M-Progesterone: Uses, Side Effects and Dosage

Serious Warnings and Precautions

What is M-PROGESTERONE used for?

M-PROGESTERONE is used with estrogen replacement therapy to help treat symptoms of menopause. It helps reduce the risk of:

• endometrial hyperplasia (thickening of the uterus lining);
• uterine cancer.

M-PROGESTERONE is intended for women with an intact uterus (has not been removed by surgery).

How does M-PROGESTERONE work?

The active ingredient in M-PROGESTERONE capsules is progesterone, a natural female hormone. In women of childbearing age, progesterone plays a role in the monthly shedding of the inner lining of the uterus (endometrium) and the menstrual bleeding that follows. M-PROGESTERONE helps protect the inner lining of the uterus from overgrowth caused by estrogen therapy during and after menopause.

What are the ingredients in M-PROGESTERONE?

Medicinal ingredients: progesterone

Non-medicinal ingredients: ammonium hydroxide, black iron oxide, gelatin, glycerin, isopropyl alcohol, medium chain triglyceride, n-butyl alcohol, propylene glycol, purified talc, shellac glaze, soya lecithin, sunflower oil and titanium dioxide.

M-PROGESTERONE comes in the following dosage forms:

Capsules. Each capsule contains 100 mg (milligrams) of progesterone.

Do not use M-PROGESTERONE if you:

• have an allergic or an unusual reaction to progesterone, soya, peanut or to any of the ingredients in M-PROGESTERONE;
• have liver disease;
• have or have had hormone dependent cancers, like cancer of the breast or uterus;
• have overgrowth of the lining of the uterus;
• have undiagnosed or unexpected vaginal bleeding;

• are pregnant or suspect you may be pregnant;

• have a history of heart disease (including heart attack) or stroke;
• have or have had blood clotting problems or disorders;
• have porphyria ( a disorder that affects how your body makes hemoglobin);
• have partially or completely lost vision due to blood vessel disease of the eye.

To help avoid side effects and ensure proper use, talk to your healthcare professional before you take M-PROGESTERONE. Talk about any health conditions or problems you may have, including if you:

• 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 personal history of breast disease (including breast lumps) and/or breast biopsies, abnormal mammograms, or a family history of breast cancer);
• have experienced undiagnosed or abnormal vaginal bleeding;
• have a history of uterine fibroids or endometriosis;
• have been diagnosed with lupus;
• have been diagnosed with hearing loss due to otosclerosis;
• have been diagnosed with gallstones;
• 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 a history of heart conditions;
• have a personal or family history of blood clots or a personal history of active thrombophlebitis (inflammation of the veins);
• are breastfeeding or planning to breastfeed;
• smoke;
• have a history of high blood pressure;
• have a history of kidney disease, epilepsy (seizures) or asthma;
• 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 a history of high cholesterol or high triglycerides;
• have a history of migraine headaches; • have a history of depression;
• have had a hysterectomy (surgical removal of the uterus).

Other warnings you should know about:

Breast Cancer

• Estrogens with or without progestins should not be taken by women who have a personal history of breast cancer.
• There is an increased risk of breast cancer in post-menopausal women taking combined estrogen plus progestin.

• You may also have an increased risk of breast cancer if you have:

  • a family history of breast cancer or have had breast lumps, breast biopsies or abnormal mammograms (breast x-rays);
  • never had a baby before or had your first full-term pregnancy at an older age;
  • you are overweight;
  • you started menstruating at an early age.

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

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

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.

Stroke and Heart Disease

There is increased risk of stroke and coronary heart disease in post-menopausal women taking combined estrogen plus progestin.

Abnormal Blood Clotting

There is an increased risk of blood clots in the lungs and large veins in post-menopausal women taking combined estrogen plus progestin.

You should discuss risk factors for blood clots with your healthcare professional since blood clots can be life-threatening or cause serious disability. The risk of blood clots also increases with:

• age;
• family history of blood clots;
• smokers;
• patients that 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.

Dementia

The Women’s Health Initiative Memory Study (WHIMS) showed an increased risk of dementia (loss of memory and intellectual function) in postmenopausal women age 65 and over taking oral combined estrogen plus progestin.

Driving and Operating Machinery

M-PROGESTERONE may cause some people to feel dizzy or sleepy, 1-4 hours after ingestion of the capsules. This is more likely if M-PROGESTERONE is taken with food. Do not drive or do anything requiring alertness until you know how M-PROGESTERONE affects you.

Medical Testing

Your healthcare professional will need to order medical tests before and during your treatment. This will help determine if it is safe for you to continue taking M-PROGESTERONE. These tests include:

• Blood pressure.
• Breast and pelvic exam.
• Pap smear.
• Mammogram.
• Blood glucose.
• Calcium.
• Triglycerides.
• Cholesterol.
• Liver function test.

You should schedule a follow-up with your healthcare professional within 3-6 months after starting M-PROGESTERONE. You should schedule an appointment with your healthcare professional at least once a year while you are taking M-PROGESTERONE. You should regularly talk with your healthcare professional about whether you still need treatment with HRT.

