Dexamethasone solution for ин. 4 mg / 1 ml No. 10
Producer: CJSC Lekhim-Kharkiv Ukraine
Code of automatic telephone exchange: H02A B02
Release form: Liquid dosage forms. Solution for injections.
General characteristics. Structure:
Active ingredient: sodium dexamethasone phosphate;
1 ml of solution contains 4 mg of dexamethasone of sodium of phosphate in terms of dry matter; excipients: propylene glycol, glycerin, dinatrium эдетат, phosphatic buffered solution рН 7,5, methylparahydroxybenzoate (Е 218), propilparagidroksibenzo-at (Е 216), water for injections. Main physical and chemical properties: transparent colourless liquid.
Pharmacodynamics. Dexamethasone – synthetic glucocorticoid drug which structure of a molecule includes fluorine atom. Has expressed antiinflammatory, antiallergic and desensibilizing, antishock and an immunodepressive effect. Slightly detains sodium and water in an organism.
The main influence on a metabolism connected with a protein catabolism, increase in a gluconeogenesis in a liver and decrease in utilization of glucose peripheral fabrics.
Dexamethasone oppresses synthesis and secretion of AKTG and for the second time - synthesis endogenous
glucocorticoids. Feature of effect of drug is lack of mineralkor-tikoidny activity.
Pharmacokinetics. Dexamethasone is a glucocorticoid of long action.
Bioavailability - more than 90%.
Plasma elimination half-life - about 3 - 4,5 hours.
The period of biological semi-removal - 36 - 72 hours.
Linkng with proteins of plasma - to 80%.
In liquor the maximum concentration of dexamethasone are found in 4 hours after intravenous administration (about 15-20% of concentration in plasma). Decrease
concentration of dexamethasone in liquor occurs very slowly (about 2/3 from
the maximum concentration can be found even in 24 hours).
Dexamethasone is metabolized in a liver much more slowly, than cortisol, forming in
small amount 6-gidroksi-and 20 dihydroxymetazones. Nearly 80% of the entered dose
it is removed by kidneys, it is preferential in the form of a glucuronide, within 24 hours.
Indications to use:
Treatment of the diseases which are giving in to system treatment by glucocorticoids (if necessary as additional treatment to the basic) if topical treatment or oral administration is impossible or is inefficient:
Shock of various genesis (anaphylactic, posttraumatic, post-operational, cardiogenic).
Brain hypostasis (at a tumoral disease, a craniocereberal injury, neurosurgical intervention, a hematencephalon, encephalitis, meningitis, radiation injury).
General diseases of connecting fabric.
Allergic diseases (allergic rhinitis, bronchial asthma, a small tortoiseshell, acute anaphylactic reaction on medicines).
Diseases of respiratory tract (pneumosclerosis).
Inflammatory diseases of intestines (ulcer ileitis / colitis).
Some diseases of kidneys (nephrotic syndrome).
Acute heavy dermatosis (pemphigus usual, erythrosis).
Blood diseases (immunohemolitic anemia, Werlhof's disease).
Replacement therapy: primary nadpochechnozhelezny insufficiency (Addison's disease); insufficiency of a front share of a hypophysis (Shikhen's syndrome); adrenogenital syndrome.
Route of administration and doses:
Doses define individually, depending on a disease of the specific patient, the provided period of treatment, portability of kortikoid and reaction of an organism.
Solution for injections can be appointed intravenously (by means of an injection or infusion from 5% solution of glucose or 0,9% chloride sodium solution), intramusculary or locally (by means of an intra joint injection or an injection to the place of defeat on skin or in infiltrate in soft tissues). It is necessary to remember that at intra joint introduction the drug cannot be administered in the labile and infected joints, unstable joints (owing to arthritis, a necrosis), the deformed joints (narrowing of a joint crack, an anchylosis). It is necessary to remember that at intra joint introduction, except local effects (antiinflammatory, antiallergic, anti-exudative action), accession of system effects (immunodepressive and anti-proliferative effect) is possible.
The recommended average initial daily dose for intravenous or intramuscular administration changes from 0,5 to 9 mg a day, if necessary the dose is increased. Initial doses of drug should be applied before emergence of clinical reaction, and then gradually to reduce a dose to an effective dose lowest clinically. If at use of dexamethasone it was not reached clinical reaction, then administration of drug needs to be stopped and passed to other glucocorticosteroids. At purpose of high doses within several days drug is sharply not cancelled, and gradually reduce a dose for several next days or more long period.
