Dexametason Abcur
1. NAME OF THE MEDICINAL PRODUCT
Dexametason Abcur 1 mg tablets
Dexametason Abcur 4 mg tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1 mg or 4 mg dexamethasone.
Excipient with known effect:
Each 1 mg tablet contains 73 mg lactose monohydrate.
Each 4 mg tablet contains 70 mg lactose monohydrate.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL form
Tablets
1 mg: Round white tablet with a score line and embossed D1 on one side, tablet dimension 7 x 2.4 mm.
4 mg: Round white tablet with a score line and embossed D4 on one side, tablet dimension 7 x 2.4 mm.
The tablet can be divided into equal doses.
4. Clinical particulars
4.1 Therapeutic indications
- Conditions in which the anti-inflammatory and immunosuppressive effect of the corticosteroids is desirable. Especially for intensive treatment for a shorter time.
- Cerebral oedema or increased intracranial pressure due to brain tumour
- In the treatment of cancer mammae, ovarii, prostatae or testis when the effect of the corticosteroids is desirable.
- Prophylaxis of emesis induced by emetogenic chemotherapy.
- Diagnostic test of the pituitary and adrenal cortex function
4.2 Posology and method of administration
Posology
The dose should be titrated to the individual response and the severity of the disease. To minimize the side effects, the lowest dose that gives effect should be used. The start dose is between 0.5 and 8 mg daily, depending on the disease being treated. More serious medical conditions may require doses of more than 8 mg. The start dose can be retained or adjusted until the patient response is satisfactory.
Conditions in which the anti-inflammatory and immunosuppressive effect of the corticosteroids is desirable:The initial dose is generally 1-4 mg daily for a few days up to a week. In severe acute cases up to 8 mg may be given for a few days. When effect is obtained, the daily dose is gradually decreased by 1‑2 mg each third day to a suitable maintenance dose, which is usually 1‑2 mg.
Cerebral oedema or increased intracranial pressure due to brain tumour: In the case of cerebral oedema or increased intracranial pressure due to brain tumour, the intravenous administration of glucocorticoids is usually started in severe cases and on improvement a change is made to oral treatment with 4-16 mg Dexametason Abcur daily. In milder cases the oral administration of 2-8 mg is sufficient.
In the treatment of cancer mammae, ovarii, prostatae or testis: The initial dose is generally 8–16 mg. The maintenance dose is 4-12 mg.
Prophylaxis of emesis induced by emetogenic chemotherapy: For the prophylaxis and therapy of cytostatic-induced vomiting, on the day before planned cytostatic therapy 8 mg orally; at the start of therapy 8-12 mg i.v., then 16-24 mg per day orally for a total of 2 days.
Diagnostic test of the pituitary and adrenal cortex function
Inhibition of the pituitary- and adrenal cortex function: 1‑4 mg daily. The daily dose should be divided in 2‑4 doses throughout the day, and the last is given as late evening dose.
Inhibition test of the pituitary- and adrenal cortex function: Usually a single dose of 2 mg is given at 11‑12 pm and a blood sample is withdrawn at 8 am the following morning.
Renal impairment: No dosage adjustment is necessary in patients with impaired renal function (see also section 5.2).
Hepatic impairment:In patients with severe liver disease dose adjustment may be necessary (see also section 5.2).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Systemic fungal infections
4.4 Special warnings and precautions for use
The patient should be informed that the dose should be increased at fever and stress.
Discontinuation of the dose should be done gradually after long-term treatment. Since the use of corticosteroids suppresses the endogenous secretion of corticotrophin (ACTH) by the anterior pituitary resulting in adrenal cortex atrophy, sudden withdrawal may precipitate acute adrenocortical insufficiency. Therefore, especially after high-dose or prolonged therapy, corticosteroids should only be withdrawn with tapering the dose.
Infections and vaccinations
Extreme caution should be taken at infections and causal treatment should be initiated.
Corticosteroids in high doses may interfere with active immunization. If vaccination with living vaccine has been done shortly before initiation of dexamethasone treatment the administration of dexamethasone should be done under close monitoring. Living vaccine should not be administered during and after dexamethasone therapy.
The use of dexamethasone in active tuberculosis should be restricted to the case of fulminating or disseminated tuberculosis in which corticosteroids are administered in conjunction with a suitable anti-tuberculosis regime. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity close observation is necessary due to the risk of reactivation of the disease. With long-term corticosteroid therapy, these patients should receive prophylaxis with antibiotics.
Children
Growth and development must be carefully monitored in children since corticosteroids may give rise to early closing of the epiphyses.
Diabetes
Increased insulin dose for diabetic patients may be necessary at treatment with corticosteroids.
Cerebral edema or increased intracranial pressure
Corticosteroids should not be used in conjunction with a head injury or stroke since they will probably not be of benefit or may even do harm.
Gastrointestinal diseases
Steroidsshould be usedwith cautionincasesofnonspecificulcerative colitis ifthere could beperforation, abscess orother pyogenicinfection, diverticulitis, intestinal anastomoses, active or latent peptic ulcer. Signs of peritonealirritationfollowinggastrointestinal perforation inpatientsreceivinglarge doses ofcorticosteroids may be minimal or nonexistent.
