Premarin

    Premarin (conjugated estrogens) Dosage and Side Effects

    This medication is a female hormone. It is used by women to help reduce symptoms of menopause (such as hot flashes, vaginal dryness). These symptoms are caused by the body making less estrogen. If you are using this medication to treat symptoms only in and around the vagina, products applied directly inside the vagina should be considered before medications that are taken by mouth, absorbed through the skin, or injected. Certain estrogen products may also be used by women after menopause to prevent bone loss (osteoporosis). However, there are other medications (such as raloxifene, bisphosphonates including alendronate) that are also effective in preventing bone loss and may be safer. These medications should be considered for use before estrogen treatment. Certain estrogen products may also be used by men and women to treat cancers (certain types of prostate cancer, breast cancer that has spread to other parts of the body) and by women who are not able to produce enough estrogen (for example, due to hypogonadism, primary ovarian failure).

    Warnings and Precautions

    Serious Warnings and Precautions

    The Women's Health Initiative (WHI) is a large clinical study that assessed the benefits and risks of oral combined estrogen plus progestin therapy and oral estrogen-alone therapy compared with placebo (a pill with no active ingredients) in postmenopausal women.

    The WHI trial indicated an increased risk of myocardial infarction (heart attack), stroke, breast cancer, pulmonary emboli (blood clots in the lungs) and deep vein thrombosis (blood clots in the large veins) in postmenopausal women taking oral combined estrogen plus progestin.

    The WHI trial indicated an increased risk of stroke and deep vein thrombosis in postmenopausal women with prior hysterectomy (surgical removal of the uterus) taking oral estrogen-alone.

    Therefore, you should highly consider the following:

    • There is an increased risk of developing invasive breast cancer, heart attack, stroke and blood clots in both lungs and large veins with the use of estrogen plus progestin therapy.
    • There is an increased risk of stroke and blood clots in the large veins with the use of estrogen-alone therapy.
    • Estrogens with or without progestins should not be used for the prevention of heart disease or stroke.
    • Estrogens with or without progestins should be used at the lowest effective dose and for the shortest period of timepossible. Regular medical follow-up is advised.

    Breast Cancer:

    The results of the WHI trial indicated an increased risk of breast cancer in postmenopausal women taking combined estrogen plus progestin compared to women taking placebo.

    The results of the WHI trial indicated no difference in the risk of breast cancer in post-menopausal women with prior hysterectomy taking estrogen-alone compared to women taking placebo.

    Estrogens should not be taken by women who have a personal history of breast cancer.

    In addition, women with a family history of breast cancer or women with a history of breast lumps, breast biopsies or abnormal mammograms (breast x-rays) should consult with their doctor before starting HRT.

    Women should have a mammogram before starting HRT and at regular intervals during treatment as recommended by their doctor.

    Regular breast examinations by a doctor and regular breast self-examination are recommended for all women. You should review technique for breast self-examination with your doctor.

    Overgrowth of the lining of the uterus and cancer of the uterus:

    The use of estrogen-alone therapy by post-menopausal women who still have a uterus increases the risk of developing endometrial hyperplasia (overgrowth of the lining of the uterus), which increases the risk of endometrial cancer (cancer of the lining of the uterus).

    If you still have your uterus, you should take a progestin medication (another hormone drug) regularly for a certain number of days of each month to reduce the risk of endometrial hyperplasia.

    You should discuss progestin therapy and risk factors for endometrial hyperplasia and endometrial carcinoma with you doctor. You should also report any unexpected or unusual vaginal bleeding to your doctor.

    If you have had your uterus removed, you are not at risk of developing endometrial hyperplasia or endometrial carcinoma. Progestin therapy is therefore not generally required in women who have had a hysterectomy.

    Ovarian Cancer:

    Some studies have indicated that taking estrogen-alone for 5 or more years may increase the risk of ovarian cancer. It is not yet known whether other kinds of hormone therapy increase the risk in the same way.

    Heart Disease and Stroke:

    The results of the WHI trial indicated an increased risk of stroke and coronary heart disease in post-menopausal women taking combined estrogen plus progestin compared to women taking placebo.

    The results of the WHI trial indicated an increased risk of stroke, but no difference in the risk of coronary heart disease in post-menopausal women with prior hysterectomy taking estrogen-alone compared to women taking placebo.

    Abnormal Blood Clotting:

    The results of the WHI trial indicated an increased risk of blood clots in the lungs and large veins in post-menopausal women taking combined estrogen plus progestin compared to women taking placebo.

    The results of the WHI trial indicated an increased risk of blood clots in the large veins, but no difference in the risk of blood clots in the lungs in post-menopausal women with prior hysterectomy taking estrogen-alone compared to women taking placebo.

    The risk of blood clots also increases with age, if you or a family member has had blood clots, if you smoke or if you are severely overweight. The risk of blood clots is also temporarily increased if you are immobilized for long periods of time and following major surgery. You should discuss risk factors for blood clots with your doctor since blood clots can be life-threatening or cause serious disability.

    Gallbladder Disease:

    The use of estrogens by postmenopausal women has been associated with an increased risk of gallbladder disease requiring surgery.

    Dementia:

    The Women's Health Initiative Memory Study (WHIMS) was a substudy of the WHI trial and indicated an increased risk of dementia (loss of memory and intellectual function) in post-menopausal women age 65 and over taking oral combined estrogen plus progestin compared to women taking placebo.

