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DEPO-PROVERA 150MG/ML SUSPENSION FOR INJECTION

Active substance(s): MEDROXYPROGESTERONE ACETATE

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Package leaflet: Information for the user
®

Depo-Provera 150mg/ml Suspension for Injection
(medroxyprogesterone acetate)
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 whether it is suitable for you,
especially if you wish to use it for more than 2 years (See section 1 )
• Depo-Provera may not be suitable for you, if you have a history of certain medical
conditions (see section 2) or if you are taking a medicine called aminoglutethiamide that
thins the blood (see section 2) Your doctor or nurse should take a full medical history before
prescribing Depo-Provera.
• Regular use of Depo-Provera causes a gradual loss of bone mineral density (see Section
4) For a small number of patients that were followed-up, the average bone mineral density
returned to average 1-3 years after they stopped using Depo-Provera. Teenagers who are
rapidly developing their bones may be at particular risk and should only use Depo-Provera if
other methods of contraception have been discussed and considered unsuitable or
unacceptable.
Your doctor may plan to conduct a general medical as well as a gynaecological examination
before they decide to prescribe Depo-Provera for you and may request you to visit the clinic
for similar examinations at appropriate intervals thereafter.
The name of your medicine is Depo-Provera 150mg/ml Suspension for Injection, but will be
referred to as Depo-Provera throughout this leaflet. Please note that this leaflet also
contains information about the other strength: Depo-Provera 50mg/ml Suspension for
Injection.
What is in this leaflet:
1. What Depo-Provera is and what it is used for
2. What you need to know before you use Depo-Provera
3. How to use Depo-Provera
4. Possible side effects
5. How to store Depo-Provera
6. Contents of this pack and other information







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:
Depo-Provera does not protect against HIV infection (AIDS) and other sexually transmitted
diseases.
Other medicines and Depo-Provera:
• Tell your doctor or pharmacist if you are taking , have recently taken or might take any
other medicines.
• Tell your doctor or healthcare professional if you are taking a medicine called
aminoglutethiamide or other medicines that thin your blood (anticoagulants) as these may
affect the way Depo-Provera works.
• Always tell your doctor or healthcare professional who treats you that you are using DepoProvera as a contraceptive if you are taking or have recently taken any other medicines,
even those you bought yourself without a prescription, because medicines can sometimes
interact with each other.
Pregnancy:
• Your doctor will check that you are not pregnant before giving you the first injection and
also if any following injection is delayed beyond 89 days (12 weeks and 5 days).
• Depo-Provera must not be taken if you are pregnant as hormonal medicines can affect the
developing baby.
• If you think you may have become pregnant while using Depo-Provera for contraception,
tell your doctor immediately.
Effect on future fertility:
• Your usual level of fertility should return when the effect of the injection has worn off.
• This takes different amounts of time in different women, and does not depend on how long
you have been using Depo-Provera.
• In studies, over 80% of women trying to get pregnant conceived within 15 months of the
last injection; however this varied from 4 months after the last injection to more than two
years.
• Some women have got pregnant as early as 14 weeks after their last injection.

1. What Depo-Provera is and what it is used for

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.

Depo-Provera is a long acting contraceptive. This medicine contains medroxyprogesterone
acetate (MPA), which is one of a group of medicines called “Progestogens”. It is similar to (but
not the same as) the natural hormone progesterone that is produced in the ovaries during the
second half of your menstrual cycle.

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

Depo-Provera contains methyl parahydroxybenzoate , propyl parahydroxybenzoate and
sodium:
Methyl parahydroxybenzoate and propyl parahydroxybenzoate may cause allergic reactions
(possibly delayed), and exceptionally, bronchospasm.
This medicinal product contains less than 1mmol sodium (23mg) per 150mg/ml, i.e. essentially
‘sodium free’.

Depo-Provera can be used:
• For long-term contraception where you and the person who provides your contraception
(e.g. your doctor or healthcare professional) have decided that this method is the most
suitable for you.
• If you wish to use Depo-Provera for more than 2 years your doctor or healthcare
professional may wish to re-evaluate the risks and benefits of using Depo-Provera to make
sure that it is still the best option for you.
• In teenagers only after other methods of contraception have been discussed with the
healthcare professional who provides your contraception and considered to be unsuitable
or unacceptable.
• For just one or two occasions in the following cases:
• if your partner is undergoing a vasectomy, to give you protection until the vasectomy
becomes effective
• if you are being immunised against rubella, to prevent pregnancy during the period of
activity of the virus
• if you are awaiting sterilisation.

