DEPO-PROVERA 150 MG/ML

Active substance: MEDROXYPROGESTERONE ACETATE

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PACKAGE LEAFLET INFORMATION FOR THE USER

Depo-Provera® 150mg/ml
(medroxyprogesterone acetate)
• In teenagers only after other methods of contraception have been
Please read all of this leaflet carefully before you start using this
discussed with the healthcare professional who provides your
medicine because it contains important information for you.
contraception and considered to be unsuitable or unacceptable.
• Keep this leaflet. You may need to read it again.
• For just one or two occasions in the following cases:
• If you have any further questions, ask your doctor, pharmacist or nurse.

if your partner is undergoing a vasectomy, to give you protection
• This medicine has been prescribed for you only. Do not pass it on to
until the vasectomy becomes effective
others. It may harm them, even if their signs of illness are the same as

if you are being immunised against rubella, to prevent pregnancy
yours.
during the period of activity of the virus
• If you get any of the side effects, talk to your doctor, nurse or

if you are awaiting sterilisation.
healthcare provider. This includes any possible side effects not listed in
this leaflet. See section 4.
2. WHAT YOU NEED TO KNOW BEFORE YOU USE DEPOIMPORTANT INFORMATION YOU SHOULD KNOW ABOUT DEPOPROVERA® 150MG/ML
®
PROVERA 150MG/ML
Depo-Provera® 150mg/ml 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.

Do not use Depo-Provera® 150mg/ml:
• 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® 150mg/ml that will require
emergency medical treatment.
• If you think you may be pregnant.
• If you have had, or think you may have, hormone-dependent cancer of
the breast or reproductive organs.
• If you have unexplained bleeding from the womb (uterus).
• If you have liver disease.
• If you have not yet started your periods.

• You must have injections of this contraceptive regularly every 12
weeks; otherwise you may risk becoming pregnant (see section 3).
• Depo-Provera® 150mg/ml 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® 150mg/ml may not be suitable for you if you have a
history of certain medical conditions (see section 2) or if you are taking
a medicine called aminoglutethiamide that thins the blood (see section
2). Your doctor or nurse should take a full medical history before
prescribing Depo-Provera® 150mg/ml.
• Regular use of Depo-Provera® 150mg/ml 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® 150mg/ml.
Teenagers who are rapidly developing their bones may be at particular
risk and should only use Depo-Provera® 150mg/ml 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 DepoProvera® 150mg/ml for you and may request you to visit the clinic for
similar examinations at appropriate intervals thereafter.
What is in this leaflet
1. WHAT DEPO-PROVERA® 150MG/ML IS AND WHAT IT IS USED
FOR
2. WHAT YOU NEED TO KNOW BEFORE YOU USE DEPO-PROVERA®
150MG/ML
3. HOW TO USE DEPO-PROVERA® 150MG/ML
4. POSSIBLE SIDE EFFECTS
5. HOW TO STORE DEPO-PROVERA® 150MG/ML
6. CONTENTS OF THE PACK AND OTHER INFORMATION

Warnings and precautions
Talk to your doctor or healthcare professional before using DepoProvera® 150mg/ml.
Before your doctor or healthcare professional prescribes Depo-Provera®
150mg/ml, 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® 150mg/ml is suitable for you.
• Migraine headaches – if you develop migraine you should consult your
doctor before receiving further injections of Depo-Provera® 150mg/ml
• 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® 150mg/ml
• Problems with your eyesight while using Depo-Provera® 150mg/ml; 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.

1. WHAT DEPO-PROVERA® 150MG/ML IS AND WHAT IT IS USED
FOR
Depo-Provera® 150mg/ml is a long acting contraceptive. This medicine
contains medroxyprogesterone acetate (MPA), which is one of a group of
medicines called ‘Progestogens’. It is similar to (but not the same as) the
natural hormone, progesterone that is produced in the ovaries during the
second half of your menstrual cycle.
Depo-Provera® 150mg/ml 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® 150mg/ml 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® 150mg/ml 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® 150mg/ml for more than 2 years your
doctor or healthcare professional may wish to re-evaluate the risks and
benefits of using Depo-Provera® 150mg/ml to make sure that it is still
the best option for you.

