Prempro 0.3mg/1.5mg Tabs28's
WARNING: Do not use this drug to prevent heart disease or dementia. A study of women taking an estrogen with a progestin showed a raised chance of heart attack, stroke, blood clot, breast cancer, and dementia. The chance of stroke, blood clot, and dementia was also raised when the estrogen was taken alone. Not all products and doses were studied. It is not known if the same effects may happen with this drug.The chance of endometrial cancer may be raised with the use of estrogen alone in patients with a uterus. Use of a progestin along with estrogen may lower the risk. Call your doctor right away if you have unexplained or long-lasting vaginal bleeding.Use this drug for the shortest time needed at the lowest useful dose. Your doctor will talk with you on a regular basis to see if you need to keep taking this drug. @ COMMON USES: It is used to treat symptoms of low estrogen levels or prevent soft, brittle bones (osteoporosis) after menopause. If you have been given this drug for some other reason, talk with your doctor for more information.
Drug Class
Hormone Replacement Therapy (HRT)
Pharmacologic Class
Estrogen Receptor Agonist; Progesterone Receptor Agonist
Pregnancy Category
Category X
FDA Approved
Jan 1995
DEA Schedule
Not Controlled
Overview
What is this medicine?
Prempro is a medication containing two female hormones, estrogen and progestin. It is used by postmenopausal women to relieve symptoms like hot flashes and to help prevent bone thinning (osteoporosis). The progestin helps protect the uterus from potential overgrowth caused by estrogen.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, it's essential to take it as directed by your doctor. Carefully read all the information provided with your prescription and follow the instructions closely. Establish a routine by taking your medication at the same time every day. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding bathrooms. Keep all medications in a secure place, out of reach of children and pets. Properly dispose of unused or expired medications. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs available in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses.
To get the most benefit from your medication, it's essential to take it as directed by your doctor. Carefully read all the information provided with your prescription and follow the instructions closely. Establish a routine by taking your medication at the same time every day. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding bathrooms. Keep all medications in a secure place, out of reach of children and pets. Properly dispose of unused or expired medications. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also want to check if there are drug take-back programs available in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses.
Lifestyle & Tips
- Maintain a healthy diet and engage in regular weight-bearing exercise.
- Quit smoking, as smoking increases the risk of serious cardiovascular events.
- Limit alcohol intake.
- Perform regular breast self-exams and attend scheduled mammograms and gynecological exams.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
One tablet (0.3 mg conjugated estrogens / 1.5 mg medroxyprogesterone acetate) orally once daily
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, use with caution.
Moderate:
No specific dose adjustment recommended, use with caution.
Severe:
No specific dose adjustment recommended, use with caution.
Dialysis:
Not available; use with caution.
Hepatic Impairment:
Mild:
Use with caution.
Moderate:
Use with caution.
Severe:
Contraindicated in severe hepatic impairment.
Pharmacology
Mechanism of Action
Conjugated Estrogens (Equine) bind to estrogen receptors (ERΞ± and ERΞ²) in target tissues, forming a complex that translocates to the nucleus, binds to estrogen response elements (EREs) on DNA, and regulates gene transcription. This leads to physiological effects such as reduction of vasomotor symptoms and maintenance of bone density. Medroxyprogesterone Acetate binds to progesterone receptors (PR) in target tissues, inducing secretory changes in the endometrium and preventing endometrial hyperplasia and carcinoma that can be caused by unopposed estrogen therapy.
Pharmacokinetics
Absorption:
Bioavailability:
Conjugated Estrogens: Variable (e.g., estrone ~30-50%); Medroxyprogesterone Acetate: High (~80-100%)
Tmax:
Conjugated Estrogens (Estrone): 4-10 hours; Medroxyprogesterone Acetate: 2-4 hours
FoodEffect:
Minimal or not clinically significant
Distribution:
Vd:
Conjugated Estrogens (Estrone): ~10 L/kg; Medroxyprogesterone Acetate: ~20 L/kg
ProteinBinding:
Conjugated Estrogens: Highly bound to SHBG and albumin; Medroxyprogesterone Acetate: ~90% bound to albumin
CnssPenetration:
Yes
Elimination:
HalfLife:
Conjugated Estrogens (Estrone): 10-16 hours; Medroxyprogesterone Acetate: 12-17 hours
Clearance:
Hepatic
ExcretionRoute:
Primarily renal (as glucuronide and sulfate conjugates), some biliary/fecal
Unchanged:
Minimal
Pharmacodynamics
OnsetOfAction:
Symptomatic relief (vasomotor) within weeks; bone effects are slower.
