Consumer medicine information

PROFEME 10

Progesterone

BRAND INFORMATION

Brand name

ProFeme 10 Cream

Active ingredient

Progesterone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using PROFEME 10.

What is in this leaflet?

This leaflet answers some of the common questions about PROFEME®. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the possible risks of you using PROFEME® against the benefits it can have for you.

If you have any concerns about using PROFEME® talk to your doctor or pharmacist. Keep this leaflet with the medicine. You may need to read it again.

What PROFEME® is used for?

PROFEME® contains the active ingredient progesterone.

This form of progesterone is identical to the progesterone produced by the ovaries of women.

Progesterone plays an important role in the menstrual cycle, reproduction, hormone production, mood, fluid balance, metabolism, energy levels and well-being in women.

Where women suffer from a deficiency of progesterone one or more of these areas may be affected and PROFEME® provides progesterone to address this deficiency. The skin readily absorbs progesterone and PROFEME® is a clean, simple and effective means of getting progesterone into the body.

Prior to using PROFEME®

PROFEME® cream should not be used if you are allergic to progesterone, or any of the ingredients contained within PROFEME®. These are listed at the end of this leaflet. This product contains almond oil and macadamia nut oil. Do not use PROFEME if you have kidney disease, liver disease, unexplained abnormal vaginal bleeding or herpes during pregnancy (herpes gestationis). Check with your doctor or pharmacist if you are unsure about whether you have any of these conditions before using PROFEME®. If you are taking other medications check with your doctor or pharmacist before using PROFEME®. PROFEME® is best applied to the inner forearm or upper thigh. The area should be clean and dry.

No perfume, deodorant or moisturising creams or gels should be used on the area because this may interfere with PROFEME® from being absorbed.

Do not use PROFEME® after the expiry date which is printed on the base (crimp) of the tube.

Do not use PROFEME® if the foil seal at the top of the tube is damaged or broken.

PROFEME® is not indicated for use in children.

How to use PROFEME®

Your doctor or pharmacist will explain how to apply PROFEME®. Follow all directions exactly as they are explained. If you are unclear clarify with your doctor or pharmacist prior to use.

The dose of PROFEME® will be determined for you by your doctor. This dose will be specific to your condition and should not be varied unless directed to do so by your doctor.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

Opening the tube

To open the tube remove the cap and peel off the foil seal. Dispose of the foil seal and replace the cap firmly after using the cream.

Measuring the correct dose of PROFEME® Cream

A measuring applicator (syringe style) in a sealed sleeve is enclosed in the PROFEME® box. The dose of PROFEME® is measured in millilitres. The applicator is marked with 0.5 mL graduations for dosing accuracy. Your doctor will have determined which dose is appropriate for you. To measure the correct dose of cream insert the tip of the applicator into the open nozzle of PROFEME® cream so that the nozzle and the shoulder of the applicator are in contact. GENTLY squeeze the base of the PROFEME® tube until cream reaches the open nozzle of the tube. At the same time slowly withdraw the plunger of the applicator. The cream will flow into the barrel of the applicator. Fill to the required dose. For example: a 1 mL dose of PROFEME® 10% (100 mg progesterone) needs the flat part of the plunger level with the 1 mL mark. If there are any air bubbles in the measured dose fill slightly past the required dose mark then depress the plunger so that the excess cream flows back into the tube. Stop at the required dose mark. Remove the applicator from the nozzle of the tube and replace the cap firmly on the tube. Depress the plunger of the applicator containing the dose of PROFEME® directly onto the skin (inner arm or upper thigh). Massage the cream into the area until absorbed. Rinse the applicator in warm water after use and replace in box with PROFEME® progesterone cream ready for the next day's application. Each 1 mL of PROFEME® 10% contains 100 mg of progesterone.

Where to apply PROFEME® cream?

Always apply PROFEME® cream to clean dry areas of skin. The best area to use PROFEME® is the inner forearms or the upper thighs. Never apply the cream to broken or damaged skin. Do not use PROFEME® on the genital area. PROFEME® cream should be applied at approximately the same time each day.