Cervical smear testing:
The results of a cervical smear and some laboratory tests could also be
affected if you are using Depo-Provera® 150mg/ml so it is important that
you tell your doctor.
Protection against sexually transmitted diseases:
Depo-Provera® 150mg/ml does not protect against HIV infection (AIDS)
and other sexually transmitted diseases.

1

Other medicines and Depo-Provera® 150mg/ml:

For effective contraceptive cover, Depo-Provera® 150mg/ml 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® 150mg/ml is used immediately following childbirth or
termination of pregnancy.

• Tell your doctor or pharmacist if you are taking, have recently taken or
might take any other medicines.
• Tell your doctor or healthcare professional if you are taking a medicine
called aminoglutethiamide or other medicines that thin your blood
(anticoagulants) as these may affect the way Depo-Provera® 150mg/ml
works.
• Always tell your doctor or healthcare professional who treats you that
you are using Depo-Provera® 150mg/ml 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.

If you forget an injection of Depo-Provera® 150mg/ml:
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®
150mg/ml and which type of contraception should be used in the
meantime.

Pregnancy:

Switching from other methods of contraception:

• 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® 150mg/ml 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®
150mg/ml for contraception, tell your doctor immediately.

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® 150mg/ml 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.

Effect on future fertility:
• Your usual level of fertility should return when the effect of the injection
has worn off.
• This takes different amounts of time in different women, and does not
depend on how long you have been using Depo-Provera® 150mg/ml.
• 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.

4. POSSIBLE SIDE EFFECTS
Like all medicines, this medicine can cause side effects although not
everybody gets them.
There is a low risk of anaphylactic responses (serious allergic reactions
which may need urgent medical attention or hospitalization). Possible
symptoms include: swelling of the face, lips, tongue or throat, or difficulty
breathing or swallowing, skin rashes, shock or collapse.
Deep vein thrombosis (DVT) is a condition in which a blood clot forms in
one of your deep veins, usually in your leg. Signs of possible DVT
include: swelling of the affected leg, pain and tenderness in the affected
leg (you may also find it difficult to stand properly with your full weight on
the affected leg), a change in the colour of your skin, for example,
redness or skin that feels warm or hot to the touch.
Women who use Depo-Provera® 150mg/ml tend to have lower bone
mineral density than women of the same age who have never used it. The
effects of Depo-Provera® 150mg/ml 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® 150mg/ml is stopped.
It is not yet possible to say whether Depo-Provera® 150mg/ml increases
the risk of osteoporosis (weak bones) and fractures in later life.
Tell your doctor immediately if you experience any of the above
symptoms.
The following other side effects may occur:

If you are breast-feeding:
• Depo-Provera® 150mg/ml 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® 150mg/ml.
• 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® 150mg/ml for contraception.
• If a baby is exposed to Depo-Provera® 150mg/ml in the breast milk, no
harmful effects have been seen in babies and children.
Driving and using machines:
Depo-Provera® 150mg/ml 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.

Common (may affect up to 1 in 10 people)
Abdominal pain or discomfort, bloating, feeling sick, vaginal discharge or
inflammation, changes in appetite, back pain, headaches, dizziness,
irregular periods, very light or no periods (amenorrhoea), breast pain or
tenderness, 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).

Depo-Provera® 150mg/ml contains methylparaben (E218),
propylparaben (E216) and sodium:
Methylparaben and propylparaben may cause allergic reactions (possibly
delayed), and exceptionally, bronchospasm.
This medicinal product contains less than 1 mmol sodium (23 mg) per 150
mg/ml, i.e. essentially ‘sodium free’.
3. HOW TO USE DEPO-PROVERA® 150MG/ML

Uncommon (may affect up to 1 in 100 people)
This medicine will be given to you by your doctor or healthcare
professional.

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.

