PMS-Conjugated Estrogens C.S.D.: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

• To relieve menopausal and post-menopausal symptoms (vasomotor symptoms like hot flushes and night sweats).
• To prevent osteoporosis caused by low estrogen levels associated with menopause. Osteoporosis is a thinning of the bones that makes them weaker and easier to break.
• To treat certain types of abnormal uterine bleeding due to hormonal imbalance when your doctor has found no serious cause of the bleeding.
• To treat vulva and vaginal atrophy associated with menopause (itching, burning, dryness in or around the vagina, difficulty or burning on urination).

pms-Conjugated Estrogens CSD tablets for the prevention of osteoporosis is recommended only for women who are at risk of developing this condition. Talk to your doctor about whether a different treatment or medicine without estrogens might be better for you.

Adequate diet, calcium and vitamin D intake, cessation of smoking as well as regular weight-bearing exercise should be discussed with your doctor or pharmacist in addition to taking pms-

Conjugated Estrogens CSD.

If you use pms-Conjugated Estrogens CSD tablets only to treat symptoms of vulvar and vaginal atrophy associated with menopause, talk with your healthcare provider about whether a vaginal (topical) treatment might be better for you.

pms-Conjugated Estrogens CSD Tablets should not be used by women with intact uteri unless it is prescribed in association with a progestin.

pms-Conjugated Estrogens CSD should be used only under the supervision of a doctor, with regular follow-up at least once a year to identify side effects associated with its use.

Your first follow-up visit should be within 3 to 6 months of starting treatment. Your visit may include a blood pressure check, a breast exam, a Pap smear and pelvic exam. You should have a mammogram before starting treatment and at regular intervals as recommended by your doctor. Your doctor may recommend some blood tests.

You should carefully discuss the risks and benefits of hormone replacement therapy (HRT) with your doctor. You should regularly talk with your doctor about whether you still need treatment with HRT.

What it does:

When taking pms-Conjugated Estrogens CSD women are using a hormone, estrogen (i.e. conjugated equine estrogen tablets). pms-Conjugated Estrogens CSD replaces estrogen in your body, which naturally decreases at menopause.

Estrogens are female hormones that are produced by a woman’s ovaries and are necessary for normal sexual development and the regulation of menstrual periods during the childbearing years.

When a woman is between the ages of 45 and 55, the ovaries normally stop making estrogens. This leads to a drop in body estrogen levels and marks the beginning of menopause (the end of monthly menstrual periods). A sudden drop in estrogen levels also occurs if both ovaries are removed during an operation before natural menopause takes place. This is referred to as surgical menopause.

When the estrogen levels begin dropping, some women develop very uncomfortable symptoms, such as feelings of warmth in the face, neck, and chest, or sudden intense episodes of heat and sweating (“hot flashes”). In some women the symptoms are mild; in others they can be severe. These symptoms may last only a few months or longer. Taking pms-Conjugated Estrogens CSD can alleviate these symptoms. If you are not taking estrogen for other reasons, such as the prevention of osteoporosis, you should take pms-Conjugated Estrogens CSD only as long as you need it for relief from your menopausal symptoms.

After menopause, some women develop osteoporosis. This is a thinning of the bones that makes them weaker and allows them to break more easily, often leading to fractures of the vertebrae, hip and wrist bones.

Using pms-Conjugated Estrogens CSD Tablets, in addition to taking adequate calcium (1000 milligrams to 1500 milligrams per day) and vitamin D, and regular weight-bearing exercise, slows down bone thinning and may prevent bones from breaking.

When it should not be used:

Before using pms-Conjugated Estrogens CSD be sure to tell your doctor if you have any of the following medical problems, as pms-Conjugated Estrogens CSD should not be used under these conditions:

• Known, suspected, or past history of breast cancer.
• Known or suspected hormone-dependent cancer.
• Estrogens may increase the chances of getting certain types of cancers, including cancer of the breast or uterus. If you have or had cancer, talk with your healthcare provider about whether you should take pms-Conjugated Estrogens CSD.
• Unexpected or unusual vaginal bleeding
• Have (or have had) blood clot disorders, including blood clots in the legs or lungs or thrombophlebitis (inflammation of the veins).
• Serious liver disease
• Active or past history of heart disease, heart attacks or stroke.

