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DEPO-PROVERA 150MG/ML VIAL

Active substance(s): MEDROXYPROGESTERONE ACETATE

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Patient Information Leaflet

Depo-Provera® 150 mg/ml Vial
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.
Your medicine is called Depo-Provera 150 mg/ml Vial 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 DepoProvera 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 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
• History of heart disease or cholesterol problems including any family
history
• If you have recently had a ‘hydatidiform mole’ which is a type of
abnormal pregnancy
• Asthma
• Epilepsy



If you are using certain medicines such as high dose glucocorticoids
(steroids), anti-epileptics, and thyroid hormones. Tell the person who
provides your contraception if you are taking these or any other
medicines – they may recommend a more suitable method of
contraception.

Cervical smear testing
The results of a cervical smear and some laboratory tests could also be
affected if you are using Depo-Provera so it is important that you tell your
doctor.
Protection against sexually transmitted diseases
Depo-Provera does not protect against HIV infection (AIDS) and other
sexually transmitted diseases.
Other medicines and Depo-Provera
• Tell your doctor or pharmacist if you are taking, have recently taken or
might take any other medicines.
• Tell your doctor or healthcare professional if you are taking a medicine
called aminoglutethiamide or other medicines that thin your blood
(anticoagulants) as these may affect the way Depo-Provera works.
• Always tell your doctor or healthcare professional who treats you that
you are using 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.
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’.
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 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.
The risk of heavy or pro-longed vaginal bleeding may be increased if
Depo-Provera is used immediately following childbirth or termination of
pregnancy.
If you forget an injection of Depo-Provera
If you forget your injection or are late getting your next injection (i.e. wait
longer than 12 weeks between injections), there is a greater risk that you
could become pregnant. Ask your doctor or healthcare professional to find
out when you should receive your next injection of Depo-Provera and
which type of contraception should be used in the meantime.
Switching from other methods of contraception
When you switch from other contraceptive methods, your doctor will make
sure you are not at risk of becoming pregnant by giving you your first
injection at the appropriate time. If you switch from oral contraceptives, you
should have your first injection of Depo-Provera within 7 days after taking
your last pill.
If you have any further questions on the use of this medicine, ask your
doctor or healthcare professional.
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 skin rash, swelling of the face, lips,
tongue or throat, wheezing or difficulty in breathing.
• A blood clot in the lungs (this occurs rarely – may affect up to 1 in
1000 people)
Symptoms include
− Shortness of breath
− Breath-related chest pains
− Coughing up blood
• A blood clot in the leg (this occurs rarely – may affect up to 1 in 1000
people)
Deep vein thrombosis (DVT) is a condition in which a blood clot forms in
one of your deep veins, usually in your leg.

These are symptoms of a deep-vein thrombosis (DVT):
− 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 DepoProvera 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 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
• uterine bleeding or excessive bleeding
• periods with abnormally heavy or prolonged bleeding
• vaginal dryness
• change in breast size
• ovarian or vaginal cyst
• premenstrual syndrome
• excessive thickening of the lining of the womb
• breast lump
• nipple bleeding
• delayed egg release with longer menstrual cycles (periods)
• feel pregnant
• fever
• tiredness
• injection site pain or tenderness
• injection site lump or dimple
• feeling thirsty
• hoarseness
• facial nerve paralysis
• decreased sugar tolerance
• abnormal smear
Possible effect on your periods
Depo-Provera will usually disturb the pattern of a woman’s period.
After the first injection it is most likely that you will have irregular, possibly
lengthy bleeding or spotting. This will continue in some women. This is
quite normal and nothing to worry about.
One third of women will not have any bleeding at all after the first injection.
After 4 injections, most women find that their periods have stopped
completely. Not having periods is nothing to worry about.
If you experience very heavy or prolonged bleeding you should talk to your
doctor. This happens rarely but can be treated.
When you stop taking Depo-Provera your periods will return to normal in a
few months.

