EDITORIAL ESPAÑOL:
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Hola amigos dermatólogos de la red, de nuevo DERMAGIC con ustedes. El DEFLAZACORT, es un esteroide relativamente nuevo, aparentemente tiene algunas ventajas sobre otros esteroides tradicionales, pero todavía la Prednisona y Metilprednisolona, siguen siendo los favoritos.

Estas referencias nos aclaran un poco este tema interesante. Al final una monografía del producto en Portugués e Ingles.

Gracias a TODOS por los correos de CONFIRMACIÓN de la lista, DERMAGIC seguirá adelante y ahora con mas fuerza que antes !!! 

Saludos a TODOS,,, 

Hasta una nueva oportunidad !!!

Dr. José Lapenta R.,,,

 

EDITORIAL ENGLISH:
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Hello friends dermatologist of the net, again DERMAGIC with you. The DEFLAZACORT, is a relatively new steroid, seemingly he has some advantages on other traditional steroids, but still the prednisone and methylprednisolone, they continue being the favorite ones.

These references clarify us a little this interesting topic. At the end a monograph of the product in Portuguese, and English

Thanks to ALL for the E-mail CONFIRMATION of the list, DERMAGIC will continue ahead and now with more impulse !!! 

Greetings to ALL, 

Dr. José Lapenta,

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DERMAGIC/EXPRESS(33)
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EL DEFLAZACORT / THE DEFLAZACORT
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1.) Changes in bone mass during low dose corticosteroid treatment in patients with polymyalgia rheumatica: a double blind, prospective comparison between prednisolone and deflazacort.
2.) [Vascular hyperfragility in systemic lupus erythematosus treated with low doses of cortisone]
3.) [Toxic epidermal necrolysis in a patient treated with high doses of deflazacort (letter)]
4.) Transient osteoporosis of the hip: successful response to deflazacort.
5.) A longterm prospective study of the equipotency between deflazacort and prednisolone in the treatment of patients with polymyalgia rheumatica.
6.) Deflazacort. A review of its pharmacological properties and therapeutic efficacy.
7.) Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone.
8.) Deflazacort versus methylprednisolone in polymyalgia rheumatica: clinical equivalence and relative antiinflammatory potency of different treatment regimens.
9.) Differential effects of glucocorticoids on human osteoblastic cell metabolism in vitro.
10.) Deflazacort protects against late-phase but not early-phase reactions induced by the allergen-specific conjunctival provocation test.
11.) Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation.
12.) Effect of low doses of deflazacort vs prednisone on bone mineral content in premenopausal rheumatoid arthritis.
13.) Juvenile pemphigus vulgaris: efficacy of moderate doses of deflazacort.
14.) Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort.
15.) Immunosuppressive effects of deflazacort - a new glucocorticoid with bone-sparing and carbohydrate-sparing properties: comparison with prednisone.
16.) Sex hormones and bone metabolism in postmenopausal rheumatoid arthritis treated with two different glucocorticoids.
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17.) CALCORT®- DeflazacortUSO ADULTO E PEDIÁTRICO, the product, in Portuguese
18.) CALCORT®- Deflazacort ADULT USE AND PEDIÁTRIC the product, in English
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1.) Changes in bone mass during low dose corticosteroid treatment in patients with polymyalgia rheumatica: a double blind, prospective comparison between prednisolone and deflazacort.
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AU: Krogsgaard-MR; Thamsborg-G; Lund-B
SO: Ann-Rheum-Dis. 1996 Feb; 55(2): 143-6
ISSN: 0003-4967
LA: ENGLISH

AB: OBJECTIVE: To compare the long term effects of low dosage prednisolone or deflazacort treatments on bone mass in patients with polymyalgia rheumatica.

METHODS: Thirty patients with polymyalgia rheumatica were allocated on a random double blind basis to receive treatment with prednisolone or deflazacort. Bone mineral content (BMC) was measured in the lumbar spine and in the distal forearm before treatment and three, six, and 12 months after treatment.

RESULTS: At three months the decrease in lumbar BMC and bone mineral density (BMD) was significantly greater in the deflazacort group than in the prednisolone group (p < 0.05), but at six and 12 months there was no difference between the two groups. In all patients after one year there was a significant loss of BMC: a 6.4% loss in lumbar BMC and a 1.8% loss in distal forearm BMC. Loss in lumbar BMC after six months was correlated to the cumulative dose of corticosteroid (r = 0.4; p < 0.05) and was significantly greater in the group of patients who had persisting symptoms of polymyalgia at six weeks, three months, or both, after treatment started (p = 0.05).

CONCLUSION: This low dose study failed to reveal any calcium sparing properties of deflazacort compared with prednisolone. Possible explanations for this finding are discussed.

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2.) [Vascular hyperfragility in systemic lupus erythematosus treated with low doses of cortisone]
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AU: Longo-F; Di-Leo-G; Lepore-L; Pennesi-M
SO: Pediatr-Med-Chir. 1995 Nov-Dec; 17(6): 535-7
ISSN: 0391-5387
LA: ITALIAN; NON-ENGLISH

AB: We report an unusual cutaneous manifestation of systemic lupus erythematosus (SLE) in a 15-year old female. The diagnosis was made on the basis of clinical symptoms, cutaneous hystology (positive "lupus band test") and on laboratory findings (hypocomplementemia, positive antinuclear antibodies and rheumatoid factor).

Treatment with methylprednisolone (0.5 mg/kg/die) improved the clinical symptoms but, after 2 months, large ecchymotic lesions appeared on the lower legs below the knee extending as far as the ankles, likely triggered by minor local traumas. Coagulative function was normal, the lupic anti-coagulant factor (LAF) was negative, anticardiolipin antibodies were absent and there was no thrombocytopenia. There was only a slight increase in clotting times in vitro, in presence of ADP. The amount of cortisone was reduced and the type of treatment modified; satisfactory control of the disease was attained with deflazacort (0.3 mg/kg/die).

The ecchymosis on the lower limbs never disappeared even though they became slightly smaller. Ecchymotic lesions are not usually included in the wide range of cutaneous manifestations associated with SLE. Moreover vascular fragility resulting from pressure and minor traumas is known to be a cutaneous complication of hypercorticism; nevertheless the doses of cortisone administered to this patient were rather low and other clinical signs of steroid hyper-dosing were absent although cortisolemia assay at base and after stimulus with ACTH was not performed.