2. What you need to know before you use Depo-Provera
Do not use Depo-Provera
• If you are allergic (hypersensitive) to the active ingredient (MPA) or any of the other
ingredients. (listed in section 6) There is a small risk of a severe allergic reaction to DepoProvera that will require emergency medical treatment.
• If you think you may be pregnant.
• If you have had, or think you may have, hormone-dependent cancer of the breast or
reproductive organs.
• If you have unexplained bleeding from the womb (uterus)
• If you have liver disease.
• If you have not yet started your periods.
Warnings and Precautions
Talk to your doctor or healthcare professional before using Depo-Provera.
Before your doctor or healthcare professional prescribes Depo-Provera, you may need to have
a physical examination. It is important to tell your doctor or healthcare professional if you have,
or have had in the past, any of the following conditions. Your doctor will then discuss with you
whether Depo-Provera is suitable for you.









Migraine headaches – if you develop migraine you should consult your doctor before
receiving further injections of Depo-Provera
Diabetes or a family history of diabetes
Severe pain or swelling in the calf (indicating a possible clot in the leg, which may be called
phlebitis)
Blood clotting disorders such as deep vein thrombosis (blood clot in the legs), pulmonary
embolus (blood clot in the lung) or a stroke you should not receive further injections of
Depo-Provera.
Problems with your eyesight while using Depo-Provera; for example a sudden partial or
complete loss of vision or double vision
Past history of or current depression
Problems with your liver or liver disease
Problems with your kidneys or kidney disease.

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 breast-feeding.
Provided that the injection is given at the times stated above, then you are protected from
pregnancy straight away and there is no need to take extra precautions.
Depo-Provera works as a contraceptive for 12 weeks in your body. There is no way of
reversing the injection once it is given.
For effective contraceptive cover Depo-Provera MUST be given every 12 weeks. Make sure
that you or your doctor makes your next appointment for 12 weeks time.
The risk of heavy or prolonged 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.