PeakEffect:
Varies by therapeutic effect.
DurationOfAction:
Maintained with daily dosing.
Safety & Warnings
BLACK BOX WARNING
Cardiovascular Disorders: Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women receiving daily conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA).
Dementia: The WHI Memory Study (WHIMS) reported an increased risk of probable dementia in postmenopausal women 65 years of age or older receiving CEE plus MPA.
Malignant Neoplasms: The WHI study reported an increased risk of invasive breast cancer with CEE plus MPA. Estrogen-alone therapy increases the risk of endometrial cancer.
Dementia: The WHI Memory Study (WHIMS) reported an increased risk of probable dementia in postmenopausal women 65 years of age or older receiving CEE plus MPA.
Malignant Neoplasms: The WHI study reported an increased risk of invasive breast cancer with CEE plus MPA. Estrogen-alone therapy increases the risk of endometrial cancer.
Side Effects
Serious Side Effects: Seek Medical Help Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or severe upset stomach or vomiting
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe upset stomach or vomiting
Weakness on one side of the body, trouble speaking or thinking, changes in balance, drooping on one side of the face, or blurred vision
Changes in eyesight or loss of eyesight, bulging eyes, or changes in how contact lenses feel
Breast lump, breast pain or soreness, or nipple discharge
Pelvic pain
Vaginal itching or discharge, or abnormal vaginal bleeding
Depression or other mood changes
Memory problems or loss
This medication may cause fluid retention, leading to swelling or weight gain. If you experience swelling, weight gain, or trouble breathing, inform your doctor.
Blood Clots and High Calcium Levels
Seek medical help immediately if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, changes in color, or pain in a leg or arm, or trouble speaking or swallowing
Signs of high calcium levels: weakness, confusion, fatigue, headache, upset stomach or vomiting, constipation, or bone pain (especially in people with cancer)
Other Side Effects
Most people do not experience severe side effects, and some may not have any side effects at all. However, if you notice any of the following side effects, contact your doctor or seek medical attention if they bother you or persist:
Fatigue or weakness
Back pain
Headache
Upset stomach or vomiting
Gas
Stomach pain or cramps
Bloating
Enlarged or tender breasts
* Hair loss
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or severe upset stomach or vomiting
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe upset stomach or vomiting
Weakness on one side of the body, trouble speaking or thinking, changes in balance, drooping on one side of the face, or blurred vision
Changes in eyesight or loss of eyesight, bulging eyes, or changes in how contact lenses feel
Breast lump, breast pain or soreness, or nipple discharge
Pelvic pain
Vaginal itching or discharge, or abnormal vaginal bleeding
Depression or other mood changes
Memory problems or loss
This medication may cause fluid retention, leading to swelling or weight gain. If you experience swelling, weight gain, or trouble breathing, inform your doctor.
Blood Clots and High Calcium Levels
Seek medical help immediately if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, changes in color, or pain in a leg or arm, or trouble speaking or swallowing
Signs of high calcium levels: weakness, confusion, fatigue, headache, upset stomach or vomiting, constipation, or bone pain (especially in people with cancer)
Other Side Effects
Most people do not experience severe side effects, and some may not have any side effects at all. However, if you notice any of the following side effects, contact your doctor or seek medical attention if they bother you or persist:
Fatigue or weakness
Back pain
Headache
Upset stomach or vomiting
Gas
Stomach pain or cramps
Bloating
Enlarged or tender breasts
* Hair loss
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Sudden chest pain, shortness of breath, or coughing up blood (signs of blood clot in lungs)
- Sudden severe headache, dizziness, vision changes, or weakness/numbness on one side of the body (signs of stroke)
- Chest pain or pressure, pain spreading to arms, back, neck, jaw, or stomach (signs of heart attack)
- Pain, swelling, or redness in one leg (signs of deep vein thrombosis)
- New breast lump or changes in breast tissue
- Unusual vaginal bleeding or spotting after menopause
- Yellowing of skin or eyes (jaundice), severe abdominal pain
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
A history of certain health conditions, including:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack or stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Previous removal of the uterus (hysterectomy)
Pregnancy or suspected pregnancy. Do not take this medication if you are pregnant, as it may cause harm to the fetus.
