Nebido 1000 mg/4ml solution for injection *
Pharmacy Only: Prescription

  • Company:

    Bayer Limited
  • Status:

    No Recent Update
  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)
  • Active Ingredient(s):

    *Additional information is available within the SPC or upon request to the company

Updated on 29 November 2022

File name

6385ef943c552.pdf

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Correction of Date of 1st Authorisation

Updated on 28 November 2022

File name

6384e1af15035.pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - what the product looks like and pack contents
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

  1. Update of the MedDRA terminology Editorial change
  2. The list of the names of the medicine in different member states in the PIL (addition of BG and RO). Editorial change

Updated on 28 November 2022

File name

6384e1367f440.pdf

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

  1. Addition of a statement informing the prescribing physician about the need for potential dose adjustment of hypoglycaemic agents to section 4.4.
  2. An editorial update for the information related to the appearance of Nebido in SmPC: Clear, colorless to yellowish-brown oily solution.

Updated on 28 November 2022

File name

6384e06a8c78a.pdf

Reasons for updating

  • Change to section 3 - Pharmaceutical form
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

  1. Addition of a statement informing the prescribing physician about the need for potential dose adjustment of hypoglycaemic agents to section 4.4.
  2. An editorial update for the information related to the appearance of Nebido in SmPC: Clear, colorless to yellowish-brown oily solution.

Updated on 06 October 2022

File name

633ec9d3a025a.pdf

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Marketing Authorisation Holder

Bayer Limited, 1st Floor, The Grange Offices, The Grange, Brewery Road, Stillorgan, Co. Dublin, A94 H2K7, Ireland 

Updated on 06 October 2022

File name

633ec946abc8b.pdf

Reasons for updating

  • Change to section 6 - marketing authorisation number
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Bayer Limited, 1st Floor The Grange Offices, The Grange, Brewery Road, Stillorgan, Co. Dublin, A94 H2K7, Ireland

Updated on 06 October 2022

File name

20200305_SPC_CC_19122_1583916806.pdf

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Marketing Auhtorisation Holder

Bayer Limited, 1st Floor The Grange Offices, The Grange, Brewery Road, Stillorgan, Co. Dublin, A94 H2K7, Ireland

Updated on 11 March 2020

File name

20200305_PL_CC_19122_1583916927.pdf

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 4 - how to report a side effect
  • Change to section 6 - date of revision

Updated on 11 March 2020

File name

20200305_SPC_CC_19122_1583916806.pdf

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 07 January 2020

File name

20191127_PL_CC_NEB_19099_1578393790.pdf

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to date of revision

Updated on 07 January 2020

File name

20191127_SPC_CC_19099_1578393642.pdf

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

EDM Updated on 01 August 2019

File name

20180522_EDM_NEB_1536051579.pdf

Reasons for updating

  • Add New Doc

Updated on 20 December 2018

File name

20181023_PL_CC_NEB_18158_1545321462.pdf

Reasons for updating

  • Change to section 2 - excipient warnings
  • Change to section 3 - how to take/use
  • Change to other sources of information section

Updated on 20 December 2018

File name

20181023_SPC_CC_18158_1545321520.pdf

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 6.6 - Special precautions for disposal and other handling

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 29 August 2017

File name

PIL_10062_906.pdf

Reasons for updating

  • New PIL for new product

Updated on 29 August 2017

Reasons for updating

  • Change to section 6 - manufacturer

Updated on 17 January 2017

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 17 January 2017

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In Section 4.4 Special warnings and precautions for use:

As a general rule, the limitations of using intramuscular injections in patients with acquired or inherited blood clotting irregularities always have to be observed.

 

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, as there have been post-marketing studies and reports of thrombotic events in these patients during testosterone therapy.

Updated on 17 January 2017

Reasons for updating

  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 6 - date of revision

Updated on 12 May 2016

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text
  • Change to section 2 - Qualitative and quantitative composition

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 2 - Qualitative and Quantitative Composition:

-Each ampoule / vial with 4 ml solution for injection contains 1000 mg testosterone undecanoate "corresponding to 631.5 mg testosterone" -was added.

In section 4.2 - Posology and Method of Administration; Under "Paediatric Population":

-
Nebido is not indicated for use in children and adolescents and it has not been clinically evaluated clinically in males under 18 years of age (see section 4.4) - Clinically was moved.

