Consumer medicine information

Testogel Metered Dose Pump

Testosterone

BRAND INFORMATION

Brand name

Testogel

Active ingredient

Testosterone

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Testogel Metered Dose Pump.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Testogel. 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 risks of you using Testogel against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

WHAT TESTOGEL IS USED FOR

Testogel is used to replace the body’s natural hormone testosterone when not enough is made by the body.

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.

Testogel is a testosterone-containing gel that is applied by the patient daily to the skin. The testosterone passes from the gel through the skin and into the bloodstream at a steady rate.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

BEFORE YOU USE TESTOGEL

When you must not use it

Do not use Testogel if you have an allergy to:

  • testosterone, the active ingredient in Testogel
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • 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

Do not use Testogel if you have or are suspected to have:

  • prostate cancer
  • breast cancer in males

Testogel must not be used by children under the age of 18 years. The safety of Testogel in children under 18 years of age has not been established.

Testogel must not be used by women.

Do not use this medicine after the expiry date printed on the pack. The expiry date is printed on the carton after “EXP” (e.g. 11 18 refers to November 2018). The expiry date refers to the last day of that month. If it has expired return it to your pharmacist for disposal.

Do not use this medicine if the packaging is torn or shows signs of tampering. If the packaging is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start using this medicine, talk to your doctor.

Before you start to use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have, or have had, any of the following medical conditions:

  • high blood calcium levels associated with 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
  • thrombophilia (an abnormality of blood coagulation that increases the risk of thrombosis-blood clots in blood vessels)
  • epilepsy
  • migraines
  • diabetes
  • sleep apnoea (abnormal pauses in breathing during sleep)
  • polycythaemia (a blood disorder where too many red blood cells are being produced)

Testogel 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.

If you use Testogel 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 Testogel.

Athletes should note that the active substance, testosterone, may produce a positive reaction in anti-doping tests.

Misuse of androgens to enhance your physical ability in sport carries serious health risks and is discouraged. Use of androgens for reasons other than what your doctor prescribed carries a serious health risk and is strongly discouraged.

Taking other medicines

Tell your doctor 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 and Testogel may interfere with each other. 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
  • cyclosporin, a medicine used to suppress the immune system
  • some herbal products.

These medicines may be affected by Testogel or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using this medicine.

HOW TO USE TESTOGEL

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

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

How much to use

The usual starting dose for is 5g of gel per day. Your doctor or pharmacist will tell you exactly how much to use. You should not use more than 10g of gel per day.

How to use it

Do not apply Testogel to the testes, scrotum or penis.

Each 1% bottle of Testogel contains 0.89g alcohol (ethanol) in each dose of 1.25g gel.

The high alcohol content may cause local skin irritation.

The product is flammable until dry.

Follow these steps when applying Testogel multidose pump:

  1. Before using the pump for the first time, prime up the pump by pushing down on the pump 3 times. Do not use any Testogel that was dispensed during priming. Wash it down the sink or throw it in the trash can to avoid accidental exposure to others. Your Testogel pump is now ready to use.
  2. Spread a thin layer of Testogel onto clean, dry, healthy skin over the upper arms, shoulders or stomach. It is not necessary to rub Testogel into the skin.
  3. Allow the gel to dry for at least 3-5 minutes before dressing.
  4. Wash your hands thoroughly with soap and water after applying the gel.
  5. Cover the application area with clothing once the gel has dried.
  6. Do not shower for at least six (6) hours after applying Testogel.

When to use it

Apply Testogel once per day at approximately the same time each day, preferably in the morning. Using it at the same time each day helps maintain a steady level of testosterone in the blood. It will also help you remember when to apply it.

How long to use it

Testogel helps control the symptoms of your condition, but does not cure it. Therefore you must use Testogel every day.

When you have finished a pack, start the next pack on the following day. Never leave a break between packs.

Continue using Testogel for as long as your doctor tells you to.