We would suggest that the negligible platelet binding defect (whether primary or SLE-associated) together with the low amounts of cortisone administered caused ecchymotic lesions to appear in this patient suffering from a disease (SLE), in which the small cutaneous vessels are favourite targets.
AN: 96274506

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3.) [Toxic epidermal necrolysis in a patient treated with high doses of deflazacort (letter)]
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AU: Navarro-Llanos-A; Elizalde-Eguinoa-J; Boto-de-los-Bueys-B; Pujol-de-la-Llave-E
SO: Med-Clin-Barc. 1996 Apr 20; 106(15): 599
ISSN: 0025-7753
LA: SPANISH; NON-ENGLISH
AN: 96243322
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4.) Transient osteoporosis of the hip: successful response to deflazacort.
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AU: Carmona-Ortells-L; Carvajal-Mendez-I; Garcia-Vadillo-JA; Alvaro-Gracia-JM; Gonzalez-Alvaro-I
SO: Clin-Exp-Rheumatol. 1995 Sep-Oct; 13(5): 653-5
ISSN: 0392-856X
LA: ENGLISH

AB: Transient osteoporosis of the hip (TOH) is an uncommon condition with a poorly defined aetiology. Despite its benign prognosis, its long clinical course causes a prolonged period of functional disability in middle-aged patients. We describe two patients with TOH who showed a rapid response to deflazacort, a bone-sparing corticoid. Deflazacort may become a useful tool to shorten the otherwise lengthy recovery period of 

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5.) A longterm prospective study of the equipotency between deflazacort and prednisolone in the treatment of patients with polymyalgia rheumatica.
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AU: Krogsgaard-MR; Lund-B; Johnsson-B
SO: J-Rheumatol. 1995 Sep; 22(9): 1660-2
ISSN: 0315-162X
LA: ENGLISH

AB: OBJECTIVE. The aim of the study was to establish the antiinflammatory equipotency between prednisolone and deflazacort.

METHODS. Thirty patients with newly diagnosed polymyalgia rheumatica (PMR) were treated double blind with either prednisolone or deflazacort in a 12-month study. The initial daily dose was 20 mg prednisolone or 24 mg deflazacort.

RESULTS. The clinical control of muscle pain was significantly inferior in the deflazacort group from 6 weeks to 3 months. Otherwise there was no difference in the clinical and biochemical variables. The ratio between antiinflammatory equipotent doses of deflazacort and prednisolone (mg:mg) stabilized at about 1.55 for the daily doses and about 1.40 for the cumulative doses.

CONCLUSION. In PMR the antiinflammatory equipotency (mg to mg) between deflazacort and prednisolone was close to 1.40 (7:5 mg). Twenty mg prednisolone/day was fully sufficient to suppress symptoms in 94% of the patients.
AN: 96064221

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6.) Deflazacort. A review of its pharmacological properties and therapeutic efficacy.
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AU: Markham-A; Bryson-HM
SO: Drugs. 1995 Aug; 50(2): 317-33
ISSN: 0012-6667
LA: ENGLISH

AB: Deflazacort is an oxazoline derivative of prednisolone with anti-inflammatory and immunosuppressive activity. Both short (4 to 6 weeks) and longer term (13 to 52 weeks) studies have shown deflazacort to be as effective as prednisone or methylprednisolone in patients with rheumatoid arthritis. The drug was at least as effective as prednisone in children with juvenile chronic arthritis.

Insufficient data are available to draw firm conclusions regarding the efficacy of deflazacort as treatment for patients with severe asthma, but the drug has demonstrated some efficacy as treatment for nephrotic syndrome and other applications such as Duchenne dystrophy, systemic lupus erythematosus, uveitis and transplantation.

The overall incidence of adverse events in deflazacort recipients (16.5%) is lower than that recorded in patients treated with prednisone (20.5%) or methylprednisolone (32.7%) and similar to that in betamethasone recipients (15.3%). Gastrointestinal symptoms are the most frequently reported adverse events in deflazacort recipients; other adverse events associated with the drug include metabolic and nutritional disorders, central and peripheral nervous system disturbances and psychiatric disorders.

In general, deflazacort appears to have less effect than prednisone on parameters which may be associated with the development of corticosteroid-induced osteoporosis. Further, the drug appears have less negative impact on growth rate in children with diseases requiring corticosteroid therapy. In a study of 2 months' duration in patients with conditions requiring corticosteroid treatment, moderate dosages of deflazacort produced no clinically relevant diabetogenic effects.

Thus, deflazacort may be associated with less serious metabolic sequelae than prednisone but further well designed long term trials are required to confirm this. In the meantime, in adults, deflazacort should be reserved for use in those pre-disposed to, or who develop, intolerable metabolic sequelae during treatment with corticosteroids. In children, however, even though available efficacy data are minimal, deflazacort should be considered as an initial option in those requiring corticosteroid therapy since the adverse effects caused by this drug class are particularly debilitating in this patient group.

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7.) Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone.
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AU: Mollmann-H; Hochhaus-G; Rohatagi-S; Barth-J; Derendorf-H
SO: Pharm-Res. 1995 Jul; 12(7): 1096-100
ISSN: 0724-8741
LA: ENGLISH

AB: PURPOSE. The pharmacokinetics and pharmacodynamics of deflazacort after oral administration (30 mg) to healthy volunteers were determined and compared with those of 20 mg of methylprednisolone and 25 mg of prednisolone.

METHODS. Methylprednisolone, prednisolone and the active metabolite of deflazacort, 21-desacetyldeflazacort, were measured in plasma using HPLC. For the assessment of pharmacodynamics, differential white blood cell counts were obtained over 24 hours. An integrated pharmacokinetic-pharmacodynamic (PK-PD) model was applied to link corticosteroid concentrations to the effect on lymphocytes and granulocytes.

RESULTS. Deflazacort is an inactive prodrug which is converted rapidly to the active metabolite 21-desacetyldeflazacort. Maximum concentrations of 21-desacetyldeflazacort averaged 116 ng/ml and were observed after 1.3 h. The average area under the curve was 280 ng/ml.h, and the terminal half-life was 1.3 h. 21-Desacetyldeflazacort was cleared significantly faster than both methylprednisolone and prednisolone. The PK-PD-model was suitable to describe time course and magnitude of the observed effects. The results were consistent with reported values for glucocorticoid receptor binding affinities for the investigated compounds.

CONCLUSIONS. Due to the short pharmacokinetic half-life of its active metabolite, pharmacodynamic effects of deflazacort are of shorter duration than those of methylprednisolone and prednisolone. The PK-PD model allows good prediction of pharmacodynamic effects based on pharmacokinetic and receptor binding data.
AN: 96114923


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8.) Deflazacort versus methylprednisolone in polymyalgia rheumatica: clinical equivalence and relative antiinflammatory potency of different treatment regimens.
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AU: Di-Munno-O; Imbimbo-B; Mazzantini-M; Milani-S; Occhipinti-G; Pasero-G
SO: J-Rheumatol. 1995 Aug; 22(8): 1492-8
ISSN: 0315-162X
LA: ENGLISH

AB: OBJECTIVE. To assess the clinical efficacy and equivalence of a daily vs alternate day regimen, and the potency ratio between 2 glucocorticoids, deflazacort and 6-methylprednisolone.

