Depot-Medrol

Depo-medrol is a glucocorticoid. Included in the category of systemic corticosteroids of a simple type.

[1], [2]

Indications of the depot-Medrol

Glucocorticoids are used exclusively to eliminate symptoms of disease. But sometimes they are used as a means of substitution treatment - with some endocrine pathologies.

Therapy for inflammatory diseases.

With pathologies of the rheumatic type used as an additional drug in maintenance therapy (the use of physio-and kinesitherapy, as well as anesthetic drugs, etc.). It can be used for a short treatment course (to remove a patient from an acute condition or exacerbate a chronic illness) with Bechterew's disease or psoriatic arthritis.

For the diseases described below, the drug should be used (if possible) in situ. Among pathologies:

• osteoarthritis of the post-traumatic type;
• developing on the background of osteoarthritis or rheumatoid arthritis (this includes the juvenile type of the disease) synovitis (sometimes only maintenance treatment with small dosages can be required);
• bursitis in acute or subacute stage;
• epicondylitis;
• nonspecific form of tenosynovitis in acute stage;
• An acute form of arthritis of the gouty type.

With collagenoses. In some cases, they are used for exacerbation or for maintaining the patient's condition during SLE, polymyositis of the systemic type, and also for rheumatic carditis in the acute stage.

Dermatological diseases: erythema polyforma in the severe stage, pemphigus, exfoliative form of dermatitis, mushroom granuloma and Dühring disease. In the latter case, the main drug is sulfone, and systemic GCS is used as an additional drug.

Allergic pathology. They are used as a control for allergies of severe character or having a disabling effect, which can not be eliminated with the help of standard medicinal techniques. Among them are:

• dermatitis (atopic or contact form);
• chronic forms of respiratory diseases of asthmatic type;
• allergic rhinitis of seasonal or year-round type;
• allergy to medicines;
• serum sickness;
• transfusion manifestations like urticaria;
• acute swelling in the larynx of non-infectious nature (in this case, the main drug is epinephrine).

Ophthalmological pathologies. Severe forms of allergy and inflammation (in acute or chronic form) that develop in the eyes and nearby organs:

• Eye disease, developed due to herpes zoster;
• iridocyclitis with irite;
• diffuse choroiditis;
• chorioretinitis;
• neuritis in the optic nerve.

Diseases affecting the organs of the digestive tract. It is used in critically acute conditions during treatment of ulcerative form of colitis and transmural ileitis (systemic therapeutic course).

In the presence of edemas Depo-medrol is used to stimulate the process of diuresis or to induce remission in the case of proteinuria development against a nephrotic syndrome without the development of uremia (idiopathic form or induced SLE).

Diseases in the respiratory system:

• sarcoidosis of respiratory organs of a symptomatic nature;
• beryllium lung disease;
• pulmonary tuberculosis of disseminated or fulminant type (used in combination with anti-tuberculosis chemotherapy procedures);
• Leffler's syndrome, which can not be eliminated by other medical methods;
• Mendelssohn's syndrome.

Therapy for cancer, as well as hematological pathologies.

Hematological diseases - hemolytic anemia (autoimmune, acquired), as well as a hypoplastic type (congenital), and in addition erythroblastopenia or secondary type of thrombocytopenia (in adults).

Oncological pathologies: it is used for palliative therapy for lymphoma or leukemia (adults), as well as for acute leukemia (children).

Endocrine disorders.

It is used in such cases:

• insufficiency of the adrenal cortex of the primary or secondary type;
• the above disease in acute form - in this case, the main drug is cortisone or hydrocortisone. If necessary, artificial analogs of these substances can be combined with mineralocorticoids (reception of these funds in early childhood is very important);
• adrenal hyperplasia of an innate nature;
• hypercalcemia, developed due to malignant neoplasm;
• Nongular form of thyroiditis.

Pathologies in the field of other systems and organs.

Used in the tubercular form of meningitis, which is accompanied by a threatening or subarachnoidal block (in combination with appropriate chemotherapy) and trichinosis with the involvement of the myocardium or NS. In the reactions of organs of the NS: for the treatment of exacerbated multiple sclerosis.

Use for injection directly into the source of the disease.

To introduce depot-medrol by this method is required for the treatment of such diseases:

• keloids;
• infiltrated inflammatory foci of the hypertrophic form of the local type (such as plaques of psoriasis, flat lichen, anular granuloma and limited neurodermatitis, as well as DKV and focal alopecia).

The drug can function effectively in the case of development of aponeurosis, cystic tumors or tendonitis.

Use for introduction into the rectal area.

The drug is introduced by this method when eliminating the ulcerative form of colitis.

[3]

Release form

Release in the form of an injection suspension in vials of 1 ml volume. Inside a separate package - 1 bottle.

[4]

Pharmacodynamics

Depo-Medrol is a sterile injectable suspension containing an artificial GCS-methylprednisolone acetate. The substance has long and powerful anti-allergic, anti-inflammatory, and immunosuppressive properties. The drug can be injected with a / m method to achieve a lasting effect, and along with this method in situ - with local therapy. The long duration of drug activity of drugs is explained by the fact that its active component is released rather slowly.

