New Zealand - English - Medsafe (Medicines Safety Authority)
Medroxyprogesterone acetate 150 mg/mL injection(depot)
Consumer Medicine Information
What is in this leaflet
This leaflet answers some common
questions about DEPO-PROVERA.
It does not contain all the available
information. It does not take the
place of talking to your doctor or
All medicines have risks and
benefits. Your doctor has weighed
the risks of you being treated with
DEPO-PROVERA against the
benefits it is expected to have for
If you have any concerns about
using this medicine, ask your
doctor or pharmacist.
Keep this leaflet.
You may need to read it again.
PROVERA is used for
The active ingredient of DEPO-
acetate, is a chemical similar to the
natural hormone progesterone.
Progesterone is produced by your
ovaries during the second half of
your monthly cycle.
There are several reasons why your
doctor may have prescribed DEPO-
PROVERA for you.
DEPO-PROVERA is used for the
DEPO-PROVERA is an injectable
form of contraception. Each injection
protects you from pregnancy for 3
DEPO-PROVERA works by
inhibiting the hormones that are
needed for the release of the eggs
from the ovaries.
Endometriosis is a condition in
which cells from the lining of the
uterus (womb) grow in places outside
During your period, these cells may
grow and break down in the same
way as those in the lining of the
uterus. This causes pain and
discomfort. DEPO-PROVERA helps
to stop the growth of the cells found
outside the uterus.
DEPO-PROVERA is also used in the
treatment of certain types of cancer
including cancer of the breast, kidney
and endometrium (lining of the
uterus). It works by inhibiting the
growth of these types of cancer cells.
DEPO-PROVERA is not a cure for
Ask your doctor if you have any
questions about why this medicine
has been prescribed for you.
Your doctor may have prescribed it
for another reason.
This medicine is available only with
a doctor's prescription.
Before treatment with
When you must not be given
DEPO-PROVERA should not be
given if you have or have had any of
the following medical conditions:
blood clots in your legs
swelling and redness along a vein
(usually extremely tender when
unusual or irregular vaginal
bleeding that has not been
blood in your urine that has not
known or suspected breast cancer
any lumps in your breasts that
have not been diagnosed
any bleeding or discharge from
severe, uncontrolled high blood
Do not use DEPO-PROVERA if
you have an allergy to any
medroxyprogesterone acetate or
any of the ingredients listed at the
end of this leaflet.
Do not use this medicine if you are
DEPO-PROVERA is not suitable for
use before menstruation (periods)
Do not breast-feed if you are
taking this medicine.
Do not use this medicine after the
expiry date printed on the pack or
if the packaging is torn or shows
signs of tampering.
If you are not sure whether you
should be treated with this
medicine, talk to your doctor.
Before treatment with DEPO-
Tell your doctor if you have
allergies to any other medicines,
foods, preservatives or dyes.
Tell your doctor if you are
pregnant or intend to become
Tell your doctor if you are breast-
feeding or plan to breast-feed.
Tell your doctor if you have or
have had any of the following
blood clots in your legs
sudden partial or complete loss of
swollen red veins
abnormal menstrual periods
including unusual or irregular
bleeding or spotting
cancer including breast cancer or
a family history of breast cancer
bone disease or a family history
of bone disease, such as brittle
any problems with your breasts
blood pressure problems
any condition that may affect
your bone mass e.g., excessive
alcohol intake, smoking,
anorexia, bone disease or long
term treatment with either
corticosteroids or medicines for
If you have not told your doctor
about any of the above, tell
him/her before you start treatment
DEPO-PROVERA is intended to
prevent pregnancy. It will not protect
you from sexually transmitted
diseases such as AIDS (HIV),
Hepatitis B and C, genital herpes,
genital warts, syphilis or gonorrhoea.
Clinical studies suggest if you are
under 35 years of age when you first
start treatment with DEPO-
PROVERA, you may have a slightly
increased risk of developing breast
cancer. This is similar to the risk with
oral contraceptives (the Pill). If you
have any concerns about this, please
discuss them with your doctor.