METHODS. Thirty-one patients with recent onset polymyalgia rheumatica (PMR) were randomly assigned to deflazacort (n = 16) or 6-methylprednisolone (n = 15), according to a 2 period (duration of each period = 6 weeks), crossover, open design for comparing 2 dose regimens (daily vs alternate day), and according to a between-patients, double blind design for comparing the therapeutic effects of the 2 glucocorticoids (deflazacort vs 6-methylprednisolone). The patients, either during alternate day or daily regimen, were treated with fixed oral doses for the first 2 weeks (assuming a potency ratio deflazacort/6-methylprednisolone of 1.5 mg/1.0 mg: deflazacort 24 mg or 6-methylprednisolone 16 mg, daily; deflazacort 48 mg or 6-methylprednisolone 32 mg, alternate day), and with titrated doses for the next 10 weeks.

RESULTS. Two patients dropped out during the first 6 week period. The time course and extent of the improvement of disease activity indices (limb-girdle pain, morning stiffness, erythrocyte sedimentation rate, C-reactive protein, and plasma fibrinogen) were not statistically different under the 2 regimens. The satisfactory equivalent glucocorticoid response observed in 12 pairs of patients treated with deflazacort and 6-methylprednisolone progressed significantly from baseline to the end of the study, under daily or alternate day regimen, with no significant difference between the 2 glucocorticoids. Deflazacort proved less potent than 6-methylprednisolone (1.78 mg: 1.0 mg minimum effective daily dose; 1.68: 1.0, alternate day), but equally effective.

CONCLUSION. The 2 dose regimens, 6-methylprednisolone and deflazacort showed no significant differences in terms of efficacy during the short term treatment of PMR. Deflazacort proved less potent than initially estimated.

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9.) Differential effects of glucocorticoids on human osteoblastic cell metabolism in vitro.
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AU: Kasperk-C; Schneider-U; Sommer-U; Niethard-F; Ziegler-R
SO: Calcif-Tissue-Int. 1995 Aug; 57(2): 120-6
ISSN: 0171-967X
LA: ENGLISH

AB: Clinical observations suggest that the onset and severity of glucocorticoid (GC) induced osteoporosis is dependent on the duration of the GC treatment and the applied GC compound. To test whether these in vivo observations are reflected by different in vitro effects of various synthetic GCs on human bone cell metabolism we isolated human osteoblast-like cells (HOC) from bone biopsies of healthy (no clinical symptoms of arthritis or arthrosis) adults who underwent selective orthopedic surgery.

HOC were identified as bone cells by 1,25-vitamin D3-stimulated increase of specific alkaline phosphatase (ALP) activity, secretion of osteocalcin and type-I procollagen peptide, and the ability to form mineral in vitro.

We investigated the effects of dexamethasone (dexa), methylprednisolone (mpred), prednisolone (pred), and deflazacort (defla) on DNA-synthesis, ALP, and osteocalcin (OC)- and type-I procollagen peptide secretion of HOC in vitro. In summary, (1) GC exposure stimulates DNA synthesis after 6-12 hour treatment periods; (2) dex and mpred strongly inhibit DNA (48-hour treatment) and collagen synthesis but stimulate ALP, whereas pred and defla exhibit smaller effects on DNA synthesis, ALP, and collagen production; and (3) all tested glucocorticoids inhibit OC secretion by HOC in vitro. Thus, the effect of GC on DNA synthesis of HOC varies with the duration of GC exposure, and dex and mpred more potently affect HOC metabolism in vitro than pred and defla.

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10.) Deflazacort protects against late-phase but not early-phase reactions induced by the allergen-specific conjunctival provocation test.
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SO - Allergy 1993 Aug;48(6):421-30
AU - Ciprandi G; Buscaglia S; Pesce GP; Iudice A; Bagnasco M; Canonica GW
AD - Department of Internal Medicine, DI.M.I., University of Genoa, Italy.
PT - CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

AB - The protective effects of deflazacort against the inflammation that follows the conjunctival provocation test (CPT) by specific allergen were assessed in 24 patients with rhinoconjunctivitis caused by Parietaria judaica in a double-blind study.

After a screening CPT, patients were randomized into four treatment groups, each being given deflazacort (oral tablets) at 6, 30, and 60 mg once daily, or matching placebo, for 3 d, outside the pollen season. Clinical evaluation (itching, hyperemia, lacrimation, and swelling of eyelids) and cytologic assessment (number of inflammatory cells in conjunctival scraping and evaluation of ICAM (intercellular adhesion molecule)-1/CD54 expression on epithelial cells) were performed at base line, 30 min (early-phase reaction (EPR), 6 h and 24 h (late-phase reaction (LPR)) after specific CPT, and before and after treatment.

Neither the EPR clinical reactions nor the EPR total number of inflammatory cells was modified by deflazacort. However, the LPR clinical effects were significantly reduced by deflazacort at 30 or 60 mg/d (P 0.01), as compared with placebo. The total number of inflammatory cells during LPR was significantly reduced by deflazacort at 30 or 60 mg/d (P 0.01), as compared with placebo.

Furthermore, CD54 expression was significantly reduced by deflazacort at 30 or 60 mg/d both in the EPR (P 0.01) and LPR (P 0.01), as compared with placebo. None of the studied indicators were modified at the 6 mg/d dose. This study shows that deflazacort has a highly protective action against clinical and cellular LPR effects induced by the specific CPT. In addition, deflazacort markedly reduces CD54 expression on the conjunctival epithelium during both EPR and LPR.

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11.) Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation.
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SO - J Pediatr 1992 Nov;121(5 Pt 1):809-13
AU - Ferraris JR; Day PF; Gutman R; Granillo E; Ramirez J; Ruiz S; Pasqualini T
AD - Departamento de Pediatria, Hospital Italiano de Buenos Aires, Argentina.
PT - JOURNAL ARTICLE

AB - Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Tanner pubertal stage 1.

Methylprednisone (mean +/- SEM: 0.2 +/- 0.02 mg/kg per day) was replaced by deflazacort (0.3 +/- 0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 1.5 +/- 0.3 to 3.2 +/- 0.5 cm/yr (p 0.005) in the nine patients. Weight/height ratio decreased from 28.4% +/- 8.5% to 16% +/- 6.7% (p 0.005).

Cushingoid appearance decreased in all patients. Mean spontaneous growth hormone secretion increased from 2.5 +/- 0.4 to 4.4 +/- 1.2 ng/ml (p 0.05).

Our findings indicate that immunosuppressive treatment with deflazacort is as effective as methylprednisone and is associated with fewer side effects.

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12.) Effect of low doses of deflazacort vs prednisone on bone mineral content in premenopausal rheumatoid arthritis.
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SO - J Rheumatol 1992 Oct;19(10):1520-6
AU - Messina OD; Barreira JC; Zanchetta JR; Maldonado-Cocco JA; Bogado CE; Sebastian ON; Flores D; Riopedre AM; Redondo G; Lazaro A
AD - Department of Rheumatology, C. Argerich Hospital, Buenos Aires, Argentina.
PT - CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

AB - Longterm administration of steroid drugs, particularly prednisone, is known to induce osteoporosis, as well as bone growth inhibition and delayed fracture union. Recently deflazacort, an oxazoline prednisone derivative, has been developed to reduce such deleterious effects. We carried out a comparative study in premenopausal patients with rheumatoid arthritis (RA).

