Consumer medicine information

Andriol Testocaps

Testosterone undecanoate

BRAND INFORMATION

Brand name

Andriol Testocaps

Active ingredient

Testosterone undecanoate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Andriol Testocaps.

What is in this leaflet

This leaflet answers some common questions about Andriol Testocaps. 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 weighted the risks of you taking Andriol Testocaps against the benefits they expect it will have for you.

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

Keep this leaflet with the medicine.

You may need to read it again.

What Andriol Testocaps is used for

The name of your medicine is Andriol Testocaps.

Andriol Testocaps is used in adult men for testosterone replacement to treat various health problems caused by a lack of testosterone (male hypogonadism). Your doctor will confirm this by blood testosterone measurements and also clinical symptoms such as inability to get or maintain an erection (impotence), infertility, low sex drive, tiredness, depressive moods, or bone loss caused by low hormone levels.

Each capsule contains 40 mg of the active ingredient called testosterone undecanoate. Testosterone undecanoate is turned into testosterone by your body. Testosterone is a natural male hormone known as an androgen, a type of sex hormone necessary for the normal sexual development of males.

In men testosterone is produced by the testicles. It is necessary for the normal growth, development and function of the male sex organs and for secondary male sex characteristics. It is necessary for the growth of body hair, the development of bones and muscles, and it stimulates the production of red blood cells. It also makes men's voices deepen.

Because of problems with the pituitary or testis, the production of testosterone by the body decreases.

Men may suffer from complaints such as depression, loss of motivation or concentration, and loss of sexual desire. Andriol Testocaps can relieve these complaints. It can also relieve these symptoms in men who have had their testis removed. Relief of symptoms usually starts within a few days, but optimal results are obtained after weeks to months of treatment.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

A doctor's prescription is required to obtain this medicine.

Before you take Andriol Testocaps

When you must not take it

Do not use Andriol Testocaps if

  • you have or have had a tumour of your prostate or breast or are suspected to have one of these tumours.
  • you have or have had severe kidney disease
  • you are allergic to testosterone undecanoate or any of the ingredients listed under Product Description, at the end of this leaflet.

Do not use Andriol Testocaps if the packaging is torn or shows signs of tampering.

Before you start to take it

Andriol Testocaps may not be suitable for you if you suffer from certain medical conditions.

Tell your doctor or pharmacist before you start using this medicine if you ever had, still have, or are suspected to have (particularly if you are elderly):

  • heart disease, high blood pressure or blood vessel problems
  • Diabetes mellitus, Kidney disease
  • Kidney or lung cancer;
  • Liver disease;
  • Breast cancer which has spread to the bones;
  • Epilepsy
  • Migraine, headaches
  • Psychiatric or emotional illness
  • Prostatic complaints, such as problems with passing urine.
  • Any unusual or allergic reactions to androgens or anabolic steroids
  • Factors that increase your risk for blood clots in a vein i.e. previous blood clots in a vein; smoking; obesity; cancer; immobility; if one of your immediate family has had a blood clot in the leg, lung or other organ at a young age (below the age of 50); or as you get older.
  • Sleep apnoea (temporarily stopping breathing during your sleep), this may get worse if you are using testosterone-containing products. Let your doctor know if you are worried about this. Extra supervision by your doctor may be necessary in case you are overweight or suffer from chronic lung disease.

Tell your doctor if

  • you are on a special diet, e.g. low salt, lower sugar and you are taking any other medicines.
  • you have or have ever had too much cholesterol or other fatty substances in the blood.
  • you have been treated with other sex hormones recently.

Caution:

During long-term treatment with Andriol Testocaps regular medical checks, including prostate examination, are recommended.

Children and adolescents:

The safety and efficacy of this medicine has not been adequately determined in children and adolescents.

Extra supervision by a doctor is necessary in the treatment of young boys and adolescents since testosterone administration in general may cause early sexual development and limits growth.