(The last section of this leaflet contains instructions for your doctor or
healthcare professional on how they should do this.)
Depo-Provera® 150mg/ml is given every 12 weeks as a single
intramuscular injection of 1 ml (150 mg medroxyprogesterone acetate)
into the buttock or upper arm. The injection is given during the first 5 days
after the beginning of a normal menstrual period.
Following childbirth the first Depo-Provera® 150mg/ml 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® 150mg/ml works as a contraceptive for 12 weeks in your
body. There is no way of reversing the injection once it is given.

2

Rare (may affect up to 1 in 1,000 people)
Tachycardia (faster heart beat), breast lumps or nipple bleeding, thirst,
hoarseness, rectal bleeding (bleeding from the anus), paralysis,
decreased glucose tolerance (abnormal blood sugar levels), breast
cancer, anaemia (reduction in red blood cells which can make the skin
pale and cause weakness or breathlessness).
Not known (frequency cannot be estimated from the available data);
Blood clotting disorders, deep vein thrombosis (blood clots forming in the
veins, usually the legs), disturbed liver function. osteoporosis (thinning of
the bones) including fractures, loss of bone mineral density (a test to
measure the strength of bones), swelling of ankles or wrists, abnormal
uterine bleeding (irregular, increase, decrease), milky discharge from
breasts in women who are not breastfeeding, vaginal cysts, milk supply
stopping (in breastfeeding mothers), feeling pregnant, delay in becoming
pregnant after stopping Depo-Provera® 150mg/ml, 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).

Possible risk of cancer:
Studies of women who have used different forms of contraception found
that women who used Depo-Provera® 150mg/ml 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® 150mg/ml 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® 150mg/ml is
greater in older women than in younger women.
In absolute terms this means that:
A 15 year old who uses Depo-Provera® 150mg/ml 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® 150mg/ml 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® 150mg/ml 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® 150mg/ml 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® 150mg/ml 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 effect on your periods:
Depo-Provera® 150mg/ml 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® 150mg/ml your periods will return to
normal in a few months.

Possible risk of weight gain:

Possible effects on your bones:

Some women gained weight while using Depo-Provera® 150mg/ml.
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.

Depo-Provera® 150mg/ml 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 DepoProvera® 150mg/ml tend to have lower bone mineral density than women
of the same age who have never used it. The effects of Depo-Provera®
150mg/ml 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® 150mg/ml is stopped. It is not yet possible to say
whether Depo-Provera® 150mg/ml 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

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® 150 MG/ML
Keep out of the sight and reach of children.
Do not store above 25°C. Keep in the original container. Do not freeze.
Do not use after the expiry date printed on the label and carton.
6. FURTHER INFORMATION
What Depo-Provera® 150 mg/ml contains:
Each 1ml of suspension contains 150mg of medroxyprogesterone acetate
as the active ingredient.
Each 1ml also contains macrogol, sodium chloride, polysorbate 80,
methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate
(E216), and water for injection.

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® 150mg/ml 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® 150mg/ml is stopped, but it is not yet known
whether the bone mineral density reaches the same levels as it would
have if Depo-Provera® 150mg/ml 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® 150mg/ml.

What Depo-Provera® 150 mg/ml looks like and contents of the pack:
It is a white, opaque suspension for injection. It is available in a clear
glass vial with a rubber stopper that has an aluminium seal and a purple
protective cap.
The vial contains 1 millilitre of suspension.
Who manufactured your medicine:

If you use Depo-Provera® 150mg/ml, 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).

Manufactured by Pfizer Manufacturing Belgium N.V/S.A., Rijksweg 12, B2870 Puurs, Belgium. Procured from within the EU and repackaged by
Product Licence Holder Beachcourse Limited, 20 Alliance Court, London
W3 0RB.
PL16378/0534
POM
Revision date: 07 Jul 2014
Leaflet reference: Depo150S/UT
Depo-Provera® is a registered trademark of Pharmacia Limited.

