Provera
Generic Name: medroxyprogesterone acetate
Dosage Form: tablet
WARNING:
CARDIOVASCULAR DISORDERS, BREAST CANCER AND PROBABLE DEMENTIA FOR ESTROGEN PLUS
PROGESTIN THERAPY
Cardiovascular Disorders and Probable Dementia
Estrogen
plus progestin therapy should not be used for the prevention of cardiovascular
disease or dementia. (See CLINICAL
STUDIES and WARNINGS, Cardiovascular Disorders and Probable
Dementia.)
The
Women's Health Initiative (WHI) estrogen plus progestin substudy reported an
increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), stroke
and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age)
during 5.6 years of treatment with daily oral conjugated estrogens (CE) [0.625
mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to
placebo. (See CLINICAL
STUDIES and WARNINGS, Cardiovascular Disorders.)
The WHI
Memory Study (WHIMS) estrogen plus progestin ancillary study reported an
increased risk of developing probable dementia in postmenopausal women 65 years
of age or older during 4 years of treatment with daily CE (0.625 mg) combined
with MPA (2.5 mg), relative to placebo. It is unknown whether this finding
applies to younger postmenopausal women. (See CLINICAL
STUDIES and WARNINGS, Probable Dementia and PRECAUTIONS,
Geriatric Use.)
Breast Cancer
The WHI
estrogen plus progestin substudy demonstrated an increased risk of invasive
breast cancer. (See CLINICAL
STUDIES and WARNINGS, Malignant Neoplasm, Breast Cancer.)
In the absence
of comparable data, these risks should be assumed to be similar for other doses
of CE and MPA, and other combinations and dosage forms of estrogens and
progestins.
Progestins
with estrogens should be prescribed at the lowest effective doses and for the
shortest duration consistent with treatment goals and risks for the individual
woman.
Provera Description
Provera® tablets contain medroxyprogesterone acetate, which is a
derivative of progesterone. It is a white to off-white, odorless crystalline
powder, stable in air, melting between 200 and 210°C. It is freely soluble in
chloroform, soluble in acetone and in dioxane, sparingly soluble in alcohol and
in methanol, slightly soluble in ether, and insoluble in water.
The
chemical name for medroxyprogesterone acetate is pregn-4-ene-3, 20-dione,
17-(acetyloxy)-6-methyl-, (6α)-. The structural formula is:
Each
Provera tablet for oral administration contains 2.5 mg, 5 mg or 10 mg of
medroxyprogesterone acetate and the following inactive ingredients: calcium
stearate, corn starch, lactose, mineral oil, sorbic acid, sucrose, and talc.
The 2.5 mg tablet contains FD&C Yellow No. 6.
SLIDESHOW
Fertility Facts: Women's Fertility Issues Explained
Provera - Clinical Pharmacology
Medroxyprogesterone
acetate (MPA) administered orally or parenterally in the recommended doses to
women with adequate endogenous estrogen, transforms proliferative into
secretory endometrium. Androgenic and anabolic effects have been noted, but the
drug is apparently devoid of significant estrogenic activity. While
parenterally administered MPA inhibits gonadotropin production, which in turn
prevents follicular maturation and ovulation, available data indicate that this
does not occur when the usually recommended oral dosage is given as single
daily doses.
Pharmacokinetics
The
pharmacokinetics of MPA were determined in 20 postmenopausal women following a
single-dose administration of eight Provera 2.5 mg tablets or a single
administration of two Provera 10 mg tablets under fasting conditions. In
another study, the steady-state pharmacokinetics of MPA were determined under
fasting conditions in 30 postmenopausal women following daily administration of
one Provera 10 mg tablet for 7 days. In both studies, MPA was quantified in
serum using a validated gas chromatography-mass spectrometry (GC-MS) method.
Estimates of the pharmacokinetic parameters of MPA after single and multiple
doses of Provera tablets were highly variable and are summarized in Table 1.
Table 1. Mean (SD) Pharmacokinetic Parameters for
Medroxyprogesterone Acetate (MPA)
|
|
Tablet Strength
|
C max
(ng/mL)
|
T max
(h)
|
Auc 0–(∞)
(ng∙h/mL)
|
t 1/2
(h)
|
Vd/f
(L)
|
CL/f
(mL/min)
|
|
*
Following Day 7 dose
|
|
Single Dose
|
|
2 × 10 mg
|
1.01 (0.599)
|
2.65 (1.41)
|
6.95 (3.39)
|
12.1 (3.49)
|
78024
(47220)
|
64110
(42662)
|
|
8 × 2.5 mg
|
0.805 (0.413)
|
2.22 (1.39)
|
5.62 (2.79)
|
11.6 (2.81)
|
62748
(40146)
|
74123
(35126)
|
|
Multiple Dose
|
|
10 mg *
|
0.71 (0.35)
|
2.83 (1.83)
|
6.01 (3.16)
|
16.6 (15.0)
|
40564
(38256)
|
41963
(38402)
|
A.
Absorption
No
specific investigation on the absolute bioavailability of MPA in humans has
been conducted. MPA is rapidly absorbed from the gastrointestinal tract, and
maximum MPA concentrations are obtained between 2 to 4 hours after oral
administration.
Administration
of Provera with food increases the bioavailability of MPA. A 10 mg dose of
Provera, taken immediately before or after a meal, increased MPA Cmax (50
to 70%) and AUC (18 to 33%). The half-life of MPA was not changed with food.
B.
Distribution
MPA is
approximately 90% protein bound, primarily to albumin; no MPA binding occurs
with sex hormone binding globulin.
C.
Metabolism
Following
oral dosing, MPA is extensively metabolized in the liver via hydroxylation,
with subsequent conjugation and elimination in the urine.
D.
Excretion
Most MPA
metabolites are excreted in the urine as glucuronide conjugates with only minor
amounts excreted as sulfates.
E.
Specific Populations
Hepatic Insufficiency
MPA is
almost exclusively eliminated via hepatic metabolism. In 14 patients with
advanced liver disease, MPA disposition was significantly altered (reduced
elimination). In patients with fatty liver, the mean percent dose excreted in
the 24-hour urine as intact MPA after a 10 mg or 100 mg dose was 7.3% and 6.4%,
respectively.
