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DEPO-PROVERA 150MG/ML

Active substance(s): MEDROXYPROGESTERONE ACETATE

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PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Depo-Provera® 150 mg/ml
(medroxyprogesterone acetate)
This medicine is known by the above name but will be referred to as Depo-Provera
throughout this leaflet.
Please read all of this leaflet carefully before you start using this medicine because it
contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.







History of heart disease or cholesterol problems including any family history
If you have recently had a ‘hydatidiform mole’ which is a type of abnormal pregnancy
Asthma
Epilepsy
If you are using certain medicines such as high dose glucocorticoids (steroids), antiepileptics, and thyroid hormones. Tell the person who provides your contraception if you
are taking these or any other medicines - they may recommend a more suitable method
of contraception.

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.

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.

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

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.

Other medicines and Depo-Provera
• Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines.
• Tell your doctor or healthcare professional if you are taking a medicine called
aminoglutethiamide or other medicines that thin your blood (anticoagulants) as these
may affect the way Depo-Provera works.
• Always tell your doctor or healthcare professional who treats you that you are using
Depo-Provera as a contraceptive if you are taking or have recently taken any other
medicines, even those you bought yourself without a prescription, because medicines
can sometimes interact with each other.
Pregnancy, breast-feeding and fertility
• Your doctor will check that you are not pregnant before giving you the first injection and
also if any following injection is delayed beyond 89 days (12 weeks and 5 days).
• Depo-Provera must not be taken if you are pregnant as hormonal medicines can affect
the developing baby.
• If you think you may have become pregnant while using Depo-Provera for contraception,
tell your doctor immediately.

IMPORTANT INFORMATION YOU SHOULD KNOW ABOUT DEPO-PROVERA
Depo-Provera is a very effective injectable contraceptive which gives 12 weeks
continuous contraception with each injection. The effect is not reversible once the
injection is given.
• You must have injections of this contraceptive regularly every 12 weeks; otherwise you
may risk becoming pregnant (see section 3).
• Depo-Provera may not be suitable for every woman. You will need to discuss with your
doctor or healthcare professional providing your contraception on whether it is suitable
for you, especially if you wish to use it for more than 2 years (See section 1).
• Depo-Provera may not be suitable for you if you have a history of certain medical
conditions (see section 2) or if you are taking a medicine called aminoglutethiamide that
thins the blood (see section 2). Your doctor or nurse should take a full medical history
before prescribing Depo-Provera.
• Regular use of Depo-Provera causes a gradual loss of bone mineral density (see
section 4). For a small number of patients that were followed-up, the average bone
mineral density returned to average 1-3 years after they stopped using Depo-Provera.
Teenagers who are rapidly developing their bones may be at particular risk and should
only use Depo-Provera if other methods of contraception have been discussed and
considered unsuitable or unacceptable.
• Your doctor may plan to conduct a general medical as well as a gynaecological
examination before they decide to prescribe Depo-Provera for you and may request you
to visit the clinic for similar examinations at appropriate intervals thereafter.
What is in this leaflet
1. What Depo-Provera is and what it is used for
2. What you need to know before you use Depo-Provera
3. How to use Depo-Provera
4. Possible side effects
5. How to store Depo-Provera
6. Contents of the pack and other information
1. What Depo-Provera is and what it is used for
Depo-Provera is a long acting contraceptive. This medicine contains the active substance
medroxyprogesterone acetate (MPA), which is one of a group of medicines called
‘Progestogens’. It is similar to (but not the same as) the natural hormone, progesterone that
is produced in the ovaries during the second half of your menstrual cycle.
Depo-Provera acts by preventing an egg from fully developing and being released from the
ovaries during your menstrual cycle. If an egg is not released it cannot become fertilised by
sperm and result in pregnancy. Depo-Provera also causes changes in the lining of your
womb that makes it less likely for pregnancy to occur. It also thickens the mucus at the
entrance of the womb, making it more difficult for sperm to enter.

