult or painful period
urinary tract infection
oedema/fluid retention
weakness

Uncommon: may affect up to 1 in 100 people


















appetite increased or decreased
difficulty sleeping
convulsions (fits)
drowsiness
tingling
hot flush
liver disorder
facial hair growth
nettle rash or hives
itchy skin
temporary brown patches
difficult or painful period
unexpected or unusual vaginal bleeding or spotting
milky discharge from the breast when not pregnant or
breastfeeding
pelvic pain
painful intercourse
prevention of lactation

Rare: may affect up to 1 in 1,000 people




















































breast cancer
reduction in red blood cell
blood disorder
difficulty reaching orgasm
behaviour change
mood change
irritability
anxiety
migraine
paralysis
fainting
feeling of dizziness or spinning
heart beats more rapidly
high blood pressure
varicose veins
rectal bleeding
digestive disorder
liver enzyme disorder
accumulation of fat (at injection site)
inflammation of the skin
scar tissue formation
stretch marks
pain in a joint
muscular cramps
bone density decreased (osteoporosis)
vaginal pain or inflammation
stopping or extended break of your periods
breast pain
inflammation of the vagina
stopping or extended break of your periods
breast pain
uterine bleeding or excessive bleeding
periods with abnormally heavy or prolonged bleeding
vaginal dryness
change in breast size
ovarian or vaginal cyst
premenstrual syndrome
excessive thickening of the lining of the womb
breast lump
nipple bleeding
delayed egg release with longer menstrual cycles
(periods)
feel pregnant
fever
tiredness
injection site pain or tenderness
injection site lump or dimple
feeling thirsty
hoarseness
facial nerve paralysis
decreased sugar tolerance
abnormal smear

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 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. 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 DepoProvera 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. DepoProvera 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.

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
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.
Do not throw away medicines via wastewater or household
waste. Ask your pharmacist how to throw away medicines
you no longer use. These measures will help protect the
environment.

6. Contents of the pack and other
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.

Page 2 of 2

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: 22.02.17

Blind or partially sighted?
Is this leaflet hard to see or
read?
Call 01302 365000
(Regulatory)
Please be ready to give the
following information: DepoProvera 150mg/ml Sterile
Suspension for Injection
Reference No: 21828/0590

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.

Depo-Provera® 150mg/ml
Sterile Suspension for Injection
(medroxyprogesterone acetate)
The following information is intended for medical or healthcare
professionals only:
(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.

Description

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

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.

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.

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.

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 DepoProvera.
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 150mg 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.

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

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.

Administration
Adults

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.

Anaphylaxis: Reports of anaphylactic responses (anaphylactic reactions, anaphylactic shock,
anaphylactoid reactions) have been received.

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 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.
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.

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 DepoProvera 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
low-density lipoprotein (LDL) cholesterol have been observed in studies. The use of DepoProvera 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 DepoProvera 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

Contraindications

Hypersensitivity to medroxyprogesterone acetate or to any of the excipients 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
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.

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.

20
30
40
*based on use for 5 years

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.

Warnings

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.

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.

Page 1 of 2

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 % Change
N
Mean % Change
N
Mean % Change
Treatment
(95% CI)
(95% CI)
(95% CI)

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

The table below provides a listing of adverse drug reactions with frequency based on allcausality data from clinical studies that enrolled more than 4200 women who received
DMPA for contraception for up to 7 years. Those most frequently (>5%) reported adverse drug
reactions were weight increased (69%), weight decreased (25%), headache (16%),
nervousness (11%), abdominal pain or discomfort (11%), dizziness (6%), and decrease in libido
(6%).
The following lists of adverse reactions are listed within the organ system classes, under
headings of frequency (number of patients expected to experience the reaction), using the
following categories:
Very common (≥1/10)
Common (≥1/100 to <1/10);
Uncommon (≥1/1000 to <1/100);
Rare (≥1/10,000 to <1/1000);
Very rare (<1/10,000);
Not known (cannot be estimated from the available data).
System Organ
Class

