Active ingredients: Deflazacort
DEFLAN 6 mg tablets
DEFLAN 30 mg tablets
DEFLAN 22.75 mg / ml oral drops, suspension
Why is Deflan used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Deflazacort is a synthetic glucocorticoid with anti-inflammatory and immunosuppressive activity.
THERAPEUTIC INDICATIONS
Insufficient primary and secondary activity of the adrenal glands (alone or in association with mineralocorticoids). Rheumatic diseases: psoriatic arthropathy, rheumatoid arthritis, ankylosing spondylitis, acute gouty arthropathy, post-traumatic osteoarthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis. Collagen diseases: systemic lupus erythematosus (SLE), acute rheumatic carditis (cardiac rheumatism), systemic dermatomyositis (polymyositis). Dermatological diseases: pemphigus, bullous herpetiform dermatitis, severe polymorphic erythema (Stevens-Johnson syndrome), exfoliative dermatitis, mycosis fungoides (cutaneous lymphoma), severe psoriasis, severe seborrheic dermatitis. Allergic states: seasonal or permanent allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, drug hyperreactivity. Respiratory diseases: symptomatic sarcoidosis, berylliosis, fulminant or disseminated pulmonary tuberculosis (in association with appropriate chemotherapy), aspiration pneumonia. Ocular diseases (severe, acute and chronic inflammatory and allergic processes): allergic marginal corneal ulcers, ocular herpes zooster, inflammation of the anterior segment of the eyeball, choroiditis and posterior diffuse uveitis, sympathetic ophthalmitis, allergic conjunctivitis, keratitis, chorioretinitis, neuritis of the " optic, iritis and iridocyclitis Haematological disorders and haematological diseases with malignant evolution: secondary thrombocytopenia of the adult, autoimmune haemolytic anemia, erythroblastopenia, congenital hypoplastic anemia; Hodgkin's disease, non-Hodgkin's lymphomas, chronic lymphatic leukemia, acute childhood leukemia, etc. Edematous states: idiopathic nephrotic syndrome or secondary to SLE. Gastro-intestinal diseases: ulcerative colitis, regional enteritis.
Contraindications When Deflan should not be used
Hypersensitivity to the active substance or to any of the excipients.
Active tuberculosis, peptic ulcer, ocular herpes simplex, systemic fungal infections, psychosis. Administration of live attenuated vaccine.
Precautions for use What you need to know before taking Deflan
In patients on corticosteroid therapy, subjected to particular stress, it is essential to adjust the dose in relation to the entity of the stressful condition.
A state of secondary adrenal insufficiency, induced by cortisone, can be contained with a gradual reduction of doses. This type of relative insufficiency can persist for months after discontinuation of therapy. Therefore in any stressful situation, which occurs during this period, adequate hormone replacement therapy should be instituted. In this situation the mineralocorticoid secretion can be compromised and therefore it would be advisable to administer, concomitantly, salt and / or mineralocorticoids.
In patients with hypothyroidism or with cirrhosis of the liver, the response to corticosteroids may be increased.
In the course of prolonged therapy and with high doses, should an alteration of the electrolyte balance occur, it is advisable to adjust the sodium and potassium intake. Corticosteroids can increase the excretion of calcium and therefore it may be necessary to monitor calcium. .
Patients on corticosteroid therapy should not be vaccinated against smallpox.
Other immunizing procedures should not be undertaken in patients receiving corticosteroids especially at high doses, due to increased risk of neurological complications and decreased antibody response.
The use of DEFLAN in active tuberculosis should be limited to cases of fulminant or disseminated disease, in which the corticosteroid is used with appropriate antituberculous therapy. If corticosteroids are administered to patients with latent tuberculosis or with a positive response to tuberculin, close surveillance as a "activation of the disease" can occur. In prolonged corticotherapy these patients should receive chemoprophylaxis.
Corticosteroids should be administered with caution in the following cases: non-specific ulcerative colitis with danger of perforation, abscesses and pyogenic infections in general, diverticulitis, recent intestinal anastomosis, renal failure, hypertension, diabetes, osteoporosis, myasthenia gravis.
