Prempro
Generic: CONJUGATED ESTROGENS AND MEDROXYPROGESTERONE ACETATE
Basic Information
Manufacturer
Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
fd0c0836-5d23-2183-da81-9dc7f4287052
Indications & Usage
1 INDICATIONS AND USAGE PREMPRO/PREMPHASE is an estrogen plus progestin indicated in a woman with a uterus for: • Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) • Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause ( 1.2 ) • Prevention of Postmenopausal Osteoporosis ( 1.3 ) 1.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause 1.2 Treatment of Moderate to Severe Vulvar and Vaginal Atrophy due to Menopause 1.3 Prevention of Postmenopausal Osteoporosis
Adverse Reactions
6 ADVERSE REACTIONS 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) ] In two prospective, randomized clinical studies, the most common adverse reactions >5% are abdominal pain, asthenia, back pain, headache, flatulence, nausea, depression, pruritus, breast pain, dysmenorrhea, and leukorrhea.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc.
at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial 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.
In a 1-year clinical trial that included 678 postmenopausal women treated with PREMPRO and 351 postmenopausal women treated with PREMPHASE, the following adverse reactions occurred at a rate ≥ 1%, see Table 1 .
Table 1: Treatment-Related Adverse Reactions at a Frequency ≥1% Body System PREMPRO 0.625 mg/2.5 mg continuous PREMPRO 0.625 mg/5 mg continuous PREMPHASE 0.625 mg/5 mg sequential Adverse event (n = 340) (n = 338) (n = 351) Body As A Whole Abdominal pain 35 (10%) 51 (15%) 58 (17%) Asthenia 13 (4%) 18 (5%) 21 (6%) Back pain 19 (6%) 16 (5%) 23 (7%) Chest pain 5 (1%) 4 (1%) 4 (1%) Flu syndrome 1 (<1%) 1 (<1%) 4 (1%) Generalized edema 12 (4%) 12 (4%) 8 (2%) Headache 64 (19%) 52 (15%) 66 (19%) Infection 2 (<1%) 4 (1)% 0 Moniliasis 4 (1%) 3 (<1%) 4 (1%) Pain 12 (4%) 14 (4%) 15 (4%) Pelvic pain 11 (3%) 13 (4%) 16 (5%) Cardiovascular System Hypertension 7 (2%) 7 (2%) 6 (2%) Migraine 6 (2%) 8 (2%) 7 (2%) Palpitation 2 (<1%) 3 (<1%) 4 (1%) Vasodilatation 2 (<1%) 7 (2%) 2 (<1%) Digestive System Diarrhea 4 (1%) 3 (<1%) 7 (2%) Dyspepsia 5 (1%) 5 (1%) 7 (2%) Eructation 0 2 (<1%) 4 (1%) Flatulence 25 (7%) 27 (8%) 24 (7%) Increased appetite 1 (<1%) 5 (1%) 5 (1%) Nausea 26 (8%) 19 (6%) 26 (7%) Metabolic and Nutritional Edema 5 (1%) 6 (2%) 3 (<1%) Glucose tolerance decreased 2 (<1%) 5 (1%) 4 (1%) Peripheral edema 11 (3%) 10 (3%) 11 (3%) Weight gain 9 (3%) 10 (3%) 11 (3%) Musculoskeletal System Arthralgia 6 (2%) 2 (<1%) 7 (2%) Leg cramps 8 (2%) 11 (3%) 12 (3%) Nervous System Depression 14 (4%) 26 (8%) 29 (8%) Dizziness 9 (3%) 8 (2%) 7 (2%) Emotional lability 5 (1%) 5 (1%) 6 (2%) Hypertonia 4 (1%) 4 (1%) 7 (2%) Insomnia 7 (2%) 6 (2%) 4 (1%) Nervousness 4 (1%) 9 (3%) 6 (2%) Skin and Appendages Acne 1 (<1%) 5 (1%) 4 (1%) Alopecia 3 (<1%) 4 (1%) 0 Dry skin 2 (<1%) 3 (<1%) 4 (1%) Pruritus 20 (6%) 18 (5%) 13 (4%) Rash 8 (2%) 6 (2%) 7 (2%) Sweating 2 (<1%) 4 (1%) 2 (<1%) Urogenital System Breast engorgement 5 (1%) 5 (1%) 0 Breast enlargement 14 (4%) 14 (4%) 14 (4%) Breast neoplasm 2 (<1%) 2 (<1%) 4 (1%) Breast pain 110 (32%) 123 (36%) 109 (31%) Cervix disorder 10 (3%) 6 (2%) 10 (3%) Dysmenorrhea 26 (8%) 18 (5%) 44 (13%) Leukorrhea 19 (6%) 13 (4%) 29 (8%) Menstrual disorder 7 (2%) 1 (<1%) 5 (1%) Menorrhagia 0 1 (<1%) 5 (1%) Metrorrhagia 13 (4%) 5 (1%) 7 (1%) Papanicolaou smear suspicious 5 (1%) 0 8 (2%) Urinary incontinence 4 (1%) 2 (<1%) 1 (<1%) Uterine spasm 7 (2%) 4 (1%) 7 (2%) Vaginal hemorrhage 5 (1%) 3 (<1%) 8 (2%) Vaginal moniliasis 5 (1%) 6 (2%) 7 (2%) Vaginitis 13 (4%) 13 (4%) 10 (3%) In addition, phargyngitis and sinusitis were reported as two of the more frequent adverse events (>5%) in the PREMPRO clinical study.