Very
Common
≥ 1/10

Common
≥ 1/100 to
< 1/10

Neoplasms
Benign,
Malignant
and Unspecified
(Incl. Cysts and
Polyps)
Blood and
lymphatic system
disorders
Immune system
disorders

Nervous system
disorders

Drug hypersensitivity

Nervousness

Headache

Depression,
Libido decreased

Dizziness

Seizure,
Somnolence,
Paraesthesia

Anorgasmia,
Emotional
disturbance,
Affective disorder,
Irritability, Anxiety
Migraine, Paralysis,
Syncope
Vertigo

Hot flush

Dyspnoea

Abdominal
pain,
Abdominal
discomfort

Nausea,
Abdominal
distension

Hepatobiliary
disorders
Skin and
subcutaneous
tissue disorders

Alopecia, Acne,
Rash

Musculoskeletal
and connective
tissue disorders

Back pain, Pain
in extremity

Reproductive
system and
breast disorders

Vaginal
discharge, Breast
tenderness,
Dysmenorrhoea,
Genitourinary
tract infection

General
disorders and
administration
site conditions

Investigation

Increased
appetite,
decreased
appetite
Insomnia

Anaphylactic
reaction,
Anaphylactoid
reaction,
Angioedema

Oedema/Fluid
retention,
Asthenia

Tachycardia
Embolism and
thrombosis,
Deep vein
thrombosis,
Thrombophlebitis,
Hypertension,
Varicose veins
Pulmonary embolism

Rectal haemorrhage,
Gastrointestinal
disorder
Hepatic
function
abnormal
Hirsutism,
Urticaria,
Pruritus,
Chloasma

Dysfunctional
uterine
bleeding
(irregular,
increase,
decrease,
spotting,
Galactorrhoea
Pelvic pain,
Dyspareunia,
Suppressed
lactation

Chest pain

Weight
increased,
Weight
decreased

Jaundice, Hepatic
enzyme abnormal
Lipodystrophy
acquired*,
Dermatitis,
Ecchymosis,
Scleroderma, Skin
striae
Arthralgia, Muscle
spasms,
Osteoporosis,
Osteoporotic
fractures
Vaginitis,
Amenorrhoea, Breast
pain, Metrorrhagia,
Menometrorrhagia,
Menorrhagia,
Vulvovaginal
dryness, Breast
atrophy, Ovarian
cyst, Premenstrual
syndrome,
Endometrial
hyperplasia, Breast
mass, Nipple
exudate bloody,
Vaginal cyst, Breast
enlargement, Lack of
return to fertility,
Sensation of
pregnancy
Pyrexia, Fatigue,
Injection site
reaction*, Injection
site persistent
atrophy/
indentation/
dimpling*,
Injection site
nodule/lump*,
Injection site pain/
tenderness*, Thirst,
Dysphonia, VIIth
nerve
paralysis, Axillary
swelling
Bone density
decreased, Glucose
tolerance decreased,
Cervical smear
abnormal

-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)

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
Study

Anaemia, Blood
disorder

Ear and
Labyrinth
Disorder
Cardiac disorder
Vascular
disorders

Respiratory,
thoracic, and
mediastinal
disorders
Gastrointestinal
disorders

Rare
≥ 1/10,000 to
< 1/1000

166

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. A longer duration of treatment was associated with a slower
rate of BMD recovery.

Breast cancer

Metabolism &
Nutrition
Disorder
Psychiatric
disorders

Uncommon
≥ 1/1000 to
< 1/100

1 year

Spine

Total Hip

Femoral Neck

Medroxyprog Control
esterone
acetate

Medroxyprog Control
esterone
acetate

Medroxyprog Control
esterone
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: 22.02.17

*ADR identified post-marketing

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, anti-androgenic and antigonadotrophic
effects.

Mechanism of action

DMPA, when administered parenterally at the recommended dose to women, inhibits the
secretion of gonadotropins which, in turn, prevents follicular maturation and ovulation and
causes thickening of cervical mucus which inhibits sperm entry into the uterus.
BMD Changes in Adult Women: A study comparing changes in BMD in women using DepoProvera 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.

Page 2 of 2

Expand Transcript

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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