If you forget to use it

If you forget to apply a dose, apply it as soon as you remember.

If you do not remember to apply the dose until the next dose is due, then just apply one dose.

Do not apply a double dose to make up for a forgotten individual dose.

If you use too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre on 13 11 26 for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have used too much Testogel. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

WHILE YOU ARE USING TESTOGEL

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using Testogel.

Tell any other doctors, dentists, and pharmacists who treat you that you are using this medicine.

Keep all of your doctor’s appointments. Your doctor may monitor your blood pressure, examine your prostate and conduct other tests (including blood tests) at least annually and more often if you are elderly. This is to make sure the medicine is working and to check for unwanted side effects.

The use of Testogel may affect the results of certain laboratory tests. If you are about to have any tests, tell your doctor that you are using this medicine.

Things you must not do

Do not use Testogel to treat any other complaints unless your doctor tells you to.

Do not give Testogel to anyone else, even if their symptoms seem similar to yours.

Do not stop using Testogel, 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.

Things to be careful of

Testosterone may be transferred to another person during close and relatively prolonged skin contact with the gel application area.

If contact occurs a number of times or for long periods of time this could cause the other person to show signs of increased testosterone such as more hair on the face and body and a deepened voice. In women, this may also cause changes in the menstrual cycle.

Unwanted transfer of testosterone to another person can be avoided 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.

You should leave a gap of 6 hours between applying Testogel and having intimate physical contact. You should also wear clothing such as a T-shirt to cover the gel application area and/or have a shower or bath beforehand.

You should also follow these precautions before coming into close contact with women and children. If a woman or child does come into contact with Testogel, thoroughly wash the area of skin exposed to the gel with soap and water.

SIDE EFFECTS

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Testogel. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • skin reactions such as irritation, redness, dry or stinging skin and/or hives
  • headaches
  • prostatic disorders such as difficulty or pain while urinating, frequent urination
  • painful, tender or enlarged breasts
  • dizziness
  • feeling of “pins and needles” or tingling sensation
  • memory loss
  • heightened senses
  • mood changes
  • high blood pressure
  • diarrhoea
  • hair loss

These are the common side effects of Testogel.

Your doctor may need to conduct blood tests to monitor red blood cell counts and increased haemoglobin which can be affected by use of testosterone.

Tell your doctor immediately, or go to Accident and Emergency department at your nearest hospital if you notice any of the following:

  • yellowing of the skin and eyes, also called jaundice
  • painful swelling of one leg or sudden change in colour of the skin e.g. turning pale, red or blue, sudden breathlessness, sudden unexplained cough which may bring up blood, or sudden chest pain, severe light headedness or dizziness, severe pain in your stomach, sudden loss of vision which can all be signs of a blood clot.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation if you experience one of these symptoms.

Other side effects that have been observed in rare or very low frequency

  • benign liver tumours
  • nervousness
  • depression
  • hostility
  • breathing problems during sleep (sleep apnoea)
  • muscle cramps
  • balding
  • acne
  • urinary obstruction
  • libido changes

Your doctor may need to monitor your blood pressure and conduct blood tests, as Testogel can increase your blood pressure and affect your liver function or profile.

You may not experience any specific symptoms.

Side effects associated with high doses or long term treatment include:

  • increased tendency to retain fluid (signs may include swollen feet or ankles)
  • weight gain
  • electrolyte changes
  • decreased sperm count, which may affect fertility
  • unwanted, frequent or prolonged and painful erections
  • severe stomach pain or tenderness, which do not disappear within a short time.

Tell your doctor if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some patients.

AFTER USING TESTOGEL

Storage

Keep Testogel in a cool dry place where the temperature stays below 25°C.

Do not store it or any other medicine in the bathroom, near a sink, or on a window-sill.

Do not leave it in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over. Return any unused medicine to your pharmacist.

PRODUCT DESCRIPTION

What it looks like

Testogel is a clear, colourless gel presented in a non-aerosol, metered-dose pump.