How often to apply PROFEME® Cream

Because each woman has a different progesterone requirement there is not a single "correct" dose of PROFEME®. PROFEME® is available in two different strengths (3.2% and 10%) and your doctor will have prescribed the strength and dose suitable for your individual condition.

Should you be unsure of the exact dose and frequency of dose contact your doctor. A dosage guide follows.

Usual dose of PROFEME®

Perimenopausal women (including moderate heavy bleeding, uterine fibroids and mild endometriosis)
Apply 0.3 mL of PROFEME® 10% cream via measured applicator (30 mg progesterone) daily or in divided doses from day 12-26 of menstrual cycle. If a menstrual period starts prior to day 26 cease using PROFEME® and consider the first day of bleeding as day 1 of the new cycle. This is a common occurrence when initiating treatment in perimenopausal women and should be considered a sign that the treatment is having a positive effect. Symptoms abate in 2nd or 3rd month of use. Where symptoms are more severe or unresponsive increase the dose to 100-200 mg (1-2 mL daily).

Premenstrual syndrome (PMS)
Apply 0.3 mL of PROFEME® 10% cream via measured applicator (30 mg progesterone) daily or in divided doses from day 12-26 of menstrual cycle. Significant alterations to this dosage may be made to achieve a crescendo effect 4-5 days prior to menses. Symptoms abate in 2nd or 3rd month of use.

Premenstrual dysphoric disorder (PMDD)
Apply 0.5-1 mL of PROFEME® 10% cream via measured applicator (50-100 mg progesterone) daily or in divided doses from day 12-26 of each menstrual cycle. Significant alteration to this dosage may be made to achieve a crescendo effect 4-5 days prior to menses. Symptoms abate in 2nd or 3rd month of use.

Severe endometriosis, sever menstrual bleeding/flooding and postpartum depression
Apply 1.0 - 2.0 mL of PROFEME® 10% cream via measured applicator (100-200 mg progesterone) daily or in divided doses depending upon the severity of the condition. In reproductive cyclical women initiate treatment on a day 12-26 basis, but this may need to be increased to three weeks use in every four if symptoms/pain emerge upon withdrawal.

Infertility/repeated first-term miscarriage
Luteal phase and first timester corpus luteal support. Apply 1 mL of PROFEME® 10% cream (100 mg progesterone) daily or in divided doses via measured applicator from day 12-26 of each cycle until pregnancy is confirmed and then 1-2 mL daily on a continual basis until at least week 13 or until full term.

Before conceiving, a women prone to miscarriage should use 0.3 mL of PROFEME® 10% cream (30 mg progesterone) from days 12-26 of the cycle until the pregnancy is confirmed. If spotting occurs at week 6 or 7 of pregnancy, a high dose of 100-200 mg progesterone cream (PROFEME® 10%) twice or three times daily. PROFEME® 10% can be used until the baby is full term (40 weeks of gestation).

NOTE: Amount and duration of application for all conditions must be tailored to individual requirements.

If you miss a dose

If you forget to apply your cream, you should apply it as soon as you remember provided this is within 9 hours of your usual time of application.

Otherwise do not apply the cream until the next application time. Missing a dose will not create a significant disruption to your treatment.

If you use too much (overdose)

Because of the way PROFEME® is used, an unintentional overdose is unlikely.

If you think that you or anyone else may have used too much PROFEME®, immediately telephone your doctor or your local Poisons Information Centre for advice.

During PROFEME® use

Do's

Inform your doctor or pharmacist that you are using PROFEME® before starting any other prescribed medicine. Some medicines interact with other medications.

Tell all doctors, dentists and pharmacists who are treating you that you are using PROFEME®.

Do Not's

Do not give PROFEME® to anyone else, even if they have the same symptoms or condition as you. Observe care when driving or operating machinery at the start of using PROFEME until you know how PROFEME® affects you. There is no evidence that PROFEME® will affect your ability to drive or to operate machinery. It is recommended that patients do not swim or shower until at least one hour after application of PROFEME® cream.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using PROFEME®. All medicines can have side effects in some people. Some side effects may need medical attention. Tell your doctor if you notice any of the following that are troublesome or ongoing:

  • Skin irritation, for example rash or slight redness and itching of the skin where the cream has been applied. Any irritation will usually disappear within a few days. If it persists contact your doctor or pharmacist.
  • Breast tenderness
  • Fatigue
  • Headache
  • Nausea
  • Light headedness

These effects are occasionally reported and usually disappear with adjustment of dose.