Sixteen cases whose mean age was 36.5 years and mean disease duration 29 months, all fulfilling ARA criteria, were evaluated in a randomized, double blind trial. Visually identical deflazacort or prednisone capsules were given and patients were instructed to maintain an adequate calcium intake. Laboratory tests focussed on bone mineral density in lumbar spine, femoral neck and Ward's triangle and whole body mineral content. Differences between baseline and 12-month values were processed statistically.

Persistent synovitis control proved similar for both drugs and features suggestive of Cushing's syndrome were only found in the prednisone group. The difference in whole body bone mineral content between the deflazacort and prednisone groups just failed to reach statistical significance. In the deflazacort group, the difference between the nonsignificant bone mineral density increase at the femoral neck and the significant decrease in the prednisone group proved statistically significant.

Ward's triangle was the most sensitive area to bone mineral density changes in patients receiving prednisone, with a highly significant intergroup difference (p 0.01). We believe this is the first study on corticosteroid induced osteoporosis, as evaluated by whole body mineral content measurements in premenopausal patients with short term RA, showing that deflazacort is a promising alternative in cases severe enough to require steroid therapy.

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13.) Juvenile pemphigus vulgaris: efficacy of moderate doses of deflazacort.
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SO - Pediatr Dermatol 1991 Sep;8(3):221-3
AU - Fimiani M; Pianigiani E; Castelli A
AD - Department of Dermatology, University of Siena, Italy.
PT - JOURNAL ARTICLE
AB - A 13-year-old girl with pemphigus vulgaris (PV) had clinical features of chronic stomatitis. The histologic and immunologic findings were typical of a diagnosis of PV. Good therapeutic results were obtained with moderate doses of deflazacort, 1 mg/kg/day slowly tapered to 0.1 mg/kg every other day. The patient had no significant side effects.

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14.) Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort.
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SO - Pediatrics 1991 Sep;88(3):428-36
AU - Loftus J; Allen R; Hesp R; David J; Reid DM; Wright DJ; Green JR; Reeve J; Ansell BM; Woo PM
AD - MRC Clinical Research Centre, Harrow, England.
PT - CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL

AB - Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (an oxazolone derivative of prednisone) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/d of prednisolone (usually as 10 mg every 2 days).

Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3-monthly intervals.

Trends (velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P less than .007) of deflazacort when spinal bone mineral growth was compared to body surface area and weight.

In part this was due to a temporary interruption in weight by children receiving deflazacort, whose gain in height was comparable with that of the prednisone group. Some children in both groups improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of deflazacort, their spinal bone mineral content at a level that was appropriate for their height and weight.

Further observations are required to establish whether this advantage can be maintained subsequently. The anti-inflammatory effects of the two glucocorticoids appeared similar.

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15.) Immunosuppressive effects of deflazacort - a new glucocorticoid with bone-sparing and carbohydrate-sparing properties: comparison with prednisone.
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SO - J Rheumatol 1981 Sep-Oct;8(5):783-90
AU - Hahn BH; Pletscher LS; Muniain M
PT - JOURNAL ARTICLE

AB - Deflazacort is a synthetic glucocorticoid with fewer adverse effects on bone and carbohydrate metabolism than prednisone or beta-methasone. Its antiinflammatory effects have compared favorably to prednisone in European studies of rheumatoid arthritis.

We compared the immune effects of prednisone and deflazacort in normal volunteers. Circulating lymphocytes were reduced similarly by equivalent doses of both drugs; monocyte numbers were reduced more by deflazacort. Each drug suppressed autologous mixed lymphocyte reaction in vitro and in vivo; this effect persisted longer with deflazacort. Deflazacort may be a superior therapeutic agent because of its lower toxicity and longer duration of one immunosuppressive effect; it might be effective in alternate day regimens.

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16.) Sex hormones and bone metabolism in postmenopausal rheumatoid arthritis treated with two different glucocorticoids.
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SO - J Rheumatol 1992 Dec;19(12):1895-900
AU - Montecucco C; Caporali R; Caprotti P; Caprotti M; Notario A
AD - Istituto di Patologia Medica, Universita di Pavia, Italy.
MJ - Anti-Inflammatory Agents, Steroidal [therapeutic use]; Arthritis, Rheumatoid [drug therapy] [metabolism]; Bone and Bones [metabolism]; Menopause [metabolism]; Prednisone [therapeutic use]; Pregnenediones [therapeutic use]; Sex Hormones [blood]
MN - Adult; Aged, 80 and over; Aged; Androstenedione [blood]; Anti-Inflammatory Agents, Steroidal [adverse effects]; Arthritis, Rheumatoid [blood]; Bone Density [physiology]; Estradiol [blood]; Menopause [blood]; Middle Age; Osteocalcin [blood]; Prasterone [analogs & derivatives] [blood]; Prednisone [adverse effects]; Pregnenediones [adverse effects]; Progesterone [blood]
MT - Comparative Study; Female; Human; Support, Non-U.S. Gov't
PT - JOURNAL ARTICLE

AB - To investigate the effect of low doses of 2 different glucocorticoids on bone mass, sex hormone status and bone metabolic indices, a study was undertaken in 16 postmenopausal women with rheumatoid arthritis (RA) receiving 15 mg/day of deflazacort and in 16 patients with RA matched for age, years postmenopause and disease duration, receiving 10 mg/day of prednisone.

Sixteen healthy postmenopausal women and 16 nonsteroid treated patients with RA were also studied as control groups. Vertebral bone density (vBMD) was lower (mean +/- SD: 0.65 +/- 0.07 vs 0.73 +/- 0.09 g/cm2; p 0.02) in prednisone treated patients than in deflazacort treated patients, whose vBMD values were similar to those of nonsteroid treated RA. No significant difference was found as for radial bone mineral content. Circulating levels of estradiol, dehydroepiandrosterone sulfate, androstenedione and progesterone were low in all patient groups with RA when compared with healthy controls.

The prednisone treated patients showed significantly lower values of all sex hormones with respect to deflazacort treated patients. Osteocalcin values were also lower (3.0 +/- 1.4 vs 3.9 +/- 1.6 ng/ml; p 0.05) in prednisone treated patients with respect to deflazacort treated group.

Glucocorticoid treated patients showed a direct correlation (r2 = 0.39) between vBMD and plasma estradiol levels, while no correlation was found with osteocalcin values. In conclusion, our postmenopausal patients with RA treated with low dose prednisone had reduced levels of sex hormones and osteocalcin and reduced vertebral bone mass.

Comparable doses of deflazacort showed only a mild inhibitory effect on sex hormones and osteocalcin, and did not show any detectable effect on bone mass.

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17.) CALCORT®- Deflazacort USO ADULTO E PEDIÁTRICO in Portuguese
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CALCORT®- Deflazacort 
USO ADULTO E PEDIÁTRICO

FORMA FARMACÊUTICA E APRESENTAÇÃO

COMPOSIÇÃO

INFORMAÇÃO AO PACIENTE

INDICAÇÕES

PROPRIEDADES

CONTRA-INDICAÇÕES

USO DURANTE A GRAVIDEZ E LACTAÇÃO

PRECAUÇÕES E ADVERTÊNCIAS

INTERAÇÕES MEDICAMENTOSAS

REAÇÕES ADVERSAS

POSOLOGIA E MODO DE USAR

SUPERDOSAGEM


Indice:
FORMA FARMACÊUTICA E APRESENTAÇÃO índice 

COMPRIMIDOS 6 mg. 
Caixas com 20 

COMPRIMIDOS 30 mg.
Caixas com 10 

GOTAS
Frascos com 13 ml.


forma farmacêutica e apresentação:
COMPOSIÇÃO índice 

COMPRIMIDOS 6 mg
Cada comprimido contém:
deflazacort ................................... .................................. 6 mg
Excipientes q.s.p............................................................ 1 comprimido
( lactose, amido de milho, avicel, estearato de magnésio)

COMPRIMIDOS 30 mg
Cada comprimido contém:
deflazacort..................................................................... 30 mg
Excipientes q.s.p........................................................... 1 comprimido
(lactose, amido de milho, avicel, estearato de magnésio)

GOTAS
Cada ml contém:
deflazacort...................................................................22,75mg
Excipientes q.s.p............................................................1,00 ml
(silicato de alumínio e magnésio, carboximetilcelulose sódica, álcool benzílico, sorbitol solução 70%, polissorbato 80, ácido acético solução à 10%, água purificada) Cada gota contém 1 mg de deflazacort.


composição: 
INFORMAÇÃO AO PACIENTE índice 

Conservar em lugar fresco e ao abrigo da luz.

Prazo de validade: vide cartucho. Não use medicamento com prazo de validade vencido.

Siga corretamente as instruções do seu médico quanto ao emprego do produto, não interrompendo ou modificando o tratamento sem antes consultá-lo. Informe a seu médico se estiver grávida, amamentando ou se ficar grávida durante o tratamento.

Qualquer reação desagradável deve ser comunicada ao médico. Podem ocorrer: problemas gastrintestinais e visuais, agitação, inchaço, alterações menstruais.

Informe ao médico caso você tenha problemas de coração, de rim ou gastrintestinais, diabete, infecções, herpes simplex ocular, miastenia grave, pressão alta, osteoporose, problemas neurológicos, hipotiroidismo, cirrose, se está estressado, se vai tomar alguma vacina, se tem ou já teve alergia ao deflazacort ou se estiver tomando outros medicamentos.

Após tratamento prolongado, a interrupção do tratamento deve ser feita lenta e gradualmente, para evitar a síndrome de retirada, na qual podem ocorrer febre, dor muscular, dor articular e mal estar geral.

TODO MEDICAMENTO DEVE SER MANTIDO FORA DO ALCANCE DAS CRIANÇAS.

NÃO TOME REMÉDIO SEM O CONHECIMENTO DE SEU MÉDICO. PODE SER PERIGOSO PARA SUA SAÚDE.


informação ao paciente:

INDICAÇÕES, índice 

DEFLAZACORT é um glicocorticóide com propriedades antiinflamatórias e imunossupressoras indicado para o tratamento de:

Doenças reumáticas: artrite reumatóide, artrite psoriásica, espondilite anquilosante, artrite gotosa aguda, osteoartrite pós-traumática, sinovite por osteoartrite, bursite aguda e sub-aguda, tenossinovite aguda não específica, epicondilite.

Doenças do tecido conjuntivo: lupus eritematoso sistêmico, dermatomiosite sistêmica (polimiosite), cardite reumática aguda, polimialgia reumática, poliarterite nodosa, arterite temporal, granulomatose de Wegener. 

Doenças dermatológicas: pênfigo, dermatite herpetiforme bolhosa, eritema multiforme grave (Síndrome de Stevens-Johnson), dermatite exfoliativa, micose fungóide, psoríase grave, dermatite seborréica grave.

Estados alérgicos: controle de reações alérgicas graves ou incapacitantes que não respondem a drogas não-esteroidais, rinite alérgica sazonal ou perene, asma brônquica, dermatite de contato, dermatite atópica, doença do soro, reações de hipersensibilidade a drogas.

Doenças respiratórias: sarcoidose sistêmica, síndrome de Loeffler, sarcoidose, pneumonia alérgica ou por aspiração, fibrose pulmonar idiopática.

Doenças oculares: inflamação da córnea, uveíte posterior difusa e coroidite, oftalmia simpática, conjuntivite alérgica, ceratite, coriorretinite, neurite óptica, irite e iridociclite, herpes zoster ocular.

Distúrbios hematológicos: púrpura trombocitopênica idiopática, trombocitopenia secundária, anemia hemolítica auto-imune, eritroblastopenia, anemia hipoplástica congênita (eritróide).

Doenças gastrintestinais: colite ulcerativa, enterite regional, hepatite crônica.

Doenças neoplásicas: leucemia, linfomas, mieloma múltiplo.

Doenças neurológicas: esclerose múltipla em exacerbação.

Doenças renais: síndrome nefrótica.

Doenças endócrinas: insuficiência suprarrenal primária ou secundária (a hidrocortisona ou cortisona são as drogas de escolha; DEFLAZACORT, devido ao seus poucos efeitos mineralocorticóides, deve ser usado em conjunto com um mineralocorticóide), hiperplasia supra-renal congênita, tiroidite não supurativa.

Devido à propriedade protetora dos ossos, DEFLAZACORT pode ser a droga de escolha para pessoas que necessitam de tratamento com glicocorticóides, especialmente aqueles que apresentam maior risco de osteoporose. Seus reduzidos efeitos diabetogênicos tornam DEFLAZACORT o glicocorticóide sistêmico de escolha em pacientes diabéticos e pré-diabéticos.


indicações:
PROPRIEDADE,  índice 

Os glicocorticóides possuem ação antiinflamatória e imunossupressora e são usados terapeuticamente em uma grande variedade de doenças.

Comparado à prednisona, em doses antiinflamatórias equivalentes, deflazacort proporciona:

- menor inibição da absorção intestinal de cálcio e um menor aumento na sua excreção urinária.

. redução significativamente menor no volume ósseo trabecular e conteúdo mineral ósseo.

. reduzidos efeitos diabetogênicos em pessoas normais, indivíduos com história familiar de diabetes e pacientes diabéticos.

Após a administração oral, deflazacort é bem absorvido e imediatamente convertido pelas esterases plasmáticas ao metabólito ativo, o qual alcança concentrações plasmáticas em 1,5 a 2 horas. Possui ligação protéica de 40% e meia-vida plasmática de 1,1 a 1,9 horas. A eliminação ocorre principalmente pelos rins, sendo 70% da dose administrada excretada pela urina e o restante pelas fezes.


propriedades:
CONTRA-INDICAÇÕES índice 

Contra-indicado em pacientes com hipersensibilidade ao deflazacort ou a qualquer um dos componentes da fórmula.


contra-indicações:
USO DURANTE A GRAVIDEZ E LACTAÇÃO índice 

Não existem estudos adequados de reprodução humana com glicocorticóides. Têm sido descritos efeitos teratogênicos em animais por uso de glicocorticóides. O uso durante a gravidez ou lactação deve ser feito somente quando os benefícios superarem os riscos potenciais de seu uso. Crianças cujas mães receberam glicocorticóides durante a gravidez devem ser cuidadosamente observadas em relação a possíveis sinais de hipoadrenalismo.

Os glicocorticóides são excretados no leite materno e podem causar supressão do crescimento e hipoadrenalismo nos lactentes, portanto, mães tratadas com glicocorticóides devem ser advertidas para que não amamentem.
uso durante a gravidez e lactação 

PRECAUÇÕES E ADVERTÊNCIAS, índice 

Pacientes em tratamento ou que se submeterão a tratamento com glicocorticóides e que comprovadamente estão submetidos a um estresse não habitual, podem necessitar de uma dose maior antes, durante e depois da condição estressante (vide Posologia e Forma de Administração).

Os corticosteróides podem mascarar alguns sinais das infecções ou podem aparecer novas infecções durante seu uso. Pacientes com infecções ativas (virais, bacterianas ou micóticas) devem ser cuidadosamente controlados. Em pacientes com tuberculose ativa ou latente, a terapia deve limitar-se aos casos nos quais deflazacort é utilizado conjuntamente com o tratamento antituberculoso adequado.

O uso prolongado de glicocorticóides pode produzir catarata posterior subcapsular ou glaucoma.

Durante o tratamento com glicocorticóides, os pacientes não devem receber imunizações, especialmente em altas doses, devido à possibilidade de disseminação de vacinas vivas (ex: anti-variólica), e/ou falha na resposta dos anticorpos.

A supressão da função hipotálamo-hipófise-adrenal induzida por glicocorticóides é dependente da dose e duração do tratamento. O restabelecimento ocorre gradualmente após redução da dose e interrupção do tratamento. Entretanto, uma relativa insuficiência pode persistir por alguns meses depois da suspensão do tratamento; portanto, em qualquer situação estressante, o tratamento deve ser reinstituído.

Considerando que a secreção mineralocorticóide pode estar prejudicada, deve-se administrar concomitantemente sais e/ou mineralocorticóides.

Após terapia prolongada, a retirada de glicocorticóides deve ser lenta e gradual para evitar a síndrome de retirada: febre, mialgia, artralgia e mal estar geral. Isso também pode ocorrer em pacientes sem evidência de insuficiência adrenal.

O uso de DEFLAZACORT requer cuidados especiais nas seguintes condições clínicas:

.-cardiomiopatias ou insuficiência cardíaca congestiva (devido ao aumento da retenção de água), hipertensão, manifestações tromboembólicas. Os glicocorticóides podem causar retenção de sal e água e aumento da excreção de potássio. Pode ser necessário adotar uma dieta com suplementação de potássio e restrição de sal. 

.-gastrite ou esofagite, diverticulite, colite ulcerativa, anastomose intestinal recente, úlcera péptica ativa ou latente.

.-diabetes mellitus, osteoporose, miastenia grave, insuficiência renal.

. -instabilidade emocional ou tendências psicóticas, epilepsia.

.-hipotiroidismo e cirrose (condições que podem aumentar os efeitos dos glicocorticóides).

.-herpes simplex ocular devido à possível perfuração da córnea.

.-o uso pediátrico prolongado pode suprimir o crescimento e o desenvolvimento.

Considerando que as complicações do tratamento com glicocorticóides são dependentes da dose e duração do tratamento, deve-se definir a dose, duração do tratamento, bem como do tipo de terapia (diária ou intermitente) baseado na relação risco/benefício para cada paciente.

precauções e advertências:
INTERAÇÕES MEDICAMENTOSAS, índice 

Embora não tenham sido detectadas interações medicamentosas durante as investigações clínicas, deve-se tomar os mesmos cuidados que para outros glicocorticóides (por exemplo, pode ocorrer diminuição dos níveis de salicilato, aumento do risco de hipocalemia com o uso concomitante com digitálicos ou diuréticos, anticolinesterásicos, substâncias que alteram o metabolismo dos glicocorticóides como: rifampicina, barbituratos e difenilhidantoína). A eritromicina e os estrógenos podem aumentar os efeitos dos corticosteróides. Os corticóides podem alterar os efeitos dos anticoagulantes do tipo cumarínico.


interações medicamentosas:
REAÇÕES ADVERSAS,  índice 

Os glicocorticóides causam reações adversas, as quais são relacionadas com a dose e duração do tratamento: aumento da suscetibilidade às infecções, efeitos gastrintestinais (dispepsia, ulceração péptica, perfuração da úlcera péptica, hemorragia e pancreatite aguda, especialmente em crianças), alterações do equilíbrio hidro-eletrolítico, balanço negativo do nitrogênio, fraqueza músculo-esquelética (miopatia e fraturas), fragilidade e afinamento da pele, atraso no processo de cicatrização, acne, alterações neuropsiquiátricas (cefaléia, vertigem, euforia, insônia, agitação, depressão, hipertensão endocraniana, convulsões, pseudotumor cerebral em crianças), reações oftálmicas (catarata posterior subcapsular, aumento da pressão intraocular), supressão da função hipotalâmica-hipófise-adrenal, alterações corporais (distribuição cushingóide, aumento de peso e "cara de lua cheia"), hirsutismo, amenorréia, diabetes mellitus, diminuição do crescimento em crianças e raros casos de reações alérgicas.

Têm-se evidenciado uma menor incidência de reações adversas a nível ósseo e do metabolismo dos carboidratos com DEFLAZACORT quando comparado a outros glicocorticóides.


reações adversas: 
POSOLOGIA E MODO DE USAR, índice 

A dose necessária é variável e deve ser individualizada de acordo com a doença a ser tratada e a resposta do paciente.

Adultos:
Dose inicial: 6 a 90 mg/dia, dependendo da gravidade dos sintomas.

Crianças: 0,22 a 1,65 mg/kg/dia ou em dias alternados. Cada gota contém 1 mg de deflazacort.

Assim como para outros glicocorticóides, a suspensão do tratamento deve ser feita reduzindo-se gradualmente a dose de deflazacort.

Em doenças menos graves, doses mais baixas podem ser suficientes, enquanto que as graves podem requerer doses maiores. A dose inicial deve ser mantida ou ajustada até a obtenção de uma resposta clínica satisfatória. Se esta não ocorrer, o tratamento deve ser interrompido e substituído por outro. Depois de se alcançar uma resposta inicial favorável, a dose de manutenção adequada deve ser determinada pela diminuição da dose inicial em pequenas frações até alcançar a menor dose capaz de manter uma resposta clínica adequada.

Manutenção: os pacientes devem ser controlados cuidadosamente, identificando os sinais e sintomas que possam indicar a necessidade de se ajustar a dose, incluindo alterações no quadro clínico resultante da remissão ou exacerbação da doença, resposta individual à droga e efeitos do estresse (por ex.: cirurgia, infecção, traumatismo). Durante o estresse, pode ser necessário aumentar temporariamente a dose.


posologia e modo de usar: 
SUPERDOSAGEM índice 

Na superdosagem aguda, recomenda-se tratamento de suporte sintomático. A DL 50 oral é maior que 4000 mg/kg em animais de laboratório.


superdosagem 

ATENÇÃO: ESTE PRODUTO É UM NOVO MEDICAMENTO E EMBORA AS PESQUISAS REALIZADAS TENHAM INDICADO EFICÁCIA E SEGURANÇA QUANDO CORRETAMENTE INDICADO, PODEM OCORRER REAÇÕES ADVERSAS IMPREVISÍVEIS AINDA NÃO DESCRITAS OU CONHECIDAS. EM CASO DE SUSPEITA DE REAÇÃO ADVERSA O MÉDICO RESPONSÁVEL DEVE SER NOTIFICADO.

HOECHST MARION ROUSSEL S.A
Av. Mário Lopes Leão, 1500 - Santo Amaro - São Paulo

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18.) CALCORT- Deflazacort ADULT USE AND PEDIATRIC in English
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CALCORT®- Deflazacort
ADULT AND PEDIATRIC USE

PHARMACEUTICAL FORM AND PRESENTATION

COMPOSITION

PATIENT INFORMATION

INDICATIONS

PROPERTIES

CONTRA-INDICATIONS

USE DURING PREGNANCY AND LACTATION

PRECAUTIONS AND WARNINGS

DRUG INTERACTIONS

ADVERSE REACTIONS

DOSAGE AND HOW TO USE

SUPERDOSAGE


Index:
PHARMACÊUTICAL FORM AND APPRESENTATION index

TABLETS 6 mg.
Boxes with 20

TABLETS 30 mg.
Boxes with 10

DROPS
Bottles with 13 ml.


pharmaceutical form and presentation:
COMPOSITION index

TABLETS 6 mg
Each tablet contains:
deflazacort ................................................................... 6 mg
Excipients q.s.p.............................................................. 1 tablet
(lactose, milho amido, avicel, magnesium stearate)

TABLETS 30 mg
Each tablet contains:
deflazacort................................................................... 30 mg
Excipients q.s.p................................................................ 1 tablet
(lactose, milho amido, avicel, magnesium stearate)

DROPS
Each ml contains:
deflazacort...................................................................22.75mg
Excipients q.s.p..............................................................1.00 ml
(aluminum and magnesium silicate, sodium carboxymethylcellulose, benzyl alcohol, sorbitol solution 70%, polyssorbate 80, acetic acid solution 10%, purified water) Each drop contains 1 mg of deflazacort.


composition:
PATIENT INFORMATION index

Store in a cool place and shelter from light.

Validity period: vide cartridge. Do not use medicine with expired validity period.

Follow your doctor's instructions correctly when using the product, do not interrupt or modify the treatment without consulting him or her beforehand. Inform your doctor if you are pregnant, breastfeeding, or become pregnant during treatment.

Any unpleasant reaction should be reported to the doctor. We may experience: gastric and visual problems, agitation, bloating, menstruation disorders.

Report to your doctor if you have heart, rim or gastric problems, diabetes, infections, ocular herpes simplex, myasthenia gravis, high blood pressure, osteoporosis, neurological problems, hypothyroidism, cirrose, are stressed, are taking some vaccine, are afraid or are allergic to deflazacort or are taking other drugs. medications.

After prolonged treatment, treatment interruption must be done slowly and gradually, to avoid withdrawal syndrome, which can cause fever, muscle pain, joint pain and general illness.

ALL MEDICATION MUST BE KEPT OUT OF REACH OF CHILDREN.

DO NOT TAKE THE MEDICIN WTHOUT KNOWLEDGE  FROM YOUR DOCTOR. IT MAY BE DANGEROUS FOR YOUR HEALTH.


information to the patient:
INDICATIONS, index

DEFLAZACORT is a glycocorticoid with anti-inflammatory and immunosuppressive properties indicated for the treatment of:

Rheumatic diseases: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylite, acute gouty arthritis, post-traumatic osteoarthritis, synovite due to osteoarthritis, acute and sub-acute bursite, acute non-specific tenossynovite, epicondylite.

Causes of connective tissue: systemic lupus erythematosus, systemic dermatomyosite (polymyosite), acute rheumatic cardite, polymyalgia rheumatica, polyarterite nodosa, temporal arterite, Wegener's granulomatose.

Dermatological diseases: pemphigus, dermatitis herpetiformis bolhosa, severe erythema multiforme (Stevens-Johnson Syndrome), exfoliative dermatitis, mycose fungoides, severe psoriasis, severe seborrheic dermatitis.

Allergic states: control of severe or disabling allergic reactions that do not respond to non-steroidal drugs, seasonal or perennial allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, sore throat, hypersensitivity reactions to drugs.

Respiratory diseases: systemic sarcoidose, Loeffler syndrome, sarcoidose, allergic or aspiration pneumonia, idiopathic pulmonary fibrosis.

Ocular diseases: corneal inflammation, diffuse posterior uveite and choroidite, sympathetic ophthalmia, allergic conjunctivite, ceratite, chorioretinite, optic neurite, irite and iridocyclite, ocular herpes zoster.

Hematological disorders: idiopathic thrombocytopenic purpura, secondary thrombocytopenia, autoimmune hemolytic anemia, erythroblastopenia, congenital hypoplastic anemia (erythroid).

Gastrintestinais symptoms: ulcerative colitis, regional enteritis, chronic hepatitis.

Neoplastic diseases: leukemia, lymphomas, multiple myeloma.

Neurological problems: multiple sclerosis in exacerbation.

Kidney diseases: nephrotic syndrome.

Endocrine diseases: primary or secondary adrenal insufficiency (hydrocortisone or cortisone is only used as a drug; DEFLAZACORT, due to its few mineralocorticoid effects, must be used in conjunction with a mineralocorticoid), congenital suprarenal hyperplasia, thyroiditis not suppurative.

Due to the property of protecting the bones, DEFLAZACORT may be a drIt is recommended for people who need treatment with glycocorticoids, especially those who present a higher risk of osteoporosis. The reduced diabetic effects of DEFLAZACORT or systemic glycocorticoid use in diabetic and pre-diabetic patients.


indications:
PROPERTIES, index

Glycocorticoids have anti-inflammatory and immunosuppressant effects and are used therapeutically in a wide variety of applications.

Compared to prednisone, in equivalent anti-inflammatory doses, deflazacort provides:

- less inhibition of intestinal absorption of calcium and a less increase in its urinary excretion.

. Significantly smaller reduction in trabecular bone volume and bone mineral content.

. Reduced diabetic effects in normal people, individuals with a family history of diabetes and diabetic patients.

