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Brand Name
Premarin Vaginal Cream
Common Name
conjugated estrogens vaginal cream
How does this medication work? What will it do for me?

Conjugated estrogens vaginal cream belongs to the class of medications known as estrogen replacement therapy. Conjugated estrogens vaginal cream is used to manage vaginal and urinary menopausal symptoms such as itching, burning, dryness in or around the vagina, difficulty or burning during urination, and painful sexual intercourse.

Estrogen is a hormone that is produced by the ovaries. Once menopause is reached, the ovaries produce less estrogen and symptoms of menopause can occur. Conjugated estrogens vaginal cream works by providing locally-acting estrogen.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are being given this medication, speak to your doctor. Do not stop using this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to use this medication if their doctor has not prescribed it.

How should I use this medication?

The dose of this medication is individualized to the person using the cream. The lowest dose that will treat the symptoms should be used.

The recommended adult dose of conjugated estrogens vaginal cream ranges from 0.5 g to 2 g of cream daily. Depending on how severe the symptoms are, the cream may be inserted into the vagina using the applicator provided, applied to the outside areas of the vagina, or both. The cream should be used on a regular cycle, with 3 weeks of use followed by 1 week off.

To use the applicator, remove the cap of the tube of cream and screw the nozzle end of the applicator onto the tube. Squeeze the cream until it reaches the mark that indicates the dose prescribed by your doctor. Unscrew the applicator from the tube, place it into the opening of the vagina, and gently press the plunger to release the medication. Clean the applicator by pulling the plunger out from the barrel and washing it with mild soap and warm water.

People who also take oral conjugated estrogens tablets may need to have the dose of their tablets adjusted when they start using the cream. Those who have not had their uterus removed should also take a progestin (such as medroxyprogesterone acetate). Talk with your doctor or pharmacist about which dosing schedule would work best for you if you are taking a progestin.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are using the medication without consulting your doctor.

It is important to use this medication exactly as prescribed by your doctor. If you miss a dose of this medication, use it as soon as you remember it. If it is almost time for your next dose, skip the missed dose and carry on with your regular dosing schedule. Do not administer a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, and keep it out of the reach of children.

What form(s) does this medication come in?

Each g of white, vaginal cream contains 0.625 mg of conjugated estrogens CSD. Nonmedicinal ingredients: cetyl alcohol, cetyl esters wax, glycerin, glyceryl monostearate, methyl stearate, mineral oil, phenylethyl alcohol, propyl glycol monostearate, sodium lauryl sulfate, water purified, and white wax. Gluten-, paraben-, sugar-, sulfite-, and tartrazine-free.

Who should NOT take this medication?

Do not use conjugated estrogens vaginal cream if you:

  • are allergic to conjugated estrogen or any ingredients of the medication
  • are or may be pregnant
  • have a history of known or suspected estrogen-dependent tumours such as breast or uterine cancer
  • have abnormal liver test results caused by liver disease or liver problems
  • have endometrial hyperplasia
  • have undiagnosed abnormal vaginal bleeding
  • have active thrombophlebitis, thrombosis, or thromboembolic disorders (blood clotting problems)
  • have or have had stroke, heart attack, or coronary heart disease
  • have migraine with or without aura
  • have certain hereditary blood clotting disorders (e.g., protein C, protein S, or antithrombin deficiency)
  • have had partial or complete loss of vision due to blood vessel-related eye disease
What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent. The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • abdominal cramps, bloating
  • abdominal or back pain
  • acne
  • breast tenderness
  • changed interest in sexual activity
  • hair loss
  • dizziness
  • headache
  • joint pain
  • leg pain
  • nausea
  • swelling of the hands or feet
  • vomiting