Effect on future fertility
• Your usual level of fertility should return when the effect of the injection has worn off.
• This takes different amounts of time in different women, and does not depend on how
long you have been using Depo-Provera.
• In studies, over 80% of women trying to get pregnant conceived within 15 months of the last
injection; however this varied from 4 months after the last injection to more than two years.
• Some women have got pregnant as early as 14 weeks after their last injection.
If you are breast-feeding
• Depo-Provera does not prevent the breast from producing milk so nursing mothers can
use it; however, it is better for the baby that for the first few weeks after birth its mother’s
milk contains no traces of any medicines, including Depo-Provera.
• Your doctor or healthcare professional may advise that you wait until at least 6 weeks
after your baby has been born before you start using Depo-Provera for contraception.
• If a baby is exposed to Depo-Provera in the breast milk, no harmful effects have been
seen in babies and children.
Driving and using machines
Depo-Provera may cause headaches and dizziness. Therefore be careful until you know
whether this medicine affects your ability to drive or use machines. If you have any
concerns discuss them with your doctor.
Depo-Provera contains methylparaben (E218), propylparaben (E216) and sodium
Methylparaben and propylparaben may cause allergic reactions (possibly delayed), and
exceptionally, bronchospasm.
This medicinal product contains less than 1 mmol sodium (23 mg) per 150 mg/ml, i.e.
essentially ‘sodium free’.

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.

3. How to use Depo-Provera

2. What you need to know before you use Depo-Provera

The risk of heavy or pro-longed vaginal bleeding may be increased if Depo-Provera is used
immediately following childbirth or termination of pregnancy.

Do not use Depo-Provera
• If you are allergic (hypersensitive) to the active ingredient (MPA) or any of the other
ingredients (listed in section 6). There is a small risk of a severe allergic reaction to
Depo-Provera that will require emergency medical treatment.
• If you think you may be pregnant.
• If you have had, or think you may have, hormone-dependent cancer of the breast or
reproductive organs.
• If you have unexplained bleeding from the womb (uterus).
• If you have liver disease.
• If you have not yet started your periods.
Warnings and precautions
Talk to your doctor or healthcare professional before using Depo-Provera.
Before your doctor or healthcare professional prescribes Depo-Provera, you may need to
have a physical examination. It is important to tell your doctor or healthcare professional if
you have, or have had in the past, any of the following conditions. Your doctor will then
discuss with you whether Depo-Provera is suitable for you.
• Migraine headaches – if you develop migraine you should consult your doctor before
receiving further injections of Depo-Provera
• Diabetes or a family history of diabetes
• Severe pain or swelling in the calf (indicating a possible clot in the leg, which may be
called phlebitis)
• Blood clotting disorders such as deep vein thrombosis (blood clot in the legs), pulmonary
embolus (blood clot in the lung) or a stroke you should not receive further injections of
Depo-Provera
• Problems with your eyesight while using Depo-Provera; for example a sudden partial or
complete loss of vision or double vision
• Past history of or current depression
• Problems with your liver or liver disease
• Problems with your kidneys or kidney disease

This medicine will be given to you by your doctor or healthcare professional.
(The last section of this leaflet contains instructions for your doctor or healthcare
professional on how they should do this.)
Depo-Provera is given every 12 weeks as a single intramuscular injection of 1 ml (150 mg
medroxyprogesterone acetate) into the buttock or upper arm. The injection is given during
the first 5 days after the beginning of a normal menstrual period.
Following childbirth the first Depo-Provera injection can be given within 5 days after
childbirth if you are not breast-feeding.
Provided that the injection is given at the times stated above, then you are protected from
pregnancy straight away and there is no need to take extra precautions.
Depo-Provera works as a contraceptive for 12 weeks in your body. There is no way of
reversing the injection once it is given.
For effective contraceptive cover, Depo-Provera MUST be given every 12 weeks. Make
sure that you or your doctor makes your next appointment for 12 weeks time.

If you 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.
Seek medical help immediately if you notice any of the following side effects:
• Hypersensitivity (allergic) reaction (it is not known how frequently this occurs) Symptoms
include sudden sudden skin rash, swelling of the face, lips, tongue or throat, wheezing
or difficulty in breathing.
• A blood clot in the lungs (this occurs rarely - may affect up to 1 in 1000 people)
Symptoms include
o Shortness of breath
o Breath-related chest pains
o Coughing up blood
• A blood clot in the leg (this occurs rarely - may affect up to 1 in 1000 people)
Deep vein thrombosis (DVT) is a condition in which a blood clot forms in one of your deep
veins, usually in your leg.