Using DEPO-PROVERA may result
in a decrease in the amount of
calcium stored in your bones. This
could increase your risk of
developing brittle bones
(osteoporosis), which can lead to
bone breakages in later life. This
affects women of all ages. However,
it can be greater if you are under 18
years old. Your doctor will assess
this risk before giving you DEPO-
PROVERA and if you continue using
DEPO-PROVERA for more than 2
years. If you are under 18 years old,
the amount of calcium in your bones
will start to recover to its original
level once you stop treatment with
DEPO-PROVERA. If you are over
18 years old, the calcium levels in
your bones may only partially
recover to its original level.
Talk to your doctor if you have any
concerns over the risk of
Taking other medicines
Tell your doctor or pharmacist if
you are taking any other
all prescription medicines
all medicines, vitamins, herbal
supplements or natural therapies
you buy without a prescription
from a pharmacy, supermarket,
naturopath or health food shop.
Some medicines may be affected by
DEPO-PROVERA or may affect
how well it works. You may need
different amounts of your medicines,
or you may need to take different
medicines. Your doctor will advise
Tell your doctor or pharmacist if
you are taking aminoglutethimide,
a medicine used to treat breast
Your doctor and pharmacist have
more information on medicines to be
careful with or avoid while using this
DEPO-PROVERA is given as an
injection into the muscle of your
upper arm or buttock. Your doctor or
a trained nurse will give you the
The dose and the treatment period for
DEPO-PROVERA will depend on
the condition for which you have
been prescribed this medicine.
The recommended dose for effective
contraception is 150 mg every three
If you are using DEPO-PROVERA
as a contraception for the first time,
your doctor or trained nurse will
advise you on the changes to expect
when you start treatment.
It is important that you make
arrangements to return to your doctor
every three months, for your
injection, to ensure that pregnancy is
If you are using DEPO-PROVERA
as a contraceptive for the first time,
your first injection should be given
during the first 5 days after the start
of your normal monthly period.
If you are using DEPO-PROVERA
as a form of contraception after the
birth of your baby and you are not
breast-feeding, the first injection
should be given within 5 days after
the baby is born.
If you are breast-feeding the first
injection should be given 6 weeks
after the baby was born, after your
doctor has checked that you are not
If you are switching from another
form of contraception, then DEPO-
PROVERA should be given in a way
that ensures you have continuous
contraceptive cover. For example,
patients switching from the oral
contraceptive pill should have their
first DEPO-PROVERA injection
within 7 days after taking the last
If you miss a scheduled injection,
your doctor will need to check that
you are not pregnant before giving
you another injection.
The usual dosage is either 50 mg
weekly or 100 mg every two weeks.
Treatment for endometriosis is
usually for at least 6 months.
Endometrial and Renal Cancer
The initial dose range is 500 to 1000
mg per week.
If you respond to treatment and your
condition is stable, a maintenance
dose of 500 mg a week or less may
Your doctor will determine how
much you will receive and how long
you should continue to receive the
The usual dosage for breast cancer is
500 mg to 1000 mg daily for 28 days.
If you respond to treatment, a dose of
500 mg twice weekly may be given.
Your doctor will determine how
much you will receive and how long
you should continue to receive the
If you use too much
Immediately telephone your doctor
or Poisons Information Centre
(telephone 0800 POISON or 0800
764 766) for advice, or go to
Accident and Emergency at the
nearest hospital, if you think that
you or anyone else may have been
given too much DEPO-PROVERA.
Do this even if there are no signs of
discomfort or poisoning.
You may need urgent medical
Overdose is unlikely as treatment
will be given by your doctor or a
health professional. Ask your doctor
or pharmacist if you have any
While you are being
treated with DEPO-
Things you must do
If you become pregnant while
using DEPO-PROVERA, tell your
If you have a sudden partial or
complete loss of vision or sudden
onset of double vision or migraine
while you are using DEPO-
PROVERA, tell your doctor
If you are about to be started on
any new medicine, remind your
doctor and pharmacist that you
are being treated with DEPO-
Tell any other doctors, dentists,
and pharmacists who treat you
that you are are being treated with
DEPO-PROVERA, particularly if
you are about to have any
pathology tests (e.g., blood or urine
DEPO-PROVERA may interfere
with the results.
Do not use DEPO-PROVERA to
treat any other complaints unless
your doctor tells you to.
