DEPO-PROVERA 150 MG/ML

Active substance: MEDROXYPROGESTERONE ACETATE

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PACKAGE LEAFLET
INFORMATION FOR THE USER
®

Depo-Provera 150 mg/ml
(medroxyprogesterone acetate)
®
Please read all of this leaflet carefully before you start using this
Depo-Provera 150 mg/ml can be used:
method of contraception.
 For long-term contraception where you and the person who provides
 Keep this leaflet. You may need to read it again.
your contraception (e.g. your doctor or healthcare professional )
have decided that this method is the most suitable for you.
 If you have any further questions, ask your doctor, nurse or
®
healthcare provider.
 If you wish to use Depo-Provera 150 mg/ml for more than 2 years
your doctor or healthcare professional may wish to re-evaluate the
 This medicine has been prescribed for you. Do not pass it on to
®
risks and benefits of using Depo-Provera 150 mg/ml to make sure
others. It may harm them, even if their symptoms are the same as
that it is still the best option for you.
yours.
 In teenagers only after other methods of contraception have been
 If any of the side effects get serious, or if you notice any side effects
discussed with the healthcare professional who provides your
not listed in this leaflet, please tell your doctor, nurse or healthcare
contraception and considered to be unsuitable or unacceptable
provider.
 For just one or two occasions in the following cases:
 If your partner is undergoing vasectomy, to give you protection
until the vasectomy becomes effective.
IMPORTANT INFORMATION YOU SHOULD KNOW ABOUT
®
 If you are being immunised against rubella, to prevent
DEPO-PROVERA 150 MG/ML
pregnancy during the period of activity of the virus.
®
Depo-Provera 150mg/ml is a very effective injectable
 If you are awaiting sterilisation.
contraceptive which gives 12 weeks` continuous
contraception with each injection. The effect is not
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2. BEFORE YOU USE DEPO-PROVERA 150MG/ML
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 ‘How to use Depo-Provera 150 mg/ml’).
®
 Depo-Provera 150 mg/ml may not be suitable for every
woman. You will need to discuss with your doctor or healthcare
professional providing your contraception whether it is suitable
for you, especially if you wish to use it more than 2 years ( see
®
Section 1 ‘What Depo-Provera 150 mg/ml is, and what it is
used for’).
®
 Depo-Provera 150 mg/ml may not be suitable for you if you
have a history of certain medical conditions (see Section 2
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under ‘ Before you use Depo-Provera 150 mg/ml’) or if you are
taking a medicine called aminoglutethiamide that thins the
blood (see Section 2 under ‘Taking other medicines’). Your
doctor or nurse should take a full medical history before
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prescribing DepoProvera 150 mg/ml.
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 Regular use of Depo-Provera 150 mg/ml causes a gradual
loss of bone mineral density (see Section 4 ‘Possible side
effects’). 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 150 mg/ml.
Teenagers who are rapidly developing their bones may be at
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particular risk and should only use Depo-Provera 150mg/ml if
other methods of contraception have been discussed and
considered unsuitable or unacceptable.

®

Do not use Depo-Provera 150 mg/ml:
 If you are allergic (hypersensitive) to the active ingredient (MPA) or
any of the other ingredients. There is small risk of a severe allergic
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reaction to Depo-Provera 150 mg/ml that will require emergency
medical treatment.
 If you think you may be pregnant.
 If you have had, or think you may have, hormone dependent cancer
of the breast or reproductive organs.
 If you have unexplained vaginal bleeding.
 If you have liver disease.
 If you have never had a period.
 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.
®

Take special care with Depo-Provera 150 mg/ml
Before your doctor or healthcare professional prescribes Depo®
Provera 150 mg/ml, you may need to have a physical examination. It
is important to tell your doctor or healthcare professional if you have,
or have had in the past, any of the following conditions. Your doctor
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will then discuss with you whether Depo-Provera 150 mg/ml is
suitable for you.
 Migraine headaches – if you develop migraine you should consult
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your doctor before receiving further injections of Depo-Provera 150
mg/ml
 Diabetes or a family history of diabetes
 Severe pain or swelling in the calf (indicating a possible clot in the
leg, which may be called phlebitis)
 Blood clotting disorders such as deep vein thrombosis (blood clot in
the legs), pulmonary embolus (blood clot in the lung) or a stroke you
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should not receive further injections of Depo-Provera 150 mg/ml
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 Problems with your eyesight while using Depo-Provera 150 mg/ml;
for example a sudden partial or complete loss of vision or double
vision
 Past history of or current depression
 Problems with your liver or liver disease
 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

In this leaflet:
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1. What Depo-Provera 150mg/ml is and what it is used for
®
2. Before you use Depo-Provera 150mg/ml
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3. How to use Depo-Provera 150mg/ml
4. Possible side effects
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5. How to store Depo-Provera 150mg/ml
6. Further information
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1. WHAT DEPO-PROVERA 150MG/ML IS AND WHAT IT IS USED
FOR
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Depo-Provera 150 mg/ml is a long acting contraceptive. The active
®
ingredient in Depo-Provera 150 mg/ml, medroxyprogesterone acetate
(MPA), 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 150 mg/ml acts by preventing an egg from fully
developing and being released from the ovaries during your menstrual
cycle. If an egg is not released it cannot become fertilised by sperm
®
and result in pregnancy. Depo-Provera 150 mg/ml also causes
changes in the lining of you 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.

