Estrogens (Conjugated/Equine) and Bazedoxifene
Medically reviewed on September 10, 2018
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- Bazedoxifene and Estrogens (Conjugated/Equine)
- Bazedoxifene and Oestrogens
- Estrogens (Conjugated/Equine) and Bazedoxifene Acetate
- Oestrogens and Bazedoxifene
Duavee: Conjugated estrogens 0.45 mg and bazedoxifene 20 mg
Brand Names: U.S.
- Estrogen Derivative
- Selective Estrogen Receptor Modulator (SERM)
- Tissue-Selective Estrogen Complex (TSEC)
Conjugated estrogens contain a mixture of estrone sulfate, equilin sulfate, 17 alpha-dihydroequilin, 17 alpha-estradiol and 17 beta-dihydroequilin. Bazedoxifene is a selective estrogen receptor modulator (SERM). Conjugated estrogens act as an estrogen agonist and bazedoxifene acts as an estrogen agonist/antagonist depending on the specific tissue. The combination of a SERM and estrogen [referred to as a tissue-selective estrogen complex (TSEC)] provides relief of vasomotor symptoms and maintenance of bone mineral density in postmenopausal women with a uterus, while reducing the risk of endometrial hyperplasia observed with estrogen use alone (Pickar, 2009).
Conjugated estrogens: Well-absorbed from the gastrointestinal tract
Bazedoxifene: Vd: ~15 L/kg
Bazedoxifene: Metabolized via glucuronidation; forms metabolites; little or no CYP mediated metabolism; undergoes hepatic recirculation
Conjugated estrogens: Hepatic via CYP3A4; estradiol is converted to estrone and estriol; also undergoes enterohepatic recirculation; estrone sulfate is the main metabolite in postmenopausal women
Conjugated estrogens: Urine (primarily estriol, also as estradiol, estrone, and conjugates)
Bazedoxifene: Biliary; feces (~85%); urine (<1%)
Onset of Action
Relief of vasomotor symptoms: A significant reduction in the number and severity of moderate/severe hot flashes was observed after 4 weeks of therapy (Pinkerton, 2009).
Osteoporosis: A significant increase in BMD measured at the lumbar spine and hip was observed at 12 months of therapy (Lindsay, 2009).
Time to Peak
Bazedoxifene: ~2.5 hours
Total estrone: ~6.5 hours
Bazedoxifene: ~30 hours
Total estrone: ~17 hours
Bazedoxifene: 98% to 99%; does not bind to sex-hormone binding globulin
Conjugated estrogens: Binds to sex-hormone-binding globulin and albumin
Use: Labeled Indications
Postmenopausal osteoporosis prophylaxis: Prevention of postmenopausal osteoporosis in women with a uterus
Limitations of use: For use only in women at significant risk of postmenopausal osteoporosis; consider use of nonestrogen medications.
Vasomotor symptoms: Treatment of moderate-to-severe vasomotor symptoms associated with menopause in women with a uterus
Hypersensitivity to estrogens, bazedoxifene, or any component of the formulation; undiagnosed abnormal uterine bleeding; active or past history of venous thromboembolism (VTE) (eg, PE, DVT); active or history of arterial thromboembolic disease (eg, stroke, MI); carcinoma of the breast (known, suspected or history of); estrogen-dependent tumor (known or suspected); hepatic impairment or disease; known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders; pregnancy or women who may become pregnant; breastfeeding
Canadian labeling: Additional contraindications (not in US labeling): Active thrombophlebitis; endometrial hyperplasia; partial or complete loss of vision due to ophthalmic vascular disease.
General dosing guidelines: When treating symptoms of menopause, hormone therapy should be evaluated routinely for appropriate dose, duration, and route of administration for each individual patient based on treatment goals, risk factors, and overall health (NAMS 2017).
Menopause (moderate-to-severe vasomotor symptoms), prevention of postmenopausal osteoporosis: Females: Oral: One tablet daily
Refer to adult dosing. Use in women >75 years of age is not recommended (has not been studied).
Dosing: Renal Impairment
No dosage adjustment provided in manufacturer’s labeling (has not been studied). Use is not recommended.
Dosing: Hepatic Impairment
Use is contraindicated with hepatic dysfunction or disease.
Administer once daily, without regard to meals. Patient should swallow tablets whole.
Ensure adequate calcium and vitamin D intake when used for the prevention of osteoporosis.
Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Dispense in original package. Protect from moisture. After opening foil pouch, product must be used within 60 days.