For intra joint introduction doses from 0,4 mg to 4 mg are recommended. The dose depends on the size of the affected joint. Usually 2-4 mg enter into big joints and 0,8-1 mg – in small. Use frequency usually fluctuates from one introduction in 3-5 days to one introduction to 2-3 weeks. Frequent intra joint introduction can injure a joint cartilage. The intra joint injection can be done at the same time no more than in 2 joints.
The dose of the dexamethasone entered into a synovial bag usually makes 2-3 mg, the dose entered into a cover of sinews makes 0,4-1 mg, the dose entered in a ganglion - from 1 to 2 mg.
The dexamethasone dose entered into the place of defeat is equated to an intra joint dose. It is possible to enter dexamethasone in parallel no more, than into two places of defeat.
Doses from 2 to 6 mg of dexamethasone are recommended for introduction to soft tissues (about a joint).
For treatment of wet brain – 10 mg intravenously at the first introduction, further on 4 mg intramusculary once for 6 hours before disappearance of symptoms. The dose can be reduced in 2-4 days with gradual cancellation within 5-7 days after elimination of wet brain. At achievement of therapeutic effect it is recommended to pass from parenteral administration to oral administration of drug.
For treatment of shock – intravenously 20 mg at the first introduction, then 3 mg/kg in 24 hours in the form of continuous intravenous infusion or 2-6 mg/kg in the form of one intravenous injection, or 40 mg are initial, then repeatedly intravenously to an injection there are each 4-6 hours while shock symptoms are observed. Also perhaps intravenous single administration of 1 mg/kg. Therapy of shock needs to be cancelled as soon as the condition of the patient is stabilized, usually treatment to last no more than 2-3 days.
At allergic diseases – intramusculary 4-8 mg at the first introduction. Further treatment is carried out by peroral medicines.
Doses for children. The recommended dose at replacement therapy makes 0,02 mg/kg of body weight or 0,67 mg/sq.m of surface area of a body a day in three injections. At all other indications the range of initial doses makes 0,02-0,3 mg/kg/days in 3-4 injections (0,6-9,0 mg/sq.m of surface area bodies/days).
The dose of 0,75 mg of dexamethasone is equivalent to a dose of 4 mg of Methylprednisolonum and Triamcinolonum, either 5 mg of Prednisolonum, or 20 mg of a hydrocortisone, or 25 mg of a cortisone, or 0,75 mg of betamethasone.
Side reactions. From endocrine system: increase in appetite, increase in body weight, steroid diabetes, decrease in tolerance to carbohydrates, a hyperglycemia, oppression гипоталамо - pituitary and epinephral system, disturbance of secretion of sex hormones (disturbance of a menstrual cycle, an amenorrhea, a hirsutism, impotence), premature epiphyseal closing, a growth inhibition at newborns, children and teenagers, cortical paralysis at premature babies, Itsenka-Cushing's syndrome;
from immune system: increase in risk of emergence or an exacerbation of fungal, viral or bacterial infections, reduction of an immune response, development of opportunistic infections, decrease in reactivity to inoculations and skin tests, the slowed-down healing of wounds, regress of an adenoid tissue, a leukocytosis;
from the central nervous system: dizziness, a headache, affective disturbances (irritability, euphoria, a depression, lability of mood, suicide thoughts), psychotic reactions (including a mania, hallucinations, psychoses and an exacerbation of schizophrenia), alarm, sleep disorders, познавательня dysfunction, including confusion of consciousness and amnesia, and also neuritis, neuropathy, paresthesia, a hyperkinesia, spasms. Drug can cause paralysis of a cerebral cortex in children. Drug can cause physical dependence;
from the alimentary system: dyspepsia, nausea, vomiting, distention of a stomach, a round ulcer with numerical perforation and hemorrhages, perforation of small and big intestines, an ulcer esophagitis, hemorrhagic pancreatitis, an atony of a digestive tract, candidiasis;
from a liver and bilious ways: increase in levels of enzymes of a liver, hepatomegalia;
from a metabolism: delay of sodium and water, increase in release of potassium, gipokaliyemichesky alkalosis, negative nitrogenous balance;
from a storna of organs of sight: increase in intraocular pressure, glaucoma, papilloedema, back subcapsular cataract, thinning of a cornea or sclera, exophthalmos, retinopathy, aggravation of ophthalmologic viral or fungus diseases, retrolental fibroplasia;
from cardiovascular system: синкопэ, bradycardia, tachycardia, a stenocardia attack, increase in heart sizes, a rupture of a myocardium as a myocardial infarction complication, polytropic ventricular premature ventricular contraction, hypostases, arterial hypertension, increase in intracranial and intraocular pressure, congestive heart failure;
from system of blood: purpura, eosinophilia, thrombocytopenia, netrombotsitope-nichesky purpura, increase in risk of a thrombogenesis, thrombophlebitis;
from system of a respiratory organs: fluid lungs, thromboembolism, bronchospasm;
dermatological reactions: the increased sweating, eels, oppression of regenerative and reparative functions of skin, thinning of skin, an erythema, petechias, extensions, a skin atrophy, an ecchymoma, a teleangiectasia, hyper - and a hypoxanthopathy, sterile abscess, disturbance of distribution of hypodermic cellulose;
reactions in an injection site: reddening and a pricking of skin, painless destruction of a joint which symptomatic reminds a neurogenic arthropathy (Sharko's joint);
from a musculoskeletal system: osteoporosis, fractures of tubular bones or ridges, avaskulyarny osteonecrosis, ruptures of sinews, weakness of muscles, atrophy of muscles, proximal myopathy;
allergic reactions: hypersensitivity reactions, Quincke's disease, small tortoiseshell, allergic dermatitis, acute anaphylaxis.
