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DEPO-PROVERA INJECTION 150MG/ML

Active substance: MEDROXYPROGESTERONE ACETATE

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Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Depo-Provera 150 mg/ml

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml of suspension contains 150 mg medroxyprogesterone acetate Ph. Eur.
For excipients, see section 6.1

3

PHARMACEUTICAL FORM
Sterile suspension for injection.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Progestogen: for contraception.
Depo-Provera is a long-term contraceptive agent suitable for use in women
who have been appropriately counselled concerning the likelihood of
menstrual disturbance and the potential for a delay in return to full fertility.
Depo-Provera may also be used for short-term contraception in the following
circumstances:
(i)
For partners of men undergoing vasectomy, for protection until the
vasectomy becomes effective.
(ii)
In women who are being immunised against rubella, to prevent
pregnancy during the period of activity of the virus.
(iii) In women awaiting sterilisation.
Since loss of bone mineral density (BMD) may occur in females of all ages
who use Depo-Provera injection long-term (see section 4.4 Special Warnings
and Special Precautions for Use), 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.
Consistent with good clinical practice a general medical as well as
gynaecological examination should be undertaken before administration of
Depo-Provera and at appropriate intervals thereafter.

4.2

Posology and method of administration
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. 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.
The site of injection should be cleansed using standard methods prior to
administration of the injection.
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.
Post Partum: To increase assurance that the patient is not pregnant at the time
of first administration, this injection should be given within 5 days post
partum 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, post partum
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 post partum, 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. (N.B. 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.
Elderly : Not appropriate.
Children: Depo-Provera is not indicated before menarche (see section 4.1
Therapeutic Indications)
Data in adolescent females (12-18 years) is available (see section 4.4 Special
Warnings and Special Precautions for Use). Other than concerns about loss of
BMD, the safety and effectiveness of Depo-Provera is expected to be the same
for adolescents after menarche and adult females
Switching from other Methods of Contraception
Depo-Provera should be given in a manner that ensures continuous
contraceptive coverage. This should be based upon the mechanism of action
of other methods, (e.g. patients switching from oral contraceptives should have
their first injection of Depo-provera within 7 days of taking their last active
pill)
Hepatic Insufficiency
The effect of hepatic disease on the pharmacokinetics of Depo-Provera is
unknown. As Depo-Provera largely undergoes hepatic elimination it may be
poorly metabolised in patients with severe liver insufficiency (see Section 4.3
– 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.

4.3

Contraindications
Depo-Provera is contra-indicated in patients with a known sensitivity to
medroxyprogesterone acetate or any ingredient of the vehicle.
Depo-Provera should not be used during pregnancy, either for diagnosis or
therapy.

Depo-Provera is contra-indicated as a contraceptive at the above dosage in
known or suspected hormone-dependent malignancy of breast or genital
organs.
Depo-Provera is contra-indicated in patients with the presence or history of
severe hepatic disease whose liver function test have not returned to normal.
Whether administered alone or in combination with oestrogen, Depo-Provera
should not be employed in patients with abnormal uterine bleeding until a
definite diagnosis has been established and the possibility of genital tract
malignancy eliminated.

4.4

Special warnings and precautions for use
Loss of Bone Mineral Density:
Use of DEPO-PROVERA reduces serum estrogen levels and is associated
with significant loss of BMD due to the known effect of estrogen deficiency
on the bone remodelling system. Bone loss is greater with increasing duration
of use, however BMD appears to increase after DEPO-PROVERA is
discontinued and ovarian 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 DEPOPROVERA 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 (DepoProvera, 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, DEPOPROVERA 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 followup 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
(Pharmacodynamic Properties). 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 coadministration 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
No of cases per 10,000 women who
are never-users
use of
DMPA
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.
Thrombo-embolic 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 premenstrualtype 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 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.

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 thrombo-embolism 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 Depo-Provera appears to be associated with a 15-20% reduction in
serum high density lipoprotein (HDL) cholesterol levels which may protect
women from cardiovascular disease. The clinical consequences of this
observation are unknown. The potential for an increased risk of coronary
disease should be considered prior to use.
Doctors should carefully consider the use of Depo-Provera in patients with
recent trophoblastic disease before levels of human chorionic gonadotrophin
have returned to normal.
Physicians should be aware that pathologists should be informed of the
patient's use of Depo-Provera if endometrial or endocervical tissue is
submitted for examination.
The results of certain laboratory tests may be affected by the use of 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.

4.5

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.

4.6

Pregnancy and lactation
Doctors should check that patients are not pregnant before 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 via breast milk have been
studied for developmental and behavioural effects to puberty. No adverse
effects have been noted.

4.7

Effects on ability to drive and use machines
None

4.8

Undesirable effects
In a large clinical trial of over 3900 women, who were treated with DepoProvera 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 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
Rare: paralysis
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

4.9

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

5

PHARMACOLOGICAL PROPERTIES

5.1

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 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
Time
on N
Mean % Change
Treatment
(95% CI)
1 year
166 -2.7
(-3.1 to -2.3)
2 year
106 - 4.1
(-4.6 to -3.5)

Total Hip
N
Mean % Change
(95% CI)
166 -1.7
(-2.1 to -1.3)
106 -3.5
(-4.2 to -2.7)

Femoral Neck
N
Mean % Change
(95% CI)
166 -1.9
(-2.5 to -1.4)
106 -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

5 years*
7 years**

Spine
Medroxypro
gesterone
acetate
n=33
-5.38%
n=12
-3.13%

Control

n=105
0.43%
n=60
0.53%

Total Hip
Medroxypro
gesterone
acetate
n=21
-5.16%
n=7
-1.34%

Control

n=65
0.19%
n=39
0.94%

Femoral Neck
Medroxypro
gesterone
acetate
n=34
-6.12%
n=13
-5.38%

Control

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

*The treatment group consisted of women who received medroxyprogesterone
acetate injection (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.

5.2

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.

5.3

Preclinical safety data
No data held.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Excipients are methylparaben, macrogol 3350, polysorbate 80, propylparaben,
sodium chloride, hydrochloric acid, sodium hydroxide and water for
injections.

6.2

Incompatibilities
None known.

6.3

Shelf life
Syringe: 36 months.
Vial: 18 months

6.4

Special precautions for storage
Do not store above 25 °C.
Do not freeze.

6.5

Nature and contents of container
1 ml disposable syringe with plunger stopper and tip cap.
1 ml vial with stopper and tip cap.

6.6

Special precautions for disposal
No special instructions are applicable.

7

MARKETING AUTHORISATION HOLDER
Pfizer Limited
Ramsgate Road
Sandwich
Kent
CT13 9NJ
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 00057/0965

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Date of Grant: 27 August 1991
Date of Renewal: 6 February 1997

10

DATE OF REVISION OF THE TEXT
20/01/2012

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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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