These are symptoms of a deep-vein thrombosis (DVT):
‒ You have pain, tenderness or swelling in your calf, ankle or foot
‒ You have painful or inflamed veins in your leg
‒ You find it difficult to put full weight on the affected leg
‒ You have purple discolouration of the skin of the leg or the skin becomes red and warm
to touch.
• Jaundice (yellowing of the skin or the whites of the eyes).
Women who use Depo-Provera tend to have lower bone mineral density than women of the
same age who have never used it. The effects of Depo-Provera are greatest in the first
2-3 years of use. Following this, bone mineral density tends to stabilise and there appears
to be some recovery when Depo-Provera is stopped. It is not yet possible to say whether
Depo-Provera increases the risk of osteoporosis (weak bones) and fractures in later life.
Other side-effects include:
Very common: may affect more than 1 in 10 people
• nervousness
• headache
• stomach pain or discomfort
• weight increase or decrease
Common: may affect up to 1 in 10 people
• depression
• libido decreased (reduced sex drive)
• dizziness
• feeling sick
• feeling bloated
• hair loss
• acne
• back pain
• vaginal discharge
• breast tenderness
• difficult or painful period
• urinary tract infection
• oedema/fluid retention
• weakness
Uncommon: may affect up to 1 in 100 people
• appetite increased or decreased
• difficulty sleeping
• convulsions (fits)
• drowsiness
• tingling
• hot flush
• liver disorder
• facial hair growth
• nettle rash or hives
• itchy skin
• temporary brown patches
• difficult or painful period
• unexpected or unusual vaginal bleeding or spotting
• milky discharge from the breast when not pregnant or breastfeeding
• pelvic pain
• painful intercourse
• prevention of lactation
Rare: may affect up to 1 in 1,000 people
• breast cancer
• reduction in red blood cell
• blood disorder
• difficulty reaching orgasm
• behavior change
• mood change
• irritability
• anxiety
• migraine
• paralysis
• fainting
• feeling of dizziness or spinning
• heart beats more rapidly
• high blood pressure
• varicose veins
• rectal bleeding
• digestive disorder
• liver enzyme disorder
• accumulation of fat (at injection site)
• inflammation of the skin
• scar tissue formation
• stretch marks
• pain in a joint
• muscular cramps
• bone density decreased (osteoporosis)
• vaginal pain or inflammation
• stopping or extended break of your periods
• breast pain
• inflammation of the vagina
• stopping or extended break of your periods
• breast pain
• uterine bleeding or excessive bleeding
• periods with abnormally heavy or prolonged bleeding
• vaginal dryness
• change in breast size
• ovarian or vaginal cyst
• premenstrual syndrome
• excessive thickening of the lining of the womb
• breast lump
• nipple bleeding
• delayed egg release with longer menstrual cycles (periods)
• feel pregnant
• fever
• tiredness
• injection site pain or tenderness
• injection site lump or dimple
• feeling thirsty
• hoarseness
• facial nerve paralysis
• decreased sugar tolerance
• abnormal smear
Possible effect on your periods
Depo-Provera will usually disturb the pattern of a woman’s period.
After the first injection it is most likely that you will have irregular, possibly lengthy bleeding
or spotting. This will continue in some women. This is quite normal and nothing to worry
about.

One third of women will not have any bleeding at all after the first injection. After 4
injections, most women find that their periods have stopped completely. Not having periods
is nothing to worry about.
If you experience very heavy or prolonged bleeding you should talk to your doctor. This
happens rarely but can be treated.
When you stop taking Depo-Provera your periods will return to normal in a few months.
Possible effects on your bones
Depo-Provera works by lowering levels of oestrogen and other hormones. However, low
oestrogen levels can cause bones to become thinner (by reducing bone mineral density).
Women who use Depo-Provera tend to have lower bone mineral density than women of the
same age who have never used it. The effects of Depo-Provera are greatest in the first 2-3
years of use. Following this, bone mineral density tends to stabilise and there appears to be
some recovery when Depo-Provera is stopped. It is not yet possible to say whether 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 DepoProvera had never been used. You should therefore discuss whether another form of
contraception might be more suitable for you with the person who provides your
contraception before starting Depo-Provera.
If you use Depo-Provera, it may help your bones if you take regular weight-bearing
exercise and have a healthy diet, including an adequate intake of calcium (e.g. in dairy
products) and vitamin D (e.g. in oily fish).
Possible risk of cancer
Studies of women who have used different forms of contraception found that women who
used Depo-Provera for contraception had no increase in overall risk of developing cancer
of the ovary, womb, cervix or liver.
Possible risk of breast cancer
Breast cancer is rare among women under 40 years of age whether or not they use
hormonal contraceptives. 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, pharmacist or nurse. This includes any
possible side effects not listed in this leaflet. You can also report side effects directly via the
Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can
help provide more information on the safety of this medicine.
5. How to store Depo-Provera
• Keep out of the sight and reach of children.
• Depo-Provera will be carefully stored at your doctor’s surgery, local pharmacy or your
clinic.
• Your doctor or pharmacist will ensure that the syringe is not stored above 25ºC and not
allowed to freeze.
• Do not use Depo-Provera after the last day of the month shown in the expiry date stated
on the pre-filled syringe label and the carton after EXP. The expiry date is the last day of
that month.
• Do not throw away medicines via wastewater or household waste. Ask your pharmacist
how to throw away medicines you no longer use. These measures will help protect the
environment.
6. Contents of the pack and other information
The active ingredient in Depo-Provera 150 mg/ml is medroxyprogesterone acetate. Each
1ml vial contains 150mg of medroxyprogesterone acetate.
Depo-Provera also contains macrogol 3350, sodium chloride, polysorbate 80, propyl
paraben, methylparaben and water for injections.
Hydrochloric acid or sodium hydroxide may also be added when the product is being made
to adjust the acidity or alkalinity of the product to the correct level.
Depo-Provera is a white, sterile suspension in a prefilled syringe with a needle for injection
enclosed in a sealed tray.
3