Ajmaline: Estrogen Derivatives may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy
Anastrozole: Estrogen Derivatives may diminish the therapeutic effect of Anastrozole. Avoid combination
Anthrax Immune Globulin (Human): Estrogen Derivatives may enhance the thrombogenic effect of Anthrax Immune Globulin (Human). Monitor therapy
Anticoagulants: Estrogen Derivatives may diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Ascorbic Acid: May increase the serum concentration of Estrogen Derivatives. Monitor therapy
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
C1 inhibitors: Estrogen Derivatives may enhance the thrombogenic effect of C1 inhibitors. Monitor therapy
Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy
Chenodiol: Estrogen Derivatives may diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any estrogen derivative. Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy
Corticosteroids (Systemic): Estrogen Derivatives may increase the serum concentration of Corticosteroids (Systemic). Monitor therapy
CYP1A2 Inducers (Moderate): May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Estrogen Derivatives. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Estrogen Derivatives. Monitor therapy
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dantrolene: Estrogen Derivatives may enhance the hepatotoxic effect of Dantrolene. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Dehydroepiandrosterone: May enhance the adverse/toxic effect of Estrogen Derivatives. Avoid combination
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Exemestane: Estrogen Derivatives may diminish the therapeutic effect of Exemestane. Avoid combination
Hemin: Estrogen Derivatives may diminish the therapeutic effect of Hemin. Avoid combination
Herbs (Estrogenic Properties): May enhance the adverse/toxic effect of Estrogen Derivatives. Monitor therapy
Hyaluronidase: Estrogen Derivatives may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving estrogens (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification
Immune Globulin: Estrogen Derivatives may enhance the thrombogenic effect of Immune Globulin. Monitor therapy
Indium 111 Capromab Pendetide: Estrogen Derivatives may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
LamoTRIgine: Estrogen Derivatives may decrease the serum concentration of LamoTRIgine. Monitor therapy
Lenalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Lenalidomide. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Mivacurium: Estrogen Derivatives may increase the serum concentration of Mivacurium. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the thrombogenic effect of Estrogen Derivatives. Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may increase the serum concentration of Estrogen Derivatives. Monitor therapy
Ospemifene: Selective Estrogen Receptor Modulators may enhance the adverse/toxic effect of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Selective Estrogen Receptor Modulators may diminish the therapeutic effect of Ospemifene. Ospemifene may also diminish the therapeutic effects of other Selective Estrogen Receptor Modulators. Avoid combination
Ospemifene: Estrogen Derivatives may enhance the adverse/toxic effect of Ospemifene. Estrogen Derivatives may diminish the therapeutic effect of Ospemifene. Avoid combination
Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification
Pomalidomide: May enhance the thrombogenic effect of Estrogen Derivatives. Management: Canadian pomalidomide labeling recommends caution with use of hormone replacement therapy and states that hormonal contraceptives are not recommended. US pomalidomide labeling does not contain these specific recommendations. Consider therapy modification
ROPINIRole: Estrogen Derivatives may increase the serum concentration of ROPINIRole. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Somatropin: Estrogen Derivatives may diminish the therapeutic effect of Somatropin. Shown to be a concern with oral hormone replacement therapy in postmenopausal women. Management: Monitor for reduced growth hormone efficacy. A larger somatropin dose may be required to reach treatment goal. This interaction does not appear to apply to non-orally administered estrogens (e.g., transdermal, vaginal ring). Consider therapy modification
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Succinylcholine: Estrogen Derivatives may increase the serum concentration of Succinylcholine. Monitor therapy
Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Monitor therapy
Thalidomide: Estrogen Derivatives may enhance the thrombogenic effect of Thalidomide. Monitor therapy
Theophylline Derivatives: Estrogen Derivatives may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Thyroid Products: Estrogen Derivatives may diminish the therapeutic effect of Thyroid Products. Monitor therapy
Tipranavir: Estrogen Derivatives may enhance the dermatologic adverse effect of Tipranavir. The combination of tipranavir/ritonavir and ethinyl estradiol/norethindrone was associated with a high incidence of skin rash. Tipranavir may decrease the serum concentration of Estrogen Derivatives. Management: Women using hormonal contraceptives should consider alternative, non-hormonal forms of contraception. Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Ursodiol: Estrogen Derivatives may diminish the therapeutic effect of Ursodiol. Monitor therapy
Percentages as reported with combination product.
