Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
Adrenal crisis

Acute adrenal insufficiency may develop in patients with known adrenal insufficiency who are on inadequate daily doses or in situations with increased cortisol need. Therefore, patients should be advised of the signs and symptoms of acute adrenal insufficiency and of adrenal crisis and the need to seek immediate medical attention. Sudden discontinuation of therapy with hydrocortisone risks triggering an adrenal crisis and death.

Efmody-S P C-0923                                                                    Efmody-5_10 mg-SPC During adrenal crisis parenteral, preferably intravenous administration of hydrocortisone in high doses, together with sodium chloride 9 mg/ml (0.9%) solution for infusion, should be administered according to current treatment guidelines.

Pre-operatively, during serious trauma or during intercurrent illness 
Pre-operatively, anaesthetists must be informed if the patient is taking corticosteroids or has previously taken corticosteroids.

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.

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.

Infections

Infection should not be more likely at a replacement dose of hydrocortisone, but all infections should be taken seriously, and an increase in steroid dose be initiated early (see section 4.2). Patients with CAH 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.

Immunisation

Treatment schedules of corticosteroids for people with CAH do not cause immunosuppression and are not, therefore, contraindications for administration of live vaccines.

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.

Impaired glucose tolerance and diabetes are associated with treatment with glucocorticoids. Patients should be warned of the signs of diabetes and the need to seek medical advice if they occur.
All glucocorticoids increase calcium excretion and reduce the bone-remodelling rate. Long-term glucocorticoid replacement therapy may therefore reduce bone mineral density (see section 4.8).

Patients should be warned that potentially severe psychiatric adverse reactions; euphoria, mania, psychosis with hallucinations and delirium have been seen in adult patients at replacement doses of hydrocortisone (see section 4.8). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure (see also section 4.5), although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary.
Patients should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroids, medical advice should be sought immediately in the case of anaphylactoid symptoms (see section 4.8).


Efmody-S P C-0923                                                                   Efmody-5_10 mg-SPC Gastric emptying and motility disorders

Modified-release formulations, such as Efmody are not recommended in patients with increased gastrointestinal motility, i.e. chronic diarrhoea, due to the risk of impaired cortisol exposure. There are no data in patients with confirmed slow gastric emptying or decreased motility disease/disorder. The clinical response should be monitored in patients with these conditions.

Growth retardation

Corticosteroids may cause growth retardation in 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. Excessive weight gain with decreased height velocity or other symptoms or signs of Cushing syndrome indicate excessive glucocorticoid replacement. Children require frequent assessment to assess growth, blood pressure, and general well-being.

Accelerated sexual maturation

Adolescents with CAH may show accelerated sexual maturation. Patients should be closely monitored; and if signs of early puberty or accelerated sexual maturation are present, an increase in dose should be considered. Careful and regular monitoring of adolescent patients with dose adjustment according to the response of the individual patient is recommended.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy which have been reported after use of systemic and topical corticosteroids.

Treatment of CAH often warrants additional treatment with mineralocorticosteroids.

Precaution
In both men and women who have lower fertility due to CAH, fertility may be restored shortly after beginning treatment with Efmody, which can lead to unexpected pregnancies. Patients should be informed of the potential for restored fertility when starting treatment with Efmody, to be able to consider if a contraceptive measure is needed (see section 4.6).

Effects on Driving

4.7    Effects on ability to drive and use machines
Efmody has minor influence on the ability to drive and use machines. Fatigue and dizziness have been reported. Untreated and poorly replaced adrenal insufficiency may affect the ability to drive and use machines.