Dexamethasone phosphate

General characteristics. Structure:

Active ingredient: dexamethasone;

1 ml of solution contains phosphate sodium dexamethasone in terms of dexamethasone phosphate of 4 mg;

excipients: sodium chloride, sodium hydrophosphate dodecahydrate, dinatrium эдетат, water for injections.

Pharmacological properties:

Pharmacodynamics. Dexamethasone – a synthetic adrenal hormone (corticosteroid) having glucocorticoid effect. Has antiinflammatory and immunosuppressive effect, and also influences power metabolism, exchange of glucose and (because of negative feedback) secretion of a factor of activation of a hypothalamus and trophic hormone of an adenohypophysis.

The mechanism of action of glucocorticoids is found still not completely out. Now there is enough messages on the mechanism of action of glucocorticoids on confirmation that they act on cellular level. In cytoplasm of cells there are two well certain systems of receptors. Because of linkng with receptors of glucocorticoids of a kortikoida have antiinflammatory and immunosuppressive effect and regulate glucose exchange, and owing to linkng with receptors of mineralokortikoid they regulate metabolism of sodium, potassium and water and electrolytic balance.

Glucocorticoids are dissolved in lipids and easily get into target cells through a cellular membrane. Linkng of hormone with a receptor leads to change of conformation of the receptor promoting increase in its affinity with DNA. The complex a hormone/receptor gets to a kernel of a cell and contacts the regulating center of molecule DNA which is also called an element of a glucocorticoid response (GRE). The activated receptor tied with GRE or with specific genes regulates a transcription m-RNK which can be increased or reduced. New formed m-RNK it is transported to a ribosome then there is a formation of new proteins. Depending on target cells and processes which happen in cells protein synthesis can be strengthened (for example formation of tyrosinetransaminase in liver cells) or reduced (for example formation of IL-2 in lymphocytes). As receptors of glucocorticoids are in all types of fabrics, it is possible to consider that glucocorticoids affect the majority of cells of an organism.

Pharmacokinetics. After intravenous administration the maximum concentration of dexamethasone of phosphate in a blood plasma are reached everything in 5 minutes, and after intramuscular introduction – in 1 hour. At topical administration in the form of injections in joints or soft tissues absorption happens more slowly. Effect of drugs begins quickly after intravenous administration. At intramuscular introduction the clinical effect is observed in 8 hours after introduction. Drug works a long time: from 17 to 28 days after intramuscular introduction and from 3 days to 3 weeks after topical administration. The biological elimination half-life of dexamethasone makes 24-72 hours. In plasma and synovial fluid dexamethasone phosphate quickly turns into dexamethasone.

In a blood plasma about 77% of dexamethasone contacts proteins, it is preferential with albumine. Only the insignificant amount of dexamethasone contacts other proteins of a blood plasma. Dexamethasone is fat-soluble substance therefore it gets in boundaries - and intracellular space. Has the effect in the central nervous system (a hypothalamus, a hypophysis) by linkng with membrane receptors. In peripheral fabrics communicates and works through cytoplasm receptors. Dexamethasone breaks up in the place of the action, i.e. in a cell. Dexamethasone is metabolized preferential in a liver. A small amount of dexamethasone is metabolized in kidneys and other fabrics. The main way of removal are kidneys.

Pharmaceutical characteristics

 

Main fiziko-himicheskiyesvoystvo: transparent colourless or yellowish color liquid.

Incompatibility.

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, potassium nitrate and Vancomycinum forms a deposit.

About 16% of dexamethasone are dissolved in 2,5% solution of glucose and 0,9% chloride sodium solution with amikacin.

Some medicines, such as lorazepam, it is necessary to mix 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 final solution equally 6,4 that exceeds the limit of stability range.

Indications to use:

Dexamethasone to enter phosphate intravenously or intramusculary in urgent cases, and also because of impossibility of oral administration of drug at the following states.