For pharyngitis, of the 121 events, six events were considered by the investigator causally related to study drug.
For sinusitis, of the 73 events, one event was considered as casually related to study drug.
During the first year of a 2-year clinical trial with postmenopausal women between 40 and 65 years of age (88% Caucasian), 989 postmenopausal women received continuous regimens of PREMPRO, and 332 received placebo tablets.
Table 2 summarizes adverse reactions that occurred at a rate ≥ 1% in at least 1 treatment group.
Table 2: All Treatment-Related Adverse Reactions at a Frequency of ≥1% Body System Adverse event PREMPRO 0.625/2.5 continuous (N=331) PREMPRO 0.45/1.5 continuous (N=331) PREMPRO 0.3/1.5 continuous (N=327) PLACEBO daily (N=332) Any adverse event 214 (65) 208 (63) 188 (57) 164 (49) Body as a Whole Abdominal pain 38 (11) 33 (10) 24 (7) 21 (6) Asthenia 11 (3) 11 (3) 12 (4) 3 (1) Back pain 12 (4) 12 (4) 8 (2) 4 (1) Chest pain 4 (1) 2 (1) 1 (0) 2 (1) Generalized edema 7 (2) 5 (2) 6 (2) 8 (2) Headache 45 (14) 45 (14) 57 (17) 46 (14) Moniliasis 3 (1) 6 (2) 4 (1) 1 (0) Pain 9 (3) 10 (3) 17 (5) 14 (4) Pelvic pain 9 (3) 7 (2) 5 (2) 4 (1) Cardiovascular System Hypertension 2 (1) 3 (1) 1 (0) 5 (2) Migraine 11 (3) 8 (2) 5 (2) 3 (1) Palpitation 1 (0) 1 (0) 2 (1) 4 (1) Vasodilatation 0 3 (1) 1 (0) 5 (2) Digestive System Constipation 5 (2) 7 (2) 6 (2) 3 (1) Diarrhea 5 (2) 2 (1) 6 (2) 8 (2) Dyspepsia 10 (3) 9 (3) 6 (2) 14 (4) Flatulence 16 (5) 18 (5) 13 (4) 8 (2) Increased appetite 6 (2) 2 (1) 0 2 (1) Nausea 13 (4) 13 (4) 16 (5) 16 (5) Metabolic and nutritional Peripheral edema 7 (2) 8 (2) 4 (1) 3 (1) Weight gain 9 (3) 8 (2) 6 (2) 14 (4) Musculoskeletal System Arthralgia 2 (1) 3 (1) 3 (1) 5 (2) Leg cramps 13 (4) 7 (2) 10 (3) 4 (1) Nervous System Anxiety 5 (2) 4 (1) 1 (0) 4 (1) Depression 23 (7) 11 (3) 11 (3) 17 (5) Dizziness 3 (1) 8 (2) 6 (2) 5 (2) Emotional lability 10 (3) 10 (3) 9 (3) 8 (2) Insomnia 8 (2) 7 (2) 9 (3) 14 (4) Nervousness 6 (2) 3 (1) 4 (1) 6 (2) Skin and Appendages Acne 7 (2) 3 (1) 0 3 (1) Alopecia 1 (0) 6 (2) 4 (1) 2 (1) Pruritus 8 (2) 10 (3) 9 (3) 3 (1) Rash 0 6 (2) 4 (1) 2 (1) Skin discoloration 5 (2) 1 (0) 3 (1) 1 (0) Sweating 3 (1) 1 (0) 0 4 (1) Urogenital System Breast disorder 7 (2) 6 (2) 5 (2) 6 (2) Breast enlargement 18 (5) 9 (3) 5 (2) 3 (1) Breast neoplasm 8 (2) 7 (2) 5 (2) 7 (2) Breast pain 87 (26) 66 (20) 41 (13) 26 (8) Cervix disorder 7 (2) 2 (1) 2 (1) 0 Dysmenorrhea 14 (4) 18 (5) 9 (3) 2 (1) Hematuria 4 (1) 3 (1) 1 (0) 2 (1) Leukorrhea 7 (2) 14 (4) 9 (3) 6 (2) Metrorrhagia 7 (2) 14 (4) 4 (1) 1 (0) Urinary tract infection 0 1 (0) 1 (0) 4 (1) Uterine spasm 13 (4) 