POM

PL: 17805/0265

This product is manufactured by Pharmacia N.V./S.A. Rijksweg 12, B-2870 Puurs, Belgium
and procured from within the EU by the Product Licence holder: Delta Pharma (Europe)
Ltd., 1 Colonial Way, P.O. Box 233, North Watford, Herts WD24 4EW and repackaged by
O.P.D. Laboratories Ltd., Watford, Herts WD24 4PR.
Leaflet revision and issue date (Ref.) 16.02.2017.
Depo-Provera is a registered trademark of Pharmacia Limited, UK.

To request a copy of this leaflet in Braille, large
print or audio please call 01923 332 796.

INFORMATION FOR MEDICAL OR HEALTHCARE PROFESSIONALS ONLY

Depo-Provera® 150mg/ml
(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 in a prefilled syringe with a needle for injection enclosed in
a sealed tray. Each 1 ml contains 150 mg medroxyprogesterone acetate. Excipients are macrogol
3350, sodium chloride, polysorbate 80, propylparaben, methylparaben and water for injections.
Hydrochloric acid or sodium hydroxide may be present as pH adjusters.
Uses
Depo-Provera is a long-term contraceptive agent suitable for use in women who have been
appropriately counselled concerning the likelihood of menstrual disturbance and the potential for a
delay in return to full fertility.
Depo-Provera may also be used for short-term contraception in the following circumstances:
(i) For partners of men undergoing vasectomy, for protection until the vasectomy becomes effective.
(ii) In women who are being immunised against rubella, to prevent pregnancy during the period of
activity of the virus.
(iii) In women awaiting sterilisation.
Since loss of bone mineral density (BMD) may occur in females of all ages who use Depo-Provera
injection long-term, a risk/benefit assessment, which also takes into consideration the decrease in
BMD that occurs during pregnancy and/or lactation, should be considered.
Use in adolescents (12 – 18 years)
In adolescents, Depo-Provera may be used, but only after other methods of contraception have been
discussed with the patient and considered unsuitable or unacceptable.
It is of the greatest importance that adequate explanations of the long-term nature of the product, of its
possible side-effects and of the impossibility of immediately reversing the effects of each injection are
given to potential users and that every effort is made to ensure that each patient receives such
counselling as to enable her to fully understand these explanations. Patient information leaflets are
supplied by the manufacturer. It is recommended that the doctor uses these leaflets to aid counselling
of the patient before giving the injection of Depo-Provera.
Consistent with good clinical practice, a general medical as well as a gynaecological examination
should be undertaken before administration of Depo-Provera and at appropriate intervals thereafter.
Dosage
Each ml of suspension contains 150 mg medroxyprogesterone acetate. The sterile aqueous
suspension of Depo-Provera should be vigorously shaken just before use to ensure that the dose
being given represents a uniform suspension of Depo-Provera. Doses should be given by deep
intramuscular injection into the buttock or arm.
Care should be taken to ensure that the depot injection is given into the muscle tissue, preferably the
gluteus maximus, but other muscle tissue such as the deltoid may be used and the site of injection
should be cleansed using standard methods prior to administration of the injection.
Assembly of syringe for single use:
1. Remove tip cap.
2. Position needle using aseptic technique.
3. Remove needle shield. The syringe is now ready for use.
Administration
Adults
First injection: To provide contraceptive cover in the first cycle of use, an injection of 150 mg i.m.
should be given during the first five days of a normal menstrual cycle. If the injection is carried out
according to these instructions, no additional contraceptive cover is required.
Postpartum: To increase assurance that the patient is not pregnant at the time of first administration,
this injection should be given within 5 days postpartum if not breast-feeding.
There is evidence that women prescribed Depo-Provera in the immediate puerperium can experience
prolonged and heavy bleeding. Because of this, the drug should be used with caution in the
puerperium. Women who are considering use of the product immediately following delivery or
termination should be advised that the risk of heavy or prolonged bleeding may be increased.
