Solu-Cortef - instructions for use, dose, side effects, contraindications

- 1 bottle contains: active substance: hydrocortisone (in the form of hydrocortisone sodium succinate) 100 mg; Excipients: sodium dihydrogen phosphate monohydrate 0.9 mg, sodium hydrogen phosphate 8.8 mg.

- Solvent composition: benzyl alcohol 18 mg, water for injection q.s. up to 2 ml.

Description:

Lyophilized powder or porous mass of white or almost white color. The solvent is a clear, colorless solution.

The reconstituted solution is a clear slightly opalescent colorless or slightly yellowish solution.

Bottles

Lyophilized powder or porous mass of white or almost white color.

Pharmacotherapeutic group:glucocorticosteroid.

ATX: & nbsp

S.01.B.A.02 Hydrocortisone

H.02.A.B.09 Hydrocortisone

D.07.A.A.02 Hydrocortisone

Pharmacodynamics:

Glucocorticosteroids (GCS), penetrating through cell membranes, form complexes with specific cytoplasmic receptors. Educated complexes penetrate into the nucleus of the cell, where they bind to deoxyribonucleic acid (DNA) (chromatin). Later, these complexes stimulate the transcription of the matrix ribonucleic acid (mRNA) followed by the synthesis of various enzymes, which explains the effect of GCS in systemic application. SCS not only have a significant effect on the inflammatory process and immune response, but also affect carbohydrate, protein and fat metabolism.

The maximum pharmacological activity of GCS is manifested not at the peak concentration - in the plasma, but after it. Thus, the effect of GCS is due primarily to their effect on enzyme activity.

Has anti-inflammatory, anti-shock, desensitizing, antitoxic, anti-allergic, immunosuppressive and antimetabolic action. Unlike cytostatics, immunosuppressive properties are not associated with mitostatic action, but are the result of suppression of different stages of immunogenesis: migration of stem cells (bone marrow), migration of B cells and interaction of T and B lymphocytes.It inhibits the release of cytokines (interleukins and interferon) from lymphocytes and macrophages, inhibits the release of eosinophils mediators of inflammation, reduces the metabolism of arachidonic acid and the synthesis of prostaglandins. Stimulating steroid receptors induces the formation of lipocortin. Promotes the deposition of glycogen in the liver, increases the glucose in the blood, inhibits the excretion of sodium and water ions, enhances the excretion of potassium ions from the body, reduces the synthesis of histamine. Reduces inflammatory cell infiltrates, reduces the migration of leukocytes and lymphocytes to the area of inflammation. In large doses, inhibits the development of lymphoid and connective tissue, including the reticuloendothelial system (RES), reduces the number of mast cells, which are the place of formation of hyaluronic acid; suppresses hyaluronidase and helps reduce the permeability of capillaries. Delays synthesis and accelerates the breakdown of proteins. Influencing the pituitary gland, depresses the production of corticotropin. Prolonged introduction into the body can lead to depression and atrophy of the adrenal cortex, inhibition of the formation of gonadotropic and thyrotropic hormones of the pituitary gland.

Pharmacokinetics:

After intramuscular (IM) administration, the maximum concentration of hydrocortisone in the blood plasma is reached approximately after 30-60 minutes.

Approximately 40 - 90% of hydrocortisone is bound by plasma proteins. Most hydrocortisone binds to one of the globulins (transcortin), and only a small amount - with albumin. A free unbound fraction of the hormone determines its biological activity, and the associated fraction serves as a reserve. The metabolism of hydrocortisone occurs mainly in the liver.

Within 24 hours, the body is excreted in the urine with 22-30% IM or intravenously (IV) administered hydrocortisone. The drug is almost completely eliminated from the body within 12 hours, so to maintain high concentrations of hydrocortisone in the blood, it must be injected / m or IV every 4-6 hours.