3

BMD Changes in Adolescent Females (12-18 years)
Results from an open-label, non-randomised, clinical study of
medroxyprogesterone acetate Injection (150 mg IM every 12 weeks for up
to 240 weeks (4.6 years), followed by post–treatment measurements) in
adolescent females (12-18 years) also showed that medroxyprogesterone
acetate IM use was associated with a significant decline in BMD from
baseline. Among subjects who received ≥ 4 injections/60-week period, the
mean decrease in lumbar spine BMD was - 2.1 % after 240 weeks (4.6
years); mean decreases for the total hip and femoral neck were -6.4 %
and -5.4 %, respectively. Post-treatment follow-up showed that, based on
mean values, lumbar spine BMD recovered to baseline levels
approximately 1 year after treatment was discontinued and that hip BMD
recovered to baseline levels approximately 3 years after treatment was
discontinued. However, it is important to note that a large number of
subjects discontinued from the study, therefore these results are based
on a small number of subjects (n=71 at 60 weeks and n=25 at 240 weeks
after treatment discontinuation). In contrast, a non-comparable cohort of
unmatched, untreated subjects, with different baseline bone parameters
from the DMPA users, showed mean BMD increases at 240 weeks of
6.4%, 1.7% and 1.9% for lumbar spine, total hip and femoral neck,
respectively.