Doctors are reminded that in the non breast-feeding postpartum patient, ovulation may occur as early
as week 4. If the puerperal woman will be breast-feeding, the initial injection should be given no sooner
than six weeks postpartum, when the infant’s enzyme system is more fully developed. Further
injections should be given at 12 week intervals.
Further doses: These should be given at 12 week intervals, however, as long as the injection is given
no later than five days after this time, no additional contraceptive measures (e.g. barrier) are required.
(NB For partners of men undergoing vasectomy a second injection of 150 mg i.m. 12 weeks after the
first may be necessary in a small proportion of patients where the partner’s sperm count has not fallen
to zero.) If the interval from the preceding injection is greater than 89 days (12 weeks and five days) for
any reason, then pregnancy should be excluded before the next injection is given and the patient
should use additional contraceptive measures (e.g. barrier) for fourteen days after this subsequent
injection.
Paediatric population (12-18 years): Depo-Provera is not indicated before menarche. Data in
adolescent females (12-18 years) is available. Other than concerns about loss of BMD, the safety and
effectiveness of Depo-Provera is expected to be the same for adolescents after menarche and adult
females.
Switching from other Methods of Contraception: Depo-Provera should be given in a manner that
ensures continuous contraceptive coverage. This should be based upon the mechanism of action of
other methods (e.g. patients switching from oral contraceptives should have their first injection of
Depo-Provera within 7 days of taking their last active pill).
Hepatic Insufficiency: The effect of hepatic disease on the pharmacokinetics of Depo-Provera is
unknown. As Depo-Provera largely undergoes hepatic elimination it may be poorly metabolised in
patients with severe liver insufficiency (see Contraindications).
Renal Insufficiency: The effect of renal disease on the pharmacokinetics of Depo-Provera is unknown.
No dosage adjustment should be necessary in women with renal insufficiency, since Depo-Provera is
almost exclusively eliminated by hepatic metabolism.
Contraindications
Hypersensitivity to medroxyprogesterone acetate or to any of the excipients of this medicine.
Depo-Provera should not be used during pregnancy, either for diagnosis or therapy.
Depo-Provera is contraindicated as a contraceptive at the above dosage in known or suspected
hormone-dependent malignancy of breast or genital organs.
Depo-Provera is contraindicated in patients with the presence or history of severe hepatic disease
whose liver function tests have not returned to normal.
Whether administered alone or in combination with oestrogen, Depo-Provera should not be employed
in patients with abnormal uterine bleeding until a definite diagnosis has been established and the
possibility of genital tract malignancy eliminated.
Special warnings and precautions for use
Warnings
Loss of Bone Mineral Density:
Use of Depo-Provera reduces serum oestrogen levels and is associated with significant loss of BMD
due to the known effect of oestrogen deficiency on the bone remodelling system. Bone loss is greater
with increasing duration of use; however BMD appears to increase after Depo-Provera is discontinued
and ovarian oestrogen production increases.
This loss of BMD is of particular concern during adolescence and early adulthood, a critical period of
bone accretion. It is unknown if use of Depo-Provera by younger women will reduce peak bone mass
and increase the risk for fracture in later life.
A study to assess the BMD effects of medroxyprogesterone acetate IM (Depo-Provera, DMPA) in
adolescent females showed that its use was associated with a significant decline in BMD from
baseline. In the small number of women who were followed-up, mean BMD recovered to around
baseline values by 1- 3 years after discontinuing treatment. In adolescents, Depo-Provera may be
used, but only after other methods of contraception have been discussed with the patients and
considered to be unsuitable or unacceptable.
In women of all ages, careful re-evaluation of the risks and benefits of treatment should be carried out
in those who wish to continue use for more than 2 years. In particular, in women with significant
lifestyle and/or medical risk factors for osteoporosis, other methods of contraception should be
considered prior to use of Depo-Provera.

