PMS-Estradiol Valerate Inj 10mg/mL: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

• To treat amenorrhea (absence of periods – either periods never start or cease to occur).
• To treat estrogen deficiency syndromes (including menopause, following surgical removal of the ovaries and other conditions in which a woman’s ovaries do not produce enough estrogen naturally).

• To treat conditions of the vagina and external genitalia associated with low estrogen levels.

  If you use pms-Estradiol Valerate Injection only to treat symptoms of the vagina and external genitalia associated with low estrogen levels, talk with your healthcare provider about whether a vaginal (topical) treatment might be better for you.

• To treat inoperable progressing prostatic cancer in men.

pms-ESTRADIOL VALERATE INJECTION should not be used by women with intact uteri unless it is prescribed in association with a progestin.

pms-ESTRADIOL VALERATE INJECTION 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 after starting treatment. Your visit may include a blood pressure check, a breast exam and 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.

Close medical supervision is mandatory for men when pms-ESTRADIOL VALERATE INJECTION is used for the treatment of prostate cancer.

You should carefully discuss all of the risks and benefits of estrogen therapy with your physician. You and your physician should talk regularly about whether you still need treatment with estrogen. The dosage, frequency (how often) and duration of your treatment with pms-ESTRADIOL VALERATE INJECTION should be based on the reason for use, as carefully determined by your physician.

What it does:

Estradiol valerate is a form of estrogen. Estrogen is a female sex hormone produced by the ovaries. During and after menopause, and in certain other medical conditions, the amount of estrogen produced by the body is reduced. pms-ESTRADIOL VALERATE INJECTION is intended for use as estrogen-replacement therapy for women with symptoms related to menopause or for women with other conditions in which too little estrogen is produced naturally. It is also intended for use in men in the treatment of inoperable progressing cancer of the prostate.

When it should not be used:

pms-ESTRADIOL VALERATE INJECTION should not be used if you:

• If you have had an unusual allergic response to estrogen or to any of the ingredients in the tablet. For a complete listing see What the medicinal ingredient is and What the non-medicinal ingredients are section of the product monograph;
• In the presence of liver disease;
• If you have had or have cancer of the breast or uterus;
• If you have been diagnosed with overgrowth of the lining of the uterus;
• If you have abnormal vaginal bleeding;

• If you are pregnant or think you may be pregnant;

• If you have had or have a problem with abnormal blood clots forming in your blood vessels. This may cause painful inflammation of the veins (thrombophlebitis) or blockage of a blood vessel in the legs (deep vein thrombosis), lungs (pulmonary embolism) or other organs;
• Have had partial or complete loss of vision due to blood vessel disease of the eye;
• If you experience migraine headaches;
• If you have had or have heart disease, a stroke or heart attack;
• If you are breastfeeding.

What the medicinal ingredient is:

Estradiol Valerate

What the non-medicinal ingredients are:

Chlorobutanol (preservative) and Sesame Oil

What dosage forms it comes in:

Vials of 10 mL

Each mL contains 10 mg Estradiol Valerate

For injection

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 post-menopausal 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-examinations 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 your 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

In some studies, the use of estrogen-alone and estrogen plus progestin therapies for 5 or more years has been associated with an increased risk of ovarian cancer.

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 pms-Estradiol Valerate Injection 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 or liver tumours, jaundice (yellowing of the eyes and/or skin) or itching related to estrogen use or during pregnancy
• have a history of migraine headaches
• 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
• are breast feeding
• have a history of endometrial hyperplasia (overgrowth of the lining of the uterus)
• have had partial or complete loss of vision due to blood vessel disease of the eye
• have a history of a psychiatric condition (including depression)
• 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 been diagnosed with hearing loss due to otosclerosis

INTERACTIONS WITH THIS MEDICATION

INTERACTIONS WITH THIS MEDICATION

Some medications can interfere with the action of pms-ESTRADIOL VALERATE INJECTION and pms-ESTRADIOL VALERATE INJECTION can interfere with the action of other medications. When you are taking pms-ESTRADIOL VALERATE INJECTION it is important to let your physician know if you are taking any other medications, including prescription medications, over-the-counter medications, vitamins and herbal products.