Indications:

1. Endocrine diseases.

- Primary or secondary adrenal insufficiency (drugs of choice - hydrocortisone or cortisone; if necessary, their synthetic analogs can be used in combination with mineralocorticoids, especially in pediatric practice).

- Acute adrenal insufficiency (drugs of choice - hydrocortisone or cortisone; there may be a need for simultaneous application of mineralocorticoids).

As symptomatic therapy:

- In the preoperative period, in the case of severe trauma or severe disease, in patients with established or suspected adrenal insufficiency.

- Shock, which can not be treated by conventional methods, when adrenal insufficiency is possible.

- Congenital hyperplasia of the adrenal glands.

- Subacute thyroiditis.

- Hypercalcemia on the background of cancer.

2. Rheumatic diseases (as an additional therapy for a short time to withdraw from the acute condition or during exacerbation).

- Acute and subacute bursitis.

- Acute gouty arthritis.

- Acute nonspecific tenosynovitis.

- Ankylosing spondylitis.

- Epicondylitis.

- Post-traumatic osteoarthritis.

- Psoriatic arthritis.

- Rheumatoid arthritis, including juvenile rheumatoid arthritis (in some cases, maintenance therapy with low doses may be required).

- Synovitis in osteoarthritis.

3. Systemic connective tissue diseases (during an exacerbation or in some cases as a maintenance therapy).

- Acute rheumatic heart disease.

- Systemic dermatomyositis (polymyositis).

- Systemic lupus erythematosus.

4. Skin diseases.

- Herpetiform bullous dermatitis.

- Exfoliative dermatitis.

- Mushroomed mycosis.

- Pemphigus.

- Malignant exudative erythema (Stevens-Johnson syndrome).

- Severe form of psoriasis.

- Severe form of seborrheic dermatitis.

5. Allergic conditions (in the case of severe or disabling conditions, in which conventional therapy is ineffective).

- Acute non-infectious edema of the larynx.

- Atopic dermatitis.

- Asthmatic status.

- Contact dermatitis.

- Reactions of hypersensitivity to medicines.

- Seasonal or all-the-year-round allergic rhinitis.

- Serum sickness.

- Posttransfusion reactions like urticaria.

6. Eye diseases (severe acute and chronic allergic and inflammatory processes with eye damage).

- Allergic conjunctivitis.

- Allergic marginal ulcers of the cornea.

- Inflammation of the anterior segment.

- Chorioretinitis.

- Diffusive posterior uveitis and choroiditis.

- Eye shape Herpes zoster.

- Irit and iridocyclitis.

- Keratitis.

- Optic neuritis.

- Sympathetic ophthalmia.

7. Diseases of the gastrointestinal tract (to remove the patient from the critical state).

- Ulcerative colitis (systemic therapy).

- Regional enteritis (systemic therapy).

8. Diseases of the respiratory tract.

- Aspiration pneumonitis.

- Berylliosis.

- Lightning and disseminated pulmonary tuberculosis in combination with appropriate antituberculous chemotherapy.

- Leffler's syndrome, not amenable to therapy by other means.

- Clinically expressed sarcoidosis.

9. Hematological diseases.

- Acquired (autoimmune) hemolytic anemia.

- Congenital (erythroid) hypoplastic anemia.

- Erythroblastopenia (erythrocyte anemia).

- Idiopathic thrombocytopenic purpura in adults (I / O only; in / m administration is contraindicated).

- Secondary thrombocytopenia in adults.

10. Oncological diseases (as a palliative therapy).

- Acute leukemia in children.

- Leukemia and lymphomas in adults.

11. Edema syndrome.

To stimulate diuresis and achieve remission of proteinuria in patients with nephrotic syndrome without uremia; with nephrotic idiopathic syndrome or with lupus erythematosus.

12. Emergency conditions.

- Shock that developed as a result of adrenal insufficiency, or resistant to standard therapy, with the possible presence of adrenal insufficiency.

- Acute allergic manifestations after the appointment of epinephrine (asthmatic status, anaphylactic reactions, insect bites, etc.).

