Methylprednisolone (When ATH H02AB04)

When ATH:
H02AB04

Characteristic.

Hormonal agents (glucocorticoids).

In medical practice using methylprednisolone (tablet form), methylprednisolone acetate (for the / m, vnutrisustavnogo, peryartykulyarnoho, intrabursalnogo administration, and introducing into soft tissue, in the pathological focus, instillation into the rectum), methylprednisolone sodium succinate (for in / and the / m).

Methylprednisolone is a white or almost white crystalline powder and odourless. It is soluble in ethanol, dioxane and methanol, slightly soluble in acetone and chloroform, very slightly soluble in ether, practically insoluble in water. Molecular weight 374,47.

Methylprednisolone acetate is white or almost white crystalline powder and odourless, which melts at a temperature of about 215 °C (wherein a small degree is decomposed). Dioxane solution, it is soluble in acetone, ethanol, chloroform and methanol, slightly soluble in ether, practically insoluble in water. Molecular weight 416,51.

Methylprednisolone sodium succinate is a white or almost white, without smell, hygroscopic, amorphous substance. It is soluble in water, ethanol, very slightly soluble in acetone, insoluble in chloroform. Molecular weight 496,52. Methylprednisolone sodium succinate as highly soluble in water, that can be introduced in a small amount of solvent in situations, as shown in / in the introduction and the need to create a high level of blood methylprednisolone.

Pharmacological action.
Glucocorticoid, anti-inflammatory, antiallergic, protivoshokovoe, immunosuppressive.

Application.

Methylprednisolone, methylprednisolone acetate and methylprednisolone sodium succinate.

For systemic use (parenterally and inwardly). Endocrine diseases: primary or secondary adrenocortical insufficiency (Drugs of choice is hydrocortisone or cortisone; If necessary, synthetic analogs may be used in conjunction with mineralokortikoidami; of particular importance is the addition of mineralocorticoid pediatric), congenital adrenal hyperplasia, purulent thyroiditis, hypercalcemia of malignancy; rheumatic diseases (as adjunctive therapy in acute exacerbation of current or); collagenoses (exacerbation or maintenance therapy), rheumatoid arthritis (including juvenile — in some cases, you might need supportive therapy to low doses), Acute rheumatic heart disease, systemic lupus erythematosus, systemic dermatomyositis (polimiozit), psoriaticheskiy arthritis, acute gouty arthritis, posttravmaticheskiy osteoarthritis, ankiloziruyushtiy spondylitis, acute or subacute bursitis, acute nonspecific tenosynovitis, synovitis of osteoarthritis, epicondylitis; diseases of the respiratory tract: symptomatic sarcoidosis, Loffler's syndrome are not amenable to treatment by other means, berylliosis, lightning or disseminated pulmonary tuberculosis in combination with an appropriate anti-tuberculosis therapy, inhalation pneumonia; hematologic diseases: idiopathic thrombocytopenic purpura in adults (Only in / introduction, i / m administration is contraindicated), secondary thrombocytopenia in adults, Acquired (autoimmunnaâ) gemoliticheskaya anemia, erythroblastopenia, Congenital (erythroid) gipoplasticheskaya anemia, agranulocytosis, oncological diseases: leukemias and lymphomas in adults, acute leukemia in children, Myeloma, lung cancer (in combination with cytostatics); edematous syndrome (to stimulate urine output or achieve regression of proteinuria in patients with nephrotic syndrome without uremia, idiopathic type, or caused by systemic lupus erythematosus); gastrointestinal diseases (to remove the patient from the critical state): yazvennыy colitis, Crohn's disease, Local enteritis, hepatitis; neurological diseases: exacerbation of multiple sclerosis; myasthenia; tuberculous meningitis with subarachnoid block or its threat (in combination with an appropriate anti-tuberculosis chemotherapy); trichinosis with nervous system or infarction; suppression of immunological compatibility for organ transplantation; nausea and vomiting during cytostatic therapy; skin diseases: pemphigus, bullous dermatitis herpetiformis, Syndrome Stevens - Johnson, exfoliative dermatitis, fungal infections, psoriasis, seborrheic dermatitis; allergic conditions (heavy state, in which conventional therapy is ineffective): seasonal or perennial allergic rhinitis, serum sickness, bronchial asthma, hypersensitivity reactions to drugs, contact dermatitis, atopic dermatitis; anaphylactic and anaphylactoid reactions; eye diseases (severe acute and chronic allergic and inflammatory processes with ocular): allergic corneal ulcers, ophthalmia, caused herpes zoster, inflammation of the anterior segment, diffuse posterior uveitis and choroiditis, transferred ophtalmia, allergic conjunctivitis, keratit, chorioretinitis, optic neuritis, Irit and iridociklit.

