Vivelle (Estradiol Transdermal) - Side Effects and Adverse Reactions

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 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.

   The following adverse events have been reported with Vivelle therapy:

Table 3 Summary of Most Frequently Reported Adverse Experiences/Medical Events Regardless of Relationship Reported at a Frequency =5%

	Vivelle 0.025 mg/ day† (N=47) N (%)	Vivelle 0.0375 mg/ day† (N=130 N (%)	Vivelle 0.05 mg/ day† (N=103) N (%)	Vivelle 0.075 mg/ day† (N=46) N (%)	Vivelle 0.1 mg/ day† (N=132) N (%)	Placebo (N=157) N (%)
Gastrointestinal Disorders
Constipation	2 (4.3)	5 (3.8)	4 (3.9)	3 (6.5)	2 (1.5)	4 (2.5)
Dyspepsia	4 (8.5)	12 (9.2)	3 (2.9)	2 (4.3)	0	10 (6.4)
Nausea	2 (4.3)	8 (6.2)	4 (3.9)	0	7 (5.3)	5 (3.2)
General Disorders and Administration Site Conditions ***
Influenza-like    Illness	3 (6.4)	6 (4.6)	8 (7.8)	0	3 (2.3)	10 (6.4)
Pain NOS*	0	8 (6.2)	0	2 (4.3)	7 (5.3)	7 (4.5)
Infections and Infestations
Influenza	4 (8.5)	4 (3.1)	6 (5.8)	0	10 (7.6)	14 (8.9)
Nasopharyngitis	3 (6.4)	16 (12.3)	10 (9.7)	9 (19.6)	11 (8.3)	24 (15.3)
Sinusitis NOS*	4 (8.5)	17 (13.1)	13 (12.6)	3 (6.5)	7 (5.3)	16 (10.2)
Upper Respiratory    Tract Infection    NOS*	3 (6.4)	8 (6.2)	11 (10.7)	4 (8.7)	6 (4.5)	9 (5.7)
Investigations
Weight Increased	4 (8.5)	5 (3.8)	2 (1.9)	2 (4.3)	0	3 (1.9)
Musculoskeletal and Connective Tissue Disorders
Arthralgia	0	11 (8.5)	4 (3.9)	2 (4.3)	5 (3.8)	9 (5.7)
Back Pain	4 (8.5)	10 (7.7)	9 (8.7)	4 (8.7)	14 (10.6)	10 (6.4)
Neck Pain	3 (6.4)	4 (3.1)	4 (3.9)	0	6 (4.5)	2 (1.3)
Pain in Limb	0	10 (7.7)	7 (6.8)	2 (4.3)	6 (4.5)	9 (5.7)
Nervous System Disorders
Headache NOS*	7 (14.9)	35 (26.9)	32 (31.1)	23 (50.0)	34 (25.8)	37 (23.6)
Sinus Headache	0	12 (9.2)	5 (4.9)	5 (10.9)	2 (1.5)	8 (5.1)
Psychiatric Disorders
Anxiety NEC**	3 (6.4)	5 (3.8)	0	0	2 (1.5)	4 (2.5)
Depression	5 (10.6)	4 (3.1)	7 (6.8)	0	4 (3.0)	6 (3.8)
Insomnia	3 (6.4)	6 (4.6)	4 (3.9)	2 (4.3)	2 (1.5)	9 (5.7)
Reproductive System and Breast Disorders
Breast
Tenderness	8 (17.0)	10 (7.7)	8 (7.8)	3 (6.5)	17 (12.9)	0
Dysmenorrhea	0	0	0	3 (6.5)	0	0
Intermenstrual    Bleeding	3 (6.4)	9 (6.9)	6 (5.8)	0	14 (10.6)	7 (4.5)
Respiratory, Thoracic and Mediastinal Disorders
Sinus Congestion	0	4 (3.1)	3 (2.9)	3 (6.5)	6 (4.5)	7 (4.5)
Vascular Disorders
Hot Flushes NOS*	3 (6.4)	0	3 (2.9)	0	0	6 (3.8)
Hypertension NOS*	2 (4.3)	0	3 (2.9)	0	0	2 (1.3)

^†   Represents milligrams of estradiol delivered daily by each system

^*   NOS represents not otherwise specified

^**   NEC represents not elsewhere classified

^***   Application site erythema and application site irritation were observed in a small number of patients (3.2% or less of patients across treatment groups)

   The following additional adverse reactions have been reported with estrogens and/or progestin therapy.

1. Genitourinary System. Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, 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, which 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; arthralgias; leg cramps; changes in libido; anaphylactoid/anaphylactic reactions including urticaria and angioedema; hypocalcemia; exacerbation of asthma; increased triglycerides.

REPORTS OF SUSPECTED VIVELLE SIDE EFFECTS / ADVERSE REACTIONS

Possible Vivelle side effects / adverse reactions in 57 year old female

Reported by a pharmacist from United States on 2011-11-07

Patient: 57 year old female

Reactions: Confusional State

Suspect drug(s):
Klor-CON
    Dosage: unk

Lipitor
    Dosage: 40 mg, unk

Bystolic
    Dosage: unk

Lasix
    Dosage: unk

Nexium
    Dosage: unk

Vivelle
    Dosage: unk

Paxil
    Dosage: unk

Flexeril
    Dosage: unk

Xanax
    Dosage: unk

Imdur
    Dosage: unk

Actonel
    Dosage: unk

Possible Vivelle side effects / adverse reactions in 12 year old female

Reported by a individual with unspecified qualification from United States on 2012-05-11

Patient: 12 year old female weighing 32.7 kg (71.8 pounds)

Reactions: Alopecia

Suspect drug(s):
Vivelle

Possible Vivelle side effects / adverse reactions in 49 year old female

Reported by a consumer/non-health professional from United States on 2012-08-02

Patient: 49 year old female

Reactions: Malaise, Nausea

Suspect drug(s):
Vivelle
    Dosage: 0.1mg patches on arms, feet, legs except breast

Estradiol

Premarin

Estrace