Endocrine disturbances:

– replacement therapy of primary or secondary (pituitary) insufficiency of adrenal glands (the hydrocortisone or a cortisone are choice drugs; if necessary synthetic analogs can be applied together with mineralokortikoida; in pediatric practice combined use from mineralokortikoida is extremely important);

– acute insufficiency of adrenal glands (the hydrocortisone or a cortisone are choice drugs; there can be necessary a combined use from mineralokortikoida, especially in case of use of synthetic analogs);

– before operations and in cases of serious injuries or diseases at patients with the established adrenal insufficiency or at an uncertain adrenocortical stock;

– the shock resistant to traditional therapy, at the available or suspected insufficiency of adrenal glands;

– inborn adrenal struma;

– not purulent inflammation of a thyroid gland;

– the hypercalcemia caused by cancer defeat.

Rheumatic diseases. As auxiliary therapy for short-term use (for the patient's conclusion from an acute state or at an exacerbation of a disease) at: posttraumatic osteoarthrosis; you sinoviit at an osteoarthrosis; a pseudorheumatism, including a juvenile pseudorheumatism (the low-dose maintenance therapy in certain cases can be required); acute and subacute bursitis; epicondylitis; acute nonspecific tendosinoviit; acute gouty arthritis; psoriasis arthritis; ankylosing spondylitis.

Collagenoses. In the period of an aggravation or in some cases as a maintenance therapy at: to a system lupus erythematosus; acute rheumatic carditis.

Skin diseases: pemphigus; heavy multiformny erythema (Stephens-Johnson's syndrome); exfoliative dermatitis; violent herpetiform dermatitis; heavy seborrheal dermatitis; heavy psoriasis; fungoidny mycosis.

Allergic diseases. Control of the serious or disabling allergic conditions which are not giving in to traditional treatment: bronchial asthma; contact dermatitis; atopic dermatitis; serum disease; chronic or seasonal allergic rhinitis; allergy to drugs; a small tortoiseshell after hemotransfusion; acute noninfectious hypostasis of a throat (drug of the choice Epinephrinum is).

Eye diseases. Heavy acute and chronic allergic and inflammatory processes with damage of eyes: the damage of eyes caused by Herpes zoster; iritis, iridocyclitis; chorioretinitis; diffusion back uveitis and choroiditis; optic neuritis; sympathetic ophthalmia; inflammation of a front segment; allergic conjunctivitis; keratitis; allergic regional helcoma.

Gastrointestinal diseases. For removal of the patient from a critical period at: ulcer colitis (system therapy); diseases Krone (system therapy).

Respiratory diseases: symptomatic sarcoidosis; berylliosis; the focal or disseminated pulmonary tuberculosis (together with the corresponding antitubercular chemotherapy); Lefler's syndrome which is not giving in to therapy by other methods; aspiration pneumonitis.

Hematologic diseases: the acquired (autoimmune) hemolitic anemia; an idiopathic Werlhof's disease at adults (only intravenous administration; intramuscular introduction is contraindicated); secondary thrombocytopenia at adults; eritroblastopeniya (erythrocyte anemia); inborn (erythroidal) hypoplastic anemia.

Oncological diseases: palliative treatment of leukemia and a lymphoma at adults; acute leukemia at children.

The states which are followed by hypostasis: stimulation of a diuresis or reduction of a proteinuria at an idiopathic nephrotic syndrome (without uraemia) and a renal failure at a system lupus erythematosus.

Diagnostic testing of function of adrenal glands.

Wet brain because of primary or metastatic tumor of a brain, a craniotomy or an injury of the head. Use at wet brain does not replace appropriate neurosurgical researches and final appointments, such as neurosurgical intervention and other specific therapy.

Other indications: tubercular meningitis with subarachnoidal blockade or threat of blockade (together with the corresponding antitubercular therapy); a trichinosis with neurologic symptoms or a myocardium trichinosis.