Additionally, to ensure safe treatment, it is crucial to:
Inform your doctor and pharmacist about all medications you are currently taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss all your health problems with your doctor to determine if it is safe to take this medication.
Never start, stop, or change the dose of any medication without first consulting your doctor to avoid potential interactions or adverse effects.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
A history of certain health conditions, including:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack or stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Previous removal of the uterus (hysterectomy)
Pregnancy or suspected pregnancy. Do not take this medication if you are pregnant, as it may cause harm to the fetus.
Additionally, to ensure safe treatment, it is crucial to:
Inform your doctor and pharmacist about all medications you are currently taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Discuss all your health problems with your doctor to determine if it is safe to take this medication.
Never start, stop, or change the dose of any medication without first consulting your doctor to avoid potential interactions or adverse effects.
Precautions & Cautions
Important Warnings and Cautions
Before taking this medication, inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are using this drug. Your doctor may instruct you to stop taking this medication before certain surgical procedures, and will advise you when to resume taking it after the surgery or procedure.
If you have diabetes (high blood sugar), it is crucial to closely monitor your blood sugar levels. Additionally, be aware that this medication may cause high blood pressure, so follow your doctor's instructions for regular blood pressure checks.
High triglyceride levels have been associated with this medication. If you have a history of high triglyceride levels, notify your doctor. Regular blood work and bone density tests are also necessary, as directed by your doctor.
To ensure your overall health, maintain a regular schedule of breast exams and gynecology check-ups, and perform breast self-exams as instructed by your doctor. This medication may affect certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug.
To minimize potential risks, limit your alcohol consumption and avoid smoking, as it increases the risk of heart disease. Discuss your smoking habits with your doctor. If you regularly consume grapefruit juice or eat grapefruit, consult with your doctor.
If you anticipate being immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged immobility may increase the risk of blood clots.
This medication may cause dark skin patches on your face, so avoid exposure to sunlight, sunlamps, and tanning beds. Use sunscreen and protective clothing and eyewear to shield yourself from the sun.
The risk of certain side effects, such as heart attack, stroke, breast cancer, ovarian cancer, and others, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects. If you are breastfeeding, consult with your doctor to discuss potential risks to your baby.
Osteoporosis (Soft, Brittle Bones)
To maximize the effectiveness of this medication, use it in conjunction with calcium and vitamin D supplements, and engage in weight-bearing exercises, such as walking or physical therapy, as directed by your doctor. Adhere to the diet and exercise plan recommended by your doctor.
Before taking this medication, inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are using this drug. Your doctor may instruct you to stop taking this medication before certain surgical procedures, and will advise you when to resume taking it after the surgery or procedure.
If you have diabetes (high blood sugar), it is crucial to closely monitor your blood sugar levels. Additionally, be aware that this medication may cause high blood pressure, so follow your doctor's instructions for regular blood pressure checks.
High triglyceride levels have been associated with this medication. If you have a history of high triglyceride levels, notify your doctor. Regular blood work and bone density tests are also necessary, as directed by your doctor.
To ensure your overall health, maintain a regular schedule of breast exams and gynecology check-ups, and perform breast self-exams as instructed by your doctor. This medication may affect certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug.
To minimize potential risks, limit your alcohol consumption and avoid smoking, as it increases the risk of heart disease. Discuss your smoking habits with your doctor. If you regularly consume grapefruit juice or eat grapefruit, consult with your doctor.
If you anticipate being immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged immobility may increase the risk of blood clots.
This medication may cause dark skin patches on your face, so avoid exposure to sunlight, sunlamps, and tanning beds. Use sunscreen and protective clothing and eyewear to shield yourself from the sun.
The risk of certain side effects, such as heart attack, stroke, breast cancer, ovarian cancer, and others, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects. If you are breastfeeding, consult with your doctor to discuss potential risks to your baby.
Osteoporosis (Soft, Brittle Bones)
To maximize the effectiveness of this medication, use it in conjunction with calcium and vitamin D supplements, and engage in weight-bearing exercises, such as walking or physical therapy, as directed by your doctor. Adhere to the diet and exercise plan recommended by your doctor.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Breast tenderness
- Abdominal pain
- Drowsiness/fatigue
- Withdrawal bleeding (in women)
What to Do:
No specific antidote. Treatment is symptomatic and supportive. Contact a poison control center immediately (e.g., 1-800-222-1222).