Vaginal Bleeding

A few days after completing a M-PROGESTERONE course of 3 capsules daily, the inner lining of the uterus will usually shed. This is accompanied by vaginal bleeding (resembling a normal monthly period). With a dosage of 2 capsules daily, many women will not have such vaginal bleedings, although the lining of the uterus will also be protected against overgrowth.

Tell your healthcare professional about all the medicines you take, including any drugs, vitamins, minerals, natural supplements or alternative medicines.

The following may interact with M-PROGESTERONE:

• anticonvulsant medicines used to prevent seizures, such as phenobarbital, carbamazepine, phenytoin;
• antiviral drugs, used to treat viral infections, such as ritonavir and efavirenz;
• antifungal drugs, used to treat fungal infections, such as fluconazole, itraconazole, ketoconazole, voriconazole;
• bosentan, used to treat high blood pressure;
• rifampicin and rifabutin, antibiotics used to treat bacterial infections;
• sedatives, such as barbiturates and meprobamate;
• tacrolimus, used in organ transplants;
• topiramate, used to treat epilepsy and migraines;
• some herbal products, such as St. John’s wort, used to treat depression.

M-PROGESTERONE may interfere with certain medical tests. This may continue for 2-4 weeks after you stop taking M-PROGESTERONE. Tell your healthcare professional that you are taking M-PROGESTERONE when they order any tests for you.

How to take M-PROGESTERONE:

• Follow the instructions given by your healthcare professional.
• Capsules of M-PROGESTERONE should be taken by mouth and swallowed whole with a glass of water.
• Do not crush, do not pierce the M-PROGESTERONE capsules.
• Do not take with food. If you are taking M-PROGESTERONE in the morning, wait 2 hours after breakfast before taking your dose.

Usual adult dose:

Your healthcare professional will adjust your dose based on how much estrogen you are taking.

200 mg daily: Take two capsules (200 mg) in the evening before bed. This dose should be taken for the last 14 days of your estrogen treatment each cycle. This means days 8 to 21 for a 28 day cycle or day 12 to 25 on a 30 day cycle.

300 mg daily: Take one capsule (100 mg) in the morning and two capsules (200 mg) in the evening before bed. This dose should be taken for the last 12-14 days of your estrogen treatment each cycle.

Overdose:

If you take too much M-PROGESTERONE (progesterone), you may experience the following symptoms: nausea, vomiting, sleepiness, dizziness, depressive mood, tiredness, acne and hairiness.

Missed Dose:

If you are taking 2 capsules a day (total dose at bedtime) and you forget to take this dose, you should take one capsule the following morning and continue taking the rest of the capsules as prescribed.

If you are taking 3 capsules a day and you forget to take a morning or evening dose, you should not take the missed dose.

What are possible side effects from using M-PROGESTERONE?

These are not all the possible side effects you may feel when taking M-PROGESTERONE. If you experience any side effects not listed here, contact your healthcare professional.

Side effects of M-PROGESTERONE:

• breast tenderness/swelling/pain;
• dizziness or vertigo;
• fatigue (tiredness);
• genital bleeding or spotting (minor vaginal bleeding) in between the normal periods (mainly during the first two months);
• headaches or depressive mood;
• irregular menstrual periods;
• lightheadedness (feeling faint);
• nausea (urge to vomit), cramps;
• sleepiness, insomnia.

Side effects observed in women taking progestins in general:

• darkening of skin in patches;
• rash with or without itching;
• swelling, bloating from water retention.

Other side effects that have been observed with estrogen and progestin combinations in general, but not necessarily with M-PROGESTERONE treatment are:

• acne;
• changes in appetite and body weight;
• change in sexual drive;
• inflammation of the bladder;
• increase in blood pressure;
• irritability;
• loss of hair, hairiness;
• menstrual cramps;
• nervousness;
• overgrowth of the lining of the uterus;
• pain during sexual intercourse;
• palpitations (unpleasant sensation of irregular and/or forceful beating of the heart);
• pain in the joints and muscles, usually lasting only 3-6 weeks;
• pain on urination or difficulty urinating;
• premenstrual syndrome (PMS);
• skin rash, tender red lumps or nodules or other skin reactions;
• vaginal itching/discharge;
• intolerance to contact lenses.

During your first 2-4 months of HRT, you may experience minor unscheduled vaginal bleeding (at times other than when you would expect a normal period). This is a normal response of your body as it adjusts to the return of estrogen and progesterone to the levels that were seen before menopause.

Should unscheduled vaginal bleeding persist, you should consult your healthcare professional.

Serious side effects and what to do about them

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough to interfere with your daily activities, talk to your healthcare professional.

Reporting Side Effects

Storage:

The capsules should be stored at controlled room temperature between 15°C and 30°C. The date the capsules should be used by is printed on the strip after the term "EXP" (expiry date). Protect from light. Keep in a safe place out of the reach and sight of children and pets.

If you want more information about M-PROGESTERONE:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for healthcare professionals and includes the Patient Medication Information by visiting the Health Canada Drug Product Database website (https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database.html) ; or by contacting Mantra Pharma Inc. at medinfo@mantrapharma.ca or at 1-833-248-7326.