Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of safety profile
A total of 30 healthy (but dexamethasone-suppressed) adult male subjects in two phase 1 studies and 24 paediatric patients with adrenal insufficiency in two phase 3 studies have been treated with Alkindi. There were no adverse reactions and no episodes of adrenal crisis seen in any of the studies.

In clinical practice most adverse reactions have been mild and self-limiting but adrenal crisis has been observed at time of changing from other hydrocortisone products and monitoring of patients at time of switch is advised (see section 4.4).


Tabulated list of adverse reactions
The following adverse reactions have been reported in the scientific literature in adult patients for other hydrocortisone medicinal products when given as adrenal insufficiency replacement therapy with frequency not known (cannot be estimated from the available data).

Table 1 – Adverse reactions

MedDRA system organ class                                  Frequency: not known 
Psychiatric disorders                                  Psychosis with hallucinations and delirium Mania
Euphoria

Gastrointestinal disorders                             Gastritis
Nausea

Renal and urinary disorders                            Hypokalaemic alkalosis 

Description of selected adverse reactions
When changing a patient from other oral hydrocortisone formulations to Alkindi, inaccuracy in the dosing possible with other oral hydrocortisone formulations can lead to a relative fall in hydrocortisone exposure on the same nominal dose, leading to symptoms of adrenal insufficiency such as tiredness, excessive sleeping, poor feeding, or adrenal crisis (see section 4.4).


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


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/