TESTIM Transdermal Gel Ref.[7123] Active ingredients: Testosterone

Prior to testosterone initiation, all patients must undergo a detailed examination in order to exclude the risk of pre-existing prostate cancer. Careful and regular monitoring of the breast and prostate gland 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 prostate cancer and benign prostatic hyperplasia.

Care should be taken in patients with skeletal metastases due to the risk of hypercalcaemia/hypercalciuria developing from androgen therapy. In these patients, serum calcium levels should be determined regularly.

Testosterone may cause a rise in blood pressure and TESTIM 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, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.

Testosterone 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 or 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.

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.

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.

TESTIM should not be used to treat non-specific symptoms suggestive of hypogonadism if testosterone deficiency has not been demonstrated and if other aetiologies responsible for the symptoms have not been excluded. Testosterone deficiency should be clearly demonstrated by clinical features and confirmed by 2 separate blood testosterone measurements before initiating therapy with any testosterone replacement, including TESTIM treatment.

TESTIM is not a treatment for male infertility or sexual dysfunction/impotence in patients without demonstrated testosterone deficiency. For the restoration of fertility in patients with hypogonadotrophic hypogonadism, therapeutic measures in addition to treatment with TESTIM are required.

Athletes treated for testosterone replacement in primary and secondary male hypogonadism should be advised that the product contains an active substance which may produce a positive reaction in anti-doping tests. Androgens are not suitable for enhancing muscular development in healthy individuals or for increasing physical ability.

TESTIM should not be used in women due to possible virilising effects.

As washing after TESTIM administration reduces testosterone levels, patients are advised not to wash or shower for at least 6 hours after applying TESTIM. When washing occurs up to six hours after the gel application, the absorption of testosterone may be reduced.

TESTIM contains propylene glycol, which may cause skin irritation.

The contents of each tube are flammable.

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). TESTIM 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 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 this type of contact is foreseen.
• For people not being treated with TESTIM:
  • 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 guarantee partner safety, the patient should be advised for example to observe a long interval between TESTIM 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 periods with children in order to avoid a contamination risk of children’s skin.

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

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

When androgens are used simultaneously with anti-coagulants, the anti-coagulant effects may be increased. Patients receiving oral anticoagulants require close monitoring, especially when androgen therapy is started or stopped.

The concurrent administration of testosterone with ACTH or corticosteroids may enhance oedema formation; thus these drugs should be administered cautiously, particularly in patients with cardiac or hepatic disease.

Laboratory Test Interactions: 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.

TESTIM is not indicated for women and must not be used in pregnant or breastfeeding women.

Testosterone may induce virilising effects on the female foetus.

Pregnant women should avoid skin contact with TESTIM application sites.

In the event that unwashed or unclothed skin to which TESTIM 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.

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

Summary of the safety profile

In double-blind clinical trials comparing TESTIM to placebo, the most frequently observed adverse drug reactions in TESTIM treated patients were application site erythema and increased PSA, both occurring in approximately 4% of patients.

Tabulated summary of adverse events

Adverse Drug Reactions terminology used for the classification of incidence: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

The cumulative safety experience of TESTIM is derived from Phase I to Phase III clinical trials and post-marketing experience.

The adverse reactions listed in the table below have been observed in clinical studies with TESTIM and/or post-marketing experience.

Gastrointestinal disorders

Not Known*: Nausea

General disorders and administration site conditions

Common: Application site reaction (including erythema, rash and pruritus)

Uncommon: Peripheral oedema

Hepatobiliary disorders

Not Known*: Jaundice and liver function test abnormalities

Investigations

Common: PSA increased, haematocrit increased, haemoglobin increased, red blood cell count increased

Not Known*: Altered blood lipid levels, reduction in HDL cholesterol and weight gain

Metabolism and nutrition disorders

Not Known*: Electrolyte changes (retention of sodium, chloride, potassium, calcium, inorganic phosphate and water)

Musculoskeletal and connective tissue disorders

Not Known*: Muscle cramps

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

Not Known*: Prostate Cancer

Nervous system disorders

Common: Headache

Not Known*: Paresthesia generalised

Psychiatric disorders

Not Known*: Decreased libido, anxiety, emotional lability

Reproductive system and breast disorders

Uncommon: Gynecomastia

(may develop and persist in patients being treated for hypogonadism with testosterone)

Very rare: Azoospermia

Not Known*: Increased frequency of erections; testosterone replacement therapy of hypogonadism can in rare cases cause persistent, painful erections (priapism), and prostate abnormalities

Skin and subcutaneous tissue disorders

Common: Acne

Uncommon: Pruritus

Not Known*: Various skin reactions may occur including hirsutism, alopecia and seborrhoea

Vascular disorders

Common: Hypertension worsened

Uncommon: Hot flushes/flushing

Not Known*: Hypertension

* cannot be estimated from the available data, majority from post-marketing reports and class effects of testosterone.

Patients should be instructed to report any of the following to a physician; too frequent or persistent erections of the penis; any changes in skin colour, ankle swelling or unexplained nausea or vomiting; any breathing disturbances including those associated with sleep.

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.