Testosterone Enantate 250 mg/ ml Solution for Injection.

Each 1ml ampoule contains 250mg Testosterone Enantate (the equivalent of about 180 mg testosterone) in oily solution.

Also contains 342 mg benzyl benzoate per ampoule

For the full list of excipients, see section 6.1.

Solution for injection.

Clear, yellowish oily solution.

Testosterone replacement therapy for male hypogonadism, when testosterone deficiency has been confirmed by clinical features and biochemical tests.

Posology

To stimulate development of underdeveloped androgen-dependent organs and for initial treatment of deficiency symptoms, 250mg Testosterone Enantate intramuscularly every two to three weeks.

For maintenance treatment: 250mg Testosterone Enantate intramuscularly every three to six weeks, according to individual requirement.

Serum testosterone levels should be measured before start of treatment and occasionally during the treatment at the end of an injection interval. Serum levels below normal range would indicate the need for a shorter injection interval. In case of high serum levels an extension of the injection interval may be considered.

Special populations

Paediatric population

Testosterone Enantate is not indicated for use in children and adolescents (see 4.4 Special warnings and precautions for use).

Safety and efficacy have not been adequately determined in children and adolescents.

Elderly patients

Limited data do not suggest the need for a dosage adjustment in elderly patients (see 4.4 Special warnings and precautions for use).

Patients with hepatic impairment

No formal studies have been performed in patients with hepatic impairment. The use of Testosterone Enantate is contraindicated in men with past or present liver tumours (see 4.3 Contraindications).

Patients with renal impairment

No formal studies have been performed in patients with renal impairment.

Method of Administration

Solution for intramuscular injection.

The injection must be administered extremely slowly (see 4.4 Special warnings and precautions for use and 4.8 Undesirable effects). The oily solution is injected immediately after its drawing up into the syringe.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Androgen-dependent carcinoma of the prostate or of the male mammary gland

• Hypercalcaemia

• Past or present liver tumours

• Nephrosis

Older patients treated with androgens may be at increased risk for the development of prostatic hyperplasia. Although there are no clear indications that androgens actually generate prostatic carcinoma, these can enhance the growth of any existing prostatic carcinoma. Therefore carcinoma of the prostate has to be excluded before starting therapy with testosterone preparations.

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

As a precaution, regular examinations of the prostate are recommended in men.

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

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.

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

Testosterone Enantate should be used with caution in patients with epilepsy, migraine, diabetes mellitus or skeletal metastases.

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.

Cases of benign and malignant liver tumours, which may lead to life-threatening intra-abdominal haemorrhage, have been observed after the use of Testosterone Enantate. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, a liver tumour should be included in the differential-diagnosis and, if necessary, the preparation should be withdrawn.

Caution should be exercised in patients predisposed to oedema, as treatment with androgens may result in increased sodium retention (see 4.8 Undesirable effects).

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.

Drug abuse and dependence

Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication(s) 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.

In children testosterone, besides masculinisation, can cause accelerated growth and bone maturation and premature epiphyseal closure, thereby reducing final height.

Testosterone Enantate should not be used in women since, depending on the individual sensitivity to androgenic impulses, women may develop signs of virilisation, e.g. acne, hirsutism, voice changes.

Pre-existing sleep apnoea may be potentiated.

Androgens should not be used for enhancing muscular development in healthy individuals or for increasing physical ability.

As with all oily solutions, Testosterone Enantate must be injected strictly intramuscularly and very slowly. Pulmonary microembolism of oily solutions can lead to signs and symptoms such as cough, dyspnoea and chest pain. There may be other signs and symptoms including vasovagal reactions such as malaise, hyperhydrosis, dizziness, paraesthesia, or syncope. These reactions may occur during or immediately after the injection and are reversible. Treatment is usually supportive, e.g. by administration of oxygen.

If, in individual cases, frequent or persistent erections occur, the dose should be reduced or the treatment discontinued in order to avoid injury to the penis.

Excipients

Also contains 342 mg benzyl benzoate per ampoule. Benzyl benzoate can be hydrolysed into benzyl alcohol and benzoic acid. Benzyl alcohol may cause allergic reactions. High volumes should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation of benzyl alcohol and toxicity (metabolic acidosis).

Barbiturates and other enzyme inducers

Interactions can occur with drugs that induce microsomal enzymes which can result in increased clearance of testosterone

Oxyphenbutazone

Increased oxyphenbutazone serum levels have been reported.

Oral anticoagulants

The clotting status should be monitored particularly closely when Testosterone Enantate is administered together with coumarin derivatives.

Hypoglycaemics

The hypoglycaemic effect of antidiabetics may be enhanced, possibly requiring a reduction in dosage of the hypoglycaemic agent.