Ocular diseases
Prolongeduse of corticosteroidsmay causeposteriorsubcapsularcataracts, glaucomawithpossible damage to theopticnerveandcanincrease the risk of secondaryocular infections due to fungiorviruses.
Corticosteroids should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.
Osteoporosis
Corticosteroids should be used cautiously in patients with osteoporosis as corticosteroids have a negative effect on the calcium balance.
Potassium balance and potassium depleting diuretics
Average andlarge dosesofcortisoneorhydrocortisonecan causeelevation of blood pressure, saltand water retention, and increased excretion ofpotassium. It is less likelytooccur withsynthetic derivativesexcept whenusedin large doses.Saltpoordietandpotassiumsupplementation may be necessary. All corticosteroidsincrease the excretion ofcalcium.
Whencorticosteroidsadministered concomitantly withpotassium-depletingdiuretics, patients should be observed carefully for the developmentofhypokalemia.
Myocardial rupture after recent myocardial infarction
According toliteraturereports, there is an obvious link between the useofcorticosteroidsandleft ventricularfreewallruptureafter a recentmyocardialinfarction. Treatment withcorticosteroidsshould be used with great caution in these patients.
Salicylates
Caution should be taken at concomitant use of salicylates, especially in patients with hypoprothrombinaemia.
If salicylics are given concomitant with a long-term treatment with corticosteroids, a reduction of the corticosteroids should be performed with great caution since otherwise there is a risk of salicylate intoxication.
Patients should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (see section 4.8).
Corticosteroids should be used cautiously in patients with cardiac failure, renal insufficiency, hypertension and migraine, as corticosteroids may cause fluid retention.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
The following combinations with Dexametason Abcur may require dose adjustment;
Phenobarbital, phenytoin, carbamazepine:
Phenobarbital (which is also a metabolite of primidone), phenytoin and carbamazepine alone and in combination induce the metabolism of hydrocortisone, prednisolone, and methylprednisolone (shown in children with asthma) with increased dosage requirements as a result. The interaction is likely for the whole group glucocorticoids. Phenytoin induces the metabolism of dexamethasone and thereby makes the dexamethasone test unreliable. At the same time dexamethasone induces the metabolism of phenytoin with decreased plasma levels as a result.
Itraconazole
Itraconazole decreases the clearance of dexamethasone administered intravenously by 68% by inhibiting CYP 3A4.
Rifampicin
Rifampicin induces the microsomal oxidation of glucocorticoids (hydrocortisone, prednisolone, methylprednisolone) This leads to an increased need of steroids during treatment with rifampicin and a decreased need of steroids after such a treatment.
Primidone
Dexametason Abcur also interacts with primidone which may give rise to a decreased effect of dexamethasone.
Salicylics
Corticosteroids increase the clearance of salicylates which gives a reduction of the plasma clearance. If salicylics are given concomitant with a long-term treatment with corticosteroids the risk of gastrointestinal hemorrhage is increased.
4.6 Fertility, pregnancy and lactation
Fertility:
Steroids may increase or decrease motility and number of spermatozoa in some patients.
Pregnancy
In animal studies, corticosteroids have been shown to cause malformations of various kinds (cleft palate, skeleton malformations), the relevance of these effects in humans is unknown. Reduced placenta- and birth weight have been verified after long-term treatment in humans and animals.
Furthermore there is a risk of adrenal cortex suppression in the newborn child at long-term treatment. A tapered substitution therapy of the newborn may become necessary.Corticosteroids should therefore be given during pregnancy only after specially consideration.
Breastfeeding
Dexamethasoneis excreted in human milk to such an extent that effects on the breastfed newborns/infants are likely.
4.7 Effects on ability to drive and use machines
Dexametason Abcur has no or negligible influence on the ability to drive and use machines.
Undesirable effects
For this medicinal product there is no modern clinical documentation which can act as base for assessment of the frequency of the undesirable effects. Apart from substitution therapy, treatment with corticosteroids always means an overdose in comparison to the physiological condition. Undesired effects of pharmacological doses of corticosteroids are a natural consequence of the pronounced corticoid effect. Unfavorable effects depend on the dose, dosing interval, treatment duration and individual sensitivity.