INFORMATION FOR DOCTORS AND PHARMACISTS

Depo-Provera® 150 mg/ml
(medroxyprogesterone acetate)
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
Description
weeks postpartum, when the infant’s enzyme system is more fully
®
Depo-Provera 150mg/ml is a white, opaque suspension for injection.
developed. Further injections should be given at 12 week intervals.
Each 1ml of suspension contains 150 mg medroxyprogesterone acetate.
Further doses: These should be given at 12 week intervals, however, as
Excipients are macrogol, sodium chloride, polysorbate 80, methyl
long as the injection is given no later than five days after this time, no
parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), and
additional contraceptive measures (e.g. barrier) are required.
water for injection. Hydrochloric acid or sodium hydroxide may be present
(NB For partners of men undergoing vasectomy a second injection of 150
as pH adjusters.
mg i.m. 12 weeks after the first may be necessary in a small proportion of
patients where the partner’s sperm count has not fallen to zero.) If the
Uses
interval from the preceding injection is greater than 89 days (12 weeks
®
Depo-Provera 150mg/ml is a long-term contraceptive agent suitable for
and five days) for any reason, then pregnancy should be excluded before
use in women who have been appropriately counselled concerning the
the next injection is given and the patient should use additional
likelihood of menstrual disturbance and the potential for a delay in return
contraceptive measures (e.g. barrier) for fourteen days after this
to full fertility.
subsequent injection.
Depo-Provera® 150mg/ml may also be used for short-term contraception
Paediatric population (12-18 years): Depo-Provera® 150mg/ml is not
in the following circumstances:
indicated before menarche. Data in adolescent females (12-18 years) is
available. Other than concerns about loss of BMD, the safety and
(i) For partners of men undergoing vasectomy, for protection until the
effectiveness of Depo-Provera® 150mg/ml is expected to be the same for
vasectomy becomes effective.
adolescents after menarche and adult females.
(ii) In women who are being immunised against rubella, to prevent
Switching from other Methods of Contraception: Depo-Provera® 150mg/ml
pregnancy during the period of activity of the virus.
should be given in a manner that ensures continuous contraceptive
(iii) In women awaiting sterilisation.
coverage. This should be based upon the mechanism of action of other
Since loss of bone mineral density (BMD) may occur in females of all
methods (e.g. patients switching from oral contraceptives should have
ages who use Depo-Provera® 150mg/ml injection long-term, a risk/benefit
their first injection of Depo-Provera® 150mg/ml within 7 days of taking
assessment, which also takes into consideration the decrease in BMD
their last active pill).
that occurs during pregnancy and/or lactation, should be considered.
Hepatic Insufficiency: The effect of hepatic disease on the
Use in adolescents (12 – 18 years)
pharmacokinetics of Depo-Provera® 150mg/ml is unknown. As DepoIn adolescents, Depo-Provera® 150mg/ml may be used, but only after
Provera® 150mg/ml largely undergoes hepatic elimination it may be poorly
other methods of contraception have been discussed with the patient and
metabolised in patients with severe liver insufficiency (see
considered unsuitable or unacceptable.
Contraindications).
It is of the greatest importance that adequate explanations of the longRenal Insufficiency: The effect of renal disease on the pharmacokinetics
term nature of the product, of its possible side-effects and of the
of Depo-Provera® 150mg/ml is unknown. No dosage adjustment should
impossibility of immediately reversing the effects of each injection are
be necessary in women with renal insufficiency, since Depo-Provera®
given to potential users and that every effort is made to ensure that each
150mg/ml is almost exclusively eliminated by hepatic metabolism.
patient receives such counselling as to enable her to fully understand
Contraindications
these explanations. Patient information leaflets are supplied by the
manufacturer. It is recommended that the doctor uses these leaflets to aid
Depo-Provera® 150mg/ml is contraindicated in patients with a known
counselling of the patient before giving the injection of Depo-Provera®
sensitivity to medroxyprogesterone acetate or any ingredient of this
150mg/ml.
medicine.
Consistent with good clinical practice, a general medical as well as a
Depo-Provera® 150mg/ml should not be used during pregnancy, either for
gynaecological examination should be undertaken before administration
diagnosis or therapy.
®
of Depo-Provera 150mg/ml and at appropriate intervals thereafter.
Depo-Provera® 150mg/ml is contraindicated as a contraceptive at the
Dosage
above dosage in known or suspected hormone-dependent malignancy of
breast or genital organs.
Each ml of suspension contains 150 mg medroxyprogesterone acetate.
®
Depo-Provera® 150mg/ml is contraindicated in patients with the presence
The sterile aqueous suspension of Depo-Provera 150mg/ml should be
or history of severe hepatic disease whose liver function tests have not
vigorously shaken just before use to ensure that the dose being given
returned to normal.
represents a uniform suspension of Depo-Provera® 150mg/ml. Doses
Whether administered alone or in combination with oestrogen, Deposhould be given by deep intramuscular injection into the buttock or arm.
Provera® 150mg/ml should not be employed in patients with abnormal
Care should be taken to ensure that the depot injection is given into the
uterine bleeding until a definite diagnosis has been established and the
muscle tissue, preferably the gluteus maximus, but other muscle tissue
possibility of genital tract malignancy eliminated.
such as the deltoid may be used and the site of injection should be
cleansed using standard methods prior to administration of the injection.
Special warnings and precautions for use
Assembly of syringe for single use:
Warnings:
1. Remove tip cap.
2. Position needle using aseptic technique.
Loss of Bone Mineral Density:
3. Remove needle shield. The syringe is now ready for use.
Use of Depo-Provera® 150mg/ml reduces serum oestrogen levels and is
associated with significant loss of BMD due to the known effect of
Administration
oestrogen deficiency on the bone remodelling system. Bone loss is
greater with increasing duration of use; however BMD appears to
Adults
increase after Depo-Provera® 150mg/ml is discontinued and ovarian
First injection: To provide contraceptive cover in the first cycle of use, an
oestrogen production increases.
injection of 150 mg i.m. should be given during the first five days of a
This loss of BMD is of particular concern during adolescence and early
normal menstrual cycle. If the injection is carried out according to these
adulthood, a critical period of bone accretion. It is unknown if use of
instructions, no additional contraceptive cover is required.
Depo-Provera® 150mg/ml by younger women will reduce peak bone mass
Postpartum: To increase assurance that the patient is not pregnant at the
and increase the risk for fracture in later life.
time of first administration, this injection should be given within 5 days
A study to assess the BMD effects of medroxyprogesterone acetate IM
postpartum if not breast-feeding.
(Depo-Provera® 150mg/ml, DMPA) in adolescent females showed that its
®
There is evidence that women prescribed Depo-Provera 150mg/ml in the
use was associated with a significant decline in BMD from baseline. In the
immediate puerperium can experience prolonged and heavy bleeding.
small number of women who were followed-up, mean BMD recovered to
Because of this, the drug should be used with caution in the puerperium.
around baseline values by 1- 3 years after discontinuing treatment. In
Women who are considering use of the product immediately following
adolescents, Depo-Provera® 150mg/ml may be used, but only after other
The following information is intended for medical or healthcare
professionals only:
(For further information, consult the Summary of Product Characteristics.)