Each 100 mL metered-dose pump contains 880 mg of testosterone in 88 g of gel (delivers 60 actuations).

Each actuation delivers 12.5mg of testosterone in 1.25g of gel.

Ingredients

Testosterone - 12.5 mg per 1.25 g gel

  • Testosterone

Inactive ingredients:

  • carbomer 980
  • isopropyl myristate
  • ethanol
  • sodium hydroxide
  • purified water

Supplier

Made in France or Belgium for

Besins Healthcare
Australia Pty Ltd
Level 16, Tower 2, Darling Park,
201 Sussex Street,
Sydney, NSW 2000

Australian Registration Numbers

AUST R 227563

Date of Preparation

September 2020

® Registered Trademark of Besins Healthcare, Belgium
All rights reserved.

Published by MIMS July 2021

BRAND INFORMATION

Brand name

Testogel

Active ingredient

Testosterone

Schedule

S4

 

1 Name of Medicine

Testosterone.

2 Qualitative and Quantitative Composition

Testogel contains 1% testosterone.
Testogel also contains the excipients: isopropyl myristate, ethanol, carbomer 980, sodium hydroxide and purified water.

Excipient with known effect.

Ethanol.

3 Pharmaceutical Form

Testogel is a clear, colourless, hydroalcoholic transdermal gel containing 1% testosterone.

4 Clinical Particulars

4.1 Therapeutic Indications

Testogel 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

Dose.

Adult men.

The recommended dose is 5 g of gel (i.e. 50 mg of testosterone which equates to four pump actuations, two 25 mg sachets* or one 50 mg sachet) 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 or laboratory response in individual patients, not exceeding 10 g of gel per day. The adjustment of dosage should be achieved by 2.5 g of gel steps.
Lower doses may be required in renal or hepatic impairment.
Steady-state plasma testosterone concentrations are reached by the end of the 2nd day of treatment with Testogel. In order to adjust the testosterone dose, serum testosterone concentrations must be measured in the morning before application from the 3rd day on after starting treatment (one week seems reasonable). The dose may be reduced if the plasma testosterone concentrations are raised above the desired level. If the concentrations are low, the dosage may be increased, not exceeding 10 g of gel per day.
* 25 mg sachet not currently marketed.

Method of administration.

Transdermal use.
The application should be administered by the patient himself, onto clean, dry, healthy skin over either shoulder or either arm or abdomen.
If using the gel sachets, after opening the sachets, the total contents must be extracted from the sachet and applied immediately onto the skin.
If using the metered dose pump pack, it is necessary to prime the pump pack only before initial use. To do so, with the pump pack in the upright position, slowly and fully depress the actuator three times. Safely discard the gel from the first three actuations. Each pump actuation delivers 12.5 mg of testosterone in 1.25 g of gel and to obtain the equivalent of 50 mg of testosterone, 4 pump actuations are needed. Please refer below to dosing information (see Table 1):
After extracting the gel, the gel has to be simply spread on the skin gently as a thin layer. It is not necessary to rub it on the skin. Allow drying for at least 3-5 minutes before dressing. Wash hands with soap and water after applications.
Do not apply to the genital areas as the high alcohol content may cause local irritation.

Paediatric use.

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

Use in women.

Testogel is not indicated for use in women.

4.3 Contraindications

Testogel is contraindicated: in cases of known or suspected prostatic cancer or breast carcinoma;
in cases of known hypersensitivity to testosterone or to any other constituent of the gel.
Testogel must not be used in women or children.