1% to 10%:
Central nervous system: Dizziness (5%)
Gastrointestinal: Diarrhea (8%), nausea (8%), dyspepsia (7%), upper abdominal pain (7%)
Neuromuscular & skeletal: Muscle spasm (9%), neck pain (5%)
Respiratory: Oropharyngeal pain (7%)
Concerns related to adverse effects:
• Breast cancer: Based on data from the Women’s Health Initiative (WHI) studies, an increased risk of invasive breast cancer was observed in postmenopausal women using conjugated estrogens (CE) in combination with medroxyprogesterone acetate (MPA). Observational studies noted this risk declines once therapy is discontinued. The WHI study did not observe an increased risk of invasive breast cancer in women with a hysterectomy using CE alone. The risk of breast cancer in postmenopausal patients on hormone therapy may depend upon type of estrogen and/or progestin, dose, timing of therapy initiation, duration of therapy, route of administration, and individual patient characteristics (AACE/ACE [Cobin 2017]; NAMS 2017). Hormone therapy may be associated with increased breast density (NAMS 2017); an increase in abnormal mammogram findings requiring further evaluation has been reported with estrogen alone or in combination with progestin therapy. Estrogen use may lead to severe hypercalcemia in patients with breast cancer and bone metastases; discontinue estrogen if hypercalcemia occurs.
• Dementia: [US Boxed Warning]: In the Women’s Health Initiative Memory Study (WHIMS), an increased incidence of probable dementia was observed in women ≥65 years of age taking CE alone. It is not known if this finding applies to younger postmenopausal women. Estrogens should not be used for the prevention of dementia. Because the WHI memory studies were conducted in women ≥ 65 years of age, it is unknown if these findings apply to younger postmenopausal women. However, hormone therapy is not recommended at any age to prevent or treat cognitive decline or dementia (AACE [Goodman 2011]; NAMS 2017).
• Endometrial cancer: [US Boxed Warning]: The use of unopposed estrogen in women with an intact uterus is associated with an increased risk of endometrial cancer. Estrogens (conjugated/equine) in combination with bazedoxifene has been shown to decrease the risk of endometrial hyperplasia, a precursor to endometrial cancer. Adequate diagnostic measures, including endometrial sampling if indicated, should be performed to rule out malignancy in postmenopausal women with undiagnosed abnormal vaginal bleeding. Women taking this combination should not take additional estrogen (may increase the risk of endometrial hyperplasia).
• Lipid effects: Estrogen compounds are generally associated with lipid effects such as increased HDL-cholesterol and decreased LDL-cholesterol. Triglycerides may also be increased; discontinue if pancreatitis occurs.
• Ovarian cancer: Available information related to the use of menopausal estrogen or estrogen/progestin therapy and risk of ovarian cancer is inconsistent. If an association is present, the absolute risk is likely rare and may be influenced by duration of therapy (AACE [Goodman 2011]; ES [Stuenkel 2015]; NAMS 2017).
• Retinal vascular thrombosis: Estrogens may cause retinal vascular thrombosis; discontinue pending examination if migraine, loss of vision, proptosis, diplopia, or other visual disturbances occur; discontinue permanently if papilledema or retinal vascular lesions are observed on examination.
• Asthma: Use caution in patients with asthma; may exacerbate disease.
• Carbohydrate intolerance: May impair glucose tolerance; use caution in patients with diabetes. Prior to therapy, consider age, cardiovascular and metabolic risk factors in patients previously diagnosed with diabetes (AACE/ACE [Cobin 2017]).
• Cardiovascular disease: [US Boxed Warning]: Estrogens should not be used to prevent cardiovascular disease. Using data from the Women’s Health Initiative (WHI) studies, an increased risk of deep vein thrombosis (DVT) and stroke has been reported with CE in postmenopausal women 50 to 79 years of age. Estrogens and bazedoxifene are known to increase the risk of venous thromboembolism (VTE). Additional risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of VTE. Risk factors should be managed appropriately; discontinue use immediately if adverse cardiovascular events occur or are suspected. Due to possible lower risk of thrombotic events, transdermal administration may be preferred for treating vasomotor symptoms of menopause in patients with risk factors for cardiovascular disease (AACE/ACE [Cobin 2017]; ACOG 556 2013; ES [Stuenkel 2015]). Use is contraindicated in women with active DVT, PE, arterial thromboembolic disease (stroke and MI), or a history of these conditions.
• Diseases exacerbated by fluid retention: Use with caution in patients with diseases which may be exacerbated by fluid retention, including cardiac or renal dysfunction.
• Epilepsy: Use caution with epilepsy; may exacerbate disease.
• Gallbladder disease: Use of postmenopausal estrogen may be associated with an increased risk of gallbladder disease requiring surgery.
• Hepatic dysfunction: Estrogens are poorly metabolized in patients with hepatic dysfunction. Use caution with a history of cholestatic jaundice associated with prior estrogen use or pregnancy. Discontinue if jaundice develops or if acute or chronic hepatic disturbances occur. Use is contraindicated with hepatic disease.
• Hepatic hemangiomas: Use with caution in patients with hepatic hemangiomas; may exacerbate disease.
• Hereditary angioedema: Exogenous estrogens may exacerbate angioedema symptoms in women with hereditary angioedema.