Elderly people:

There is limited experience on the safety and efficacy of the use of Andriol Testocaps in patients over 65 years of age.

Taking other medicines

Please tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines - even those not prescribed that you buy from your pharmacy, supermarket or healthfood shop.

Other medicines may influence the effects of Andriol Testocaps, or Andriol Testocaps may affect other medicines.

Therefore you must tell your doctor or pharmacist if you are taking (or intend to take) other medicines such as:-

  • Barbiturates, (medicines for epilepsy or sleeplessness)
  • Ciclosporin
  • Insulin and/or other medicines to control your blood sugar levels (antidiabetic drugs)*
  • Medicines to reduce the clotting of your blood (anti-coagulants)*

* The use of androgens like Andriol Testocaps may lead to a reduction of the doses of these medicines.

Also tell your doctor or pharmacist if you are using or about to use

  • the hormone ACTH or corticosteroids (used to treat various conditions such as rheumatism, arthritis, allergic conditions and asthma).

The use of androgens like Andriol Testocaps may increase the risk of water retention especially if your heart and liver are not working properly.

Andriol Testocaps may interfere with some laboratory tests (e.g for glucose tolerance, thyroid function and clotting factors).

Therefore you must tell your doctor or the laboratory staff performing the tests that you are using this medicine.

Andriol Testocaps are not intended for use in female patients. Therefore this medicine must not be taken by women who are pregnant or think that they are pregnant, or by women who are breast-feeding.

In men, treatment with Andriol Testocaps can lead to fertility disorders by repressing sperm formation.

If you are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

This medicine contains Sunset Yellow FCF which may cause allergic reactions.

Improper use:

If you are a patient who participates in competitions governed by the World Anti-Doping Agency (WADA), then you should consult the WADA-code before using this medicine as Andriol Testocaps can interfere with anti-doping testing.

The misuse of this medicine to enhance ability in sports carries serious health risks and is to be discouraged.

Drug abuse and dependence:

Always take this medicine exactly as your doctor or pharmacist has told you.

Abuse of testosterone, especially if you take too much of this medicine alone or with other anabolic androgenic steroids, can cause serious health problems to your heart and blood vessels (that can lead to death), mental health and/or the liver. Individuals who have abused testosterone may become dependent and may experience withdrawal symptoms when the dosage changes significantly or is stopped immediately. You should not abuse this medicine alone or with other anabolic androgenic steroids because it carries serious health risks. (See "Side Effects.")

How to take Andriol Testocaps

Take Andriol Testocaps exactly as directed by your doctor. You should also read the instructions on the label of your medicine. If you are not sure how to take Andriol Testocaps, ask your doctor or pharmacist.

How and when to take it

Take the capsules daily, as directed by your doctor. Andriol Testocaps are to be swallowed after the morning and evening meal.

Swallow the capsules whole with some water or other drink. Do not chew them.

If you are taking an uneven number of capsules, the larger dose should be taken in the morning.

Food allows testosterone undecanoate, the active substance of this medicine, to be taken up by your body. Therefore, Andriol Testocaps must be taken with a meal.

If you have the impression that the effect of this medicine is too strong or too weak, talk to your doctor or pharmacist immediately.

Use in children and adolescents:

The safety and efficacy of this medicine have not been adequately determined in children and adolescents. Pre-pubertal children using this medicine will be monitored by your doctor

If you forget to take it

If you forget to take a capsule, take it as soon as you remember. If you do not remember to take the dose until the next dose is due, then just take one dose, do not double up.

If you take too much (overdose)

It is not a medical emergency if someone has taken several capsules at once. However, you should consult a doctor, or the Australian Poisons Information Centre (telephone 131 126) or the New Zealand National Poisons Centre (telephone 0800 POISON or 0800 764 766) if you think you or anyone else may have taken too much Andriol Testocaps. Symptoms that may arise are nausea and vomiting and oily bowel motions. The oily substance in the capsule may cause diarrhoea.