Children undergoing prolonged corticotherapy must be closely monitored from the point of view of growth and development.
In case of concomitant treatment with diuretics (thiazides, furosemide, etc.) and beta 2 agonists (reproterol, etc.) which induce potassium loss, check potassium and blood pH.
Interactions Which drugs or foods may change the effect of Deflan
Although there are no known interactions and incompatibilities with DEFLAN, under contemporary treatment with:
- anticonvulsants (phenobarbital, diphenylhydantoin), some antibiotics (rifampicin), anticoagulants (warfarin) or bronchodilators (ephedrine), rifabutin, carbamazepine, phenytoin primidone and aminoglutethimide, it is suggested to increase the maintenance dose of the glucocorticoid
- other antibiotics (erythromycin, troleandomycin), it is recommended to reduce the dose of glucocorticoid
- acetylsalicylic acid: in patients with hypoprothrombinemia, caution is advised in associating acetylsalicylic acid with corticosteroids
- antacids: antacids administered simultaneously to decrease the dyspepsia induced by them, reduce the intestinal absorption of glucocorticoids, worsening the control of disease symptoms.
- quetiapine: taking deflazacort may cause decreased serum concentration of quetiapine
- estrogen: concomitant use of glucocorticoids and oral contraceptives should be carefully monitored, plasma glucocorticoid levels may be increased. This effect may be due to a change in metabolism or serum protein binding
- anti-infectives: since glucocorticoids can suppress the body's normal responses to attacks by microorganisms, it is important to ensure that any anti-infective therapy is effective and it is recommended that patients be carefully monitored
- medicines that inhibit liver enzymes (e.g. ketoconazole): reduction of the maintenance dose of deflazacort should be considered
- hypoglycemic agents (including insulin), antihypertensives and diuretics can be antagonized by corticosteroids and the hypokalaemic effect of acetazolamide, loop diuretics, thiazide diuretics, beta-2 agonists, xanthines and carbenoxolone may be increased
- coumarin anticoagulants: the efficacy of coumarin anticoagulants can be increased in case of concomitant therapy with corticosteroids. Prothrombin time or INR should be carefully monitored to avoid spontaneous bleeding
- non-depolarizing muscle relaxants: in patients treated with systemic corticosteroids, the use of non-depolarizing muscle relaxants can cause prolonged relaxation and acute myopathy.
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Warnings It is important to know that:
The tablets contain lactose so in case of ascertained intolerance to sugars contact your doctor before taking the medicine.
The oral drops suspension contain sorbitol so if your doctor has diagnosed you with an intolerance to some sugars, contact your doctor before taking this medicine.
Corticosteroids can mask some signs of infection, and intercurrent infections can occur during their use. In these cases, the opportunity to institute adequate antibiotic therapy must always be evaluated.
Psychic alterations of various kinds can occur during corticotherapy: euphoria, insomnia, changes in mood or personality, severe depression or symptoms of real psychosis. A pre-existing emotional instability or psychotic tendencies can be aggravated by corticosteroids.
Patients treated with deflazacort who have not already contracted chickenpox if they come into contact with people with chickenpox or shingles should see their doctor immediately. If the patient is a child, parents should be warned of this precaution.
Patients should be advised to take special care to avoid exposure to measles and to seek immediate medical attention if this occurs.
Patients on corticosteroid therapy should not be vaccinated.
Pregnancy and breastfeeding
In pregnant women, during lactation and in very early childhood, the product should be administered in cases of real need, under the direct supervision of the doctor.
Pregnancy
The ability of corticosteroids to cross the placenta varies between different drugs. Deflazacort crosses the placenta. Administration of corticosteroids to pregnant animals can cause fetal development abnormalities such as cleft palate, intrauterine growth retardation and effects on brain growth and development.
There is no evidence that the use of corticosteroids results in an increased incidence of congenital abnormalities, such as cleft lip / palate in humans.