• Hypoparathyroidism: Use caution in patients with hypoparathyroidism; estrogen-induced hypocalcemia may occur.
• Migraine: Use caution with migraine; may exacerbate disease.
• Porphyria: Use with caution in patients with porphyria; may exacerbate disease.
• SLE: Use with caution in patients with SLE; may exacerbate disease.
Concurrent drug therapy issues:
• Thyroid replacement therapy: Estrogens may increase thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels. Women on thyroid replacement therapy may require higher doses of thyroid hormone while receiving estrogens.
• Overweight/Obese: Bazedoxifene exposure is decreased in women with a BMI >27 kg/m2 which may be associated with an increased risk of endometrial hyperplasia. Women with a BMI >34 kg/m2 or >32.2 kg/m2 were excluded from some initial vasomotor or osteoporosis studies, respectively (Lindsay 2009; Pinkerton 2009). Regardless of BMI, monitoring should be done to rule out malignancy in postmenopausal women with undiagnosed persistent or recurrent abnormal genital bleeding.
• Surgical patients: Whenever possible, estrogens should be discontinued at least 4 to 6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
• Duration of use: Extended use of menopausal hormone therapy may be considered for persistent vasomotor symptoms, issues related to quality of life, or for osteoporosis prevention in women at increased risk of fracture. Menopausal hormonal therapy does not need to be routinely discontinued in women >60 years of age and may continue in women >65 years of age after clinical evaluation and discussion of benefits and risks of treatment. Annual exams should be performed with a review of comorbidities; possible adjustments to safer lower-dose and/or route of administration should be discussed (ACOG 565 2013; NAMS 2017).
• Laboratory changes: The use of estrogens and/or progestins may change the results of some laboratory tests (eg, coagulation factors, lipids, glucose tolerance, binding proteins). The dose, route, and the specific estrogen/progestin influences these changes.
• Osteoporosis use: In women with premature menopause, hormone therapy to prevent bone loss may be used unless otherwise contraindicated; therapy should be reassessed when the average age of menopause is reached. It is also an appropriate bone-active therapy for women with vasomotor symptoms who are <60 years of age or within 10 years of menopause onset. Use may be considered for women at high risk of fractures who are not candidates for other osteoporosis therapies (NAMS 2017).
• Risks vs benefits: When used for the relief of menopausal symptoms or increased risk of bone fracture/loss, the benefit-risk of hormone therapy is most favorable if started in patients who have no contraindications to therapy, are <60 years of age, within 10 years of menopause onset, have a favorable lipid profile, and do not have the factor V Leiden genotype or metabolic syndrome. Risk factors for cardiovascular disease should also be considered when evaluating therapy and route of administration (AACE/ACE [Cobin 2017]; NAMS 2017). [US Boxed Warning]: Women taking estrogens (conjugated/equine) in combination with bazedoxifene should not take additional estrogen. Estrogens should be used for the shortest duration possible at the lowest effective dose consistent with treatment goals. Women taking this combination should also not take progestins or additional estrogen agonists/antagonists. Patients should be reevaluated as clinically appropriate to determine if treatment is still necessary. Available data related to treatment risks are from Women’s Health Initiative (WHI) studies, which evaluated oral CE 0.625 mg relative to placebo in postmenopausal women. Other combinations and dosage forms of estrogens were not studied; outcomes should be assumed to be similar for other doses and other dosage forms of estrogens until comparable data becomes available.
Prior to therapy, baseline risk for breast cancer and CVD. During therapy, age appropriate breast and pelvic exams; blood pressure; unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer); serum triglycerides (2 weeks after starting therapy in patients with baseline level >200 mg/dL); TSH (6 to 12 weeks after starting oral therapy in patients taking thyroid replacement) (ES [Stuenkel 2015]).
Menopausal symptoms: Efficacy beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate. Duration of treatment should be evaluated at least annually (ES [Stuenkel 2015]).
Note: Monitoring of FSH and serum estradiol is not useful when managing vasomotor symptoms of menopause
Prevention of osteoporosis: Bone density measurement
Pregnancy Risk Factor
Use is contraindicated in women who are or who may become pregnant.
This combination product is approved for use in postmenopausal women only.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience muscle spasms, diarrhea, pharyngitis, or neck pain. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; tachycardia; or coughing up blood), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of gallstones (pain in the upper right abdominal area, right shoulder area, or between the shoulder blades; jaundice; or fever with chills), edema, severe loss of strength and energy, severe headache, severe dizziness, passing out, severe nausea, vomiting, severe abdominal pain, vaginitis, abnormal vaginal bleeding, bulging eyes, contact lens discomfort, vision changes, blindness, lump in breast, breast soreness or pain, nipple discharge, depression, mood changes, or memory impairment (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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Other brands: Duavee