4

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

1

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Taking other medicines:

For effective contraceptive cover Depo-Provera 150 mg/ml MUST be
given every 12 weeks. Make sure that you or your doctor makes your
next appointment for 12 weeks time.

 Tell your doctor or healthcare professional if you are taking a
medicine called aminoglutethimide or other medicines that thin your
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blood (anticoagulants) as these may affect the way Depo-Provera
150 mg/ml works.
 Always tell your doctor or healthcare professional who treats you
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that you are using Depo-Provera 150 mg/ml as a contraceptive if
you are taking or have recently taken any other medicines, even
those you bought yourself without a prescription, because medicines
can sometimes interact with each other.

®

If you miss an injection of Depo-Provera 150 mg/ml:
If you miss your injection or are late getting your next injection (ie 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 150 mg/ml and which type of contraception should be
used in the meantime.

Pregnancy:

Switching from other methods of contraception:
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 Because Depo-Provera 150 mg/ml is such an effective
contraceptive method, the risk of accidental pregnancy for women
who have their injections regularly (every 12 weeks) is very low.
 If you think you may have become pregnant while using
®
Depo-Provera 150 mg/ml for contraception, tell your doctor
immediately.

When you switch from other contraceptive methods, your doctor will
make sure you are not at risk of becoming pregnant by giving you your
first injection at the appropriate time. If you switch from oral
®
contraceptives, you should have your first injection of Depo-Provera
150 mg/ml within 7 days after taking your last pill.
If you have any further questions on the use of this product ask your
doctor or healthcare professional.

Effects on future fertility:
 Your usual level of fertility will 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 150
mg/ml.
 In most women the effect will have worn off 5 to 6 months after the
last injection.
 Over 80% of women trying to get pregnant will conceive within a
year of the first missed injection.
 Some women have got pregnant in the first month after missing an
injection.

4. POSSIBLE SIDE EFFECTS

Rare side effects (occurs in less than 1 out of every 1,000 patients)
These include:
tachycardia (faster heart beat), breast lumps or nipple bleeding, thirst,
hoarseness, rectal bleeding (bleeding from the anus), paralysis,
decreased glucose tolerance (abnormal blood sugar levels), breast
cancer, anaemia (reduction in red blood cells which can make the skin
pale and cause weakness or breathlessness) .

Possible risk of cancer:
Studies of women who have used different forms of contraception
®
found that women who used Depo-Provera 150 mg/ml for
contraception had no increase in overall risk of developing cancer of
the ovary, womb, cervix, or liver.

Other side effects that have been observed include:

Breast cancer is rare among women under 40 years of age whether or
®
not they use hormonal contraceptives. Depo-Provera 150 mg/ml may
increase the risk of breast cancer slightly compared with women who
have never used it. However, any excess risk is small in relation to the
overall risk of breast cancer, particularly in young women.
Older women have a higher baseline risk of breast cancer and
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therefore the increase in the number of cases due to Depo-Provera
150 mg/ml is greater in older women than in younger women.
In absolute terms this means that:
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A 15 year old who uses Depo-Provera 150 mg/ml for 5 years
increases her chance of developing breast cancer by a negligible
amount by the age of 30.
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A 25 year old who uses Depo-Provera 150mg/ml for 5 years
increases her chance of developing breast cancer by the age of 40
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from 44 cases per 10,000 women (without Depo-Provera 150 mg/ml
use) to up to 47 cases per 10,000 women i.e. an extra 3 cases/10,000
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A 35 year old who uses Depo-Provera 150 mg/ml for 5 years
increases her chance of developing breast cancer by the age of 50
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from 160 cases per 10,000 women (without Depo-Provera 150 mg/ml
use) to 170 cases per 10,000 women i.e. an extra 10 cases/10,000.

