Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2021 Publisher: Aventis Pharma Limited, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK Trading as: Sanofi, 410 Thames Valley Park Drive, Reading, Berkshire, RG6 1PT, UK
Systemic infection unless specific anti-infective therapy is employed.
Hypersensitivity to the active substance, deflazacort or any of the excipients listed in section 6.1. Patients receiving live virus immunisation.
A patient information leaflet should be supplied with this product.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
Undesirable effects may be minimised by using the lowest effective dose for the minimum period, and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternate days. Frequent patient review is required to appropriately titrate the dose against disease activity (see section 4.2).
Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment. Withdrawal of corticosteroids after prolonged therapy must therefore always be gradual to avoid acute adrenal insufficiency which could be fatal, being tapered off over weeks or months according to the dose and duration of treatment. During prolonged therapy, any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy, they may need to be temporarily re-introduced.
Patients should carry ‘Steroid treatment’ cards which give clear guidance on the precautions to be taken to minimise risk and which provide details of prescriber, drug, dosage and the duration of treatment.
Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognised.
Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) without a definite history of chicken pox should be advised to avoid close personal contact with chickenpox or herpes zoster and, if exposed, they should seek urgent medical attention. Passive immunisation with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.
Patients should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.
Live vaccines should not be given to individuals with impaired responsiveness. The antibody response to other vaccines may be diminished.
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.
Prolonged use of glucocorticoids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves and may enhance the establishment of secondary ocular infections due to fungi or viruses.
Use in active tuberculosis should be restricted to those cases of fulminating and disseminated tuberculosis in which deflazacort is used for management with appropriate antituberculosis regimen. If glucocorticoids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged glucocorticoid therapy, these patients should receive chemoprophylaxis.
Tendonitis and tendon rupture are known class effect of glucocorticoids. The risk of such reactions may be increased by co-administration of quinolones (see section 4.8).
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 (see section 4.8).
The following clinical conditions require special caution and frequent patient monitoring is necessary:
Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (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 pharmacokinetic interactions that can increase the risk of side effects) 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/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers 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.
Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.
Glucocorticoids are known to cause irregular menstruation and leukocytosis, care should be taken with deflazacort.
Corticosteroids cause dose-related growth retardation in infancy, childhood and adolescence which may be irreversible.
Hypertrophic cardiomyopathy has been reported after systemic administration of glucocorticosteroids in preterm infants. In infants receiving administration of systemic glucocorticosteroids, echocardiograms should be performed to monitor myocardial structure and function (see section 4.8).
The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.
Since complications of glucocorticoid therapy are dependent on dose and duration of therapy, the lowest possible dose must be given and a risk/benefit decision must be made as to whether intermittent therapy should be used.
The same precautions should be exercised as for other glucocorticoids. Deflazacort is metabolised in the liver. It is recommended to increase the maintenance dose of deflazacort if drugs which are liver enzyme inducers are co-administered, e.g. rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone and aminoglutethimide. For drugs which inhibit liver enzymes, e.g. ketoconazole it may be possible to reduce the maintenance dose of deflazacort.
In patients taking estrogens, corticosteroid requirements may be reduced.
The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids and the hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics, beta 2-agonists, xanthines and carbenoxolone are enhanced.
The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.
In patients treated with systemic corticosteroids, use of non-depolarising muscle relaxants can result in prolonged relaxation and acute myopathy. Risk factors for this include prolonged and high dose corticosteroid treatment, and prolonged duration of muscle paralysis. This interaction is more likely following prolonged ventilation (such as in the ITU setting).
The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.
As glucocorticoids can suppress the normal responses of the body to attack by micro-organisms, it is important to ensure that any anti-infective therapy is effective and it is recommended to monitor patients closely. Concurrent use of glucocorticoids and oral contraceptives should be closely monitored as plasma levels of glucocorticoids may be increased. This effect may be due to a change in metabolism or binding to serum proteins. Antacids may reduce bioavailability; leave at least 2 hours between administration of deflazacort and antacids.
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.
The ability of corticosteroids to cross the placenta varies between individual drugs, however, deflazacort does cross the placenta.
Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man. However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important. As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential however, patients with normal pregnancies may be treated as though they were in the non-gravid state.
Corticosteroids are excreted in breast milk, although no data are available for deflazacort. Doses of up to 50 mg daily of deflazacort are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this may have a degree of adrenal suppression but the benefits of breast feeding are likely to outweigh any theoretical risk.
No data is available on Deflazacort and its effects on fertility.
The effect of corticosteroids on the ability to drive or use machinery has not been systematically evaluated. Vertigo is a possible undesirable effect after treatment with deflazacort. If affected, patients should not drive or operate machinery.
The incidence of predictable undesirable effects, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage; timing of administration and the duration of treatment (see section 4.4).
The following CIOMS frequency rating is used: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10 000 to <1/1000); very rare (<1/10 000), not known (cannot be estimated from the available data).
Uncommon: suppression of the hypothalamic-pituitary-adrenal axis, amenorrhoea, Cushingoid facies.
Not known: growth suppression in infancy, childhood and adolescence.
Common: weight gain.
Uncommon: impaired carbohydrate tolerance with increased requirement for anti-diabetic therapy, sodium and water retention with hypertension, potassium loss and hypokalaemic alkalosis when co-administered with beta 2-agonist and xanthines.
Not known: negative protein and calcium balance, increased appetite.
Uncommon: increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis (see section 4.4).
Not known: candidiasis.
Uncommon: osteoporosis, vertebral and long bone fractures.
Rare: muscle wasting.
Not known: avascular osteonecrosis, tendonitis and tendon rupture when co-administered with quinolones (see section 4.4), myopathy (acute myopathy may be precipitated by non-depolarising muscle relaxants – see section 4.5), negative nitrogen balance.
Not known: menstrual irregularity.
Not known: heart failure, hypertrophic cardiomyopathy in preterm infants.
Uncommon: headache, vertigo.
Not known: restlessness, Increased intra-cranial pressure with papilloedema in children (pseudotumour cerebri), usually after treatment withdrawal, aggravation of epilepsy.
A wide range of psychiatric reactions including affective disorders such as:
Uncommon: depressed and labile mood.
Not known: irritable, euphoric, suicidal thoughts.
Psychotic reactions including:
Not known: mania, delusions, hallucinations, aggravation of schizophrenia
Other reactions including:
Uncommon: behavioural disturbances.
Not known: anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported.
Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.
Not known: vision blurred (see section 4.4), increased intra-ocular pressure, glaucoma, papilloedema, posterior subcapsular cataracts especially in children, chorioretinopathy (see section 4.4), corneal or scleral thinning, exacerbation of ophthalmic viral or fungal diseases.
Uncommon: dyspepsia, peptic ulceration, haemorrhage, nausea.
Not known: perforation of peptic ulcer, acute pancreatitis (especially in children), candidiasis.
Uncommon: hirsutism, striae, acne.
Rare: bruising.
Not known: Skin atrophy, telangiectasia.
Uncommon: oedema.
Not known: impaired healing.
Uncommon: hypersensitivity including anaphylaxis has been reported.
Not known: leukocytosis.
Not known: thromboembolism in particular in patients with underlying conditions associated with increased thrombotic tendency, rare incidence of benign intracranial hypertension.
Not known: too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death (see section 4.4).
A ‘withdrawal syndrome’ may also occur including fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight. This may occur in patients even without evidence of adrenal insufficiency.
Pheochromocytoma crisis has been reported with other systemic corticosteroids and is a known class effect (see section 4.4).
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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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