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 tend to have lower bone mineral density than women of
the same age who have never used it. The effects of Depo-Provera are greatest in the first 2-3
years of use. Following this, bone mineral density tends to stabilise and there appears to be
some recovery when Depo-Provera is stopped. It is not yet possible to say whether
Depo-Provera increases the risk of osteoporosis (weak bones) and fractures in later life.
Tell your doctor immediately if you experience any of the above symptoms.
The following other side effects may occur:
Common (may affect up to 1 in 10 people)
Abdominal pain or discomfort, bloating, feeling sick, vaginal discharge or inflammation,
changes in appetite, back pain, headaches, dizziness, irregular periods, very light or no
periods (amenorrhoea), breast pain or tenderness, pelvic pain, hot flushes, acne, hair loss,
rash, weakness or tiredness, injection site reactions, feeling of weakness, tingling or numbness
in the hands and feet, depression, nervousness, insomnia (difficulty sleeping), irritability,
anorgasmia (failure to climax during sexual intercourse), emotional disturbance, intermenstrual
bleeding (bleeding between periods), menorrhagia (heavy periods).
Uncommon (may affect up to 1 in 100 people)
Jaundice (this will cause yellowing of the skin and the whites of the eyes), hypertension,
varicose veins, thrombophlebitis (inflammation of part of a vein), pulmonary embolism (blood
clot in the lungs which causes chest pain and breathlessness), allergic reactions (such as
swelling on the face and throat), abnormal liver enzymes (blood tests used to measure liver
function), feeling of dizziness or ‘spinning’, abdominal discomfort, change in weight, fluid
retention, joint pain, muscle cramps, pain in legs and arms, somnolence (sleepiness), migraine,
convulsion (‘fit’), vaginal dryness, painful periods, change in breast size, painful intercourse,
ovarian cyst, premenstrual syndrome, infections of the urinary tract or reproductive organs, an
increase in thickness of the lining of the womb, dark patches on the skin, bruising, excessive
hair growth, itching, skin rash, swelling, chest pain, fever, abnormal cervical smear results,
anxiety, difficulty breathing.
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 breast feeding
mothers), feeling pregnant, delay in becoming pregnant after stopping Depo-Provera, scaling
of skin, scleroderma (a rare autoimmune disease that affects the skin and other parts of the
body), weakness in the face muscles, fainting, blood disorder, skin striae (stretch marks).
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 DepoProvera increases the risk of osteoporosis (weak bones) and fractures in later life.
The following are risk factors in the development of osteoporosis in later life. You should
discuss with your doctor before starting treatment if you have any of the following as an
alternative contraceptive may be more suitable to your needs;
• Chronic alcohol and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g. epilepsy medication or steroids
• Low body mass index or eating disorder, e.g. anorexia nervosa or bulimia
• Previous low trauma fracture that was not caused by a fall
• Strong family history of osteoporosis
Teenagers (up to 18 years): Normally, the bones of teenagers are rapidly growing and
Increasing in strength. The stronger the bones are when adulthood is reached, the greater the
protection against osteoporosis in later life. Since Depo-Provera may cause teenage bones to
become thinner at a time when they should be growing, its effect may be particularly important
in this age group. Bones start to recover when Depo-Provera is stopped, but it is not yet known
whether the bone mineral density reaches the same levels
as it would have if Depo-Provera had never been used. You should therefore discuss
whether another form of contraception might be more suitable for you with the person
who provides your contraception before starting Depo-Provera.
If you use Depo-Provera, it may help your bones if you take regular weight-bearing exercise
and have a healthy diet, including an adequate intake of calcium (e.g. in dairy products) and
vitamin D (e.g. in oily fish).
Possible risk of cancer:
Studies of women who have used different forms of contraception found that women who used
Depo-Provera for contraception had no increase in overall risk of developing cancer of the
ovary, womb, cervix or liver.
Possible risk of breast cancer
Breast cancer is rare among women under 40 years of age whether or not they use hormonal
contraceptives. Depo-Provera may increase the risk of breast cancer slightly compared with
women who have never used it. However, any excess risk is small in relation to the overall risk
of breast cancer, particularly in young women.
Older women have a higher baseline risk of breast cancer and therefore the increase in the
number of cases due to Depo-Provera is greater in older women than in younger women.
In absolute terms this means that:
A 15 year old who uses Depo-Provera for 5 years increases her chance of developing breast
cancer by a negligible amount by the age of 30.
A 25 year old who uses Depo-Provera for 5 years increases her chance of developing
breast cancer by the age of 40 from 44 cases per 10,000 women (without Depo-Provera
use) to up to 47 cases per 10,000 women i.e. an extra 3 cases/10,000.
A 35 year old who uses Depo-Provera for 5 years increases her chance of developing breast
cancer by the age of 50 from 160 cases per 10,000 women (without Depo-Provera use) to 170
cases per 10,000 women i.e. an extra 10 cases/10,000.

Possible risk of forming an abscess at the injection site:
As with any intramuscular injection, there is a risk of an abscess forming at the site of injection.
This may require medical or surgical attention.
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 Depo-Provera after the expiry date stated on the carton/ vial label after ‘Exp’.
The expiry date refers to the last day of that month.
Do not store above 25°C
Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. These measures will help to protect the
environment.

6. Contents of the pack and other information
What Depo-Provera contains:
The active ingredient in Depo-Provera is medroxyprogesterone acetate.
Each ml of suspension contains 150mg of medroxyprogesterone acetate.
Other ingredients are: macrogol 4000, polysorbate 80, sodium chloride, methyl
parahydroxybenzoate, propyl parahydroxybenzoate, and water for injections.
What Depo-Provera looks like and contents of the pack
Depo-Provera is a white sterile suspension.
It is available in vials containing 1ml suspension. Each pack contains 1 vial.
Manufactured by: Pfizer Manufacturing Belgium N.V., Rijksweg 12-2870 Puurs, Belgium.
Procured from within the EU and repackaged by the Product Licence holder:
B&S Healthcare, Unit 4, Bradfield Road, Ruislip, Middlesex, HA4 0NU, UK.
®
Depo-Provera 150mg/ml Suspension for Injection
POM
PL No: 18799/2393
Leaflet date: 09.01.2015
Depo-Provera is a registered trademark of Pfizer.

