Consumer medicine information

Androforte 5

Testosterone

BRAND INFORMATION

Brand name

AndroForte 5

Active ingredient

Testosterone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Androforte 5.

SUMMARY CMI

ANDROFORTE® 5

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using ANDROFORTE 5?

ANDROFORTE 5 contains the active ingredient testosterone. ANDROFORTE 5 is used to replace the body's natural hormone testosterone when not enough is made by the body. For more information, see Section 1. Why am I using ANDROFORTE 5? in the full CMI.

2. What should I know before I use ANDROFORTE 5?

Do not use if you have ever had an allergic reaction to testosterone, tree nuts (almond oil), or any of the ingredient listed at the end of the CMI. Do not use ANDROFORTE 5 if you have or are suspected to have prostate cancer or breast cancer. ANDROFORTE 5 must not be used by children or women, particularly if they are pregnant or anticipate becoming pregnant, or breastfeeding. Talk to your doctor if you have any other medical conditions. For more information, see Section 2. What should I know before I use ANDROFORTE 5? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ANDROFORTE 5 and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use ANDROFORTE 5?

Your doctor or pharmacist will explain how and where on the body to apply ANDROFORTE 5. Your doctor or pharmacist will tell you exactly how much to use. It is very important to use the correct dose of cream on the correct part of the body. Detailed instructions can be found in Section 4. How do I use ANDROFORTE 5? in the full CMI.

5. What should I know while using ANDROFORTE 5?

Things you should do
  • Tell any doctors, dentists, and pharmacists who treat you that you are using this medicine.
  • Keep all of your doctor's appointments so that your progress can be checked.
  • Contact your doctor immediately if you think someone has come into regular contact with the cream on your skin. Avoid unwanted transfer to another by wearing clothes which cover the application area and/or by showering before contact.
Things you should not do
  • Do not stop using ANDROFORTE 5, or change the dosage, without checking first with your doctor.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how ANDROFORTE 5 affects you.
Looking after your medicine
  • Keep ANDROFORTE 5 in a cool, dry place where the temperature stays below 25°C. Do not freeze.

For more information, see Section 5. What should I know while using ANDROFORTE 5? in the full CMI.

6. Are there any side effects?

Less serious side effects include skin reactions, headaches or migraines, prostatic disorders, changes in sexual drive, breast changes, dizziness, difficulty in breathing or worsening of sleep apnoea, memory loss, changes in sense of smell or taste, mood changes, blood pressure changes, flushing, increased appetite, weight gain, hair changes, muscle cramps or pain, unusual weakness, generally feeling unwell, blood glucose (sugar) changes, swollen feet or ankles, reduction in the size of the testicles, changes in heartbeat, feeling tired, nausea, and vomiting. Serious side effects include symptoms of an allergic reaction, such as shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, rash, or itching or hives on the skin. Other serious side effects include unwanted frequent or prolonged and painful erections, yellowing of the skin and eyes, and numbness, heat or swelling in your arms or legs, which could indicate a blood clot. For more information, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

ANDROFORTE® 5 (And-ro-fort)

Active ingredient(s): testosterone

Consumer Medicine Information (CMI)

This leaflet answers some common questions about ANDROFORTE 5. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using ANDROFORTE 5.

Where to find information in this leaflet:

1. Why am I using ANDROFORTE 5?
2. What should I know before I use ANDROFORTE 5?
3. What if I am taking other medicines?
4. How do I use ANDROFORTE 5?
5. What should I know while using ANDROFORTE 5?
6. Are there any side effects?
7. Product details

1. Why am I using ANDROFORTE 5?

ANDROFORTE 5 contains the active ingredient testosterone.

Testosterone is a natural hormone, known as an androgen, which controls normal sexual development and function in men.

Testosterone is essential for the development and maintenance of the male reproductive organs as well as other male characteristics, such as facial and body hair growth, deep voice, sexual drive, muscle mass and body fat distribution.

ANDROFORTE 5 is used to replace the body's natural hormone testosterone when not enough is made by the body.

ANDROFORTE 5 is a testosterone containing cream that is applied by the patient daily to the skin. It is a simple and effective way of getting testosterone into your body. Your skin absorbs testosterone, which then travels into your bloodstream and throughout your body.

