A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Prometrium Side Effects, and Drug Interactions - Progesterone
Prometrium Side Effects, and Drug Interactions - Progesterone
SIDE EFFECTS
Endometrial Protection
Table 7 lists adverse experiences which were reported in ³2%
of patients (regardless of relationship to treatment) who received
cyclic PROMETRIUM Capsules, 200 mg
daily (12 days per calendar
month cycle) with daily 0.625 mg
conjugated estrogen,
in a multicenter, randomized, double-blind, placebo-controlled clinical
trial in 875 postmenopausal
women.
Table 7
|
Placebo-Controlled Trial in Postmenopausal
Women over a 3-Year Period
(Percentage(%) of Patients Reporting)
|
| |
PROMETRIUM Capsules
200 mg
with Conjugated
Estrogens 0.625 mg
(N=178)
|
Conjugated
Estrogens 0.625
mg (only)
(N= 176)
|
Placebo
(N=174)
|
| Headache |
31
|
30
|
27
|
| Breast Tenderness
|
27
|
16
|
6
|
| Joint Pain |
20
|
22
|
29
|
| Depression |
19
|
18
|
12
|
| Dizziness |
15
|
5
|
9
|
| Abdominal Bloating
|
12
|
10
|
5
|
| Hot Flashes |
11
|
14
|
35
|
| Urinary Problems
|
11
|
10
|
9
|
| Abdominal Pain |
10
|
13
|
10
|
| Vaginal Discharge
|
10
|
10
|
3
|
| Nausea / Vomiting
|
8
|
6
|
7
|
| Worry |
8
|
5
|
4
|
| Chest Pain |
7
|
4
|
5
|
| Diarrhea |
7
|
7
|
4
|
| Night Sweats |
7
|
5
|
17
|
| Breast Pain |
6
|
6
|
2
|
| Swelling of Hands
and Feet |
6
|
9
|
9
|
| Vaginal Dryness |
6
|
8
|
10
|
| Constipation |
3
|
3
|
2
|
| Breast Carcinoma
|
2
|
<1
|
<1
|
| Breast Excisional
Biopsy |
2
|
1
|
<1
|
| Cholecystectomy |
2
|
<1
|
<1
|
Secondary Amenorrhea
Table 8 lists adverse experiences which were reported in ³5%
of patients receiving PROMETRIUM Capsules, 400 mg/day, in a multicenter,
randomized, double-blind, placebo-controlled clinical
trial in estrogen-primed (6 weeks) postmenopausal
women receiving conjugated estrogens 0.625 mg/day and cyclic
(10 days per calendar month
cycle) PROMETRIUM Capsules at a dose of 400 mg/day, for three cycles.
Table 8
Adverse Experiences ( ³
5%) Reported in Patients Using 400 mg/day in a Placebo-Controlled
Trial in Estrogen-Primed Postmenopausal Women
| Adverse Experience |
PROMETRIUM
Capsules 400 mg
N=25
|
Placebo N=24
|
| |
Percentage (%) of Patients
|
| Fatigue |
8
|
4
|
| Headache |
16
|
8
|
| Dizziness |
24
|
4
|
| Abdominal Distention
(Bloating) |
8
|
8
|
| Abdominal Pain (Cramping)
|
20
|
13
|
| Diarrhea |
8
|
4
|
| Nausea |
8
|
0
|
| Back Pain |
8
|
8
|
| Musculoskeletal Pain
|
12
|
4
|
| Irritability |
8
|
4
|
| Breast Pain |
16
|
8
|
| Infection Viral |
12
|
0
|
| Coughing |
8
|
0
|
The most common adverse experiences reported in ³5%
of patients in all PROMETRIUM Capsules dosage
groups studied in this trial (100 mg/day to 400 mg/day) were: dizziness
(16%), breast pain
(11%), headache (10%), abdominal
pain (10%), fatigue
(9%), viral infection
(7%), abdominal distention (6%), musculoskeletal
pain (6%), emotional lability
(6%), irritability (5%), and upper respiratory
tract infection
(5%).