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

No of cases per 10,000 women who
are never-users

Possible additional cases per 10,000
DMPA users

20

Less than 1

Much less than 1

44
160

2-3
10

30
40
*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 Depo-Provera therapy.
Abscess formation: As with any intramuscular injection, especially if not administered correctly, there is
a risk of abscess formation at the site of injection, which may require medical and/or surgical
intervention.
Precautions
History or emergence of the following conditions requires careful consideration and appropriate
investigation: migraine or unusually severe headaches, acute visual disturbances of any kind,
pathological changes in liver function and hormone levels. Patients with thromboembolic or coronary
vascular disease should be carefully evaluated before using Depo-Provera.
A decrease in glucose tolerance has been observed in some patients treated with progestogens. The
mechanism for this decrease is obscure. For this reason, diabetic patients should be carefully
monitored while receiving progestogen therapy.
Rare cases of thromboembolism have been reported with use of Depo-Provera, but causality has not
been established.
The effects of medroxyprogesterone acetate on lipid metabolism have been studied with no clear
impact demonstrated. Both increases and decreases in total cholesterol, triglycerides and low-density
lipoprotein (LDL) cholesterol have been observed in studies. The use of Depo-Provera appears to be
associated with a 15-20 % reduction in serum high density lipoprotein (HDL) cholesterol levels which
may protect women from cardiovascular disease. The clinical consequences of this observation are
unknown.
The potential for an increased risk of coronary disease should be considered prior to use.
Doctors should carefully consider the use of Depo-Provera in patients with recent trophoblastic disease
before levels of human chorionic gonadotrophin have returned to normal.
Physicians should be aware that pathologists should be informed of the patient’s use of Depo-Provera
if endometrial or endocervical tissue is submitted for examination.
The results of certain laboratory tests may be affected by the use of Depo-Provera. These include
gonadotrophin levels (decreased), plasma progesterone levels (decreased), urinary pregnanediol
levels (decreased), plasma oestrogen levels (decreased), plasma cortisol levels (decreased), glucose
tolerance test, metyrapone test, liver function tests (may increase), thyroid function tests (protein
bound iodine levels may increase and T3 uptake levels may decrease). Coagulation test values for
prothrombin (Factor II), and Factors VII, VIII, IX and X may increase.
Interaction with other medicinal products and other forms of interaction
Aminoglutethimide administered concurrently with Depo-Provera may significantly depress the
bioavailability of Depo-Provera.
Interactions with other medicinal treatments (including oral anticoagulants) have rarely been reported,
but causality has not been determined. The possibility of interaction should be borne in mind in
patients receiving concurrent treatment with other drugs.
The clearance of medroxyprogesterone acetate is approximately equal to the rate of hepatic blood
flow. Because of this fact, it is unlikely that drugs which induce hepatic enzymes will significantly affect
the kinetics of medroxyprogesterone acetate. Therefore, no dose adjustment is recommended in
patients receiving drugs known to affect hepatic metabolising enzymes.
Medroxyprogesterone acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the CYP3A4.
Specific drug-drug interaction studies evaluating the clinical effects with CYP3A4 inducers or inhibitors
on MPA have not been conducted and therefore the clinical effects of CYP3A4 inducers or inhibitors
are unknown.
Fertility, pregnancy and lactation
Doctors should check that patients are not pregnant before the initial injection of Depo-Provera, and
also if administration of any subsequent injection is delayed beyond 89 days (12 weeks and five days).
Infants from accidental pregnancies that occur 1-2 months after injection of Depo-Provera may be at
an increased risk of low birth weight, which in turn is associated with an increased risk of neonatal
death. The attributable risk is low because such pregnancies are uncommon.
Children exposed to medroxyprogesterone acetate in utero and followed to adolescence, showed no
evidence of any adverse effects on their health including their physical, intellectual, sexual or social
development.