2. What should I know before I use ANDROFORTE 5?

Warnings

Do not use ANDROFORTE 5 if:

  • you are allergic to testosterone, tree nuts (almond oil) or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.
  • you have or have had any of the following:
    - prostate cancer
    - breast cancer (a rare condition in men)
  • you are a woman, especially if you are pregnant or breastfeeding
  • you are a child

Check with your doctor if you:

  • have any other medical conditions, especially:
    - a blood clot, or a condition which makes your blood more likely to form a clot
    - high blood calcium levels associated with bone cancer and tumours (hypercalcaemia)
    - high levels of calcium in the urine (hypercalciuria)
    - high blood pressure or heart disease
    - a tendency to retain fluid (signs may include swollen feet or ankles)
    - liver or kidney disease
    - epilepsy (fits)
    - migraines
    - diabetes
    - difficulty in passing water (urinating) due to enlarged prostate gland
    - abnormal pauses in breathing during sleep (sleep apnoea)
  • take any medicines for any other condition
  • are a high-level athlete. You need to be aware of the rules governing testosterone (an androgen) use if prescribed ANDROFORTE 5 cream, as testosterone may enhance athletic performance. Misuse of androgens to enhance your physical abilities in sport carries serious health risks and is discouraged. Athletes should note that the active substance, testosterone, may produce a positive reaction in anti-doping tests.
  • ANDROFORTE 5 may quicken the growth of existing prostatic tumours and benign prostatic hyperplasia (enlargement of the prostate gland). It may also increase the risk of breast cancer in males. Before treatment, your doctor should conduct tests to check that you do not have existing prostate or breast cancer. During treatment, your doctor may monitor the effects of this medicine.
  • Worsening of breathing problems during sleep has been reported during treatment with testosterone replacement in people prone to breathing problems during sleep. This is especially true if you are overweight or have lung problems.
  • If you use ANDROFORTE 5 over long periods of time, you may develop an abnormal increase in the number of red blood cells in the blood (polycythaemia). Your doctor may organise regular blood counts to monitor this.

If you have not told your doctor about any of the above, tell them before you start using ANDROFORTE 5.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

  • Do you not use this medicine if you are a woman, particularly if you are pregnant or breastfeeding.

ANDROFORTE 5 may cause harm to the unborn child when administered to pregnant women. Pregnant women must also avoid any contact with the ANDROFORTE 5 treated skin.

ANDROFORTE 5 may cause serious reactions in nursing infants.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with ANDROFORTE 5 and affect how it works. These include:

  • oral anticoagulants, medicines used to thin blood and to treat or prevent blood clots
  • corticosteroids or adrenocorticotropic hormone (ACTH), hormones used to control inflammation
  • oxyphenbutazone, a medicine used to treat pain and inflammation
  • insulin, a medicine used to control blood sugar levels
  • bupropion, a medicine used to aid in smoking cessation
  • ciclosporin, a medicine used to suppress the immune system
  • some herbal products such as ancreamica dahurica, chapparal, comfrey, eucalyptus, germander tea, Jin Bu Huan, kava, penny royal oil, skullcap, and valerian.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect ANDROFORTE 5.

4. How do I use ANDROFORTE 5?

How much to use

  • Follow the instructions provided and use ANDROFORTE 5 until your doctor tells you to stop.
  • When you have finished a tube, start the next tube on the following day. Never leave a break between tubes.
  • ANDROFORTE 5 helps control the symptoms of your condition, but does not cure it. Therefore you must use ANDROFORTE 5 every day.
  • Your doctor or pharmacist will explain how and where on the body to apply ANDROFORTE 5.
  • It is very important to use the correct dose of cream on the correct part of the body because the two sites of application absorb testosterone very differently.
  • Application to the scrotum:
    - The usual starting dose is 0.5 mL of cream by measured applicator per day applied to the entire scrotum (the skin sack that holds the testicles).
    - Your doctor or pharmacist will tell you exactly how much to use.
    - You should not use more than 1 mL (50 mg testosterone) of cream per day.
    - The dose should not be varied unless directed to do so by your doctor.
    - You will need to return to your doctor at regular intervals so that the dose can be checked via a blood test.
  • Application to the upper body:
    - The usual starting dose is 2 mL of cream by measured applicator per day applied to the upper body (torso, abdomen and sides of the body).
    - Your doctor or pharmacist will tell you exactly how much to use.
    - You should not use more than 4 mL (200 mg testosterone) of cream per day.
    - The dose should not be varied unless directed to do so by your doctor. You will need to return to your doctor at regular intervals so that the dose can be checked via a blood test.

When to use ANDROFORTE 5

  • Apply ANDROFORTE 5 once per day at approximately the same time each day, preferably in the morning.
  • Using it at the same time each day will have the best effect. It will also help you remember when to apply it.
  • Do not shower or swim for at least six (6) hours after applying the cream to the upper body or two (2) hours after applying the cream to the scrotum.

How to use ANDROFORTE 5

  • To open the tube, remove the cap and peel off the foil seal.
  • A measuring applicator (syringe style) in a sealed sleeve is enclosed in the ANDROFORTE 5 box. The applicator is marked with 0.25 mL graduations for dosing accuracy.