Depo-Provera® 150mg/ml 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.
Description
Depo-Provera is a white, sterile suspension for injection. Each 1ml contains 150mg
medroxyprogesterone acetate. The excipients are: methyl parahydroxybenzoate, macrogol
4000, polysorbate 80, propyl parahydroxybenzoate,sodium chloride, water for injection.
Uses
Depo-Provera is a long-term contraceptive agent suitable for use in women who have been
appropriately counselled concerning the likelihood of menstrual disturbance and the potential
for a delay in return to full fertility.
Depo-Provera may also be used for short-term contraception in the following circumstances:
(i) For partners of men undergoing vasectomy, for protection until the vasectomy
becomes effective.
(ii) In women who are being immunised against rubella, to prevent pregnancy during the
period of activity of the virus.
(iii) In women awaiting sterilisation.
Since loss of bone mineral density (BMD) may occur in females of all ages who use DepoProvera injection long-term, a risk/benefit assessment, which also takes into consideration the
decrease in BMD that occurs during pregnancy and/or lactation, should
be considered.
Use in adolescents (12-18 years)
In adolescents, Depo-Provera may be used. but only after other method 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, both other muscle tissue such as the deltoid may be used and
the site of injection should be cleansed using standard methods prior to administration of the
injection.
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.
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.
Contra-indications
Depo-Provera is contraindicated in patients with a known sensitivity to medroxyprogesterone
acetate or any ingredient of this medicine.
Depo-Provera should not be used during pregnancy, either for diagnosis or therapy.
Depo-Provera is contraindicated as a contraceptive at the above dosage in known or
suspected hormone-dependent malignancy of breast or genital organs.
Depo-Provera is contraindicated in patients with the presence or history of severe hepatic
disease whose liver function tests have not returned to normal.
Whether administered alone or in combination with oestrogen, Depo-Provera should not
be employed in patients with abnormal uterine bleeding until a definite diagnosis has been
established and the possibility of genital tract malignancy eliminated.
Special warnings and precautions for use
Warnings:
Loss of Bone Mineral Density:
Use of Depo-Provera reduces serum oestrogen levels and is associated with significant loss
of BMD due to the known effect of oestrogen deficiency on the bone remodelling system.
Bone loss is greater with increasing duration of use, however BMD appears to increase
after Depo-Provera is discontinued and ovarian oestrogen production increases.