Although most of these side effects listed below don't happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • breast lumps
  • breast pain
  • fast, pounding heartbeat
  • high blood pressure (e.g., headaches, dizziness, vision problems, shortness of breath)
  • itching of the vagina or genitals
  • stinging or redness in the genital area
  • rash, hives
  • signs of a blood clot in the arm or leg (tenderness, pain, swelling, warmth, or redness in the arm or leg) or lungs (difficulty breathing, sharp chest pain that is worse when breathing in, coughing, coughing up blood, sweating, or passing out)
  • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
  • signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
  • symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odour)
  • symptoms of gallbladder problems (e.g., severe, dull pain in the upper right part of the abdomen that comes and goes, nausea; vomiting; intolerance of fatty or greasy foods)
  • thick, white vaginal discharge without odour or with a mild odour
  • unusual or unexpected uterine bleeding or spotting

Stop taking the medication and seek immediate medical attention if any of the following occur:

  • migraine
  • severe leg pain or numbness affecting any part of the body
  • shortness of breath
  • sudden vision changes
  • tightness of the chest
  • signs of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
  • signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
  • signs of stroke (e.g., sudden or severe headache; sudden loss of coordination; vision changes; sudden slurring of speech; or unexplained weakness, numbness, or pain in arm or leg)
  • worsening asthma symptoms (e.g., wheezing, coughing, shortness of breath, difficulty breathing)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Note the following important information about estrogen replacement therapy: The Women's Health Initiative (WHI) study results indicated an increased risk of heart attack, stroke, breast cancer, blood clots in the lungs, and blood clots in the leg veins in postmenopausal people during 5 years of treatment with 0.625 mg conjugated equine estrogens and 2.5 mg medroxyprogesterone compared to people receiving sugar tablets. Other combinations of estrogen and progestins were not studied. However, until additional data are available, the risks should be assumed to be similar for other hormone replacement products. Therefore,

  • estrogen with or without progestins should be used at the lowest dose that relieves your menopausal symptoms for the shortest time period possible, as directed by your doctor.
  • estrogen with or without progestins should not be used to prevent heart disease, heart attacks, or strokes.

Blood clotting disorders: Estrogen with or without progestins is associated with an increased risk of blood clots in the lungs and legs. This risk also increases with age, a personal or family history of blood clots, smoking, and obesity. The risk of blood clots is also increased if you are immobilized for prolonged periods and with major surgery. If possible, this medication should be stopped 4 to 6 weeks before major surgery. Talk about the risk of blood clots with your doctor.

Breast cancer: Some studies have found an association between a modest increase in the risk of developing breast cancer and the use of hormone replacement therapy after menopause. People who have a history of breast cancer should not use estrogens. If you have a family history of breast cancer, breast nodules, fibrocystic disease of the breast, or abnormal mammograms, you should be closely monitored by your doctor if you use estrogens. People using estrogens should have regular breast examinations and should be taught how to do a breast self-examination. Your doctor may also recommend regular mammograms, depending on your age, risk factors, and previous mammogram results. This medication must not be applied to the breasts, as it may have harmful effects on the breast tissue. Discuss the benefits and risks with your doctor so that you can make an informed choice about using this medication.

Condoms, diaphragms, or cervical caps: Conjugated estrogens vaginal cream may weaken the latex rubber of condoms, diaphragms, and cervical caps. Therefore, they may not be effective in preventing pregnancy for people who use the cream.

Dementia: People over age 65 receiving combined estrogen and progestin replacement therapy may be at increased risk of developing dementia (loss of memory and intellectual function). If you are over 65 years of age, your doctor should closely monitor you for loss of memory and intellectual function.

Diabetes: People with diabetes should monitor their blood glucose closely to detect any changes in blood glucose control that sometimes occur with use of estrogens. If you have risk factors for diabetes, your doctor will monitor your blood glucose regularly while taking this medication.

Endometrial cancer: Several studies suggest that estrogen replacement therapy increases the risk of cancer of the endometrium (uterus). Taking a progestin along with the estrogen reduces the risk to the same level as that of a woman not using estrogens. For this reason, all people who have not had their uterus removed should also take a progestin if they are using estrogens.