Renal Insufficiency
The
effect of renal impairment on the pharmacokinetics of Provera has not been
studied.
F.
Drug Interactions
Medroxyprogesterone
acetate (MPA) is metabolized in-vitro primarily by hydroxylation via the
CYP3A4. Specific drug-drug interaction studies evaluating the clinical effects
with CYP3A4 inducers or inhibitors on MPA have not been conducted. Inducers
and/or inhibitors of CYP3A4 may affect the metabolism of MPA.
Clinical Studies
Effects on the Endometrium
In a
3-year, double-blind, placebo-controlled study of 356 nonhysterectomized,
postmenopausal women between 45 and 64 years of age randomized to receive
placebo (n=119), 0.625 mg conjugated estrogen only (n=119), or 0.625 mg
conjugated estrogen plus cyclic Provera (n=118), results showed a reduced risk
of endometrial hyperplasia in the treatment group receiving 10 mg Provera plus
0.625 mg conjugated estrogens compared to the group receiving 0.625 mg
conjugated estrogens only. See Table
2.
Table 2. Number (%) of Endometrial Biopsy Changes Since Baseline
After 3 Years of Treatment *
|
|
Histological
Results
|
Placebo
(n=119)
|
CEE †
(n=119)
|
Provera ‡ + CEE
(n=118)
|
|
*
Includes most
extreme abnormal result
†
CEE = conjugated
equine estrogens 0.625 mg/day
‡
Provera = medroxyprogesterone acetate tablets 10
mg/day for 12 days
|
|
Normal/No hyperplasia (%)
|
116 (97)
|
45 (38)
|
112 (95)
|
|
Simple (cystic)
hyperplasia (%)
|
1 (1)
|
33 (28)
|
4 (3)
|
|
Complex
(adenomatous) hyperplasia (%)
|
1 (1)
|
27 (22)
|
2 (2)
|
|
Atypia (%)
|
0
|
14 (12)
|
0
|
|
Adenocarcinoma
(%)
|
1 (1)
|
0
|
0
|
In a
second 1-year study, 832 postmenopausal women between 45 and 65 years of age
were treated with daily 0.625 mg conjugated estrogen (days 1–28), plus either 5
mg cyclic Provera or 10 mg cyclic Provera (days 15–28), or daily 0.625 mg
conjugated estrogen only. The treatment groups receiving 5 or 10 mg cyclic
Provera (days 15–28) plus daily conjugated estrogens showed a significantly
lower rate of hyperplasia as compared to the conjugated estrogens only group.
See Table
3.
Table 3. Number (%) of Women with Endometrial Hyperplasia at 1 Year
|
|
|
CEE *
|
MPA † + CEE *
|
|
|
(n=283)
|
MPA 5 mg
(n=277)
|
MPA 10 mg
(n=272)
|
|
*
CEE = conjugated
equine estrogen 0.625 mg every day of a 28-day cycle.
†
Cyclic medroxyprogesterone acetate on days 15 to 28
|
|
Cystic
hyperplasia (%)
|
55 (19)
|
3 (1)
|
0
|
|
Adenomatous
hyperplasia without atypia
|
2 (1)
|
0
|
0
|
Women's Health Initiative Studies
The WHI
enrolled approximately 27,000 predominantly healthy postmenopausal women in two
substudies to assess the risks and benefits of daily oral CE (0.625 mg)-alone
or in combination with MPA (2.5 mg) compared to placebo in the prevention of
certain chronic diseases. The primary endpoint was the incidence of coronary
heart disease (CHD) (defined as nonfatal MI, silent MI and CHD death), with
invasive breast cancer as the primary adverse outcome. A "global
index" included the earliest occurrence of CHD, invasive breast cancer,
stroke, PE, endometrial cancer (only in the CE plus MPA substudy), colorectal
cancer, hip fracture, or death due to other cause. These substudies did not
evaluate the effects of CE-alone or CE plus MPA on menopausal symptoms.
WHI
Estrogen Plus Progestin Substudy
The WHI
estrogen plus progestin substudy was stopped early. According to the predefined
stopping rule, after an average follow-up of 5.6 years of treatment, the
increased risk of invasive breast cancer and cardiovascular events exceeded the
specified benefits included in the "global index." The absolute
excess risk of events included in the "global index" was 19 per
10,000 women-years.
For those
outcomes included in the WHI "global index" that reached statistical
significance after 5.6 years of follow-up, the absolute excess risks per 10,000
women-years in the group treated with CE plus MPA were 7 more CHD events, 8
more strokes, 10 more PEs, and 8 more invasive breast cancers, while the
absolute risk reduction per 10,000 women-years were 6 fewer colorectal cancers
and 5 fewer hip fractures.
Results
of the CE plus MPA substudy, which included 16,608 women (average 63 years of
age, range 50 to 79; 83.9 percent White, 6.8 percent Black, 5.4 percent
Hispanic, 3.9 percent Other) are presented in Table 4. These results reflect
centrally adjudicated data after an average follow-up of 5.6 years.
Table 4 : RELATIVE AND ABSOLUTE RISK SEEN IN THE ESTROGEN PLUS
PROGESTIN SUBSTUDY OF WHI AT AN AVERAGE OF 5.6 YEARS *,†
|
|
|
Event
|
Relative
Risk
CE/MPA vs placebo
(95%nCI ‡)
|
CE/MPA
n = 8,506
|
Placebo
n = 8,102
|
|
|
Absolute
Risk per 10,000 Women-Years
|
|
|
*
Adapted from
numerous WHI publications. WHI publications can be viewed at
www.nhlbi.nih.gov/whi.
†
Results are
based on centrally adjudicated data.
‡
Nominal
confidence intervals unadjusted for multiple looks and multiple comparisons.
§
Not included in
"global index".
¶
Includes
metastatic and non-metastatic breast cancer, with the exception of in situ
breast cancer.
#
All deaths,
except from breast or colorectal cancer, definite or probableCHD,PEor cerebrovascular disease.