Tell your doctor if you observe any other side effects not listed above.

After using PROFEME®

Storage

Keep the tube sealed until time of use.

Replace cap firmly on the tube once opened.

Do not transfer the cream out of the original tube into another container. Keep the tube in a cool dry place where the temperature stays below 25°C.

DO NOT FREEZE.

Keep medicines out of reach of children.

Disposal

If your doctor tells you to stop using PROFEME® return your tube to your pharmacy to be correctly disposed of.

Product description

PROFEME® cream is a white opaque odorless cream in a laminated tube. The crimp at the base of the tube has the batch number and expiry date imprinted on it. The tube is boxed and in the box is a consumer information sheet and a graduated measuring applicator.

Ingredients

Each 50 mL tube of PROFEME® 10% contains 5000 milligrams (5000 mg) of progesterone. Each 1mL dose via measured applicator delivers 100 mg of progesterone. Other ingredients in the cream include cetomacrogol 1000, cetostearyl alcohol, almond oil, macadamia nut oil, dl-a-tocopherol acetate (vitamin E acetate), butylated hydroxytoluene, anhydrous citric acid, triethanolamine, Carbomer 940, B&J Phenonip® and purified water.

PROFEME® 10% progesterone creams are available in a 50 mL sealed laminated tube.

Name and Address of Supplier

Lawley Pharmaceuticals Pty Ltd for Lawley Pharmaceuticals
Unit 2/15A Harrogate Street, West Leederville, 6007
Western Australia, AUSTRALIA

Postal Address
PO Box 1146, West Leederville, 6901
Western Australia, AUSTRALIA

International Telephone : +618 9388 0096
Fax: +61 8 9388 0098

Website: www.lawleypharm.com.au

Email: [email protected]

Date of preparation: Sept 2011.

PROFEME® is a registered trademark.

BRAND INFORMATION

Brand name

ProFeme 10 Cream

Active ingredient

Progesterone

Schedule

S4

 

Name of the medicine

Progesterone BP.

Excipients.

Contains dl-α-tocopherol acetate (vitamin E), almond oil and macadamia oil formulated to optimise systemic absorption of the active ingredient. Also contains cetomacrogol 1000, cetostearyl alcohol, butylated hydroxytoluene, propyl hydroxybenzoate, citric acid, methyl hydroxybenzoate, triethanolamine, carbomer 940, B&J Phenonip and purified water.

Description

Chemical name: prog-4-ene-3,20 dione. Molecular formula: C21H30O2. MW: 314.47. CAS: 57-83-0. ProFeme is a transdermal drug delivery system consisting of a white oil in water cream intended for topical administration of progesterone. ProFeme contains the naturally occurring hormone progesterone.

Pharmacology

Progesterone is secreted primarily from the corpus luteum of the ovary during the latter half of the menstrual cycle. Progesterone is formed from steroid precursors in the ovary, testes, adrenal cortex and placenta. Lutenizing hormone (LH) stimulates the synthesis and secretion of progesterone from the corpus luteum. Progesterone is multifactorial in its actions. Maintenance of a secretory endometrium, precursor to steroid synthesis and a host of intrinsic biological properties make progesterone a hormone vital in providing a balance to estradiol, the estrogenic hormone secreted by the ovary. Progesterone has minimal estrogenic and androgenic activity. Orally administered progesterone is rapidly metabolised by the liver and the first-pass effect is extremely high. The hormone is reduced to inactive metabolites pregnanedione, pregnenadone and pregnanediol in the liver, conjugated with glucuronic acid, then excreted in the bile and urine. Transdermal absorption of progesterone avoids the first-pass metabolism. Progesterone has a short plasma half-life of several minutes. Progesterone is extremely lipophilic and binds to plasma protein carriers, cortisol binding globulin (CBG), sex hormone binding globulin (SHBG), red blood cellular membranes1,2 and fatty tissue. 2-10% progesterone circulates unbound through plasma.
Progesterone administration achieves improvement in lipid and lipoprotein profiles and when combined with estrogen therapies indicates no increased risk of endometrial hyperplasia3,4 and may prevent breast epithelial hyperplasia5.