• If you are allergic to pms-Conjugated Estrogens CSD or any of its ingredients, or have had any unusual reactions to its ingredients (see What the medicinal ingredients are and What the nonmedicinal ingredients are).

  • If you are pregnant or suspect you may be pregnant. Since pregnancy may be possible early in the pre-menopause while you are still having spontaneous periods, the use of non-hormonal birth control should be discussed with your physician at this time. If you accidentally take estrogen during pregnancy, there is a small risk of your unborn child having birth defects.

  • If you have partially or completely lost vision due to blood vessel disease of the eye.
  • If you have overgrowth of the lining of the uterus.

What the medicinal ingredient is:

Conjugated estrogens

What the nonmedicinal ingredients are:

• 0.3 mg (green) also contain: titanium dioxide and Opalux green AS-3385.
• 0.625 mg (red) also contains: Opalux maroon AS-3911.
• 0.9 mg (pink) also contains: titanium dioxide and Opalux pink AS-1481.
• 1.25 mg (yellow) also contains: titanium dioxide and Opalux yellow AS-2110.

What dosage forms it comes in:

Tablets: 0.3 mg (green), 0.625 mg (red), 0.9 mg (pink) and 1.25 mg (yellow)

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 time possible. 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.

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.

Galbladder 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 pms-Conjugated Estrogens CSD 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, liver tumors, or 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 a history of high cholesterol or high triglycerides
  • are pregnant or may be pregnant
  • have had a hysterectomy (surgical removal of the uterus)
  • smoke

Other existing conditions you should discuss with your health professional include lupus, 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.

INTERACTIONS WITH THIS MEDICATION

INTERACTIONS WITH THIS MEDICATION Tell your doctor or pharmacist if you are taking any other medications, including prescription medications, over-the-counter medications, vitamins or herbal products (such as St. John’s wort). Some medications (such as medications for high blood pressure, diabetes, blood clots, sleeping, anxiety, seizures, pain-relief and tuberculosis) may affect how pms-Conjugated Estrogens CSD works. pms-Conjugated Estrogens CSD may also affect how other medicines work.

PROPER USE OF THIS MEDICATION

Usual dose:

You should follow the dosage regimen prescribed by your healthcare provider.

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 pms-Conjugated Estrogens CSD.

Do not give pms-Conjugated Estrogens CSD to other people, even if they have the same symptoms you have. It may harm them.

Overdose:

Contact your physician or local Poison Control Center in case of accidental ingestion of high doses of pms-Conjugated Estrogens CSD.

Overdosage with estrogens may cause nausea and vomiting, breast discomfort, fluid retention, bloating or vaginal bleeding may occur in women. There is no specific antidote and further treatment if necessary should be symptomatic.

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. No cases of overdosage in male patients have been reported.

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.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Possible side effects include:

Common Breast pain;

≥ 1% and < 10% Breakthrough bleeding;

spotting; joint pain; hair loss, change in weight (increase or decrease)

Uncommon Change in menstrual flow; ≥ 0.1% and <1% nausea; bloating; abdominal pain; dizziness; headache (including migraine); changes in libido; mood disturbances; rash; itching; inflammation of the vagina

Rare A spontaneous flow of milk ≥ 0.01% and < 0.1% from the nipple; painful periods; vomiting;

irritability; hives; worsening of asthma

Very Rare < 0.01% Tender red nodules on the shins and legs; increase in blood pressure.

This is not a complete list of side effects. If you have any unexpected effects while taking this drug, contact your doctor or pharmacist.

HOW TO STORE IT

Store pms-Conjugated Estrogens CSD at 15º C and 30º C (room temperature).

Keep out of reach of children.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

• Report online at

  www.healthcanada.gc.ca/medeffect

• Call toll-free at 1-866-234-2345

• Complete a Canada Vigilance Reporting Form and:

  -Fax toll-free to 1-866-678-6789, or

  • Mail to: Canada Vigilance Program Health Canada

    Postal Locator 0701C Ottawa, ON K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect^TM Canada Web site at www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be obtained by contacting Pharmascience Inc., at 1-888-550-6060.

Last revised: August 28, 2009