Signs of a withdrawal of glucocorticoids.
At patients who a long time were treated by dexamethasone during too bystry dose decline the withdrawal can be observed and thereof to be observed cases of insufficiency of epinephral glands, arterial hypotension or a lethal outcome.
In certain cases signs of a withdrawal can be similar to signs of deterioration or a recurrence of a disease for which the patient was treated.
If there are heavy undesirable reactions, treatment should be stopped.
Features of use:
Use during pregnancy or feeding by a breast.
To apply during pregnancy, especially in the first trimester, it is possible only according to vital indications.
Breastfeeding during treatment by drug is not allowed.
Children. To children appoint drug only on absolute measures, intramusculary on 0,01 - 0,02 mg/kg each 12 - 24 hours. During treatment by dexamethasone careful supervision of growth and development of children is necessary.
Features of use. During parenteral treatment by corticosteroids in single cases hypersensitivity reactions therefore it is necessary to take appropriate measures prior to treatment by dexamethasone can be observed, considering an opportunity (especially at patients with allergic reactions to any other drugs in the anamnesis) allergic reactions.
At patients who a long time are treated by dexamethasone at the termination of treatment the withdrawal (without visible signs of insufficiency of epinephral glands) from symptoms can be observed: the increased temperature, cold, reddening of a conjunctiva, a headache, dizziness, drowsiness or irritability, muscle and joints pain, vomiting, decrease in body weight, the general weakness, convulsions. In this connection the dose of dexamethasone should be reduced gradually. The sudden termination of reception can have a lethal outcome.
If the patient is in a condition of an unusual stress (because of an injury, operation or a serious illness) during therapy or during the therapy termination by dexamethasone, a dose it is necessary to increase or use a hydrocortisone or a cortisone.
To patients who applied dexamethasone a long time and have a heavy stress after the therapy termination, it is necessary to update dexamethasone reception as the caused insufficiency of epinephral glands can proceed within several months after the treatment termination.
Treatment by dexamethasone or natural glucocorticosteroids can hide symptoms of the existing or new infection, and also symptoms of intestinal perforation.
Dexamethasone can cause an exacerbation of a system fungal infection, a latent amebiasis and a pulmonary tuberculosis.
Patients with a pulmonary tuberculosis in an active form have to receive dexamethasone (together with means against tuberculosis) only at the fast-proceeding or disseminated pulmonary tuberculosis. Patients with an inactive form of a pulmonary tuberculosis who are treated by dexamethasone or patients who react to tuberculine have to receive chemical and prophylactics.
Care and medical observation are recommended to patients for osteoporosis, an arterial hypertension, heart failure, tuberculosis, glaucoma, a liver or renal failure, a diabetes mellitus, an active round ulcer, a recent intestinal anastomosis, colitis and epilepsy. Special leaving is required to patients within the first weeks after a myocardial infarction, patients with a thromboembolism, a heavy myasthenia, a hypothyroidism, psychosis or a psychoneurosis, and also patients of advanced age.
During treatment by dexamethasone the aggravation of a diabetes mellitus or transition from a latent phase before clinical displays of diabetes can be observed.
At prolonged treatment by dexamethasone it is necessary to control potassium level in blood serum.
Vaccination by a live vaccine is contraindicated during treatment by dexamethasone. Vaccination by a lifeless virus or bacterial vaccine does not lead to the expected development of antibodies and does not give the expected protective effect.