Indications for intra joint introduction or introduction to soft tissues. As auxiliary therapy for short-term use (for the purpose of the patient's conclusion from an acute state or at an exacerbation of a disease) at: pseudorheumatism (heavy inflammation of a separate joint); you sinoviit at an osteoarthritis; acute and subacute bursitis; acute gouty arthritis; epicondylitis; acute nonspecific tendosinoviit; posttraumatic osteoarthritis.

Local introduction (introduction to the place of defeat): keloid defeats; the localized hypertrophic, inflammatory and infiltrative defeats at shingles, psoriasis, a ring-shaped granuloma; diskoidny lupus erythematosus; lipoid atrophic dermatitis of Oppengeym; the localized allopecia.

Perhaps also use at cystous tumors of an aponeurosis or sinews (ganglion).

Route of administration and doses:

To appoint to adults and children since the birth. To enter intravenously (in the form of an injection or infusion), intramusculary or locally – by means of an intra joint injection or an injection into the place of defeat on skin or in infiltrate of soft tissues.

As solvent to apply 0,9% to intravenous infusion solution of sodium of chloride or  5% glucose solution.

The solutions intended for intravenous administration or further dissolution of drug should not contain preservatives if to apply them to babies, especially premature. 

When mixing drug with solvent for infusion it is necessary to observe sterile security measures. As solutions for infusions usually do not contain preservatives, mixes need to be used within 24 hours.

Drugs for parenteral administration should be checked visually for existence of foreign parts and discoloration every time before introduction for definition of suitability of solution and a container.

The dose needs to be defined individually, according to a disease of the specific patient, the provided period of treatment, portability of kortikoid and reaction of an organism.

Intravenous and intramuscular administration

The recommended initial dose changes from 0,5 to 9 mg a day depending on the diagnosis. In less hard cases dosing can sufficient be lower than 0,5 mg while at a serious illness dosing can necessary be higher than 9 mg a day.

Initial doses of Dexamethasone of phosphate need to be applied before emergence of clinical reaction, and then effective needs to reduce a dose gradually to the lowest clinically. If to appoint high doses during the period exceeding several days, the dose needs to be reduced then gradually for several next days or even throughout longer period.

If through the corresponding span satisfactory clinical reaction is not noted, it is necessary to stop injections of dexamethasone and to appoint to the patient other treatment.

It is necessary to watch carefully symptoms which can demand dosing correction, namely – changes of a clinical state as a result of remission or an exacerbation of a disease, individual reaction to drug and influence of a stress (for example surgical intervention, an infection, an injury). During a stress there can be a need for temporary increase in dosing.

If administration of drug needs to be stopped after several days of treatment, as a rule, cancellation it is necessary to carry out gradually.

Shock

There is following dosing of an injection of dexamethasone of phosphate:

– 3 mg/kg of body weight in 24 hours by continuous intravenous infusion after an initial intravenous injection of 20 mg;

– 2-6 mg/kg of body weight in the form of a one-time intravenous injection;

– the initial dose – 40 mg, then repeated intravenous injections is each 4-6 hours while shock symptoms are observed;

– the initial dose – 40 mg, then repeated intravenous injections is each 2-6 hours while shock symptoms are observed;

– 1 mg/kg of body weight in the form of a one-time intravenous injection.

Use of high-dose corticosteroid therapy lasts only before stabilization of a condition of the patient and usually not longer than 48-72 hours.

Wet brain

Dexamethasone phosphate usually it is necessary to appoint in an initial dose 10 mg intravenously, then on 4 mg each 6 hours intramusculary before disappearance of symptoms.

Reaction to treatment should be traced within 12-24 hours, dosing can be reduced after 2-4 days of treatment, gradually to cancel drug within 5-7 days. For palliative use to patients with repeated or nonresectable tumors of a brain there can be effective a maintenance therapy in a dose of 2 mg 2-3 times a day.

Serious allergic illness

At acute allergic diseases which samokupirutsya, or at heavy exacerbations of chronic allergic diseases to appoint Dexamethasone phosphate in the first day on 1 or 2 ml (4 or 8 mg), intramusculary, from the second day to continue treatment by peroral forms of drug.