Medroxyprogesterone acetate and/or its metabolites are secreted in breast milk, but there is no
evidence to suggest that this presents any hazard to the child. Infants exposed to
medroxyprogesterone acetate via breast milk have been studied for developmental and behavioural
effects to puberty. No adverse effects have been noted.
Effects on ability to drive and use machines
Depo-Provera may cause headaches and dizziness. Patients should be advised not to drive or operate
machinery if affected.
Undesirable effects
The table below provides a listing of adverse drug reactions with frequency based on all-causality data
from clinical studies that enrolled more than 4200 women who received DMPA for contraception for up
to 7 years. Those most frequently (>5%) reported adverse drug reactions were weight increased
(69%), weight decreased (25%), headache (16%), nervousness (11%), abdominal pain or discomfort
(11%), dizziness (6%), and decrease in libido (6%).
The following lists of adverse reactions are listed within the organ system classes, under headings of
frequency (number of patients expected to experience the reaction), using the following categories:
Very common (≥1/10);
Common (≥1/100 to <1/10);
Uncommon (≥1/1000 to <1/100);
Rare (≥1/10,000 to <1/1000);
Very rare (<1/10,000);
Not known (cannot be estimated from the available data).
System Organ
Class

Very
Common
≥ 1/10

Common
≥ 1/100 to
<1/10

Uncommon
≥ 1/1000 to
< 1/100

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

Breast cancer

Drug
hypersensitivity

Nervousness

Headache

Depression,
Libido
decreased

Dizziness

Ear and
Labyrinth
Disorder
Cardiac disorder
Vascular
disorders

Respiratory,
thoracic, and
mediastinal
disorders
Gastrointestinal
disorders

Increased
appetite,
decreased
appetite
Insomnia

Seizure,
Somnolence,
Paraesthesia

Anaphylactic
reaction,
Anaphylactoid
reaction,
Angioedema

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

Hot flush

Dyspnoea

Abdominal
pain,
Abdominal
discomfort

Nausea,
Abdominal
distension

Hepatobiliary
disorders

Hepatic function
abnormal

Skin and
subcutaneous
tissue disorders

Alopecia, Acne,
Rash

Musculoskeletal
and connective
tissue disorders

Back pain, Pain
in extremity

Reproductive
system and,
breast disorders

Vaginal
discharge,
Breast
tenderness,
Dysmenorrhea
Genitourinary
tract infection

General
disorders and
administration
site conditions

Common
≥ 1/100 to
<1/10

Rare ≥ 1/10,000
to < 1/1000

Uncommon
≥ 1/1000 to
< 1/100

Bone density
decreased, Glucose
tolerance
decreased, Cervical
smear abnormal

*ADR identified post-marketing
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard
Overdose
No positive action is required other than cessation of therapy.
Pharmacodynamic properties
Pharmacotherapeutic group: Progestogens, ATC code: G03AC06
Medroxyprogesterone acetate exerts anti-oestrogenic, anti-androgenic and antigonadotrophic effects.
Mechanism of action
DMPA, when administered parenterally at the recommended dose to women, inhibits the secretion of
gonadotropins which, in turn, prevents follicular maturation and ovulation and causes thickening of
cervical mucus which inhibits sperm entry into the uterus.
BMD Changes in Adult Women: A study comparing changes in BMD in women using Depo-Provera
with women using medroxyprogesterone acetate injection (150 mg IM) showed no significant
differences in BMD loss between the two groups after two years of treatment. Mean percent changes
in BMD in the Depo-Provera group are listed in Table 1.
Table 1. Mean Percent Change from Baseline in BMD in Women Using Depo-Provera by Skeletal Site

Metabolism &
Nutrition
Disorder

Nervous system,
disorders

Very
Common
≥ 1/10
Weight
increased,
Weight
decreased

Investigation

Anaemia, Blood
disorder

Immune system
disorders

Psychiatric
disorders

Rare ≥ 1/10,000
to < 1/1000

System Organ
Class

Odema/Fluid
Retention,
Asthenia

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

Rectal
haemorrhage,
Gastrointestinal
disorder
Jaundice, Hepatic
enzyme abnormal

Hirsutism,
Urticaria,
Pruritus,
Chloasma

Lipodystrophy
acquired*,
Dermatitis,
Ecchymosis,
Scleroderma,
Skin striae
Arthralgia, Muscle
spasms,
Osteoporosis,
Osteoporotic
fractures