Possible effects on your bones
Depo-Provera works by lowering levels of oestrogen and other hormones.
However, low oestrogen levels can cause bones to become thinner (by
reducing bone mineral density). Women who use Depo-Provera tend to
have lower bone mineral density than women of the same age who have
never used it. The effects of Depo-Provera are greatest in the first 2-3
years of use. Following this, bone mineral density tends to stabilise and
there appears to be some recovery when Depo-Provera is stopped.
It is not yet possible to say whether Depo-Provera increases the risk of
osteoporosis (weak bones) and fractures in later life.
The following are risk factors in the development of osteoporosis in later
life. You should discuss with your doctor before starting treatment if you
have any of the following as an alternative contraceptive may be more
suitable to your needs;
• Chronic alcohol and/or tobacco use
• Chronic use of drugs that can reduce bone mass, e.g. epilepsy
medication or steroids
• Low body mass index or eating disorder, e.g. anorexia nervosa or
bulimia
• Previous low trauma fracture that was not caused by a fall
• Strong family history of osteoporosis
Teenagers (up to 18 years)
Normally, the bones of teenagers are rapidly growing and increasing in
strength. The stronger the bones are when adulthood is reached, the
greater the protection against osteoporosis in later life. Since DepoProvera 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 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 sight and reach of children.
Do not store above 25°C.
Do not freeze.
Do not use Depo-Provera after the last day of the month shown in the
expiry date stated on the vial and the carton.
The expiry date refers to the last day of that month
If the medicine becomes discoloured or shows any other signs of
deterioration, you should seek the advice of your pharmacist who will tell
you what to do.
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
(MPA). Each dose (1 millilitre) of Depo-Provera contains 150 mg of
medroxyprogesterone acetate. Depo-Provera also contains methyl
parahydroxybenzoate, macrogol, polysorbate 80, propyl
parahydroxybenzoate, sodium chloride and water. 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.
What Depo-Provera looks like and contents of the pack:
Depo-Provera is a white sterile suspension. Each vial contains 1 millilitre
(ml) of Depo-Provera. Depo-Provera is supplied in cartons containing one
vial.
Manufacturer:
Pfizer Manufacturing Belgium NV/SA, Rijksweg 12, B-2870 Puurs
Belgium.
Procured from within the EU
Product licence holder: Ecosse Pharmaceuticals Limited,
POM
3 Young Place, East Kilbride G75 0TD
Re-packaged by: Munro Wholesale Medical Supplies Limited,
3 Young Place, East Kilbride G75 0TD
PL: 19065/0467 Depo-Provera® 150 mg/ml Vial
This leaflet was revised: 13.09.2017 E0467/3-P

If you are blind or partially sighted
and require this leaflet in a different
format, call 01355 574450 and ask
for the Regulatory Department.
® is a registered trademark of Pharmacia Ltd

Depo-Provera® 150 mg/ml Vial
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 1 ml vial
contains 150 mg medroxyprogesterone acetate Ph. Eur. Excipients are
methyl parahydroxybenzoate, macrogol, polysorbate 80, propyl
parahydroxybenzoate, sodium chloride, water for injection. 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:
• For partners of men undergoing vasectomy, for protection until the
vasectomy becomes effective.
• In women who are being immunised against rubella, to prevent
pregnancy during the period of activity of the virus.
• 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 Ph.
Eur. 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 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 DepoProvera 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, DepoProvera 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 DepoProvera 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. 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

No of cases per
10,000 women who
are never-users
20
Less than 1
30
44
40
160
*based on use for 5 years

Possible additional
cases per 10,000 DMPA
users
Much less than 1
2-3
10

Weight Gain: There is a tendency for women to gain weight while on DepoProvera 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 DepoProvera, but causality has not been established.
The effects of medroxyprogesterone acetate on lipid metabolism have
been studied with no clear impact demonstrated. Both increases and
decreases in total cholesterol, triglycerides and low-density lipoprotein
(LDL) cholesterol have been observed in studies. The use of DepoProvera appears to be associated with a 15-20 % reduction in serum high
density lipoprotein (HDL) cholesterol levels which may protect women from
cardiovascular disease. The clinical consequences of this observation are
unknown.
The potential for an increased risk of coronary disease should be
considered prior to use.
Doctors should carefully consider the use of Depo-Provera in patients with
recent trophoblastic disease before levels of human chorionic
gonadotrophin have returned to normal.
Physicians should be aware that pathologists should be informed of the
patient’s use of Depo-Provera if endometrial or endocervical tissue is
submitted for examination.
The results of certain laboratory tests may be affected by the use of DepoProvera. 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
Very
Common
Uncommon
Rare >1/10,000
Organ Class
Common
>1/100 to
> 1/1000 to
to <1/1000
>1/10
<1/10
<1/100
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

Nervous
system
disorders
Ear and
Labyrinth
Disorder
Cardiac
disorder
Vascular
disorders

Respiratory,
thoracic, and
mediastinal
disorders
Gastrointestinal
disorders

Nervousness

Headache

Depression
Libido
decreased

Dizziness

Musculoskeletal and
connective
tissue
disorders
Reproductive
system and
breast
disorders