However, when given for prolonged periods or repeatedly during pregnancy, corticosteroids can increase the risk of intrauterine growth retardation.
Hypoadrenalism can, theoretically, occur in the neonate after prenatal exposure to corticosteroids, but usually resolves spontaneously after birth and is rarely clinically important.
Feeding time
Corticosteroids are excreted in breast milk, although no data are available for deflazacort. Doses of up to 50 mg per day of deflazacort do not cause systemic effects in the newborn. Adrenal suppression may occur in infants of mothers treated with doses above the indicated dosage, but the benefits of breastfeeding may outweigh any theoretical risk.
Ask your doctor or pharmacist for advice before taking any medicine
Effects on ability to drive and use machines
Deflan does not affect the ability to drive or use machines.
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Dosage and method of use How to use Deflan: Dosage
DEFLAN is a medicine that is given by mouth. The initial daily dosage in adults can vary from 6 to 90 mg (one or more tablets or more drops per day), in consideration of the severity and evolution of the specific disease to be treated.
The starting dosage should be maintained or modified until a satisfactory clinical response is achieved. IT IS IMPORTANT TO EMPHASIZE THAT THE CORTICOSTEROID NEEDS IS VARIABLE AND THEREFORE THE DOSAGE MUST BE INDIVIDUALIZED TAKING INTO ACCOUNT THE DISEASE AND THE THERAPEUTIC RESPONSE OF THE PATIENT.
The maintenance dosage must always be the minimum capable of controlling the symptoms: the dosage reduction must always be done gradually.
With regard to the presentation in drops, it should be noted that the dropper of the suspension delivers on average 1 mg of deflazacort per drop. It is suggested to shake the bottle before use and to dilute the suspension, immediately before administration, in sugared water or in drinks without carbon dioxide added.
It is advisable to take the daily dose of DEFLAN in a single administration, in the morning, together with small amounts of food.
Overdose What to do if you have taken too much Deflan
In case of overdose it is recommended to carry out, in concomitance with the usual measures for the elimination of the unabsorbed drug (gastric lavage, charcoal, etc.), a clinical check of the patient's vital functions. In case of accidental intake of a overdose of the medicine notify your doctor immediately or go to the nearest hospital.
If you have any further questions on the use of DEFLAN, ask your doctor or pharmacist.
Side Effects What are the side effects of Deflan
Like all medicines, DEFLAN can cause side effects, although not everybody gets them.
It should be borne in mind that during corticosteroid therapy, especially for intense and prolonged treatments, some of the following effects may occur:
Metabolism and nutrition disorders:
weight gain, increased appetite, decreased tolerance to carbohydrates with the possible occurrence of latent diabetes mellitus as well as an increased need for hypoglycemic drugs in diabetics, to be determined in the opinion of the doctor; alterations in the electrolyte balance which, rarely and in particularly predisposed patients, they can lead to hypertension and congestive heart failure;
Infections and infestations:
increased susceptibility to infections and severity with suppression of clinical symptoms and signs, recurrence of latent tuberculosis, candidiasis;
Musculoskeletal and connective system disorders:
osteoporosis, bone fragility, myopathies, vertebral and long bone fractures, avascular necrosis, tendonitis, tendon rupture when administered concomitantly with quinolones;
Nervous system disorders:
dizziness, headache and increased intracranial pressure, aggravation of epilepsy, psychiatric disorders of various kinds: irritability, anxiety, suicidal thoughts, mania, delusion, hallucinations, aggravation of schizophrenia, euphoria, insomnia, mood or personality changes, depression severe, cognitive disturbances including confusion and amnesia;
Skin and subcutaneous tissue disorders:
delays in the processes of scarring, thinning and fragility of the skin, hirsutism, acne, striae, bruising, telangiectasia, edema;
Eye disorders:
posterior subcapsular cataract and increased intraocular pressure, chorioretinopathy, corneal or sclera thinning, exacerbation of viral or mycotic ophthalmic diseases;
Gastrointestinal disorders
peptic ulcer; dyspepsia, bleeding, nausea;
Pathologies of the reproductive system
menstrual irregularities;
Cardiac pathologies
heart failure;
Diagnostic tests
negativization of the nitrogen balance, alterations in the electrolyte balance, including hypokalaemia and hypersodemia;
Endocrine pathologies
interference with the functionality of the pituitary-adrenal axis particularly in times of stress; alteration of endocrine function, changes in physiognomy ("moon face"), growth disturbances in children and adolescents;
Disorders of the blood and lymphatic system
leukocytosis;
Disorders of the immune system
hypersensitivity;
Vascular pathologies
thromboembolism particularly in patients with underlying diseases associated with an increased tendency to thrombosis, rare incidence of benign intracranial hypertension, hypertension.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Expiry and Retention
EXPIRY: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date shown on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
KEEP THE MEDICINAL PRODUCT OUT OF THE SIGHT AND REACH OF CHILDREN
Composition and pharmaceutical form
COMPOSITION
Deflan 6 mg tablets
One tablet contains:
Active ingredient: Deflazacort 6 mg. Excipients: Lactose; Magnesium stearate; Cornstarch; Microcrystalline cellulose.
Deflan 30 mg tablets
One tablet contains:
Active ingredient: 30 mg Deflazacort. Excipients: Lactose, Magnesium stearate, Corn starch; Microcrystalline cellulose.
Deflan 22.75 mg / ml oral drops, suspension
1 ml of suspension contains: Active ingredient: Deflazacort 22.75 mg. Excipients: Aluminum and magnesium silicate; Carmellose sodium; Benzyl alcohol; Sorbitol 70% solution; Polysorbate 80; Acetic acid; Purified water.
PHARMACEUTICAL FORM AND CONTENT
- Box of 10 tablets of 6 mg in blister.
- Box of 10 tablets of 30 mg in blister.
- Drops: - 8 ml bottle of suspension with dropper - 13 ml bottle of suspension with dropper.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
DEFLAN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Deflan 6 mg tablets
One tablet contains:
Active principle: Deflazacort 6 mg
Excipients with known effects: lactose.
Deflan 30 mg tablets
One tablet contains:
Active principle: Deflazacort 30 mg
Excipients with known effects: lactose.
Deflan 22.75 mg / ml oral drops, suspension
1 ml of suspension contains:
Active principle: Deflazacort 22.75 mg
Excipients with known effects: sorbitol.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets.
Oral drops, suspension.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Primary and secondary adrenocortical insufficiency (alone or in association with mineralocorticoids).
Rheumatic diseases: psoriatic arthropathy, rheumatoid arthritis, ankylosing spondylitis, acute gouty arthropathy, post-traumatic osteoarthritis, acute and subacute bursitis, acute non-specific tenosynovitis, epicondylitis.
Collagen diseases: systemic lupus erythematosus (SLE), acute rheumatic carditis (cardiac rheumatism), systemic dermatomyositis (polymyositis).
Dermatological diseases: pemphigus, bullous herpetiform dermatitis, severe polymorphic erythema (Stevens-Johnson syndrome), exfoliative dermatitis, mycosis fungoides (cutaneous lymphoma), severe psoriasis, severe seborrheic dermatitis.
Allergic states: seasonal or permanent allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, drug hyperreactivity.
Respiratory diseases: symptomatic sarcoidosis, berylliosis, fulminant or disseminated pulmonary tuberculosis (in association with appropriate chemotherapy), aspiration pneumonia.
Eye diseases (severe, acute and chronic inflammatory and allergic processes): allergic marginal corneal ulcers, ocular herpes zooster, inflammation of the anterior segment of the globe, choroiditis and posterior diffuse uveitis, sympathetic ophthalmitis, allergic conjunctivitis, keratitis, chorioretinitis, optician neuritis, iritis and iridocyclitis.
Haematological disorders and haematological diseases with malignant evolution: secondary thrombocytopenia in adults, autoimmune hemolytic anemia, erythroblastopenia, congenital hypoplastic anemia; Hodgkin's disease, non-Hodgkin's lymphomas, chronic lymphocytic leukemia, acute childhood leukemia, etc.