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

Vaginitis,
Amenorrhoea,
Breast pain,
Metrorrhagia,
Menometrorrhagia,
Menorrhagia,
Vulvovaginal
dryness,
Breast atrophy,
Ovarian cyst,
Premenstrual
syndrome
Endometrial
hyperplasia,
Breast mass, Nipple
exudate
bloody, Vaginal
cyst, Breast
enlargement, Lack
of return to fertility,
Sensation of
pregnancy
Pyrexia, Fatigue,
Injection site
reaction*, Injection
site persistent
atrophy/
indentation/
dimpling*,
Injection site
nodule/lump*,
Injection site pain/
tenderness* Thirst,
Dysphonia, VIIth
nerve paralysis,
Axillary swelling

Chest pain

Lumbar Spine
Mean % Change
(95% CI)

Total Hip

Femoral Neck

Time on
Treatment

N

1 year

166

-2.7
(-3.1 to -2.3)

166

-1.7
(-2.1 to -1.3)

166

-1.9
(-2.5 to -1.4)

2 year

106

- 4.1
(-4.6 to -3.5)

106

-3.5
(-4.2 to -2.7)

106

-3.5
(-4.3 to -2.6)

N

Mean % Change
(95% CI)

N

Mean % Change
(95% CI)

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

Femoral Neck

Medroxyprogesterone
acetate

Control

Medroxyprogesterone
acetate

Control

Medroxyprogesterone
acetate

Control

5 years*

n = 33
-5.38%

n = 105
0.43%

n = 21
-5.16%

n = 65
0.19%

n = 34
-6.12%

n = 106
-0.27%

7
years**

n = 12
-3.13%

n = 60
0.53%

n=7
-1.34%

n = 39
0.94%

n = 13
-5.38%

n = 63
-0.11%

*The treatment group consisted of women who received medroxyprogesterone acetate injection (150
mg IM) for 5 years and the control group consisted of women who did not use hormonal contraception
for this time period.
** The treatment group consisted of women who received medroxyprogesterone acetate Injection (150
mg IM) for 5 years and were then followed up for 2 years post-use and the control group consisted of
women who did not use hormonal contraceptive for 7 years.
BMD Changes in Adolescent Females (12-18 years)
Results from an open-label, non-randomised, clinical study of medroxyprogesterone acetate Injection
(150 mg IM every 12 weeks for up to 240 weeks (4.6 years), followed by post–treatment measurements)
in adolescent females (12-18 years) also showed that medroxyprogesterone acetate IM use was
associated with a significant decline in BMD from baseline. Among subjects who received ≥ 4
injections/60-week period, the mean decrease in lumbar spine BMD was - 2.1 % after 240 weeks (4.6
years); mean decreases for the total hip and femoral neck were -6.4 % and -5.4 %, respectively. Posttreatment 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 noncomparable cohort of unmatched, untreated subjects, with different baseline bone parameters from the
DMPA users, showed mean BMD increases at 240 weeks of 6.4%, 1.7% and 1.9% for lumbar spine, total
hip and femoral neck, respectively.
Pharmacokinetic properties
Parenteral medroxyprogesterone acetate (MPA) is a long acting progestational steroid. The long duration
of action results from its slow absorption from the injection site. Immediately after injection of 150 mg/ml
MPA, plasma levels were 1.7 ± 0.3 nmol/l. Two weeks later, levels were 6.8 ± 0.8 nmol/l. Concentrations
fell to the initial levels by the end of 12 weeks. At lower doses, plasma levels of MPA appear directly
related to the dose administered. Serum accumulation over time was not demonstrated. MPA is
eliminated via faecal and urinary excretion. Plasma half-life is about six weeks after a single intramuscular
injection. At least 11 metabolites have been reported. All are excreted in the urine, some, but not all,
conjugated.
Shelf life
The expiry date is printed on the pre-filled syringe label and carton after EXP. The 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°C and protect from freezing. Do not mix with other agents. Discard any
remaining contents after use.
Keep out of the sight and reach of children.
POM
PL: 17805/0265
This product is manufactured by Pharmacia N.V./S.A. Rijksweg 12, B-2870 Puurs, Belgium and
procured from within the EU by the Product Licence holder: Delta Pharma (Europe) Ltd., 1 Colonial
Way, P.O. Box 233, North Watford, Herts WD24 4EW and repackaged by O.P.D. Laboratories Ltd.,
Unit 6 Colonial Way, Watford, Herts WD24 4PR.
Leaflet revision and issue date (Ref.) 16.02.2017.
Depo-Provera is a registered trademark of Pharmacia Limited, UK.

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Source: Medicines and Healthcare Products Regulatory Agency

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