Information for healthcare professionals

Frequently asked questions about Nebido®

Nebido® FAQs

 
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  • Treatment with Nebido®
    • How long can Nebido® be used?
      There is no time limit for Nebido® treatment but regular monitoring should be performed in compliance with the guidelines.
    • Is Nebido® licensed for the treatment of men with normal testosterone levels who show signs of deficiency?
      No, Nebido® is not licensed for this indication. However, ISSAM, EAU, ISA, EAA and ASA recommendations suggest that, in the presence of a clinical picture of testosterone deficiency and borderline testosterone levels, a short therapeutic trial (e.g. 3 months) may be justified.1
    • What are the advantages of Nebido® compared to therapy with other testosterone medications?
      In comparison to conventional testosterone injections the use of Nebido® allows to avoid frequent unphysiological peaks and troughs and to reduce drastically the frequency of injections, the most frequent complaints of the patients. With Nebido® thinking about the condition “every day” is not necessary, a patient is not restricted in the activities of daily routine like bathing or swimming. As an injection Nebido® does not cause skin irritations like testosterone patches or gels and its resorption has no dependency on food intake like oral forms of testosterone.
    • What are the effects of Nebido®?
      1. Testosterone levels:
      Pharmacokinetic studies have shown that Nebido® maintains testosterone levels within the physiologic range. The recommended administration regime consists of one loading dose 6 weeks after the initial injection followed by intervals of 10 to 14 weeks (usually 3 months The initial short interval (loading dose) is advisable to quickly achieve steady state conditions. In order to adjust the treatment regimen to individual needs, a blood sample prior to the 4th injection, i.e. at trough level, is suggested. If testosterone levels are below the normal range, a shortening of the interval to 10 weeks may be considered. If testosterone levels are in the lower third of the normal range the 3-monthly interval should be maintained. If testosterone levels are above the lower third of the normal range, an extension of injection intervals can be considered. In any case, the clinical symptomatology of the patient must be taken into consideration.2

      2. Clinical symptoms:
      As a consequence of the restoration of testosterone levels, significant improvements of certain clinical signs associated with the androgen deficit can be shown:
      • Nebido® has a favorable effect on body composition by increasing muscle mass and decreasing fat mass.
      • Muscle strength improves under therapy with Nebido®.
      • Sexual function parameters are improved with Nebido®.
      • Nebido® exerts a positive effect on mood, thus improving self-confidence and activity, and reduces fatigue and the feeling of exhaustion.
    • How is Nebido® used?
      The injections must be administered very slowly (over 1 to 2 minutes). It is possible and advisable to use a 22 G injection needle. Care should be taken to inject Nebido® deeply into the gluteal muscle following the usual precautions for intramuscular administration. Special care must be given to avoid intravasal injection. The content of an ampoule has to be injected intramuscularly immediately after opening the ampoule.

      Pulmonary microembolism of oily solutions can in rare cases lead to signs and symptoms such as cough, dyspnea, malaise, hyperhidrosis, chest pain, dizziness, paresthesia, or syncope. These reactions may occur during or immediately after the injections and are reversible. This is not specific for Nebido® and has been described for injections of testosterone in oily solutions in general.3 This can usually be avoided by injecting the solution very slowly and by making sure that the injection is strictly intramuscular.
    • What is the recommended treatment regimen, and how should the dosage be adjusted (figure 1)?
      It is advisable to reduce the interval between the first and second administration of Nebido® to 6 weeks. With this loading dose, sufficient steady state testosterone levels may be achieved more rapidly. After that “loading interval”, further injections should be given in intervals of about 12 weeks. Measurement of serum trough testosterone levels and clinical symptoms should be considered for individualization of therapy with Nebido®. Serum trough testosterone levels should be in the lower third of the normal range. 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. The injection interval should remain within the recommended range of 10 to 14 weeks.

      Figure 1: Nebido® injection interval
      Figure 1: Nebido® injection interval

      Since steady state serum testosterone levels can be assumed to be achieved after the first six months of treatment, it appears advisable to control serum testosterone before the fourth injection for individualization of therapy (usual spacing between administrations provided).
    • Why is a loading interval required and for which patients?
      The first injection interval is shorter so that the sustained active drug levels are reached more rapidly and the shorter interval at the beginning of therapy will make sure that testosterone levels are normalized quickly which will ensure fast alleviation of symptoms and complaints.

      This shorter starting interval is advisable for every patient, regardless of whether the patient has already used other testosterone preparations or not. It is advisable that patients switching from shorter-acting testosterone injections (such as Testoviron®, Sustanon®) receive their first injection of Nebido® at the time point when their usual testosterone injection would have been due.
    • Is injection site pain a frequent complaint with Nebido® therapy?
      No, injection site pain was reported in less than 3 % of patients during the development of the product and is not different from injections with short-acting testosterone preparations. In the clinical development program, there was no case of drop-out of a patient due to injection pain.