SCS can be effective in the treatment of hemorrhagic traumatic and surgical shocks, in which standard therapy is ineffective (see section "SPECIAL INSTRUCTIONS"),

13. Other indications for use.

- Trichinosis with damage to the nervous system or myocardium.

- Tuberculous meningitis with a subarachnoid block or with a block threat (in combination with appropriate anti-tuberculosis chemotherapy).

Contraindications:

- Systemic fungal infections.

- Hypersensitivity to any components of the drug in history.

It is not recommended to use the drug in patients with acute and subacute myocardial infarction, since the use of GCS in them can lead to the spread of necrosis, slowing the formation of scar tissue and, consequently, to rupture of the heart muscle.

The drug supplied in two-bottle vials ACT-Q-VIAL, It is not recommended to use in newborns, since the solvent contains benzyl alcohol.

Carefully:

- with eye damage caused by herpes simplex virus, as this can lead to perforation of the cornea;

- with ulcerative colitis, if there is a threat of perforation, abscess or other purulent infection, and also with diverticulitis, with fresh intestinal anastomoses, with active or latent peptic ulcer, renal failure, arterial hypertension, osteoporosis, myasthenia gravis gravis.

Pregnancy and lactation:

In a number of animal studies It is shown that the administration of high doses SCS for pregnant females can lead to the appearance of ugliness in the fetus. Relevant studies action on the reproductive human function was not performed, so the use of these drugs in during pregnancy, during the period of or in women reproductive age requires estimates of probable positive effect of the drug in comparison with potential risk to the mother, embryo or fetus. The GCS follows prescribe for pregnancy only by absolute indications.

SCS easily penetrate the placenta. Children born of mothers, received during pregnancy significant doses of GCS, should carefully screened for adrenal insufficiency. The effect of GCS on the course and outcome of delivery is unknown.

SCS is excreted into breast milk, so when it is necessary to prescribe preparation of SOLU-CORTEIF in the period of Breastfeeding should be discontinued.

In studies on animals against the background of the use of GCS, there was a violation of fertility.

Benzyl alcohol, used as a solvent, penetrates the placenta.

Dosing and Administration:The drug can be administered as an intravenous or intravenous injection or as an intravenous infusion, but in urgent conditions it is preferable to begin treatment with iv injection. At the end of the acute period, parenterally prescribed dosage forms with a longer duration of action or oral forms of the drug are administered. Treatment with the drug begins with iv administration for 30 seconds (eg, 100 mg) and up to 10 minutes (eg, 500 mg or more). High doses of SOLU-CORTEIF® should be prescribed only until the patient's condition stabilizes, but no longer than 48 to 72 hours. The initial dose of the drug is 100 - 500 mg or more, depending on the severity of the patient's condition.

The dose of the drug is repeated every 2, 4 or 6 hours in depending on the response patient's organism and clinical pictures of the disease. Children should introduce lower doses (but not less than 25 mg / day), however, when choosing a dose in first of all take into account the severity condition and reaction of the patient to therapy, not age and body weight.

In patients with liver disease hydrocortisone can intensify. It should be assessed possibility of dose reduction.

Preparation of solutions:

Preparations for parenteral administration should be checked visually for change in color or appearance of particles. Use only transparent solution.

Bottle

For intravenous or intravenous injection, a solution is prepared, adding to the vial (following the rules antiseptics) no more than 2 ml of water for injection or aqueous sodium solution chloride for injection. For IV infusion The solution is first prepared by adding a bottle of no more than 2 ml of water for injection, Further, this solution can be added to 100-1000 ml of a 5% aqueous solution dextrose (or 0.9% sodium solution chloride, or 5% dextrose solution in 0.9 % solution of sodium chloride, if the patient does not need to limit the amount sodium).

