active ingredient: methylprednisolone; 1 tablet contains methylprednisolone 4 mg or 16 mg, or 32 mg
auxiliary substances: tablets containing 4 mg of methylprednisolone-lactose, corn starch, sucrose, calcium stearate 16 mg-lactose, corn starch, sucrose, calcium stearate, mineral oil; 32 mg-lactose, corn starch, sucrose, calcium stearate, mineral oil.
Corticosteroids for systemic use. Glucocorticoid. ATC code H02A B04.
Primary and secondary insufficiency of the adrenal cortical layer (the first row preparations are hydrocortisone or cortisone, if necessary, synthetic analogues can be used in combination with mineralocorticoids, the simultaneous use of mineralocorticoids is especially important for the treatment of children).
Congenital adrenal hyperplasia.
Hypercalcemia in malignant tumors.
1. rheumatic disease.
As an additional therapy for short-term use (for removal from acute condition or exacerbation of the process) in the following diseases:
rheumatoid arthritis, including juvenile rheumatoid arthritis (in some cases, maintenance therapy with low doses may be required);
acute and subacute bursitis,
acute nonspecific tendosynovit;
acute gouty arthritis
synovitis with osteoarthritis;
During exacerbation or in some cases as maintenance therapy for the following diseases:
systemic lupus erythematosus,
systemic dermatomyositis (polymyositis)
acute rheumatic heart disease;
the rheumatic polimialgia in giant cell, arteriitis.
3. Skin disease.
bullous dermatitis herpetiformis
severe erythema multiforme (Stevens-Johnson syndrome)
severe seborrheic dermatitis.
4. Allergic condition.
For the treatment of the following severe and allergic conditions in case of ineffectiveness of standard treatment:
seasonal or year-round allergic rhinitis
5. Eye disease.
Severe acute and chronic allergic and inflammatory processes with involvement of the eye and adnexa, such as:
allergic marginal corneal ulcers
eye damage caused by Herpes zoster ;
inflammation of the anterior eye;
diffuse posterior uveitis and choroidal;
iritis and iridocyclitis.
6. Diseases of the respiratory system.
Leffler syndrome, not amenable to therapy by other methods;
fulminant or disseminated tuberculosis of the lungs (used in combination with appropriate anti-TB chemotherapy);
7. Hematological diseases.
Idiopathic thrombocytopenic purpura in adults,
secondary thrombocytopenia in adults,
acquired (autoimmune) hemolytic anemia
erythroblastopenia (erythrocytic anemia);
congenital (erythroid) hypoplastic anemia.
8. Oncological disease.
As palliative care for the following diseases:
leukemia and lymphoma in adults;
acute leukemia in children.
9. Edema syndrome.
For induction of diuresis or elimination of proteinuria in nephrotic syndrome without uremia, idiopathic or due to systemic lupus erythematosus.
10. Diseases of the digestive tract.
For removal of the patient from critical condition in such diseases:
11. Nervous system disease.
Multiple sclerosis in the acute phase;
brain edema caused by a brain tumor.
12. Diseases of other organs and systems.
Tuberculous meningitis with subarachnoid block or impending development unit, in conjunction with the appropriate anti-TB chemotherapy;
trichinellosis with damage to the nervous system or myocardium.
13. Organ transplantation.
Systemic fungal infections. Systemic infections in cases where specific antimicrobial therapy is not prescribed. Hypersensitivity to the components of the drug or to methylprednisolone in the history.
The introduction of live or live Atanasova vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.
Method of application and doses
The initial dose for adults may vary depending on the nature of the reading. In less severe diseases are usually sufficient, and lower doses, although individual patients may require higher starting doses. High doses can be used in diseases and conditions such as multiple sclerosis (200 mg/day), brain edema (200-1000 mg/day) and organ transplantation (up to 7 mg/kg/day).
If after an appropriate period of time will not be achieved satisfactory clinical effect, treatment with tablets of methylprednisolone should be withdrawn and patient should be administered an alternative therapy. If after long-term therapy, the drug should be canceled, it is recommended to carry out this gradually, and not suddenly.
