Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Bayer plc, 400 South Oak Way, Reading, RG2 6AD
The use of Nebido is contraindicated in men with:
The use of Nebido in women is contraindicated.
Nebido is not recommended 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.
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.
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.
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.
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.
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.
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.
Caution should be exercised in patients predisposed to oedema, e.g. in case of severe cardiac, hepatic, or renal insufficiency or ischaemic 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.
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, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.
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.
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.
As with all oily solutions, Nebido must be injected strictly intramuscularly and very slowly (over two minutes). 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 oily microembolism. Treatment is usually supportive, e.g. by administration of supplemental oxygen.
Suspected anaphylactic reactions after Nebido injection have been reported.
This medicine contains 2000 mg Benzyl benzoate in each 4 ml ampoule/vial which is equivalent to 500 mg/ml.
Testosterone and derivatives have been reported to increase the activity of coumarin derived oral anti-coagulants. Patients receiving oral anti-coagulants require close monitoring, especially at the beginning or end of androgen therapy. Increased monitoring of the prothrombin time, and INR determinations, are recommended.
The concurrent administration of testosterone with ACTH or corticosteroids may enhance oedema formation; thus these active substances should be administered cautiously, particularly in patients with cardiac or hepatic disease or in patients predisposed to oedema.
Laboratory test interactions: Androgens may decrease levels of thyroxin-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.
Testosterone replacement therapy may reversibly reduce spermatogenesis (see sections 4.8 and 5.3).
Nebido is not indicated for use in women and must not be used in pregnant or breast-feeding women (see section 4.3).
Nebido has no influence on the ability to drive and use machines.
Regarding undesirable effects associated with the use of androgens, please also refer to section 4.4.
The most frequently reported undesirable effects during treatment with Nebido are acne and injection site pain.
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. Cases suspected by the company or the reporter to represent oily pulmonary microembolism have been reported rarely in clinical trials (in ≥1/10,000 and <1/1,000 injections) as well as from postmarketing experience (see section 4.4).
Suspected anaphylactic reactions after Nebido injection have been reported.
Androgens may accelerate the progression of sub-clinical prostatic cancer and benign prostatic hyperplasia.
Table 1 below reports adverse drug reactions (ADRs) by MedDRA system organ classes (MedDRA SOCs) reported with Nebido. The frequencies are based on clinical trial data and defined as common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100) and rare (≥1/10,000 to <1/1,000). The ADRs were recorded in 6 clinical studies (N=422) and considered at least possibly causally related to Nebido.
Table 1. Categorised relative frequency of men with ADRs, by MedDRA SOC – based on pooled data of six, clinical trials, N=422 (100.0%), i.e. N=302 hypogonadal men treated with i.m. injections of 4 ml and N=120 with 3ml of TU 250 mg/ml:
Common: Polycythaemia, Haematocrit increased*, Red blood cell count increased*, Haemoglobin increased*
Uncommon: Hypersensitivity
Common: Weight increased
Uncommon: Increased appetite, Glycosylated haemoglobin increased, Hypercholesterolaemia, Blood triglycerides increased, Blood cholesterol increased
Uncommon: Depression, Emotional disorder, Insomnia, Restlessness, Aggression, Irritability
Uncommon: Headache, Migraine, Tremor
Common: Hot flush
Uncommon: Cardiovascular disorder Hypertension, Dizziness
Uncommon: Bronchitis, Sinusitis, Cough, Dyspnoea, Snoring, Dysphonia
Uncommon: Diarrhoea, Nausea
Uncommon: Liver function test abnormal, Aspartate aminotransferase increased
Common: Acne
Uncommon: Alopecia, Erythema, Rash1, Pruritus, Dry skin
Uncommon: Arthralgia, Pain in extremity, Muscle disorders2, Musculoskeletal stiffness, Blood creatine phosphokinase increased
Uncommon: Urine flow decreased, Urinary retention, Urinary tract disorder, Nocturia, Dysuria
Common: Prostate specific antigen increased, Prostate examination abnormal, Benign prostate hyperplasia
Uncommon: Prostatic intraepithelial neoplasia, Prostate induration, Prostatitis, Prostatic disorder, Libido changes, Testicular pain, Breast induration, Breast pain, Gynaecomastia, Oestradiol increased, Testosterone increased
Common: Various kinds of injection site reactions3
Uncommon: Fatigue, Asthenia, Hyperhidrosis4
Rare: Pulmonary oil microembolism**
* Respective frequency has been observed in relation to the use in testosterone containing products.
** Frequency is based on the number of injections.
The most appropriate MedDRA term to describe a certain adverse reaction is listed. Synonyms or related conditions are not listed, but should be taken into account as well.
1 Rash including Rash papular
2 Muscle disorders: Muscle spasm, Muscle strain and Myalgia
3 Various kinds of injection site reaction: Injection site pain, Injection site discomfort, Injection site pruritus, Injection site erythema, Injection site haematoma, Injection site irritation, Injection site reaction
4 Hyperhidrosis: Hyperhidrosis and Night sweats
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 rarely in clinical trials (in ≥1/10,000 and <1/1,000 injections) as well as from postmarketing experience (see section 4.4).
In addition to the above mentioned adverse reactions, nervousness, hostility, sleep apnoea, various skin reactions including seborrhoea, increased hair growth, increased frequency of erections and in very rare cases jaundice have been reported under treatment with testosterone containing preparations.
Therapy with high doses of testosterone preparations commonly reversibly interrupts or reduces spermatogenesis, thereby reducing the size of the testicles; testosterone replacement therapy of hypogonadism can in rare cases cause persistent, painful erections (priapism). High-dosed or long-term administration of testosterone occasionally increases the occurrences of water retention and oedema.
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.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