Edematous states: idiopathic nephrotic syndrome or secondary to SLE.
Gastro-intestinal diseases: ulcerative colitis, regional enteritis.
04.2 Posology and method of administration
The initial daily dosage in adults can vary from 6 to 90 mg in consideration of the severity and evolution of the specific disease to be treated.
The starting dosage should be maintained or modified until a satisfactory clinical response is achieved. It is important to underline that the corticosteroid requirement is variable and therefore the posology must be individualized taking into account the disease and the patient's therapeutic response.
The maintenance dosage must always be the minimum capable of controlling the symptoms, minimizing the risk of secondary effects: the reduction of the dosage must always be implemented gradually.
With regard to the presentation in drops, it should be noted that the dropper of the suspension delivers on average 1 mg of deflazacort per drop.
It is suggested to shake the bottle before use and to dilute the suspension, immediately before administration, in sugared water or in drinks without carbon dioxide added.
It is advisable to take the daily dose of Deflan in a single administration, in the morning, together with small amounts of food.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Active tuberculosis, peptic ulcer, ocular herpes simplex, systemic fungal infections, psychosis.
Administration of live attenuated vaccine.
04.4 Special warnings and appropriate precautions for use
In patients on corticosteroid therapy, subjected to particular stress, it is essential to adapt the dose of the glucocorticoid in relation to the extent of the stressful condition.
Corticosteroids can mask some signs of infection and intercurrent infections may occur during their use (opportunity to institute adequate antibiotic therapy).
A state of secondary adrenal insufficiency, induced by cortisone, can be contained with a gradual reduction of doses. This type of relative insufficiency can persist for months after discontinuation of therapy. Therefore in any stressful situation, which occurs during this period, adequate hormone replacement therapy should be instituted. In this situation the mineralocorticoid secretion can be compromised and therefore it would be advisable to administer, concomitantly, salt and / or mineralocorticoids.
In patients with hypothyroidism or with cirrhosis of the liver, the response to corticosteroids may be increased.
Psychic alterations of various kinds can occur during corticotherapy: euphoria, insomnia, changes in mood or personality, severe depression or symptoms of real psychosis. A pre-existing emotional instability or psychotic tendencies can be aggravated by corticosteroids.
Patients on deflazacort who have not already contracted chickenpox if they come into contact with people with chickenpox or shingles should see their doctor immediately. If the patient is a child, parents should be warned of this precaution.
Patients should be advised to take special care to avoid exposure to measles and to seek immediate medical attention if this occurs.
Patients on corticosteroid therapy should not be vaccinated against smallpox. Other immunizing procedures should not be undertaken in patients receiving corticosteroids especially at high doses, due to increased risk of neurological complications and decreased antibody response.
The use of Deflan in active tuberculosis should be limited to cases of fulminant or disseminated disease, in which the corticosteroid is used with appropriate antituberculous therapy. If corticosteroids are administered to patients with latent tuberculosis or with a positive response to tuberculin, close surveillance as disease activation may occur. In prolonged corticotherapy these patients should receive chemoprophylaxis.
Corticosteroids should be administered with caution in the following cases: non-specific ulcerative colitis with danger of perforation, abscesses and pyogenic infections in general, diverticulitis, recent intestinal anastomosis, renal failure, hypertension, diabetes, osteoporosis, myasthenia gravis.
Children undergoing prolonged corticotherapy must be closely monitored from the point of view of growth and development.
In case of concomitant treatment with diuretics (thiazides, furosemide, etc.) and beta2 agonists (reproterol, etc.) that induce loss of potassium, check potassium and blood pH.
The tablets contain lactose therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
The oral drops, suspension, contain sorbitol so patients with rare hereditary problems of fructose intolerance should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Although there are no known drug interactions and incompatibility with DEFLAN, however in the course of simultaneous treatment with:
- anticonvulsants (phenobarbital, diphenylhydantoin), some antibiotics (rifampicin), anticoagulants (warfarin) or bronchodilators (ephedrine), rifabutin, carbamazepine, phenytoin primidone and aminoglutethimide, it is suggested to increase the maintenance dose of the glucocorticoid.