Þ
A subset of the events was combined in a "global
index", defined as the earliest occurrence of CHD events, invasive
breast cancer, stroke, pulmonary embolism, colorectal cancer, hip fracture,
or death due to other causes.
|
|
|
CHD events
|
1.23 (0.99–1.53)
|
41
|
34
|
|
|
Non-fatal MI
|
1.28
(1.00–1.63)
|
31
|
25
|
|
|
CHD death
|
1.10
(0.70–1.75)
|
8
|
8
|
|
|
All strokes
|
1.31 (1.03–1.68)
|
33
|
25
|
|
|
Ischemic stroke
|
1.44
(1.09–1.90)
|
26
|
18
|
|
|
Deep vein
thrombosis§
|
1.95 (1.43–2.67)
|
26
|
13
|
|
|
Pulmonary
embolism
|
2.13 (1.45–3.11)
|
18
|
8
|
|
|
Invasive breast
cancer¶
|
1.24 (1.01–1.54)
|
41
|
33
|
|
|
Colorectal
cancer
|
0.61 (0.42–0.87)
|
10
|
16
|
|
|
Endometrial
cancer§
|
0.81 (0.48–1.36)
|
6
|
7
|
|
|
Cervical cancer§
|
1.44 (0.47–4.42)
|
2
|
1
|
|
|
Hip fracture
|
0.67 (0.47–0.96)
|
11
|
16
|
|
|
Vertebral
fractures§
|
0.65 (0.46–0.92)
|
11
|
17
|
|
|
Lower arm/wrist
fractures§
|
0.71 (0.59–0.85)
|
44
|
62
|
|
|
Total fractures§
|
0.76 (0.69–0.83)
|
152
|
199
|
|
|
Overall
mortality#
|
1.00 (0.83–1.19)
|
52
|
52
|
|
|
Global IndexÞ
|
1.13 (1.02–1.25)
|
184
|
165
|
|
Timing of
the initiation of estrogen plus progestin therapy relative to the start of
menopause may affect the overall risk benefit profile. The WHI estrogen plus
progestin substudy stratified by age showed in women 50 to 59 years of age a
nonsignificant trend toward reduced risk in overall mortality [hazard ration
(HR) 0.69 (95 percent CI, 0.44–1.07)].
Women's Health Initiative Memory Study
The WHIMS
estrogen plus progestin ancillary study of WHI enrolled 4,532 predominantly
healthy postmenopausal women 65 years of age and older (47 percent were aged 65
to 69 years of age, 35 percent were 70 to 74 years of age, and 18 percent were
75 years of age and older) to evaluate the effects of daily CE (0.625 mg) plus
MPA (2.5 mg) on the incidence of probable dementia (primary outcome) compared
to placebo.
After an
average follow-up of 4 years, the relative risk of probable dementia for CE
plus MPA versus placebo was 2.05 (95 percent CI, 1.21–3.48). The absolute risk
of probable dementia for CE plus MPA versus placebo was 45 versus 33 per 10,000
women-years. Probable dementia as defined in this study included Alzheimer's
disease (AD), vascular dementia (VaD) and mixed type (having features of both
AD and VaD). The most common classification of probable dementia in the
treatment group and the placebo group was AD. Since the ancillary study was
conducted in women 65 to 79 years of age, it is unknown whether these findings
apply to younger postmenopausal women. (See WARNINGS,
Probable Dementia and PRECAUTIONS, Geriatric Use).
Indications and Usage for Provera
Provera
tablets are indicated for the treatment of secondary amenorrhea and abnormal
uterine bleeding due to hormonal imbalance in the absence of organic pathology,
such as fibroids or uterine cancer. They are also indicated for use in the
prevention of endometrial hyperplasia in nonhysterectomized postmenopausal
women who are receiving daily oral conjugated estrogens 0.625 mg tablets.
Contraindications
Provera
is contraindicated in women with any of the following conditions:
1. Undiagnosed abnormal genital bleeding.
2. Known, suspected, or history of breast cancer.
3. Known or suspected estrogen- or
progesterone-dependent neoplasia.
4. ActiveDVT,PE, or a history of these
conditions
5. Active arterial thromboembolic disease (for example,
stroke and MI), or a history of these conditions.
6. Known anaphylactic reaction or angioedema to Provera.
7. Known liver impairment or disease.
8. Known or suspected pregnancy.
Warnings
See BOXED WARNINGS.
1. Cardiovascular Disorders
An
increased risk of PE, DVT, stroke, and MI has been reported with estrogen plus
progestin therapy. Should any of these events occur or be suspected, estrogen
plus progestin therapy should be discontinued immediately.
Risk
factors for arterial vascular disease (for example, hypertension, diabetes
mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous
thromboembolism (VTE) (for example, personal history or family history of VTE,
obesity, and systemic lupus erythematosus) should be managed appropriately.
a.
Stroke
In the
WHI estrogen plus progestin substudy, a statistically significant increased
risk of stroke was reported in women 50 to 79 years of age receiving CE (0.625
mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo
(33 versus 25 per 10,000 women-years). (See CLINICAL
STUDIES.) The
increase in risk was demonstrated after the first year and persisted. Should a
stroke occur or be suspected, estrogen plus progestin therapy should be discontinued
immediately.
b.
Coronary Heart Disease
In the
WHI estrogen plus progestin substudy, there was a statistically non-significant
increased risk of CHD events reported in women receiving daily CE (0.625 mg)
plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000
women-years). An increase in relative risk was demonstrated in year 1, and a
trend toward decreasing relative risk was reported in years 2 through 5.
In
postmenopausal women with documented heart disease (n = 2,763, average 66.7
years of age), in a controlled clinical trial of secondary prevention of
cardiovascular disease (Heart and Estrogen/Progestin Replacement Study [HERS]),
treatment with daily CE (0.625 mg) plus MPA (2.5mg) demonstrated no
cardiovascular benefit. During an average follow-up of 4.1 years, treatment
with CE plus MPA did not reduce the overall rate of CHD events in
postmenopausal women with established coronary heart disease. There were more
CHD events in the CE plus MPA-treated group than in the placebo group in year
1, but not during the subsequent years. Two thousand three hundred and
twenty-one (2,321) women from the original HERS trial agreed to participate in
an open label extension of HERS, HERS II. Average follow-up in HERS II was an
additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events
were comparable among women in the CE plus MPA group and the placebo group in
HERS, HERS II, and overall.
c.