Do not give your medicine to anyone
else, even if they have the same
condition as you.
Do not stop using your medicine or
lower the dosage without checking
with your doctor.
Things to be careful of
Be careful driving or operating
machinery until you know how
DEPO-PROVERA affects you.
DEPO-PROVERA generally does
not cause any problems with your
ability to drive a car or operate
machinery. However, DEPO-
PROVERA may cause dizziness,
drowsiness or fatigue in some people.
Make sure you know how DEPO-
PROVERA affects you.
Tell your doctor or pharmacist as
soon as possible if you do not feel
well during or after treatment with
All medicines can have side effects.
Sometimes they are serious, most of
the time they are not. However, you
may need medical treatment if you
get certain side effects.
Ask your doctor or pharmacist to
answer any questions you may
Most women using DEPO-
PROVERA for contraception
experience changes in their normal
monthly period. This includes
irregular or unpredictable bleeding or
spotting, or rarely, heavy or
continuous bleeding. If abnormal
bleeding continues or is severe, see
your doctor immediately.
With continued use of DEPO-
PROVERA, it is usual for vaginal
bleeding to decrease. Your periods
may stop completely.
When you stop treatment with
DEPO-PROVERA, your periods will
return. However, this may take up to
18 months. Most women find that it
takes about 10 months after their last
injection to become pregnant. The
length of time that you use DEPO-
PROVERA does not affect the time it
takes for you to become pregnant. If
you do not wish to become pregnant
after you stop treatment with DEPO-
PROVERA, you or your partner
should use another form of
A reduction in the amount of calcium
stored in your bones leading to brittle
bones (osteoporosis) or fractures may
occur. Talk to your doctor if you
have any concerns over the risk of
Tell your doctor or pharmacist if
you notice any of the following and
they worry you:
loss of concentration
drowsiness or sleepiness
tremor or shaking
hives, rash or itching
excessive hair growth
unusual hair loss or thinning
breast tenderness, pain or
changes in vaginal secretions
irregular vaginal bleeding or
lack of menstrual periods
weight changes (increase or
abdominal pain, bloating or
decreased libido or the inability to
pain and inflammation of the
swelling or puffiness
change in facial shape (round
change in appetite
generally feeling unwell
impotence (in men being treated
Tell your doctor as soon as possible
if you notice the following:
yellowing of the skin and eyes
abnormal liver function test
changes in body fat (e.g., an
increased amount of fat in the
upper back, neck, breast, and
trunk, and loss of fat from the
legs, arms, and face
pain, tenderness, lump,
indentation, thinning of the skin,
inflammation or abscess
formation at the injection site.
Tell your doctor immediately or go
to Accident and Emergency at
your nearest hospital, if you notice
any of the following:
sudden signs of allergy such as
rash, itching or hives on the skin,
swelling of the face, lips, tongue
or other parts of the body,
shortness of breath, wheezing or
sharp chest pain or coughing up
weakness or numbness in your
arms or legs
severe headaches or changes in
speech or vision, loss of
coordination, slurred speech,
shortness of breath, chest pain,
numbness heat or painful
swelling in the arms or
legsswollen or tender veins
sudden, painless loss of vision in
one eye as a result of blood clots
in the retina at the back of the eye
sudden onset of migraine
severe abdominal pain
increase in heart rate
abnormal heart beat
These may be signs of a serious side
effect. You may need urgent medical
attention. Serious side effects are
Some side effects (e.g, increase in
blood pressure, increases in white
blood cells and blood platelet count,
osteoporosis) can only be found
when your doctor does tests from
time to time to check your progress.
Tell your doctor or pharmacist if
you notice anything that is making
you feel unwell.
Do not be alarmed by this list of
possible side effects. You may not
experience any of them.
After treatment with
Normally you should take your
DEPO-PROVERA straight from the
pharmacy to your doctor.
If, for any reason you take your
DEPO-PROVERA home, always
ensure that it is stored in a place
where children cannot reach it.
It is important to store your DEPO-
PROVERA in a safe place that is
cool and dry (below 25°C).
Do not leave your DEPO-
PROVERA in a car.