      In practical use since the broad commercial availability of the product from late 2004 onwards, no major problems were encountered with application site reactions.
    • What happens if you divide one ampoule of Nebido® and give 2ml into each muscle instead of 4ml into the same muscle? How does that change kinetics and efficacy of Nebido®?
      In fact, that was never studied in clinical trials. Our continued experience and feedback with Nebido® has been that the 4ml injection is very well tolerable. Complaints about injection site tenderness or pain can be reduced by following the instructions to inject very slowly. Practical use has so far confirmed this.
      From a theoretical point of view, increasing the resorption surface by increasing the number of depots could alter the pharmacokinetic profile.

      There also is no clinical experience with subcutaneous injection for adequate therapeutic efficacy. The volume is considered too large for this route of administration and may not provide the clinical effects.
    • What happens if only 1-2 ml of Nebido® (250-500mg testosterone undecanoate) are injected?
      No clinical studies have been performed applying such regimens. It would lead to insufficient testosterone substitution requiring a shorter interval until the next injections and therefore losing one of the products main features, the long intervals of about 3 months between administrations.
    • Is there any information available as to the size of the needle most suitable for the delivery of Nebido®?
      The following needles were used for the clinical trials with Nebido®: 1.10 x 50 mm (19 G x 2") (e.g. produced by Braun Melsungen). However, under practical clinical conditions, the use of a 22 G (0.9 mm) has been found to be most suitable for the injection of Nebido®. The small needles have two advantages: 1. the injection pain is further reduced; 2. the injection must be performed very slowly.
    • Risks and side effects

      When is the use of Nebido® contraindicated?

      Like every androgen therapy, the use of Nebido® is contraindicated in diagnosed or suspected carcinoma of the prostate or of the male mammary gland; hypercalcemia accompanying malignant tumors, past or present liver tumors; hypersensitivity to the active substance or to any of the excipients.

      Nebido® is not indicated for use in children and adolescents and it has not been evaluated clinically in males under 18 years of age. Furthermore, the use of Nebido® in women is contra-indicated.
    • Side efects
      The most frequent side effects of Nebido® observed are acne and injection site pain. These reactions are generally mild and transient. Other common side effects observed are typical of testosterone (e.g. polycythemia, weigth increase, hot flushes, prostate specific antigen increased, prostate examination abnormal, benign prostate hyperplasia).

      Pulmonary microembolism of oily solutions can in rare cases lead to signs and symptoms such as cough, dyspnea, malaise, hyperhidrosis, chest pain, dizziness, paresthesia, or syncope. These reactions may occur during or immediately after the injections and are reversible. This is not specific for Nebido® and has been described for injections of testosterone in oily solutions in general. This can usually be avoided by injecting the solution very slowly and by making sure that the injection is strictly intramuscular. Like with any medication, allergic reactions to any of the ingredients of the preparation may occur. With Nebido®, this has only been observed in extremely rare cases.
    • Interactions
      What happens if Nebido® and alcohol are used together?
      Intake of alcoholic drinks has no influence on the mode of action of Nebido®.

      Does acne occur more frequently during Nebido® therapy or can it make pre-existing acne worse?
      As with every testosterone therapy, acne can occur at the beginning of Nebido® therapy. This is not permanent, however, but subsides at varying rates. This is comparable to the occurrence of acne in adolescent boys during puberty, which is also linked to the rise in testosterone levels, but which subsides again either during or at the end of puberty.
  • Clinical Studies with Nebido®
    • How many studies studies are there available with Nebido®, and how many patients have been enrolled in these studies?
      In more than 15 completed and ongoing studies, more than 1,500 patients have been treated with Nebido®, either in studies sponsored by Bayer or in investigator sponsored studies (ISS).
    • For what duration of administration are data available?
      The duration of one study is 4 years.4 Currently there is experience with Nebido® available of up to 9.5 years in individual patients.5
    • Is Bayer conducting further clinical studies?
      Bayer has initiated and supports a series of different studies with Nebido® with the aim to further elaborate the efficacy and safety of testosterone on a variety of conditions related to hypogonadism. These studies include two long-term, placebo-controlled studies in patients with LOH (Late-Onset Hypogonadism), one study in elderly frail men, one study in hypogonadal men with the metabolic syndrome, and one study in men with erectile dysfunction who do not respond adequately to PDE-5 inhibitors. Furthermore, several studies were initiated by external sponsors testing the effect of Nebido® in hypogonadal men with comorbidities such as metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is meanwhile a wealth of publications available from all these studies.
  • Nebido® and sports
    • Can I treat my hypogonadism by doing sport, i.e., by using the body’s own testosterone?
      Sport and a healthy diet are good supportive measures and contribute to general well-being but are not sufficient on their own. The amount of the body’s own testosterone which is released through the reduction of obesity by exercise is usually not sufficient to correct the hypogonadism.
    • What is the association between testosterone and doping?
      If the testosterone levels of a hypogonadal man (testosterone deficiency) are brought within the range of normal levels, this leads to a breakdown of fat and a build-up of muscle, the so-called anabolic effect. A very large testosterone overdose could be abused for doping purposes. However, all testosterone products are strictly prescription-only medicines. The indications for which they can be prescribed are listed in the package leaflet and have to be complied with very closely.
    • What is Bayer doing to avoid abuse/doping?
      Nebido® is only available on medical prescription, which lessens the risk of abuse. Since Nebido® is usually administered at the doctor’s office, the potential for abuse is largely reduced.