Dexamethasone is not appointed in 8 weeks prior to vaccination and does not begin to be appointed earlier, than in 2 weeks after vaccination.
Patients who a long time are treated by high doses of dexamethasone and never had measles, have to avoid contact with the infected persons; at accidental contact preventive treatment by immunoglobulin is recommended.
It is recommended to be careful to patients who recover after operation or a fracture of bones as dexamethasone can slow down healing of wounds and an osteogenesis.
Action of glucocorticosteroids amplifies at patients with cirrhosis or a hypothyroidism.
Intra joint purpose of dexamethasone can result in local or system effects. Frequent use can cause damage of a cartilage or a necrosis of a bone.
Before intra joint introduction it is necessary to remove synovial fluid from a joint and to investigate it (to check for existence of an infection). It is necessary to avoid introduction of corticosteroids to the infected joints. If the infection of a joint develops after an injection, it is necessary to begin appropriate therapy with antibiotics.
Patients need to avoid an exercise stress on the affected joints until the inflammation is cured.
It is necessary to avoid administration of dexamethasone in unstable joints.
Kortikoida can break results of allergic cutaneous tests.
Children and teenagers can be treated dexamethasone only in case of explicit need. During treatment by dexamethasone careful observation of growth and development of children and teenagers is necessary.
Patients with disturbance of water and electrolytic balance have to be careful at dexamethasone reception because averages and high doses of glucocorticosteroids can cause in an organism a delay of salt and water, and also the raised potassium excretion. In these cases restriction of the use of salt and additional reception of potassium is shown. All corticosteroids increase calcium removal process owing to what secretion of mineralkortikoid can be broken. Therefore additional purpose of salt and/or mineralkortikoid is shown. At cancellation of long therapy by corticosteroids the possible development of a withdrawal which is followed by increase in body temperature, muscle and joints pains, a febricula. These symptoms can appear also at patients without signs of insufficiency of bark of epinephral glands.
Immunization by live vaccines is contraindicated to persons who apply immunosuppressive doses of corticosteroids. In cases of immunization of such patients with the inactivated virus or bacterial vaccines reaction of antibodies of blood serum can be reduced.
At active forms of tuberculosis use of dexamethasone should be limited to cases of the fulminant or disseminated disease forms at which corticosteroids are used in parallel with specific therapy.
Patients with latent forms of tuberculosis or positive tuberkulinovy reactions to which corticosteroids are shown have to be under constant observation of the doctor for avoidance of emergence of a recurrence.
It is necessary to appoint corticosteroids with care the patient with bubbly we deprive of eyes (herpes simplex) because their use can lead to perforation of a cornea. Long reception of corticosteroids can lead to development of a back subkapsullyarny cataract, glaucoma, with possible injury of an optic nerve, and also to increase risk of consecutive viral or fungal eye infections.
Drug is contraindicated to patients at whom at intra joint introduction of corticosteroids the pain which is followed by a swelling and further restriction of mobility of a joint, fever and a febricula considerably amplified (these symptoms demonstrate developing of septic arthritis). In case of development of septic arthritis and at confirmation of the diagnosis sepsis it is necessary to appoint the corresponding antibacterial therapy. It is necessary to avoid introduction of corticosteroids directly in the infection center. It is necessary to investigate carefully any intra joint liquid for an exception of septic process. Corticosteroids cannot be entered into labile joints. Frequent intra joint injections can injure joint tissues. Excessive loads of the injured joints before total disappearance of inflammatory process, even are contraindicated to patients at approach of symptomatic improvement.
Drug with care is appointed by the infectious patient, especially with chicken pox and measles because these diseases at use of dexamethasone pass in more severe form. Therefore to persons who had no these diseases,
it is necessary to be careful as much as possible to exclude infection. In case of contact with patients it is necessary to see a doctor at once.
Ability to influence speed of response at control of motor transport or work with other mechanisms. There are no data.
Interaction with other medicines:
Parallel use of dexamethasone and non-steroidal anti-inflammatory drugs increases risk of gastrointestinal bleeding and formation of ulcers.
Efficiency of dexamethasone decreases if in parallel to accept rifampicin, carbamazepine, Phenobarbitonum, Phenytoinum (diphenylhydantoin), Primidonum, ephedrine or аминоглутетимид therefore the dexamethasone dose in such combinations needs to be increased.
Combined use of dexamethasone and the drugs inhibiting CYP 3A4 fermental activity such as кетоконазол, antibiotics macroleads, increase in concentration of dexamethasone in serum and a blood plasma can cause.
