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
Alora Side Effects, and Drug Interactions - Estradiol transdermal
Alora Side Effects, and Drug Interactions - Estradiol transdermal
SIDE EFFECTS
See BOXED WARNINGS, WARNINGS
and PRECAUTIONS.
Because clinical trials are conducted under widely varying
conditions, adverse reactions 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 adverse reaction information
from clinical trials does, however, provide a basis for identifying the adverse
events that appear to be related to drug use and for approximating rates.
Incidence of adverse events > 2% of each treatment group
is given in Table 4.
|
Table 5 Incidence of Adverse Events > 2% for Alora
and Placebo Systems (data are expressed as N and (%) of treatment group)
|
|
Body System
Preferred Term
|
Placeboa (N=87)
|
Aloraa 0.025 mg/day (N=89)
|
Aloraa 0.05 mg/day (N=90)
|
Aloraa 0.075 mg/day (N=89)
|
Alorab 0.1 mg/day (N=174)
|
|
Body As A Whole
|
|
Accidental Injury
|
4 (4.6)
|
6 (6.7)
|
8 (8.9)
|
4 (4.5)
|
9 (5.2)
|
|
Allergic Reaction
|
2 (2.3)
|
4 (4.5)
|
4 (4.4)
|
2 (2.2)
|
1 (0.6)
|
|
Asthenia
|
4 (4.6)
|
7 (7.9)
|
4 (4.4)
|
0 (0)
|
4 (2.3)
|
|
Cyst
|
3 (3.4)
|
0 (0)
|
6 (6.7)
|
3 (3.4)
|
0 (0)
|
|
Flu Syndrome
|
9 (10.3)
|
8 (9)
|
12 (13.3)
|
9 (10.1)
|
6 (3.4)
|
|
Headache
|
11 (12.6)
|
10 (11.2)
|
8 (8.9)
|
5 (5.6)
|
37 (21.3)
|
|
Infection
|
2 (2.3)
|
2 (2.2)
|
3 (3.3)
|
3 (3.4)
|
2 (1.1)
|
|
Infection Fungal
|
1 (1.1)
|
3 (3.4)
|
9 (10)
|
4 (4.5)
|
0 (0)
|
|
Pain
|
11 (12.6)
|
9 (10.1)
|
5 (5.6)
|
6 (6.7)
|
16 (9.2)
|
|
Pain Abdominal
|
4 (4.6)
|
7 (7.9)
|
5 (5.6)
|
1 (1.1)
|
5 (2.9)
|
|
Pain Back
|
5 (5.7)
|
5 (5.6)
|
3 (3.3)
|
7 (7.9)
|
11 (6.3)
|
|
Pain Chest
|
4 (4.6)
|
4 (4.5)
|
2 (2.2)
|
1 (1.1)
|
2 (1.1)
|
|
Cardiovascular
|
|
Hypertension
|
3 (3.4)
|
3 (3.4)
|
3 (3.3)
|
6 (6.7)
|
0 (0)
|
|
Migraine
|
2 (2.3)
|
6 (6.7)
|
2 (2.2)
|
0 (0)
|
2 (1.1)
|
|
Vasodilation
|
13 (14.9)
|
6 (6.7)
|
2 (2.2)
|
1 (1.1)
|
0 (0)
|
|
Digestive
|
|
Constipation
|
4 (4.6)
|
3 (3.4)
|
6 (6.7)
|
1 (1.1)
|
3 (1.7)
|
|
Diarrhea
|
2 (2.3)
|
1 (1.1)
|
3 (3.3)
|
2 (2.2)
|
5 (2.9)
|
|
Dyspepsia
|
1 (1.1)
|
8 (9)
|
4 (4.4)
|
3 (3.4)
|
2 (1.1)
|
|
Flatulence
|
5 (5.7)
|
1 (1.1)
|
2 (2.2)
|
3 (3.4)
|
8 (4.6)
|
|
Gastroenteritis
|
2 (2.3)
|
3 (3.4)
|
4 (4.4)
|
3 (3.4)
|
0 (0)
|
|
Nausea
|
3 (3.4)
|
6 (6.7)
|
5 (5.6)
|
3 (3.4)
|
7 (4)
|
|
Metabolic And Nutritional
|
|
Edema Peripheral
|
4 (4.6)
|
3 (3.4)
|
4 (4.4)
|
3 (3.4)
|
3 (1.7)
|
|
Weight Increased
|
4 (4.6)
|
3 (3.4)
|
2 (2.2)
|
4 (4.5)
|
1 (0.6)
|
|
Musculoskeletal
|
|
Arthralgia
|
12 (13.8)
|
5 (5.6)
|
10 (11.1)
|
11 (12.4)
|
2 (1.1)
|
|
Bone Fracture Spontaneous
|
7 (8)
|
1 (1.1)
|
3 (3.3)
|
0 (0)
|
0 (0)
|
|
Joint Disorder
|
2 (2.3)
|
4 (4.5)
|
4 (4.4)
|
1 (1.1)
|
0 (0)
|
|
Myalgia
|
4 (4.6)
|
3 (3.4)
|
2 (2.2)
|
5 (5.6)
|
3 (1.7)
|
|
Nervous
|
|
Anxiety
|
3 (3.4)
|
0 (0)
|
9 (10)
|
2 (2.2)
|
3 (1.7)
|
|
Depression
|
8 (9.2)
|
1 (1.1)
|
3 (3.3)
|
1 (1.1)
|
6 (3.4)
|
|
Dizziness
|
0 (0)
|
1 (1.1)
|
7 (7.8)
|
4 (4.5)
|
1 (0.6)
|
|
Hypesthesia
|
2 (2.3)
|
3 (3.4)
|
3 (3.3)
|
0 (0)
|
0 (0)
|
|
Insomnia
|
7 (8)
|
4 (4.5)
|
2 (2.2)
|
1 (1.1)
|
8 (4.6)
|
|
Respiratory
|
|
Asthma
|
1 (1.1)
|
3 (3.4)
|
3 (3.3)
|
1 (1.1)
|
2 (1.1)
|
|
Bronchitis
|
6 (6.9)
|
7 (7.9)
|
4 (4.4)
|
4 (4.5)
|
6 (3.4)
|
|
Cough Increased
|
2 (2.3)
|
1 (1.1)
|
4 (4.4)
|
1 (1.1)
|
6 (3.4)
|
|
Infection Respiratory
|
23 (26.4)
|
22 (24.7)
|
22 (24.4)
|
19 (21.3)
|
28 (16.1)
|
|
Pharyngitis
|
1 (1.1)
|
4 (4.5)
|
2 (2.2)
|
2 (2.2)
|