In section 4.4 - Special Warnings and Precautions For Use; Under "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 sodium 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) -was added and 'sodium' moved.

In section 4.5 - Interaction with other medicinal products and other forms of interaction;

-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 -was added.

In section 4.8 - Undesirable effects :

-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 (³ 1/100 to < 1/10), and uncommon (³ 1/1000 to < 1/100) and rare (³ 1/10,000 to < 1/1,000). -was added.

Within Table 1: "Injury, Poisoning and Procedural Complications" -was added as a category.

-Pulmonary oil microembolism** -was added as a 'Rare ADR' under the above category.

In section 6.6 - Special Precautions for Disposal and Other Handling:

Under "Vial":

-The vial is for single use only. The content of a vial is to be injected intramuscularly immediately after drawing up into the syringe. After removal of the plastic cap (A) do not remove the metal ring (B) or the crimp cap (C).-was added.

In section 10 - Date of Revision of Text

April 2016 -was added.

Updated on 12 May 2016

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions
  • Change to information about pregnancy or lactation
  • Change to date of revision

Updated on 20 October 2015

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.4:
  • Elderly population has been list as a seperate heading and this statement has been altered as follows: There is limited experience on the safety and efficacy of the use of Nebido in elderly patients over 65 years of age.
  • The title Medical Examination becomes Medical examination and laboratory tests
  • Medical examination has been list as a separate heading
  • The following section has been changed as indicated:
Besides laboratory tests Laboratory Tests

In patients receivingon long-term androgen therapy, the following laboratory parameters should be checked periodicallyalso be monitored regularly: haemoglobin, and haematocrit, and liver function tests and lipid profile (see section 4.8).

Testosterone level should be monitored at baseline and at regular intervals during treatment. Clinicians should adjust the dosage individually to ensure maintenance of theeugonadal testosterone concentrations inlevels.
  • The following have been introduced as separate headings:
Cardiac, hepatic or renal insufficiency

Hepatic or renal insufficiency

Cardiac insufficiency

Other conditions

  • The following statement has been introduced;

    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 blood clotting irregularities always have to be observed.



Section 4.8
The following part of this sentence has been removed:

  • Cases suspected by the company or the reporter to represent oily pulmonary micro embolism 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 Special warnings and precautions for use).
The following chart has been changed to:

System Organ Class

Common
(
³ 1/100 to < 1/10)

 

Uncommon
(
³ 1/1000 to < 1/100)

 

Blood and lymphatic system disorders

Polycythaemia

Haematocrit increased*

Red blood cell count increased*

Haemoglobin increased*

Haematocrit increased

Red blood cell count increased

Haemoglobin increased

Immune system disorders

 

Hypersensitivity



The following statement has been introduced:

  • *              Respective frequency has been observed in relation to the use in testosterone containing products.
The following statement has been altered

Cases suspected by the company or the reporter to represent oily pulmonary micro embolism 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 Special warnings and precautions for use).



Updated on 20 October 2015

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to improve clarity and readability

Updated on 12 June 2015

Reasons for updating

  • Improved electronic presentation

Updated on 18 February 2015

Reasons for updating

  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 10 - Date of revision of the text
  • Change to improve clarity and readability

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In section 4.3, " (listed in section 6.1)” has been added after  “hypersensitivity to the active substance or to any of the excipients”

In  section 4.8 the paragraph on Reporting of suspected adverse reactions has been added.

In section 4.2 Metabolism has been renamed Biotransformation

 

Updated on 05 February 2015

Reasons for updating

  • Addition of information on reporting a side effect.
  • Change to improve clarity and readability

Updated on 20 December 2012

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

In  Section 2: Qualitative and Quantitative Composition , the sentence " Each ampoule with 4ml solution for injection contains 1000mg testerone udecanoate. " has been updated to incorporate the vial container such that it reads " Each ampoule / vial with 4 ml solution for injection contains 1000mg testerone udecanoate. "

In Section 4.2: Posology and Method of Administration, vial has been added to the first sentence to reflect the new type of container available. This sentence now reads " One ampoule /  vial of Nebido (corresponding to 1000mg testerone undecanoate) is injected every 10 to 14 weeks.".

In Section 4.2; Posology and Method of Administration, under the heading Method of Administration, the text has been updated to include reference to the vial container which is now available alongside the ampoule. The updated text reads " The contents of an ampoule / vial are to be injected intramuscularly immediately after opening. (For the ampoule see section 6.6 for instructions on opening the ampoule safely.)"