If you stop taking Andriol Testocaps:

When treatment with this medicine is stopped, complaints such as those experienced before treatment may re-occur within a few weeks.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

While you are taking Andriol Testocaps

Things you must do

Stop taking Andriol Testocaps if you develop jaundice (yellowing of the eyes or skin).

Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

Take special care with Andriol Testocaps

Treatment with male hormones like testosterone may increase the size of the prostate gland, especially in elderly men. Therefore your doctor will examine your prostate gland at regular intervals by digital rectal examination (DRE) and blood tests for prostate-specific antigen (PSA).

Additionally, at regular intervals, blood tests will be done to check the oxygen-carrying substance in your red blood cells (haemoglobin). In very rare cases the number of red blood cells will increase too much leading to complications.

Your doctor will measure testosterone blood levels before and during your treatment. Based on the blood test results, your doctor may adjust the dose of Andriol Testocaps.

Medical checks may also be necessary in some other conditions.

If you are unsure of any of the aspects of this product, please discuss with your doctor or pharmacist.

Things you must not do

Do not give Andriol Testocaps to anyone else, even if they have the same condition as you. Remember that your doctor has prescribed this medicine only for you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Things to be careful of

Ability to drive or operate machinery

As far as is known, this medicine has no influence on driving and using machines.

Side Effects

Andriol Testocaps are generally well tolerated.

Tell your doctor or pharmacist if you notice any of the following and they worry you.

In general side effects which are reported with testosterone therapy include:

  • stomach or bowel complaints: oily bowel motions, abdominal or stomach pain, black, tarry or light coloured stools or dark coloured urine, vomiting, nausea, diarrhoea
  • acne, itching (pruritus) skin irritation: pimply spotty rash, hives
  • sleeplessness, chills, generalised tingling, unusual tiredness
  • headache, anxiety, mental depression, excitation, confusion, dizziness, nervousness, mood alterations
  • muscle pain (myalgia)
  • prolonged abnormal, painful irreversible erection, inflamed testis, bladder irritability
  • sexual dysfunction, changes in sexual desire, disturbed sperm formation
  • Feminization (gynecomastia)
  • prostatic growth to a size representative for the concerned age group
  • high blood pressure (hypertension)
  • blood disorders, increase in the number of red blood cells (the cells which carry the oxygen in your blood),
  • increase in percentage of red blood cells relative to the total blood volume (haematocrit);
  • increased concentration of the red blood cell component that carries oxygen (haemoglobin);
  • increased levels of a blood marker which is associated with prostate cancer (PSA increased)
  • changes in cholesterol levels (changes in lipid metabolism)
  • shortness of breath
  • fluid retention in the tissues, usually marked by swelling of ankles, feet or lower legs (oedema)
  • breast enlargement
  • increased growth of a small prostate cancer which had not been detected yet (progression of a sub-clinical prostatic cancer)
  • changes in liver function tests
  • weight gain
  • blood clot in the deep vein (venous thromboembolism)

These symptoms usually go away when treatment is stopped for a short while. Your doctor will then probably advise you to start at a lower dosage.

In a few patients diarrhoea and stomach pain or discomfort have been reported during the use of this medicine.

Drug abuse and dependence:

Abuse of this medicine can cause serious health problems, especially if you take too much testosterone alone or with other androgenic anabolic steroids.

Some of these health problems include significant side effects on the heart and blood vessels (that can lead to death), mental health and/or the liver. (See "Before you use Andriol Testocaps").

Children and adolescents:

The following side effects have been reported in pre-pubertal children using androgens:

  • early sexual development;
  • penis enlargement;
  • an increased frequency of erections;
  • growth limitation (limited body height)

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

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

After Taking Andriol Testocaps

Storage

Store Andriol Testocaps below 30°C. Do not refrigerate or freeze. Store in the original package and keep the blister in the outer carton in order to protect from light.

Keep this medicine out of reach and sight of children

Do not use this medicine after the expiry date stated on the carton or label after the term "Expiry date". The expiry date refers to the last day of that month.