Two-bottle ACT-O-VIAL

1. Click on the plastic activator, so that the solvent is transferred to the lower capacity.

2. Gently shake the bottle until while the lyophilisate does not dissolve.

3. Remove the plastic disc, covering the center of the cork.

4. Treat the surface of the cork antiseptic.

5. Pierce the center of the tube with a needle, so that the tip of the needle can be seen. Turn the vial and select with a syringe the required amount of solution.

For intravenous or intravenous injections, further breeding is not required. For IV infusion a solution is prepared as described above, then the resulting solution is added to 100-1000 ml of 5% aqueous solution of dextrose (or 0.9% solution sodium chloride, or 5% solution Dextrose in a 0.9% solution of sodium chloride, if the patient does not need limiting the amount of sodium). If it is desirable to introduce a small volume liquid, you can add 100 - 3000 mg hydrocortisone (in the form of hydrocortisone sodium succinate) to 50 ml of the above solutions. The solutions obtained are stable for 4 hours and can be administered intravenously or via a second dropper.

If the solutions of the preparation are prepared as indicated above, then pH = 7-8, and osmolarity = 0.36 osmol (osmolarity 0.9% sodium chloride solution 0.28 osmol).

Side effects:

Note: listed below side effects are typical for all SCS with parenteral application, and not just for this drug.

Co hand water-electrolyte balance:

sodium retention in the body; chronic heart failure patients with the relevant predisposition; arterial hypertension; fluid retention in the body; a loss potassium; hypokalemic alkalosis; increased excretion of calcium.

Co hand musculoskeletal apparatus:

"steroid" myopathy; muscle weakness; osteoporosis; osteonecrosis; pathological fractures; compression fractures of vertebrae; aseptic necrosis of the epiphyses of tubular bones; tendon ruptures, especially the Achilles tendon.

From the digestive system:

peptic ulcer with possible perforation and bleeding (can be indicated the appointment of preventive antacid therapy); gastric bleeding; pancreatitis; esophagitis; perforation of the intestine; an increase in the activity of alanine transaminase (ALT), aspartatetransaminase (ACT) and alkaline phosphatase in the blood serum (usually these changes are insignificant, not associated with any clinical syndromes, and reversible after discontinuation of treatment).

From the skin:

slow healing of wounds; petechiae and ecchymosis; thinning and reducing the strength of the skin; Kaposi's sarcoma. It is reported that patients treated with SCS, noted Kaposi's sarcoma. With the cancellation of GCS, clinical remission may occur.

From the side of metabolism: negative nitrogen balance due to protein catabolism.

From the nervous system:

increased intracranial pressure with edema of the optic disc; benign intracranial hypertension; convulsions; mental disorders, including euphoria, insomnia, mood swings, personality changes, depression; acute psychotic manifestations; strengthening of already existing emotional instability or propensity to psychotic reactions.

From the endocrine system:

violation of the menstrual cycle; development of Isenko-Cushing syndrome; suppression of the function of the pituitary-adrenal system; decreased glucose tolerance; manifestation of latent diabetes mellitus; increased need for insulin or oral hypoglycemic agents in diabetic patients, growth retardation in children.

From the sense organs:

subcapsular cataract; increased intraocular pressure; exophthalmos.

From the immune system: erased clinical picture in infectious diseases; activation of latent infections, including reactivation of tuberculosis; the emergence of infections caused by opportunistic pathogens, any localization occurring both in mild form and with the possibility lethal outcome; hypersensitivity reactions, including anaphylaxis and anaphylactic reactions (eg, bronchospasm, laryngeal edema, urticaria); Suppression of reactions during skin tests.

Other: The solvent contains benzyl alcohol, which can cause a "suffocation syndrome" (Gasping Syndrome - violations from the respiratory system, manifested in the form of suffocation) with a fatal outcome in premature newborns. The use of CEN can lead to the development of sympathetic-adrenal crises in patients with pheochromocytoma, central serous chorioretinopathy and epidural lipomatosis.