  • To measure the correct dose of cream:
    - gently squeeze the base of the ANDROFORTE 5 tube until cream reaches the open nozzle of the tube.
    - insert the tip of the applicator into the open nozzle of ANDROFORTE 5 cream so that the nozzle and the shoulder of the applicator are in contact.
    - invert the tube and the applicator so the cream will flow with gravity when squeezed.
    - carefully squeeze the base of the ANDROFORTE 5 tube and at the same time slowly withdraw the plunger of the applicator. The cream will flow into the barrel of the applicator. Do not try to squeeze the cream into the syringe.
    - fill the applicator to the required dose. For example: a 0.5 mL dose of ANDROFORTE 5 (25 mg testosterone) for scrotal application needs the flat part of the plunger level with the 0.5 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.

To view a demonstration video of how to use syringe applicator see: www.lawleypharm.com.au/products

  • To apply the cream:
    - depress the plunger of the applicator containing the dose of ANDROFORTE 5 directly onto clean, dry and healthy skin on the part of your body as directed by your doctor:
    -- on the scrotum (the skin sack that holds the testicles). The scrotum does not need to be shaved prior to application of the cream.
    -- on the upper body including the torso, abdomen and the sides of the body from the waist to just below the arm pits. It is preferable to apply to areas on the upper body with minimal hair and body fat.

- massage the cream into the area until absorbed. Typically, this takes 30 seconds or so.
- avoid using perfume, deodorant or moisturising creams/gels on the area because this may interfere with ANDROFORTE 5 being absorbed.
- cover the application area with clothing once applied.
- never apply the cream to broken or damaged skin.
  • Following application:
    - Wash your hands thoroughly with soap and water after applying the cream.
    - be careful to avoid potential transfer to pregnant women.
    - rinse the applicator in hot water after use and replace in the box with the ANDROFORTE 5 cream ready for the next day's application.

For contacts:

  • if someone you know comes into regular contact with the skin where you have applied the cream, advise them to wash the affected area on their body with warm, soapy water as soon as possible.

If you forget to use ANDROFORTE 5

ANDROFORTE 5 should be used regularly at the same time each day. If you forget to apply your dose at the usual time, apply it as soon as you remember and continue to apply it as you would normally.

If it is almost time for your next dose, skip the dose you missed and apply your next dose when you are meant to. Do not apply a double dose to make up for the dose you missed.

If you use too much ANDROFORTE 5

Wash the skin with soap and water. If you think that you may have used too much ANDROFORTE 5, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26) for advice, or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using ANDROFORTE 5?

Things you must do

  • If you are about to have any blood tests, tell your doctor that you are taking this medicine. The use of ANDROFORTE 5 may interfere with some of the results.
  • Keep all of your doctor's appointments so that your progress can be checked. Your doctor may monitor your blood pressure, examine your prostate and conduct other tests (including blood tests) from time to time, particularly if you are elderly. This is to make sure the medicine is working and to check for unwanted side effects. ANDROFORTE 5 may increase your blood pressure and affect your liver function.
  • If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using ANDROFORTE 5.
  • Tell any other doctors, dentists and pharmacists who treat you that you are using this medicine.

Call your doctor straight away if you:

  • See any signs of increased levels of testosterone in a child or partner that may have occurred through accidental exposure to ANDROFORTE 5.

ANDROFORTE 5 may be transferred to another person during close skin contact with the area where the cream has been applied.

If close contact occurs repeatedly or for long periods of time, especially with children, this could cause signs of increased testosterone (virilisation), such as more hair on the face or the body and a deepened voice. In women, this may also cause changes in the menstrual cycle. Signs of increased testosterone in children include:

  • enlarged penis or clitoris
  • early development of pubic hair
  • increased erections or sex drive
  • aggressive behaviour.

Avoid unwanted transfer to another by wearing clothes which cover the application area and/or by showering before contact. You need to ensure that your partner is not put at risk of receiving testosterone by accident. If your partner is pregnant, it is extra important that you take care to protect her from testosterone.

To avoid unwanted transfer to another person, you should:

  • leave a gap of 6 hours between applying ANDROFORTE 5 to the upper body and having intimate physical contact. You should also wear clothing such as a T-shirt to cover the application area and/or have a shower or bath beforehand
  • leave a gap of at least 2 hours between applying ANDROFORTE 5 to the scrotum and having intimate physical contact, and/or wash the genital area with a damp warm flannel beforehand.

If a woman or child comes into contact with ANDROFORTE 5, thoroughly wash the area of skin exposed to the cream with soap and water immediately.

Things you should not do

  • Do not use ANDROFORTE 5 to treat any other complaints unless your doctor tells you to.
  • Do not give ANDROFORTE 5 to anyone else, even if they have the same condition as you.
  • Do not stop using ANDROFORTE 5, or change the dosage, without checking first with your doctor. If you stop using it suddenly, your condition may worsen or you may have unwanted side effects.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how ANDROFORTE 5 affects you.

Looking after your medicine

Follow the instructions in the carton on how to take care of your medicine properly.