4.4 Special Warnings and Precautions for Use

Testogel should be used only if hypogonadism (hypergonadotrophic and hypogonadotrophic) has been demonstrated and if other aetiologies responsible for the symptoms have 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 biochemical tests (two separate blood testosterone measurements). However, it should be taken into account that physiologically testosterone serum levels fall with increasing age.
Due to variability in laboratory values, all measures of testosterone should be carried out in the same laboratory.
Testogel is not a treatment for male sterility or impotence.
Prior to testosterone initiation, all patients must undergo a detailed examination in order to exclude the risk of pre-existing prostatic cancer. Careful and regular monitoring of the prostate gland and breast must be performed in accordance with recommended methods (digital rectal examination and estimation of serum PSA) in patients receiving testosterone therapy at least once yearly and twice yearly in elderly patients and at risk patients (those with clinical or familial factors).
Androgens may accelerate the progression of subclinical prostatic cancer and benign prostatic hyperplasia.
Testogel 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.
In patients suffering from severe cardiac, hepatic or renal insufficiency, treatment with Testogel may cause severe complications characterised by oedema with or without congestive cardiac failure. In this case, treatment must be stopped immediately. In addition, diuretic therapy may be required.
Testogel should be used with caution in patients with ischaemic heart disease.
Testosterone may cause a rise in blood pressure and Testogel should be used with caution in patients with hypertension.

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 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.
Testosterone level should be monitored at baseline and at regular intervals during treatment. Clinicians should adjust the dosage individually to ensure maintenance of eugonadal testosterone levels.
In patients receiving long-term androgen therapy, the following laboratory parameters should be monitored regularly: haemoglobin and haematocrit (to detect polycythaemia), liver function tests, and lipid profile.
There is limited experience on the safety and efficacy of the use of Testogel in 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 physiologically, testosterone serum levels are lower with increasing age.
Testogel should be used with caution in patients with epilepsy and migraine as these conditions may be aggravated.
There are published reports of increased risk of sleep apnoea in hypogonadal subjects treated with testosterone esters, especially in those with risk factors such as obesity and chronic respiratory disease.
Improved insulin sensitivity may occur in patients treated with androgens who achieve normal testosterone plasma concentrations following replacement therapy.
Certain clinical signs: irritability, nervousness, weight gain, prolonged or frequent erections may indicate excessive androgen exposure requiring dosage adjustment.
If the patient develops a severe application site reaction, treatment should be reviewed and discontinued if necessary.
The attention of athletes is drawn to the fact that this proprietary medicinal product contains an active substance (testosterone) which may produce a positive reaction in antidoping tests.
Testogel must not be used in women, due to possible virilising effects.
Each 2.5 g sachet of Testogel contains 1.8 g alcohol (ethanol).
Each 5 g sachet of Testogel contains 3.6 g alcohol (ethanol).
Each 1% bottle of Testogel contains 0.89 g alcohol (ethanol) in each dose of 1.25 g gel.
It may cause a burning sensation on damaged skin.
This product is flammable until dry.

Potential testosterone transfer.

If no precaution is taken, testosterone gel can be transferred to other persons by close skin to skin contact, resulting in increased testosterone serum levels and possibly adverse effects (e.g. growth of facial and/or body hair, deepening of the voice, irregularities of the menstrual cycle) in case of repeated contact (inadvertent androgenisation).
The doctor should inform the patient carefully about the risk of testosterone transfer, for instance during close bodily contact between individuals, including children, and about safety instructions (see below). Testogel should not be prescribed in patients with a major risk of noncompliance with safety instructions (e.g. severe alcoholism, drug abuse, severe psychiatric disorders).
This transfer is avoided by wearing clothes covering the application area or washing the application areas with soap and water prior to contact.
The following precautions are recommended:

For the patient.

Wash hands with soap and water after applying the gel, cover the application area with clothing once the gel has dried, wash the application area before any situation in which close contact is foreseen.

For people not being treated with Testogel.