The undesirable effects are presented within each frequency interval after descending seriousity with the use of the following categories: very common (1/10); common (1/100, <1/10); uncommon (1/1 000, <1/100), rare (1/10 000, <1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data)
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System Organ Class |
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Infections and infestations |
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Common: |
Increased susceptibility to infections. |
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Endocrine disorders |
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Common: |
Adrenal suppression, Cushing-like symptoms, growth retardation in children, Diabetes mellitus |
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Not known: |
Menstrual disorders |
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Metabolism and nutrition disorders |
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Common: |
Negative nitrogen balance. |
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Uncommon: |
Hypokalemia, sodium retention. |
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Not known: |
Fluid retention, hypokalemic alkalosis, decreased carbohydrate tolerance |
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Psychiatric disorders |
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Uncommon: |
Psychiatric disorders ranging from euphoria, insomnia, mood changes, depression to psychosis. |
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Nervous system disorders |
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Rare: |
Increased intracranial pressure. |
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Not known: |
Cramps, vertigo, headache |
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Eye disorders |
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Uncommon: |
Increased intraocular pressure, glaucoma, posterior cataract, exophthalmia. |
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Cardiac disorders |
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Uncommon: |
Cardiac decompensation, hypertension. |
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Not known: |
Myocardial rupture following recent myocardial infarction |
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Vascular disorders |
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Uncommon: |
Thrombosis. |
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Not known: |
Thromboembolism |
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Gastrointestinal disorders |
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Uncommon: |
Gastrointestinal disorders such as nausea, peptic ulcer. |
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Not known: |
Haemorrhagic perforation of the intestine, ulcerative esophagitis, pancreatitis, abdominal distension. |
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Skin and subcutaneous tissue disorders |
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Common: |
Acne, hirsutism. |
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Uncommon: |
Skin atrophy, impaired wound healing, suppression of skin tests, skin reactions such as allergic dermatitis, urticaria, angioneurotic edema. |
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Not known: |
Petechiae, erythema, ecchymoses, hyperhidrosis |
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Musculoskeletal and connective tissue disorders |
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Common: |
Muscle atrophy, osteoporosis. |
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Rare: |
Aseptic necrosis of bone, tendon rupture. |
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Not known: |
Proximal myopathy, vertebral and longbone fractures |
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General disorders and administration site conditions |
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Uncommon: |
Hypersensibility reactions, oedema, increased appetite, weight increase |
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Not known: |
Malaise |
The incidence of predictable undesirable effects, including hypothalamic-pituitary adrenal suppression (causing inhibition of ACTH and cortisol), correlates with the duration of treatment, dosage and timing of administration.
Diabetes mellitus may be worsened and latent diabetes become manifest.
The infection defense may be inhibited and thereby the disposition for infection increases. Infections may be activated e.g. tuberculosis.
4.9 Overdose
Toxicity and symptom: Acute toxicity, even with very high doses, does generally not give clinical problems. An acute overdose may possibly aggravate pre-existing disease conditions such as ulcus, electrolyte disturbances, infections and oedema. Most reactions are neuropsychiatric, but seizures and anaphylaxis have been observed. Repeated large doses of methylprednisolone have given liver necrosis and increase of amylase. Bradyarrhythmias, ventricular arrhythmias and cardiac arrest were observed at intravenous adminstration of large doses of methylprednisolon and dexamethasone.
Treatment: Is not generally required. Gastric lavage and medical coal can be given if needed, moreover symptomatic treatment.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Glukokortikoid, ATC code: H02AB02
Dexametason Abcur contains dexamethasone, a synthetic corticosteroid with mainly a glucocorticoid effect. The substance has an anti-allergenic, anti-inflammatory and immunosuppressive effect.
The following equivalents facilitate changing to dexamethasone from other glucocorticoids:
Milligram for milligram, dexamethasone is approximately equivalent to betamethasone, 4 to 6 times more potent than methylprednisolone and triamcinolone, 6 to 8 times more potent than prednisone and prednisolone, 25 to 30 times more potent than hydrocortisone, and about 35 times more potent than cortisone.
. The effect on the electrolyte balance is insignificant with practically no sodium- or fluid retention. The pituitary inhibiting effect is high.
5.2 Pharmacokinetic properties
Absorption
Dexamethasone is rapidly and to a large extent absorbed from the gastrointestinal region (80%). The maximum plasma concentration is reached after 1-2 hours.
Distribution
Dexamethasone is bound to plasma proteins to 77%, mainly to albumin. The distribution volume is approx. 0.75 l/kg.
Elimination
The plasma elimination half-life of dexamethasone is 3.5-4.5 hours. The half-life for the anti‑inflammatory effect is 36-54 hours. Dexamethasone is metabolised mainly in the liver but also in the kidney. Dexamethasone and its metabolites are excreted in the urine. After oral administration approx. 30% of the total dose is excreted in the urine as unchanged dexamethasone.
In patients with liver disease the clearance for dexamethasone is decreased due to a decreasedmetabolism in the liver, on the other hand the clearance is increased in patients with kidney failure due to an accelerated metabolism.
5.3 Preclinical safety data
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6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate
Microcrystalline cellulose
Croscarmellose sodium
Magnesium stearate.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions
Nature and contents of container
PVC/PVDC/Al blisters containing 20, 28, 30, 50, 56, 60, 98 or 100 tablets.
Unit dose PVC/PVDC/Al blisters packs containing 20x1, 28x1, 30x1, 50x1, 56x1, 60x1, 98x1 or 100x1 tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
Abcur AB
P.O. Box 1452
251 14 Helsingborg
Sweden
8. MARKETING AUTHORISATION NUMBER(S)
<[To be completed nationally]>
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
2013-03-21
10. DATE OF REVISION OF THE TEXT
2015-03-06
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