In Section 6.5: Nature and Contents of Container, the text has been updated to reflect the fact that a new vial container is now available alongside the ampoule. The new text reads:

Ampoule
5-ml brown glass (type I) ampoules, containing a fill volume of 4 ml
Pack size; 1 x 4 ml

Vial
6-ml brown glass (type I) vial with gray bromobutyl (foil-clad ETFE) injection stopper and bordered cap, containing a fill volume of 4 ml
Pack size 1 x 4 ml "


Section 6.6, Special Precautions for Disposal and Other Handling has been updated to contain the warning,

Vial
The vial is for single use only
"

Section 10. Date of Revision of the Text has been updated with the new revision date of the text, " November 2012 "

Updated on 12 December 2012

Reasons for updating

  • Change to packaging
  • Change to date of revision

Updated on 18 June 2012

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

(Inserted text; deleted text)

 

Section 4.2: Posology and method of administration

……………………………………….

 

Method of administration

For intramuscular use.

 

The injections must be administered very slowly (over two minutes). Nebido is strictly for intramuscular injection. Care should be taken to inject Nebido deeply into the gluteal muscle following the usual precautions for intramuscular administration. Special care must be taken to avoid intravasal injection (see section 4.4 under “Application”). The contents of an ampoule are to be injected intramuscularly immediately after opening the ampoule (see section 6.6 for instructions on opening the ampoule safely).

 

 

Section 4.4: Special warnings and precautions for use

…………………………………….

 

Medical examination

 

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.

……………………………………..

 

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 symptons of pulmonary oily micro embolism. Treatment is usually supportive, e.g. by administration of supplemental oxygen.

 

 

Section 4.8: Undesirable effects

 

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 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. Cases suspected by the company or the reporter to represent oily pulmonary micro embolism have been reported rarely in clinical trials (in  ≥ 1/10,000 and <1/1,000 injections) as well as from postmarketing experience (see 4.4 Special warnings and precautions for use).

 

Suspected anaphylactic reactions after Nebido injection have been reported.

 

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

……………………………………………..

 

Pulmonary micro embolism of oily solutions can in rare cases lead to signs and symptoms such as cough, dyspnea, malaise, hyperhydrosis, chest pain, dizziness, paresthesia, 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 micro embolism have been reported rarely in clinical trials (in ≥ 1/10,000 and < 1/1,000 injections) as well as from postmarketing experience (see 4.4 Special warnings and precautions for use).

 

Suspected anaphylactic reactions after Nebido injection have been reported.

………………………………………………..

 

6.6          Special precautions for disposal and other handling

……………………………………………………..

 

Notes on handling the OPC (One-Point-Cut) ampoule:

 

There is a pre-scored mark beneath the coloured point on the ampoule eliminating the need to file the neck. Prior to opening, ensure that any solution in the upper part of the ampoule flows down to the lower part. Use both hands to open; while holding the lower part of the ampoule in one hand, use the other hand to break off the upper part of the ampoule in the direction away from the coloured point.

 

 

9.            DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

Date of first authorisation: 12 November 2004

Date of last latest renewal: 25 November 2008

 

10.          DATE OF REVISION OF THE TEXT

 

August 2011 May 2012

 

Updated on 30 January 2012

Reasons for updating

  • Change to further information section
  • Change to date of revision

Updated on 07 September 2011

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.4     Special warnings and precautions for use

 

The following sentence has been inserted at the end of section 4.4:

“Suspected anaphylactic reactions after Nebido injection have been reported.”

 

 

4.8         Undesirable effects

 

The following sentences have been inserted in section 4.8:

 

“Pulmonary microembolism of oily solutions can in rare cases lead to signs and symptoms such as cough, dyspnea, malaise, hyperhydrosis, chest pain, dizziness, paresthesia, 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 4.4 Special warnings and precautions for use).

 

Suspected anaphylactic reactions after Nebido injection have been reported.”

 

10.     Date of revision of the text

 

The date of revision of the text (section 10) has been updated to “August 2011”

Updated on 05 September 2011

Reasons for updating

  • Change to side-effects
  • Change to further information section

Updated on 21 February 2011

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Correction of spelling/typing errors

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes for Nebido FI/H/313/001/II/023 IMB ref. C2086941

Approved Febraury 2011

Superceded

Newly approved

 

 

4.2         Posology and method of administration

 

4.3         Posology and method of administration

 

For intramuscular use.