In the event of contact with Testogel, the person affected should wash the affected area with soap and water immediately, report the development of signs of excessive androgen exposure such as acne or hair modification.
According to in vitro absorption studies on testosterone conducted with Testogel, it seems preferable for patients to observe at least six hours between gel application and bathing or showering. Occasional baths or showers taken between one and six hours after application of the gel should not significantly influence the treatment outcome.
To facilitate partner safety, the patient should be advised, for example, to observe a long interval between Testogel application and sexual intercourse, to wear a T-shirt covering the application site during contact period or to shower before sexual intercourse. In the case of a pregnant partner, the patient must reinforce his attention to the precautions for use.
Furthermore, it is recommended to wear a T-shirt, covering the application site, during contact period with children, in order to avoid a contamination risk to the child's skin.

Use in hepatic impairment.

In patients suffering from severe cardiac, hepatic or renal insufficiency, treatment with Testogel may cause severe complications characterised by oedema with or without congestive cardiac failure. In this case, treatment must be stopped immediately. In addition, diuretic therapy may be required.

Use in renal impairment.

See Section 4.4 Special Warnings and Precautions for Use, Use in hepatic impairment.

Use in the elderly.

Currently, there is no consensus about age specific testosterone reference values.

Paediatric use.

Testogel must not be used in children.

Effects on laboratory tests.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

Oral anticoagulants.

Changes in anticoagulant activity (the increased effect of the oral anticoagulant by modification of coagulation factor hepatic synthesis and competitive inhibition of plasma protein binding):
Increased monitoring of the prothrombin time, and INR determinations are recommended. Patients receiving oral anticoagulants require close monitoring especially when androgens are started or stopped.

Corticosteroids.

Concomitant administration of testosterone and ACTH or corticosteroids may increase the risk of developing oedema. As a result, these medicinal products should be administered cautiously, particularly in patients suffering from cardiac, renal or hepatic disease.
Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone.

Diabetic medication.

Changes in insulin sensitivity, glucose tolerance, glycaemic control, blood glucose and glycosylated haemoglobin levels have been reported with androgens. In diabetic patients, the dose of antidiabetic medications may need reduction (see Section 4.4 Special Warnings and Precautions for Use).
Concurrent administration of testosterone and buproprion may result in a lowered seizure threshold.
Concurrent administration with cyclosporin may result in increased cyclosporin toxicity and elevated cyclosporin 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 Testogel. Examples of herbal products include Angelica 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.

Spermatogenesis may be reversibly suppressed with Testogel.
(Category D)
Testogel intended for use by men only.
Testogel must not be used in pregnant women under any circumstance. No clinical study has been conducted with this treatment in women, but testosterone is known to have potential adverse virilising effects on the fetus.
Pregnant women must avoid any contact with Testogel application sites (see Section 4.4 Special Warnings and Precautions for Use). In the event of contact, wash with soap and water as soon as possible.
 Testogel should not be used in breastfeeding women. Care should be taken by breastfeeding women to avoid contact with Testogel application sites. In the event of contact, wash with soap and water as soon as possible.

4.7 Effects on Ability to Drive and Use Machines

Testogel has no influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

a. Summary of the safety profile.

The most frequently observed adverse drug reactions at the recommended dosage were skin reactions: reaction at the application site, erythema, acne, and dry skin.

b. Tabulated list of adverse reactions.

Clinical trial data.

Adverse drug reactions reported in 1 - < 10% of patients treated with Testogel in the controlled clinical trials are listed (see Table 2):
Adverse effects have been ranked under headings of frequency using the following convention: very common (≥ 1/10); common (≥ 1/100; < 1/10); uncommon (≥ 1/1,000; < 1/100); rare (≥ 1/10,000; < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).

Post-marketing experience.

The following (Table 3) includes adverse reactions identified during post-approval use of Testogel in addition to other known undesirable effects reported in the literature following testosterone oral, injectable or transdermal treatment:
Adverse effects have been ranked under headings of frequency using the following convention: very common (≥ 1/10); common (≥ 1/100; < 1/10); uncommon (≥ 1/1,000; < 1/100); rare (≥ 1/10,000; < 1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated from the available data).
Post marketing reports of venous thromboembolism.
The pivotal clinical trial of Testogel versus a transdermal testosterone patch showed that some individuals would achieve suboptimal bioavailability.

