TESTAVAN Transdermal gel Ref.[27746] Active ingredients: Testosterone

Testavan should be used only if male hypogonadism has been demonstrated and if other etiology, responsible for the symptoms, has been excluded before treatment is started. Testosterone deficiency should be clearly demonstrated by clinical features (regression of secondary sexual characteristics, change in body composition, asthenia, reduced libido, erectile dysfunction etc.) and confirmed by two separate blood testosterone measurements before initiating therapy with any testosterone replacement, including Testavan treatment.

Prior to initiation of testosterone replacement therapy, 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 prostate specific antigen (PSA)) in patients receiving testosterone therapy at least annually and twice yearly in elderly patients and at risk patients (those with clinical or familial factors).

Testosterone levels should be monitored at baseline and at regular intervals during treatment. Clinicians should adjust the dosage individually to ensure maintenance of eugonadal testosterone levels. Certain clinical signs: irritability, nervousness, weight gain, prolonged or frequent erections may indicate excessive androgen exposure requiring dosage adjustment.

Androgens may accelerate the progression of sub-clinical prostate cancer and benign prostatic hyperplasia.

Testavan 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.

Testavan is not a treatment for male sterility or impotence.

There is limited experience on the safety and efficacy of the use of Testavan in patients over 65 years of age. Currently, there is no consensus concerning age specific reference values for testosterone. However, it should be taken into consideration that the physiologically testosterone serum levels are lower with increasing age.

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

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 this case, treatment must be stopped immediately.

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.

Testosterone should be used with caution in patients with ischemic heart disease, epilepsy and migraine as these conditions may be aggravated.

There are published reports of increased risk of sleep apnoea in hypogonadal men treated with testosterone esters, especially in those with risk factors such as obesity or chronic respiratory disease.

If the patient develops a severe application site reaction, treatment should be reviewed and discontinued if necessary.

In patients receiving long-term androgen therapy, the following laboratory parameters should also be monitored regularly: haemoglobin, and haematocrit, liver function tests and lipid profile.

Testavan should not be used in women due to possible virialising effects.

As washing after Testavan administration reduces testosterone levels, patients are advised not to wash or shower for at least 2 hours after applying Testavan. When washing occurs up to 2 hours after the gel application, the absorption of testosterone may be reduced.

Testavan contains propylene glycol, which may cause skin irritation.

Alcohol based products including Testavan are flammable; therefore avoid fire, flame or smoking until the gel has dried.

Potential for 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, acne, deepening of the voice, irregularities of the menstrual cycle) in case of repeat contact (inadvertent androgenisation).

The physician should inform the patient carefully about the risk of testosterone transfer and about safety instructions (see below). Testavan 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:

• use the cap applicator for hands-free administration to reduce the risk of secondary exposure to testosterone.
• if the gel was touched with the hands during the application procedure, wash hands thoroughly 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 skin to skin contact with another person is foreseen.

For people not being treated with Testavan:

• in the event of contact with an application area which has not been washed or is not covered with clothing, wash the area of skin onto which testosterone may have been transferred as soon as possible, using soap and water.
• report the development of signs of excessive androgen exposure such as acne or hair modification.

To improve partner safety, the patient should be advised for example 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 periods with children in order to avoid a contamination risk of children’s skin.

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

Patients must be cautioned to minimise use of body lotion and sunscreen products at the area of application, at and just after application of Testavan gel.

Laboratory test interactions: Androgens may decrease concentrations of thyroxin-binding globulins, resulting in decreased total thyroxine (T4) serum concentration and increased resin uptake of triiodothyronine (T3) and T4. Free thyroid hormone concentration remains unchanged and there is no clinical evidence of thyroid dysfunction.

When androgens are given simultaneously with anticoagulants, the anticoagulant effects can increase. Patients receiving oral anticoagulants require close monitoring of their international normalized ratio (INR) especially when androgen treatment is started or stopped.

The concurrent administration of testosterone with adrenocorticotropic hormone (ACTH) or corticosteroids may increase likelihood of oedema; thus these drugs should be administered with caution, particularly in patients with cardiac, renal or hepatic disease.

Improved insulin sensitivity may occur in patients treated with androgens who achieve normal testosterone plasma concentrations following replacement therapy.

Interaction studies with body lotion and sunscreen products have not been performed.

Testavan is intended for use by men only.

No clinical trials have been conducted with Testavan for assessment of male fertility. Spermatogenesis may be reversibly suppressed with Testavan (see section 5.3).

Pregnant women should avoid skin contact with Testavan application sites (see section 4.4).

In the event that unwashed or unclothed skin to which Testavan has been applied does come into direct contact with the skin of a pregnant woman, the general area of contact on the woman should be washed with soap and water immediately.

Testosterone may induce virilising effects on the foetus.

Testavan has no or negligible influence on the ability to drive and use machines.

a. Summary of the safety profile

The most commonly reported adverse reactions in phase 2 and phase 3 clinical trials lasting up to 9 months were application site reactions (4%) including: rash, erythema, pruritus, dermatitis, dryness, and skin irritation. The majority of these reactions were mild to moderate in severity.

b. Tabulated summary of adverse events

Adverse drug reactions reported in phase 2 and phase 3 clinical trials with Testavan are listed in the following table. All adverse reactions reported with a suspected relationship are listed by class and are listed according to the following frequency: common (≥1/100 to <1/10); uncommon (≥1/1.000 to <1/100).

Testavan drug-related adverse reactions reported during clinical trials with more than one case (N=379):

According to literature and spontaneous reporting from testosterone gels, other known undesirable effects are listed in the below table:

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

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

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.