It is especially important to let your doctor know if you are taking any of the following:

• anticoagulant (anti-blood clotting) medications
• diabetic medications
• blood pressure medications
• barbiturates, hydantoins, carbamazepine, meprobamates, phenylbutazone, rifampicin
• herbal products such as St. John’s Wort

Some drug interactions are also suspected with the following medications: phenobarbital, phenytoin, ascorbic acid, acetaminophen, cyclosporine, prednisolone, theophylline, temazepam, salicylic acid, morphine, clofibric acid and atorvastatin.

PROPER USE OF THIS MEDICATION

Usual dose:

pms-ESTRADIOL VALERATE INJECTION is administered by intramuscular injection. pms-ESTRADIOL VALERATE INJECTION should only be used under a physician’s supervision. The dosage, frequency and duration of your treatment with pms-ESTRADIOL VALERATE INJECTION should be based on the reason for use, as carefully determined by your physician.

You and your physician should talk regularly about whether you still need treatment with estrogen.

For women:

Cyclic Therapy Schedule (28-day cycle; repeated every 4 weeks)

Day 1 of each cycle: 20 mg pms-ESTRADIOL VALERATE INJECTION

2 weeks after Day 1: 5 mg pms-ESTRADIOL VALEREATE INJECTION

4 weeks after Day 1: This is Day 1 of next cycle.

Amenorrhea primary and secondary (the suppression or unusual absence of menstruation)

See Cyclic Therapy Schedule. Repeat every 4 weeks. Stop after 4 cycles.

Deficiency Syndroms (castration, primary ovarian failure, menopause)

See Cyclic Therapy Schedule: Start therapy any time. Repeat every 4 weeks. Stop after 4 cycles.

Local Manifestations (signs and indications) of Estrogen Deficiency (senile vaginitis, pruritus vulvae)

See Cyclic Therapy Schedule: Start therapy any time. Repeat every 4 weeks. Stop after 4 cycles.

For men:

(For palliation only – reduce the intensity only) inoperable progressing prostatic carcinoma (prostate cancer)

30 mg or more every 1 to 2 weeks. Schedule and duration of treatment should be determined by the treating physician. Close medical supervision is mandatory.

Overdose:

In case of overdosage or ingestion of pms-Estradiol Valerate Injection, contact your physician or local poison control centre.

Over dosage with pms-ESTRADIOL VALERATE INJECTION may cause nausea, vomiting, abdominal cramps, headache, dizziness, breast discomfort, vaginal bleeding, water retention, bloating and general malaise (general feeling of discomfort or feeling unwell).

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

All medicines can have side effects. Sometimes they are serious, most of the time they are not.

Check with your doctor as soon as possible if any of the following occur: swelling ankles, fingers or abdomen due to fluid retention (oedema) persisting for more than 6 weeks, change in weight, change in your sex drive, change in vaginal discharge (may be a sign that too much estrogen is taken), vaginal thrush (vaginal fungal infection with severe itching, vaginal discharge), hair loss, excessive hairiness, spotty darkening of the skin, particularly on the face or abdomen (chloasma), rash, itching, acne, dryness or discoloration of the skin, purple skin patches, contact lens discomfort. It may be irritating at the site of injection.

In males, the most common side effects are gynecomastia (breast enlargement) and soreness of breast, reduced potency and feminization. Hypercalcemia may develop.

For management of a suspected drug overdose, contact your regional Poison Control Center.

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 the vials between 15°C and 30°C. Low temperatures may result in separation of some crystalline material, which dissolves readily on rewarming. pms-ESTRADIOL VALERATE INJECTION should not be used after the expiry date shown on the package label.

This medicine has been prescribed for your current medical problem only. Do not give it to other people.

Remember to take any unused medicine back to your pharmacist.

Keep out of reach of children.

REPORTING SUSPECTED SIDE EFFECTS

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: June 29, 2009