For methylprednisolone acetate and methylprednisolone sodium succinate further: acute adrenal insufficiency (It may be necessary to add mineralocorticoids); post-transfusion reactions such as urticaria; acute noninfectious laryngeal edema (the drug of choice is epinephrine).

Methylprednisolone sodium succinate for further: acute conditions, which require rapid hormonal effect of maximum intensity, incl. shock, which is a consequence of adrenal insufficiency, or shock, resistant to treatment by conventional methods, when possible presence of adrenal insufficiency (incl. anaphylactic, ambustial, traumatic, cardiogenic); Preoperative, in the case of serious injury or serious illness, in patients with known or suspected adrenal insufficiency; cephaledema, acute traumatic spinal cord injury (treatment should begin in the first 8 h after injury).

For intra-articular, peryartykulyarnoho, intrabursalnogo use or introduction into the soft tissue (aqueous suspension of methylprednisolone acetate): as adjunctive therapy for short-term use (to remove the patient from a state of acute or exacerbation of) the following diseases — sinovit osteoartroze, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, post-traumatic osteoarthritis.

For an introduction to the pathological focus (aqueous suspension of methylprednisolone acetate): keloid scars and localized foci of inflammation in lichen planus (Wilson zoster), psoriatic plaques, granuloma annulare, simple chronic zoster (neurodermatitis limited), discoid lupus erythematosus, diabetic lipodystrophy, alopecia areata; cystic tumor fascia and tendons.

For instillation into the rectum (aqueous suspension of methylprednisolone acetate): yazvennыy colitis.

Contraindications.

Hypersensitivity.

For methylprednisolone, methylprednisolone acetate and methylprednisolone sodium succinate when administered systemically: acute and chronic bacterial or viral diseases, Systemic fungal infections, HIV or AIDS, active and latent tuberculosis (without appropriate chemotherapy), congestive heart failure, arterial hypertension, recent myocardial infarction (may spread necrosis, slowing the formation of scar tissue and, thereby, rupture of the heart muscle), severe liver dysfunction and / or kidney, intestinal anastomosis (in the immediate history), esophagitis, gastritis, acute or latent peptic ulcer, diabetes, myasthenia gravis, glaucoma, severe osteoporosis, gipotireoz, mental disorders, polio (except bulbar-brain forms), Lymphoma after BCG vaccination, during vaccination.

To a suspension of methylprednisolone acetate: for intra-articular use: artificial joint, violation of blood coagulation, intraarticular fracture, periarticular infectious process (incl. history); w / w and intrathecal.

Some formulations of methylprednisolone acetate and methylprednisolone sodium succinate: (may contain benzyl alcohol, that can cause apnea syndrome "— the gasping syndrome fatal): use in preterm infants.

Pregnancy and breast-feeding.

The use of corticosteroids during pregnancy is possible, if the effect of therapy outweighs the potential risk to the fetus (adequate and well-controlled studies of the safety of not performed). Women of childbearing age should be warned about the potential risk to the fetus (Corticosteroids cross the placenta). It should be carefully monitored for newborns, whose mothers during pregnancy were treated with corticosteroids (adrenal insufficiency may develop in the fetus and newborn). Do not use often, large doses, over a long period of time. Nursing women should stop any breastfeeding, or use of drugs, especially in high doses (corticosteroids penetrate into breast milk and may inhibit the production of endogenous corticosteroids, suppress growth and cause adverse effects in the offspring).

Side effects.

The frequency and severity of side effects depend on the duration of use and magnitude of the dose used.

Systemic effects

On the part of the endocrine system: Cushing's syndrome, atrophy of the adrenal cortex, hypothalamic-pituitary insufficiency (particularly during times of stress, such as illness, trauma, surgical intervention), reduced tolerance to carbohydrates, steroidnыy diabetes, increase the need for insulin or oral hypoglycemic drugs in patients with diabetes, glycosuria, menstrual disorders, girsutizm, impotence, growth retardation in children.