      A single injection of Nebido® cannot lead to overdosage, at least not to an elevation of mean testosterone serum levels above the normal range, provided that the testosterone serum levels have been in the low normal range or below. There have been studies with repeated injections in intervals of 6 weeks. Even then, most of the patients showed mean testosterone serum levels that remained within the normal range within 2-3 consecutive injections. One week after the injection, testosterone serum levels are at their maximum level. As with other depot-preparations, this peak may reach supraphysiological levels. However, peak levels have not been found to be of clinical relevance and sufficient for abuse as they are moderate and transient. In particular mood swings have not been reported under Nebido®, which could be explained by the slower velocity of level changes and the reduced absolute height.
    • Is it possible to overdose slightly with Nebido® with a subsequent risk of abuse? What happens then?
      Nebido® is packed in single units of one ampoule. Injections should be performed in the physician’s office in intervals of 10 to 14 weeks. Serum testosterone measurements should be performed for individualization of the therapy. An inadvertent overdose can thus be practically excluded. There have been reports of extreme overdoses with injection products. Normally, abuse should not occur if both the prescription (strictly according to the indication) and use (strictly according to the doctor’s instructions) are carried out in accordance with the treatment recommendations.

      A single injection of Nebido® cannot lead to overdosage, at least not to an elevation of mean testosterone serum levels above the normal range, provided that the testosterone serum levels have been in the low normal range or below. There have been studies with repeated injections in intervals of 6 weeks. Even then, most of the patient showed mean testosterone serum levels that remained within the normal range within 2-3 consecutive injections. One week after the injection, testosterone serum levels are at their maximum level. As with other depot-preparation, this peak may reach supraphysiological levels. However, peak levels have not been found to be of clinical relevance and sufficient for abuse as they are moderate and transient. In particular mood swings similar to short acting injections have not been reported under Nebido®, which could be explained by the slower velocity of level changes and the reduced absolute height.
  • Environment

    Does Nebido® cause any hormonal environmental pollution (shower water, urine, washing water, empty packs)?

    Men treated with Nebido® have an underlying hormone deficiency which is being compensated by Nebido® therapy. Men treated with Nebido® will have the same hormonal levels as “normal” men. This problem has been critically investigated by individual national authorities and the substance has been declared safe. None of the authorities recommended any additional precautions.
  • Nebido® and products for treatment of erectile dysfunction
    • What is the relation between hypogonadism and erectile dysfunction?
      International guidelines today emphasize the need for screening for hypogonadism in patients with erectile dysfunction.6 Impaired erectile function is a classical symptom of hypogonadism.7 The prevalence for male hypogonadism amongst men with erectile dysfunction is estimated to be around 20%.8,9

      Testosterone therapy of hypogonadal men significantly improves erectile function. Positive effects of testosterone are mediated by central stimulation of libido and sexual activity. Loss of libido has been shown to be one of the first symptoms of declining testosterone levels and may occur already at low-normal testosterone concentrations.10

      However, also has a direct effect on the penis.11 Recent studies have shown that more than 50% of hypogonadal ED patients reported restored erectile function sufficient for sexual intercourse after 10 to 12 weeks of testosterone therapy alone12,13, indicating that men with erectile dysfunction and low serum testosterone may benefit from testosterone treatment alone. Testosterone given as adjunctive therapy with phosphodiesterase-inhibitors (PDE-5i) converts the majority of hypogonadal non-responders to monotherapy with PDE-5 inhibitors into responders within 10 to 12 weeks of added testosterone therapy14. The combination of phosphodiesterase 5-inhibitors and testosterone may be indicated in hypogonadal men who do not respond sufficiently to either treatment alone.15