Venous Thromboembolism
In the
WHI estrogen plus progestin substudy, a statistically significant 2-fold
greater rate of VTE (DVT and PE) was reported in women receiving daily CE
(0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17
per 10,000 women-years). Statistically significant increases in risk for both
DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000
women-years) were also demonstrated. The increase in VTE risk was demonstrated
during the first year and persisted. (See CLINICAL
STUDIES.) Should
a VTE occur or be suspected, estrogen plus progestin therapy should be
discontinued immediately.
If
feasible, estrogens plus progestins should be discontinued at least 4 to 6
weeks before surgery of the type associated with an increased risk of
thromboembolism, or during periods of prolonged immobilization.
2. Malignant Neoplasms
a.
Breast Cancer
The most
important randomized clinical trial providing information about breast cancer
in estrogen plus progestin users is the WHI substudy of daily CE (0.625 mg)
plus MPA (2.5 mg). After a mean follow-up of 5.6 years, the estrogen plus
progestin substudy reported an increased risk of invasive breast cancer in
women who took daily CE plus MPA.
In this
substudy, prior use of estrogen-alone or estrogen plus progestin therapy was
reported by 26 percent of the women. The relative risk of invasive breast
cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000
women-years, for CE plus MPA compared with placebo. Among women who reported
prior use of hormone therapy, the relative risk of invasive breast cancer was
1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for
CE plus MPA compared with placebo. Among women who reported no prior use of
hormone therapy, the relative risk of invasive breast cancer was 1.09, and the
absolute risk was 40 versus 36 cases per 10,000 women-years, for CE plus MPA
compared with placebo. In the same substudy, invasive breast cancers were
larger, were more likely to be node positive, and were diagnosed at a more
advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the
placebo group. Metastatic disease was rare with no apparent difference between
the two groups. Other prognostic factors such as histologic subtype, grade, and
hormone receptor status did not differ between the groups. (See CLINICAL STUDIES.)
Consistent
with the WHI clinical trial, observational studies have also reported an
increased risk of breast cancer for estrogen plus progestin therapy, and a
smaller risk for estrogen-alone therapy, after several years of use. The risk
increased with duration of use, and appeared to return to baseline over about 5
years after stopping treatment (only the observational studies have substantial
data on risk after stopping). Observational studies also suggest that the risk
of breast cancer was greater, and became apparent earlier, with estrogen plus
progestin therapy as compared to estrogen-alone therapy. However, these studies
have not found significant variation in the risk of breast cancer among
different estrogen plus progestin combinations, or routes of administration.
The use
of estrogen plus progestin has been reported to result in an increase in
abnormal mammograms requiring further evaluation. All women should receive
yearly breast examinations by a healthcare provider and perform monthly breast
self-examinations. In addition, mammography examinations should be scheduled
based on patient age, risk factors, and prior mammogram results.
b.
Endometrial Cancer
An
increased risk of endometrial cancer has been reported with the use of
unopposed estrogen therapy in women with a uterus. The reported endometrial
cancer risk among unopposed estrogen users is about 2 to 12 times greater than
in non-users, and appears dependent on duration of treatment and on estrogen
dose. Most studies show no significant increased risk associated with the use
of estrogens for less than 1 year. The greatest risk appears associated with
prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or
more. This risk has been shown to persist for at least 8 to 15 years after
estrogen therapy is discontinued.
Clinical
surveillance of all women using estrogen plus progestin therapy is important.
Adequate diagnostic measures, including endometrial sampling when indicated,
should be undertaken to rule out malignancy in all cases of undiagnosed
persistent or recurring abnormal genital bleeding. There is no evidence that
the use of natural estrogens results in a different endometrial risk profile
than synthetic estrogens of equivalent estrogen dose. Adding a progestin to
estrogen therapy has been shown to reduce the risk of endometrial hyperplasia,
which may be a precursor to endometrial cancer.
c.
Ovarian Cancer
The WHI
estrogen plus progestin substudy reported a statistically non-significant
increased risk of ovarian cancer. After an average follow-up of 5.6 years, the
relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95
percent CI, 0.77–3.24). The absolute risk for CE plus MPA was 4 versus 3 cases
per 10,000 women-years. In some epidemiologic studies, the use of estrogen plus
progestin and estrogen-only products, in particular for 5 or more years, has
been associated with increased risk of ovarian cancer. However, the duration of
exposure associated with increased risk is not consistent across all
epidemiologic studies and some report no association.
3. Probable Dementia
In the
WHIMS estrogen plus progestin ancillary study of WHI, a population of 4,532
postmenopausal women aged 65 to 79 years was randomized to daily CE (0.625 mg)
plus MPA (2.5 mg) or placebo.
After an
average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in
the placebo group were diagnosed with probable dementia. The relative risk of
probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI,
1.21–3.48). The absolute risk of probable dementia for CE plus MPA versus
placebo was 45 versus 22 cases per 10,000 women-years. It is unknown whether
these findings apply to younger postmenopausal women. (See CLINICAL STUDIES and PRECAUTIONS,
Geriatric Use.)
4. Visual Abnormalities
Discontinue
estrogen plus progestin therapy pending examination if there is sudden partial
or complete loss of vision, or a sudden onset of proptosis, diplopia or
migraine. If examination reveals papilledema or retinal vascular lesions,
estrogen plus progestin therapy should be permanently discontinued.
Precautions
A. General
1.
Addition of a progestin when a woman has not had a hysterectomy
Studies
of the addition of a progestin for 10 or more days of a cycle of estrogen
administration, or daily with estrogen in a continuous regimen, have reported a
lowered incidence of endometrial hyperplasia than would be induced by estrogen
treatment alone. Endometrial hyperplasia may be a precursor to endometrial
cancer.
There
are, however, possible risks that may be associated with the use of progestins
with estrogens compared to estrogen-alone regimens. These include an increased
risk of breast cancer.
2.
Unexpected abnormal vaginal bleeding
In cases
of unexpected abnormal vaginal bleeding, adequate diagnostic measures are
indicated.