If the treatment achieved satisfactory effect, you should pick up the patient individual maintenance dose by gradually reducing the initial dose after a certain period of time until, until you find the lowest dose that will maintain the achieved clinical effect. It should be remembered that constant control of dosing is necessary. The situations in which there may be a need to adjust the dose of the drug include: changes in the clinical state due to the onset of remission or exacerbation of the disease; individual response of the patient to the drug; the impact on the patient of stressful situations, not directly related to the main disease, which is directed therapy. In the latter case, it may be necessary to increase the dose of methylprednisolone at a certain time, depending on the patient's condition.
It should be emphasized that the desired dosage may vary and should be individualized, depending on the nature of the disease and patient response to therapy.
Alternating therapy (AO)
Alternating therapy is a mode of dosing corticosteroids, in which a double daily dose of GCS is prescribed every other day, in the morning. The purpose of this type of therapy is to achieve in a patient who needs long-term therapy, the maximum benefits of using corticosteroids while minimizing certain undesirable effects, such as inhibition of the pituitary-adrenal system, kushingoid state, corticosteroid withdrawal syndrome and inhibition of growth in children.
Below are the adverse reactions associated with the treatment indicated by organ system class, frequency and severity. In each group, the frequency of adverse reactions specified in the order of gravity reduction.
Frequency is defined as: very often (?1/10), often (>1/100,<1/10), infrequently (>1/1000,<1/100), rarely (>1/10000,<1/1000 ), the frequency is unknown (frequency cannot be estimated based on available data).
Infections and parasitic diseases: often infection; rarely, opportunistic infections; frequency is unknown - recurrence of latent tuberculosis.
Neoplasms of benign, malignant or unknown behaviour (including cysts and polyps): frequency unknown - Kaposi sarcoma.
From the blood and lymphatic system: frequency unknown-leukocytosis.
From the immune system: the frequency is unknown-hypersensitivity to the drug (including anaphylactic and anaphylactoid reactions), inhibition of reactions during skin tests.
Metabolic and nutritional disorders: often - sodium retention, fluid retention in the body frequency unknown - hypokalemic alkalosis, metabolic acidosis, impaired glucose tolerance, increased requirements of insulin or oral antidiabetic remedies in diabetes mellitus, increased appetite (which may lead to weight gain). Reduced tolerance to carbohydrates, possible manifestation of latent diabetes mellitus and increased need for hypoglycemic medications in patients with diabetes.
Mental disorders : often - affective disorder (including depressed mood and euphoric mood) frequency unknown - brief psychotic disorder (particularly mania, delusions, hallucinations and aggravation of schizophrenia), psychotic behavior, affective disorder (particularly affective lability, psychological dependence, suicidal ideation), mental disorder, personality changes, mood swings, confusion, anxiety, abnormal behaviour , insomnia, irritability.
From the heart: the frequency is unknown-changes in the water-electrolyte balance, which in some cases can lead to hypertension and congestive heart failure (in patients with a tendency to do so), myocardial rupture in the area of myocardial infarction.
Vascular side: often-arterial hypertension; frequency unknown-arterial hypotension, thrombosis.
From the respiratory system, chest and mediastinum: the frequency is unknown-hiccups, pulmonary embolism.
From the side of musculoskeletal system and connective tissue: often - delayed growth, muscle weakness, frequency unknown arthralgia, muscle atrophy, myalgia, myopathy, Neuropathic arthropathy, osteonecrosis, osteoporosis, pathological fractures.
From the digestive tract: often - complications affecting the gastrointestinal tract that can cause or activate peptic ulcer (with possible perforation and hemorrhage) frequency unknown - bloating, abdominal pain, diarrhoea, dyspepsia, gastric bleeding, intestinal perforation, nausea, esophagitis, ulcerative esophagitis, pancreatitis.
From the skin and subcutaneous tissue: often-acne, skin atrophy; the frequency is unknown-angioedema, ecchymosis, erythema, hirsutism, hyperhidrosis, petechia, itching, rash, skin striae, urticaria, telangioectasia.
On the part of the reproductive system and mammary glands: the frequency is unknown - irregular menstruation.