Reporting suspected adverse effects.

Reporting suspected adverse effects 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

Symptoms.

Serum testosterone levels should be measured if clinical signs and symptoms indicative of over-exposure to androgen are observed.
Application site rash has also been reported in case reports of overdose with Testogel.

Treatment.

Treatment of overdosage consists of washing the application site immediately and discontinuing treatment if advised by the treating physician.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Testogel 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.

The pivotal study was a phase III, randomised, positive controlled, parallel group study of Testogel and a commercially available nonscrotal transdermal testosterone patch. Hypogonadal men (n = 227) were assigned to receive 5 g Testogel (50 mg testosterone) per day, 10 g Testogel (100 mg testosterone) per day or 5 mg testosterone patch (2 x 2.5 mg) per day for 90 days. The primary efficacy analysis was designed to demonstrate the comparability of Testogel with the testosterone patch on the basis of Cmin and Cavg serum testosterone levels being within the eugonadal range. Other efficacy variables that were examined included testosterone concentrations at day 90, dihydrotestosterone, oestradiol, luteinising hormone, follicle stimulating hormone and steroid hormone binding globulin trough concentrations, sexual questionnaire, muscle strength, body composition and bone markers. Testogel was demonstrated to be noninferior to the testosterone patch for the outcomes investigated.
Table 4 demonstrates the Cavg serum testosterone levels (nanogram/dL) achieved from baseline up to 90 days of treatment in hypogonadal men (number of patients in parenthesis).

5.2 Pharmacokinetic Properties

Absorption.

Approximately 10% of the testosterone dose applied on the skin surface from Testogel is absorbed into the systemic circulation. The surface area of skin contact does not greatly affect the level of testosterone absorption.

Distribution.

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, reaching steady state from the end of day two. 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 5 g of Testogel produces an average testosterone concentration increase in hypogonadal men of approximately 8.7 nanomol/L in plasma.
When treatment is stopped, testosterone concentrations start decreasing approximately 24 hours after the last dose. Concentrations return to baseline approximately 72 to 96 hours after the final dose.

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.

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 promotes hepatocarcinogenesis in mice and rats.

Carcinogenicity.

Hepatocellular carcinoma has been reported in patients receiving long-term therapy with androgens. Chronic androgen deficiency is a protective factor for prostatic disease and hypogonadal men receiving androgen replacement therapy require surveillance for prostatic disease similar to that recommended for eugonadal men of comparable age.
The genotoxic potential of testosterone has not been fully investigated, although limited data available to date suggest that it is not genotoxic.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Testogel is available for use in the following two presentations:

Sachet.

As individual doses of 1% testosterone gel in a sachet (multi-layer sachet (PET/Al/LDPE). Each sachet contains either 25 mg testosterone in 2.5 g gel* or 50 mg testosterone in 5 g gel.
* 25 mg sachet not currently marketed.
Boxes of sachets contain 1, 2, 7, 10, 14, 28, 30, 50, 60, 90 or 100 sachets. Not all pack sizes may be marketed.
Each sachet should not be opened until immediately prior to application of the gel.
or

Metered-dose pump pack.

As a metered-dose pump (polypropylene (PP) bottle and a multi-layer pouch (PET/Al/LDPE)) containing 880 mg testosterone in 88 g of gel (delivering 60 actuations). Each individual pump actuation delivers 12.5 mg of testosterone in 1.25 g of gel.
Boxes of metered-dose pump contain 1 or 2 bottles. Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

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.
Testosterone is an androgen. Chemically testosterone is 17β-hydroxyandrost-4-en-3-one and has the following structural formula:

Chemical structure.


Chemical Formula: C19H28O2.
Molecular Weight: 288.4.

CAS number.

58-22-0.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes