Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Diprospan cannot be used for intravenous or subcutaneous administration.
Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use.

Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.

ANTISEPTIC TECHNIQUES ARE NECESSARY.

Diprospan contains two betamethasone esters, one of which, betamethasone sodium phosphate, disappears rapidly from the injection site. Therefore, when using this product, the physician must take into account that this soluble portion of Diprospan may have a systemic effect.

Eliminating or abruptly reducing administration during chronic use (at very high doses, after only a short time), or when an increase in corticosteroid requirements (following stress: infection, trauma, surgery) may precipitate adrenal insufficiency. It is therefore necessary to reduce the dose gradually. In stressful situations, it is sometimes necessary to administer corticosteroids again or to increase the dose.

The dose reduction should be achieved under close medical supervision and it is sometimes necessary to monitor the patient for up to 1 year after cessation of prolonged or high-dose treatment.

The symptoms of adrenal insufficiency are: discomfort, muscle weakness, mental disorders, lethargy, muscle and bone pain, desquamation of the skin, dyspnea, anorexia, nausea, vomiting, fever, hypoglycemia, hypotension, dehydration, and even death following abrupt discontinuation of the treatment. Treatment of adrenal insufficiency consists in administering corticosteroids, mineralocorticoids, water, sodium chloride and glucose.

Rapid intravenous injection of high doses of corticosteroids can cause cardiovascular collapse; this is why the injection has to be administered over a 10-minute period.

Rare instances of anaphylactoid/anaphylactic reactions with a possibility of shock have occurred in patients receiving parenteral corticosteroid therapy. Appropriate precautionary measures should be taken with patients who have a history of allergic reactions to corticosteroids.


During prolonged corticosteroid therapy, consider switching from parenteral to oral administration after weighing the potential benefits and risks.

For intra-articular injections, it is important to know that:
-      This type of administration can have local and systemic effects.
-      It is essential to examine any liquid that may be present in the joint, in order to exclude a septic process.
-      Avoid local injection into a previously infected joint.
-      A net increase in pain and local swelling, further decrease in joint mobility, fever and discomfort should raise the question of septic arthritis. If the diagnosis of infection is confirmed, appropriate antimicrobial treatment must be initiated.
-      Do not inject corticosteroids in unstable joints, infected areas or intervertebral spaces.
-      Repeated injections into osteoarthritis-affected joints can aggravate the destruction of the joint.
-      Avoid injecting corticosteroids directly into tendons because tendon rupture may occur subsequently.

Intramuscular injection of corticosteroids should be performed deep in large muscle masses to avoid local tissue atrophy.

The administration of a corticosteroid in soft tissue, or intralesional and intra-articular administration, can induce systemic and local effects.

Specific groups at risk
In diabetics, betamethasone may be used only for a short period and only under close medical supervision, given its glucocorticoid properties (transformation of glucose into proteins).

There is an increase in the glucocorticoid effect in patients with hypothyroidism or cirrhosis.

The use of Diprospan in ocular herpes simplex should be avoided, given the possibility of perforation of the cornea.

Psychotic disorders can occur during treatment with corticosteroids. Predisposition to emotional instability or psychosis may worsen during treatment with corticosteroids.

Caution is advised in case of:
-     nonspecific ulcerative colitis, impending perforation, abscess and other pyogenic infections; -     diverticulitis;
-     intestinal anastomosis;
-     gastroduodenal ulcer;
-     renal insufficiency;
-     hypertension;
-     osteoporosis;
-     myasthenia gravis;
-     glaucoma;
-     acute psychoses;
-     viral and bacterial infections;
-     growth retardation;
-     tuberculosis;
-     Cushing's syndrome;
-     diabetes;
-     heart failure;
-     difficult-to-treat epilepsy;
-     thromboembolism or thrombophlebitis tendencies;
-     pregnancy.

Since the complications of corticosteroid treatment depend on the dose and duration of treatment, the risk/benefit ratio for each patient regarding the dose and duration of treatment needs to be considered.

Corticosteroids may mask certain signs of infection or make the detection of infection more difficult.
Due to a decrease in resistance, new infections can occur during use.

Prolonged use can lead to a posterior subcapsular cataract (especially in children) or to glaucoma, which can damage the optic nerves and may exacerbate secondary ocular infections due to fungi or viruses.
In case of prolonged treatment (over 6 weeks), it is necessary to undergo regular ophthalmological examinations.
Average and large doses of corticosteroids can induce hypertension, fluid retention and increased potassium excretion. These effects are less likely to occur with the synthetic derivatives, except when used at high doses. A low sodium diet and potassium supplements may be considered. All corticosteroids increase calcium excretion.

PATIENTS ON CORTICOTHERAPY CANNOT RECEIVE THE FOLLOWING TREATMENTS:
-    SMALLPOX VACCINATION.
-    OTHER METHODS OF IMMUNIZATION (ESPECIALLY AT HIGH DOSE) BECAUSE OF THE RISK OF NEUROLOGICAL COMPLICATIONS AND INADEQUATE ANTIBODY
RESPONSE.

However, patients receiving corticosteroids as replacement therapy may be immunized (e.g., Addison's disease).
Patients, especially children, receiving immunosuppressive doses of corticosteroids should be warned to avoid exposure to chickenpox or measles.

In case of active tuberculosis, corticosteroids should be limited to cases of fulminating or disseminated tuberculosis, in which corticosteroids are used in combination with a suitable anti-tubercular treatment regimen.

If corticosteroids are indicated in patients with latent tuberculosis or reacting to tuberculin, strict monitoring is necessary because disease reactivation can occur. During prolonged corticosteroid therapy, patients should receive chemoprophylaxis.

If using rifampicin in a chemoprophylaxis program, its enhancing effect on the metabolic hepatic clearance of corticosteroids must be remembered; it may be necessary to adjust the dose of the corticosteroid.

As corticosteroids can disturb the growth of infants and children and inhibit the endogenous production of corticosteroids, it is important to monitor their growth and development carefully in the event of prolonged treatment.

Corticosteroids may sometimes alter the motility and number of spermatozoa in some patients.

Diprospan contains benzyl alcohol.
Benzyl alcohol may cause allergic reactions. Benzyl alcohol has been linked with the risk of severe side effects including breathing problems (called “gasping syndrome”) in young children. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Do not administer to premature babies or newborns at term (up to 4 weeks). Do not administer for more than a week in young children (less than 3 years old).
Large amounts of benzyl alcohol may cause metabolic acidosis. Special precautions should be taken when prescribing Diprospan to neonates, pregnant or breast-feeding patients and patients with liver or kidney disease.

Diprospan contains sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per injection, that is to say essentially ‘sodium-free’.

Diprospan contains (methyl parahydroxybenzoate) and (propyl parahydroxybenzoate) which may cause allergic reactions (possibly delayed) and exceptionally, bronchospasm.

Visual disturbance

Visual disturbance may be reported with systemic and topical (including, intranasal, inhaled and intraocular) 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 of visual disturbances which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Effects on Driving

4.7   Effects on ability to drive and use machines

Caution should be exercised concerning the central effects when administered at high doses (euphoria, insomnia) and with regard to the vision disorders that can occur with prolonged treatment.