Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of safety profile
In the clinical trial programme the overall most common serious adverse events were acute adrenal insufficiency (4.2% of patients treated with Efmody), another common reaction, in relation to Efmody was fatigue (11.7% of patients), headache (7.5%), increased appetite (5.8%), dizziness (5.8%) and increased weight (5.8%).

Tabulated list of adverse reactions

Efmody-S P C-0923                                                                Efmody-5_10 mg-SPC The commonest reactions reported to Efmody in the pooled population in the clinical trial programme, are tabulated below. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100).


Efmody-S P C-0923                                                               Efmody-5_10 mg-SPC Table 1. Tabulated summary of adverse reactions seen in clinical trial programme 
MedDRA system organ classification               Event                                   Frequency Endocrine disorders                              Adrenal insufficiency including         Common acute events
Metabolism and nutrition disorders               Increased appetite                      Common Decreased appetite                      Common
Impaired fasting glucose                Common
Psychiatric disorders                            Insomnia                                Common Abnormal dreams                         Common
Depressed mood                          Common
Sleep disorder                          Common
Nervous System Disorders                         Headache                                Common Dizziness                               Common
Carpal tunnel syndrome                  Common
Paraesthesia                            Common
Gastrointestinal disorders                       Nausea                                  Common Abdominal pain upper                    Common
Skin and subcutaneous tissue disorders           Acne                                    Common Hair growth abnormal                    Common
Musculoskeletal and connective tissue            Arthralgia                              Common disorders                                        Muscle fatigue*                         Common Myalgia                                 Common
Pain in extremity                       Common
General disorders and administration site        Asthenia                                Common conditions
Fatigue                                 Very
Common
Investigations                                   Weight increased                        Common Renin increased                         Common
*Includes muscular weakness

Description of selected adverse reactions

Adrenal insufficiency (including acute events).
Events of acute adrenal insufficiency were reported during the clinical trial programme but none were considered related to Efmody. Acute adrenal insufficiency should be monitored for and treated promptly in patients with adrenal insufficiency (see section 4.2 and 4.4).

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroids especially when a patient has a history of allergies to medicinal products.

Historical cohorts of adults treated from childhood for CAH have been found to have reduced bone mineral density and increased fracture rates (see section 4.4) - it is unclear if these relate to hydrocortisone therapy using current replacement regimens.

Historical cohorts of adults treated from childhood for CAH have been found to have raised cardiovascular risk factors and a higher risk of cerebrovascular disease than the general population - it is unclear if these relate to hydrocortisone therapy using current replacement regimens.

Paediatric population

No paediatric patients were included in the clinical development programme for Efmody.
Hydrocortisone has been used for more than 60 years in paediatrics with a safety profile similar to that Efmody-S P C-0923                                                                   Efmody-5_10 mg-SPC in adults. Growth retardation has been seen in children treated with hydrocortisone for CAH and can be caused by both the disorder and hydrocortisone. Accelerated sexual maturation has been seen in hydrocortisone-treated paediatric CAH patients and is associated with excess adrenal androgen production (see section 4.4).

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