11 (3) 7 (2) 2 (1) Vaginal dryness 2 (1) 1 (0) 0 6 (2) Vaginal hemorrhage 18 (5) 14 (4) 7 (2) 0 Vaginal moniliasis 13 (4) 11 (3) 8 (2) 5 (2) Vaginitis 6 (2) 8 (2) 7 (2) 1 (0) In addition, the following events were considered as related to the study drug with an incidence less than 1%, including accidental injury, infection, myalgia, cough increased, rhinitis, sinusitis, and upper respiratory infection.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of PREMPRO or PREMPHASE.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Genitourinary System Abnormal uterine bleeding, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis, vaginal candidiasis, amenorrhea, changes in cervical secretion, ovarian cancer, endometrial hyperplasia, endometrial cancer.
Breasts Tenderness, enlargement, pain, nipple discharge, galactorrhea, fibrocystic breast changes, breast cancer.
Cardiovascular Deep and superficial venous thrombosis, pulmonary embolism, superficial thrombophlebitis, myocardial infarction, stroke, increase in blood pressure.
Gastrointestinal Nausea, vomiting, abdominal pain, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, changes in appetite, ischemic colitis.
Skin Chloasma or melasma that may persist when drug is discontinued, erythema multiforme, erythema nodosum, loss of scalp hair, hirsutism, pruritus, urticaria, rash, acne.
Eyes Retinal vascular thrombosis, intolerance of contact lenses.
Central Nervous System Headache, migraine, dizziness, mental depression, exacerbation of chorea, mood disturbances, anxiety, irritability, exacerbation of epilepsy, dementia, growth potentiation of benign meningioma.
Miscellaneous Increase or decrease in weight, arthralgia, glucose intolerance, edema, changes in libido, exacerbation of asthma, increased triglycerides, hypersensitivity.
Additional postmarketing adverse reactions have been reported in patients receiving other forms of hormone therapy.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc.
at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial 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.
In a 1-year clinical trial that included 678 postmenopausal women treated with PREMPRO and 351 postmenopausal women treated with PREMPHASE, the following adverse reactions occurred at a rate ≥ 1%, see Table 1 .