General
disorders and
administration
site
conditions

Increased
appetite,
decreased
appetite
Insomnia

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

Tachycardia
Hot flush

Dyspnoea

Abdominal
pain,
Abdominal
discomfort

Nausea,
Abdominal
distension

Hepatobiliary
disorders
Skin and
subcutaneous
tissue
disorders

Anaphylactic
reaction,
Anaphylactoid
reaction,
Angioedema

Alopecia, Acne,
Rash

Hepatic
function
abnormal
Hirsutism,
Urticaria,
Pruritus,
Chloasma

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

Rectal
haemorrhage,
Gastrointestinal
disorder
Jaundice, Hepatic
enzyme abnormal

Lipodystrophy
acquired*,
Dermatitis,
Ecchymosis,
Scleroderma, Skin
striae
Back pain,
Arthralgia, Muscle
Pain in
spasms,
extremity
Osteoporosis,
Osteoporotic
fractures
Vaginal
Dysfunctional
Vaginitis,
discharge,
uterine
Amenorrhoea,
Breast
bleeding
Breast pain,
tenderness,
(irregular,
Metrorrhagia,
increase,
Dysmenorrhea,
Menometrorrhagia,
decrease,
Genitourinary
Menorrhagia,
spotting,
tract infection
Vulvovaginal
Galactorrhoea dryness, Breast
atrophy, Ovarian
Pelvic pain,
Dyspareunia, cyst, Premenstrual
Suppresed
syndrome,
lactation
Endometrial
hyperplasia, Breast
mass, Nipple
exudate bloody,
Vaginal cyst,
Breast
enlargement, Lack
of return to fertility,
Sensation of
pregnancy
Odema/Fluid
Chest pain
Pyrexia, Fatigue,
retention,
Injection site
Asthenia
reaction*,
Injection site
persistent
atrophy/indentation
/dimpling*, Injection
site nodule/lump*,
Injection site
pain/tenderness*
Thirst, Dysphonia,
Vllth nerve
paralysis, Axillary
swelling

System
Organ Class

Very
Common
>1/10

Investigation

Weight
increased,
Weight
decreased

Common
>1/100 to
<1/10

Uncommon Rare >1/10,000
> 1/1000 to
to <1/1000
<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
Lumbar Spine

Total Hip

Femoral Neck

Time on
Treatment

N

N

N

1 year

166

2 year

106

Mean %
Change
(95% CI)
-2.7
(-3.1 to
-2.3)
- 4.1
(-4.6 to
-3.5)

166

106

Mean %
Change
(95% CI)
-1.7
(-2.1 to
-1.3)
-3.5
(-4.2 to
-2.7)

166

106

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

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

Spine

Total Hip

Medroxyprog Control
esterone
acetate

Femoral Neck

Medroxyprog Control
esterone
acetate

Medroxyprog Control
esterone
acetate

5 years*

n=33
-5.38%

n=105
0.43%

n=21
-5.16%

n=65
0.19%

n=34
-6.12%

n=106
-0.27%

7 years**

n=12
-3.13%

n=60
0.53%

n=7
-1.34%

n=39
0.94%

n=13
-5.38%

n=63
-0.11%

*The treatment group consisted of women who received
medroxyprogesterone acetate injection (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. 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 150 mg/ml
MPA, plasma levels were 1.7 ± 0.3 nmol/l. Two weeks later, levels were
6.8 ± 0.8 nmol/l. Concentrations fell to the initial levels by the end of 12
weeks. At lower doses, plasma levels of MPA appear directly related to the
dose administered. Serum accumulation over time was not demonstrated.
MPA is eliminated via faecal and urinary excretion. Plasma half-life is
about six weeks after a single intramuscular injection. At least 11
metabolites have been reported. All are excreted in the urine, some, but
not all, conjugated.
Shelf-life
The shelf-life is printed on labels and cartons. Do not use Depo-Provera
after this date.
Storage of the product
Do not store above 25°C.
Do not freeze.
Do not mix with other agents.
Discard any remaining contents after use.
Manufacturer :
Pfizer Manufacturing Belgium NV/SA, Rijksweg 12, B-2870 Puurs,
Belgium.
Procured from within the EU
Product licence holder: Ecosse Pharmaceuticals Limited,
3 Young Place, East Kilbride G75 0TD
Re-packaged by: Munro Wholesale Medical Supplies Limited,
3 Young Place, East Kilbride G75 0TD
PL: 19065/0467 Depo-Provera® 150 mg/ml Vial
POM
This leaflet was revised: 13.09.2017 E0467/3-Dr-Ph
® is a registered trademark of Pharmacia Ltd

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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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