Disposal

Return any unused medicine to your pharmacist.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

Product Description

What it looks like

Andriol Testocaps packs are available in 3, 6# or 12 sachets, each containing a blister pack with 10 capsules. Andriol Testocaps capsules are soft oval, glossy, transparent orange coloured capsules marked with ORG DV3 printed in white. They contain a yellow oil.

# commercially available pack.

Ingredients

Each Andriol Testocap capsule consists of 40 mg of testosterone undecanoate (equivalent to 25.3 mg testosterone) in hydrogenated castor oil and propylene glycol monolaurate. The capsule shells contain the following inactive ingredients: gelatin, glycerol, medium chain triglycerides, lecithin, sunset yellow FCF and printed with Opacode WB water based monogramming ink NSP-78-18022 White.

If you have any further questions or require the full prescribing information for this medicine, please consult your doctor or pharmacist.

Supplier

Andriol Testocaps is supplied:

In Australia by:

Merck Sharp & Dohme (Australia) Pty Limited
Level 1 Building A, 26 Talavera Road, Macquarie Park, NSW 2113
Australia

In New Zealand by:

Merck Sharp & Dohme (New
Zealand) Ltd
PO Box 99 851
Newmarket
Auckland 1149
New Zealand

Australian Registration Number:

AUST R 92904

This leaflet was prepared in October 2020.

S-CCPPI-MK3033-CP-052017

Published by MIMS December 2020

BRAND INFORMATION

Brand name

Andriol Testocaps

Active ingredient

Testosterone undecanoate

Schedule

S4

 

1 Name of Medicine

Testosterone undecanoate.

2 Qualitative and Quantitative Composition

Each capsule contains 40.0 mg testosterone undecanoate, which is equivalent to 25.3 mg testosterone.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Soft oval glossy, transparent orange coloured gelatin capsules, containing a clear yellow oil fill. The capsules are encoded with a white imprint marked ORG DV3.

4 Clinical Particulars

4.1 Therapeutic Indications

Androgen replacement therapy for confirmed testosterone deficiency in males, when testosterone deficiency has been confirmed by clinical features and biochemical tests.

4.2 Dose and Method of Administration

Adults including elderly.

Andriol Testocaps must be taken orally with the morning and evening meal.
The capsules should be taken with some fluid and swallowed whole without chewing.
If an uneven number of capsules are to be taken, the greater dose should be taken in the morning.
The dosage of Andriol Testocaps should be determined by the physician according to the severity of the symptoms.
The initial dose is usually 120-160 mg/day for 2-3 weeks.
Subsequent dosage (40-120 mg/day) should be based on the clinical effect obtained in the first weeks of therapy.
Responses to dosage should be more closely monitored in those patients referred (see Section 4.4 Special Warnings and Precautions for Use).
In general, the dose should be adjusted according to the response of the individual patient.

Paediatric population.

Safety and efficacy have not been adequately determined in children and adolescents. Prepubertal children treated with Andriol Testocaps should be treated with caution.

4.3 Contraindications

Like any androgen therapy, testosterone undecanoate is contraindicated in male patients with known or suspected carcinoma of the prostate gland or breast.
Patients with nephrosis or nephrotic phase of nephritis.
Andriol Testocaps should not be used in case of known hypersensitivity to the active substance or any of the excipients.

4.4 Special Warnings and Precautions for Use

Identified precautions.

The following precautions are common to all testosterone containing preparations:
1. Patients with myocardial or renal dysfunction, hypertension, migraine, diabetes mellitus or epilepsy (or a history of these conditions) should be observed carefully, since androgen therapy may cause fluid retention.
2. Conditions which may be aggravated by the possible fluid retention or oedema caused by Andriol Testocaps.
3. Androgen use in prepubertal boys should be cautious and monitored carefully to avoid the possibility of premature epiphyseal fusion, or precocious sexual development. Skeletal maturation should be monitored regularly.
4. Patients with psychological disturbances should be cautiously treated since suicide due to treatment-aggravated depression has been reported.
5. The size and consistency of the prostate should be monitored periodically.
Andriol Testocaps contains Sunset Yellow FCF which may cause allergic reactions.