Local introduction

Or in soft tissues usually to apply intra joint introduction, introduction to the place of defeat in cases when defeat is limited to one or two joints (sites). Dosing and frequency of injections depends on conditions and an injection site. A usual dose – 0,2-6 mg. Use frequency usually fluctuates from one introduction for      3-5 days to one introduction for 2-3 weeks. Frequent intra joint introduction can injure a joint cartilage.

The intra joint injection of corticosteroids can result in system effects in addition to local.

It is necessary to avoid intra joint introduction of corticosteroids to the infected joints.

Corticosteroids should not be entered into unstable joints.

Some of usual single doses are given below:

Place of an injection                                                      Dose of dexamethasone of phosphate (mg)
Big joints (for example knee)                                        2-4
Small joints (for example interphalanx,

temporal and mandibular)                                                        0,8-1
Intermuscular bags                                                                 2-3
Tendinous covers                                                             0,4-1
Infiltration of soft tissues                                                       2-6
Ganglion                                                                                     1-2

Dexamethasone phosphate is especially recommended for use in combination with one of less soluble steroids of long action for intra joint introduction and introduction to soft tissues.

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 for three injections.

At all other indications the range of initial doses makes 0,02-0,3 mg/kg/days for 3-4 injections (0,6-9 mg/sq.m of surface area bodies/days).

For the purpose of comparison equivalent doses in mg for different corticosteroids are included below:

The dose of 0,75 mg of dexamethasone is equivalent to a dose of 2 mg a parametazone or 4 mg of Methylprednisolonum and Triamcinolonum, or 5 mg of Prednisonum and Prednisolonum, either 20 mg of a hydrocortisone, or 25 mg of a cortisone, or 0,75 mg of betamethasone.

Such ratios of dosing belong only to oral or intravenous administration of these drugs. When these drugs or their derivatives are entered intramusculary or vnutrisustavno, their relative properties can change considerably.

Features of use:

Use during pregnancy or feeding by a breast

The harmful effect on a fruit and the newborn cannot be excluded. Medicine oppresses pre-natal development of the child. Pregnant women can appoint dexamethasone only in isolated urgent cases when the expected advantage for mother exceeds potential risk for a fruit. Extra care is recommended at an eclampsia. According to the general recommendations at treatment during pregnancy by glucocorticosteroids the maximum operating dose for control of a basic disease has to be used. The children born by mothers to whom appointed glucocorticoids during pregnancy it is necessary to check for existence of insufficiency of adrenal glands carefully.

Glucocorticoids pass through a placenta and reach high concentration in a fruit. Dexamethasone is less actively metabolized in a placenta, than for example Prednisonum, proceeding from it in blood serum of a germ high concentration of dexamethasone can be observed. According to some information, even pharmacological doses of glucocorticoids can increase risk of insufficiency of a placenta, oligogidramnion, bradygenesis of a fruit or its intrauterine death, increase in quantity of leukocytes (neutrophils) at a fruit and insufficiency of adrenal glands. There are no proofs confirming teratogenic action of glucocorticosteroids.

It is recommended to apply additional doses of glucocorticosteroids at the time of delivery to the women accepting glucocorticosteroids during pregnancy. In case of long childbirth or planning of kesarevy section intravenous administration of 100 mg of a hydrocortisone is recommended each 8 hours.

Small amounts of glucocorticoids find in breast milk therefore mothers who are treated by dexamethasone are not recommended to nurse, especially at its reception over physiological norms (about 1 mg). It can lead to delay of growth of the child and reduction of secretion of endogenous corticosteroids.

Children

To apply to children since the birth only in urgent cases. During treatment by dexamethasone careful observation of growth and development of children is necessary.

During parenteral treatment of a kortikoidama hypersensitivity reactions therefore it is necessary to take appropriate measures before an initiation of treatment dexamethasone can seldom be observed, considering a possibility of allergic reactions (especially at patients with allergic reactions to any other medicines in the anamnesis).