Fibroids: This medication may worsen fibroids, causing sudden enlargement, pain, or tenderness. If you notice these effects, contact your doctor.

Gallbladder: An increased risk of gallbladder disease has been reported by postmenopausal people who take oral estrogens. If you have a history of gall bladder disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you experience symptoms of gallbladder disease such as abdominal pain, possibly with fever and chills, contact your doctor as soon as possible.

Heart disease and stroke: Studies indicate an increased risk of heart disease and stroke with estrogen (with or without progestins) for postmenopausal people. If you experience symptoms of a heart attack (chest pain, tightness or pressure, sweating, nausea, feeling of impending doom) or stroke (sudden dizziness, headache, loss of speech, changes in vision, weakness or numbness in the arms and legs) while taking this medication, get immediate medical attention.

High cholesterol or triglycerides: Estrogen may increase triglyceride (a type of fat found in the blood) levels, especially for those who already have high levels of triglycerides. Your doctor will monitor your triglyceride levels closely while you are using this medication.

Kidney disease: People with kidney disease should be monitored by their doctor while using estrogen.

Liver disease: If you have or have had liver problems, you may require special monitoring by your doctor while you use this medication. Make sure to tell your doctor if you have ever had liver problems.

Seizures: Estrogens may cause an increase in seizures. If you have a history of epilepsy or medical conditions that increase the risk of seizures, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Thyroid disease: Estrogens can increase the amount of thyroid hormone your body needs to work properly. If you are hypothyroid (have reduced amount of thyroid hormone in your body) and need estrogens, you may require an increased amount of thyroid hormone for it to continue to work properly. Discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Water retention: Estrogen may cause sodium (salt) and water retention; therefore, people with epilepsy, asthma, or kidney or heart dysfunction should be closely monitored by their doctor while using this medication.

Pregnancy: Estrogen should not be used during pregnancy. If you become pregnant while using this medication, contact your doctor immediately.

Breast-feeding: Estrogen passes into breast milk. If you are breast-feeding and are using this medication, it may affect your baby. This medication is not recommended for those who are breast-feeding.

Children: The safety and effectiveness of this medication have not been established for children.

What other drugs could interact with this medication?

There may be an interaction between conjugated estrogens vaginal cream and any of the following:

  • anastrozole
  • apalutamide
  • "azole" antifungals (e.g., itraconazole, ketoconazole, voriconazole)
  • bosentan
  • bromocriptine
  • celecoxib
  • clarithromycin
  • clozapine
  • cobicistat
  • corticosteroids (hydrocortisone, prednisolone, prednisone)
  • dantrolene
  • diabetes medications (e.g., acarbose, canagliflozin, dulaglutide, insulin, gliclazide, metformin, sitagliptin)
  • enzalutamide
  • grapefruit juice
  • HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., efavirenz, etravirine)
  • HIV protease inhibitors (e.g., atazanavir, darunavir, ritonavir, tipranavir)
  • hyaluronidase
  • lenalidomide
  • lumacaftor and ivacaftor
  • melatonin
  • mifepristone
  • mitotane
  • modafinil
  • nirmatrelvir
  • ospemifene
  • pomalidomide
  • phenobarbital
  • protein kinase inhibitors (e.g., dabrafenib, idelalisib)
  • rifabutin
  • rifampin
  • ropinirole
  • St. John's wort
  • seizure medications (e.g., carbamazepine, lamotrigine, phenytoin, primidone)
  • somatrogon
  • somatropin
  • tacrolimus
  • thalidomide
  • theophyllines (e.g., aminophylline, theophylline)
  • thyroid replacements (e.g., desiccated thyroid, levothyroxine, liothyronine)
  • tizanidine
  • ursodiol
  • vaccines

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

  • stop taking one of the medications,
  • change one of the medications to another,
  • change how you are taking one or both of the medications, or
  • leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

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