Possible risk of breast cancer

Blood clotting disorders, deep vein thrombosis (blood clots forming in
the veins, usually the legs), disturbed liver function, osteoporosis
(thinning of the bones) including fractures, loss of bone mineral density
(a test to measure the strength of bones), swelling of ankles or wrists,
abnormal uterine bleeding (irregular, increase, decrease), milky
discharge from breasts in women who are not breastfeeding, vaginal
cysts, milk supply stopping (in breastfeeding mothers), feeling
®
pregnant, delay in becoming pregnant after stopping Depo-Provera
150 mg/ml, scaling of skin, scleroderma (a rare autoimmune disease
that affects the skin and other parts of the body),weakness in the face
muscles, fainting, blood disorder, skin striae (stretch marks).
If any of the side effects get serious, or if you notice any side effect not
listed in this leaflet please tell your doctor or healthcare professional.
Possible effects on your periods:

®

Like all medicines Depo-Provera 150 mg/ml can cause side effects
although not everybody gets them.
There is a low risk of anaphylactic responses (serious allergic
reactions which may need urgent medical attention or hospitalization).
Possible symptoms include: swelling of the face, lips, tongue or throat,
or difficulty breathing or swallowing, skin rashes, shock or collapse.
Deep vein thrombosis (DVT) is a condition in which a blood clot forms
in one of your deep veins, usually in your leg. Signs of possible DVT
includes: swelling of the affected leg, pain and tenderness in the
affected leg (you may also find it difficult to stand properly with your full
weight on the affected leg), a change in the colour of your skin, for
example, redness or skin that feels warm or hot to the touch.
®
Women who use Depo-Provera 150 mg/ml tend to have lower bone
mineral density than women of the same age who have never used it.
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The effects of Depo-Provera 150 mg/ml are greatest in the first 2-3
years of use. Following this, bone mineral density tends to stabilise
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and there appears to be some recovery when Depo-Provera 150
®
mg/ml is stopped. It is not yet possible to say whether Depo-Provera
150 mg/ml increases the risk of osteoporosis (weak bones) and
fractures in later life.
Tell your doctor immediately if you experience any of the above
symptoms.

If you are breast-feeding:
®

 Depo-Provera 150 mg/ml does not prevent the breast from
producing milk so nursing mothers can use it, however, it is better
for the baby that for the first few weeks after birth its mother’s milk
®
contains no traces of any medicines, including Depo-Provera 150
mg/ml.
 Your doctor or healthcare professional may advise that you wait until
at least 6 weeks after your baby has been born before you start
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using Depo-Provera 150 mg/ml for contraception.
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 If a baby is exposed to Depo-Provera 150 mg/ml in the breast milk,
no harmful effects have been seen in babies and children.
Driving and using machines:
®

Depo-Provera 150 mg/ml may cause headaches and dizziness.
Therefore be careful until you know whether this medicine affects your
ability to drive or use machines. If you have any concerns discuss
them with your doctor.

Common side effects (occur in more than 10 out of every 1,000
patients)
These include:
abdominal pain or discomfort, bloating, feeling sick, vaginal discharge
or inflammation, changes in appetite, backpain, headaches, dizziness,
irregular periods, very light or no periods (Amenorrhoea), breast pain
or tenderness, pelvic pain, hot flushes, acne, hair loss, rash, weakness
or tiredness, injection site reactions, feeling of weakness, tingling or
numbness in the hands and feet, depression, nervousness, insomnia
(difficulty sleeping), irritability, anorgasmia (failure to climax during
sexual intercourse), emotional disturbance, intermenstrual bleeding
(bleeding between periods), menorrhagia (heavy periods).

Important information about some of the ingredients of Depo®
Provera 150 mg/ml:
®

The active ingredient in Depo-Provera 150 mg/ml is
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medroxyprogesterone acetate (MPA). Depo-Provera 150 mg/ml 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.

Uncommon side effects (occurs in fewer than 10 out of every 1,000
patients)

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3. HOW TO USE DEPO-PROVERA 150MG/ML

These include:
jaundice (this will cause yellowing of the skin and the whites of the
eyes), hypertension, varicose veins, thrombophlebitis (inflammation of
part of a vein), pulmonary embolism (blood clot in the lungs which
causes chest pain and breathlessness), allergic reactions (such as
swelling on the face and throat), abnormal liver enzymes (blood tests
used to measure liver function), feeling of dizziness or ‘spinning’,
abdominal discomfort, change in weight, fluid retention, joint pain,
muscle cramps, pain in legs and arms, somnolence (sleepiness),
migraine, convulsion (‘fit’), vaginal dryness, painful periods, change in
breast size, painful intercourse, ovarian cyst, premenstrual syndrome,
infections of the urinary tract or reproductive organs, an increase in
thickness of the lining of the womb, dark patches on the skin, bruising,
excessive hair growth, itching, skin rash, swelling, chest pain, fever,
abnormal cervical smear results, anxiety, difficulty breathing.