3.
Elevated blood pressure
Blood
pressure should be monitored at regular intervals with estrogen plus progestin
therapy.
4.
Hypertriglyceridemia
In women
with pre-existing hypertriglyceridemia, estrogen plus progestin therapy may be
associated with elevations of plasma triglycerides leading to pancreatitis.
Consider discontinuation of treatment if pancreatitis occurs.
5.
Hepatic Impairment and/or past history of cholestatic jaundice
Estrogens
plus progestins may be poorly metabolized in women with impaired liver
function. For women with a history of cholestatic jaundice associated with past
estrogen use or with pregnancy, caution should be exercised, and in the case of
recurrence, medication should be discontinued.
6.
Fluid Retention
Progestins
may cause some degree of fluid retention. Women who have conditions which might
be influenced by this factor, such as cardiac or renal impairment, warrant
careful observation when estrogen plus progestin are prescribed.
7.
Hypocalcemia
Estrogen
plus progestin therapy should be used with caution in women with
hypoparathyroidism as estrogen-induced hypocalcemia may occur.
8.
Exacerbation of other conditions
Estrogen
plus progestin therapy may cause an exacerbation of asthma, diabetes mellitus,
epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic
hemangiomas and should be used with caution in women with these conditions.
B. Patient Information
Physicians
are advised to discuss the Patient Information leaflet with women for whom they
prescribe Provera.
There may
be an increased risk of minor birth defects in children whose mothers are
exposed to progestins during the first trimester of pregnancy. The possible
risk to the male baby is hypospadias, a condition in which the opening of the
penis is on the underside rather than the tip of the penis. This condition
occurs naturally in approximately 5 to 8 per 1000 male births. The risk may be
increased with exposure to Provera. Enlargement of the clitoris and fusion of
the labia may occur in female babies. However, a clear association between
hypospadias, clitoral enlargement and labial fusion with use of Provera has not
been established.
Inform
the patient of the importance of reporting exposure to Provera in early
pregnancy.
C. Drug-Laboratory Test Interactions
The
following laboratory results may be altered by the use of estrogen plus
progestin therapy:
1. Accelerated prothrombin time, partial thromboplastin
time, and platelet aggregation time; increased platelet count; increased
factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII,
VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of
anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased
levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and
activity.
2. Increased thyroid-binding globulin (TBG) levels
leading to increased circulating total thyroid hormone levels as measured by
protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3
levels by radioimmunoassay, T3 resin uptake is decreased, reflecting the
elevated TBG. Free T4 and free T3 concentrations are unaltered. Women on
thyroid replacement therapy may require higher doses of thyroid hormone.
3. Other binding proteins may be elevated in serum, for
example, corticosteroid binding globulin (CBG), sex hormone binding globulin
(SHBG) leading to increased circulating corticosteroid and sex steroids,
respectively. Free hormone concentrations, such as testosterone and estradiol,
may be decreased. Other plasma proteins may be increased (angiotensinogen/renin
substrate, alpha-1-antitrypsin, ceruloplasmin).
4. Increased plasma high-density lipoprotein (HDL) and
HDL2 cholesterol subfraction concentrations, reduced low-density lipoprotein
(LDL) cholesterol concentration, increased triglycerides levels.
5. Impaired glucose tolerance
D. Carcinogenesis, Mutagenesis, Impairment of
Fertility
Carcinogenicity
Long-term
intramuscular administration of medroxyprogesterone acetate has been shown to
produce mammary tumors in beagle dogs. There was no evidence of a carcinogenic
effect associated with the oral administration of medroxyprogesterone acetate
to rats and mice.
Long-term
continuous administration of estrogen plus progestin therapy has shown an
increased risk of breast cancer and ovarian cancer. (See WARNINGS and PRECAUTIONS.)
Genotoxicity
Medroxyprogesterone
acetate was not mutagenic in a battery of in vitro or in
vivo genetic toxicity assays.
Fertility
Medroxyprogesterone
acetate at high doses is an antifertility drug and high doses would be expected
to impair fertility until the cessation of treatment.
E. Pregnancy
Provera
should not be used during pregnancy. (See CONTRAINDICATIONS.)
There may
be increased risks for hypospadias, clitoral enlargement and labial fusion in
children whose mothers are exposed to Provera during the first trimester of
pregnancy. However, a clear association between these conditions with use of
Provera has not been established.
F. Nursing Mothers
Provera
should not be used during lactation. Detectable amounts of progestin have been
identified in the breast milk of nursing mothers receiving progestins.
G. Pediatric Use
Provera
tablets are not indicated in children. Clinical studies have not been conducted
in the pediatric population.
H. Geriatric Use
There
have not been sufficient numbers of geriatric women involved in clinical
studies utilizing Provera alone to determine whether those over 65 years of age
differ from younger subjects in their response to Provera alone.
The
Women's Health Initiative Studies
In the
WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg]
versus placebo), there was a higher relative risk of nonfatal stroke and
invasive breast cancer in women greater than 65 years of age. (See CLINICAL STUDIES.)
The
Women's Health Initiative Memory Study
In the
WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there
was an increased risk of developing probable dementia in women receiving
estrogen-alone or estrogen plus progestin when compared to placebo. (See WARNINGS, Probable Dementia.)
Since
both ancillary studies were conducted in women 65 to 79 years of age, it is
unknown whether these findings apply to younger postmenopausal women.
(See WARNINGS,
Probable Dementia.)
Adverse Reactions
See BOXED WARNINGS, WARNINGS,
and PRECAUTIONS.
Because
clinical trials are conducted under widely varying conditions, adverse reaction
rates observed in the clinical trials of a drug cannot be directly compared to
rates in the clinical trials of another drug and may not reflect the rates
observed in practice.
The following
adverse reactions have been reported in women taking Provera tablets, without
concomitant estrogens treatment:
1. Genitourinary system
Abnormal
uterine bleeding (irregular, increase, decrease), change in menstrual flow,
breakthrough bleeding, spotting, amenorrhea, changes in cervical erosion and
cervical secretions.
2. Breasts
Breast
tenderness, mastodynia or galactorrhea has been reported.