Do not store DEPO-PROVERA or
any other medicine in the
bathroom or near a sink.
If the DEPO-PROVERA has
passed its expiry date, return it to
What it looks like
DEPO-PROVERA is a white cloudy
DEPO-PROVERA is available as a 1
mL disposable syringe.
Each syringe of DEPO-PROVERA
acetate as active ingredient.
It also contains:
Water for Injections.
This medicine does not contain
lactose, sucrose, gluten, tartrazine or
any other azo dyes.
DEPO-PROVERA is supplied in
New Zealand by:
Pfizer New Zealand Limited
PO Box 3998
Auckland, New Zealand
Toll Free Number: 0800 736 363.
Date of preparation
This leaflet was prepared in
© Pfizer Australia Pty Ltd 2016.
Page 1 of 18
NEW ZEALAND DATA SHEET
1. PRODUCT NAME
150 mg/mL Injection (depot)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 1 mL vial contains 150 mg/mL Medroxyprogesterone acetate
Each 1 mL disposable syringe contains 150 mg/mL Medroxyprogesterone acetate
Excipients with known effects:
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
DEPO-PROVERA 150 mg/mL Injection (depot) is a white, aqueous, suspension containing
medroxyprogesterone acetate (MPA) as the active ingredient.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
DEPO-PROVERA is indicated for:
Since loss of bone mineral density (BMD) may occur in pre-menopausal women who use
DEPO-PROVERA, particularly if treated long-term (greater than 2 years), women should be
assessed for risk factors for low BMD including a review of their medical history, to determine
the risk of developing osteoporosis. This should be conducted before the commencement of
treatment. A careful re-evaluation of the risks and benefits of treatment beyond 2 years should
be carried out in those patients who need to remain on DEPO-PROVERA.
Women under the age of 18 years may be at risk of failing to achieve their predicted peak BMD
(see section 4.4).
the treatment of endometriosis.
adjunctive and/or palliative treatment of recurrent and/or metastatic endometrial or
the treatment of hormonally-dependent recurrent breast cancer in post-menopausal
Page 2 of 18
4.2 Dose and method of administration
DEPO-PROVERA should be vigorously shaken just before use to ensure that the dose being
administered represents a uniform suspension. The IM suspension is not formulated for
The recommended dose is 150 mg of DEPO-PROVERA every 3 months administered by IM
injection in the gluteal or deltoid muscle. The initial injection should be given during the first
5 days after the onset of a normal menstrual period; within 5 days post-partum if not breast-
feeding; or if exclusively breast-feeding at or after 6 weeks post-partum.
It is recommended that physicians or others directly responsible for these patients advise them
at the beginning of treatment that their menstrual cycle may be disrupted, that irregular and
unpredictable bleeding or spotting are produced, but that this usually decreases to the point of
amenorrhoea as treatment with DEPO-PROVERA continues without other therapy being
Routine or long-term cyclic use of supplemental estrogens with DEPO-PROVERA is not
recommended. Excessive or prolonged bleeding which becomes troublesome to the patient
can usually be controlled by the administration of oral or parenteral estrogens in the equivalent
of 0.05 mg to 0.1 mg ethinylestradiol daily for 7 to 21 days. This therapy can be continued for
1 to 2 cycles, but should not be considered for long-term administration.
Based on limited experience, some investigators favour the use of a second injection of DEPO-
PROVERA before 90 days to control troublesome bleeding. The third and subsequent
injections should be administered at separate 90 day intervals.
If abnormal bleeding persists, appropriate investigation should be instituted to rule out the
possibility of organic pathology. Uterine curettage may be required on rare occasions.
The recommended dose of DEPO-PROVERA given intramuscularly is 50 mg weekly or
100 mg every 2 weeks for at least 6 months.
Endometrial and renal carcinoma
recommended initially. If improvement is noted within a few weeks or months and the disease
appears stabilised, it may be possible to maintain improvement with 500 mg per week or less.
DEPO-PROVERA is not recommended as primary therapy, but as adjunctive and palliative
treatment in advanced inoperable cases including those with recurrent or metastatic disease.
to 1000 mg
intramuscularly for 28 days. The patient should then be placed on a maintenance schedule of
500 mg twice weekly as long as she is responding to treatment. Response to hormonal therapy
(DEPO-PROVERA) for breast cancer may not be evident until 8 to 10 weeks of therapy.