From the nervous system: the frequency is unknown - amnesia, cognitive impairment, convulsions, dizziness, headache, increased intracranial pressure (with optic disc edema (benign intracranial hypertension)), epidural lipomatosis.
From the endocrine system: often - the emergence cushingoid States; frequency is unknown - hypopituitarism, withdrawal of corticosteroids. Inhibition of the pituitary-adrenal system, especially during stress. Suppression of growth in children.
From the organ of vision: often-subcapsular cataract; the frequency is unknown-glaucoma and exophthalmos, thinning of the sclera and cornea, Central serous chorioretinopathy.
On the part of the hearing and balance: the frequency is unknown-vertigo.
General disorders and reactions at the site of administration : often - a violation of recovery; the frequency is unknown - fatigue, General malaise.
Research: often-decrease of potassium level in the blood frequency is unknown-increase of alanine aminotransferase level, increase of aspartate aminotransferase level, increase of alkaline phosphatase level of blood, decrease of tolerance to carbohydrates, increase of intraocular pressure, increase of calcium level of urine. A negative nitrogen balance.
Injuries, poisoning and complications of procedures : frequency unknown - compression fracture of the spine, rupture of the tendon (especially Achilles tendon).
Report on suspected adverse reactions
It is important to report suspected adverse reactions after registration of the drug. This allows you to further control the ratio of "benefit/risk" for the drug. Skilled workers in health care are asked to report any suspected adverse reactions.
Was no clinical syndrome of acute overdosage with corticosteroids. The message about the acute toxicity and/or death after an overdose of corticosteroids have been reported rarely. In case of overdose, there is no specific antidote; maintenance and symptomatic treatment is carried out. Methylprednisolone undergoes dialysis.
Application during pregnancy and lactation
The results of studies on animals showed that the introduction of females of corticosteroids in high doses can cause malformations in fetuses. However, it seems that corticosteroids, which are prescribed to pregnant women, do not cause the occurrence of congenital malformations.
Despite the results of studies in animals, when using this drug during pregnancy, the possibility of causing harm to the fetus is unlikely. Adequate studies of the effect of corticosteroids on human reproductive function was not carried out. Since there is no adequate evidence for the safety of corticosteroids in their use in pregnant women, these drugs should be prescribed only when absolutely necessary during pregnancy.
Some corticosteroids readily cross the placental barrier. In one retrospective study, mothers taking GCS reported an increase in the incidence of low birth weight. Infants whose mothers during pregnancy were receiving rather high doses of corticosteroids should be monitored carefully for signs of insufficiency of the adrenal cortex, although this insufficiency in newborns exposed to corticosteroids in utero, it is noted rarely.
The effect of corticosteroids on the course and effects of childbirth is unknown.
In infants whose mothers received long-term treatment with corticosteroids during pregnancy, cataracts were observed.
Corticosteroids penetrate into breast milk. Corticosteroids are secreted in breast milk, can inhibit the growth and affect the endogenous production of glucocorticoids in infants who are breastfed. Since the relevant studies on the impact of glucocorticoids on the reproductive function of people was conducted, these drugs have mothers who are breastfeeding should only be applied in cases where the benefits of the drug outweighs the potential risk to the baby.
The results of studies on animals have shown that corticosteroids reduce reproductive function.
The drug is used in pediatric practice.
It is necessary to carefully monitor the development and growth of infants and children when applying long-term therapy with corticosteroids.
Children who receive GCS daily for a long time, several times a day, may experience stunting. Therefore, this dosing regimen should be used only for the most urgent indications. The use of alternating therapy, as a rule, allows to avoid this side effect or to minimise it (see Section "Method of application and doses. Alternation therapy").
Infants and children who receive long-term GCS therapy have a particular risk of increased intracranial pressure.
High doses of corticosteroids can cause pancreatitis in children.
Immunosuppressive effects/increased susceptibility to infections
GCS can increase susceptibility to infections; they can mask certain symptoms of infections; in addition, new infections can develop against corticosteroids. When using corticosteroids, resistance to infections may decrease and there may be an inability of the body to localize the infection. Infections caused by any pathogen, including viruses, bacteria, fungi, protozoa or helminths in any part of the body, can be associated with the use of corticosteroids as monotherapy or in combination with other immunosuppressants that affect cellular immunity, humoral immunity or neutrophil function. These infections can be mild, but can be severe, and in some cases lethal. As the dose of corticosteroids increases, the incidence of infectious complications increases.