3. Cardiovascular
Thromboembolic
disorders including thrombophlebitis and pulmonary embolism have been reported.
4. Gastrointestinal
Nausea,
cholestatic jaundice.
5. Skin
Sensitivity
reactions consisting of urticaria, pruritus, edema and generalized rash have
occurred. Acne, alopecia and hirsutism have been reported.
6. Eyes
Neuro-ocular
lesions, for example, retinal thrombosis, and optic neuritis.
7. Central nervous system
Mental
depression, insomnia, somnolence, dizziness, headache, nervousness.
8. Miscellaneous
Hypersensitivity
reactions (for example, anaphylaxis and anaphylactoid reactions, angioedema),
rash (allergic) with and without pruritus, change in weight (increase or
decrease), pyrexia, edema/fluid retention, fatigue, decreased glucose
tolerance.
The following
adverse reactions have been reported with estrogen plus progestin therapy.
1. Genitourinary system
Abnormal
uterine bleeding/spotting, or flow; breakthrough bleeding; spotting;
dysmenorrheal/pelvic pain; increase in size of uterine leiomyomata; vaginitis,
including vaginal candidiasis; change in amount of cervical secretion; changes
in cervical ectropion; ovarian cancer; endometrial hyperplasia; endometrial
cancer.
2. Breasts
Tenderness,
enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes;
breast cancer.
3. Cardiovascular
Deep and
superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial
infarction; stroke; increase in blood pressure.
4. Gastrointestinal
Nausea,
vomiting; abdominal cramps, bloating; cholestatic jaundice; increased incidence
of gallbladder disease; pancreatitis; enlargement of hepatic hemangiomas.
5. Skin
Chloasma
or melasma that may persist when drug is discontinued; erythema multiforme;
erythema nodosum; hemorrhagic eruption; loss of scalp hair; hirsutism;
pruritus, rash.
6. Eyes
Retinal
vascular thrombosis, intolerance to contact lenses.
7. Central nervous system
Headache;
migraine; dizziness; mental depression; chorea; nervousness; mood disturbances;
irritability; exacerbation of epilepsy, dementia.
8. Miscellaneous
Increase
or decrease in weight; reduced carbohydrate tolerance; aggravation of
porphyria; edema; arthalgias; leg cramps; changes in libido; urticaria,
angioedema, anaphylactoid/anaphylactic reactions; hypocalcemia; exacerbation of
asthma; increased triglycerides.
Overdosage
Overdosage
of estrogen plus progestin therapy may cause nausea and vomiting, breast
tenderness, dizziness, abdominal pain, drowsiness/fatigue and withdrawal
bleeding may occur in women. Treatment of overdose consists of discontinuation
of CE plus MPA together with institution of appropriate symptomatic care.
Provera Dosage and Administration
Secondary Amenorrhea
Provera
tablets may be given in dosages of 5 or 10 mg daily for 5 to 10 days. A dose
for inducing an optimum secretory transformation of an endometrium that has
been adequately primed with either endogenous or exogenous estrogen is 10 mg of
Provera daily for 10 days. In cases of secondary amenorrhea, therapy may be
started at any time. Progestin withdrawal bleeding usually occurs within three
to seven days after discontinuing Provera therapy.
Abnormal Uterine Bleeding Due to Hormonal Imbalance
in the Absence of Organic Pathology
Beginning
on the calculated 16th or 21st day of the menstrual cycle, 5 or 10 mg of
Provera may be given daily for 5 to 10 days. To produce an optimum secretory
transformation of an endometrium that has been adequately primed with either
endogenous or exogenous estrogen, 10 mg of Provera daily for 10 days beginning
on the 16th day of the cycle is suggested. Progestin withdrawal bleeding
usually occurs within three to seven days after discontinuing therapy with
Provera. Patients with a past history of recurrent episodes of abnormal uterine
bleeding may benefit from planned menstrual cycling with Provera
Reduction of Endometrial Hyperplasia in
Postmenopausal Women Receiving Daily 0.625 mg Conjugated Estrogens
When
estrogen is prescribed for a postmenopausal woman with a uterus, a progestin
should also be initiated to reduce the risk of endometrial cancer. A woman
without a uterus does not need progestin. Use of estrogen, alone or in
combination with a progestin, should be with the lowest effective dose and for
the shortest duration consistent with treatment goals and risks for the
individual woman. Patients should be re-evaluated periodically as clinically
appropriate (for example, 3 to 6 month intervals) to determine if treatment is
still necessary (see WARNINGS).
For women who have a uterus, adequate diagnostic measures, such as endometrial
sampling, when indicated, should be undertaken to rule out malignancy in cases
of undiagnosed persistent or recurring abnormal vaginal bleeding.
Provera
tablets may be given in dosages of 5 or 10 mg daily for 12 to 14 consecutive
days per month, in postmenopausal women receiving daily 0.625 mg conjugated
estrogens, either beginning on the 1st day of the cycle or the 16th day of the
cycle.
Patients
should be started at the lowest dose.
The
lowest effective dose of Provera has not been determined.
How is Provera Supplied
Provera
Tablets are available in the following strengths and package sizes:
|
2.5 mg (scored, round, orange)
|
|
|
Bottles
of 30
|
NDC 0009-0064-06
|
|
Bottles
of 100
|
NDC 0009-0064-04
|
|
5 mg (scored, hexagonal, white)
|
|
|
Bottles
of 100
|
NDC 0009-0286-03
|
|
10 mg (scored, round, white)
|
|
|
Bottles
of 100
|
NDC 0009-0050-02
|
|
Bottles
of 500
|
NDC 0009-0050-11
|
Store at
controlled room temperature 20° to 25°C (68° to 77°F) [see USP].
"Keep out of reach of children"
Rx only
LAB-0144-7.0
July 2017
PATIENT INFORMATION
Provera
(pro-VE-rah)
(medroxyprogesterone acetate tablets, USP)
Read this
Patient Information before you start taking Provera and read what you get each
time you refill your Provera prescription. There may be new information. This
information does not take the place of talking to your healthcare provider
about your medical condition or your treatment.
What
is the most important information I should know about Provera (a progestin hormone)?