At patients who a long time are treated by dexamethasone the withdrawal can be observed (also without visible signs of insufficiency of adrenal glands) at the treatment termination (the increased body temperature, cold, reddening of a conjunctiva, a headache, dizziness, drowsiness or irritability, muscle and joints pain, vomiting, a body degrowth, weakness, it is frequent also convulsions). Therefore the dose of dexamethasone should be reduced gradually. The sudden termination of treatment can have lethal effects.

If the patient is in a condition of a heavy stress (because of an injury, operation or a serious illness) throughout therapy, the dose of dexamethasone needs to be increased and if it occurs during the treatment termination, it is necessary to apply a hydrocortisone or a cortisone.

Patients to whom entered dexamethasone a long time and who have a heavy stress after the therapy termination need to recover dexamethasone use as the insufficiency of adrenal glands caused by it can last within several months after the treatment termination.

Treatment by dexamethasone or natural glucocorticoids can disguise symptoms of the existing or new infection, and also symptoms of intestinal perforation. Dexamethasone can aggravate 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 antitubercular drugs) only at the rapid or disseminated pulmonary tuberculosis. Patients with an inactive form of a pulmonary tuberculosis who are treated by dexamethasone or the patients reacting to tuberculine have to receive chemical prophylactics.

Care and medical observation are recommended by sick osteoporosis, with arterial hypertension, heart failure, tuberculosis, glaucoma, a liver or renal failure, a diabetes mellitus, an active round ulcer, a recent intestinal anastomosis, ulcer colitis and epilepsy. Special leaving is demanded by 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 the aggravation of a diabetes mellitus or transition from a latent phase to clinical manifestations of a diabetes mellitus can be observed.

At long treatment it is necessary to control potassium level in blood serum.

Vaccination by a live vaccine is contraindicated during treatment by dexamethasone. Vaccination by the inactivated virus or bacterial vaccine does not lead to the expected synthesis of antibodies and has no the expected protective effect. Dexamethasone phosphate is usually not appointed in 8 weeks prior to vaccination and does not begin to be applied earlier than in 2 weeks after vaccination.

Patients who 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 glucocorticoids amplifies at patients with cirrhosis or a hypothyroidism.

Heavy mental reactions can accompany system use of corticosteroids. Usually symptoms appear in several days or weeks after an initiation of treatment. The risk of development of these symptoms increases at use of high doses. The majority of reactions takes place at reduction of a dose or at drug withdrawal. It is necessary to observe and in time to reveal changes of a mental state, especially depressive mood, suicide thoughts and intentions. With special care it is necessary to apply corticosteroids at patients with affective frustration available or in the anamnesis, also at the immediate family. Emergence of undesirable effects can be prevented applying minimal effective doses during the shortest period or applying a necessary day dose of drug of 1 times in the morning.  

Intra joint use of dexamethasone can result in 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 kortikoid to the infected joints. If the infection of a joint develops after an injection, it is necessary to begin the corresponding therapy with antibiotics.

Patients should report about that they avoided an exercise stress on the affected joints until the inflammation is cured.

It is necessary to avoid administration of drug in unstable joints.

Kortikoida can distort results of skin allergic tests.

Special cautions concerning excipients. Drug contains 1 mmol (23 mg) of sodium on a dose that is very insignificant quantity.
Ability to influence speed of response at control of motor transport or work with other mechanisms

Considering that sensitive patients at use of drug can have side reactions (dizziness, confusion of consciousness, etc.), for use of drug it is necessary to refrain from control of motor transport and performance of other works which demand concentration of attention.

Side effects:

From the hemopoietic and lymphatic systems: thromboembolism cases, reduction of quantity of monocytes and/or lymphocytes, a leukocytosis, an eosinophilia (as well as at use of other glucocorticoids), thrombocytopenia and not Werlhof's disease.

From immune system: hypersensitivity reactions, rash, allergic dermatitis, a small tortoiseshell, a Quincke's disease, a bronchospasm and anaphylactic reactions, reduction of an immune response and increase in a susceptibility to infections.