This loss of BMD is of particular concern during adolescence and early adulthood, a critical
period of bone accretion. It is unknown if use of Depo-Provera by younger women will
reduce peak bone mass and increase the risk for fracture in later life.
A study to assess the BMD effects of medroxyprogesterone acetate IM (Depo-Provera,
DMPA) in adolescent females showed that its use was associated with a significant decline
in BMD from baseline. In the small number of women who were followed-up, mean BMD
recovered to around baseline values by 1 – 3 years after discontinuing treatment. In
adolescents, Depo-Provera may be used, but only after other methods of contraception
have been discussed with the patients and considered to be unsuitable or unacceptable.
In women of all ages, careful re-evaluation of the risks and benefits of treatment should
be carried out in those who wish to continue use for more than 2 years. In particular, in
women with significant lifestyle and/or medical risk factors for osteoporosis, other
methods of contraception should be considered prior to use of Depo-Provera.
Significant risk factors for osteoporosis include:
• Alcohol abuse and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g., anticonvulsants or corticosteroids
• Low body mass index or eating disorder e.g. anorexia nervosa or bulimia
• Previous low trauma fracture
• Family history of osteoporosis
A retrospective cohort study using data from the General Practice Research Database
(GPRD) reported that women using MPA injections (DMPA), have a higher risk of fracture
compared with contraceptive users with no recorded use of DMPA (incident rate ratio 1.41,
95% CI 1.35-1.47 for the five year follow-up period); it is not known if this is due to DMPA, or to
other related lifestyle factors which have a bearing on fracture rate. By contrast, in women
using DMPA, the fracture risk before and after starting DMPA was not increased (relative risk
1.08, 95% CI 0.92-1.26). Importantly, this study could not determine whether use of DMPA has
an effect on fracture rate later in life.
For further information on BMD changes in both adult and adolescent females, as reported in
recent clinical studies, refer to section 5.1 of the SPC. Adequate intake of calcium and Vitamin
D, whether from the diet or from supplements, is important for bone health in women of all
ages.
Menstrual irregularity: The administration of Depo-Provera usually causes disruption of the
normal menstrual cycle. Bleeding patterns include amenorrhoea (present in up to 30% of
women during the first 3 months and increasing to 55% by month 12 and 68% by month
24); irregular bleeding and spotting, prolonged (>10 days) episodes of bleeding (up to 33%
of women in the first 3 months of use decreasing to 12% by month 12). Rarely, heavy
prolonged bleeding may occur. Evidence suggests that prolonged or heavy bleeding
requiring treatment may occur in 0.5-4 occasions per 100 women years of use. If abnormal
bleeding persists or is severe, appropriate investigation should take place to rule out the
possibility of organic pathology and appropriate treatment should be instituted when
necessary. Excessive or prolonged bleeding can be controlled by the co-administration of
oestrogen. This may be delivered either in the form of a low dose (30 micrograms oestrogen)
combined oral contraceptive pill or in the form of oestrogen replacement therapy such as
conjugated equine oestrogen (0.625-1.25mg daily). Oestrogen therapy may need to be
repeated for 1-2 cycles. Long-term co-administration of oestrogen is not recommended.
Return to Fertility: There is no evidence that Depo-Provera causes permanent infertility.
Pregnancies have occurred as early as 14 weeks after a preceding injection, however, in
clinical trials, the mean time to return of ovulation was 5.3 months following the preceding
injection. Women should be counselled that there is a potential for delay in return to full fertility
following use of the method, regardless of the duration of use, however, 83% of women may
be expected to conceive within 12 months of the first “missed” injection (i.e. 15 months after
the last injection administered). The median time to conception was 10 months (range 4-31)
after the last injection.
Cancer risks: Long-term case-controlled surveillance of Depo-Provera users found no overall
increased risk of ovarian, liver, or cervical cancer and a prolonged, protective effect of reducing
the risk of endometrial cancer in the population of users.
Breast cancer is rare among women under 40 years of age whether or not they use hormonal
contraceptives.
Results from some epidemiological studies suggest a small difference in risk of the disease
in current and recent users compared with never-users. Any excess risk in current and recent
DMPA users is small in relation to the overall risk of breast cancer, particularly in young
women (see below), and is not apparent after 10 years since last use. Duration of use does not
seem to be important.
Possible number of additional cases of breast cancer diagnosed up to 10 years after
stopping injectable progestogens*
Age at last use of No of cases per 10,000 women
Possible additional cases
DMPA
who are never-users
per 10,000 DMPA users
20
Less than 1
Much less than 1
30
44
2-3
40
160
10
* based on use for 5 years
Weight Gain: There is a tendency for women to gain weight while on Depo-Provera therapy.
Studies indicate that over the first 1-2 years of use, average weight gain was 5-8 lbs. Women
completing 4-6 years of therapy gained an average of 14-16.5 lbs. There is evidence that
weight is gained as a result of increased fat and is not secondary to an anabolic effect or fluid
retention.
Anaphylaxis: Reports of anaphylactic responses (anaphylactic reactions, anaphylactic shock,
anaphylactoid reactions) have been received.
Thromboembolic Disorders: Should the patient experience pulmonary embolism,
cerebrovascular disease or retinal thrombosis while receiving Depo-Provera, the drug should
not be readministered.
Psychiatric Disorders: Patients with a history of endogenous depression should be carefully
monitored. Some patients may complain of premenstrual-type depression while on 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 Depo-Provera appears to be associated with a 15-20% reduction in serum high
density lipoprotein (HDL) cholesterol levels which may protect women from cardiovascular
disease. The clinical consequences of this observation are unknown.
The potential for an increased risk of coronary disease should be considered prior to use.
Doctors should carefully consider the use of Depo-Provera in patients with recent
trophoblastic disease before levels of human chorionic gonadotrophin have returned to
normal.
Physicians should be aware that pathologists should be informed of the patient’s use of
Depo-Provera if endometrial or endocervical tissue is submitted for examination.
The results of certain laboratory tests may be affected by the use of Depo-Provera. These
include gonadotrophin levels (decreased), plasma progesterone levels (decreased), urinary
pregnanediol levels (decreased), plasma oestrogen levels (decreased), plasma cortisol levels