This medicine will be given to you by your doctor or healthcare
professional. (The leaflet contains instructions for your doctor or
healthcare professional on how they should do this)
®

Depo-Provera 150 mg/ml is given every 12 weeks as s 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 150 mg/ml injection can be
given within 5 days after childbirth if you are not breastfeeding.
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 150 mg/ml works as a contraceptive for 12 weeks in
your body. There is no way of reversing the injection once it is given.

2

®

Depo-Provera 150 mg/ml will usually disturb the pattern of women’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 using Depo-Provera 150 mg/ml your periods will
return to normal in a few months.

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 150 mg/ml.
Studies show that over the first 1-2 years of use, the average weight
gain was 5-8 lbs. Women completing 4-6 years of therapy gained an
average of 14-16.5 lbs.

Possible effect on your bones:
®

Depo-Provera 150 mg/ml works by lowering levels of oestrogen and
other hormones. However, low oestrogen levels can cause bones to
become thinner (by reducing bone mineral density). Women who use
®
Depo-Provera 150 mg/ml tend to have lower bone mineral density
than women of the same age who have never used it. The effects of
®
Depo-Provera 150 mg/ml are greatest in the first 2-3 years of use.
Following this, bone mineral density tends to stabilise and there
®
appears to be some recovery when Depo-Provera 150mg/ml is
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stopped. It is not yet possible to say whether Depo-Provera 150
mg/ml increases the risk of osteoporosis (weak bones) and fractures in
later life.
The following are risk factors in the development of osteoporosis in
later life. You should discuss with your doctor before starting treatment
if you have any of the following as an alternative contraceptive may be
more suitable to your needs;
 Chronic alcohol and/or tobacco use
 Chronic use of drugs that can reduce bone mass, e.g. epilepsy
medication or steroids
 Low body mass index or eating disorder, e.g. anorexia nervosa or
bulimia
 Previous low trauma fracture that was not caused by a fall
 Strong family history of osteoporosis
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 150 mg/ml may cause
teenage bones to become thinner at a time when they should be
growing, its effect may be particularly important in this age group.
®
Bones start to recover when Depo-Provera 150 mg/ml is stopped, but
it is not yet known whether the bone mineral density reaches the same
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levels as it would have if Depo-Provera 150 mg/ml had never been
used. You should therefore discuss whether another form of
contraception might be more suitable for you with the person who
®
provides your contraception before starting Depo-Provera 150
mg/ml.
®
If you use Depo-Provera 150 mg/ml, it may help your bones if you
take regular weight-bearing exercise and have a healthy diet, including
an adequate intake of calcium (e.g. in dairy products) and vitamin D
(e.g. in oily fish).

®

5. HOW TO STORE DEPO-PROVERA 150 MG/ML
Keep out of the reach and sight of children.
Do not store above 25°C. Keep in the original container. Do not freeze.
Do not use after the expiry date printed on the label and carton.
6. FURTHER INFORMATION
®

What Depo-Provera 150 mg/ml contains:
Each 1ml of suspension contains 150mg of medroxyprogesterone
acetate as the active ingredient.
Each 1ml also contains macrogol, sodium chloride, polysorbate 80,
methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate
(E216), and water for injection.
®

What Depo-Provera 150 mg/ml looks like and contents of the
pack:
It is a white, opaque suspension for injection. It is available in a clear
glass vial with a rubber stopper that has an aluminium seal and a
purple protective cap.
The vial contains 1 millilitre of suspension.
Who manufactured your medicine:
Manufactured by Pfizer Manufacturing Belgium N.V/S.A., Rijksweg 12,
B-2870 Puurs, Belgium. Procured from within the EU and repackaged
by Product Licence Holder Beachcourse Limited, 20 Alliance Court,
London W3 0RB.
PL16378/0534

POM

Revision date: 19 May 2011
Leaflet reference: Depo150S/UT
®

Depo-Provera is a registered trademark of Pharmacia Limited.

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Pharmacokinetic properties

INFORMATION FOR DOCTORS AND PHARMACISTS
®

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.