- other antibiotics (erythromycin, troleandomycin), estrogen or preparations containing estrogen, it is recommended to reduce the glucocorticoid dose.
- acetylsalicylic acid: in patients with hypoprothrombinemia, caution is advised in associating acetylsalicylic acid with corticosteroids.
- antacids: antacids administered simultaneously to decrease the dyspepsia induced by them, reduce the intestinal absorption of glucocorticoids, worsening the control of disease symptoms.
- quetiapine: taking deflazacort may cause a decreased serum concentration of quetiapine.
- estrogens: concomitant use of glucocorticoids and oral contraceptives should be carefully monitored, plasma glucocorticoid levels may be increased. This effect may be due to a change in metabolism or serum protein binding.
- anti-infectives: since glucocorticoids can suppress the body's normal responses to attacks by microorganisms, it is important to ensure that any anti-infective therapy is effective and it is recommended that patients be carefully monitored.
- medicines that inhibit liver enzymes (eg ketoconazole): a reduction in the maintenance dose of deflazacort should be considered.
- hypoglycemic agents (including insulin), antihypertensives and diuretics can be antagonized by corticosteroids and the hypokalaemic effect of acetazolamide, loop diuretics, thiazide diuretics, beta-2 agonists, xanthines and carbenoxolone may be increased.
- coumarin anticoagulants: the efficacy of coumarin anticoagulants can be increased in case of concomitant therapy with corticosteroids. Prothrombin time or INR should be carefully monitored to avoid spontaneous bleeding.
- non-depolarizing muscle relaxants: in patients treated with systemic corticosteroids, the use of non-depolarizing muscle relaxants can cause prolonged relaxation and acute myopathy.
04.6 Pregnancy and lactation
In pregnant, lactating and early childhood women, the product should be administered in cases of real need, under the direct supervision of the doctor.
Pregnancy
The ability of corticosteroids to cross the placenta varies between different drugs. Deflazacort crosses the placenta. Administration of corticosteroids to pregnant animals can cause fetal development abnormalities such as cleft palate, intrauterine growth retardation and effects on brain growth and development.
There is no evidence that the use of corticosteroids results in an increased incidence of congenital abnormalities, such as cleft lip / palate in humans.
However, when given for prolonged periods or repeatedly during pregnancy, corticosteroids can increase the risk of intrauterine growth retardation.
Hypoadrenalism can, theoretically, occur in the neonate after prenatal exposure to corticosteroids, but usually resolves spontaneously after birth and is rarely clinically important.
Feeding time
Corticosteroids are excreted in breast milk, although no data are available for deflazacort. Doses of up to 50 mg per day of deflazacort do not cause systemic effects in the newborn. Adrenal suppression may occur in infants of mothers treated with doses above the indicated dosage, but the benefits of breastfeeding may outweigh any theoretical risk.
04.7 Effects on ability to drive and use machines
Deflan does not affect the ability to drive or use machines.
04.8 Undesirable effects
It should be borne in mind that during corticosteroid therapy, especially for intense and prolonged treatments, some of the following effects may occur:
Metabolism and nutrition disorders:
weight gain; increased appetite; decreased tolerance to carbohydrates with possible manifestation of latent diabetes mellitus as well as an increased need for hypoglycemic drugs in diabetics; to be determined in the opinion of the doctor; alterations in the electrolyte balance which, rarely and in particularly predisposed patients, can lead to " hypertension and congestive heart failure.
Infections and infestations:
increased susceptibility to infections and severity with suppression of clinical symptoms and signs, recurrence of latent tuberculosis, candidiasis.
Musculoskeletal and connective system disorders:
osteoporosis, bone fragility, myopathies, vertebral and long bone fractures; avascular necrosis, tendonitis, tendon rupture when administered concomitantly with quinolones.
