COMPOSITION

Hydrocortison. 20 mg - Lactos. - Gelatin. - Amyl. solan. - Talc. - Magnes. stearas q.s. pro compres. uno

PROPERTIES

Hydrocortisone (also called cortisol) is the glucocorticoid hormone of the adrenal cortex; it also possesses a mineralocorticoid activity, producing water and salt retention, which represents 1:3,000 and 1:100 of aldosterone's and respectively of desoxycorticosterone's activity.

At dosages higher than physiological, hydrocortisone possesses anti-inflammatory and immunosuppressive properties.

PHARMACOKINETICS

After oral administration, it reaches the peak concentration in one hour; the half-life is around 100 minutes and the protein binding is 90%.

The drug is metabolized mainly by the liver and in a less amount by the kidneys.

Excretion is mainly urinary, as conjugated glycuronides.

INDICATIONS

- Primary or secondary corticoadrenal insufficiency (Addison disease, panhypopituitarism, adrenalectomy, hypophysectomy)
- Adrenogenital syndrome and rare forms of congenital adrenal hyperplasia.

POSOLOGY

In adrenal insufficiency, replacement therapy usually involves a daily dosage of 30 mg of hydrocortisone. Preferably this amount is to be administered as a morning dose of 20 mg plus an evening dose of 10 mg, in order to comply with the human biorhythm.

In cases when stress factors occur (e.g. infection, trauma…), the dosage has to be at least doubled for the necessary period (e.g. several days). If the stress is important (surgery requiring general anesthesia), the I.V. form of hydrocortisone or of another glucocorticoid has to be administered.

Patients with adrenogenital syndrome will have all the dosage administered the evening in order to inhibit the ACTH production (10 to 40 mg, as necessary).

With the exception of short-term therapy, never stop brutally the treatment but proceed with slowly reducing the dosage, in accordance with the total duration of the therapy and under medical supervision.
In cases of long-term treatment, the minimum effective dosage will be established by gradually reducing the daily amount, and depends on the pathology for which the treatment was required.

CONTRAINDICATIONS

The usual contraindications of systemic therapy with corticoids do not apply to the hormone replacement therapy with hydrocortisone.

ADVERSE EFFECTS

They can be expected during long-term treatments or while using a dosage higher than the physiological dosage (30 mg daily).

- Disturbances in water and electrolytes: hypokaliemia with alkalosis, saline and water retention, sometimes hypertension, congestive heart failure
- Endocrine and metabolic disturbances: iatrogenic Cushing syndrome, impaired glucose tolerance (reversible), reversible diabetes mellitus, stunting children's growth, menstrual irregularities.
- Musculoskeletal disorders: weakness and atrophia in muscles, osteoporosis, pathological fractures, especially vertebral compression fractures; aseptic necrosis of the femoral head.
- Digestive disorders: gastroduodenal ulcers (possible hemorrhagic or perforated), exceptionally acute pancreatitis.
- Skin disorders: acne, hypertrichosis, ecchymoses, purpura, delayed cicatrization.

PRECAUTIONS

For the replacement therapy there is no special precaution to be observed. If higher dosage is used for a certain period, it is required to regularly check the glucidic balance, blood pressure, kaliemia and the occurrence of infections (ordinary bacteria, Koch bacillus or fungi).

During the periods of high dosage immunizations are forbidden and in some cases it is recommended to proceed with a tuberculostatic prophylaxis. A low sodium and low glucidic diet could be sometimes required.

PREGNANCY AND LACTATION

Hydrocortisone dosage has to be adapted (usually increased) to the physiological needs of pregnant and lactating women. ACTH and urinary cortisol excretion measurements can guide the adjustments.

INTERACTIONS

Interactions appear only with therapeutical overdose:

Do not associate the drug with:
I.V. erythromycin, sultopride, vincamine - there is an increased risk for torsade de pointes (hypokaliemia, bradycardia and a preexisting long QT are predisposing to this).

Special precautions when associating this drug with:
- Antiarrhythmic drugs that might generate torsade de pointes:
- Bepridil, bretylium, disopyramide, sotalol and amiodarone.
- Hypokaliemia is a predisposing factor as well as bradycardia and a preexistent long QT interval. Regularly check ECG and especially the QT interval. In case of torsade, do not administer antiarrhythmic drugs (proceed with defibrillator).

- Digoxin and its class:
- Hypokaliemia predispose the digitalized patients to toxic effects

- Other drugs that decrease kaliemia:
- Increased risk for hypokaliemia

For all the above cases, kaliemia has to be checked on a regular base, ECG should be performed and when necessary hypokaliemia has to be corrected.

- Acetylsalicylate:
- During treatment with corticoids, salicylemia decreases (caused by increased salicylate excretion). After corticoids are withdrawn, there is a risk of salicylate overdose. An adjustment of dosages has to take place during and after the corticoid treatment.

- Oral anticoagulants and parenteral heparin:
- Increased risk of hemorrhage due to the corticoids' effects on digestive mucosa and also to the vascular fragility. This risk has to be considered at high dosage or when the treatment is for a period longer than 10 days. When these two treatments need to be associated, patients have to be closely monitored.

- Insulin, metformin, hypoglycemic sulfonylureas:
- Hyperglycemia and sometimes ketosis (corticoids decrease glucose tolerance) require that patients to be advised to perform more frequently their blood and urine tests.
- Adjust the dosage of antidiabetic drugs during and after the corticoid treatment.

- Phenobarbital, phenytoin, primidone, rifampicin (enzyme inducing drugs):
- Decreased effectiveness of corticoids (their catabolism is increased). Clinical and biological control, adjustment of the corticoid dosage during and after the treatment with the enzyme inducing drugs.

Notifiable associations:
- Antihypertensive drugs:
- Corticoids decreased the antihypertensive effect (water and salt retention).
- Alpha interferon:
- There is a risk that interferon's activity might be inhibited.
- Live attenuated vaccines: risk of generalized disease, potentially lethal. The risk is increased in patients who are already immunocompromised because of the disease's effect. When possible (poliomyelitis) use an inactive vaccine.

OVERDOSE

There is no clinical risk related to acute overdose.

Chronic overdose appears as a Cushing syndrome.

STORAGE

Preserve at normal temperature (15 to 25 Celsius degrees).

KEEP THE DRUGS OUT OF THE REACH OF CHILDREN!

VALIDITY

See expiry date printed on the container.
Expiry date is the first day of the printed month.

AVAILABILITY

Prescription drug.