Depo-Provera 150 mg/ml
(medroxyprogesterone acetate)
(N.B. For partners of men undergoing vasectomy a second injection of
For further information consult the Summary of Product Characteristics.
150 mg i.m. 12 weeks after the first may be necessary in a small
Description
proportion of patients where the partner’s sperm count has not fallen to
®
Depo-Provera 150mg/ml is a white, opaque suspension for injection.
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
Each 1ml of suspension contains 150 mg medroxyprogesterone acetate.
excluded before the next injection is given and the patient should use
Excipients are macrogol, sodium chloride, polysorbate 80, methyl
additional contraceptive measures (e.g. barrier) for fourteen days after
parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), and
this subsequent injection.
water for injection.
®
Children: Depo-Provera 150mg/ml is not indicated before menarche.
Hydrochloric acid or sodium hydroxide may be present as pH adjusters.
Data in adolescent females (12-18 years) is available. Other than
Uses
concerns about loss of BMD, the safety and effectiveness of Depo®
®
Provera 150mg/ml is expected to be the same for adolescents after
Depo-Provera 150mg/ml is a long-term contraceptive agent suitable for
menarche and adult females
use in women who have been appropriately counselled concerning the
®
likelihood of menstrual disturbance and the potential for a delay in return
Switching from other Methods of Contraception: Depo-Provera 150mg/ml
to full fertility.
should be given in a manner that ensures continuous contraceptive
®
coverage. This should be based upon the mechanism of action of other
Depo-Provera 150mg/ml may also be used for short-term contraception
methods, (e.g. patients switching from oral contraceptives should have
in the following circumstances:
®
their first injection of Depo-Provera 150mg/ml within 7 days of taking
(i) For partners of men undergoing vasectomy, for protection until the
their last active pill).
vasectomy becomes effective.
Hepatic Insufficiency: The effect of hepatic disease on the
(ii) In women who are being immunised against rubella, to prevent
®
pharmacokinetics of Depo-Provera 150mg/ml is unknown. As Depopregnancy during the period of activity of the virus.
®
Provera 150mg/ml largely undergoes hepatic elimination it may be poorly
(iii) In women awaiting sterilisation.
metabolised in patients with severe liver insufficiency (see
Since loss of bone mineral density (BMD) may occur in females of all
Contraindications).
®
ages who use Depo-Provera 150mg/ml injection long-term, a risk/benefit
Renal Insufficiency: The effect of renal disease on the pharmacokinetics
assessment, which also takes into consideration the decrease in BMD
®
of Depo-Provera 150mg/ml is unknown. No dosage adjustment should
that occurs during pregnancy and/or lactation, should be considered. It is
®
be necessary in women with renal insufficiency, since Depo-Provera
of the greatest importance that adequate explanations of the long-term
150mg/ml is almost exclusively eliminated by hepatic metabolism.
nature of the product, of its possible side-effects and of the impossibility of
Contra-indications
immediately reversing the effects of each injection are given to potential
®
Depo-Provera 150mg/ml is contra-indicated in patients with a known
users and that every effort is made to ensure that each patient receives
sensitivity to medroxyprogesterone acetate or any ingredient of the
such counselling as to enable her to fully understand these explanations.
vehicle.
Patient information leaflets are supplied by the manufacturer. It is
®
recommended that the doctor uses these leaflets to aid counselling of the
Depo-Provera 150mg/ml should not be used during pregnancy, either for
®
patient before giving the injection of Depo-Provera 150mg/ml.
diagnosis or therapy.
®
Depo-Provera 150mg/ml is contra-indicated as a contraceptive at the
Dosage
above dosage in known or suspected hormone-dependent malignancy of
Each ml of suspension contains 150 mg medroxyprogesterone acetate
breast or genital organs.
Ph. Eur. The sterile aqueous suspension of Depo-Provera® 150mg/ml
Whether administered alone or in combination with oestrogen, Deposhould be vigorously shaken just before use to ensure that the dose being
®
Provera 150mg/ml should not be employed in patients with abnormal
given represents a uniform suspension of Depo-Provera® 150mg/ml.
uterine bleeding until a definite diagnosis has been established and the
Doses should be given by deep intramuscular injection into the buttock or
possibility of genital tract malignancy eliminated.
arm.

Shelf-life
®

The shelf-life is printed on labels and cartons. Do not use Depo-Provera
150mg/ml after this date.
Storage of the product
Do not store above 25°C. Do not freeze. Keep in the original container.
Do not mix with other agents. Discard any remaining contents after use.
Manufacturer and Product Licence Holder

Manufactured by Pfizer Manufacturing Belgium N.V/S.A., Rijksweg 12, B2870 Puurs, Belgium. Procured from within the EU and repackaged by
Product Licence Holder Beachcourse Limited., 20 Alliance Court. London
W3 0RB.
PL16378/0534

POM

Revision date: 19 May 2011
Leaflet Reference: Depo150S/2
®

Depo-Provera is a registered trademark of Pharmacia Limited

Special warnings and special precautions for use

Care should be taken to ensure that the depot injection is given into the
muscle tissue, preferably the gluteus maximus, but other muscle issue
such as the deltoid may be used and the site of injection should be
cleansed using standard methods prior to administration of the injection.
Assembly of syringe for single use:
1. Remove tip cap.
2. Position needle using aseptic technique.
3. Remove needle shield. The syringe is now ready for use.