After oral administration, deflazacort is absorbed and immediately converted by plasma esterases to the active metabolite, which reaches plasma concentrations in 1.5 to 2 hours. Possui protein binding of 40% and plasma half-life of 1.1 to 1.9 hours. Elimination occurs primarily in kidney hair, with 70% of the administered dose excreted in urine and the remainder in feces.


properties:
CONTRA-INDICATIONS, index

Contra-indicated in patients with hypersensitivity to flazacort or any of the two components of the formula.


contra-indications:
USE DURING PREGNANCY AND LACTATION, index

There are no adequate studies of human reproduction with glycocorticoids. Teratogenic effects have been described in animals due to the use of glycocorticoids. Use during pregnancy or lactation should only be done when the benefits outweigh the potential risks of use. Children who most receive glycocorticoids during pregnancy should be carefully observed in relation to possible symptoms of hypoadrenalism.

Glycocorticoids are excreted without maternal milk and can cause growth suppression and hypoadrenalism in lactating infants, therefore, those treated with glycocorticoids should be warned not to breastfeed.
use during pregnancy and lactation

PRECAUTIONS AND WARNINGS, index

Patients undergoing treatment or undergoing treatment with glycocorticoids and who are clearly subjected to unusual stress may need a higher dose before, during and after the stressful condition (see Dosage and Administration).

Corticosteroids can mask some sinais of infections or new infections can appear during their use. Patients with active infections (viral, bacterial or fungal) must be carefully monitored. In patients with active or latent tuberculosis, therapy should be limited to cases in which deflazacort is used together as an appropriate anti-tuberculosis treatment.

Prolonged use of glycocorticoids may cause posterior subcapsular cataract or glaucoma.

During treatment with glycocorticoids, patients should not receive immunizations, especially in high doses, due to the possibility of dissemination of live vaccines (eg, anti-smallpox), and/or failure to respond to two antibodies.

The suppression of hypothalamic-pituitary-adrenal function induced by glycocorticoids is dependent on the dose and duration of treatment. Restoration occurs gradually after dose reduction and treatment interruption. Meanwhile, a relative insufficiency may persist for some months after treatment is suspended; Therefore, in any stressful situation, the treatment must be reinstituted.

Considering that mineralocorticoid secretion may be impaired, both and/or mineralocorticoids should be administered concomitantly.

After prolonged therapy, withdrawal of glycocorticoids must be slow and gradual to avoid withdrawal syndrome: fever, myalgia, arthralgia and general malaise. This can also occur in patients without evidence of adrenal insufficiency.

The use of DEFLAZACORT requires special care in the following clinical conditions:

.-cardiomyopathy or congestive heart failure (due to increased water retention), hypertension, thromboembolic manifestations. Glycocorticoids can cause salt and water retention and increased potassium excretion. It may be necessary to adopt a diet with potassium supplementation and salt restriction.

.-gastrite or esophagite, diverticulite, ulcerative colitis, recent intestinal anastomose, active or latent peptic ulcer.

.-diabetes mellitus, osteoporosis, myasthenia gravis, renal failure.

. -emotional instability or psychotic tendencies, epilepsy.

.-hypothyroidism and cirrhosis (conditions that can increase the effects of glycocorticoids).

.-Ocular herpes simplex due to possible perfuração of the cornea.

.-Prolonged pediatric use can suppress growth and development.

Considering that the complications of treatment with glycocorticoids are dependent on the dose and duration of the treatment, it is necessary to defineThe duration of treatment is also the type of therapy (daily or intermittent) based on the risk/benefit ratio for each patient.

precautions and warnings:
DRUG INTERACTIONS, index

Since drug interactions have not been detected during clinical investigations, the same care should be taken as for other glycocorticoids (for example, it may reduce the levels of salicylate, increase the risk of hypokalemia, or concomitant use with digitalis or diuretics, anticholinesterases, substances that alter or metabolism of two glycocorticoids such as: rifampicin, barbiturates and diphenylhydantoin). Erythromycin and estrogens can increase the effects of corticosteroids. Corticosteroids can alter the effects of coumarin-type anticoagulants.


drug interactions:
ADVERSE REACTIONS, index

Glycocorticoids cause adverse reactions, as they are related to the dose and duration of treatment: increased suscetibility to infections, gastrintestinais effects (dyspepsia, peptic ulcer, perfuração of peptic ulcer, hemorrhage and acute pancreatitis, especially in children), Alterations in the hydro-electrolytic balance, negative nitrogen balance, musculoskeletal frailty (myopathy and fractures), frailty and thinning of the skin, delay in the healing process, acne, neuropsychiatric alterations (cephalia, vertigo, euphoria, insônia, agitation, depression, intracranial hypertension, convulsions, pseudotumor cerebri in children), ophthalmic reactions (posterior subcapsular cataract, increased intraocular pressure), suppression of hypothalamic-pituitary-adrenal function, corporeal alterations (cushing's distribution, weight gain and "cheia face"), hirsutism, amenorrhea, diabetes mellitus, decreased growth in children and rare cases of allergic reactions.

There is evidence of a lower incidence of adverse reactions at the bone level and in the metabolism of carbohydrates with DEFLAZACORT when compared to other glycocorticoids.


adverse reactions:
DOSAGE AND DIRECTIONS FOR USE, index

The dose required is variable and must be individualized according to the condition to be treated and the patient's response.

Adults:
Initial dose: 6 to 90 mg/day, depending on the severity of two symptoms.

Children: 0.22 to 1.65 mg/kg/day on alternate days. Each drop contains 1 mg of deflazacort.

As with other glycocorticoids, treatment suspension should be done by gradually reducing the dose of deflazacort.

In less serious cases, lower doses may be sufficient, while more serious cases may require higher doses. The initial dose must be maintained or adjusted to obtain a satisfactory clinical response. If this does not occur, the treatment must be interrupted and replaced by another. After a favorable initial response is achieved, a dose of adequate maintenance must be determined by diminution of the initial dose in small fractions to achieve a lower dose capable of maintaining an adequate clinical response.

Management: patients must be carefully monitored, identifying the sinuses and symptoms that may indicate the need to adjust to the dose, including alterations in the clinical picture resulting from remission or exacerbation of the disease, individual response to drugs and effects of stress (for example: surgery, infection, trauma). During stress, it may be necessary to temporarily increase the dosage.


Posology and method of use:
OVERDOSE, index

In acute overdose, symptomatic supportive treatment is recommended. An oral LD ​​50 is greater than 4000 mg/kg in laboratory animals.


overdose:

ATTENTION: THIS PRODUCT IS A NEW MEDICATION AND ALTHOUGH RESEARCH HAS INDICATED EFFICACY AND SAFETY WHEN CORRECTLY INDICATED, UNPREDICTABLE ADVERSE REACTIONS MAY OCCUR THAT HAVE NOT YET BEEN DESCRIBED OR ARE NOT KNOWN. IN CASE OF SUSPECTED ADVERSE REACTION, THE DOCTOR IN CHARGE MUST BE NOTIFIED.

HOECHST MARION ROUSSEL S.A
Av. Mário Lopes Leão, 1500 - Santo Amaro - São Paulo

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DATA-MÉDICOS/DERMAGIC-EXPRESS No (33) 05/02/99 DR. JOSÉ LAPENTA R. 
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