Indications

ProFeme is indicated in progesterone deficient conditions.
Progesterone deficiency is associated with natural or surgical menopause, premenstrual syndrome (PMS), breast cancer, ovarian cysts, uterine fibroids, endometrial hyperplasia and associated estrogen dependent malignancies, fibrocystic breasts, postpartum depression, repeat first term miscarriages and endometriosis. ProFeme is not a substitute for estrogen replacement therapy.

Contraindications

Progesterone should not be used by women with any of the following conditions.
Severe liver disease, i.e. cholestatic jaundice, Rotor syndrome or Dubin-Johnson syndrome.
Any unexplained abnormal vaginal bleeding.
History of herpes gestationis.
Jaundice of pregnancy.
Known sensitivity to ProFeme cream or any of its individual components.

Precautions

Use In pregnancy

Progesterone is the hormone essential for promotion and maintenance of pregnancy. Ovarian output of progesterone in the nonpregnant state is 25-30 mg daily during the luteal phase. The placental output during the third trimester of pregnancy is 350-400 mg per day. Whereas progestagens are contraindicated in pregnancy, progesterone exhibits no adverse effects on the fetus.

Interactions

Thyroid stimulating agents.

Potential interaction exists in patients using thyroid supplementation. Progesterone may cause a potentiation of thyroxine’s effects leading to hyperthyroidism. Normal T3 and T4 levels with elevated TSH suggests impaired thyroid hormone activity rather than insufficiency. Periodical TSH testing should be adopted on initiation of progesterone treatment in these patients.

Adverse Effects

Because ProFeme contains the hormone identical to that produced by the human ovary side effects are usually minimal. If experienced these may include breast tenderness and swelling, fluid retention or slight vaginal bleeding. Dizziness, nausea, fatigue, headache and light headedness have been reported occasionally and usually disappear with adjustment of dose.

Dosage and Administration

General considerations.

A) Distribution.

Maximum absorption is achieved by using ProFeme over a large skin area. The optimal skin sites to apply ProFeme progesterone cream are to the inner aspects of the arms and the upper thigh. Other areas suitable for use include the abdomen and upper chest/ neck.
Progesterone is first absorbed into the subcutaneous fat layer then passively diffuses throughout the body via the circulation. The rate at which this is achieved is dependant on the amount of body fat. In general most significant physiological results are not experienced by patients until the fourth to sixth week of usage. In women using estrogen supplements the initial effect of progesterone is to sensitise estrogen receptors. A reduction in estrogen dosage may be required should breast swelling and tenderness, fluid retention or scant bleeding result.

Warning.

To date, ProFeme cream has not been shown to be protective against estrogen induced endometrial hyperplasia. Caution should be exercised and patients monitored if combination therapy is to be initiated.
In perimenopausal women with irregular menstrual flows the addition of ProFeme may result in a return of menses. This may lead to the conclusion that progesterone caused the menses when in fact estrogen created the endometrial proliferation. This effect is not abnormal when starting ProFeme and there is no reason to cease use of ProFeme.

B) Cycling.

In a normal menstrual cycle progesterone is produced as the dominant hormone for approximately fourteen days per cycle (luteal phase). Progesterone receptor stimulation is not continuous. Aim of treatment is to mimic natural ovarian production as much as possible, thus monthly cycling is recommended. In postmenopausal women progesterone should be used for 21-25 days per calendar month followed by a 5-7 day progesterone free state. In perimenopausal women administration should be synchronised with normal corpus luteal progesterone production, i.e. day 12 to day 26 of the menstrual cycle. If, after initiating treatment, menstruation occurs after 5-10 days it is recommended to cease application of ProFeme and recommence 12 days later.

C) Eligibility.

