Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile

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 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), and 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.

Tabulated list of adverse reactions

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

System Organ Class      Common                    Uncommon                  Rare (≥ 1/100 to < 1/10)       (≥ 1/1000 to <1/100)      (≥ 1/10,000 to < 1/1,000)
Blood and lymphatic     Polycythaemia system disorders
Haematocrit increased*
System Organ Class      Common                 Uncommon                Rare (≥ 1/100 to < 1/10)    (≥ 1/1000 to <1/100)    (≥ 1/10,000 to < 1/1,000)
Red blood cell count increased*

Haemoglobin increased*
Immune system                                  Hypersensitivity disorders
Metabolism and          Weight increased       Increased appetite nutrition disorders
Glycosylated haemoglobin increased

Hypercholesterolaemia
Blood triglycerides increased

Blood cholesterol increased
Psychiatric disorders                          Depression

Emotional disorder
Insomnia

Restlessness

Aggression
Irritability
Nervous system                                 Headache disorders
Migraine

Tremor
Vascular disorders      Hot flush              Cardiovascular disorder

Hypertension
Dizziness
Respiratory, thoracic                          Bronchitis and mediastinal
System Organ Class    Common                Uncommon               Rare (≥ 1/100 to < 1/10)   (≥ 1/1000 to <1/100)   (≥ 1/10,000 to <
1/1,000) disorders                                   Sinusitis

Cough

Dyspnoea
Snoring

Dysphonia
Gastrointestinal                            Diarrhoea disorders
Nausea
Hepatobiliary                               Liver function test disorders                                   abnormal

Aspartate aminotransferase increased
Skin and              Acne                  Alopecia subcutaneous tissue disorders                                   Erythema

Rash1

Pruritus
Dry skin
Musculoskeletal and                         Arthralgia connective tissue disorders                                   Pain in extremity

Muscle disorder2

Musculoskeletal stiffness
Blood creatine phosphokinase increased
Renal and urinary                           Urine flow decreased disorders
Urinary retention
System Organ Class       Common                    Uncommon                  Rare (≥ 1/100 to < 1/10)       (≥ 1/1000 to <1/100)      (≥ 1/10,000 to < 1/1,000)

Urinary tract disorder

Nocturia
Dysuria
Reproductive system      Prostatic specific        Prostatic dysplasia and breast disorders     antigen increased
Prostate induration
Prostate examination abnormal                  Prostatitis

Benign prostatic          Prostatic disorder hyperplasia
Libido disorder

Testicular pain
Breast induration

Breast pain

Gynaecomastia
Oestradiol increased

Blood testosterone increased

General disorders        Various kinds of          Fatigue and administration       injection site reactions3 site conditions                                    Asthenia
Hyperhidrosis4

Injury, poisoning and                                                        Pulmonary oil procedural                                                                   microembolism** complications

*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 disorder: Muscle spasms, 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



Description of selected adverse reactions

Pulmonary micro embolism of oily solutions can in rare cases lead to signs and symptoms such as cough, dyspnea, 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 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).

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 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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/