Treatment with DEPO-PROVERA should be terminated should rapid progression of disease
occur at any time during therapy.
Page 3 of 18
Women should be assessed for risk factors for low BMD when treated for ovulation
suppression or endometriosis. If these are found to be present, a full risk-benefit evaluation
should be undertaken by the prescriber to determine the appropriateness of using DEPO-
PROVERA. 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.
contraception or treatment of endometriosis beyond 2 years. An evaluation of BMD may also
DEPO-PROVERA is not indicated before menarche. Data are available in adolescent females
(12 to 18 years) (see section 5.1, Clinical trial data). The safety and effectiveness of DEPO-
PROVERA are expected to be the same for postmenarcheal adolescent and adult females.
Use in hepatic insufficiency
No clinical studies have evaluated the effect of hepatic disease on the pharmacokinetics of
MPA. However, MPA is almost exclusively eliminated by hepatic metabolism and steroid
hormones may be poorly metabolised in patients with severe liver insufficiency (see section
Use in renal insufficiency
No clinical studies have evaluated the effect of renal disease on the pharmacokinetics of MPA.
However, since MPA is almost exclusively eliminated by hepatic metabolism, no dosage
adjustment should be necessary in women with renal insufficiency.
DEPO PROVERA is contraindicated in patients with:
thrombophlebitis, thromboembolic disorders, cerebral apoplexy or patients with a past
history of these conditions
known or suspected pregnancy (see section 4.4)
undiagnosed vaginal bleeding
known or suspected malignancy of the breast (when used for ovulation suppression or
undiagnosed breast pathology
undiagnosed urinary tract bleeding
severe uncontrolled hypertension
severe liver dysfunction
known hypersensitivity to MPA or any component of the injection (see section 6.1).
Page 4 of 18
4.4 Special warnings and precautions for use
DEPO-PROVERA has not been causally associated with the induction of thrombotic or
thromboembolic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism,
and retinal thrombosis), however, MPA is not recommended in any patient with a history of
venous thromboembolism (VTE). The physician should be alert to the earliest manifestations
of thrombotic or thromboembolic disorders. Should any of these occur or be suspected, the
drug should be discontinued immediately.
Medication should not be readministered pending examination if there is a sudden partial or
complete loss of vision, or if there is a sudden onset of proptosis, diplopia, or migraine. If
examination reveals papilloedema or retinal vascular lesions, medication should not be
Most women using DEPO-PROVERA experience disruption of menstrual bleeding patterns
following the administration of either a single or multiple doses of MPA (e.g., irregular or
unpredictable bleeding/spotting, rarely, heavy or continuous bleeding). If unexpected vaginal
bleeding occurs or abnormal bleeding persists or is severe, appropriate investigations should
be instituted to rule out the possibility of organic pathology and appropriate treatment should
be instituted when necessary.
As women continue using DEPO-PROVERA fewer experience irregular bleeding and more
experience amenorrhoea. By month 12, amenorrhoea was reported by 57% of women, and by
month 24, amenorrhoea was reported by 68% of women using DEPO-PROVERA.
Infertility and anovulation with amenorrhoea and/or erratic menstrual patterns may persist for
periods of up to 18 months and occasionally longer following either single or multiple
injections of DEPO-PROVERA.
Loss of BMD
Contraception and endometriosis
Use of DEPO-PROVERA reduces serum estrogen levels in premenopausal women and is
associated with a statistically significant loss of BMD as bone metabolism accommodates to a
lower estrogen level. Decreases in serum estrogen due to DEPO-PROVERA may result in a
decrease in BMD in a pre-menopausal woman and may increase her risk for developing
osteoporosis later in life.
Bone loss may be greater with increasing duration of use and may not be completely reversible
in some women. It is unknown if use of DEPO-PROVERA during adolescence and early
adulthood, a critical period of bone accretion, will reduce peak bone mass. In both adult and
adolescent females, the decrease in BMD during treatment appears to be substantially
reversible after DEPO-PROVERA is discontinued and ovarian estrogen production increases.