Medical examination.

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.
Physicians should consider monitoring patients receiving Andriol Testocaps before the start of treatment, at quarterly intervals for the first 12 months and yearly thereafter for the following parameters:
Digital rectal examination (DRE) of the prostate and PSA to exclude benign prostate hyperplasia or a sub-clinical prostate cancer (see Section 4.3 Contraindications).
Haematocrit and haemoglobin to exclude polycythaemia.

Conditions that need supervision.

Patients, especially the elderly, with the following conditions should be monitored for:

Tumours.

Mammary carcinoma, hypernephroma, bronchial carcinoma and skeletal metastases. In these patients hypercalcaemia may develop spontaneously, also during androgen therapy. The latter can be indicative of a positive tumour response to the hormonal treatment. Nevertheless, the hypercalcaemia should first be treated appropriately and after restoration of normal calcium levels, hormone therapy can be resumed.

Pre-existing conditions.

In patients with pre-existing cardiac-, renal- or hepatic insufficiency/ disease androgen treatment may cause complications characterised by oedema with or without congestive heart failure. In such cases treatment must be stopped immediately.
Patients who experienced myocardial infarction, cardiac, hepatic or renal insufficiency, hypertension, epilepsy, or migraine should be monitored due to the risk of deterioration of or reoccurrence of disease. In such cases treatment must be stopped immediately.

Diabetes mellitus.

Androgens in general and Andriol Testocaps can improve the glucose tolerance in diabetic patients (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Anticoagulant therapy.

Androgens in general and Andriol Testocaps can enhance the anticoagulant action of coumarin-type agents (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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.

Sleep apnoea.

There is insufficient evidence for a recommendation regarding the safety of treatment with testosterone esters in men with sleep apnoea. Good clinical judgment and caution should be employed in patients with risk factors such as adiposity or chronic lung diseases.

Adverse events.

If androgen associated adverse reactions occur, treatment with Andriol Testocaps should be discontinued and, upon resolution of complaints, resumed with a lower dose.

(Mis)use in sports.

Patients who participate in competitions governed by the World Anti-Doping Agency (WADA) should consult the WADA-code before using this product as Andriol Testocaps can interfere with anti-doping testing. The misuse of androgens to enhance ability in sports carries serious health risks and is to be discouraged.

Drug abuse and dependence.

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids. Abuse of testosterone and other anabolic androgenic steroids can lead to serious adverse reactions including: cardiovascular (with fatal outcomes in some cases), hepatic and/or psychiatric events. Testosterone abuse may result in dependence and withdrawal symptoms upon significant dose reduction or abrupt discontinuation of use.
The abuse of testosterone and other anabolic androgenic steroids carries serious health risks and is to be discouraged (see Section 4.8 Adverse Effects (Undesirable Effects)).

Use in hepatic impairment.

For use in hepatic impairment see Section 4.4 Special Warnings and Precautions for Use, Pre-existing conditions.

Use in renal impairment.

For use in renal impairment see Section 4.4 Special Warnings and Precautions for Use, Pre-existing conditions.

Use in the elderly.

There is limited experience on the safety and efficacy of the use of Andriol Testocaps 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.

Paediatric use.

In pre-pubertal children statural growth and sexual development should be monitored since androgens in general and Andriol Testocaps in high dosages may accelerate epiphyseal closure and sexual maturation.