  • Keep the tube sealed until time for use. Replace cap firmly on the tube once opened.
  • Do not transfer the cream out of the original tube into another container
  • Rinse the applicator in hot water after use and replace in box with ANDROFORTE 5 cream ready for the next day's application.

Store it in a cool dry place where the temperature stays below 25°C. Store away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Do not freeze.

Keep it where young children cannot reach it.

When to discard your medicine

Once opened, the contents of the tube should be used within 125 days.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below, and if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

These are the possible side effects of ANDROFORTE 5.

Less serious side effectsWhat to do
Hormone-related:
  • changes in sexual drive
  • painful, tender or enlarged breasts
  • mood changes, nervousness, anger
  • increased appetite and weight gain
  • hair loss, discoloured hair, excessive hairiness
  • reduction in the size of the testicles
  • changes in the levels of blood glucose (sugar)
  • oily skin, acne
  • prostatic disorders such as difficulty or pain while urinating, frequent urination
Cardiovascular or heart-related:
  • increased or decreased blood pressure, flushing
  • changes in heart beat, feeling tired, nausea and vomiting which may be a sign of changes in your electrolytes
Skin-related:
  • skin reactions such as irritation, redness, dry or stinging skin, hives
  • increased feeling or sensitivity of skin
Breathing-related:
  • difficulty in breathing or worsening of sleep apnoea
Neurological or brain-related:
  • headaches or migraines
  • dizziness
  • memory loss
  • changes in the sense of smell or taste
Other side effects:
  • muscle cramps or pain
  • unusual weakness, generally feeling unwell
  • swollen feet or ankles (signs of increased tendency to retain fluid)
Speak to your doctor if you notice any of the following and they worry you.

Serious side effects

Serious side effectsWhat to do
Hormone-related:
  • yellowing of the skin and eyes, also called jaundice
  • sudden severe headache, loss of vision, loss of coordination, slurred speech, shortness of breath, chest pain, numbness, heat or swelling in your arm or leg, which could indicate a blood clot
  • unwanted, frequent or prolonged and painful erections
Allergic reaction-related:
  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice this serious side effect. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed above may also occur in some patients. Some of these side effects can only be found when your doctor does tests from time to time to check your progress, including:

  • increases in blood cholesterol, increased haematocrit (percentage of red blood cells in the blood), haemoglobin and red blood cell count
  • increased creatinine
  • increased Prostate Specific Antigen (PSA). PSA is a protein produced by the prostate which can be used to detect prostate disease
  • reduction in your sperm count, which may affect your fertility

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What ANDROFORTE 5 contains

Active ingredient
(main ingredient)		ANDROFORTE 5 - 50 mg testosterone per 1 mL of cream
Other ingredients
(inactive ingredients)		butylated hydroxytoluene
carbomer 940
cetomacrogol 1000
cetostearyl alcohol
citric acid
dl-alpha-tocopherol acetate
phenoxyethanol
purified water
trolamine
Potential allergensalmond oil
butyl hydroxybenzoate
ethyl hydroxybenzoate
isobutyl hydroxybenzoate
methyl hydroxybenzoate
propyl hydroxybenzoate

Do not take this medicine if you are allergic to any of these ingredients.

What ANDROFORTE 5 looks like

ANDROFORTE 5 is a white, opaque odourless cream in a sealed laminated 50 mL tube.

The crimp at the base of the tube has the batch number and expiry date imprinted on it.

ANDROFORTE 5 is supplied as a 50 mL sealed tube with a dose applicator marked with 0.25 mL graduations in a carton.

(AUST R 123764)

Who distributes ANDROFORTE 5

Lawley Pharmaceuticals Pty Ltd
Unit 2/15A Harrogate Street
West Leederville WA 6007
Telephone: +61 8 9388 0096
Toll-Free phone (Australia): 1800 627 506
Email: [email protected]

This leaflet was prepared in September 2023.

Published by MIMS November 2023

BRAND INFORMATION

Brand name

AndroForte 5

Active ingredient

Testosterone

Schedule

S4

 

1 Name of Medicine

Testosterone.

2 Qualitative and Quantitative Composition

AndroForte 5 contains 5% w/v testosterone (50 mg in 1 mL or 100 mg in 2 mL).
Contains tree nut products (almond oil) and hydroxybenzoates.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Cream.
AndroForte 5 is a white, opaque, oil-in-water cream.

4 Clinical Particulars

4.1 Therapeutic Indications

AndroForte 5 is indicated for use as testosterone replacement therapy for male hypogonadism when testosterone deficiency has been confirmed by clinical features and biochemical tests.

4.2 Dose and Method of Administration

Adult men (18 years old and above).

Application to the scrotum.

The recommended starting dose of AndroForte 5 when applied to the entire scrotum is 0.5 mL of cream (i.e. 25 mg of testosterone) applied once daily at about the same time, preferably in the morning. The daily dose should be adjusted by the doctor depending on the clinical and/or laboratory response in individual patients, not exceeding 1 mL of cream per day. The adjustment of dosage should be achieved by 0.25 mL increments.
The application should be administered by the patient himself, onto clean, dry, healthy skin on the scrotum. The scrotum is not required to be shaved prior to application.