After discontinuing Depo-Provera injection in adolescents, full recovery of mean BMD
required 1.2 years at the lumbar spine, 4.6 years at the total hip and 4.6 years at the femoral
neck (see section 5.1, Clinical trial data).
In adults, BMD was observed for a period of 2 years after DEPO-PROVERA injection was
discontinued and partial recovery of mean BMD towards baseline was observed at total hip,
Page 5 of 18
femoral neck and lumbar spine (see section 5.1, Clinical trial data). A large observational
study of female contraceptive users showed that use of Depo-Provera injection has no effect
on a woman’s risk for osteoporotic or non-osteoporotic fractures (see
section 5.1, Clinical trial
DEPO-PROVERA should only be used as a long-term (e.g., longer than 2 years) contraceptive
method or treatment for endometriosis if other contraceptive methods or endometriotic
treatments are inadequate. BMD should be evaluated when a female needs to continue to use
DEPO-PROVERA long term. In adolescent females, interpretation of BMD results should
take into account patient age and skeletal maturity. Since loss of BMD may occur in pre-
menopausal women who use DEPO-PROVERA long-term (greater than 2 years) a risk/benefit
assessment, which also takes into consideration the decrease in BMD that occurs during
pregnancy and/or lactation, should be considered (see section 5.1, Clinical trial data).
risk/benefit analysis for the use of DEPO-PROVERA in women with osteoporotic risk factors
chronic alcohol 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
metabolic bone disease
strong family history of osteoporosis.
There are no studies on the BMD effects of high doses of parenteral DEPO-PROVERA for
However, 2 clinical studies of adult women of childbearing potential and of adolescent females
significant decreases in BMD (see section 5.1, Clinical trial data). Decreases in serum estrogen
due to DEPO-PROVERA may result in a decrease in BMD in a pre-menopausal woman and
may increase her risk for developing osteoporosis later in life.
An evaluation of BMD may be appropriate in some cancer patients who use DEPO-PROVERA
It is recommended that all patients have adequate calcium and vitamin D intake.
Long-term case-controlled surveillance of users of DEPO-PROVERA found slight or no
increased overall risk of breast cancer and no overall increased risk of ovarian, liver, or cervical
cancer. There was a prolonged effect of reducing the risk of endometrial cancer in the
population of users, with a relative risk (RR) of 0.21 (95% Confidence Interval [CI] of 0.06-
0.79). This protective effect lasts for at least 8 years after the cessation of DEPO-PROVERA
The overall RR of breast cancer associated with the use of DEPO-PROVERA appears to be
1.2 (95% CI 0.96-1.52). However, an increased RR of 2.19 (95% CI 1.23-3.89)
associated with use of DEPO-PROVERA in women whose first exposure to the drug was
within the previous 4 years and were under 35 years of age. The RR increases in women aged
Page 6 of 18
between 25 and 34 years of age (RR of 2 (95% CI 1.0-3.8) and rises to 4.6 (95% CI 1.4-15.1))
in women aged less than 25 years with more than 2 years exposure to DEPO-PROVERA.
risk of breast cancer was comparable in similar groups of women who used either DEPO-
PROVERA or an oral contraceptive.
The Australian Institute of Health & Welfare report, between 1983 to 1985, an average
incidence rate for breast cancer of 20.97/100,000 in Australian women, aged 30 to 34 years. A
RR of 2.19 increases the possible risk from 20.97 to 45.92 cases per 100,000 women. The
attributable risk, therefore, is 24.95 per 100,000 women per year.
The overall, non-significant, relative rate of invasive squamous cell cervical cancer in women
who ever used DEPO-PROVERA was estimated at 1.11 (95% CI 0.95-1.28). A statistically
insignificant increase in RR estimates of invasive squamous cell cervical cancer has been
associated with the use of DEPO-PROVERA in women who were first exposed before the age
of 35 years (RR 1.22 to 1.28 and 95% CI 0.93-1.70). No trends in risk with duration of use or
times since initial or most recent exposure were observed.
Additional precautions for oncology patients.
MPA may produce cushingoid symptoms.
Some patients receiving high dose MPA, used in the treatment of cancer, may exhibit
suppressed adrenal function. MPA may decrease ACTH and hydrocortisone blood levels.
