Brand Name: Deflacort
Generic Name: Deflazacort
Preparations: 6/ 30 mg Tablets
Pharmacological Category: Glucocorticoids
Mechanism of Action (MOA)
DEFLACORT (Deflazacort) is a corticosteroid prodrug; its active metabolite, 21-desDFZ, acts on the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The mechanism of action by which Deflazacort works in Duchenne Muscle Dystrophy is still unknown.
Pharmacokinetics
Peak Plasma Time: About 1 hour (fasting); about 2 hour (high fat meal)
Protein Binding: 40%
Metabolism: Rapidly converted to the active metabolite 21-desDFZ by esterases after oral administration. 21-desDFZ is further metabolized by CYP3A4 to several inactive metabolites
Elimination Half-life: 1.1 to 1.9 hours
Excretion: Predominantly urine (nearly 68%)
Indications and Dosage
• Rheumatoid arthritis
• Polymyalgia rheumatica
• Sarcoidosis
• Idiopathic nephrotic syndrome
• Duchenne muscular dystrophy
• Immune suppression in transplantation
• Bronchial asthma
Dosage:
Usual dose: 0.25 to 1.5 mg/kg daily (also used for calculating paediatric dose). For acute disorders, up to 120 mg/day deflazacort may need to be given initially. Maintenance doses in most conditions are within the range 3–18 mg/day.
Rheumatoid arthritis: The smallest effective dose should be used and increased if necessary. Maintenance dose: 3-18 mg/day.
Bronchial asthma: acute attack: high doses of 48-72 mg/day may be needed depending on severity and gradually reduced once the attack has been controlled. Chronic attack: dose should be titrated to the lowest dose that controls symptoms.
Side Effects
COMMON: Weight gain
UNCOMMON: Amenorrhoea, cushingoid facies, impaired carbohydrate tolerance, increased susceptibility and severity of infection, recurrence of dormant tuberculosis, osteoporosis, headache, vertigo, depressed and labile mood, behavioural disturbance, dyspepsia, peptic ulceration, haemorrhage, nausea, hirsutism, striae, acne, oedema, hypersensitivity including anaphylaxis
RARE: muscle wasting, bruising
NOT KNOWN: Growth suppression in infancy, childhood and adolescence, hypoproteinemia, hypocalcemia, increased appetite, candidiasis, heart failure, restlessness, anxiety, sleep disturbance, congnitive dysfunction including confusion and amnesia, blurred vision, increased intra-ocular pressure, glaucoma, papilloedema, posterior subcapsular cataracts especially in children, chorioretinopathy, corneal or sclera thinning, exacerbation of ophthalmic viral or fungal disease, perforation of peptic ulcer, acute pancreatitis, skin atrophy, telangiectasia, impaired wound healing, leukocytosis, thromboembolism, benign intracranial hypertension
Contraindications
Hypersensitivity, patients receiving live virus immunization and having systemic infection unless specific anti-infective therapy is employed.
Warnings / Precautions
• Patients with galactose intolerance or glucose-galactose malabsorption should not take this medicine.
• Withdrawal of corticosteroids after prolonged therapy must always be tapering over weeks or months according to the dose and duration of treatment.
• If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should see to an ophthalmologist.
• 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.
• Tendonitis and tendon rupture are known class effect of glucocorticoids. The risk of such reactions may be increased by co-administration of quinolones.
• Special precautions and frequent patient monitoring is required in cardiac disease or congestive heart failure, hypertension, thromboembolic disorders, gastritis or oesophagitis, diverticulitis, ulcerative colitis, abscess or pyogenic infections, fresh intestinal anastomosis, active or latent peptic ulcer, diabetes mellitus or a family history, osteoporosis, myasthenia gravis, renal insufficiency, emotional instability or psychotic tendency, epilepsy, previous corticosteroid-induced myopathy, liver failure, hypothyroidism and cirrhosis, ocular herpes simplex.
• Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids and seek medical advice if worrying psychological symptoms develop especially if depressed mood or suicidal ideation is suspected.
• 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. Echocardiograms should be performed in infants receiving glucocorticoids to monitor myocardial structure and function.
• Close clinical supervision is required in elderly to avoid life-threatening reactions.
• The lowest possible dose must be given and a risk/benefit decision must be made as to whether intermittent therapy should be used.
Drug Interactions
• It is recommended to increase the maintenance dose of deflazacort if 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 antagonized 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 International Normalized Ration (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.
• 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 with oral contraceptives may increase plasma levels of glucocorticoids.
• 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.
Pregnancy Category: C
Presentations
• DEFLACORT 6 : 10 X 10’s
• DEFLACORT 30 : 4 X 1 X 10’s