Application to the upper body.

The recommended starting dose of AndroForte 5 when applied to the upper body is 2 mL of cream (i.e. 100 mg of testosterone) applied once daily at about the same time, preferably in the morning. The daily dose should be adjusted by the doctor depending on the clinical and/or laboratory response in individual patients, not exceeding 4 mL of cream per day. The adjustment of dosage should be achieved by 1 mL increments.
The application should be administered by the patient himself, onto clean, dry, healthy skin to the torso. The torso includes the abdomen and the sides of the body from the waist to just below the armpits. It is preferable to apply to areas with minimal hair and body fat.

Method of administration.

After opening the tube, the patient should be directed to measure the appropriate dose using the graduated applicator and immediately apply to clean dry skin. The cream should be spread on the skin gently and massaged in until vanished. Typically, this takes 30 seconds or so. Wash hands with soap and water after applications. To clean the applicator after use, rinse in hot water.

Monitoring.

Hypogonadal symptom control is the primary aim of testosterone therapy via achieving a serum testosterone concentration sufficient to restore physiological androgen status to that comparable with eugonadal men. Biochemistry is an adjunct indicator of treatment response together with the identification and monitoring of the man's leading symptom. Trough testosterone levels should be within the lower limit of the reference interval for eugonadal men.

Application to the scrotum.

Eugonadal serum testosterone concentrations are generally reached within 24 hours of a single dose of AndroForte 5 applied scrotally. Absorption is variable between individuals and will have a different pharmacokinetic profile for men changing from non-scrotal testosterone products. In order to adjust the testosterone dose for scrotal application it is recommended that two (2) serum testosterone concentrations be measured at 3 hours (peak) and 24 hours (trough) from prior application after the 15th day of starting treatment. Results of clinical and/or biochemical monitoring may prompt dose titration.

Application to the upper body.

Eugonadal serum testosterone concentrations are generally reached within 24 hours of a single dose of AndroForte 5. Absorption is variable between individuals. In order to adjust the testosterone dose, serum testosterone concentrations must be measured in the morning before application after the 15th day of starting treatment. Results of clinical and/or biochemical monitoring may prompt dose titration.

Paediatric use.

AndroForte 5 is not indicated for use in children and has not been evaluated clinically in males under 18 years of age.

4.3 Contraindications

Testosterone is contraindicated in men with known or suspected carcinoma of the breast or prostate.
Hypersensitivity to the active substance (testosterone) or to any of the excipients.

4.4 Special Warnings and Precautions for Use

Androgens may accelerate the progression of subclinical prostate cancer and benign prostatic hyperplasia.
AndroForte 5 should not be used by women or children due to possible virilising effects.
Prior to testosterone initiation, all patients must undergo a detailed examination in order to assess for pre-existing prostate cancer. Careful and regular monitoring of the prostate gland (digital rectal examination and estimation of serum PSA (prostate specific antigen)) and breast must be performed in accordance with recommended practice in patients receiving testosterone therapy at least once yearly and twice yearly in elderly and at risk patients (those with clinical or familial risk factors).
Testosterone should be used only if hypogonadism (hyper- and hypogonadotropic) has been demonstrated and if other aetiology, responsible for the symptoms, has been excluded before treatment is started. Testosterone insufficiency should be clearly demonstrated by clinical features (regression of secondary sexual characteristics, change in body composition, asthenia, reduced libido, erectile dysfunction etc.) and confirmed by two separate blood testosterone measurements. Due to variability in laboratory values, all measures of testosterone should be carried out in the same laboratory.
Testosterone concentrations should be monitored when switching the patient from another testosterone product to AndroForte 5 or when switching from AndroForte 5 upper body application to scrotal application and vice versa.
Modest elevations of serum dihydrotestosterone (DHT) concentrations are commonly observed after scrotal and non-scrotal administration of testosterone, however there is no evidence to suggest that high circulating DHT concentrations have a deleterious effect on the prostate and cardiovascular safety profile.
In addition to monitoring the testosterone concentrations in patients on long-term androgen therapy the following laboratory parameters should be checked periodically: haemoglobin, haematocrit (to avoid the risk of polycythaemia), liver function tests, and lipid profile.
Increases in haematocrit may require reductions in dose or discontinuation of testosterone therapy. Increased haematocrit may increase the risk for a thromboembolic event. Changes in serum lipid profile may require dose adjustment or discontinuation of testosterone therapy.

Clotting disorders.