·
Do not use estrogens with
progestins to prevent heart disease, heart attacks, strokes, or dementia
(decline in brain function).
·
Using estrogens with progestins
may increase your chance of getting heart attacks, strokes, breast cancer, and
blood clots.
·
Using estrogens with progestins
may increase your chance of getting dementia, based on a study of women age 65
years or older.
·
You and your healthcare provider
should talk regularly about whether you still need treatment with Provera.
What is Provera?
Provera
is a medicine that contains medroxyprogesterone acetate, a progestin hormone.
What is Provera used for?
Provera
is used to:
Treat menstrual periods that have stopped or to treat abnormal
uterine bleeding. Women with a uterus who are not pregnant, who stop
having regular menstrual periods or who begin to have irregular menstrual
periods may have a drop in their progesterone level. Talk with your
healthcare provider about whether Provera is right for you.Reduce your chances of getting cancer of the uterus (womb). In
postmenopausal women with a uterus who use estrogens, taking progestin in
combination with estrogen will reduce your chance of getting cancer of the
uterus (womb)
Who should not take Provera?
Do not start taking Provera if you:
· have
unusual vaginal bleeding
· currently
have or have had certain cancers
Estrogen plus progestin may increase your chance of getting certain types of
cancers, including cancer of the breast. If you have or have had cancer, talk
with your healthcare provider about whether you should use Provera.
· had a
stroke or heart attack
· currently
have or have had blood clots
· currently
have or have had liver problems
· are
allergic to Provera or any of its ingredients
See the list of ingredients in Provera at the end of this leaflet.
· think
you may be pregnant
Provera is not for pregnant women. If you think you may be pregnant, you should
have a pregnancy test and know the results. Do not use Provera if the test is
positive and talk to your healthcare provider. There may be an increased risk
of minor birth defects in children whose mothers take Provera during the first
4 months of pregnancy.
Provera should not be used as a test for pregnancy.
What should I tell my healthcare
provider before taking Provera? Before you take Provera, tell your healthcare
provider if you:
· have
any other medical problems
Your healthcare provider may need to check you more carefully if you have
certain conditions such as asthma (wheezing), epilepsy (seizures), diabetes,
migraine, endometriosis (severe pelvic pain), lupus, or problems with your
heart, liver, thyroid, kidneys, or have high calcium in your blood.
· are
going to have surgery or will be on bed rest
Your healthcare provider will let you know if you need to stop taking Provera.
· are
breast feeding
The hormone in Provera can pass into your breast milk.
Tell your healthcare provider about
all the medicines you take including prescription and nonprescription
medicines, vitamins, and herbal supplements. Some medicines may affect how
Provera works. Provera may also affect how other medicines work.
How should I take Provera?
Start at the lowest dose and talk to your
healthcare provider about how well that dose is working for you. The lowest
effective dose of Provera has not been determined. You and your healthcare
provider should talk regularly (every 3 to 6 months) about the dose you are
taking and whether you still need treatment with Provera.
1. Absence
of menstrual period: Provera may be given in doses ranging from 5 to 10 mg daily for 5
to 10 days.
2. Abnormal
Uterine Bleeding: Provera may be given in doses ranging from 5 to 10 mg daily for 5
to 10 days.
3. Overgrowth
of the lining of the uterus: When used in combination with oral conjugated
estrogens in postmenopausal women with a uterus, Provera may be given in doses
ranging from 5 or 10 mg daily for 12 to 14 straight days per month.
What are the possible side effects of
Provera?
The following side effects have been
reported with the use of Provera alone:
· breast tenderness
· breast milk secretion
· breakthrough bleeding
· spotting (minor vaginal
bleeding)
· irregular periods
· amenorrhea (absence of
menstrual periods)
· vaginal secretions
· headaches
· nervousness
· dizziness
· depression
· insomnia, sleepiness,
fatigue
· premenstrual syndrome-like
symptoms
· thrombophlebitis (inflamed
veins)
· blood clot
· itching, hives, skin rash
· acne
· hair loss, hair growth
· abdominal discomfort
· nausea
· bloating
· fever
· increase in weight
· swelling
· changes in vision and
sensitivity to contact lenses
Call your healthcare provider right
away if you get hives, problems breathing, swelling of the face, mouth, tongue
or neck
The following side effects have been
reported with the use of Provera with an estrogen
Side effects are grouped by how
serious they are and how often they happen when you are treated.
Serious, but less common side effects
include:
· heart attack
· stroke
· blood clots
· dementia
· breast cancer
· cancer of the uterus
· cancer of the ovary
· high blood pressure
· high blood sugar
· gallbladder disease
· liver problems
· changes in your thyroid
hormone levels
· enlargements of benign
tumors ("fibroids")
Call your healthcare provider right
away if you get any of the following warning signs or any other unusual
symptoms that concern you:
· new breast lumps
· unusual vaginal bleeding
· changes in vision and
speech
· sudden new severe
headaches
· severe pains in your chest
or legs with or without shortness of breath, weakness and fatigue
· memory loss or confusion
Less serious, but common side effects
include:
· headache
· breast pain
· irregular vaginal bleeding
or spotting
· stomach or abdominal
cramps, bloating
· nausea and vomiting
· hair loss
· fluid retention
· vaginal yeast infection
These are not all the possible side effects of
Provera with or without estrogen. For more information, ask your healthcare
provider or pharmacist for advice about side effects. Tell your healthcare
provider if you have side effect that bothers you or does not go away. You may
report side effects to Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088.
What can I do to lower my chances of
a serious side effect with Provera?
Talk with your healthcare provider
regularly about whether you should continue taking Provera. The addition
of a progestin is generally recommended for women with a uterus to reduce
the chance of getting cancer of the uterus (womb).See your healthcare provider right
away if you get vaginal bleeding while taking Provera.Have a pelvic exam, breast exam and
mammogram (breast X-ray) every year unless your healthcare provider tells
you something else. If members of your family have had breast cancer or if
you have ever had breast lumps or an abnormal mammogram, you may need to
have breast exams more often.If you have high blood pressure,
high cholesterol (fat in the blood), diabetes, are overweight, or if you
use tobacco, you may have a higher chance of getting heart disease. Ask
your healthcare provider for ways to lower your chance of getting heart
disease.