 

Adult and Elderly men

One ampoule of Nebido (corresponding to 1000 mg testosterone undecanoate) is injected every 10 to 14 weeks. Injections with this frequency are capable of maintaining sufficient testosterone levels and do not lead to accumulation.

 

The injections must be administered very slowly. 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 contents of an ampoule are to be injected intramuscularly immediately after opening the ampoule.

 

Start of treatment

Serum testosterone levels should be measured before start and during initiation of treatment. Depending on serum testosterone levels and clinical symptoms, the first injection interval may be reduced to a minimum of 6 weeks as compared to the recommended range of 10 to 14 weeks for maintenance. With this loading dose, sufficient steady state testosterone levels may be achieved more rapidly.

 

Maintenance and individualisation of treatment

The injection interval should be within the recommended range of 10 to 14 weeks. Careful monitoring of serum testosterone levels is required during maintenance of treatment. It is advisable to measure testosterone serum levels regularly. Measurements should be performed at the end of an injection interval and clinical symptoms considered. These serum levels should be within 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.

 

Children and Adolescents

Nebido is not indicated for use in children and adolescents and it has not been evaluated clinically in males under 18 years of age.

 

Posology

 

One ampoule of Nebido (corresponding to 1000 mg testosterone undecanoate) is injected every 10 to 14 weeks. Injections with this frequency are capable of maintaining sufficient testosterone levels and do not lead to accumulation.

 

Start of treatment

 

Serum testosterone levels should be measured before start and during initiation of treatment. Depending on serum testosterone levels and clinical symptoms, the first injection interval may be reduced to a minimum of 6 weeks as compared to the recommended range of 10 to 14 weeks for maintenance. With this loading dose, sufficient steady state testosterone levels may be achieved more rapidly.

 

Maintenance and individualisation of treatment

 

The injection interval should be within the recommended range of 10 to 14 weeks. Careful monitoring of serum testosterone levels is required during maintenance of treatment. It is advisable to measure testosterone serum levels regularly. Measurements should be performed at the end of an injection interval and clinical symptoms considered. These serum levels should be within 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.

 

Special populations

 

Paediatric population

 

Nebido is not indicated for use in children and adolescents and it has not been evaluated clinically in males under 18 years of age (see section 4.4)

 

Geriatric patients

 

Limited data do not suggest the need for a dosage adjustment in elderly patients (see section 4.4).

 

Patients with hepatic impairment

 

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

 

Patients with renal impairment

 

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

 

Method of administration

For intramuscular use.

 

The injections must be administered very slowly. Nebido is strictly for intramuscular injection. Care should be taken to inject Nebido deeply into the gluteal muscle following the usual precautions for intramuscular administration. Special care must be taken to avoid intravasal injection (see section 4.4 under “Application”). The contents of an ampoule are to be injected intramuscularly immediately after opening the ampoule (see section 6.6 for instructions on opening the ampoule safely).

 

4.3     Contraindications

 

4.3     Contraindications

 

The use of Nebido is contraindicated in androgen-dependent carcinoma of the prostate or of the male mammary gland; past or present liver tumours; hypersensitivity to the active substance or to any of the excipients.

 

The use of Nebido is contraindicated in men with:

·            androgen-dependent carcinoma of the prostate or of the male mammary gland

·            past or present liver tumours

·            hypersensitivity to the active substance or to any of the excipients

 

The use of Nebido in women is contraindicated.

 

4.4     Special warnings and precautions for use

 

4.4     Special warnings and precautions for use

 

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 of the use of Nebido in elderly 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

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).

 

Besides laboratory tests of the testosterone concentrations in patients on long-term androgen therapy the following laboratory parameters should be checked periodically: hemoglobin, hematocrit and liver function tests.

 

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.

 

Rarely, benign and malignant liver tumours have been reported in patients receiving testosterone replacement therapy.

 

Other conditions

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. 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.

 

As a general rule, the limitations of using intramuscular injections in patients with acquired or inherited blood clotting irregularities always have to be observed.

 

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.

 

Application

As with all oily solutions, Nebido 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, dyspnea, malaise, hyperhydrosis, chest pain, 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 supplemental oxygen. 