Testosterone should be used with caution in patients with thrombophilia or risk factors for venous thromboembolism (VTE), as there have been post-marketing studies and reports of thrombotic events (e.g. deep-vein thrombosis, pulmonary embolism, ocular thrombosis) in these patients during testosterone therapy. In thrombophilic patients, VTE cases have been reported even under anticoagulation treatment, therefore continuing testosterone treatment after first thrombotic event should be carefully evaluated. In case of treatment continuation, further measures should be taken to minimise the individual VTE risk.
With specific reference to AndroForte 5, erythrocytosis and skin reactions are at the lowest end of the risk scale when transdermal testosterone is the mode of delivery. If the patient develops a severe application site reaction, treatment should be assessed and discontinued if necessary.
Testosterone is not a treatment for male sterility or impotence in men with normal serum testosterone levels.
With large doses of exogenous androgens, spermatogenesis may be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH) which could possibly lead to adverse effects on semen parameters including sperm count.
Certain clinical signs: irritability, nervousness, weight gain, prolonged or frequent erections may indicate excessive androgen exposure requiring dosage adjustment.
In patients suffering from severe cardiac, hepatic or renal insufficiency or ischemic heart disease, treatment with testosterone may cause severe complications characterised by oedema with or without congestive cardiac failure. In such case, treatment must be stopped immediately. There are no studies undertaken to demonstrate the efficacy and safety of AndroForte 5 in patients with renal or hepatic impairment.
Patients with pre-existing cardiac, hepatic or renal diseases need to be monitored closely when undergoing androgen treatment. Because AndroForte 5 is not taken orally hepatotoxicity is not a risk factor.
Gynecomastia occasionally develops and occasionally persists in patients being treated with androgens for hypogonadism.
There are published reports of increased risk of sleep apnoea in hypogonadal men treated with testosterone, especially those with risk factors such as obesity or chronic lung disease.
Testosterone should be used with caution in patients with epilepsy and migraine as these conditions may be aggravated.
Testosterone should be used with caution in cancer patients at risk of hypercalcaemia (and associated hypercalciuria), due to bone metastases. Regular monitoring of serum calcium concentrations is recommended in these patients.
Testosterone may cause an increase in blood pressure and should be used with caution in patients with hypertension.
Changes in insulin sensitivity may occur in patients treated with androgens who achieve normal testosterone plasma concentrations following replacement therapy.
Athletes should be informed that AndroForte 5 contains an active substance (testosterone), which may give positive results in an antidoping test.
Androgens are not indicated for enhancing muscular development in healthy individuals.

Potential for transfer.

Transdermal testosterone cream can be transferred to other persons by close skin to skin contact, resulting in increased testosterone serum levels and, with repeated contact, possibly adverse effects. In women, this may cause growth of facial and/or body hair, deepening of the voice, irregularities of the menstrual cycle; in children this may cause premature puberty and genital enlargement, in case of repeat contact (inadvertent androgenisation). If virilisation occurs, testosterone therapy should be promptly discontinued until the cause has been identified.
The physician should inform the patient carefully about the risk of testosterone transfer and about safety instructions (see below). AndroForte 5 should not be prescribed to patients with a major risk of noncompliance with safety instructions (e.g. severe alcoholism, drug abuse and severe psychiatric disorders).
The risk of transfer is substantially reduced by wearing clothes covering the application area. The majority of residual testosterone is removed from the skin surface by washing with soap and water prior to contact.
As a result, the following precautions are recommended:

For the patient.

Wash hands thoroughly with soap and water after applying the cream.
Cover the application area with clothing once the cream has dried.
Wash before any situation in which skin-to-skin contact is foreseen.

For people not being treated with AndroForte 5.

In the event of contact with an application area which has not been washed or is not covered with clothing, wash the area of skin onto which testosterone may have been transferred as soon as possible, using soap and water.
Report the development of signs of excessive androgen exposure such as acne or hair modification.
To improve partner safety the patient should be advised to wear a T-shirt covering the upper body application site during the contact period or to shower before sexual intercourse.
To improve partner safety using scrotal application wash the genital area with a damp warm flannel before sexual intercourse.
Furthermore, it is recommended to wear clothing covering the upper body application site during contact periods with children in order to avoid transference to children.
Pregnant women must avoid any contact with AndroForte 5 application sites. In case of pregnancy of the partner, the patient must be particularly careful to avoid potential transfer.

Use in hepatic impairment.

No formal studies were conducted with AndroForte 5 involving patients with hepatic impairment. Lower doses may be required in hepatic impairment.

Use in renal impairment.

No formal studies were conducted with AndroForte 5 involving patients with renal impairment. Lower doses may be required in renal impairment.

Use in the elderly.

There is limited experience of the use of testosterone in elderly patients over 65 years of age. Currently, there is no consensus about age specific testosterone reference values. However, it should be taken into account that physiological testosterone serum levels are lower with increasing age.

Paediatric use.

The safety and efficacy of AndroForte 5 in children and adolescents aged under 18 years of age has not been established.
The patient should be advised to wash their hands well with soap and water after AndroForte 5 has been applied in case of contact with children.