Animal studies show that MPA possesses adrenocorticoid activity.
Infants from unintentional pregnancies that occur 1 to 2 months after injection of DEPO-
PROVERA may be at increased risk of low birth weight, which in turn, is associated with an
increased risk of neonatal death. Because there is a low incidence of pregnancies in women on
MPA, the attributable risk is low. There is no definitive information for the other formulations
A significant increase in polysyndactyly and chromosomal anomalies was observed among
infants of DEPO-PROVERA users, the former being most pronounced in women under
30 years of age. The unrelated nature of these defects, the lack of confirmation from other
studies, the distant preconceptual exposure to DEPO-PROVERA, and the chance effects due
to multiple statistical comparisons, make a causal association unlikely.
As with all forms of hormonal contraception, health-care providers should be alert to the
possibility of an ectopic pregnancy among women using DEPO-PROVERA who become
pregnant or complain of severe abdominal pain.
Sexually transmitted infections
counselled that DEPO-PROVERA does not protect against sexually transmitted infections
(STIs) including HIV infections (AIDS) but equally, DMPA is a sterile injection and, used as
directed, will not expose them to sexually transmitted infections. Safer sex practices including
correct and consistent use of condoms reduce the transmission of STIs through sexual contact,
Page 7 of 18
In all situations where cessation of therapy is warranted, the physician should be aware of the
slow elimination of the depot formulation.
Anaphylactic and anaphylactoid reactions
Anaphylactic and anaphylactoid reactions have occasionally been reported in patients treated
with IM MPA.
A complete medical and family history should be taken before the initiation of any hormone
therapy. The pre-treatment and periodic physical examination should include special reference
DEPO-PROVERA may cause some degree of fluid retention, therefore, caution should be
exercised in treating any patient with a pre-existing medical condition that might be adversely
affected by fluid retention, such as epilepsy, migraine, asthma, or cardiac or renal dysfunction.
Unexpected vaginal bleeding during therapy with DEPO-PROVERA should be investigated.
Breakthrough bleeding is likely to occur in patients being treated for endometriosis. No other
hormonal intervention is recommended for managing this bleeding. Non-functional causes
should also be borne in mind and in cases of undiagnosed vaginal bleeding, adequate diagnostic
measures are indicated.
Some patients receiving DEPO-PROVERA may exhibit a decreased glucose tolerance. The
mechanism of this decrease is obscure. For this reason, diabetic patients should be carefully
observed while receiving such therapy.
CNS disorders and convulsions
Patients with a history of treatment for clinical depression should be carefully monitored while
receiving DEPO-PROVERA therapy and the drug discontinued if the depression recurs to a
There was a tendency for women to gain weight while on therapy with MPA. From an initial
average body weight of 61.8 kg women who completed 1 year of therapy with DEPO-
PROVERA gained an average of 2.45 kg. Women who completed 2 years of therapy gained
an average of 3.68 kg. Women who completed 4 years gained an average of 6.3 kg. Women
who completed 6 years gained an average of 7.5 kg. Two per cent of women withdrew from a
large-scale clinical trial because of excessive weight gain.
Return of fertility
DEPO-PROVERA (150 mg IM injection) has a prolonged contraceptive effect. In a large US
study of women who discontinued use of DEPO-PROVERA to become pregnant, data are
available for 61% of them. Based on Life-Table analysis of these data, it is expected that 65%
of women who do become pregnant may conceive within 12 months. 83% may conceive
within 15 months, and 93% may conceive within 18 months from the last injection. The
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median time to conception for those who do conceive is 10 months following the last injection
with a range of 4 to 31 months, and is unrelated to the duration of use. No data are available
for 39% of the patients who discontinued DEPO-PROVERA and were lost to follow-up or
changed their mind.
Certain endocrine and possible liver function tests may be affected by treatment with DEPO-
PROVERA. Therefore, if such tests are abnormal in a patient taking DEPO-PROVERA, it is
recommended that they be repeated after the drug has been withdrawn. If jaundice develops,
consideration should be given to not readminister the drug.
The age of the patient constitutes no absolute limiting factor, although treatment with
progestogens may mask the onset of the climacteric.