Pharmacokinetic properties
Parenteral medroxyprogesterone acetate (MPA) is a long acting
progestational steroid. The long duration of action results from its slow
absorption from the injection site.
Immediately after injection of 150 mg/ml MPA, plasma levels were 1.7 ±
0.3 nmol/l. Two weeks later, levels were 6.8 ± 0.8 nmol/l. Concentrations
fell to the initial levels by the end of 12 weeks. At lower doses, plasma
levels of MPA appear directly related to the dose administered. Serum
accumulation over time was not demonstrated. MPA is eliminated via
faecal and urinary excretion. Plasma half-life is about six weeks after a
single intramuscular injection. At least 11 metabolites have been reported.
All are excreted in the urine, some, but not all, conjugated.
Shelf-life
The shelf-life is printed on labels and cartons. Do not use Depo-Provera®
150mg/ml after this date.
Storage of the product
Do not store above 25°C. Do not freeze. Keep in the original container.
Do not mix with other agents. Discard any remaining contents after use.
Manufacturer and Product Licence Holder
Manufactured by Pfizer Manufacturing Belgium N.V/S.A., Rijksweg 12, B2870 Puurs, Belgium. Procured from within the EU and repackaged by
Product Licence Holder Beachcourse Limited., 20 Alliance Court. London
W3 0RB.
PL16378/0534

POM

Revision date: 07 Jul 2014
Leaflet Reference: Depo150S/2
Depo-Provera® 150mg/ml is a registered trademark of Pharmacia Limited

4

1

Weight Gain: There is a tendency for women to gain weight while on
Depo-Provera® 150mg/ml 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® 150mg/ml, 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® 150mg/ml 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.

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® 150mg/ml.
Significant risk factors for osteoporosis include:
• Alcohol abuse and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g., anticonvulsants
or corticosteroids
• Low body mass index or eating disorder, e.g., anorexia nervosa or
bulimia
• Previous low trauma fracture
• Family history of osteoporosis
A retrospective cohort study using data from the General Practice
Research Database (GPRD) reported that women using MPA injections
(DMPA), have a higher risk of fracture compared with contraceptive users
with no recorded use of DMPA (incident rate ratio 1.41, 95% CI 1.35-1.47
for the five year follow-up period); it is not known if this is due to DMPA, or
to other related lifestyle factors which have a bearing on fracture rate. By
contrast, in women using DMPA, the fracture risk before and after starting
DMPA was not increased (relative risk 1.08, 95% CI 0.92-1.26).
Importantly, this study could not determine whether use of DMPA has an
effect on fracture rate later in life.
For further information on BMD changes in both adult and adolescent
females, as reported in recent clinical studies, refer to section 5.1 of the
SPC. Adequate intake of calcium and Vitamin D whether from the diet or
from supplements is important for bone health in women of all ages.
Menstrual Irregularity: The administration of Depo-Provera® 150mg/ml
usually causes disruption of the normal menstrual cycle. Bleeding
patterns include amenorrhoea (present in up to 30% of women during the
first 3 months and increasing to 55% by month 12 and 68% by month 24);
irregular bleeding and spotting; prolonged (>10 days) episodes of
bleeding (up to 33% of women in the first 3 months of use decreasing to
12% by month 12). Rarely, heavy prolonged bleeding may occur.
Evidence suggests that prolonged or heavy bleeding requiring treatment
may occur in 0.5-4 occasions per 100 women years of use. If abnormal
bleeding persists or is severe, appropriate investigation should take place
to rule out the possibility of organic pathology and appropriate treatment
should be instituted when necessary. Excessive or prolonged bleeding
can be controlled by the co-administration of oestrogen. This may be
delivered either in the form of a low dose (30 micrograms oestrogen)
combined oral contraceptive pill or in the form of oestrogen replacement
therapy such as conjugated equine oestrogen (0.625-1.25 mg daily).
Oestrogen therapy may need to be repeated for 1-2 cycles. Long-term coadministration of oestrogen is not recommended.
Return to Fertility: There is no evidence that Depo-Provera® 150mg/ml
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®
150mg/ml 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 neverusers. 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
No of cases per
Possible additional
DMPA
10,000 women who
cases per 10,000
are never-users
DMPA users
20
Less than 1
Much less than 1
30
44
2-3
40
160
10
*based on use for 5 years