Nervous system disorders:
dizziness, headache and increased intracranial pressure; aggravation of epilepsy; psychiatric disorders of various kinds: irritability, anxiety, suicidal thoughts, mania, delusion, hallucinations, aggravation of schizophrenia, euphoria, insomnia, changes in mood or personality, severe depression, cognitive disturbances including confusion and amnesia.
Skin and subcutaneous tissue disorders:
delays in the processes of scarring, thinning and fragility of the skin; hirsutism, acne, striae, bruising, telangiectasia; edema.
Eye disorders:
posterior subcapsular cataract and increased intraocular pressure, chorioretinopathy; corneal or sclera thinning, exacerbation of ophthalmic viral or fungal diseases.
Gastrointestinal disorders:
peptic ulcer; dyspepsia, haemorrhage, nausea.
Diseases of the reproductive system:
menstrual irregularities.
Cardiac disorders:
heart failure.
Diagnostic tests:
negativization of the nitrogen balance, alterations in the electrolyte balance including hypokalemia and hypersodemia.
Endocrine disorders:
interference with the functionality of the pituitary-adrenal axis, particularly in times of stress, alteration of endocrine function, changes in physiognomy ("moon face"), growth disturbances in children and adolescents.
Disorders of the blood and lymphatic system:
leukocytosis.
Immune system disorders:
hypersensitivity.
Vascular disorders:
thromboembolism in particular in patients with underlying diseases associated with an increased tendency to thrombosis; rare incidence of benign intracranial hypertension; hypertension in predisposed individuals.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous 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. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
During prolonged therapy and with high doses, should an alteration of the electrolyte balance occur, it is advisable to adjust the sodium and potassium intake. Corticosteroids increase urinary excretion of calcium.
In case of overdose it is recommended to carry out, in concomitance with the usual measures for the elimination of the unabsorbed drug (gastric lavage, charcoal, etc.), a clinical check of the patient's vital functions.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Systemic, unassociated corticosteroids; glucocorticoids. ATC code: H02AB13.
The study of different experimental models indicates that Deflan is an effective inhibitor of the early exudative phase of inflammation (edema induced by carrageenan and nystatin), as well as the formation of slowly evolving granulomatous inflammatory tissue (granuloma from cotton pellets). It has also been shown to inhibit experimentally induced chronic (joint) inflammatory manifestations (adjuvant arthritis). The study of the ability of glucocorticoids to induce glycogen storage in the liver of adrenalectomized rats has shown that Deflan is able to produce an increase in glyconeogenesis and hepatic glycogenosynthesis about 10 times that of prednisolone administered in equally active doses. The anti-inflammatory potency of Deflan, estimated on the basis of these well-established experimental models, is about 10-20 times that of prednisolone or 40 times that of cortisol (hydrocortisone), while its duration of anti-inflammatory effects is greater than that a of other glucocorticoids administered in equally active doses (prednisolone, triamcinolone, etc.).
The study of the ability of glucocorticoids to induce a reduction in renal excretion of Na + in adrenalectomized animals (mineralocorticoid effect), showed that Deflan did not induce, unlike a typical mineralocorticoid hormone such as DOCA, tissue retention of Na +, while causing like prednisolone an "increased renal excretion of fluids and K +.
The study of the ability of glucocorticoids to induce fasting hyperglycemia and after glucose loading, showed that Deflan administered orally in rats, induced fasting and after glucose hyperglycemic levels comparable to those produced by prednisolone, while intraperitoneally produced a reduction in glucose tolerance after loading, significantly lower than that induced by prednisolone in equactive doses.
The study of the secondary effects of Deflan at the level of other systems of apparatus, has shown that it interferes in an insignificant way on the central nervous system and cardiovascular during repeated administration (a few days) in the rat.