      Although, from a scientific perspective, it would be best to start the evaluation of a patient with erectile dysfunction by measuring testosterone, psychological facts have to be considered. A patient presenting with ED has usually been waiting for years to come forward with an embarrassing condition. He expects a quick solution to his problem. Since the majority of men will respond favorably to treatment with a PDE5 inhibitor such as Levitra®, he should receive a prescription for a PDE5 inhibitor. At the same time, the physician should keep in mind that “ED does not come alone”16 and take the opportunity to examine risk factors such as blood pressure and waist circumference (for assessing visceral obesity) and draw a blood sample to measure testosterone, lipids and blood sugar. In a very simplified phrase: “Treat ED and check for T.” This will also help to keep the patient who is at risk for cardiometabolic diseases under surveillance. If only a PDE5 inhibitor is prescribed, many patients never return to the doctor’s office, and an opportunity is lost to assess the patient’s overall health.
    • What is the difference between Nebido® and products for treatment of erectile dysfunction?
      Nebido® is not indicated to treat erectile dysfunction. Standard therapy for the treatment of erectile dysfunction are oral phosphodiesterase type 5-inhibitors (PDE5i; such as Viagra®, Cialis®, Levitra®). Nebido® restores sexual desire, i.e., it increases libido, and has a positive effect on erectile function in cases of testosterone deficiency. Lack of libido is only one symptom of hypogonadism. Further signs are: fatigue, concentration problems, changes in body composition (muscle breakdown/increase in fat).17 In order to determine the cause of sexual dysfunction, a thorough medical examination is required. However, it has also been shown that a certain threshold level of testosterone may be necessary for the full effect of ED medications. This threshold level might vary greatly between patients.

      Frequent causes for erectile disorder can be:
      • vascular diseases
      • peripheral nerve diseases
      • testosterone deficiency
      • various medications
      • excessive alcohol and nicotine consumption
      • mental disorders

      Even when testosterone therapy alone fails to improve erectile function, and PDE5I therapy is instituted, continuing with testosterone substitution in combination with the latter is often indicated as:
      • providing testosterone therapy is the only way of restoring sexual desire which is often low in such ED patients, while additional low sexual desire is a frequent cause of discontinuation of therapy with PDE 5-inhibitors
      • testosterone therapy may also improve other symptoms associated with hypogonadism, including lack of energy, mood disturbances and negative changes in body composition
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References

1 Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, ,Thompson IM, Weidner W, Wu FCW: Investigation, Treatment and Monitoring of Late-Onset Hypogonadism in Males – ISA, ISSAM, EAU, EAA, and ASA Recommendations. Aging Male 2008; in print (published online Sept. 2, 2008). Eur Urol 2008, in print

2 Gooren LJ and Behre HM: Andrologia 2008; 40: 195-199

3 Mackey M-A et al.: Human Reprod 1995; 10: 862-865.

4 Minnemann T et al. Aging Male 2007; 10: 155-158

5 Zitzmann M and Nieschlag E. J Clin Endocrinol Metab 2007; 92: 3844-3853

6 Morales A, Buvat J, Gooren L, Guay A, Kaufman JM, Tan H, Torres O: Endocrine Aspects of Sexual Dysfunction in Men. J Sex Med 2004; 1: 69-81

7 Behre: Testosterone and erections, in Nieschlag, Behre: Testosterone: Action, Deficiency, Substitution, 2004

8 Corona G, Mannucci E, Mansani R, Petrone L, Bartolini M, Giommi R, Forti G, Maggi M: Organic, relational and psychological factors in erectile dysfunction in men with diabetes mellitus. Europ Urol 2004; 46: 222-228

9 Bodie J, Lewis, J, Schow D, Monga M: Laboratory evaluations of erectile dysfunction: an evidence based approach. J Urol 2003; 169: 2262-2264.

10 Zitzmann M, Faber S, Nieschlag E: Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab 2006, 91(11): 4335-4343

11 Behre: Testosterone and erections, in Nieschlag, Behre: Testosterone: Action, Deficiency, Substitution, 2004

12 Greenstein A, Mabjeesh N, Sofer M, Kaver I, Matzkin H, Chen J: Does sildenafil combined with testosterone gel improve erectile dysfunction in hypogonadal men in whom testosterone supplementation therapy alone failed? J Urol 2005; 173: 530-532.

13 Yassin A, Saad F: Modulation of Erectile Function with a Long-Acting i.m. Injection of Testosterone Undecanoate (Nebido®) in Hypogonadal Patients. Int J Androl 2005, 28 (1): 63

14 Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H: Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. j Urol 2004; 172: 658-663.

15 Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, ,Thompson IM, Weidner W, Wu FCW: Investigation, Treatment and Monitoring of Late-Onset Hypogonadism in Males – ISA, ISSAM, EAU, EAA, and ASA Recommendations. Aging Male 2008; in print (published online Sept. 2, 2008). Eur Urol 2008, in print

16 Yassin AA et al. Andrologia 2008; 40: 259-264

17 Jockenhövel F: Male Hypogonadism. UNI-MED Verlag Bremen 2004., p.32
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Last updated: 2016
G.GM.MH.04.2015.0334