Drug Interactions
Major Interactions
- CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenobarbital, St. John's Wort): Decreased estrogen/progestin levels, reduced efficacy.
- CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin, ritonavir, grapefruit juice): Increased estrogen/progestin levels, potential for increased adverse effects.
- Thyroid Hormone Replacement (e.g., levothyroxine): Estrogens can increase thyroid-binding globulin (TBG), potentially increasing thyroid hormone dose requirement.
- Anticoagulants (e.g., warfarin): Estrogens can affect coagulation factors, requiring close INR monitoring.
Moderate Interactions
- Corticosteroids: Estrogens can decrease corticosteroid clearance, increasing their effects.
- Hypoglycemic agents: Estrogens may affect glucose tolerance, requiring adjustment of antidiabetic therapy.
Monitoring
Baseline Monitoring
Complete medical history and physical examination (including blood pressure, breast exam, pelvic exam)
Rationale: To assess overall health, identify contraindications, and establish baseline.
Timing: Prior to initiation of therapy.
Mammogram
Rationale: To screen for breast cancer.
Timing: Prior to initiation and periodically thereafter.
Lipid panel
Rationale: Estrogens can affect lipid profiles.
Timing: Prior to initiation.
Liver function tests (LFTs)
Rationale: Drug is hepatically metabolized; to assess baseline liver function.
Timing: Prior to initiation.
Routine Monitoring
Annual physical examination (including blood pressure, breast exam, pelvic exam)
Frequency: Annually
Target: Normal
Action Threshold: Abnormal findings require further investigation.
Mammogram
Frequency: Annually or as clinically indicated.
Target: Normal
Action Threshold: Abnormal findings require further investigation.
Blood pressure
Frequency: Regularly
Target: Normal
Action Threshold: Elevated readings require management.
Symptoms of adverse events (e.g., VTE, stroke, MI, breast cancer, endometrial cancer)
Frequency: Ongoing
Target: Absence of symptoms
Action Threshold: Presence of symptoms requires immediate medical evaluation.
Symptom Monitoring
- Abnormal vaginal bleeding (especially postmenopausal)
- Breast lumps or changes
- Chest pain, shortness of breath, sudden severe headache, vision changes (signs of VTE/stroke/MI)
- Leg pain or swelling (signs of DVT)
- Jaundice or severe abdominal pain (signs of liver issues)
Special Patient Groups
Pregnancy
Contraindicated. Prempro should not be used during pregnancy.
Trimester-Specific Risks:
First Trimester:
Not applicable, contraindicated. Exposure during pregnancy has been associated with an increased risk of birth defects in the fetus.
Second Trimester:
Not applicable, contraindicated.
Third Trimester:
Not applicable, contraindicated.
Lactation
Not recommended. Estrogens and progestins are excreted in breast milk and may decrease the quantity and quality of breast milk.
Infant Risk:
Potential for adverse effects on the infant (e.g., feminization of male infants, effects on development).
Pediatric Use
Not indicated for use in pediatric patients. Safety and effectiveness have not been established.
Geriatric Use
Use with caution, especially in women 65 years or older, due to increased risk of probable dementia (WHIMS study). Use the lowest effective dose for the shortest duration consistent with treatment goals and risks.
Clinical Information
Clinical Pearls
- Prempro is indicated for postmenopausal women with an intact uterus to prevent endometrial hyperplasia, in addition to treating vasomotor symptoms and preventing osteoporosis.
- Always use the lowest effective dose for the shortest duration consistent with treatment goals and risks.
- Thoroughly counsel patients on the Black Box Warnings regarding cardiovascular events, stroke, and certain cancers.
- Not indicated for the prevention of cardiovascular disease or dementia.
- Regular monitoring for cardiovascular risk factors, breast cancer, and endometrial cancer is crucial.
- Discontinue therapy if pregnancy is suspected.
Alternative Therapies
- For vasomotor symptoms: SSRIs/SNRIs (e.g., paroxetine, venlafaxine), gabapentin, clonidine, non-hormonal therapies.
- For osteoporosis prevention: Bisphosphonates, SERMs (e.g., raloxifene), denosumab, teriparatide, calcium and vitamin D supplementation.
- For genitourinary symptoms: Local vaginal estrogen preparations.
Cost & Coverage
Average Cost:
Variable, typically $150-$300+ per 28 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (depending on insurance plan and generic availability)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.