Metabolism: negative nitrogen balance, sodium and water retention, swelling, potassium loss, hypokalemic alkalosis, weight gain.

From the digestive tract: peptic ulcer with possible perforation and hemorrhage, nausea, vomiting, ulcerative esophagitis, pancreatitis, abdominal distention.

From the nervous system and sensory organs: headache, dizziness, intracranial hypertension, pseudotumor of the brain, mental disorders, convulsions, increased intraocular pressure, exophthalmos.

Cardio-vascular system and blood (hematopoiesis, hemostasis): arterial hypertension, congestive heart failure (in predisposed patients), arrhythmia, tromʙofilija. There are reports of arrhythmias and / or the development of vascular insufficiency and / or cardiac arrest following the rapid on / in the high-dose methylprednisolone sodium succinate (the introduction of more 0,5 g for less 10 m); during or after the administration of high doses of methylprednisolone sodium succinate marked bradycardia (connection with the speed and duration of administration is not established).

On the part of the musculoskeletal system: muscular weakness, steroidnaya myopathy, reduced muscle mass, osteoporosis (especially among women and children); tendon rupture, especially Achilles; vertebral compression fractures, aseptic necrosis of the humeral head and femur, pathological fractures of the long bones.

For the skin: thinning and atrophy of the epidermis, dermis and subcutaneous tissue, regeneration degradation, slow healing of wounds, petechiae, striae, Steroid acne, pyoderma, candidiasis, Hypo- and hyperpigmentation, ecchymosis,

Allergic reactions: hives, anaphylactic shock, bronchospasm.

Other: reduced resistance to infectious diseases; injection site reactions: burning, numbness, pain, paresthesia, and infection at the injection site, Hyper- or hypopigmentation, scarring at the injection site; atrophy of the skin and subcutaneous tissue, sterile abscess.

Cooperation.

The combined use of methylprednisolone and cyclosporine It is mutual inhibition of metabolism and increase the likelihood of side effects (the joint application of methylprednisolone and cyclosporine have been reports of seizures). Phenobarbital, difengidramin, phenytoin, rifampicin and other inducers of liver enzymes increase the rate of elimination and reduce the therapeutic efficacy (You may need a dose adjustment). Methylprednisolone may increase the clearance acetylsalicylic acid, taken in high doses for a long time, that may reduce its blood level (the abolition of methylprednisolone levels of acetylsalicylic acid in the blood increases, and increases the risk of manifestation of its side effects). It should be used with caution in conjunction with acetylsalicylic acid in patients with corticosteroid gipoprotrombinemiey. Methylprednisolone affect the action of oral anticoagulants: perhaps as strengthening, and a decrease in the effect of anticoagulants, taken together with methylprednisolone (to maintain the desired anticoagulant effect is recommended constant monitoring of coagulation parameters). In combination with paracetamol It increases the risk of hepatotoxicity (induction of liver enzymes and the formation of toxic metabolites of paracetamol). Action reinforces ACTH. Alcohol, antacids (inhibit absorption), NSAIDs, incl. salicilaty, ʙutadion, Indomethacin increases the likelihood of stomach ulceration and bleeding, kalisberegate preparations — severe hyperkalemia, amphotericin b and inhibitors carboangidraza-hypokalemia, Heart Failure, osteoporosis, heart glycosides-arrhythmias, natrijsoderžaŝie preparations — edema and hypertension.

Ergocalciferol and paratgormon prevent osteopathy, called methylprednisolone. High-dose methylprednisolone reduce efficiency somatotropin.

Reduces the activity of oral antidiabetic agents, vaccine efficacy (live vaccines against the backdrop of methylprednisolone can cause disease). Mitotane and other inhibitors of adrenocortical function may necessitate increasing the dose.

Overdose.

Symptoms: swelling, the appearance of urinary protein, decline in filtration, arterial hypertension, Arrhythmia, kardiopatija, kaliopenia. Repeated frequent use of the drug (daily or several times a week) for a long time may lead to the development of Cushing's syndrome (necessitates discontinuation).

Treatment: diurez, potassium chloride, When depression and psihozah-dose reduction or elimination of the drug and the appointment fenotiazinovykh drugs or lithium salts (Tricyclic antidepressants are not recommended).

Dosing and Administration.

