TESTOGEL Gel Ref.[7122] Active ingredients: Testosterone

Testogel should be used only if hypogonadism (hyper- and hypogonadotrophic) has been demonstrated and if other etiology, 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 2 separate blood testosterone measurements. 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.

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 a 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 sub-clinical 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 or ischaemic 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. In addition, diuretic therapy may be required.

Testogel should be used with caution in patients with ischemic heart disease.

Testosterone may cause a rise in blood pressure and Testogel should be used with caution in men with hypertension.

Clotting disorders

Testosterone should be used with caution in patients with thrombophilia, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.

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.

Beside laboratory tests of the testosterone concentrations in patients receiving long-term androgen therapy the following laboratory parameters should also be monitored regularly: haemoglobin, 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 anti-doping tests.

Testogel should not be used by women, due to possibly virilizing effects.

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 repeat contact (inadvertent androgenization).

The physician should inform the patient carefully about the risk of testosterone transfer and about safety instructions (see below). Testogel should not be prescribed in patients with a major risk of non-compliance with safety instructions (e.g. severe alcoholism, drug abuse, severe psychiatric disorders).

This transfer is avoided by wearing clothes covering the application area or showering prior to contact.

As a result, 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,
  • shower before any situation in which this type of contact is foreseen.
• for people not being treated with Testogel:
  • 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.

According to in vitro absorption studies on testosterone conducted with Testogel, it seems preferable for patients to observe at least 6 hours between gel application and bathing or showering. Occasional baths or showers taken between 1 and 6 hours after application of the gel should not significantly influence the treatment outcome.

To guarantee 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.

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 of children skin.

Pregnant women must avoid any contact with Testogel application sites. In case of pregnancy of the partner, the patient must reinforce his attention to the precautions for use (see section 4.6).

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.

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.

Interaction with laboratory tests: androgens may decrease levels of thyroxin 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.

Testogel is intended for use by men only.

Testogel is not indicated in pregnant or breast feeding women. No clinical trials have been conducted with this treatment in women.

Pregnant women must avoid any contact with Testogel application sites (see section 4.4). This product may have adverse virilizing effects on the fœtus. In the event of contact, wash with soap and water as soon as possible.

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

The most frequently observed adverse drug reactions at the recommended dosage of 5 g of gel per day were skin reactions (10%): reaction at the application site, erythema, acne, dry skin.

Adverse drug reactions reported in 1 - <10% of patients treated with Testogel in the controlled clinical trials are listed in the following table:

Blood and lymphatic system disorders: Changes in laboratory tests (polycythaemia, lipids), Haematocrit increased, Red blood cell count increased, Haemoglobin increased

General disorders and administration site conditions: Headache

Renal and urinary disorders: Prostatic disorders

Reproductive system and breast disorders: Gynaecomastia, mastodynia

Nervous system disorders: Dizziness, paraesthesia, amnesia, hyperaesthesia

Psychiatric disorders: Mood disorders

Vascular disorders: Hypertension

Gastro-intestinal disorders: Diarrhoea

Skin and subcutaneous disorders: Alopecia, urticaria

Gynaecomastia, which may be persistent, is a common finding in patients treated for hypogonadism.

According to the literature, other known undesirable effects have been reported following testosterone oral or inject able treatment and are listed in the following table:

Metabolism and nutrition disorders: Weight gain, electrolyte changes (retention of sodium, chloride, potassium, calcium, inorganic phosphate and water) during high dose and/or prolonged treatment

Musculoskeletal system: Muscle cramps

Nervous system: Nervousness, depression, hostility

Respiratory system: Sleep apnoea

Hepatobiliary disorders: In very rare cases jaundice and liver function test abnormalities

Skin and appendages: Various skin reactions may occur including acne, seborrhoea, and balding

Reproductive system and breast disorders: Libido changes, increased frequency of erections; therapy with high doses of testosterone preparations commonly reversibly interrupts or reduces spermatogenesis, thereby reducing the size of the testicles; testosterone replacement therapy of hypogonadism can in rare cases cause persistent, painful erections (priapism), prostate abnormalities, prostate cancer*, urinary obstruction

General disorders and administration site conditions: High dose or long-term administration of testosterone occasionally increases the occurrences of water retention and oedema; hypersensitivity reactions may occur.

* Data on prostate cancer risk in association with testosterone therapy are inconclusive.

Other rare known undesirable effects associated with excessive dosages of testosterone include hepatic neoplasms.

Because of the alcohol contained in the product, frequent applications to the skin may cause irritation and dry skin.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.

Not applicable.