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® 150mg/ml.
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 DepoProvera® 150mg/ml, 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® 150mg/ml 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® 150mg/ml 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® 150mg/ml if endometrial or endocervical
tissue is submitted for examination.
The results of certain laboratory tests may be affected by the use of
Depo-Provera® 150mg/ml. These include gonadotrophin levels
(decreased), plasma progesterone levels (decreased), urinary
pregnanediol levels (decreased), plasma oestrogen levels (decreased),
plasma cortisol levels (decreased), glucose tolerance test, metyrapone
test, liver function tests (may increase), thyroid function tests (protein
bound iodine levels may increase and T3 uptake levels may decrease).
Coagulation test values for prothrombin (Factor II), and Factors VII, VIII,
IX and X may increase.
Interaction with other medicinal products and other forms of
interaction
Aminoglutethimide administered concurrently with Depo-Provera®
150mg/ml may significantly depress the bioavailability of Depo-Provera®
150mg/ml.
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.

2

Fertility, pregnancy and lactation

Investigations: Uncommon: Cervical smear abnormal. Rare: Decreased
glucose tolerance.
Psychiatric Disorders: Common: Anorgasmia, depression, nervousness,
emotional disturbance, libido decreased, mood disorder, irritability,
insomnia. Uncommon: Anxiety.
Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps):
Rare: Breast cancer.
Blood and lymphatic system disorders: Rare: Anaemia. Not known: Blood
dyscrasia.
Respiratory, thoracic, and mediastinal disorders: Uncommon: Dyspnoea.
Reporting 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

Doctors should check that patients are not pregnant before the initial
injection of Depo-Provera® 150mg/ml, 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® 150mg/ml 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.

Overdose

Effects on ability to drive and use machines

No positive action is required other than cessation of therapy.

Depo-Provera® 150mg/ml may cause headaches and dizziness. Patients
should be advised not to drive or operate machinery if affected.

Pharmacodynamic properties
Pharmacotherapeutic group: Progestogens, ATC code: G03AC06
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® 150mg/ml with women using
medroxyprogesterone acetate injection (150 mg IM) showed no significant
differences in BMD loss between the two groups after two years of
treatment. Mean percent changes in BMD in the Depo-Provera®
150mg/ml group are listed in Table 1
Table 1. Mean Percent Change from Baseline in BMD in Women Using
DEPO-PROVERA® 150MG/ML by Skeletal Site