Inside, inaektsionno (I /, / m, epidural, in the bursa and vagina, a joint cavity, Damage to the skin) and rectally. The route of administration and dosage regimen are selected individually depending on the nature and severity of the disease, age and condition of the patient, response to treatment.

Inside, adult: 4-60 mg/day once or in divided doses; the initial dose is 4-48 mg/day, in some cases - to 100 mg / day; supporting dose-4-12 mg/day. Babies: in case of insufficiency of the adrenal glands inside 0,14 mg / kg or 4 mg / m² daily 3 admission, v/m is the same dose in two days or-0.0585 0.039 mg/kg/day daily; for other indications — inside 0.417-1.67 mg/kg or 12.5-50 mg/m² in three divided doses, v/m is 0.139-0.835 mg/kg or 4.16-25 mg/m² every 12-24 h.

/ M, in suspension (depot) adult: 40-120 Mg for 1-4 weeks.

If the disease, for which directed therapy, also develop symptoms of stress, dose of suspension should be increased. If you want to get a quick and maximum effect of hormone therapy, shown in/with the introduction of dosage form with a high degree of solubility is methylprednisolone sodium succinate.

B / ("Pulse therapy") introduced 30 mg/kg of methylprednisolone succinate during 30 m, If necessary, reapply every 6 no.

Vnutrisustavno, in bursae and the vagina-20-60 mg, the abdominal and pleural space — up to 100 mg, epidural is to 80 mg, in/in is 100-500 mg, in the area of skin damage is 20-60 mg.

With retention enema with ulcerative colitis impose 40-120 mg, for the relief of nausea and vomiting: adults-dose 250 mg for 20 minutes before and after 6 h after administration of drugs, children-not less than 25 mg / day.

Upon the occurrence of spontaneous remission treatment is stopped.

Precautions.

Since complications of treatment with glucocorticoids are dependent on the magnitude of the applied dose and duration of treatment, in each case must be weighed risk / benefit ratio for a decision on treatment with glucocorticoids, dosing regimen, duration of treatment. After treatment with corticosteroids showed an increase of ALT, AST and ALP in serum. Generally these changes are minor, not associated with any clinical syndrome and are reversible after discontinuation of treatment. Prolonged use of corticosteroids may lead to the development of posterior subcapsular cataracts, glaucoma with possible damage to the optic nerve, may increase the incidence of secondary viral or fungal infections of the eyes. For parenteral administration of corticosteroids may develop acute myopathy, the most often is in the application of high doses of glucocorticoids in patients with impaired neuromuscular transmission (myasthenia e.g. gravis) or in patients, while receiving the peripheral muscle relaxants (for example bromide pankuroniya). This acute myopathy is generalized, It can affect the muscles of the eyes and respiratory system, lead to the development of tetraparesis. Perhaps the increase in creatine kinase. In this clinical improvement or recovery after steroid withdrawal can occur only after many weeks or even a few years. It should apply the lowest dose, providing sufficient therapeutic effect. Check out the necessary course, gradually reducing the dose. Depot forms do not enter an incorrect way (incl. I /). With prolonged use is necessary to control the function of the hypothalamic-pituitary-adrenal axis, glucose in blood serum, conduct ophthalmic research.

Do not enter into the deltoid muscle. When w / and / m the introduction of the injection site should be changed. Intra-application is carried out no more 1 times a 3 Sun.

It should be taken into account, that benzyl alcohol in the composition of certain dosage forms methylprednisolone sodium succinate and acetate is potentially dangerous when applied topically to the nervous tissue.

It may contribute to the spread of infections or accession, caused by viruses, Mushrooms, protozoa and parasites (worms). The danger of these complications increases with increasing dose of methylprednisolone or combination with other immunosuppressive.

Patients, receiving immunosuppressive doses of methylprednisolone, They should be warned about the dangers of contact with sick chicken pox or measles.

The children in the period of growth of glucocorticoids should be used only if absolutely indicated and especially careful medical supervision. With prolonged use in children may slowdown.

Cancellation may be accompanied by abdominal pain and joint pain, weakness, toshnotoy, headache, dizziness, fever, loss of appetite, weight loss.

Prolonged use should reduce calorie intake, increase the intake of potassium, reduced-sodium. Calculation of the dose in children is best done not on body weight (kg), and surface area (m²). Formulations for injection is not recommended to be mixed with other injectable solutions.