(decreased), glucose tolerance test, metyrapone test, liver function tests (may increase),
thyroid function tests (protein bound iodine levels may increase and T3 uptake levels may
decrease). Coagulation test values for prothrombin (Factor II), and Factors VII, VIII, IX, and X
may increase.
Interaction with Other medicinal products and Other Forms of Interaction
Aminoglutethimide administered concurrently with Depo-Provera may significantly depress the
bioavailability of Depo-Provera.
Interactions with other medicinal treatments (including oral anticoagulants) have rarely been
reported, but causality has not been determined. The possibility of interaction should be borne
in mind in patients receiving concurrent treatment with other drugs.
The clearance of medroxyprogesterone acetate is approximately equal to the rate of hepatic
blood flow.
Because of this fact, it is unlikely that drugs which induce hepatic enzymes will significantly
affect the kinetics of medroxyprogesterone acetate. Therefore, no dose adjustment is
recommended in patients receiving drugs known to affect hepatic metabolising enzymes.
Medroxyprogesterone acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the
CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects with CYP3A4
inducers or inhibitors on MPA have not been conducted and therefore the clinical effects of
CYP3A4 inducers or inhibitors are unknown.
Fertility,Pregnancy and Lactation
Doctors should check that patients are not pregnant before the initial injection of DepoProvera, and also if administration of any subsequent injection is delayed beyond 89 days (12
weeks and five days).
Infants from accidental pregnancies that occur 1-2 months after injection of Depo-Provera may
be at an increased risk of low birth weight, which in turn is associated with an increased risk of
neonatal death.
The attributable risk is low because such pregnancies are uncommon.
Children exposed to medroxyprogesterone acetate in utero and followed to adolescence,
showed no evidence of any adverse effects on their health including their physical, intellectual,
sexual or social development.
Medroxyprogesterone acetate and/or its metabolites are secreted in breast milk, but there
is no evidence to suggest that this presents any hazard to the child. Infants exposed to
medroxyprogesterone acetate via breast milk have been studied for developmental and
behavioural effects to puberty. No adverse effects have been noted.
Effects on ability to drive and use machines
Depo-Provera may cause headaches and dizziness. Patients should be advised not to drive or
operate machinery if affected.
Undesirable effects
In a large clinical trial of over 3900 women, who were treated with Depo-Provera for up to
7 years, the following adverse events were reported.
The following adverse events were commonly (by more than 5% of subjects) reported:
menstrual irregularities (bleeding and/or amenorrhoea), weight changes, headache,
nervousness, abdominal pain or discomfort, dizziness, asthenia (weakness or fatigue).
Adverse events reported by 1% to 5% of subjects using Depo-Provera were: decreased
libido or anorgasmia, backache, leg cramps, depression, nausea, insomnia, leucorrhoea, acne,
vaginitis, pelvic pain, breast pain, no hair growth or alopecia, bloating, rash, oedema, hot
flushes.
Adverse reactions are listed according to the following categories:
Very Common >10%, Common ≥1% and <10%, Uncommon >0.1% and <1%, Rare < 0.1%,
Unknown (cannot be estimated from the available data)
Ear and Labyrinth Disorders: Uncommon: Vertigo
Gastrointestinal Disorders: Very common: Abdominal pain or discomfort. Common:
Bloating, nausea. Uncommon: Abdominal distension, gastrointestinal disturbances. Rare:
rectal bleeding.
Infection and Infestations: Common: Vaginitis.
Metabolism & Nutrition Disorders: Common: Appetite decrease, appetite increase.
Uncommon: weight increase, weight decrease, fluid retention.
Musculoskeletal, Connective Tissue & Bone Disorders: Common: Backpain. Uncommon:
Arthralgia, muscle cramps, pain in limbs. Not known: Osteoporosis including osteoporotic
fractures, loss of bone mineral density, axillary swelling.
Nervous System Disorders: Very common: Headaches. Common: Dizziness. Uncommon:
Somnolence, migraine, convulsions. Rare: Paralysis. Not known: Syncope.
Reproductive System & Breast Disorders: Common: Amenorrhea, breast pain/tenderness,
intermenstrual bleeding, menometrorrhagia, menorrhagia, pelvic pain, leucorrhoea.
Uncommon: Vaginal discharge, vulvovaginal dryness, dysmenorrhea, change in breast size,
dyspareunia, ovarian cyst, premenstrual syndrome, genitourinary infection, uterine hyperplasia.
Rare: Breast lumps or nipple bleeding. Not known: Abnormal uterine bleeding (irregular,
increase, decrease), galactorrhea, vaginal cysts, prevention of lactation, sensation
of pregnancy, lack of return to fertility.
Vascular Disorders: Common: Hot flushes. Uncommon: Hypertension, varicose veins,
thrombophlebitis, pulmonary embolism. Not known: Thromboembolic disorders, deep vein
thrombosis.
Cardiovascular Disorders: Rare: Tachycardia.
Immune System Disorders: Uncommon: Hypersensitivity reactions (e.g. anaphylaxis &
anaphylactoid reactions, angioedema).
Hepato-biliary disorders: Uncommon: Abnormal liver enzymes, jaundice. Not known: Disturbed
liver function.
Skin & Subcutaneous Tissue Disorders: Common: Acne, alopecia, rash. Uncommon:
Chloasma, dermatitis, ecchymosis, hirsutism, pruritus, melasma, urticaria, oedema.
Not known: skin striae, scleroderma.
General Disorders and Administration Site Conditions: Common: Fatigue, injection site
reactions (such as pain or abscess), asthenia, paraesthesia. Uncommon: Chest pain, pyrexia.
Rare: Thirst, hoarseness, paralysis. Not known: Facial palsy.
Investigations: Uncommon: Cervical smear abnormal. Rare: Decreased glucose tolerance.
Psychiatric Disorders: Common: Anorgasmia, depression, nervousness, emotional
disturbance, libido decreased, mood disorder, irritability, insomnia. Uncommon: Anxiety.
Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps): Rare: Breast cancer.
Blood and lymphatic system disorders: Rare: Anaemia. Not known: Blood dyscrasia.
Respiratory, thoracic, and mediastinal disorders: Uncommon: Dyspnoea.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important.
It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions via
the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Overdose
No positive action is required other than cessation of therapy.
Pharmacodynamic Properties
Pharmacotherapeutic group: Progestogens, ATC code: G03AC06
Medroxyprogesterone acetate exerts anti-oestrogenic, anti-androgenic and antigonadotrophic
effects.
BMD Changes in Adult Women: A study comparing changes in BMD in women using
Depo-Provera with women using medroxyprogesterone acetate injection (150mg IM) showed
no significant differences in BMD loss between the two groups after two years of treatment.
Mean percent changes in BMD in the Depo-provera group are listed in Table 1.
Table 1. Mean Percent Change from Baseline in BMD in Women Using DEPO-PROVERA by
Skeletal Site
Lumbar Spine