Patients taking medicines that suppress the immune system are more susceptible to infections than healthy people. Chickenpox and measles, for example, may have a more serious or even fatal in non-immune children or adults who are taking corticosteroids.
The use of live or live weakened vaccines in patients who receive corticosteroids in immunosuppressive doses is contraindicated. Patients receiving corticosteroids in immunosuppressive doses can be vaccinated by killing or inactivating vaccines, but their response to such vaccines may be weakened. These immunization procedures can be carried out in patients who receive corticosteroids in non-immunosuppressive doses.
The use of corticosteroids in active tuberculosis should be limited to cases of fulminant or disseminated tuberculosis, in these cases corticosteroids are used in combination with appropriate anti-tuberculosis chemotherapy. If corticosteroids are shown to patients with latent tuberculosis or with the superelevation of tuberkulin samples, treatment should be carried out under supervision, since reactivation of the disease is possible. During prolonged corticosteroids, such patients need to receive chemoprophylactic drugs.
Cases of Kaposi's sarcoma were reported in patients treated with corticosteroids. In such cases, discontinuation of therapy with corticosteroids can lead to clinical remission.
In addition, corticosteroids should be used with great caution in patients with confirmed or suspected parasitic infections, for example in the case of strongyloidosis (acne infection). In these patients the immunosuppression induced by corticosteroids can lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal septicemia caused by gram-negative organisms.
There is no consensus on the role of corticosteroids in the treatment of patients with septic shock. Early studies have reported both positive and negative effects of corticosteroids in this clinical setting. The studies conducted later showed that corticosteroids as adjunctive therapy had a beneficial effect in patients with septic shock, where there had been under-stateness of the adrenal glands. However, routine use of these drugs in patients with septic shock is not recommended. As a result of a systematic review of data after short courses of high doses of corticosteroids, such patients were concluded that there was no evidence in favor of such use of these drugs. However, according to meta-analysis and one review it was shown that longer (5-11 days) courses of treatment with corticosteroids in low doses can cause a decrease in mortality, especially in patients with septic shock, dependent on vasopressor therapy.
The effect on the immune system
May occur allergic reactions (e.g., angioedema). Since skin reactions and anaphylactic/anaphylactoid reactions were rare in patients receiving corticosteroid therapy, appropriate measures should be taken before use, especially if the patient has a history of allergies to any drug.
Effect on endocrine system
Patients treated with corticosteroids and exposed to stress are shown to increase the dose of fast-acting corticosteroids before, during and after a stressful situation.
Corticosteroids used for a long period of time in pharmacological doses can lead to depression of the hypothalamic-pituitary-adrenal system (secondary adrenal cortex). The degree and duration of adrenocortical insufficiency vary in different patients and depend on the dose, frequency, time of use, as well as the duration of therapy GCS. This effect can be minimized with the use of alternating therapy.
With the sudden abolition of glucocorticoids can develop acute adrenal insufficiency, which can lead to death.
Adrenal insufficiency caused by the introduction of the drug can be minimized by gradually reducing the dose. This type of relative insufficiency can be retained for several months after the withdrawal of therapy; so if during this period there are stressful situations, hormonal therapy must be restored.
After a sharp cessation of glucocorticoids can also develop "withdrawal syndrome" corticosteroids, at first glance not associated with adrenal cortex insufficiency. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, weight loss and/or arterial hypotension, rhinitis, conjunctivitis, painful skin nodes with a sense of itching. It is believed that these effects are the result of sudden changes in the concentration of glucocorticoids, rather than low levels of corticosteroids.
Since GCS can cause or exacerbate Cushing's syndrome, patients with Cushing's disease should avoid their use.
There is a more pronounced effect of corticosteroids on patients with hypothyroidism.
Disorders of metabolism and nutrition.
Corticosteroids, including methylprednisolone, can increase blood glucose levels, worsen the condition of patients with diabetes mellitus and cause a predisposition to diabetes mellitus in patients who use GCS for a long time.