General information about safe and
effective use of Provera
· Medicines are sometimes
prescribed for conditions that are not mentioned in patient information
leaflets.
· Do not take Provera for
conditions for which it was not prescribed.
· Do not give Provera to
other people, even if they have the same symptoms you have. It may harm them.
Keep Provera out of the reach of
children.
This leaflet provides a summary of the most
important information about Provera. If you would like more information, talk
with your health care provider or pharmacist. You can ask for information about
Provera that is written for health professionals. You can get more information
by calling the toll-free number, 1-800-438-1985
What are the ingredients in Provera?
Each
Provera tablet for oral administration contains 2.5 mg, 5 mg or 10 mg of
medroxyprogesterone acetate.
Inactive
ingredients: calcium stearate, corn starch, lactose, mineral oil, sorbic acid,
sucrose, talc. The 2.5 mg tablet contains FD&C Yellow No. 6.
This
product's label may have been updated. For current full prescribing
information, please visit www.pfizer.com
Rx only
LAB-0365-7.0
May 2015
PRINCIPAL DISPLAY PANEL - 2.5 mg Tablet Bottle Label
Pfizer
NDC
0009-0064-04
Provera®
medroxyprogesterone
acetate tablets, USP
2.5 mg
100
Tablets
Rx only
PRINCIPAL DISPLAY PANEL - 2.5 mg Tablet Bottle Carton
Pfizer
NDC
0009-0064-04
Provera®
medroxyprogesterone
acetate tablets, USP
2.5 mg
100 Tablets
Rx only
PRINCIPAL DISPLAY PANEL - 5 mg Tablet Bottle Label
Pfizer
NDC
0009-0286-03
Provera®
medroxyprogesterone
acetate tablets, USP
5 mg
100
Tablets
Rx only
PRINCIPAL DISPLAY PANEL - 5 mg Tablet Bottle Carton
Pfizer
NDC
0009-0286-03
Provera®
medroxyprogesterone
acetate tablets, USP
5 mg
100
Tablets
Rx only
PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Label
Pfizer
NDC 0009-0050-02
Provera®
medroxyprogesterone
acetate tablets, USP
10 mg
100
Tablets
Rx only
PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Carton
Pfizer
NDC
0009-0050-02
Provera®
medroxyprogesterone
acetate tablets, USP
10 mg
100
Tablets
Rx only
|
Provera medroxyprogesterone acetate tablet
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0009-0064
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
MEDROXYPROGESTERONE ACETATE (MEDROXYPROGESTERONE)
|
MEDROXYPROGESTERONE
ACETATE
|
2.5 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
CALCIUM STEARATE
|
|
|
STARCH, CORN
|
|
|
LACTOSE, UNSPECIFIED FORM
|
|
|
MINERAL OIL
|
|
|
SORBIC ACID
|
|
|
SUCROSE
|
|
|
TALC
|
|
|
FD&C YELLOW NO. 6
|
|
|
|
Product
Characteristics
|
|
Color
|
ORANGE
|
Score
|
2 pieces
|
|
Shape
|
ROUND
|
Size
|
6mm
|
|
Flavor
|
|
Imprint Code
|
Provera;2;5
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0009-0064-06
|
30 TABLET in 1
BOTTLE
|
|
|
2
|
NDC:0009-0064-04
|
1 BOTTLE in 1
CARTON
|
|
|
2
|
|
100 TABLET in 1
BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA011839
|
06/03/1959
|
|
|
|
Provera medroxyprogesterone acetate tablet
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0009-0286
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
MEDROXYPROGESTERONE ACETATE (MEDROXYPROGESTERONE)
|
MEDROXYPROGESTERONE
ACETATE
|
5 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
CALCIUM STEARATE
|
|
|
STARCH, CORN
|
|
|
LACTOSE, UNSPECIFIED FORM
|
|
|
MINERAL OIL
|
|
|
SORBIC ACID
|
|
|
SUCROSE
|
|
|
TALC
|
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
2 pieces
|
|
Shape
|
HEXAGON (6
SIDED)
|
Size
|
6mm
|
|
Flavor
|
|
Imprint Code
|
Provera;5
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0009-0286-03
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
100 TABLET in 1
BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA011839
|
06/03/1959
|
|
|
|
Provera medroxyprogesterone acetate tablet
|
|
Product
Information
|
|
Product Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0009-0050
|
|
Route of
Administration
|
ORAL
|
DEA Schedule
|
|
|
|
Active
Ingredient/Active Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
MEDROXYPROGESTERONE ACETATE (MEDROXYPROGESTERONE)
|
MEDROXYPROGESTERONE
ACETATE
|
10 mg
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
CALCIUM STEARATE
|
|
|
STARCH, CORN
|
|
|
LACTOSE, UNSPECIFIED FORM
|
|
|
MINERAL OIL
|
|
|
SORBIC ACID
|
|
|
SUCROSE
|
|
|
TALC
|
|
|
|
Product
Characteristics
|
|
Color
|
WHITE
|
Score
|
2 pieces
|
|
Shape
|
ROUND
|
Size
|
7mm
|
|
Flavor
|
|
Imprint Code
|
Provera;10
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0009-0050-02
|
1 BOTTLE in 1
CARTON
|
|
|
1
|
|
100 TABLET in 1
BOTTLE
|
|
|
2
|
NDC:0009-0050-11
|
500 TABLET in 1
BOTTLE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
NDA
|
NDA011839
|
06/03/1959
|
|
|
|
Labeler - Pharmacia and Upjohn Company LLC
(618054084)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Pharmacia and
Upjohn Company LLC
|
|
618054084
|
API
MANUFACTURE(0009-0050, 0009-0064, 0009-0286)
|
|
Establishment
|
|
Name
|
Address
|
ID/FEI
|
Operations
|
|
Pfizer Italia
S.r.l.
|
|
458521908
|
ANALYSIS(0009-0050,
0009-0064, 0009-0286), MANUFACTURE(0009-0050, 0009-0064, 0009-0286),
PACK(0009-0050, 0009-0064, 0009-0286)
|
Revised: 08/2017
Pharmacia
and Upjohn Company LLC
