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DEPO-PROVERA 150MG/ML SUSPENSION FOR INJECTION

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

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Package leaflet: Information for the patient



®

Depo-Provera 150mg/ml 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.
The name of your medicine is Depo-Provera 150mg/ml Suspension for Injection but will be
referred to as Depo-Provera throughout this leaflet.
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.
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
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.
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, 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.
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 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’.

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 pro-longed vaginal bleeding may be increased if Depo-Provera is used
immediately following childbirth or termination of pregnancy.
If you forget an injection of Depo-Provera
If you forget your injection or are late getting your next injection (i.e. wait longer than 12 weeks
between injections), there is a greater risk that you could become pregnant. Ask your doctor or
healthcare professional to find out when you should receive your next injection of DepoProvera 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 DepoProvera 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 breast-feeding
 pelvic pain
 painful intercourse
 prevention of lactation
Rare: may affect up to 1 in 1,000 people
 breast cancer
 reduction in red blood cell
 blood disorder
 difficulty reaching orgasm
 behaviour change
 mood change
 irritability
 anxiety
 migraine
 paralysis
 fainting
 feeling of dizziness or spinning
 heart beats more rapidly
 high blood pressure
 varicose veins
 rectal bleeding
 digestive disorder
 liver enzyme disorder
 accumulation of fat (at injection site)
 inflammation of the skin
 scar tissue formation
 stretch marks
 pain in a joint
 muscular cramps
 bone density decreased (osteoporosis)
 vaginal pain or inflammation
 stopping or extended break of your periods
 breast pain
 inflammation of the vagina
 stopping or extended break of your periods
 breast pain
 uterine bleeding or excessive bleeding
 periods with abnormally heavy or prolonged bleeding
 vaginal dryness
 change in breast size
 ovarian or vaginal cyst
 premenstrual syndrome
 excessive thickening of the lining of the womb
 breast lump
 nipple bleeding
 delayed egg release with longer menstrual cycles (periods)
 feel pregnant
 fever
 tiredness
 injection site pain or tenderness
 injection site lump or dimple
 feeling thirsty
 hoarseness
 facial nerve paralysis
 decreased sugar tolerance
 abnormal smear
Possible effect on your periods
Depo-Provera will usually disturb the pattern of a woman’s period.
After the first injection it is most likely that you will have irregular, possibly lengthy bleeding or
spotting. This will continue in some women. This is quite normal and nothing to worry about.

One third of women will not have any bleeding at all after the first injection. After 4 injections,
most women find that their periods have stopped completely. Not having periods is nothing to
worry about.
If you experience very heavy or prolonged bleeding you should talk to your doctor. This
happens rarely but can be treated.
When you stop taking Depo-Provera your periods will return to normal in a few months.
Possible effects on your bones
Depo-Provera works by lowering levels of oestrogen and other hormones. However, low
oestrogen levels can cause bones to become thinner (by reducing bone mineral density).
Women who use Depo-Provera tend to have lower bone mineral density than women of the
same age who have never used it. The effects of Depo-Provera are greatest in the first 2-3
years of use. Following this, bone mineral density tends to stabilise and there appears to be
some recovery when Depo-Provera is stopped. It is not yet possible to say whether 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, pharmacist or nurse. This includes any possible
side effects not listed in this leaflet. You can also report any 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 which is stated on the carton and vial label after
‘Exp’. The expiry date refers to the last day of that month.
Do not store above 25°C.
Do not freeze.
If the suspension becomes discoloured or show any signs of deterioration, seek the advice of
your pharmacist.
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.
The 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; PL 18799/2393
Leaflet date: 23.02.2017

POM

Depo-Provera is a registered trademark of Pfizer.

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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. Excipients are: macrogol 4000, polysorbate 80, sodium chloride, methyl parahydroxybenzoate,
propyl parahydroxybenzoate, and water for injections.
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 150mg medroxyprogesterone acetate. The sterile aqueous suspension of
Depo-Provera should be vigorously shaken just before use to ensure that the dose being given represents
a uniform suspension of Depo-Provera. Doses should be given by deep intramuscular injection into the
buttock or arm.
Care should be taken to ensure that the depot injection is given into the muscle tissue, preferably the
gluteus maximus, but other muscle tissue such as the deltoid may be used and the site of injection should
be cleansed using standard methods prior to administration of the injection.
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.
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 hormonedependent 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
DMPA
20
30
40

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

Possible additional cases
per 10,000 DMPA users
Much less than 1
2-3
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 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 ≥
Uncommon ≥
Rare ≥ 1/10,000
Common ≥ 1/100 to < 1/10 1/1000 to <1/100
to < 1/1000
1/10
Neoplasms
Benign, Malignant
and Unspecified (Incl.
Cysts and Polyps)
Blood and lymphatic
system disorders
Immune system
disorders

Breast cancer

Anaemia, Blood disorder
Drug
hypersensitivity

Metabolism &
Nutrition Disorder

Psychiatric disorders Nervousnes Depression,
s
Libido
decreased
Nervous system
Headache
Dizziness
disorders
Ear and Labyrinth
Disorder
Cardiac disorder
Vascular disorders

Respiratory, thoracic,
and mediastinal
disorders
Gastrointestinal
Abdominal
disorders
pain,
Abdominal
discomfort
Hepatobiliary
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