Overdose:

The clinical syndrome of acute drug overdose is not described.

Hydrocortisone is excreted during dialysis.

Interaction:

Inducers of microsomal liver enzymes, such as phenobarbital, phenytoin and rifampicin, can increase the clearance of GCS, which may require increasing the dose of the drug to obtain the desired effect.

Such drugs as troleandomisin and ketoconazole. can inhibit the metabolism of GCS and reduce its clearance. In this case, the dose of GCS should be reduced to avoid overdose phenomena.

The GCS can increase the clearance acetylsalicylic acid, taken in high doses for a long period, which can lead to a decrease in the concentration of salicylates in the serum or increase the risk of toxicity of salicylates when GCS is abolished. In patients with hypoprothrombinemia, acetylsalicylic acid in combination with GCS should be administered with caution.

SCS has a variety of effects on the action of indirect anticoagulants. Both enhancement and reduction of the effect of anticoagulants taken simultaneously with hydrocortisone are reported. To maintain the necessary effect of anticoagulant, a constant determination of the coagulability indices is necessary.

Special instructions:

When administering high doses of hydrocortisone for a period longer than 48 to 72 hours, hypernatremia may develop.In this case, it is recommended to replace SOLU-CORTEX® with another CEN, for example, methylprednisolone sodium succinate, which causes little or no sodium retention in the body.

Patients who may be exposed to stress on the background of therapy with the drug SOLU-CORTEIF®, an increase in the dose of the drug before, during and after a stressful situation. Such patients should be under strict medical supervision because of possible development of the adrenal insufficiency.

There was an increase in mortality 2 weeks or 6 months after head trauma in patients who received treatment with parenteral forms of SCS without clear indications. In this regard, not high doses of GCS should be used; including, SOLU-CORTEF® , with edema of the brain due to trauma head.

Against the background of therapy with SOLO- CORTEF® some infections can flow in an erased form, in addition, new infections can develop. When application of SOLO-CORTEF® possible to reduce resistance to infections, and also decreases ability of the organism to localize infectious process. Development infections caused by various pathogenic organisms, such as viruses, bacteria, fungi, protozoa or helminths, which are localized in various systems of the human body, can be associated with the application of of SOLO-CORTEIF®, as in as a monotherapy, and in combination with other immunosuppressants, affecting the cellular immunity, humoral immunity or neutrophil function. These infections can be mild, however, in some cases, a severe course and even a lethal outcome is possible. The higher the dose of SOLU-CORTEIF® is used, the higher the probability of developing infectious complications.

The use of hydrocortisone in active tuberculosis should be limited to cases of fulminant and disseminated tuberculosis, when SCS is used to treat the disease in combination with appropriate antituberculous chemotherapy. If the preparation is SOLO-CORTEIF ® Mr.refer to patients with latent tuberculosis or positive tuberculin samples, then treatment should be carried out under strict medical supervision, since it is possible to reactivate the disease.During prolonged therapy with the drug, such patients should receive appropriate preventive treatment.

Patients receiving treatment with SOLU-CORTEIF® in doses that have an immunosuppressive effect are prohibited from administering live or live attenuated vaccines, but it is possible to administer killed or inactivated vaccines, however, the response to the administration of such vaccines may be reduced. Patients receiving treatment with SOLO-CORTEIF® in doses that do not have immunosuppressive action, immunization can be performed according to the indications.

The introduction of hydrocortisone can lead to increased blood pressure, to water and salt retention in the body and to increased excretion of potassium. There may be a need to limit the intake of salt with food and the additional prescription of potassium preparations. All GCSs increase the excretion of calcium from the body. It is reported that patients treated with SCS, noted Kaposi's sarcoma. With the withdrawal of the drug may come a clinical remission. Cases (including fatal outcome) of the development of sympathetic adrenal crises have been reported in patients with pheochromocytoma receiving systemic therapy with GCS (including methylprednisolone).In patients with suspected pheochromocytoma or confirmed disease, GCS should be used only after a thorough assessment of the risk / benefit ratio.