Table 1: Treatment-Related Adverse Reactions at a Frequency ≥1% Body System PREMPRO 0.625 mg/2.5 mg continuous PREMPRO 0.625 mg/5 mg continuous PREMPHASE 0.625 mg/5 mg sequential Adverse event (n = 340) (n = 338) (n = 351) Body As A Whole Abdominal pain 35 (10%) 51 (15%) 58 (17%) Asthenia 13 (4%) 18 (5%) 21 (6%) Back pain 19 (6%) 16 (5%) 23 (7%) Chest pain 5 (1%) 4 (1%) 4 (1%) Flu syndrome 1 (<1%) 1 (<1%) 4 (1%) Generalized edema 12 (4%) 12 (4%) 8 (2%) Headache 64 (19%) 52 (15%) 66 (19%) Infection 2 (<1%) 4 (1)% 0 Moniliasis 4 (1%) 3 (<1%) 4 (1%) Pain 12 (4%) 14 (4%) 15 (4%) Pelvic pain 11 (3%) 13 (4%) 16 (5%) Cardiovascular System Hypertension 7 (2%) 7 (2%) 6 (2%) Migraine 6 (2%) 8 (2%) 7 (2%) Palpitation 2 (<1%) 3 (<1%) 4 (1%) Vasodilatation 2 (<1%) 7 (2%) 2 (<1%) Digestive System Diarrhea 4 (1%) 3 (<1%) 7 (2%) Dyspepsia 5 (1%) 5 (1%) 7 (2%) Eructation 0 2 (<1%) 4 (1%) Flatulence 25 (7%) 27 (8%) 24 (7%) Increased appetite 1 (<1%) 5 (1%) 5 (1%) Nausea 26 (8%) 19 (6%) 26 (7%) Metabolic and Nutritional Edema 5 (1%) 6 (2%) 3 (<1%) Glucose tolerance decreased 2 (<1%) 5 (1%) 4 (1%) Peripheral edema 11 (3%) 10 (3%) 11 (3%) Weight gain 9 (3%) 10 (3%) 11 (3%) Musculoskeletal System Arthralgia 6 (2%) 2 (<1%) 7 (2%) Leg cramps 8 (2%) 11 (3%) 12 (3%) Nervous System Depression 14 (4%) 26 (8%) 29 (8%) Dizziness 9 (3%) 8 (2%) 7 (2%) Emotional lability 5 (1%) 5 (1%) 6 (2%) Hypertonia 4 (1%) 4 (1%) 7 (2%) Insomnia 7 (2%) 6 (2%) 4 (1%) Nervousness 4 (1%) 9 (3%) 6 (2%) Skin and Appendages Acne 1 (<1%) 5 (1%) 4 (1%) Alopecia 3 (<1%) 4 (1%) 0 Dry skin 2 (<1%) 3 (<1%) 4 (1%) Pruritus 20 (6%) 18 (5%) 13 (4%) Rash 8 (2%) 6 (2%) 7 (2%) Sweating 2 (<1%) 4 (1%) 2 (<1%) Urogenital System Breast engorgement 5 (1%) 5 (1%) 0 Breast enlargement 14 (4%) 14 (4%) 14 (4%) Breast neoplasm 2 (<1%) 2 (<1%) 4 (1%) Breast pain 110 (32%) 123 (36%) 109 (31%) Cervix disorder 10 (3%) 6 (2%) 10 (3%) Dysmenorrhea 26 (8%) 18 (5%) 44 (13%) Leukorrhea 19 (6%) 13 (4%) 29 (8%) Menstrual disorder 7 (2%) 1 (<1%) 5 (1%) Menorrhagia 0 1 (<1%) 5 (1%) Metrorrhagia 13 (4%) 5 (1%) 7 (1%) Papanicolaou smear suspicious 5 (1%) 0 8 (2%) Urinary incontinence 4 (1%) 2 (<1%) 1 (<1%) Uterine spasm 7 (2%) 4 (1%) 7 (2%) Vaginal hemorrhage 5 (1%) 3 (<1%) 8 (2%) Vaginal moniliasis 5 (1%) 6 (2%) 7 (2%) Vaginitis 13 (4%) 13 (4%) 10 (3%) In addition, phargyngitis and sinusitis were reported as two of the more frequent adverse events (>5%) in the PREMPRO clinical study.
For pharyngitis, of the 121 events, six events were considered by the investigator causally related to study drug.
For sinusitis, of the 73 events, one event was considered as casually related to study drug.
During the first year of a 2-year clinical trial with postmenopausal women between 40 and 65 years of age (88% Caucasian), 989 postmenopausal women received continuous regimens of PREMPRO, and 332 received placebo tablets.
Table 2 summarizes adverse reactions that occurred at a rate ≥ 1% in at least 1 treatment group.