05.2 Pharmacokinetic properties
The study of the pharmacokinetics, tissue distribution and metabolism of Deflan was carried out in rats, guinea pigs, monkeys and humans, using methods of analytical determination on the compound as such and on the labeled one (C14). After being rapidly absorbed from the intestine (plasma peak between 1 and 2 hours), deflazacort is immediately hydrolyzed to its metabolites, 21-desacetyl deflazacort (the main or active metabolite II) and 6-beta hydroxy derivative (or metabolite III). inactive), there being no more traces of the compound as such in the circulation (pro-drug). The active metabolites of Deflan then follow the same metabolic fate as prednisolone and other synthetic glucocorticoids. The plasma half-life of metabolite II ranges from 2 hours in humans to 4 hours in monkeys. The study of the tissue distribution of the labeled drug in the rat, having revealed that its preferential "target organs" are the kidney and blood cells, suggests that the longer persistence of the drug in these compartments is responsible for its longer duration of effects. The elimination of metabolites occurs in humans within 24 hours, mainly through the urine.
05.3 Preclinical safety data
The study of the effects deriving from the administration of single doses indicates that the LD50 are: after oral administration 5200 mg / kg in the mouse and> 4000 mg / kg in the dog; after SC administration 1610 mg / kg in the mouse, 109 mg / kg in the rat and 50 mg / kg in the dog.
The study of the effects resulting from repeated oral administration in the rat (1.75 - 7.0 mg / kg / day), dog (0.1 - 1 mg / kg / day) and monkey (0.5 - 1, 5 mg / kg / day), lasting 6-12 months, showed that Deflan is satisfactorily tolerated, with secondary effects affecting organs, comparable to those usually detected with other glucocorticoids, under the same experimental conditions.
The study of the effects on reproduction (fertility, embryotoxicity and peripostnatal) showed that Deflan induced secondary alterations comparable to those usually observed with other glucocorticoids, under the same experimental conditions. Deflan never produced mutagenic effects.
Carcinogenicity studies conducted in rodents have shown no tumorigenic effect in mice, while in rats some neoplastic effects similar to those already known for other corticosteroids have been observed, without any confirmation with the use of these compounds in humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Deflan 6 mg tablets
Lactose; magnesium stearate; cornstarch; microcrystalline cellulose.
Deflan 30 mg tablets
Lactose; magnesium stearate; cornstarch; microcrystalline cellulose.
Deflan 22.75 mg / ml oral drops, suspension
Aluminum and magnesium silicate; carmellose sodium; benzyl alcohol; sorbitol 70% solution; polysorbate 80; acetic acid; purified water.
06.2 Incompatibility
Patients on corticosteroid therapy should not be vaccinated against smallpox. Other immunizing procedures should not be undertaken in patients receiving corticosteroids especially at high doses, due to increased risk of neurological complications and decreased antibody response.
Antacids administered simultaneously to decrease the dyspepsia they induce reduce intestinal absorption of glucocorticoids, worsening the control of disease symptoms.
06.3 Period of validity
Tablets: 3 years.
Oral drops, suspension: 3 years.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Box of 10 tablets of 6 mg in blister
Box of 10 tablets of 30 mg in blister
Oral drops, suspension: 13 ml bottle of suspension with dropper
Oral drops, suspension: 8 ml bottle of suspension with dropper
06.6 Instructions for use and handling
It is important to remember to shake the bottle of the oral suspension well before use.
07.0 MARKETING AUTHORIZATION HOLDER
LABORATORI GUIDOTTI S.p.A. - Via Livornese 897, PISA - La Vettola
08.0 MARKETING AUTHORIZATION NUMBER
Deflan 6 mg tablets, 10 tablets - AIC: 026046019
Deflan 30 mg tablets, 10 tablets - AIC: 026046021
Deflan 22.75 mg / ml oral drops, suspension:
- 13 ml bottle - AIC: 026046033
- 8 ml bottle - AIC: 026046045
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Deflan 6 mg tablets, 10 tablets - 04/16/86 - May 2010
Deflan 30 mg tablets, 10 tablets - 04/16/86 - May 2010
Deflan 22.75 mg / ml oral drops, suspension:
- 13 ml bottle - 11/15/94 - May 2010
- 8 ml bottle - 27/05/00 - May 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of September 2014
