Testosterone Enantate 250 mg/ ml Solution for Injection Ampoules

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 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 oil microembolism. Treatment is usually supportive, e.g. by administration of supplemental 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.

Concomitant use of testosterone replacement therapy and sodium-glucose co-transporter 2 (SGLT-2) inhibitors has been associated with an increased risk of erythrocytosis. Since both substances may independently elevate haematocrit levels, a cumulative effect is possible. Monitoring of haematocrit and haemoglobin levels is recommended in patients receiving both treatments.

Pregnancy

Testosterone Enantate is intended for use by men only. Testosterone Enantate is not indicated in pregnant women (see 5.3 Preclinical safety data).

Lactation

Testosterone Enantate is intended for use by men only. Testosterone Enantate is not indicated in breast feeding women (see 5.3 Preclinical safety data).

Fertility

Testosterone Enantate replacement therapy may reversibly reduce spermatogenesis (see 4.8 Undesirable effects and 5.3 Preclinical safety data).

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

Undesirable effects are listed by MedDRA System Organ Classes. Assessment of undesirable effects is based on the following frequency groupings:

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

Not known: cannot be estimated from the available data

¹In pre-pubertal males

²Muscle disorder: Muscle spasms, Muscle strain

³Injection site pain, Injection site erythema, Injection site induration, Injection site swelling, Injection site inflammation, Injection site hematoma, Injection site reaction.

Description of selected adverse reactions

Pulmonary microembolism 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 injections and are reversible. Cases suspected by the company or the reporter to represent oily pulmonary microembolism have been reported from post marketing experience (see section 'Special warnings and precautions for use').

High-dosed or long-term administration of testosterone increases the tendency to water retention and oedema.

Spermatogenesis is inhibited by long-term and high-dosed treatment with Testosterone Enantate.

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

Hostility, nervousness and increased hair growth have been reported under treatment with testosterone containing preparations.

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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

No special therapeutic measure apart from termination of therapy with the drug or dose reduction is necessary after overdosage.

Acute toxicity data show that Testosterone Enantate can be classified as non-toxic following a single intake. Even in the case of an inadvertent administration of a multiple of the dose required for therapy, no acute toxicity risk is expected.

Pharmacotherapeutic group:

Androgens, 3-oxoandrosten (4) derivatives

ATC Code: G03BA03

Testosterone Enantate is an ester of the natural male sex hormone testosterone and exhibits all the pharmacological effects of the natural hormone. It differs in that it has a depot effect, due to the fact that Testosterone Enantate is only slowly degraded to testosterone in the body.

Following intramuscular administration of 200mg of Testosterone Enantate to 7 hypogonadal males:-

• Peak serum testosterone levels of 1233 ± 484 ng/dL were achieved at 24 hours.

• Physiological levels of testosterone (approx. 500 ng/dL) were maintained for 11 days.

Half-life in blood was 2-3 days (healthy male volunteers).

Studies in animals showed that the formulation has minimal potential for causing sensitisation or local irritation following intramuscular injection. Long-term systemic studies showed no evidence of testicular toxicity although a temporary inhibition of spermatogenesis may occur. No fertility studies with Testosterone Enantate have been carried out. Testosterone Enantate should not be administered during pregnancy due to the possibility of virilisation of the female foetus. However, investigations into embryotoxic, in particular teratogenic, effects gave no indication that further impairment of organ development may occur.

In vitro investigations of mutagenicity gave negative results.

Benzyl benzoate

Castor oil refined

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

5 years.

Protect from light.

Clear glass ampoules of 1 ml in packs of 3.

The product should be inspected visually for particles prior to administration. Only clear solution free from particles should be used.