The pathologist (laboratory) should be informed of the patient’s use of DEPO-PROVERA if
endometrial or endocervical tissue is submitted for examination.
Gluteal infiltration and abscess formation may occur with IM administration.
Because of the prolonged action and the resulting difficulty in predicting the time of withdrawal
secondary amenorrhoea or dysfunctional uterine bleeding. In these conditions, oral therapy is
4.5 Interaction with other medicines and other forms of interaction
Aminoglutethimide administered concomitantly with high doses of MPA may significantly
depress the serum concentrations of MPA. Users of DEPO-PROVERA should be warned of
the possibility of decreased efficacy with the use of aminoglutethimide or any related drugs.
MPA is metabolised
primarily by hydroxylation via the CYP3A4. While specific drug-
drug interaction studies evaluating the clinical effect of CYP3A4 inhibitors or inducers on
MPA have not been conducted or reported in the literature, physicians should consider that
interactions could occur which may result in compromised efficacy. Co-administration of
MPA with CYP3A4 inducers may result in decreased systemic levels of MPA whilst co-
administration of MPA with CYP3A4 inhibitors may increase MPA levels.
Effects on laboratory tests
The physician/laboratory should be informed that the use of DEPO-PROVERA may decrease
the levels of the following endocrine biomarkers or affect the following laboratory tests:
plasma/urinary steroids (e.g., cortisol, estrogen, pregnanediol, progesterone,
plasma/urinary gonadotrophins (e.g., LH and FSH)
glucose tolerance test
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metyrapone test - the use of DEPO-PROVERA may also cause partial adrenal
insufficiency (decrease in pituitary-adrenal axis response) during metyrapone testing.
Thus, the ability of adrenal cortex to respond to ACTH should be demonstrated before
metyrapone is administered.
coagulation test values for prothrombin (Factor II) and Factors VII, VIII, IX and X may
4.6 Fertility, pregnancy and lactation
DEPO-PROVERA IS NOT TO BE USED AS A TEST FOR PREGNANCY OR WHERE
PREGNANCY IS SUSPECTED.
DEPO-PROVERA is contraindicated in women who are pregnant.
Studies in animals have shown that progestogens, including MPA, may have an adverse effect
on the developing fetus, including teratogenicity and fetotoxicity.
In addition, other animal studies have shown that high doses of progestogens can cause
masculinisation of the female fetus.
Some reports suggest an association between intrauterine exposure to progestational drugs in
the first trimester of pregnancy and genital abnormalities in male and female fetuses.
The risk of hypospadias (5 to 8 per 1000 male births in the general population) may be
approximately doubled with exposure to these drugs. There are insufficient data to quantify
the risks to female fetuses, but because some of these drugs induce mild virilisation of the
external genitalia of the female fetus and because of the increased association of hypospadias
in the male fetus, it is prudent to avoid use of these drugs during the first trimester of pregnancy.
Children exposed to MPA
and followed to adolescence showed no evidence of any
If DEPO-PROVERA is used during pregnancy, or if the patient becomes pregnant while using
this drug, the patient should be apprised of the potential hazard to the fetus.
To ensure that DEPO-PROVERA is not administered inadvertently to a pregnant woman, it is
important that the first injection only be given:
during the first 5 days after the onset of a normal menstrual period
within 5 days post-partum if not breast feeding and
if breast feeding, at the sixth week post-partum, after having excluded pregnancy.
When switching from other contraceptive methods, MPA IM should be given in a manner that
ensures continuous contraceptive coverage based upon the mechanism of action of both
methods, (e.g., patients switching from oral contraceptives should have their first injection of
MPA within 7 days after taking their last active pill).
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MPA and its metabolites are excreted in breast milk. In mothers who are breastfeeding and
who are treated with DEPO-PROVERA, milk composition, quality and amount are not
adversely affected. Infants exposed to medroxyprogesterone via breast milk have been studied
for developmental and behavioural effects through puberty and there is no evidence to suggest
that this presents any hazard to the nursing child.
4.7 Effects on ability to drive and use machines
The effect of medroxyprogesterone acetate on the ability to drive and use machinery has not
been systematically evaluated.