 

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 of the use of Nebido in elderly 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

 

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).

 

Besides laboratory tests of the testosterone concentrations in patients on long-term androgen therapy the following laboratory parameters should be checked periodically: haemoglobin, haematocrit, and liver function tests (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.

 

Other conditions

 

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. 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, as treatment with androgens may result in increased sodium retention (see section 4.8).

 

As a general rule, the limitations of using intramuscular injections in patients with acquired or inherited blood clotting irregularities always have to be observed.

 

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.

 

Application

 

As with all oily solutions, Nebido 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. Treatment is usually supportive, e.g. by administration of supplemental oxygen.

 

4.6 Pregnancy and lactation

 

4.6 Fertility, pregnancy and lactation

Nebido is not indicated for use in women and must not be used in pregnant or breastfeeding women.

 

Fertility

Testosterone replacement therapy may reversibly reduce spermatogenesis (see sections 4.8 and 5.3).

 

Pregnancy and lactation

Nebido is not indicated for use in women and must not be used in pregnant or breast-feeding women, see section 4.3.

 

4.8 Undesirable effects

 

4.8 Undesirable effects

 

Regarding undesirable effects associated with the use of androgens, please also refer to section 4.4.

 

The most frequent undesirable effects under treatment with Nebido are acne and    injection site pain.

 

Table 1 below reports adverse reactions (ADRs) by MedDRA system organ classes (MedDRA SOCs). The frequencies are based on clinical trial data. The adverse reactions were recorded in 6 clinical studies (N=422) and considered at least possibly causally related to Nebido.

 

Table 1, adverse reactions, 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.

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:

 

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 (³ 1/100 to < 1/10) and uncommon (³ 1/1000 to < 1/100). 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 3 ml of TU 250 mg/ml

 

Although these adverse reactions were not reported during the clinical studies performed with Nebido, the possibility that they also occur under treatment cannot be ruled out.

 

 

6.6 Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

 

6.6 Special precautions for disposal and other handling

 

The solution for intramuscular injection is to be visually inspected prior to use and only clear solution free from particles should be used.

 

The medicinal product is for single use only and any unused solution should be discarded.

 

The solution for intramuscular injection is to be visually inspected prior to use and only clear solutions free from particles should be used.

 

The medicinal product is for single use only and any unused solution should be discarded in accordance with local requirements.

 

Notes on handling the OPC (One-Point-Cut) ampoule:

 

There is a pre-scored mark beneath the coloured point on the ampoule eliminating the need to file the neck. Prior to opening, ensure that any solution in the upper part of the ampoule flows down to the lower part. Use both hands to open; while holding the lower part of the ampoule in one hand, use the other hand to break off the upper part of the ampoule in the direction away from the colored point.

 

 

 

10. Date of Revision of the Text

 

10. Date of Revision of the Text

 

April 2009

 

February 2011

 

 

 

 

Updated on 16 February 2011

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to instructions about overdose
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to further information section
  • Change to dosage and administration

Updated on 20 April 2009

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text
  • Change to section 9 - Date of renewal of authorisation

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.4: additional text re pulmonary microembolism.
Section 4.8: section revised
Section 6.9: date of last renewal 25.11.08
Section 10: date of revision of text April 2009

Updated on 14 April 2009

Reasons for updating

  • Change to further information section
  • Change due to harmonisation of patient information leaflet
  • Change of contraindications
  • Change to side-effects
  • Change to drug interactions
  • Change to warnings or special precautions for use
  • Change to instructions about overdose
  • Change to date of revision

Updated on 15 September 2008

Reasons for updating

  • Change to marketing authorisation holder

Updated on 09 September 2008

Reasons for updating

  • Change to section 8 - MA number
  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 7, 8 and 10 changed to:
7. Marketing Authorisation Holder

Bayer Limited

The Atrium

Blackthorn Road

Dublin 18

8. Marketing Authorisation Number(s)

PA 1410/20/1

 

10. Date of Revision of the Text

November 2007

 

Updated on 30 January 2007

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 6.3 Shelf Life

Extension of the approved shelf life from 3 years to 5 years.

Updated on 22 August 2006

Reasons for updating

  • Improved electronic presentation

Updated on 26 October 2005

Reasons for updating

  • Improved electronic presentation

Updated on 05 August 2005

Reasons for updating

  • New PIL for new product

Updated on 01 July 2005

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)