Alkindi

Posology Dose must be individualised according to the response of the individual patient. The lowest possible dose should be used. g. surgery, infection, trauma). During stress it may be necessary to increase the dose temporarily. Replacement therapy in primary and secondary adrenal insufficiency Alkindi is given as replacement therapy by oral administration of granules according to clinical practice, in a dose to be titrated against individual clinical response.

Recommended replacement doses of hydrocortisone are 8-10 mg/m2/day for patients with adrenal insufficiency alone and 10-15 mg/m2/day in patients with congenital adrenal hyperplasia (CAH), typically in three or four divided doses. In patients with some remaining endogenous cortisol production a lower dose may be sufficient.

In situations when the body is exposed to excessive physical and/or mental stress, patients may need an increased dose, especially in the afternoon or evening. Pre-operatively, during serious trauma or illness in patients with known adrenal insufficiency or doubtful adrenal reserve Pre-operatively, anaesthetists must be informed if the patient is taking corticosteroids or has previously taken corticosteroids.

In less severe situations when parenteral administration of hydrocortisone is not required, for instance low grade infections, moderate fever of any aetiology and stressful situations such as minor surgical procedures, there should be high awareness of the risk of developing acute adrenal insufficiency, and the normal oral daily replacement dose should be increased temporarily; the Alkindi total daily dose should be increased by doubling or tripling the usual dose.

Once the intercurrent illness episode is over, patients can return to the normal replacement dose of Alkindi. In severe situations, an increase in dose is immediately required and oral administration of hydrocortisone must be replaced with parenteral treatment.

Parenteral administration of hydrocortisone is warranted during transient illness episodes such as severe infections, in particular gastroenteritis associated with vomiting and/or diarrhoea, high fever of any aetiology or extensive physical stress, such as for instance serious accidents and surgery under general anaesthesia.

Where parenteral hydrocortisone is required, the patient should be treated in a facility with resuscitation facilities in case of evolving adrenal crisis. 4 Changing from conventional oral glucocorticoid treatment to Alkindi When changing patients from conventional oral hydrocortisone replacement therapy, crushed or compounded, to Alkindi, an identical total daily dose may be given.

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.

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).

4). 4). It is unclear if these relate to hydrocortisone therapy using current replacement regimens. 8 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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Adrenal crisis Where a child is vomiting or acutely unwell parenteral hydrocortisone should be started without delay, carers should be trained in adminstering this in an emergency. Sudden discontinuation of therapy with hydrocortisone risks triggering an adrenal crisis and death.

Medicinal product-induced secondary adrenocortical insufficiency may result from too rapid a withdrawal of corticosteroids and may be minimised by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, corticosteroid therapy should be reinstated.

Adrenal crisis can occur when switching from conventional oral hydrocortisone formulations, crushed or compounded, to Alkindi. Close monitoring of patients is recommended in the first week after switch. Healthcare professionals should inform carers and patients that extra doses of Alkindi should be given if symptoms of adrenal insufficiency are seen.

If this is required, then an increase in the total daily dose of Alkindi should be considered and immediate medical advice should be sought. Immunisation Replacement schedules of corticosteroids for people with adrenal insufficiency do not cause immunosuppression and are not, therefore, contraindications for administration of live vaccines.

2). Patients with adrenal insufficiency are at risk of life-threatening adrenal crisis during infection so clinical suspicion of infection should be high and specialist advice should be sought early. Undesirable effects of corticosteroid replacement therapy Most undesirable effects of corticosteroids are dose and duration of exposure related.

Undesirable effects are therefore less likely when using corticosteroids as replacement therapy. Corticosteroids may cause growth retardation in infancy, childhood and adolescence; this may be irreversible. Treatment should be limited to the minimum dose required to achieve desired clinical response and when reduction in dose is possible, the reduction should be gradual.

1. Patients with dysphagia or premature infants where oral feeding has not been established. 5