Dexamethasone is the moderate inductor CYP 3A4. Combined use with drugs which are metabolized by CYP 3A4, such as индинавир, erythromycin, can increase their clearance.
Ketokonazol can oppress epinephral synthesis of glucocorticoids. Thus, owing to decrease in concentration of dexamethasone epinephral insufficiency can be observed.
Dexamethasone reduces therapeutic effect of medicines against a diabetes mellitus, an arterial hypertension, coumarinic anticoagulants, a prazikvantel and natriuretics (therefore the dose of these medicines should be increased).
Dexamethasone increases activity of heparin, albendazole and kaliyuretik (the dose of these medicines should be reduced in case of need).
Dexamethasone can change effect of coumarinic anticoagulants, therefore when using such combination of medicines the thicket should check a prothrombin time.
Parallel use of dexamethasone and high doses of glucocorticosteroids or agonists β2-адренорецепторов increases risk of a hypopotassemia. At patients with a hypopotassemia cardiac glycosides more promote disturbance of a rhythm and have big toxicity.
Glucocorticosteroids strengthen renal clearance of salicylates therefore it is sometimes heavy to receive therapeutic concentration of salicylates in blood serum. It is necessary to show care to patients who gradually reduce a corticosteroid dose as at the same time increase in concentration of salicylates in serum and intoxication can be observed.
If oral contraceptives are in parallel applied, time of semi-removal of glucocorticoids can increase that will strengthen their biological effect and can increase risk of side effects.
Simultaneous use of a ritordin and dexamethasone contraindicated as it can lead to a fluid lungs. It was reported about a lethal outcome of the woman in labor during childbirth because of development of such state.
Simultaneous use of dexamethasone and thalidomide can cause a toxic epidermal necrolysis.
At simultaneous use of dexamethasone with Amphotericinum In and drugs which bring potassium out of an organism (diuretics) the hypopotassemia is observed that can lead to heart failure.
Simultaneous use of dexamethasone with antikholinesterazny drugs can result in the expressed weakness at patients with gravis myasthenia.
Holestiramin can increase clearance of creatinine. Simultaneous use of cyclosporine and corticosteroids leads to increase in their activity, at their simultaneous use developing of spasms is possible.
Types of the interactions having therapeutic advantages: parallel purpose of dexamethasone and Metoclopramidum, difengidramin, prochlorperazine or antagonists of receptors 5-HT3 (receptors of serotonin or 5-hydroxy-triptamina, type 3, such as ондансетрон or гранисетрон) are effective for the prevention of nausea and vomiting caused by chemotherapy Cisplatinum, cyclophosphamide, a methotrexate, ftoruratsily.
Drug should not be mixed with other drugs, except the following: 0,9% solution of sodium of chloride or 5% glucose solution.
When mixing dexamethasone with Chlorpromazinum, difengidraminy, doksapramy, doxorubicine, daunorubitsiny, idarubitsiny, hydromorphone, ondansetrony, prochlorperazine, gallium nitrate and Vancomycinum forms a deposit.
About 16% of dexamethasone decay in 2,5% solution of glucose and 0,9% chloride sodium solution with amikacin.
Some medicines, such as lorazepam, have to mix up with dexamethasone in glass bottles, but not in plastic packages (concentration of lorazepam falls to values below of 90% in 3-4 hours of storage in polyvinyl chloride packages at the room temperature).
Some medicines, such as метапаминол, have so-called "incompatibility which develops slowly" - develops within a day when mixing with dexamethasone.
Dexamethasone with glycopyrolat: value рН residual solution equals 6,4 that exceeds the limit of stability range.
Hypersensitivity to medicine components.
Heavy myopathies (except for a myasthenia).
Viral infections (for example, chicken pox, a herpes simplex of eyes, shingles (a viremiya phase), poliomyelitis (except for a bulbarnoentsefalitichesky form).
Lymphadenitis after vaccination of BTsZh.
Closed-angle and open-angle glaucomas.
There are single messages on acute overdose or on a lethal outcome because of acute to overdose.
The overdose arises usually only after several weeks of use of overdoses. The overdose can cause the majority of the undesirable effects specified in the section "Side reactions", first of all Cushing's syndrome.
There is no specific antidote. Treatment of overdose has to be supporting and symptomatic. The hemodialysis is not an effective method of the accelerated removal of dexamethasone and an organism.
Storage conditions. To store in the unavailable to children, protected from light place at a temperature not above 25 °C.
Period of validity - 2 years.
According to the recipe
On 1 ml in ampoules