Table 2: All Treatment-Related Adverse Reactions at a Frequency of ≥1% Body System Adverse event PREMPRO 0.625/2.5 continuous (N=331) PREMPRO 0.45/1.5 continuous (N=331) PREMPRO 0.3/1.5 continuous (N=327) PLACEBO daily (N=332) Any adverse event 214 (65) 208 (63) 188 (57) 164 (49) Body as a Whole Abdominal pain 38 (11) 33 (10) 24 (7) 21 (6) Asthenia 11 (3) 11 (3) 12 (4) 3 (1) Back pain 12 (4) 12 (4) 8 (2) 4 (1) Chest pain 4 (1) 2 (1) 1 (0) 2 (1) Generalized edema 7 (2) 5 (2) 6 (2) 8 (2) Headache 45 (14) 45 (14) 57 (17) 46 (14) Moniliasis 3 (1) 6 (2) 4 (1) 1 (0) Pain 9 (3) 10 (3) 17 (5) 14 (4) Pelvic pain 9 (3) 7 (2) 5 (2) 4 (1) Cardiovascular System Hypertension 2 (1) 3 (1) 1 (0) 5 (2) Migraine 11 (3) 8 (2) 5 (2) 3 (1) Palpitation 1 (0) 1 (0) 2 (1) 4 (1) Vasodilatation 0 3 (1) 1 (0) 5 (2) Digestive System Constipation 5 (2) 7 (2) 6 (2) 3 (1) Diarrhea 5 (2) 2 (1) 6 (2) 8 (2) Dyspepsia 10 (3) 9 (3) 6 (2) 14 (4) Flatulence 16 (5) 18 (5) 13 (4) 8 (2) Increased appetite 6 (2) 2 (1) 0 2 (1) Nausea 13 (4) 13 (4) 16 (5) 16 (5) Metabolic and nutritional Peripheral edema 7 (2) 8 (2) 4 (1) 3 (1) Weight gain 9 (3) 8 (2) 6 (2) 14 (4) Musculoskeletal System Arthralgia 2 (1) 3 (1) 3 (1) 5 (2) Leg cramps 13 (4) 7 (2) 10 (3) 4 (1) Nervous System Anxiety 5 (2) 4 (1) 1 (0) 4 (1) Depression 23 (7) 11 (3) 11 (3) 17 (5) Dizziness 3 (1) 8 (2) 6 (2) 5 (2) Emotional lability 10 (3) 10 (3) 9 (3) 8 (2) Insomnia 8 (2) 7 (2) 9 (3) 14 (4) Nervousness 6 (2) 3 (1) 4 (1) 6 (2) Skin and Appendages Acne 7 (2) 3 (1) 0 3 (1) Alopecia 1 (0) 6 (2) 4 (1) 2 (1) Pruritus 8 (2) 10 (3) 9 (3) 3 (1) Rash 0 6 (2) 4 (1) 2 (1) Skin discoloration 5 (2) 1 (0) 3 (1) 1 (0) Sweating 3 (1) 1 (0) 0 4 (1) Urogenital System Breast disorder 7 (2) 6 (2) 5 (2) 6 (2) Breast enlargement 18 (5) 9 (3) 5 (2) 3 (1) Breast neoplasm 8 (2) 7 (2) 5 (2) 7 (2) Breast pain 87 (26) 66 (20) 41 (13) 26 (8) Cervix disorder 7 (2) 2 (1) 2 (1) 0 Dysmenorrhea 14 (4) 18 (5) 9 (3) 2 (1) Hematuria 4 (1) 3 (1) 1 (0) 2 (1) Leukorrhea 7 (2) 14 (4) 9 (3) 6 (2) Metrorrhagia 7 (2) 14 (4) 4 (1) 1 (0) Urinary tract infection 0 1 (0) 1 (0) 4 (1) Uterine spasm 13 (4) 11 (3) 7 (2) 2 (1) Vaginal dryness 2 (1) 1 (0) 0 6 (2) Vaginal hemorrhage 18 (5) 14 (4) 7 (2) 0 Vaginal moniliasis 13 (4) 11 (3) 8 (2) 5 (2) Vaginitis 6 (2) 8 (2) 7 (2) 1 (0) In addition, the following events were considered as related to the study drug with an incidence less than 1%, including accidental injury, infection, myalgia, cough increased, rhinitis, sinusitis, and upper respiratory infection.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of PREMPRO or PREMPHASE.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Genitourinary System Abnormal uterine bleeding, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis, vaginal candidiasis, amenorrhea, changes in cervical secretion, ovarian cancer, endometrial hyperplasia, endometrial cancer.
Breasts Tenderness, enlargement, pain, nipple discharge, galactorrhea, fibrocystic breast changes, breast cancer.
Cardiovascular Deep and superficial venous thrombosis, pulmonary embolism, superficial thrombophlebitis, myocardial infarction, stroke, increase in blood pressure.
Gastrointestinal Nausea, vomiting, abdominal pain, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, changes in appetite, ischemic colitis.
Skin Chloasma or melasma that may persist when drug is discontinued, erythema multiforme, erythema nodosum, loss of scalp hair, hirsutism, pruritus, urticaria, rash, acne.
Eyes Retinal vascular thrombosis, intolerance of contact lenses.
Central Nervous System Headache, migraine, dizziness, mental depression, exacerbation of chorea, mood disturbances, anxiety, irritability, exacerbation of epilepsy, dementia, growth potentiation of benign meningioma.
Miscellaneous Increase or decrease in weight, arthralgia, glucose intolerance, edema, changes in libido, exacerbation of asthma, increased triglycerides, hypersensitivity.
Additional postmarketing adverse reactions have been reported in patients receiving other forms of hormone therapy.