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

Enzyme inducing agents such as barbiturates may exert decreasing effects on testosterone levels.
Enzyme inhibiting drugs may increase testosterone levels. Therefore adjustment of the dose of Andriol may be necessary. Andriol may potentiate the effects of ciclosporin and increase the risk of nephrotoxicity.
Androgens may improve glucose tolerance and thereby in diabetic patients decrease the need for insulin or other antidiabetic drugs (see Section 4.4 Special Warnings and Precautions for Use). Patients with diabetes mellitus should therefore be monitored especially at the beginning or end of treatment and at periodic intervals during Andriol Testocaps treatment.
High doses of androgens may enhance the anticoagulant action of coumarin type agents. Therefore close monitoring of prothrombin time, and if necessary a dose reduction of the anticoagulant is required during therapy.
The concurrent administration of testosterone with ACTH or corticosteroids may enhance oedema formation; thus these active substances should be administered cautiously, particularly in patients with cardiac or hepatic disease or in patients predisposed to oedema (see Section 4.4 Special Warnings and Precautions for Use).
Andriol may interfere with a number of clinical laboratory tests, e.g. those for glucose tolerance and thyroid function, suppression of clotting factors II, V, VII and X.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In men treatment with androgens can lead to fertility disorders by repressing sperm-formation.
(Category D)
This drug is not intended for use in female patients and is contraindicated in pregnancy. Androgenic substances may have a virilising effect on the female foetus and should be avoided during pregnancy.
 This drug is not intended for use in female patients.

4.7 Effects on Ability to Drive and Use Machines

No specific studies have been conducted to assess the direct effect of Andriol on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Andriol is generally well tolerated. Very few side effects have been associated with the clinical use of testosterone undecanoate.

Gastrointestinal complaints.

Common (1 to 10%).

Oily stools. However, these side effects were attributed to the oily solvent and were not considered serious.

Uncommon (0.1 to 1%).

Nausea.

Genitourinary disorders.

Rare (< 0.1%).

Priapism, epididymitis, bladder irritability, gynaecomastia, impotence, inhibition of testicular function and testicular atrophy. It is possible that prolonged administration of testosterone undecanoate may induce oligospermia, or decreased ejaculatory volume, which are reversible upon cessation of the drug.

Blood disorders.

Rare (< 0.1%).

Leukocytosis, polycythaemia and Serum cholesterol concentration may increase during androgen therapy. It is possible that prolonged administration of testosterone undecanoate may induce sodium and water retention.

Neurological disorders.

Rare (< 0.1%).

Generalised paraesthesia, insomnia, excitation, headache, anxiety, mental depression (see Section 4.4 Special Warnings and Precautions for Use).

Hypersensitivity and skin disorders.

Uncommon (0.1 to 1.0%).

Chills, maculopapular rash, acne, flushing of skin.

Others (frequency unknown).

Neoplasms benign, malignant and unspecified (incl. cysts and polyps).

Prostatic cancer (progression of a sub-clinical prostatic cancer).

Psychiatric disorders.

Nervousness, Mood altered, Libido increased, Libido decreased.

Vascular disorders.

Hypertension, venous thromboembolism.

Hepatobiliary disorders.

Hepatic function abnormal.

Skin and subcutaneous tissue disorders.

Pruritus.

Metabolism and nutrition disorders.

Weight increased.

Musculoskeletal and connective tissue disorders.

Myalgia.

Reproductive system and breast disorders.

Benign prostatic hyperplasia (prostatic growth to normogonadal size).

Investigations.

Lipids abnormal (decrease in serum LDL-C, HDL-C and triglycerides), PSA increased, Haematocrit increased, Red blood cell count increased, Haemoglobin increased.
The terms used to describe the undesirable effects above are also meant to include synonyms and related terms.
These symptoms are remedied by a pause in treatment after which therapy should be resumed at a lower dosage.
In a few patients diarrhoea and abdominal pain/ discomfort have been reported during use of Andriol Testocaps.

Drug abuse and dependence.

Testosterone, often in combination with other anabolic androgenic steroids (AAS) has been subject to abuse at doses higher than recommended for the approved indication (see Section 4.4 Special Warnings and Precautions for Use). The following additional adverse reactions have been reported in the context of testosterone/AAS abuse:

Endocrine disorders.

Secondary hypogonadism1.