Effects on laboratory tests.

Androgens may decrease levels of thyroxine binding globulin resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Changes in insulin sensitivity, glucose tolerance, glycaemic control, blood glucose and glycosylated haemoglobin have been reported with androgens. In diabetic patients, medication requirements may change.
When androgens are used simultaneously with anticoagulants, the anticoagulant effects may be increased. More frequent monitoring of INR and prothrombin time is recommended in patients taking anticoagulants, especially at the initiation and termination of androgen therapy.
The concurrent use of testosterone with ACTH or corticosteroids may result in increased fluid retention and should be monitored, particularly in patients with cardiac, renal or hepatic disease.
Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.
In diabetic patients, the metabolic effects of androgens may decrease blood glucose levels, and therefore, insulin requirements.
Concurrent administration of testosterone and bupropion may result in a lowered seizure threshold.
Concurrent administration with ciclosporin may result in increased ciclosporin toxicity and elevated ciclosporin blood levels.
Theoretically, in general, any substance which affects liver function should not be taken with testosterone, although this may not be as problematic with transdermal preparations such as AndroForte 5. Examples of herbal products include: ancreamica dahurica, chapparal, comfrey, eucalyptus, germander tea, Jin Bu Huan, kava, penny royal oil, skullcap, and valerian.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility studies in rodents and primates have shown that treatment with testosterone can impair fertility by suppressing spermatogenesis in a dose dependent manner.
(Category D)
Testosterone is contraindicated in women who are or who anticipate becoming pregnant. Pregnant women must avoid any contact with AndroForte 5 application sites. Exposure of a fetus to androgens may result in varying degrees of virilisation. In the event of contact, women are advised to wash with soap and water as soon as possible.
 Testosterone should not be used by breastfeeding women. In the event of accidental contact, women are advised to immediately wash with soap and water.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Adverse Effects (Undesirable Effects)

According to the literature or post-marketing reports or studies, additional undesirable events that are possibly or probably related to testosterone use are shown in Table 1.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
No cases of overdose with AndroForte 5 have been reported in clinical trials.
Treatment of overdose would consist of discontinuation of AndroForte 5 together with appropriate symptomatic and supportive care. Wash the skin with soap and water.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

AndroForte 5 is an androgen replacement therapy containing the male hormone testosterone.
Endogenous androgens, principally testosterone, secreted by the testes and its major metabolite dihydrotestosterone (DHT), are responsible for the development of the external and internal genital organs and for maintaining the secondary sexual characteristics (stimulating hair growth, deepening of the voice, development of the libido); for a general effect on protein anabolism; for development of skeletal muscle and body fat distribution; for a reduction in urinary nitrogen, sodium, potassium, chloride, phosphate and water excretion.
Testosterone does not produce testicular development: it reduces the pituitary secretion of gonadotropins.
The effects of testosterone in some target organs arise after peripheral conversion of testosterone to oestradiol, which binds to oestrogen receptors in the target cell nucleus e.g. the pituitary, fat, brain, bone and testicular Leydig cells.

Clinical trials.

Application to upper body.

The pivotal study was a phase II, randomised, crossover bioequivalence study of AndroForte 5 and a commercially available nonscrotal 1% transdermal testosterone gel (Testogel). Hypogonadal men (N = 15) were assigned to receive 2 mL AndroForte 5 (100 mg testosterone) per day, or 50 mg testosterone gel (5 mL of a 1% gel) per day for 30 days. The primary efficacy analysis was designed to demonstrate the bioequivalence of AndroForte 5 with the 1% testosterone gel on the basis of AUC and Cavg serum testosterone levels being within the eugonadal range. Other efficacy variables that were examined included: testosterone concentrations at day 30, dihydrotestosterone, oestradiol, luteinising hormone, follicle stimulating hormone and steroid hormone binding globulin concentrations, sexual questionnaire, mood/ energy questionnaire, general health survey and erectile function questionnaire. AndroForte 5 was bioequivalent to Testogel for the key pharmacokinetic parameters of Cmax, Cavg and AUC using adjusted and unadjusted for baseline values.
Table 2 demonstrates the Cmax and Cavg serum testosterone levels (nanomol/L) achieved from baseline up to 30 days of treatment in hypogonadal men from the pivotal phase II comparator trial in the same hypogonadal subjects.

Application to the scrotum.

A three-phase single-dose cross-over pharmacokinetic study of AndroForte 5 in endogenous testosterone suppressed healthy volunteers (n=11) described by Iyer 20171 demonstrated a nonlinear dose-dependent increase in serum testosterone Cmax following scrotal administration of testosterone doses of 12.5 mg, 25 mg and 50 mg. Testosterone was rapidly absorbed from the scrotal skin with a mean Tmax of 3.3-5.3 h. The mean Cmax (± SEM) for the 12.5 mg, 25 mg and 50 mg testosterone doses was 19.8 ± 3.8, 21.9 ± 2.8 and 28.8 ± 3.8 nanomol/L, respectively. Serum testosterone concentrations were maintained within the physiological reference range of 1.8-7.8 nanogram/mL (6.2-26.9 nanomol/L) for at least 12 h at the lowest 12.5 mg dose and for over 16 h for the 25 mg and 50 mg dose levels. Serum DHT concentrations after scrotal testosterone administration were higher than the physiological reference range of 0.07-0.64 nanogram/mL (0.24-2.21 nanomol/L) and independent of dose with a mean Cmax of 4.5-4.9 nanomol/L. Serum estradiol concentrations were independent of testosterone dose and remained within the physiological range of 15-68 picogram/mL (55-250 picomol/L) for 16 h post-dose. AndroForte 5 cream was well tolerated when applied to the scrotum with no complaints of skin irritation or discomfort after application. See Figure 1.
1 Iyer R, Mok SF, Savkovic S, et al. Pharmacokinetics of testosterone cream applied to scrotal skin. Andrology. 2017 Jul;5(4):725-731.

5.2 Pharmacokinetic Properties

Absorption.

Following percutaneous absorption, testosterone diffuses into the systemic circulation at relatively constant concentrations during the 24 hour cycle.
Serum testosterone concentrations increase from the first hour after an application of AndroForte 5, reaching eugonadal levels within 24 hours. Daily changes in testosterone concentrations are then of similar amplitude to those observed during the circadian rhythm of endogenous testosterone. The percutaneous route avoids blood peaks or the first pass effect of oral androgen therapy.
Administration of 2 mL of AndroForte 5 (100 mg testosterone) to the torso produces an average testosterone concentration increase in hypogonadic men of approximately 7.7 nanomol/L in serum with a Tmax around 14.8 hours after application.
Administration of a single dose 0.5 mL of AndroForte 5 (25 mg testosterone) to the scrotum of healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate produced a Cmax serum testosterone concentration of 19.1 nanomol/L with a Tmax around 2.8 hours after application.
The half-life of testosterone is controlled by skin permeation and not clearance/ metabolism.

Metabolism.

The major active metabolites of testosterone are DHT and oestradiol.

Excretion.

Testosterone is excreted, mostly in urine, and in faeces as conjugated testosterone metabolites.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of testosterone has not been fully investigated in a comprehensive battery of genotoxicity studies. However, testosterone was found not to be clastogenic when tested in vitro in assays with hamster lung fibroblasts or in mouse or hamster embryo fibroblasts, or in in vivo chromosome aberration assays in mouse bone marrow cells and spermatocytes. Testosterone was also negative in assays for unscheduled DNA synthesis in rat and human hepatocytes.

Carcinogenicity.

A relationship between androgen treatment and certain cancers has been found in laboratory animals. Experimental data in rats have shown increased incidences of prostate cancer after treatment with testosterone.
Sex hormones are known to promote the growth of certain hormone dependent tissues and tumours. Subcutaneous implantation of testosterone produced cervical-uterine tumours in female mice, which metastasised in some cases. Metastasising prostatic adenocarcinomas occurred in male rats after chemical induction and subcutaneous implantation of testosterone. Testosterone is also known to increase the number of tumours and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Hepatocellular carcinoma has been reported in patients receiving long-term therapy with androgens.
Hypogonadal men receiving androgen replacement therapy require surveillance for prostatic disease similar to that recommended for eugonadal men of comparable age.

6 Pharmaceutical Particulars

6.1 List of Excipients

Almond oil, butyl hydroxybenzoate, butylated hydroxytoluene, carbomer 940, cetomacrogol 1000, cetostearyl alcohol, citric acid, dl-alpha-tocopherol acetate, ethyl hydroxybenzoate, isobutyl hydroxybenzoate, methyl hydroxybenzoate, phenoxyethanol, propyl hydroxybenzoate, purified water, trolamine.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

The tube should not be opened until immediately prior to application of the cream.
Store below 25°C. Do not freeze.
In-use storage: AndroForte 5 should be used within 125 days of opening.

6.5 Nature and Contents of Container

AndroForte 5 is supplied in a 50 mL sealed tube with a dose applicator marked with 0.25 mL graduations in a carton.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Testosterone is an androgen. Chemically, testosterone is 17β-hydroxyandrost- 4-en-3-one and has the following structural formula:
Chemical Formula: C19H28O2.
Molecular Weight: 288.4 g/mol.
Testosterone is a white, crystalline powder, odourless or almost odourless produced semisynthetically from plant origin. It is practically insoluble in water, freely soluble in ethanol (96%); slightly soluble in ethyl oleate.

CAS number.

58-22-0.

7 Medicine Schedule (Poisons Standard)

S4 Prescription Only Medicine.

Summary Table of Changes