6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
- Cardiovascular Disorders [see Warnings and Precautions (5.2)]
- Malignant Neoplasms [see Warnings and Precautions (5.3)]
- Gallbladder Disease [see Warnings and Precautions (5.5)]
- Hypertriglyceridemia [see Warnings and Precautions (5.8)]
6.1 Clinical Trials Experience
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 clinical practice.
The safety of conjugated estrogens/bazedoxifene was evaluated in four Phase 3 clinical trials ranging from 12 weeks to 24 months in duration and enrolling 6,210 postmenopausal women age 40 to 75 years (mean age 55 years). A total of 1,224 patients were treated with DUAVEE and 1,069 patients received placebo. Women enrolled in Studies 1 and 2 received calcium (600–1200 mg) and vitamin D (200–400 IU) daily, while women in Studies 3 and 4 received no calcium and vitamin D supplementation as part of the protocol.
The incidence of all-cause mortality was 0.0% in the DUAVEE group and 0.2% in the placebo group. The incidence of serious adverse reactions was 3.5% in the DUAVEE group and 4.8% in the placebo group. The percentage of patients who withdrew from treatment due to adverse reactions was 7.5% in the DUAVEE group and 10.0% in the placebo group. The most common adverse reactions leading to discontinuation were hot flush, abdominal pain upper, and nausea.
The most commonly observed adverse reactions (incidence ≥ 5%) more frequently reported in women treated with DUAVEE than placebo are presented in Table 1.
|Nausea||100 (8)||58 (5)|
|Diarrhea||96 (8)||57 (5)|
|Dyspepsia||84 (7)||59 (6)|
|Abdominal pain upper||81 (7)||58 (5)|
|Musculoskeletal and connective tissue disorders|
|Muscle spasms||110 (9)||63 (6)|
|Neck pain||62 (5)||46 (4)|
|Nervous system disorders|
|Dizziness||65 (5)||37 (3)|
|Respiratory, thoracic, and mediastinal disorders|
|Oropharyngeal pain||80 (7)||61 (6)|
Venous thromboembolism: In the clinical studies with DUAVEE, the reporting rates for venous thromboembolism (deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis) were low in all treatment groups. Adverse reactions of venous thromboembolism were reported in 0.0% of patients treated with DUAVEE and 0.1% of patients treated with placebo. Due to the low rate of events in both groups, it is not possible to conclude that the risk of venous thromboembolism with DUAVEE is different from that seen with other estrogen therapies [see Warnings and Precautions (5.2)].