Deflazacort oral suspension
Each 5 ml contains:
Deflazacort: 6mg
Excipients: q.s.
Oral suspension, 6mg/5
For asthma, rheumatoid arthritis when glucocorticosteriod therapy is warranted.
Deflazacort is a glucocorticoid derived from prednisolone and 6mg of deflazacort has approximately the same anti-inflammatory potency as 5mg prednisolone or prednisone.
Doses vary widely in different diseases and different patients. In more serious and life-threatening conditions, high doses of deflazacort may need to be given. When deflazacort is used long term in relatively benign chronic diseases, the maintenance dose should be kept as low as possible. Dosage may need to be increased during periods of stress or in exacerbation of illness.
The dosage should be individually titrated according to diagnosis, severity of disease and patient response and tolerance. The lowest dose that will produce an acceptable response should be used.
There has been limited exposure of children to deflazacort in clinical trials.
In children, the indications for glucocorticoids are the same as for adults, but it is important that the lowest effective dosage is used. Alternate day administration may be appropriate.
Doses of deflazacort usually lie in the range 0.25 - 1.5 mg/kg/day.
The following ranges provide general guidance:
Hepatic Impairment
In patients with hepatic impairment, blood levels of deflazacort may be increased. Therefore, the dose of deflazacort should be carefully monitored and adjusted to the minimum effective dose.
Renal Impairment
In renally impaired patients, no special precautions other than those usually adopted in patients receiving glucocorticoid therapy are necessary.
Deflazacort withdrawal
In patients who have received more than physiological doses of systemic corticosteroids (approximately 9 mg/day or equivalent) for > 3 weeks, withdrawal should not be abrupt. How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. Clinical assessment of disease activity may be needed during withdrawal.
If the disease is unlikely to relapse on withdrawal of systemic corticosteroids but there is uncertainty about HPA suppression, the dose of systemic corticosteroids may be reduced rapidly to physiological doses. Once a daily dose equivalent to 9 mg deflazacort is reached, dose reduction should be slower to allow the HPA-axis to recover.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it is considered that the disease is unlikely to relapse. Abrupt withdrawal of doses up to 48 mg daily of deflazacort, or equivalent for 3 weeks is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of patients.
In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting 3 weeks or less:
Systemic infection unless specific anti-infective therapy is employed.
Hypersensitivity to the active substance, deflazacort or any of the excipients.
Patients receiving live virus immunisation.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.
Undesirable effects may be minimised by using the lowest effective dose for the minimum period, and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternate days. Frequent patient review is required to appropriately titrate the dose against disease activity.
Adrenal suppression
Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment. Withdrawal of corticosteroids after prolonged therapy must therefore always be gradual to avoid acute adrenal insufficiency which could be fatal, being tapered off over weeks or months according to the dose and duration of treatment.
During prolonged therapy, any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy, they may need to be temporarily re-introduced.
Patients should carry 'Steroid treatment' cards which give clear guidance on the precautions to be taken to minimise risk and which provide details of prescriber, drug, dosage and the duration of treatment.
Anti-inflammatory/immunosuppressive effects and infection
Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognised.
Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients.
Patients (or parents of children) without a definite history of chicken pox should be advised to avoid close personal contact with chickenpox or herpes zoster and, if exposed, they should seek urgent medical attention.
Passive immunisation with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox.
If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.
Patients should be advised to take particular care to avoid exposure to measles and to seek immediate medical advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.
Live vaccines should not be given to individuals with impaired responsiveness. The antibody response to other vaccines may be diminished.
Visual disturbance
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Prolonged use of glucocorticoids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves and may enhance the establishment of secondary ocular infections due to fungi or viruses.
Use in active tuberculosis should be restricted to those cases of fulminating and disseminated tuberculosis in which deflazacort is used for management with appropriate antituberculosis regimen.
If glucocorticoids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged glucocorticoid therapy, these patients should receive chemoprophylaxis.
Tendonitis and tendon rupture are known class effect of glucocorticoids. The risk of such reactions may be increased by co-administration of quinolones.
Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
Special precautions
The following clinical conditions require special caution and frequent patient monitoring is necessary:
Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids.
Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure, although dose levels do not allow prediction of the onset, type, severity or duration of reactions.
Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary.
Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected.
Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.
Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first-degree relatives.
These would include depressive or manic-depressive illness and previous steroid psychosis.
Glucocorticoids are known to cause irregular menstruation and leukocytosis, care should be taken with deflazacort.
Paediatric population
Corticosteroids cause dose-related growth retardation in infancy, childhood and adolescence which may be irreversible.
Hypertrophic cardiomyopathy has been reported after systemic administration of glucocorticosteroids in preterm infants.
In infants receiving administration of systemic glucocorticosteroids, echocardiograms should be performed to monitor myocardial structure and function.
Pregnancy
The ability of corticosteroids to cross the placenta varies between individual drugs, however, deflazacort does cross the placenta.
Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development.
There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man.
However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation.
Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important.
As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks.
When corticosteroids are essential however, patients with normal pregnancies may be treated as though they were in the non-gravid state.
Breast-feeding
Corticosteroids are excreted in breast milk, although no data are available for deflazacort.
Doses of up to 50 mg daily of deflazacort are unlikely to cause systemic effects in the infant.
Infants of mothers taking higher doses than this may have a degree of adrenal suppression but the benefits of breast feeding are likely to outweigh any theoretical risk.
Fertility
No data is available on Deflazacort and its effects on fertility.
The effect of corticosteroids on the ability to drive or use machinery has not been systematically evaluated.
Vertigo is a possible undesirable effect after treatment with deflazacort. If affected, patients should not drive or operate machinery.