From heart: polytopic ventricular premature ventricular contraction, paroxysmal bradycardia, heart failure, a cardiac standstill, a cardiorrhesis at the patients who recently had a myocardial infarction.

From vessels: arterial hypertension, hypertensive encephalopathy.

From the central nervous system: after treatment emergence of a papilledema and the increased intracranial pressure is possible (pseudoneoplasm). Also such neurologic side effects as dizziness (вертиго), spasms and a headache, sleep disorders, confusion of consciousness, nervousness, concern can be observed.

Mental disturbances: change of the personality and behavior which are most often shown as euphoria; it was reported also about such side effects: sleeplessness, irritability, hyperkinesia, depression and psychoses, and also maniac-depressive psychosis, delirium, disorientation, hallucinations, paranoia, lability of mood, thought of suicide, deterioration in a course of schizophrenia, amnesia, deterioration in a course of epilepsy.

From endocrine system and metabolism: oppression of function and an atrophy of adrenal glands (reduction of reaction to a stress), Cushing's syndrome, delay of growth at children and teenagers, disturbances of a menstrual cycle, an amenorrhea, a hirsutism, transition of latent diabetes to clinically active form, reduction of tolerance to carbohydrates, increase in appetite and increase in body weight, a gipertriglitseridemiya, obesity, the increased need for insulin or peroral means against diabetes at patients with diabetes, negative nitric balance because of a catabolism of proteins, a gipokaliyemichesky alkalosis, a delay in an organism of sodium and water, the increased potassium loss, a hypocalcemia.

From digestive tract: the esophagitis, dyspepsia, nausea, vomiting, a hiccups, round ulcers of a stomach and duodenum, are possible also ulcer perforation and bleeding in a digestive tract (vomiting with blood impurity, a melena), pancreatitis and perforation of a gall bladder and intestines (especially at patients with a chronic inflammation of intestines).

From a musculoskeletal system and connecting fabric: muscular weakness, a steroid myopathy (muscular weakness serves as the reason of a muscular catabolism), osteoporosis (the increased calcium removal) and compression spinal fractures, fractures of tubular bones, an aseptic osteonecrosis (it is more frequent – an aseptic necrosis of heads of bones of hips and shoulders), ruptures of sinews (especially at parallel use of some hinolon), injury of a joint cartilage and a necrosis of bones (owing to an intra joint infection), premature closing of epiphyseal regions of growth.

From skin and hypodermic fabrics: the slowed-down healing of wounds, an itch, thinning and increase in sensitivity of skin, a striya, petechia and bruises, an acne, a telangiectasia, an erythema, the raised potovydeleniye, oppressed reaction to skin tests.

From organs of sight: the increased intraocular pressure, glaucoma, a cataract or an exophthalmos, thinning of a cornea, an exacerbation of bacterial, fungal or viral infections of eyes.

Infections and invasions: development of opportunistic infections, recurrence of a healed tuberculosis.

From reproductive system: impotence.

General disturbances: hypostasis, hyper - or a hypoxanthopathy, an atrophy of skin or a hypodermic, sterile abscess and erubescence, a tranzitorny burning sensation and tinglings in a crotch at intravenous administration or at introduction of high doses.

The general frustration and frustration in an injection site: at intramuscular introduction of change in an injection site, including hypostasis, burning, numbness, pain, paresthesias and infections in an injection site, seldom a necrosis of surrounding fabrics, formation of hems in the place of injections, an atrophy of skin and hypodermic cellulose, at intramuscular introduction (introduction to a deltoid muscle is especially dangerous).

At intravenous administration: arrhythmias, rushes of blood to the person, spasms.

At intracranial introduction – nasal bleedings.

At intra joint introduction – strengthening of pain in a joint.

Signs of a withdrawal of glucocorticoids

At patients who a long time were treated by dexamethasone during a bystry dose decline the withdrawal and cases of insufficiency of adrenal glands, arterial hypotension or a lethal outcome can be observed.