Warnings:
Loss of Bone Mineral Density:
®
Use of Depo-Provera 150mg/ml 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 150mg/ml is discontinued and ovarian
estrogen 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® 150mg/ml injection 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®
150mg/ml, 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® 150mg/ml 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-Provera150mg/ml.

Administration
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 150mg/ml 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.

4

1

Significant risk factors for osteoporosis include:
 Alcohol abuse and/or tobacco use
 Chronic use of drugs that can reduce bone mass, e.g.,
anticonvulsants or corticosteroids
 Low body mass index or eating disorder, e.g., anorexia nervosa or
bulimia
 Previous low trauma fracture
 Family history of osteoporosis
A retrospective cohort study using data from the General Practice
Research Database (GPRD) reported that women using MPA injections
(DMPA), have a higher risk of fracture compared with contraceptive users
with no recorded use of DMPA (incident rate ratio 1.41, 95% CI 1.35-1.47
for the five year follow-up period); it is not known if this is due to DMPA, or
to other related lifestyle factors which have a bearing on fracture rate. By
contrast, in women using DMPA, the fracture risk before and after starting
DMPA was not increased (relative risk 1.08, 95% CI 0.92-1.26).
Importantly, this study could not determine whether use of DMPA has an
effect on fracture rate later in life.
For further information on BMD changes in both adult and adolescent
females, as reported in recent clinical studies, refer to section 5.1 of the
SPC. Adequate intake of calcium and Vitamin D, whether from the diet or
from supplements, is important for bone health in women of all ages.
®
Menstrual Irregularity: The administration of Depo-Provera 150mg/ml
usually causes disruption of the normal menstrual cycle. Bleeding
patterns include amenorrhoea (present in up to 30 % of women during the
first 3 months and increasing to 55 % by month 12 and 68 % by month
24); irregular bleeding and spotting; prolonged (>10 days) episodes of
bleeding (up to 33 % of women in the first 3 months of use decreasing to
12 % by month 12). Rarely, heavy prolonged bleeding may occur.
Evidence suggests that prolonged or heavy bleeding requiring treatment
may occur in 0.5-4 occasions per 100 women years of use. If abnormal
bleeding persists or is severe, appropriate investigation should take place
to rule out the possibility of organic pathology and appropriate treatment
should be instituted when necessary. Excessive or prolonged bleeding
can be controlled by the co-administration of oestrogen. This may be
delivered either in the form of a low dose (30 micrograms oestrogen)
combined oral contraceptive pill or in the form of oestrogen replacement
therapy such as conjugated equine oestrogen (0.625-1.25 mg daily).
Oestrogen therapy may need to be repeated for 1-2 cycles. Long-term coadministration of oestrogen is not recommended.
®
Return to Fertility: There is no evidence that Depo-Provera 150mg/ml
causes permanent infertility. Pregnancies have occurred as early as 14
weeks after a preceding injection, however, in clinical trials, the mean
time to return of ovulation was 5.3 months following the preceding
injection. Women should be counselled that there is a potential for delay
in return to full fertility following use of the method, regardless of the
duration of use, however, 83 % of women may be expected to conceive
within 12 months of the first "missed" injection (i.e. 15 months after the
last injection administered). The median time to conception was 10
months (range 4-31) after the last injection.
®
Cancer Risks: Long-term case-controlled surveillance of Depo-Provera
150mg/ml users found no overall increased risk of ovarian, liver, or
cervical cancer and a prolonged, protective effect of reducing the risk of
endometrial cancer in the population of users.
Breast cancer is rare among women under 40 years of age whether or not
they use hormonal contraceptives.
Results from some epidemiological studies suggest a small difference in
risk of the disease in current and recent users compared with neverusers. Any excess risk in current and recent DMPA users is small in
relation to the overall risk of breast cancer, particularly in young women
(see below), and is not apparent after 10 years since last use. Duration of
use does not seem to be important.
Possible number of additional cases of breast cancer diagnosed up to
10 years after stopping injectable progestogens*
Age at last use of
No of cases per
Possible additional
DMPA
10,000
cases per
Women who are
10,000 DMPA users
never-users
20
Less than 1
Much less than 1
30
44
2-3
40
160
10