Since in patients receiving parenteral therapy with Solu-KORTEF®, in rare cases may develop anaphylactoid reactions (eg, bronchospasm), should take appropriate preventive measures, especially if this patient had a history of allergic reactions to any drugs prior to administration of the drug.

The effect of hydrocortisone can be enhanced in patients with liver disease, since in such patients metabolism and excretion of hydrocortisone are significantly increased.

With prolonged daily therapy with SOLO-CORTEIF®, growth retardation may occur in children, so this dosage regimen should only be given to children if they have serious indications.

GKS therapy can lead to the development of central serous chorioretinopathy, which in turn can lead to detachment of the retina.

Acute myopathy most often develops when using high doses of the drug SOLU-CORTEIF® in patients with impaired neuromuscular transmission (for example,with myasthenia gravis gravis), or in patients who are simultaneously treated with peripheral muscle relaxants (e.g., pancuronium). Such acute myopathy It has a generalized character, can damage the muscles of the eye and respiratory system, lead to development tetraparesis. Possible increase the content of creatine phosphokinase. When this improvement or recovery after the withdrawal of the drug SOLO-CORTEF® can only occur through many weeks or even a few years.

Against the background of therapy with SOLO-CORTEF® the development of various mental disorders: from euphoria, insomnia, mood imbalances, personality changes and severe depression to acute psychotic manifestations. In addition, the already existing emotional instability or propensity to psychotic reactions.

There are reports of development epidural lipomatosis in patients, CEN, as a rule, with long-term therapy with high doses.

Potentially severe mental disorders can occur when application of SOLO-CORTEF®.

Symptoms usually appear in for days or weeks after the start of therapy. Most reaction disappears, either after dose, or after withdrawal of the drug.

Despite this, it may be necessary specific treatment. Patients and / or their relatives should be warned that in the case of the appearance of changes in the psychological status of the patient (especially when developing depressive state and suicide attempts) is necessary seek medical attention.

Also, patients should be warned or their relatives about the possibility development of mental disorders in time or immediately after dose reduction drug or complete withdrawal.

In the long-term therapy preparation SOLU-CORTEF® should be to prevent ulcerative lesions of the gastrointestinal tract, and if necessary, discontinuation of the drug gradually reduce the dose (abrupt abolition of admission is contraindicated preparation).

Effect on the ability to drive transp. cf. and fur:

In connection with the possibility of development side effects from the nervous system (for example, convulsions, fainting, Vertigo), as well as by the body to people taking the drug SOLU-CORTEF®, it is necessary to observe caution in managing vehicles and occupations with other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Lyophilizate for the preparation of a solution for intravenous and intramuscular administration of 100 mg.

Packaging:

100 mg hydrocortisone and 2 ml solvent in a two-vial bottle Act-o-Vial from colorless glass class I, sealed with 2 stoppers made of butyl rubber (one separates the two containers, the other closes the bottle from above), with a plastic activator on top of the top plug.

100 mg hydrocortisone in a vial of Class I colorless glass, sealed with a butyl rubber stopper, coated with an aluminum cap, with a plastic protective cover.

One two-bottle Act-o-Vial or one bottle together with the instructions for use in a cardboard pack with the control of the first autopsy.

Storage conditions:

At a temperature of 15 ° C to 25 ° C out of the reach of children. The prepared solution should be stored at room temperature not more than 72 hours in a dark place.

Shelf life:

5 years

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:P N008915

Date of registration:19.09.2011

The owner of the registration certificate:Pfizer IFG Belgium N.V.Pfizer IFG Belgium N.V. Belgium

Manufacturer: & nbsp

PFIZER MFG. BELGIUM, N.V. Belgium

Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation

Information update date: & nbsp03.03.2014

Illustrated instructions

Instructions

Solu-Cortef® (Solu-Cortef® )