All women, regardless of whether the uterus is intact or not, exhibiting signs of estrogen imbalance (estrogen dominance) have a requirement for progesterone. Hysterectomized women are not exempt from using ProFeme. ProFeme cream is available in two strengths 3.2% and 10% w/w. Dosage should be tailored to individual requirements and the patient reviewed on a regular basis. Dosage adjustments may be made by altering the volume of cream applied or alteration of the percentage strength prescribed. When applying ProFeme use the supplied graduated applicator to achieve correct dosage. Massage the cream until completely absorbed.

Usual therapeutic doses.

Menopausal women.

Apply 0.3 mL of ProFeme 10% cream via measured applicator (30 mg progesterone) daily or in divided doses for either 25 days per calendar month or for 3 weeks on and 1 week off. Symptoms abate in 2nd or 3rd month of use.

Perimenopausal women.

Apply 0.3 mL of ProFeme 10% cream via measured applicator (30 mg progesterone) daily or in divided doses from day 12-26 of each menstrual cycle. If a menstrual period starts prior to day 26 cease using ProFeme and consider the first day of bleeding as day 1 of the new cycle. This is a common occurrence when initiating treatment in perimenopausal women and should be considered a sign that the treatment is having a positive effect. Symptoms abate in 2nd or 3rd month of use.

Premenstrual syndrome (PMS).

Apply 0.3 mL of ProFeme 10% cream via measured applicator (30 mg progesterone) daily or in divided doses from day 12-26 of each menstrual cycle. Significant alterations to this dosage may be made to achieve a crescendo effect 4-5 days prior to menses. Symptoms abate in 2nd or 3rd month of use.

Premenstrual dysphoric disorder (PMDD).

Apply 0.5-1 mL of ProFeme 10% cream via measured applicator (50-100 mg progesterone) daily or in divided doses from day 12-26 of each menstrual cycle. Significant alterations to this dosage may be made to achieve a crescendo effect 4-5 days prior to menses. Symptoms abate in 2nd or 3rd month of use.

Endometriosis, menorrhagia and postpartum depression.

Apply 1.0-2.0 mL of ProFeme 10% cream via measured applicator (100-200 mg progesterone) daily or in divided doses depending upon the severity of the condition. In reproductive cyclical women initiate treatment on a day 12-26 basis, but can increase frequency to 3 week in 4 if symptoms/ pain emerge upon withdrawal.

Infertility/ repeated first term miscarriage.

Luteal phase and first trimester corpus luteal support. Apply 1 mL of ProFeme 10% cream (100 mg progesterone) daily or in divided doses via measured applicator from day 12-26 of each cycle until pregnancy is confirmed and then 1-2 mL daily on a continuous basis until at least week 13 or until full term.

Note.

Amount and duration of application for all conditions must be tailored to individual requirements.

Overdosage

Toxicity of progesterone is extremely low.

Presentation

Cream (white), 10% w/v (100 mg/mL): 50 mL (boxed tube).
ProFeme is available in two strengths, 3.2% and 10%.
ProFeme 10% is supplied with a dose measuring applicator calibrated in 0.5 mL graduations. The patient should measure the appropriate dose using the applicator and apply directly to the skin massaging until absorbed. Directions for use of the applicator are contained within the box.

Storage

Store below 25°C. Do not freeze.
Shelf life under these conditions is 2 years.

References

1. M. Holzbauer: The Association of Steroids with blood cells in vivo. J. Steroid Biochem 3: 579-92, 1972.
2. E. Ohtsuka and S.S. Koide: Incorporation of Steriods into human, dog and duck erythrocytes. Gen Camp Endo 12: 598-603, 1969.
3. J. Hargrove: Menopausal Hormone Replacement Therapy with Continuous Daily Oral Micronized Estradiol and Progesterone. Obstet Gynecol 73; 4: 606-12, 1989.
4. The Writing Group for the PEPI Trial: Effects of Hormone Replacement Therapy on Endometrial Histology In Postmenopausal Women. JAMA 275; 5: 371-5, 1996.
5. K-J Chang: Influence of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril 63; 4: 785-91, 1995.