Studies indicate that over the first 1-2 years of use, average weight gain
was 5-8 lbs. Women completing 4-6 years of therapy gained an average
of 14-16.5 lbs. There is evidence that weight is gained as a result of
increased fat and is not secondary to an anabolic effect or fluid retention.
Anaphylaxis: Reports of anaphylactic responses (anaphylactic reactions,
anaphylactic shock, anaphylactoid reactions) have been received.
Thromboembolic Disorders: Should the patient experience pulmonary
embolism, cerebrovascular disease or retinal thrombosis while receiving
®
Depo-Provera 150mg/ml, the drug should not be readministered.
Psychiatric Disorders: Patients with a history of endogenous depression
should be carefully monitored. Some patients may complain of
®
premenstrual-type depression while on Depo-Provera 150mg/ml therapy.
Abscess formation: As with any intramuscular injection, especially if not
administered correctly, there is a risk of abscess formation at the site of
injection, which may require medical and/or surgical intervention.
Precautions:
History or emergence of the following conditions require careful
consideration and appropriate investigation: migraine or unusually severe
headaches, acute visual disturbances of any kind, pathological changes
in liver function and hormone levels. Patients with thromboembolic or
coronary vascular disease should be carefully evaluated before using
®
Depo-Provera 150mg/ml.
A decrease in glucose tolerance has been observed in some patients
treated with progestogens. The mechanism for this decrease is obscure.
For this reason, diabetic patients should be carefully monitored while
receiving progestogen therapy.
Rare cases of thromboembolism have been reported with use of Depo®
Provera 150mg/ml, but causality has not been established.
The effects of medroxyprogesterone acetate on lipid metabolism have
been studied with no clear impact demonstrated. Both increases and
decreases in total cholesterol, triglycerides and low-density lipoprotein
(LDL) cholesterol have been observed in studies. The use of Depo®
Provera 150mg/ml appears to be associated with a 15-20 % reduction in
serum high density lipoprotein (HDL) cholesterol levels which may protect
women from cardiovascular disease. The clinical consequences of this
observation are unknown.
The potential for an increased risk of coronary disease should be
considered prior to use.
®
Doctors should carefully consider the use of Depo-Provera 150mg/ml in
patients with recent trophoblastic disease before levels of human
chorionic gonadotrophin have returned to normal.
Physicians should be aware that pathologists should be informed of the
®
patient’s use of Depo-Provera 150mg/ml if endometrial or endocervical
tissue is submitted for examination.
The results of certain laboratory tests may be affected by the use of
®
Depo-Provera 150mg/ml.
These include gonadotrophin levels (decreased), plasma progesterone
levels (decreased), urinary pregnanediol levels (decreased), plasma
oestrogen levels (decreased), plasma cortisol levels (decreased), glucose
tolerance test, metyrapone test, liver function tests (may increase), thyroid
function tests (protein bound iodine levels may increase and T3 uptake
levels may decrease). Coagulation test values for prothrombin (Factor II),
and Factors VII, VIII, IX and X may increase.
Interaction with Other Medicaments and Other Forms of Interaction
®

Aminoglutethimide administered concurrently with Depo-Provera
®
150mg/ml may significantly depress the bioavailability of Depo-Provera
150mg/ml.
Interactions with other medicinal treatments (including oral
anticoagulants) have rarely been reported, but causality has not been
determined. The possibility of interaction should be borne in mind in
patients receiving concurrent treatment with other drugs.
The clearance of medroxyprogesterone acetate is approximately equal to
the rate of hepatic blood flow.
Because of this fact, it is unlikely that drugs which induce hepatic
enzymes will significantly affect the kinetics of medroxyprogesterone
acetate. Therefore, no dose adjustment is recommended in patients
receiving drugs known to affect hepatic metabolising enzymes.
Pregnancy and Lactation
Doctors should check that patients are not pregnant before initial injection
®
of Depo-Provera 150mg/ml, and also if administration of any subsequent
injection is delayed beyond 89 days (12 weeks and five days).
Infants from accidental pregnancies that occur 1-2 months after injection
®
of Depo-Provera 150mg/ml may be at an increased risk of low birth
weight, which in turn is associated with an increased risk of neonatal
death.
The attributable risk is low because such pregnancies are uncommon.

*Based on use for 5 years
Weight Gain: There is a tendency for women to gain weight while on
®
Depo-Provera 150mg/ml therapy.

2

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 via breast
milk have been studied for developmental and behavioural effects to
puberty. No adverse effects have been noted.

Pharmacodynamic Properties
Medroxyprogesterone acetate exerts anti-oestrogenic, anti-androgenic
and antigonadotrophic effects.
BMD Changes in Adult Women: A study comparing changes in BMD in
®
women using Depo-Provera 150mg/ml with women using
medroxyprogesterone acetate injection (150 mg IM) showed no significant
differences in BMD loss between the two groups after two years of
treatment.
®
Mean percent changes in BMD in the Depo-Provera 150mg/ml group are
listed in Table 1
Table 1. Mean Percent Change from Baseline in BMD in Women Using
®
Depo-Provera 150mg/ml by Skeletal Site