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 needs to be stopped.

Interaction with other medicines:

Parallel use of dexamethasone and non-steroidal anti-inflammatory drugs increases risk of gastrointestinal bleedings and formation of ulcers.

Efficiency of dexamethasone decreases if at the same time to accept rifampicin, рифамбутин, carbamazepine, Phenobarbitonum, Phenytoinum (diphenylhydantoin), Primidonum, ephedrine or аминоглутетимид therefore the dexamethasone dose in such combinations should be increased.

Interaction between dexamethasone and all above-stated medicines can pervert the test of oppression of dexamethasone. It needs to be considered at assessment of test results.

Dexamethasone reduces therapeutic effect of the antikholinesterazny means applied at a myasthenia.

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 causing decrease in concentration in blood serum.

Ketokonazol can oppress epinephral synthesis of glucocorticoids, thus, owing to decrease in concentration of dexamethasone adrenal insufficiency can develop.

Dexamethasone reduces therapeutic effect of drugs for treatment of a diabetes mellitus, arterial hypertension, coumarinic anticoagulants, a prazikvantel and natriuretics (therefore the dose of these medicines needs to be increased); it increases activity of heparin, albendazole and kaliyuretik (the dose of these drugs needs to be reduced in case of need).

Dexamethasone can change effect of coumarinic anticoagulants therefore at use of such combination of drugs the thicket needs to check a prothrombin time.

Parallel use of dexamethasone and high doses of other glucocorticoids 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.

Antacids reduce absorption of dexamethasone in a stomach. Effect of dexamethasone at a concomitant use with food and alcohol is not investigated, however the simultaneous use of drugs and food with the high content of sodium is not recommended. Smoking does not influence dexamethasone pharmacokinetics.

Glucocorticoids strengthen renal clearance of salicylate therefore it is sometimes heavy to receive therapeutic concentration of salicylates in blood serum. It is necessary to be careful to patients to whom gradually reduce a corticosteroid dose as at the same time increase in concentration of salicylate in blood serum and intoxication can be observed.

If in parallel to apply oral contraceptives, the elimination half-life of glucocorticoids can increase that strengthens their biological effect and can increase risk of side effects.

Simultaneous use of Ritodrinum and dexamethasone contraindicated at the time of delivery as it can lead to a fluid lungs. It was reported about a lethal outcome at the woman in labor because of development of such state.

Simultaneous use of dexamethasone and thalidomide can cause a toxic epidermal necrolysis.

Types of interaction which have therapeutic advantages: parallel purpose of dexamethasone and Metoclopramidum, difengidramid, prochlorperazine or antagonists of retsetor 5-HT3 (receptors of serotonin or a 5-gidroksitriptamin, type 3, such, as ондансетрон or гранисетрон) effective for the prevention of nausea and vomiting caused by chemotherapy Cisplatinum, cyclophosphamide, a methotrexate, ftoruratsily.

Contraindications:

Hypersensitivity to dexamethasone or to any other ingredient of drug.

Acute viral, bacterial or system fungal infections (if appropriate therapy is not applied). Cushing's syndrome. Vaccination by a live vaccine.

Intramuscular introduction is contraindicated to patients with heavy disturbances of a blood coagulation.

Local introduction is contraindicated at bacteremia, system fungal infections, at patients with unstable joints, infections in the place of use, including septic arthritis owing to gonorrhea or tuberculosis.

Overdose:

Very seldom messages on acute overdose or a lethal outcome because of acute overdose arrived.

The overdose, usually only after several weeks of use of overdoses, 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 has to be supporting and symptomatic. The hemodialysis is not an effective method of the accelerated phosphate dexamethasone removal from an organism.

Storage conditions:

Period of validity. 2 years. Not to use drug after the termination of the period of validity specified on packaging. To store at a temperature not above 25 °C. To keep ampoules in an external pack for protection against effect of light. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 1 ml in an ampoule. On 5 or 10 ampoules in a pack.