Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Nebido is not indicated for use in children and adolescents.
Nebido 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 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 two separate blood testosterone measurements.

Elderly population

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

Medical examination and laboratory tests

Medical examinations
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). Local guidelines for safety monitoring under testosterone replacement therapy should be taken into consideration.

Laboratory tests
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. 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 (see section 4.8).

Due to variability in laboratory values, all measures of testosterone should be carried out in the same laboratory.
Tumours

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

Nebido 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.

Cases of benign and malignant liver tumours have been reported in users of hormonal substances such as androgen compounds. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur in men using Nebido, a liver tumour should be included in the differential-diagnostic considerations.

Cardiac, hepatic or renal insufficiency

In patients suffering from severe cardiac, hepatic or renal insufficiency or ischemic 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.

Hepatic or renal insufficiency
There are no studies undertaken to demonstrate the efficacy and safety of this medicinal product in patients with renal or hepatic impairment. Therefore, testosterone replacement therapy should be used with caution in these patients.

Cardiac insufficiency
Caution should be exercised in patients predisposed to oedema, e.g. in case of severe cardiac, hepatic, or renal insufficiency or ischemic heart disease, as treatment with androgens may result in increased retention of sodium and water. In case of severe complications characterized by oedema with or without congestive heart failure treatment must be stopped immediately (see section 4.8).
Testosterone may cause a rise in blood pressure and Nebido should be used with caution in men with hypertension.

Clotting disorders
As a general rule, the limitations of using intramuscular injections in patients with acquired or inherited bleeding disorders always have to be observed.

Testosterone and derivatives have been reported to increase the activity of coumarin derived oral anticoagulants (see also section 4.5).
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.

Other conditions

Nebido should be used with caution in patients with epilepsy and migraine, as the conditions may be aggravated.

Improved insulin sensitivity may occur in patients treated with androgens who achieve normal testosterone plasma concentrations following replacement therapy. Therefore, the dosage of hypoglycaemic agents may need to be lowered.


Certain clinical signs: irritability, nervousness, weight gain, prolonged or frequent erections may indicate excessive androgen exposure requiring dosage adjustment.

Pre-existing sleep apnoea may be potentiated.

Athletes treated for testosterone replacement in primary and secondary male hypogonadism should be advised that the medicinal 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.

Nebido should be permanently withdrawn if symptoms of excessive androgen exposure persist or reappear during treatment with the recommended dosage regimen.

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.

Application

As with all oily solutions, Nebido must be injected strictly intramuscularly and very slowly (over two minutes). Pulmonary micro embolism of oily solutions can in rare cases lead to signs and symptoms such as cough, dyspnoea, malaise, hyperhidrosis, chest pain, dizziness, paraesthesia, or syncope. These reactions may occur during or immediately after the injection and are reversible. The patient should therefore be observed during and immediately after each injection in order to allow for early recognition of possible signs and symptoms of pulmonary oily micro embolism. Treatment is usually supportive, e.g.
by administration of supplemental oxygen.

Suspected anaphylactic reactions after Nebido injection have been reported.

Information about excipients
This medicine contains 2000 mg Benzyl benzoate in each 4 ml vial which is equivalent to 500 mg/ml.

Effects on Driving

4.7 Effects on ability to drive and use machines
Nebido has no influence on the ability to drive and use machines.