Testogel 50 mg/5 g Transdermal gel.

Testosterone replacement therapy for male hypogonadism in adult men when testosterone deficiency has been confirmed by clinical features and biochemical tests (see section 4.4). TESTOGEL is not for use in children.

Posology
Adults and elderly men
The recommended dose is 5 g of gel (i.e. 50 mg of testosterone) applied once daily at about the same time, preferably in the morning. The adjustment of posology should be achieved in steps of 2,5 g of gel. Steady state plasma testosterone concentrations are reached approximately on the 2nd day of treatment with TESTOGEL. In order to adjust the TESTOGEL dose, serum testosterone concentrations must be measured in the morning before application, from the 3rd day after starting treatment (one week is 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, but not exceeding 10 g of gel per day.
Children
TESTOGEL is not indicated for use in children.
Method of administration
Transdermal use. The application should be administered by the patient himself, onto clean, dry, healthy skin over both shoulders, both arms or abdomen. After opening the sachets, the total contents must be extracted from the sachet and applied immediately onto the skin. TESTOGEL should be gently spread on the skin, as a thin layer. It is not necessary to rub it on the skin. Allow drying for at least 3 u2013 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.

TESTOGEL is contraindicated:
u2022 In cases of known hypersensitivity to testosterone or to any other ingredients of TESTOGEL (see section 6.1).
u2022 In cases of known or suspected prostatic cancer or breast carcinoma.

u2022 TESTOGEL is indicated for use only in men with primary or secondary hypogonadism resulting from certain medical conditions.
u2022 TESTOGEL should not be used for age-related hypogonadism.
u2022 Before initiating TESTOGEL, ensure that the diagnosis of hypogonadism has been confirmed with laboratory testing. Verify that serum testosterone concentrations have been measured on at least two separate mornings and are consistently below the normal range. Avoid measuring testosterone concentrations later in the day, when measurements can be low even in men who do not have hypogonadism.
u2022 Inform patients of the potential increased cardiovascular risk associated with TESTOGEL. Increases in myocardial infarction and stroke have been reported.
u2022 Encourage patients to read the patient information leaflet they receive with TESTOGEL. TESTOGEL should be used only if hypogonadism (hyper- and hypogonadotrophic) has been demonstrated and if other aetiology responsible for the symptoms has been excluded before treatment is initiated. 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. Due to variability in laboratory values, all measures of testosterone should be carried out in the same laboratory.
Prior to TESTOGEL 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 breasts must be performed in accordance with recommended methods (digital rectal examination and estimation of serum PSA) in patients receiving TESTOGEL therapy at least once yearly and twice yearly in elderly patients and at-risk patients (those with clinical or familial factors). TESTOGEL may accelerate the progression of sub-clinical prostatic cancer and benign prostatic hyperplasia. TESTOGEL should not be used 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 who have experienced myocardial infarction, suffering from severe cardiac, hepatic or renal insufficiency or ischaemic heart disease, treatment with TESTOGEL may cause severe complications characterised by oedema with or without congestive cardiac failure. In this case, treatment must be stopped immediately. TESTOGEL may cause a rise in blood pressure and should be used with caution in men with hypertension. TESTOGEL 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. The testosterone level should be monitored at baseline and at regular intervals during treatment. Health care providers should adjust the dosage individually to ensure maintenance of eugonadal testosterone levels. In patients receiving long-term TESTOGEL 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 is an increased risk of sleep apnoea in hypogonadal patients treated with testosterone esters, such as TESTOGEL, especially in those with risk factors such as obesity and chronic respiratory disease. Improved insulin sensitivity may occur in patients treated with TESTOGEL and may require a decrease in the dose of antidiabetic medicine (see section 4.5). Monitoring of the glucose level and HbA1c is advised for patients treated with TESTOGEL. Certain clinical signs such as irritability, nervousness, weight gain, and prolonged or frequent erections may indicate excessive TESTOGEL 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 TESTOGEL contains an active substance (testosterone) which may produce a positive reaction in anti-doping tests. TESTOGEL should not be used by women, due to its potential virilising effects.
Potential testosterone transfer
TESTOGEL 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 health care practitioner 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 non-compliance with safety instructions (e.g. severe alcoholism, drug abuse, severe psychiatric disorders). Transfer of TESTOGEL is avoided by wearing clothes covering the application area or showering prior to contact. The following precautions are recommended:
For the patient
u2022 Wash hands with soap and water after applying the gel.
u2022 Cover the application area with clothing once the gel has dried.
u2022 Wash the application area before any situation in which close contact is foreseen.
For people not being treated with TESTOGEL
u2022 In the event of adventitious contact with TESTOGEL, the person affected should wash the affected area with soap and water, immediately.
u2022 Report the development of signs of excessive androgen exposure, such as acne or hair modification. Patients should wait at least 1 hour before showering or bathing after applying TESTOGEL. 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 the contact period or to shower before sexual intercourse. Furthermore, it is recommended to wear a T-shirt covering the application site during any contact period with children, to avoid the risk of contaminating childrenu2019s 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). TESTOGEL is not a treatment for male sterility or impotence.