    The WHIMS indicated no difference in the risk of dementia in post-menopausal women age 65 and over with prior hysterectomy taking oral estrogen-alone compared to women taking placebo.

    BEFORE you use PREMARIN talk to your doctor or pharmacist if you:

    • have a history of allergy or intolerance to any medications or other substances
    • have a personal history of breast disease (including breast lumps) and/or breast biopsies, or a family history of breast cancer
    • have experienced any unusual or undiagnosed vaginal bleeding
    • have a history of uterine fibroids or endometriosis
    • have a history of liver disease, jaundice (yellowing of the eyes and/or skin) or itching related to estrogen use or during pregnancy
    • have a history of migraine headache
    • have a history of high blood pressure
    • have a personal or family history of blood clots, or a personal history of heart disease or stroke
    • have a history of kidney disease, asthma or epilepsy (seizures)
    • have a history of bone disease (this includes certain metabolic conditions or cancers that can affect blood levels of calcium and phosphorus)
    • have been diagnosed with diabetes
    • have been diagnosed with porphyria (a disease of blood pigment)
    • have been diagnosed with otosclerosis (hearing loss due to a problem with the bones in your ear)
    • have a history of high cholesterol or high triglycerides
    • are pregnant or may be pregnant. If pregnancy occurs while using PREMARIN contact your doctor immediately.
    • have had a hysterectomy (surgical removal of the uterus)
    • smoke
    • have been told that you have a condition called hereditary angioedema or if you have had episodes of rapid swelling of the hands, feet, face, lips, eyes, tongue, throat (airway blockage), or digestive tract
    • have been diagnosed with lupus
    • have a history of depression
    • have one of the following rare hereditary diseases:
      • Galactose intolerance
      • Lapp lactase deficiency
      • Glucose-galactose malabsorption
    • Because lactose is a nonmedicinal ingredient in PREMARIN.

    Other existing conditions you should discuss with your health professional include very low calcium levels, thyroid problems, fluid retention, gallbladder disease, depression, and breastfeeding. If you have upcoming surgery or prolonged bedrest, you should also discuss these.

    Clinical studies have not been conducted in the pediatric population. PREMARIN is not indicated for use in children.

    Side Effects

    Side effects may include:

    • Breast pain, leaking of milk from the nipple
    • Inflammation of the vagina, vaginal itching and/or discharge
    • Breakthrough bleeding, spotting, changes in menstrual flow, painful periods
    • Joint pain, leg pain
    • Hair loss
    • Changes in weight (increase or decrease)
    • Nausea, vomiting, bloating, abdominal pain, diarrhea
    • Dizziness
    • Headache (including migraine)
    • Changes in libido
    • Mood disturbances, irritability, problems sleeping
    • Rash, itching, hives, tender red nodules on the shins and legs, acne

    If any of these affects you severely, tell your doctor, nurse or pharmacist.

    Interactions with this medication

    As with most medicines, interactions with other drugs are possible. Tell your doctor, nurse, or pharmacist about all the medicines you take, including drugs prescribed by other doctors, vitamins, minerals, natural supplements, or alternative medicines.

    The following may interact with PREMARIN:

    • acetaminophen used to treat pain and fever
    • anticoagulant medications used to thin the blood
    • antidiabetic medications (eg. troglitazone)
    • antihypertensives (for high blood pressure)
    • antiviral medications (such as, ritonavir)
    • ascorbic acid (such as vitamin C)
    • atorvastatin, clofibric acid (medication to lower cholesterol)
    • carbamazepine, phenytoin, or phenobarbital (medications to prevent epilepsy or seizures)
    • cimetidine (medication generally used to treat stomach problems)
    • cyclosporin (medication used in suppressing the immune system)
    • dexamethasone, prednisolone (corticosteroids used to treat joint pain and swelling)
    • erythromycin, clarithromycin (antibiotic medications to treat infections)
    • grapefruit juice
    • herbal products containing St. John’s Wort
    • ketoconazole, itraconazole (medications to treat fungal infections)
    • morphine
    • oral contraceptives (birth control pills) and other medicines containing estrogen
    • rifampicin (medication used in the treatment of tuberculosis)
    • salicylic acid
    • temazepam (medication used to treat insomnia)
    • theophylline (medication used to treat breathing problems such as asthma)

    PREMARIN may interfere with laboratory testing.

    Proper Use of this medication

    Usual adult dose:

    You should follow the dosage regimen prescribed by your healthcare provider. PREMARIN may be taken without regard to meals. Tablets should be taken whole; do not divide, crush, chew, or dissolve tablets in mouth.

    Estrogens should be used at the lowest dose possible for your treatment only as long as needed. You and your healthcare provider should talk regularly (for example every 3 to 6 months) about the dose you are taking and whether you still need treatment with PREMARIN.

    Do not give PREMARIN to other people, even if they have the same symptoms you have. It may harm them.

    Overdose:

    If you think you have taken too much PREMARIN contact your doctor, nurse, pharmacist, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

    Overdosage with estrogens may cause nausea and vomiting, breast discomfort, fluid retention, bloating or vaginal bleeding may occur in women.

    Overdosage may result in a period of amenorrhea (lack of menses) of a variable length and may be followed by irregular menses for several cycles.

    Missed dose:

    If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time.

    Other related products

    The above information is an educational aid only. It is not intended as medical advice for individual conditions or treatments. Talk to your doctor, nurse or pharmacist before following any medical regimen to see if it is safe and effective for you.