Psychiatric disorders.

Hostility, Aggression, Psychotic disorder, Mania, Paranoia and Delusion.

Cardiovascular disorders.

Myocardial infarction, Cardiac failure, Cardiac failure chronic1,2, Cardiac arrest, Sudden cardiac death1, Cardiac hypertrophy1,2, Cardiomyopathy1, Ventricular arrhythmia, Ventricular tachycardia, Venous/arterial thrombotic and embolic events (including Deep Venous Thrombosis, Pulmonary embolism, Coronary artery thrombosis, Carotid artery occlusion1,2, Intracranial venous sinus thrombosis1,2), Cerebrovascular accident, Ischaemic stroke.

Hepatobiliary disorders.

Peliosis hepatis, Cholestasis1, Liver injury, Jaundice, Hepatic failure.

Skin and subcutaneous tissue disorders.

Alopecia.

Reproductive system and breast disorders.

Testicular atrophy, Azoospermia Infertility (in males), Enlarged clitoris and Breast atrophy (in females).
1 Has been reported with Andriol.
2 With fatal outcomes in some cases.

Paediatric population.

The following undesirable effects have been reported in pre-pubertal children using androgens (see Section 4.4 Special Warnings and Precautions for Use): precocious sexual development, an increased frequency of erections, phallic enlargement and premature epiphyseal closure.

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

The acute oral toxicity of testosterone undecanoate is very low. High dosages of Andriol Testocaps may cause gastrointestinal complaints due to the oily solvent contained in the capsule. Treatment may consist of emptying the stomach and supportive measures.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

Pharmacotherapeutic group: Androgens. ATC code G03B A03.

5.1 Pharmacodynamic Properties

Mechanism of action.

Testosterone undecanoate is able to bypass the liver via the lymphatic system and is therefore orally bioavailable. Testosterone undecanoate is intended as a replacement therapy for those who have abnormally low levels of natural testosterone. Testosterone undecanoate may induce a fall in LH and FSH levels to just above normal in hypergonadotrophic hypogonadal patients and may decrease hyperreactivity to gonadorelin stimulation. However, there are also reports where there have been no changes or changes in the opposite direction. It does not change the LH and FSH plasma levels in normal patients. Restoration of testosterone levels towards normal is associated with a significant improvement in feelings of well-being.
Testosterone undecanoate has been shown to induce sexual maturation in agonadal boys.
Some increase in plasma oestriol is observed. In patients with a subnormal prolactin response to thyrotrophin releasing hormone (TRH), response is normalised during testosterone undecanoate therapy. Testosterone undecanoate does not change the response of the pituitary to luteinising hormone releasing hormone (LHRH) or to TRH; nor does it cause any abnormal effects on haematological, blood biochemical or urinary parameters or on the size and consistency of the prostate gland. Normal prolactin levels are not affected by testosterone undecanoate administration.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following oral administration of Andriol Testocaps, an important part of the active substance testosterone undecanoate is coabsorbed with the lipophilic solvent from the intestine into the lymphatic system, thus circumventing the first-pass inactivation by the liver. During absorption testosterone undecanoate is partly reduced to dihydrotestosterone undecanoate.

Distribution.

From the lymphatic system it is released into the plasma. In plasma and tissues both testosterone undecanoate and dihydrotestosterone undecanoate are hydrolysed to yield the natural male androgens testosterone and dihydrotestosterone.
Single administration of 80-160 mg Andriol Testocaps leads to a clinically significant increase of total plasma testosterone with peak levels of approximately 40 nanomol/L (Cmax), reached approximately 4-5 hours (Tmax) after administration. Plasma testosterone levels remain elevated for at least 8 hours.
Because of the new Andriol Testocaps presentation a new bioequivalence study was conducted. An open label, replicate, four period, crossover trial was performed in 28 healthy postmenopausal women aged 45-65 years, with a body mass index between 18 and 30 kg/m2 and testosterone levels ≤ 0.87 nanogram/mL. This study was designed to assess bioequivalence between testosterone undecanoate administration in the Andriol Testocaps and Andriol formulation, by comparing the AUC and Cmax of serum testosterone after administration of both formulations.
The geometric least squares mean values (CV%) of the pharmacokinetic parameters for testosterone and baseline corrected testosterone, and the results of average bioequivalence testing are summarized in Table 1. Based on Cmax and AUC of testosterone and baseline corrected testosterone, average bioequivalence between testosterone undecanoate in Andriol Testocaps and Andriol is concluded.