Nausea,
Abdominal
distension

Skin and
subcutaneous tissue
disorders

Alopecia,
Acne, Rash

Musculoskeletal and
connective tissue
disorders
Reproductive system
and breast disorders

Back pain, Pain
in extremity

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

Rectal haemorrhage,
Gastrointestinal disorder

Hepatic
Function
abnormal
Hirsutism,
Urticaria,
Pruritus,
Chloasma

Jaundice, Hepatic enzyme
abnormal
Lipodystrophy acquired*,
Dermatitis, Ecchymosis,
Scleroderma, Skin striae

Arthralgia, Muscle spasms,
Osteoporosis, Osteoporotic
fractures
Vaginal
Dysfunctional
Vaginitis, Amenorrhoea, Breast
discharge,
uterine bleeding
pain, Metrorrhagia,
Breast
(irregular,
Menometrorrhagia, Menorrhagia,
tenderness,
increase,
Vulvovaginal dryness, Breast
Dysmenorrhea,
decrease,
atrophy, Ovarian cyst,
Centiourinary
spotting,
Premenstrual
tract infection Galactorrhoea
syndrome, Endometrial
Pelvic pain,
hyperplasia, Breast mass, Nipple
Dyspareunia,
exudate bloody, Vaginal cyst,
Suppressed
Breast enlargement, Lack of
lactation
return to fertility, Sensation of
pregnancy
General disorders
Odema/Fluid
Chest pain
Pyrexia, Fatigue, Injection site
and administration
retention,
reaction*, Injection site persistent
site conditions
Asthenia
atrophy/ indentation/dimpling*,
Injection site nodule/lump*,
Injection site pain/ tenderness*
Thirst, Dysphonia, VIIth nerve
paralysis, Axillary swelling
Investigation
Weight
Bone density decreased, Glucose
increased,
tolerance decreased, Cervical
Weight
smear abnormal
decreased
*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
Lumbar Spine

Total Hip

Femoral Neck

Time on
Treatment

N

Mean% Change
(95% CI)

N

Mean % Change
(95% CI)

N

Mean % Change
(95% CI)

1 year

166

-2.7
(-3.1 to -2.3)

166

-1.7
(-2.1 to -1.3)

166

-1.9
(-2.5 to -1.4)

2 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)

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

5 years*
7 years**

Spine
Medroxyprogesterone
acetate
n=33
-5.38%
n=12
-3.13%

Total Hip
Control

n= 105
0.43%
n=60
0.53%

Medroxyprogesterone
acetate
n=21
-5.16%
n=7
-1.34%

Femoral Neck
Control

n=65
0.19%
n=39
0.94%

Medroxyprogesterone
acetate
n=34
-6.12%
n=13
-5.38%

Control

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

*The treatment group consisted of women who received medroxyprogesterone acetate injection (150mg
IM) for 5 years and the control group consisted of women who did not use hormonal contraception for this
time period.
** The treatment group consisted of women who received medroxyprogesterone acetate Injection (150mg
IM) for 5 years and were then followed up for 2 years post-use and the control group consisted of women
who did not use hormonal contraceptive for 7 years.
BMD Changes in Adolescent Females (12-18 years)
Results from an open-label, non-randomised, clinical study of medroxyprogesterone acetate Injection
(150mg IM every 12 weeks for up to 240 weeks (4.6 years), followed by post-treatment measurements) in
adolescent females (12-18 years) also showed that medroxyprogesterone acetate IM use was associated
with a significant decline in BMD from baseline. Among subjects who received ≥ 4 injections/60-week
period, the mean decrease in lumbar spine BMD was -2.1% after 240 weeks (4.6 years); mean decreases
for the total hip and femoral neck were -6.4% and -5.4%, respectively. Post-treatment follow-up showed
that, based on mean values, lumbar spine BMD recovered to baseline levels approximately 1 year after
treatment was discontinued and that hip BMD recovered to baseline levels approximately 3 years after
treatment was discontinued. However, it is important to note that a large number of subjects discontinued
from the study, therefore these results are based on a small number of subjects (n=71 at 60 weeks and
n=25 at 240 weeks after treatment discontinuation). In contrast, a non-comparable cohort of unmatched,
untreated subjects, with different baseline bone parameters from the DMPA users, showed mean BMD
increases at 240 weeks of 6.4%, 1.7% and 1.9% for lumbar spine, total hip and femoral neck, respectively.
Pharmacokinetic properties
Parenteral medroxyprogesterone acetate (MPA) is a long acting progestational steroid. The long duration
of action results from its slow absorption from the injection site. Immediately after injection of 150mg/ml
MPA, plasma levels were 1.7 ± 0.3 nmol/l. Two weeks later, levels were 6.8 ± 0.8 nmol/l. Concentrations
fell to the initial levels by the end of 12 weeks. At lower doses, plasma levels of MPA appear directly
related to the dose administered. Serum accumulation over time was not demonstrated. MPA is eliminated
via faecal and urinary excretion. Plasma half-life is about six weeks after a single intramuscular injection.
At least 11 metabolites have been reported. All are excreted in the urine, some, but not all, conjugated.
Shelf life
The expiry date is printed on the carton and 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; PL 18799/2393
Leaflet date: 23.02.2017
Depo-Provera is a registered trademark of Pfizer.

POM

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Source: Medicines and Healthcare Products Regulatory Agency

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

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