When using corticosteroids, there may be different mental disorders from euphoria, insomnia, mood changes, personality changes to severe depression with the expression of psychotic manifestations. In addition, in patients receiving corticosteroids may worsen existing emotional instability and a propensity for psychotic reactions.
When using systemic corticosteroids may develop a potentially severe mental disorders (see Section "Adverse reactions"). Symptoms usually occur within a few days or weeks after initiation of therapy. Most reactions disappear after dose reduction or discontinuation of the drug, although it may be necessary to appoint a special treatment. There were reactions from the psyche in the abolition of corticosteroids; their frequency is unknown. Patients/persons who care for them should be encouraged to go to the doctor if the patient developed any violations on the part of the psyche, especially if there is suspicion that he/she is in a depressed mood or experiencing suicidal thoughts. Patients/persons being cared for should be vigilant about possible mental disorders that may occur when administered or immediately after a gradual dose reduction or withdrawal of systemic corticosteroids.
From the nervous system
Patients with convulsions, as well as with myasthenia gravis should use corticosteroids with caution (see information about myopathy in the section " from the musculoskeletal system ").
Although controlled clinical studies have shown the efficacy of corticosteroids in accelerating the reduction of multiple sclerosis, they have not demonstrated the effect of corticosteroids on the end result or the natural course of the disease. According to the results of these studies, relatively high doses of corticosteroids should be used to achieve a significant effect (see section "dosage and Administration").
By the organs of vision
In case of eye damage caused by herpes simplex virus, corticosteroids should be used with caution, since corneal perforation is possible. Prolonged use of corticosteroids may develop back subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos or increased intraocular pressure that may cause glaucoma with possible damage to the visual nerve. In patients who use glucocorticoids, increases the likelihood of secondary eye infections caused by fungi and viruses.
The use of corticosteroids has been associated with the development of Central serous homeopatie, which can lead to retinal detachment.
From the heart and blood vessels
Patients with congestive heart failure systemic corticosteroids should be used with caution and only if absolutely necessary.
The negative impact of glucocorticoids on the cardiovascular system, as the development of dyslipidemia and hypertension, can incline patients with pre-existing risk factors for cardiovascular complications to the development of additional cardiovascular effects, if used in high doses and long courses. In this regard, corticosteroids should be used wisely in such patients, as well as take into account the modification of risk and, if necessary, additionally monitor cardiac activity.
Reported cases of thrombosis, including thromboembolic events with the use of corticosteroids. Patients with thromboembolic disorders or may be exposed to them, care should be taken when using corticosteroids.
Patients with hypertension corticosteroids should be used with caution.
The gastro-intestinal tract
There is no consensus that it is corticosteroids that cause the development of gastric ulcer disease during therapy. However, GCS can mask the symptoms of peptic ulcer disease, so there may be perforation or bleeding without severe pain syndrome. In combination with NSAIDs the risk of developing gastrointestinal ulcers is increased.
Corticosteroids should be prescribed with caution in non-specific ulcerative colitis, if there is a risk of perforation, the formation of an abscess or other purulent infection; in the case of diverticules; in the case of recently imposed intestinal anastomoses; with active or latent peptic ulcer.
Disorders of the digestive system
High doses of corticosteroids can cause the development of acute pancreatitis.
From the musculoskeletal system
Reported cases of acute myopathy with the use of corticosteroids in high doses, most frequently encountered in patients with disorders of neuromuscular transmission (e.g. myasthenia gravis) or in patients receiving therapy with anticholinergic agents such as agents that block the nerve-" muscle transfer (e.g., pancuronium). This acute myopathy-generalized, can affect the muscles of the eyes and respiratory muscles and lead to quadriparesis. There may be an increase in CFC levels. To improve the clinical condition or recovery after discontinuation of corticosteroids may take from several weeks to several years.
Osteoporosis is a common (but rarely diagnosed) side effect associated with prolonged use of high doses of glucocorticoids.
From the kidneys and urinary system
Corticosteroids should be used with caution in patients with renal insufficiency.
