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Duavee

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Duavee

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

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.

Table 1: Adverse Reactions (Incidence ≥ 5%) More Common in the DUAVEE Treatment Group in Placebo-controlled Trials

  DUAVEE
(N=1224)
n (%)
Placebo
(N=1069)
n (%)
Gastrointestinal disorders
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].

Read the Duavee (conjugated estrogens and bazedoxifene tablets) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

No drug interaction studies were conducted with DUAVEE. Results from in vitro and in vivo studies and clinical studies conducted with the conjugated estrogens or bazedoxifene components of DUAVEE are noted below:

Cytochrome P450 (CYP)

In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4, such as St. John's Wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.

Inhibitors of CYP3A4, such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice, may increase the exposure of conjugated estrogens resulting in an increased risk of endometrial hyperplasia. Therefore, for chronically administered CYP3A4 inhibitors ( > 30 days) concurrently administered with DUAVEE, adequate diagnostic measures, including directed or random endometrial sampling when indicated by signs and symptoms of endometrial hyperplasia, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Bazedoxifene undergoes little or no cytochrome P450 (CYP)-mediated metabolism. Bazedoxifene does not induce or inhibit the activities of major CYP isoenzymes. In vitro data suggest that bazedoxifene is unlikely to interact with co-administered drugs via CYP-mediated metabolism.

Uridine Diphosphate Glucuronosyltransferase (UGT)

Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as rifampin, phenobarbital, carbamazepine, and phenytoin. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Atorvastatin

Concomitant administration of bazedoxifene (40 mg daily) and atorvastatin (20 mg, single-dose) to healthy postmenopausal women did not affect the pharmacokinetics of bazedoxifene, atorvastatin or its active metabolites.

Last reviewed on RxList: 11/7/2013
This monograph has been modified to include the generic and brand name in many instances.

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