Undesirable effects
In a large clinical trial of over 3900 women, who were treated with DepoProvera® 150mg/ml 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® 150mg/ml were:
decreased libido or anorgasmia, backache, leg cramps, depression,
nausea, insomnia, leucorrhoea, acne, vaginitis, pelvic pain, breast pain,
no hair growth or alopecia, bloating, rash, oedema, hot flushes.
Adverse reactions are listed according to the following categories:
Very Common >10%, Common ≥1% and < 10%, Uncommon >0.1% and
<1%, Rare < 0.1%, Not known (frequency cannot be estimated from the
available data)
Ear and Labyrinth Disorders: Uncommon: Vertigo.
Gastrointestinal Disorders: Very common: Abdominal pain or discomfort.
Common: Bloating, nausea. Uncommon: Abdominal distension,
gastrointestinal disturbances. Rare: Rectal bleeding.
Infection & Infestations: Common: Vaginitis.
Metabolism & Nutrition Disorders: Common: Appetite decrease, appetite
increase Uncommon: Weight increase, weight decrease, fluid retention.
Musculoskeletal, Connective Tissue & Bone Disorders: Common: Back
pain. Uncommon: Arthralgia, muscle cramps, pain in limbs. Not known:
Osteoporosis including osteoporotic fractures, loss of bone mineral
density, axillary swelling.
Nervous System Disorders: Very common: Headaches. Common:
Dizziness. Uncommon: Somnolence, migraine, convulsions. Rare:
Paralysis. Not known: Syncope.
Reproductive System & Breast Disorders: Common: Amenorrhea, breast
pain/tenderness, intermenstrual bleeding, menometrorrhagia,
menorrhagia, pelvic pain, leucorrhoea. Uncommon: Vaginal discharge,
vulvovaginal dryness, dysmenorrhea, change in breast size, dyspareunia,
ovarian cyst, premenstrual syndrome, genitourinary infection, uterine
hyperplasia. Rare: Breast lumps or nipple bleeding. Not known: Abnormal
uterine bleeding (irregular, increase, decrease), galactorrhea, vaginal
cysts, prevention of lactation, sensation of pregnancy, lack of return to
fertility.
Vascular Disorders: Common: Hot flushes. Uncommon: Hypertension,
varicose veins, thrombophlebitis, pulmonary embolism. Not known:
Thromboembolic disorders, deep vein thrombosis.
Cardiovascular Disorders: Rare: Tachycardia.
Immune System Disorders: Uncommon: Hypersensitivity reactions (e.g.
anaphylaxis & anaphylactoid reactions, angioedema).
Hepato-biliary disorders: Uncommon: Abnormal liver enzymes, jaundice.
Not known: Disturbed liver function.
Skin & Subcutaneous Tissue Disorders: Common: Acne, alopecia, rash.
Uncommon: Chloasma, dermatitis, ecchymosis, hirsutism, pruritus,
melasma, urticaria, oedema. Not known: Skin striae, scleroderma.
General Disorders and Administration Site Conditions: Common: Fatigue,
injection site reactions (such as pain or abscess), asthenia, paraesthesia.
Uncommon: Chest pain, pyrexia. Rare: Thirst, hoarseness, paralysis. Not
known: Facial palsy.

Lumbar Spine

Total Hip

Time on
Treatment

N

N

1 year

166

Mean %
Change
(95% CI)
-2.7
(-3.1 to -2.3)

2 year

106

-4.1
(-4.6 to -3.5)

106

166

Femoral Neck
Mean %
Change
(95% CI)
-1.7
(-2.1 to -1.3)

N

-3.5
(-4.2 to -2.7)

106

166

Mean %
Change
(95% CI)
-1.9
(-2.5 to
-1.4)
-3.5
(-4.3 to
- 2.6)

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

Spine

Total Hip

Medroxypro
gesterone
acetate
5
years*
7
years**

Control

n=33
-5.38%
n=12
-3.13%

n=105
0.43%
n=60
0.53%

Medroxyp
rogestero
ne
acetate
n=21
-5.16%
n=7
-1.34%

Femoral Neck
Control

n=65
0.19%
n=39
0.94%

Medroxyp
rogestero
ne
acetate
n=34
-6.12%
n=13
-5.38%

Control

n=106
-0.27%
n=63
-0.11%

*The treatment group consisted of women who received
medroxyprogesterone acetate injection (150 mg IM) for 5 years and the
control group consisted of women who did not use hormonal
contraception for this time period.
** The treatment group consisted of women who received
medroxyprogesterone acetate Injection (150 mg IM) for 5 years and were
then followed up for 2 years post-use and the control group consisted of
women who did not use hormonal contraceptive for 7 years.

3

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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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