Oral anticoagulants
Changes in anticoagulant activity (the increased effect of the oral anticoagulant by modification of hepatic synthesis of the coagulation factor and competitive inhibition of plasma protein binding): Increased monitoring of the prothrombin time and international normalised ratio (INR) determinations, are recommended. Patients receiving oral anticoagulants require close monitoring, especially when treatment with androgens are started or stopped.
Adrenocorticotropic hormone (ACTH) or corticosteroids
Concomitant administration of TESTOGEL and ACTH or corticosteroids may increase the risk of developing oedema. As a result, these medicines should be administered cautiously, particularly in patients suffering from cardiac, renal or hepatic disease.
Interaction with laboratory tests
TESTOGEL may decrease levels of thyroxin binding globulin, resulting in decreased T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone levels, however, remain unchanged and there is no clinical evidence of thyroid insufficiency.
Diabetic medicine
Improved insulin sensitivity, glucose tolerance, glycaemic control, blood glucose and glycosylated haemoglobin levels have been reported with androgens. In diabetic patients, the dose of antidiabetic medicine may need reduction (see section 4.4).

Fertility
Spermatogenesis may be reversibly suppressed with TESTOGEL.
Pregnancy
TESTOGEL is intended for use by men only. TESTOGEL is not indicated in pregnant women. No clinical trials have been conducted with the treatment of TESTOGEL in women. Pregnant women must avoid any contact with TESTOGEL application sites (see section 4.4). TESTOGEL may cause virilising effects on the fetus. In the event of contact, wash with soap and water as soon as possible.
Breastfeeding
TESTOGEL is not indicated in women who are breastfeeding.

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

Summary of the safety profile
The most frequently observed adverse reactions at the recommended dosage of gel per day were skin reactions: reaction at the application site, erythema, acne, dry skin.
Tabulated list of adverse reactions
Clinical trial data
Adverse reactions reported in 1 - < 10 % of patients treated with TESTOGEL in the controlled clinical trials are listed in the following table:
Adverse effects have been ranked under headings of frequency using the following convention: very common (u2265 1/10); common (u2265 1/100; < 1/10); uncommon (u2265 1/1 000; < 1/100); rare (u2265 1/10 000; < 1/1 000); very rare (< 1/10 000); frequency not known (cannot be estimated from the available data).
Adverse reactions u2013 Preferred term MedDRA System organ class Common adverse reactions (> 1/100; < 1/10) Uncommon adverse reactions (u2265 1/1 000; < 1/100) Psychiatric disorders Mood disorders Nervous system disorders Dizziness, paraesthesia, amnesia, hyperaesthesia Vascular disorders Hypertension Arterial vasodilation Respiratory, thoracic and mediastinal disorders Asthma Gastro-intestinal disorders Diarrhoea Nausea Skin and subcutaneous tissue disorders Alopecia, urticaria Pruritus Musculoskeletal and connective tissue disorders Myalgia Reproductive system and breast disorders Gynaecomastia (which may be persistent, is a common finding in patients treated for hypogonadism), mastodynia, prostatic disorders Oligospermia General disorders and administration site conditions Headache Investigations Changes in laboratory tests (polycythaemia, lipids), increased: haematocrit, red blood count and haemoglobin.
Post-marketing experience
The following table 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 (u2265 1/10); common (u2265 1/100; < 1/10); uncommon (u2265 1/1 000; < 1/100); rare (u2265 1/10 000; < 1/1 000); very rare (<1/10 000); frequency not known (cannot be estimated from the available data).

Symptoms
In overdose, side effects will be exacerbated and exaggerated (see section 4.8). Serum testosterone levels should be measured if clinical signs and symptoms indicative of overexposure to androgen are observed. Application site rash has also been reported in case reports of overdose with TESTOGEL.
Treatment
Treatment is symptomatic and supportive. Treatment of overdosage consists of washing the application site immediately and discontinuing treatment if advised by the treating health care practitioner.