MEDOPRED Solution for injection / infusion Ref.[28364] Active ingredients: Prednisolone

• Glucocorticoid therapy should in principle only be undertaken with a proven diagnosis and when a simpler therapy is not possible or has failed (except in a life-threatening situation).
• Special attention should be paid to patients who seem predestined to develop complications because of:
  • ulcer anamnesis;
  • latent tuberculosis (recent Mantoux test);
  • history of psychic disorders;
  • osteoporosis;
  • hypertension;
  • diabetes mellitus (or a family history of diabetes);
• Caution is also advised in patients with:
  • previous glucocorticoid-induced myopathy;
  • liver failure;
  • renal insufficiency
  • epilepsy
• Glucocorticoids may mask some symptoms of infection and new infections may appear during their use.
• In bacterial infections, the pathogen(s) should be identified first where possible. Thereafter, the infection must be treated before starting glucocorticoid administration.
• Vaccinations should preferably not be carried out during glucocorticoid therapy.
• To prevent growth inhibition during systemic glucocorticoid therapy, an alternate-day dosing should be attempted in children, even more than in adults.
• In elderly patients, the common side-effects of systemically administered glucocorticoids may appear, such as osteoporosis, hypertension, hypokalemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life threatening reactions.
• Adrenal cortical atrophy develops during long-term treatment and may persist for years after stopping treatment. After prolonged therapy, corticoids should be tapered off gradually, over a period of weeks or months, according to the dose and duration of treatment, to avoid acute adrenal insufficiency.
• During prolonged therapy, stress (surgery, trauma, infection) may require a temporary increase in dosage; if a prolonged therapy with corticoids has been stopped abruptly, the therapy may need to be temporarily re-introduced (see sections 4.2 and 4.6).
• During systemic glucocorticoid therapy, regular ophthalmic control is advisable.
• Local injection of glucocorticoids may produce systemic effects.
• Corticosteroids should not be used to treat head injury or a cerebral seizure; because their effect could be doubtful or even harmful.
• In relation to the risk of aseptic bone necrosis with repeated injections, a patient should not be given more than 5 injections per joint during his whole life.

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 (CSCR) which have been reported after use of systemic and topical corticosteroids.

Scleroderma renal crisis

Caution is required in patients with systemic sclerosis because of an increased incidence of (possibly fatal) scleroderma renal crisis with hypertension and decreased urinary output observed with a daily dose of 15mg or more prednisolone. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.

This product contains sodium metabisulphite. May rarely cause severe hypersensitivity reactions and bronchospasm.

Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Enzyme inductors (such as phenytoin, barbiturates and rifampicin) may increase the metabolic clearance of corticosteroids, resulting in decreased blood levels and reduced physiological activity, thus necessitating adjustment of the prednisolone dosage. This interaction may interfere with the dexamethasone suppression test.

Short-term use of ritonavir inhibits the metabolism of prednisofone inhibited. With long-term use of ritonavir, the metabolism of prednisolone will be accelerated through induction of cytochrome P450 3A4.

With the concomitant administration of corticosteroids and ulcerogenic drugs account should be taken of an additive ulcerogenic effect. Preventive measures are recommended in risk patients (elderly patients with a history of ulcers). Corticosteroids used in combination with diuretics give an increased risk of hypokalemia.

The concomitant use of cyclosporine and corticosteroids may raise cyclosporine serum levels and reduce the metabolic clearance of corticosteroids.

The response to toxoids and live and inactivated vaccines may be reduced in patients receiving long-term corticosteroid therapy (see section 4.4).

High doses of corticosteroids may antagonize neuromuscular blocking agents and increase the risk of myopathy.

Corticosteroids may influence the effect of coumarin derivatives. In patients using concomitantly corticosteroids and coumarin-type anticoagulants, the prothrombin time should also be checked regularly.

The blood glucose lowering action of sulfonyfurea derivatives may be reduced.

Glucocorticoids increase the renal clearance of salicylates and steroid withdrawal may result in salicylate intoxication.

A treatment with corticosteroids may suppress skin reactions to skin tests.

