ACTIVELLA

AbsorptionEstradiol Estradiol is absorbed through the gastrointestinal tract. Following oral administration of Activella tablets, peak plasma estradiol concentrations are reached within 5 to 8 hours. The oral bioavailability of estradiol following administration of Activella 1 mg/0.5 mg when compared to a combination oral solution is 53%. Administration of Activella 1 mg/0.5 mg with food did not modify the bioavailability of estradiol. Norethindrone Acetate After oral administration, norethindr...

14.1 Effects on Vasomotor Symptoms in Postmenopausal Women In a 12-week randomized clinical trial involving 92 subjects, Activella 1 mg/0.5 mg was compared to 1 mg of estradiol and to placebo. The mean number and intensity of hot flushes were significantly reduced from baseline to week 4 and 12 in both the Activella 1 mg/0.5 mg and the 1 mg estradiol group compared to placebo (see Figure 2). Figure 2 Mean Weekly Number of Moderate and Severe Hot Flushes in a 12-Week Study In a study conducted in Europe a total of 577 postmenopausal women were randomly assigned to either Activella 0.5 mg/0.1 mg...

The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions ( 5.1 )] Malignant Neoplasms [see Boxed Warning, Warnings and Precautions ( 5.2 )] The most common adverse reactions (incidence ≥ 5 percent) with Activella are: back pain, headache, pain in the extremity, nausea, diarrhea, gastroenteritis, insomnia, emotional lability, upper respiratory tract infection, sinusitis, nasopharyngitis, weight increase,...

Activella is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.2) ] Breast cancer or history of breast cancer [see Warnings and Precautions (5.2) ] Estrogen-dependent neoplasia [see Warnings and Precautions (5.2) ] Active DVT, PE, or history of these conditions [see Warnings and Precautions (5.1) ] Active arterial ...

Estrogens increase the risk of gall bladder disease (5.4) Discontinue estrogen if severe hypercalcemia, loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs (5.5 , 5.6 , 5.9 , 5.10) Monitor thyroid function in women on thyroid replacement therapy (5.11 , 5.18) 5.1 Cardiovascular Disorders Increased risks of PE, DVT, stroke and MI are reported with estrogen plus progestin therapy. Increased risks of stroke and DVT are reported with estrogen-alone therapy. Immediately discont...

7 DRUG INTERACTIONS Co-administration of estradiol with norethindrone acetate did not elicit any apparent influence on the pharmacokinetics of norethindrone acetate. Similarly, no relevant interaction of norethindrone acetate on the pharmacokinetics of estradiol was found within the NETA dose range investigated in a single dose study. Estradiol In-vitro and in-vivo studies have shown that estrogen...