When using hydrocortisone or cortisone in medium and high doses may increase blood pressure, salt and water retention, increased potassium excretion. These effects are less common when using synthetic derivatives of these drugs, except when high doses are used. It is recommended to use a diet with limited salt intake and potassium supplements. All corticosteroids increase calcium excretion.
Injuries, poisoning and complications of procedures
Systemic corticosteroids are not intended for the treatment of traumatic brain injuries and should therefore be used in the case of such injuries. The results of the multicenter study revealed an increase in mortality 2 weeks or 6 months after injury in patients receiving sodium methylprednisolone succinate compared to patients of the placebo group. The causal relationship with the treatment of sodium methylprednisolone succinate is not established.
The drug contains lactose, so it should not be used in patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome. The drug contains sucrose, which should be considered for patients with diabetes.
Since complications in the treatment of GCS depend on the dose of the drug and the duration of therapy, in each case, a thorough assessment of the ratio of benefit from the use of the drug and the potential risk in determining both the dose and duration of treatment, and the choice of the mode of application - daily or intermittent course.
When carrying out treatment with corticosteroids, the lowest dose should be prescribed, which provides sufficient therapeutic effect, and when it becomes possible to reduce the dose, this reduction should be carried out gradually.
Aspirin and nonsteroidal anti-inflammatory drugs should be used with caution in combination with corticosteroids.
After the use of systemic corticosteroids reported on the development of pheochromocytoma crisis, which can lead to death. Corticosteroids should be prescribed to patients with suspected or prescribed pheochromocytoma only after an appropriate assessment of the risk/benefit ratio.
The ability to influence the reaction rate when driving motor transport or operating other mechanisms
The effect of corticosteroids on the reaction rate when driving or working with other mechanisms has not been systematically evaluated. After treatment corticosteroids may occur side effects such as dizziness, visual impairment, fatigue. In this case, patients should not drive vehicles or work with mechanisms.
Interaction with other medicinal products and other forms of interaction
Methylprednisolone is a substrate of the cytochrome P450 (CYP) enzyme and is metabolized with CYP3A4 enzyme. CYP3A4 is the dominant enzyme of CYP's most common subspecies in adult liver. It catalyzes 6-?-hydroxylation of steroids, which is a key step in phase I metabolism for both endogenous and synthetic corticosteroids. Many other compounds are also CYP3A4 substrates, some of them (like other drugs) alter glucocorticoid metabolism, inducing (increasing activity) or inhibiting CYP3A4 isoenzyme.
CYP3A4 INHIBITORS - drugs that inhibit CYP3A4 activity generally decrease hepatic clearance and increase plasma concentrations of drugs-substrates of CYP3A4, such as methylprednisolone. In the presence of the CYP3A4 inhibitor, it may be necessary to titrate the dose of methylprednisolone to avoid steroid toxicity. To CYP3A4 inhibitors include grapefruit juice; macrolide antibiotics: troleandomycin, isoniazid.
CYP3A4 inductor-drugs that stimulate the activity of CYP3A4, as a rule, increase liver clearance, which leads to a decrease in plasma concentrations of drugs-substrates CYP3A4. With the simultaneous use of these drugs may require an increase in the dose of methylprednisolone to achieve the desired result. Such medicines include antibiotics, anti-TB drugs - rifampin, anticonvulsants - phenobarbital, phenytoin.
CYP3A4 SUBSTRATES - the presence of another CYP3A4 substrate, may lead to effects on the hepatic clearance of methylprednisolone, with appropriate dose adjustment. It is possible that adverse reactions associated with the use of one of these drugs as monotherapy will be more likely if they are used simultaneously. These include immunosuppressants: cyclophosphamide, tacrolimus.
Inducer of CYP3A4 and SUBSTRATES - anti-convulsants: carbamazepine.
INHIBITORS and SUBSTRATES of CYP3A4 - antiemetics: aprepitant, fosaprepitant; antifungal agents: Itraconazole, ketoconazole; calcium channel blockers: diltiazem; contraceptives (oral administration) ethinyl estradiol/norethindrone; macrolide antibiotics: clarithromycin, erythromycin.
while the use of ciclosporin