Undesirable effects
In a large clinical trial of over 3900 women, who were treated with Depo®
Provera 150mg/ml for up to 7 years, the following adverse events were
reported.
The following adverse events were commonly (by more than 5 % of
subjects) reported: menstrual irregularities (bleeding and/or
amenorrhoea), weight changes, headache, nervousness, abdominal pain
or discomfort, dizziness, asthenia (weakness or fatigue).
®
Adverse events reported by 1 % to 5 % of subjects using Depo-Provera
150mg/ml were: decreased libido or anorgasmia, backache, leg cramps,
depression, nausea, insomnia, leucorrhoea, acne, vaginitis, pelvic pain,
breast pain, no hair growth or alopecia, bloating, rash, oedema, hot
flushes.
Adverse reactions are listed according to the following categories:
Very Common >10% Common >1% and < 10% Uncommon >0.1% and
<1% Rare < 0.1% Unknown (cannot be estimated from the available data)
Ear and Labyrinth Disorders: Uncommon: Vertigo.
Gastrointestinal Disorders: Very common: Abdominal pain or discomfort.
Common: Bloating, nausea. Uncommon: Abdominal distension,
gastrointestinal disturbances. Rare: Rectal bleeding.
Infection & Infestations: Common: Vaginitis.
Metabolism & Nutrition Disorders: Common: Appetite decrease, appetite
increase. Uncommon: weight increase, weight decrease, fluid retention.
Musculoskeletal, Connective Tissue & Bone Disorders: Common:
Backpain. Uncommon: Arthralgia, muscle cramps, pain in limbs.
Frequency not known: Osteoporosis including osteoporotic fractures, loss
of bone mineral density, axillary swelling.
Nervous System Disorders: Very common: Headaches. Common:
Dizziness. Uncommon: Somnolence, migraine, convulsions. Unknown:
Syncope.
Reproductive System & Breast Disorders: Common: Amenorrhea, breast
pain/tenderness, intermenstrual bleeding, menometrorrhagia,
menorrhagia, pelvic pain, leucorrhoea. Uncommon: Vaginal discharge,
vulvovaginal dryness, dysmenorrhea, change in breast size, dyspareunia,
ovarian cyst, premenstrual syndrome, genitourinary infection, uterine
hyperplasia. Rare: Breast lumps or nipple bleeding. Frequency not
known: Abnormal uterine bleeding (irregular, increase, decrease),
galactorrhea, vaginal cysts, prevention of lactation, sensation of
pregnancy, lack of return to fertility.
Vascular Disorders: Common: Hot flushes. Uncommon: Hypertension,
varicose veins, thrombophlebitis, pulmonary embolism. Frequency not
known: Thromboembolic disorders, deep vein thrombosis.
Cardiovascular Disorders: Rare: Tachycardia.
Immune System Disorders: Uncommon: Hypersensitivity reactions (e.g.
anaphylaxis & anaphylactoid reactions, angioedema).
Hepato-biliary disorders: Uncommon: Abnormal liver enzymes, jaundice.
Frequency not known: Disturbed liver function.
Skin & Subcutaneous Tissue Disorders: Common: Acne, alopecia, rash.
Uncommon: Chloasma, dermatitis, ecchymosis, hirsutism, pruritus,
melasma, urticaria, oedema. Frequency not known: Skin striae,
scleroderma.
General Disorders and Administration Site Conditions: Common: Fatigue,
injection site reactions (such as pain or abscess), asthenia, paraesthesia.
Uncommon: Chest pain, pyrexia. Rare: Thirst, hoarseness, paralysis.
Frequency not known: Facial palsy.
Investigations: Uncommon: Cervical smear abnormal. Rare: Decreased
glucose tolerance.
Psychiatric Disorders: Common: Anorgasmia, depression, nervousness,
emotional disturbance, libido decreased, mood disorder, irritability,
insomnia. Uncommon: Anxiety.
Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps):
Rare: Breast cancer.
Blood and lymphatic system disorders: Rare: Anaemia. Frequency
unknown: Blood dyscrasia.
Respiratory, thoracic, and mediastinal disorders: Uncommon: Dyspnoea.

Lumbar Spine
Time on
Treatment

N
166

1 year
106
2 year

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

Total Hip

Femoral Neck

166

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

106

-3.5
(-4.2 to -2.7)

N

166

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

106

-3.5
(-4.3 to - 2.6)

N

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

Spine

Total Hip

Femoral Neck

Medroxyp
rog
esterone
acetate
5
years*
7
years**

Control

Medroxyp
rog
esterone
acetate

Control

Medroxyp
rog
esterone
acetate

Control

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

n=105
0.43%
n=60
0.53%

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

n=65
0.19%
n=39
0.94%

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

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

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

Overdose
No positive action is required other than cessation of therapy.

3

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Source: Medicines and Healthcare Products Regulatory Agency

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

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