The incidence of predictable undesirable effects, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and the duration of treatment.
The following CIOMS frequency rating is used:
Endocrine disorders
Metabolism and nutrition disorders
Infections and infestations
Musculoskeletal and connective tissue disorders
Reproductive system and breast disorders
Cardiac disorders
Nervous system disorders
Psychiatric disorders
A wide range of psychiatric reactions including affective disorders such as:
Psychotic reactions including:
Other reactions including:
Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5-6%.
Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.
Eye disorders
Gastrointestinal disorders
Skin and subcutaneous tissue disorders
General disorders and administration site conditions
Immune system disorders
Blood and lymphatic system disorders
Vascular disorders
Withdrawal symptoms and signs
A 'withdrawal syndrome' may also occur including fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight. This may occur in patients even without evidence of adrenal insufficiency.
Class effect
Pheochromocytoma crisis has been reported with other systemic corticosteroids and is a known class effect.
Reporting of Suspected Adverse Reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via email to:
medico@zorvia.com
By reporting side effects, you can help provide more information on the safety of this medicine.
It is unlikely that treatment is needed in cases of acute overdosage.
The LD50 for the oral dose is greater than 4000 mg/kg in laboratory animals.
Pharmacotherapeutic group: corticosteroids for systemic use; Glucocorticoids.
Deflazacort is a glucocorticoid. Its anti-inflammatory and immunosuppressive effects are used in treating a variety of diseases and are comparable to other anti-inflammatory steroids.
Clinical studies have indicated that the average potency ratio of deflazacort to prednisolone is 0.69–0.89.
Absorption
Orally administered deflazacort appears to be well absorbed.
Distribution
The active metabolite D 21-OH achieves peak plasma concentrations in 1.5 to 2 hours.
It is 40% protein-bound and has no affinity for corticosteroid-binding-globulin (transcortin).
Biotransformation
Orally administered deflazacort is immediately converted by plasma esterases to the pharmacologically active metabolite (D 21-OH).
Metabolism of D 21-OH is extensive.
The metabolite of D 21-OH is deflazacort 6-beta-OH.
Elimination
Its elimination plasma half-life is 1.1 to 1.9 hours.
Elimination takes place primarily through the kidneys; 70% of the administered dose is excreted in the urine.
The remaining 30% is eliminated in the faeces.
Metabolism of D 21-OH is extensive; only 18% of urinary excretion represents D 21-OH.
The metabolite of D 21-OH, deflazacort 6-beta-OH, represents one third of the urinary elimination.
Safety studies have been carried out in the rat, dog, mouse and monkey.
The findings are consistent with other glucocorticoids at comparable doses.
Teratogenic effects demonstrated in rodents and rabbits are typical of those caused by other glucocorticoids.
Deflazacort was not found to be carcinogenic in the mouse, but studies in the rat produced carcinogenic findings consistent with the findings with other glucocorticoids.
The active ingredient in Glazenta Suspension/Glazenta-XL Suspension is deflazacort (a corticosteroid).
Corticosteroids are adrenocortical steroids, both naturally occurring and synthetic.
Molecular Formula: C25H31NO6
Chemical Name:
(11β,16β)-21-(acetyloxy) 11-hydroxy-2'-methyl-5'H-pregna-1,4-dieno[17,16-d]oxazole-3,20-dione
Molecular Weight: 441.5 g/mol
Not applicable.
Refer on pack.
Glazenta Suspension: a bottle of 30 ml
Glazenta-XL Suspension: a bottle of 60 ml
Administration
Increased Risk of Infection
Tell patients and/or caregivers to inform their healthcare provider if the patient has had recent or ongoing infections or if they have recently received a vaccine.
Medical advice should be sought immediately if the patient develops fever or other signs of infection.
Patients and/or caregivers should be made aware that some infections can potentially be severe and fatal.
Warn patients who are on corticosteroids to avoid exposure to chickenpox or measles and to alert their healthcare provider immediately if they are exposed.
Alterations in Cardiovascular/Renal Function
Inform patients and/or caregivers that Glazenta/Glazenta-XL suspension can cause an increase in blood pressure and water retention.
If this occurs, dietary salt restriction and potassium supplementation may be needed.
Behavioural and Mood Disturbances
Advise patients and/or caregivers about the potential for severe behavioral and mood changes with Glazenta/Glazenta-XL suspension and encourage them to seek medical attention if psychiatric symptoms develop.
Decreases in Bone Mineral Density
Advise patients and/or caregivers about the risk of osteoporosis with prolonged use of Glazenta/Glazenta-XL suspension, which can predispose the patient to vertebral and long bone fractures.
Ophthalmic Effects
Inform patients and/or caregivers that Glazenta/Glazenta-XL suspension may cause cataracts or glaucoma and advise monitoring if corticosteroid therapy is continued for more than 6 weeks.
Vaccination
Advise patients and/or caregivers to bring immunizations up-to-date according to immunization guidelines prior to starting therapy with Glazenta/Glazenta-XL suspension.
Live-attenuated or live vaccines should be administered at least 4 to 6 weeks prior to starting Glazenta/Glazenta-XL suspension.
Inform patients and/or caregivers that they may receive concurrent vaccinations with use of Glazenta/Glazenta-XL suspension, except for live-attenuated or live vaccines.
Serious Skin Rashes
Instruct patients and/or caregivers to seek medical attention at the first sign of a rash.
Drug Interactions
Certain medications can cause an interaction with Glazenta/Glazenta-XL suspension. Advise patients and/or caregivers to inform their healthcare provider of all medications the patient is taking, including prescription and non-prescription medicines, vitamins and herbal products.