Total Hip

Femoral Neck

Time on
Treatment

N

Mean% Change N
(95%CI)

Mean % Change
(95% CI)

N

Mean % Change
(95% CI)

1 year

166
106

-1.7
(-2.1 to -1.3)
-3.5
(-4.2 to -2.7)

166

2 year

-2.7
(-3.1 to -2.3)
- 4.1
(-4.6 to -3.5)

-1.9
(-2.5 to -1.4)
-3.5
(-4.3 to -2.6)

166
106

106

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 lumber 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.
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 PostTherapy or 7 Years or Observation (Control)
Time in Spine
Total Hip
Femoral Neck
study
Medroxypro- Control
Medroxypro- Control
Medroxypro- Control
gesterone
gesterone
gesterone
acetate
acetate
acetate
5 years* n=33
n= 105
n=21
n=65
n=34
n=106
-5.38%
0.43%
-5.16%
0.19%
-6.12%
-0.27%
7 years** n=12
n=60
n=7
n=39
n=13
n=63
-3.13%
0.53%
-1.34%
0.94%
-5.38%
-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 posttreatment 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 (4.6years); 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
overtime 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 expiry date is printed on the carton/ vial label after ‘Exp’. The expiry date refers to the last
day of that month. Do not use Depo-Provera after this date.
Storage of the product
Do not store above 25°. Do not freeze. Do not mix with other agents. Discard any remaining
contents after use.
Manufactured by: Pfizer Manufacturing Belgium N.V, Rijksweg 12-2870 Puurs, Belgium.
Procured from within the EU and repackaged by the Product Licence Holder:
B&S Healthcare, Unit 4, Bradfield Road, Ruislip, Middlesex, HA4 0NU, UK.
®
Depo-Provera 150mg/ml Suspension for Injection
POM
PL No: 18799/2393
Leaflet date: 09.01.2015
Depo-Provera is a registered trademark of Pfizer.

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Source: Medicines and Healthcare Products Regulatory Agency

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