Other adverse events reported in <5% of patients taking PROMETRIUM
Capsules include:
Autonomic Nervous System Disorders: dry mouth
Body As A Whole:
accidental injury, chest
pain, fever
Cardiovascular System Disorders: hypertension
Central and Peripheral Nervous System Disorders:
confusion, somnolence, speech
disorder
Gastrointestinal System Disorders: constipation,
dyspepsia, gastroenteritis, hemorrhagic
rectum, hiatus hernia,
vomiting
Hearing and Vestibular Disorders: earache
Heart Rate and Rhythm Disorders: palpitation
Metabolic and Nutritional Disorders: edema, edema
peripheral
Musculoskeletal System Disorders: arthritis, leg
cramps, hypertonia, muscle
disorder, myalgia
Myo/Endo/Pericardial and Valve Disorders: angina
pectoris
Psychiatric Disorders: anxiety,
impaired concentration, insomnia, personality
disorder
Reproductive System Disorders: leukorrhea, uterine
fibroid, vaginal dryness, fungal vaginitis,
vaginitis
Resistance Mechanism Disorders: abscess,
herpes simplex
Respiratory System Disorders: bronchitis,
nasal congestion, pharyngitis,
pneumonitis, sinusitis
Skin and Appendages Disorders: acne,
verruca, wound debridement
Urinary System Disorders: urinary
tract infection
Vision Disorders: abnormal
vision
White Cell and Resistance Disorders: lymphadenopathy
The following adverse experiences have been reported with PROMETRIUM
Capsules in other U.S. clinical
trials: increased sweating, asthenia,
tooth disorder, anorexia,
increased appetite, nervousness, and breast
enlargement.
The following spontaneous
adverse events have been reported during the foreign marketing of
PROMETRIUM Capsules: reversible
cases of hepatitis and elevated transaminases. These events occurred
mainly in patients receiving high doses of up to 1200 mg.
The following additional adverse experiences have been observed
in women taking progestins in general: breakthrough bleeding,
spotting, change in menstrual flow, amenorrhea,
changes in weight (increase
or decrease), changes in the cervical
squamo-columnar junction
and cervical secretions,
cholestatic jaundice, anaphylactoid reactions and anaphylaxis,
rash (allergic) with and
without pruritus, melasma
or chloasma, pyrexia,
and insomnia.
DRUG INTERACTIONS
Drug Lab Test Interactions
The following laboratory
results may be altered by the use of estrogen-progestin combination
drugs:
- Increased sulfobromophthalein
retention and
other hepatic function
tests.
- Coagulation tests: increase in prothrombin
factors VII, VIII, IX and X.
- Metyrapone test.
- Pregnanediol determination.
- Thyroid function: increase in PBI, and butanol extractable
protein bound iodine
and decrease in T3 uptake
values.
Food-Drug Interaction:
Concomitant food ingestion
increased the bioavailability
of PROMETRIUM Capsules relative to a fasting
state when administered
to postmenopausal women at a dose
of 200 mg.
Drug-Drug Interaction:
The metabolism
of progesterone
by human liver
microsomes was inhibited by ketoconazole (IC50 <0.1
µM). Ketoconazole is a known inhibitor of cytochrome
P450 3A4, hence these data suggest that ketoconazole or other known
inhibitors of this enzyme
may increase the bioavailability of progesterone. The clinical
relevance of the in vitro findings is unknown.
Coadministration of conjugated estrogens and PROMETRIUM Capsules
to 29 postmenopausal
women over a 12 day period
resulted in an increase in total estrone
concentrations (Cmax 3.68 ng/ml to 4.93 ng/ml) and total
equilin concentrations
(Cmax 2.27 ng/ml to 3.22 ng/ml) and a decrease in circulating
17b estradiol concentrations
(Cmax 0.037 ng/ml to 0.030 ng/ml). The half-life
of the conjugated estrogens was similar with coadministration of
PROMETRIUM Capsules.
Also see CLINICAL PHARMACOLOGY.
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