4 (2.3)
|
|
Pneumonia
|
4 (4.6)
|
4 (4.5)
|
4 (4.4)
|
1 (1.1)
|
1 (0.6)
|
|
Sinusitis
|
16 (18.4)
|
9 (10.1)
|
11 (12.2)
|
6 (6.7)
|
13 (7.5)
|
|
Skin
|
|
Application Site Reaction
|
51 (58.6)
|
47 (52.8)
|
51 (56.7)
|
49 (55.1)
|
10 (5.7)
|
|
Hirsutism
|
0 (0)
|
2 (2.2)
|
2 (2.2)
|
4 (4.5)
|
1 (0.6)
|
|
Pruritus
|
4 (4.6)
|
2 (2.2)
|
1 (1.1)
|
6 (6.7)
|
9 (5.2)
|
|
Rash
|
5 (5.7)
|
6 (6.7)
|
8 (8.9)
|
4 (4.5)
|
5 (2.9)
|
|
Special Senses
|
|
Conjunctivitis
|
2 (2.3)
|
2 (2.2)
|
3 (3.3)
|
2 (2.2)
|
0 (0)
|
|
Otitis Media
|
2 (2.3)
|
3 (3.4)
|
2 (2.2)
|
1 (1.1)
|
0 (0)
|
|
Urogenital
|
|
Breast Enlargement
|
3 (3.4)
|
1 (1.1)
|
2 (2.2)
|
6 (6.7)
|
4 (2.3)
|
|
Infection Urinary Tract
|
2 (2.3)
|
5 (5.6)
|
4 (4.4)
|
2 (2.2)
|
3 (1.7)
|
|
Leukorrhea
|
1 (1.1)
|
3 (3.4)
|
2 (2.2)
|
4 (4.5)
|
3 (1.7)
|
|
Neoplasm Breast
|
6 (6.9)
|
3 (3.4)
|
5 (5.6)
|
1 (1.1)
|
3 (1.7)
|
|
Pain Breast
|
7 (8)
|
13 (14.6)
|
16 (17.8)
|
31 (34.8)
|
12 (6.9)
|
|
Vaginitis
|
6 (6.9)
|
0 (0)
|
3 (3.3)
|
0 (0)
|
14 (8)
|
|
Vaginal Bleedingc
|
4 (12.9)
|
NA
|
6 (8.7)
|
NA
|
29 (33.3)
|
|
a – Adverse events for the three lower Alora doses
and placebo were obtained from the two year prevention of osteoporosis
study
|
|
b – Adverse events for the highest Alora doses
were obtained from two 12-week studies of the treatment of menopausal
symptoms
|
|
c – Data reported for women with partially or fully intact
uteri in the menopausal symptom study only (N=31 for Placebo; N=69 for
Alora 0.05 mg/day and N=87 for Alora 0.1 mg/day)
|
|
NA – data not available
|
The following additional adverse reactions have been reported
with estrogens:
1. Genitourinary system. Changes in vaginal bleeding
pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting;
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 gall bladder
disease; pancreatitis.
5. Skin. Chloasma or melasma, which may persist when
drug is discontinued; erythema multiform; erythema nodosum; hemorrhagic eruption;
loss of scalp hair; hirsutism; pruritus, rash.
6. Eyes. Retinal vascular thrombosis; steepening
of corneal curvature; intolerance to contact lenses.
7. Central nervous system. Headache; migraine; dizziness;
mental depression; chorea; nervousness; mood disturbances; irritability; exacerbation
of epilepsy.
8. Miscellaneous. Increase or decrease in weight;
reduced carbohydrate tolerance; aggravation of porphyria; edema; arthalgias;
leg cramps; changes in libido; anaphylactoid/anaphylactic reactions including
urticaria and angioedema; hypocalcemia; exacerbation of asthma; increased triglycerides.
D. DRUG/LABORATORY TEST INTERACTIONS
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) leading to increased
circulating total thyroid hormone, 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.
Patients on thyroid replacement therapy may require higher doses of thyroid
hormone.
3. Other binding proteins may be elevated in serum, i.e.,
corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG),
leading to increased circulating corticosteroids and sex steroids, respectively.
Free or biologically active hormone concentrations are unchanged. Other plasma
proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin,
ceruloplasmin).
4. Increased plasma HDL and HDL2 subfraction
concentrations, reduced LDL cholesterol concentration, increased triglycerides
levels.
5. Impaired glucose tolerance.
6. Reduced response to the metapyrone test.
7. Reduced serum folate concentration.
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