Food effect.

An open label, single centre, two way crossover, food interaction study with Andriol Testocaps was performed in 16 healthy postmenopausal women aged 45-65 years, with a body mass index between 18 and 30 kg/m2 and testosterone levels ≤ 1.0 nanogram/mL. This study was designed to assess the effect of food on the bioavailability of testosterone (as measured by Cmax and AUC) after a single administration of Andriol Testocaps.
Following administration of Andriol Testocaps in the fasted state a poor bioavailability of testosterone was observed, which was considerably increased when Andriol Testocaps was taken with food (see Figure 1). Food effect testing based on Cmax and AUC0-tlast of testosterone as well as baseline corrected testosterone confirmed the presence of a food effect (see Table 2). This leads to the conclusion that Andriol Testocaps must be taken with a meal.

Metabolism.

Testosterone and dihydrotestosterone are metabolised via the normal pathways.

Excretion.

Excretion mainly takes place via the urine as conjugates of etiocholanolone and androsterone.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

The potential carcinogenicity of testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical uterine tumours, which metastasized in some cases. There is suggestive evidence that injection of testosterone in some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to act as a tumour promoter and has been shown to increase the number of tumours and decrease the degree of differentiation of chemically induced carcinomas in the liver of rats. There are rare reports of hepatocellular carcinoma in patients receiving long term therapy with androgens, particularly the 17-alpha-alkyl-androgens, in high doses. Withdrawal of the drugs did not lead to regression of the tumours in all cases. Whether there is a causal relationship or a connection between testosterone administration and formation of tumours occurring by chance remains unclarified. Chronic and androgen deficiency, however, is a protective factor for prostatic disease and hypogonadal men receiving androgen replacement therapy require surveillance for prostate disease similar to that recommended for eugonadal men of comparable age. Geriatric patients treated with androgens may be at an increased risk for the development for prostatic hyperplasia and prostatic cancer. However, there is no clear understanding of the formation and progression of prostatic carcinoma nor of the role of androgens.

6 Pharmaceutical Particulars

6.1 List of Excipients

Capsule contents.

Each capsule contains about 293 mg of a mixture of hydrogenated castor oil and propylene glycol monolaurate.

Capsule shell ingredients.

The soft capsule shell contains the non active substances: gelatin, glycerol, medium chain triglycerides, lecithin, sunset yellow FCF and printed with Opacode WB water based monogramming ink NSP-78-18022 White.

6.2 Incompatibilities

Not applicable.

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

Store below 30°C.
Do not refrigerate.
Keep the blister in the outer carton to protect from light.

6.5 Nature and Contents of Container

Andriol Testocaps pack sizes are: 30s*, 60s and 120s*.
The capsules are packed in PVC/Aluminium blister pack of 10, further packed into PE/AL/LDPE sachet in a carton.
*Some pack sizes may not be currently marketed.

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 name: 3-oxo-androst-4-en-17β-yl undecanoate.
Molecular Formula: C30H48O3.
Molecular Weight: 456.7.

Chemical structure.

The structural formula of testosterone undecanoate is:
Testosterone undecanoate, is a white to creamy-white crystalline powder. It is practically insoluble in water, soluble in 2% (w/v) dioxane and in ethanol (96%) and has a melting point of 60-65°C. It is a fatty acid ester of the naturally occurring androgen testosterone.

CAS number.

5949-44-0.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Medicine.

Summary Table of Changes