Pregnancy

Experience so far shows no increased incidence of congenital abnormalities after using prednisolone in pregnant women. With higher dosage, inhibition of the cortex function in the foetus/ new-born cannot be excluded. Therefore these children should be carefully checked after birth. Data from animal studies has shown reproduction toxicity (see section 5.3).

Prednisolone should be used only if absolutely indicated. Chronic use of high doses should be avoided as much as possible.

Breast-feeding

Prednisolone is excreted in small quantities in breast milk. Breastfeeding is possible during treatment with prednisolone. If prednisolone should be used over a longer period, it is recommended to wait 3 to 4 hours after use before feeding.

Glucocorticoids may cause side effects such as mood changes (euphoria, depression; see section 4.8), visual disorders or amyosthenia. If affected, caution should be exercised in driving and using machines.

It is not so much a question of undesirable effects or complications, but of effects inherent in the corticosteroid therapy that are undesirable.

Infections and Infestations:

• infections in immunocompromised patients;
• unfavourable evolution of infections;
• sepsis;
• reactivation of latent tuberculosis; masked infections.

Blood and lymphatic system disorders:

• erythrocytosis and granulocytosis;
• lymphopenia and eosinopenia.

Immune system disorders:

• allergic reaction;
• hypersensitivity;
• anaphylactic reactions;
• immunosuppression.

Endocrine disorders:

• inhibition of hypothalamic-pituitary activity;
• adrenocortical insufficiency;
• Cushing’s syndrome;
• hirsutism.

Metabolism and nutrition disorders:

• sodium and fluid retention;
• reduced carbohydrate tolerance;
• steroid-induced diabetes mellitus;
• increased requirement for antidiabetics;
• uncontrolled diabetes mellitus;
• centripetal adiposity (face, trunk);
• increased appetite.

Psychic disorders:

• mood swings;
• euphoria;
• fear;
• depressions;
• insomnia;
• psychoses.

Nervous system disorders:

• increased intracranial pressure;
• pseudotumour cerebri;
• convulsions;
• headache.

Eye disorders:

• vision, blurred (see also section 4.4)
• papilloedema;
• posterior subcapsular cataract;
• exophthalmos;
• glaucoma.

Ear and labyrinth disorders:

• vertigo.

Cardiac disorders:

• heart failures (cardiac insufficiency).
• bradycardia (following high doses).

Vascular disorders:

• hypertension;
• petechial;
• ecchymosis;
• thromboembolism.

Gastrointestinal disorders:

• peptic ulcer;
• gastrointestinal bleeding;
• perforated ulcer, including masked perforations;
• ulcerative esophagitis;
• pancreatitis;
• nausea;
• abdominal distension.

Skin or subcutaneous tissue disorders:

• skin atrophy;
• facial erythema;
• acne;
• suppression of reactions to skin tests;
• urticarial;
• increased sweating;
• allergic dermatitis.

Musculoskeletal and connective tissue disorders:

• muscle weakness;
• muscle atrophy;
• steroid myopathy;
• osteoporosis;
• vertebral compression fractures;
• pathologic fracture or long bones;
• aseptic necrosis of femoral and humeral heads.

Reproductive system and breast disorders:

• disturbance of the menstrual pattern.

Renal and urinary disorders:

• scleroderma renal crisis*

^* Scleroderma renal crisis:

Amongst te different subpopulations the occurence of scleroderma renal crisis varies. The highest risk has been reported in patients with diffuse systemic sclerosis. The lowest risk has been reported in patients with limited systemic sclerosis (2%) and juvenile onset systemic sclerosis (1%).

General disorders and administration site conditions:

• wound healing disorders; growth inhibition in children;
• malaise;
• redness;
• hypopigmentation and atrophy at the administration site;
• painless destruction of the joint like Charcot arthropathy, mostly after repeated intra-articular injections.

Investigations:

• hypokalaemia;
• hypokalemic alkalosis;
• weight gain;
• negative nitrogen balance.

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.

(Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs Fax: +357 22608649.)

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.