The general characteristics of the active substance are similar to the parameters of GCS methylprednisolone, but it dissolves more poorly and undergoes a slower metabolism, which explains the high duration of its effect.

Glucocorticoids with the participation of diffusion penetrate the cell membranes, then forming a complex that contains specific endings of the cytoplasmic type. Further, these complexes pass into the cell nucleus, are synthesized with DNA (chromatin substance) and promote transcription of mRNA with further protein binding within different enzymes, which are responsible for the appearance of various effects due to systemic use of glucocorticoids.

The active component not only has a significant effect on immune responses and inflammatory processes, but also affects the metabolism of fats and proteins with carbohydrates. In addition, the drug affects the functions of the CNS and CCC, as well as musculature of the skeleton.

Effects on immune reactions and inflammation.

Antiallergenic, anti-inflammatory, as well as immunosuppressive effect lead to the development of the following actions:

• the number of active cells of the immunocompetent type decreases on the site of the inflammatory focus;
• weakened vasodilation;
• the function of lysosome membranes is restored;
• the process of phagocytosis is suppressed;
• the number of formed prostaglandins decreases, as well as their related elements.

Dosage of methylprednisolone acetate in the amount of 4.4 mg (or 4 mg of methylprednisolone) has an anti-hydrocortisone effect of 20 mg anti-inflammatory effect. Methylprednisolone has weak mineralocorticoid properties (200 mg of methylprednisolone is equal to 1 mg of deoxycorticosterone substance).

Exposure to carbohydrate and protein metabolism.

Glucocorticoids have a catabolic effect on protein metabolism. The amino acids released during this process are converted inside the liver into glycogen with glucose (with the participation of gluconeogenesis). The absorption of glucose in the peripheral tissues is reduced, resulting in the development of glucosuria with hyperglycemia (in particular, people with a tendency to develop diabetes).

Effects on the metabolism of fats.

The drug has lipolytic properties, which are most pronounced in the limbs. It also has a lipogenetic effect, which is most evident in the head with the neck and sternum. As a result of these processes, there is a redistribution of available fat stores.

The peak of its drug activity of GCS reaches later than its maximum values within the blood are observed. This allows us to conclude that the most pronounced properties of drugs are more likely to develop due to a change in enzyme activity, and not because of direct effects of the drug.

[5], [6]

Pharmacokinetics

Methylprednisolone acetate passes the process of hydrolysis, as a result of which it acquires its active form (with the participation of serum cholinesterases). Forms of substance in men are poorly synthesized with transcortin, as well as albumin. Synthesis is approximately 40-90% of the drug. The activity of glucocorticoids within cells is explained by the significant difference between the plasma half-life and the pharmacological half-life. Drug activity continues to persist even after the decrease in the plasma level of drugs is below the indicators that can be determined.

The duration of the anti-inflammatory effect of GCS is approximately the same as the duration of the suppression of the GHA system.

After an IV injection in a 40 mg / ml method after approximately 7.3 ± 1 hour, a peak serum value of 1.48 ± 0.86 μg / 100 ml is observed. The half-life is 69.3 hours. With a one-time injection of drugs in the amount of 40-80 mg, the duration of the GGA system suppression can be 4-8 days.

When the drug is administered inside the joint (40 mg inwards to both knee joints - in the sum of 80 mg), its peak plasma value is about 21.5 μg / 100 ml and comes after 4-8 hours. Diffusion helps the substance to penetrate from the joint into the circulatory system (about 7 days). This indicator is confirmed by the duration of the inhibition of the GGA system, as well as by the serum level of the active drug component.

Methylprednisolone is exposed to hepatic metabolism in amounts similar to cortisol. Its main degradation products are 20-beta-hydroxymethylprednisolone together with 20-beta-hydroxy-6-alpha-methylprednisone. Decay products are mainly excreted in the urine in the form of sulfates with glucuronides, as well as compounds of unconjugated type. Similar conjugation reactions are predominantly carried out inside the liver, as well as a little inside the kidneys.

[7], [8]

Dosing and administration

The medication is administered in / with either the / m method, and in addition, either intrabusally or periarticularly, into the soft tissue or foci of the disease and into the rectum.

Use to obtain systemic effects.

The size of the / m dose depends on the severity of the pathology. To obtain a lasting effect, the size of the weekly dosage is calculated by multiplying the daily oral dosage by 7, and then administered by a single injection.

Dosages are determined individually, depending on the person's reaction to the drug and on the severity of the disease. The total duration of the course should be as short as possible. The patient needs medical care.

For children (also newborns), the recommended dosage should be lowered, but it should be changed first, taking into account the severity of the disease. Following the instructions of proportions relative to the weight and age of the child is secondary.

For people with adrenogenital syndrome, a one-time injection of 40 mg of medication is usually given, which is administered at intervals of 2 weeks.

With maintenance treatment, people with rheumatoid arthritis type receive a drug dose of 40-120 mg once a week.

The standard dosage for people with dermatological lesions is reduced in the case of a systemic course using SCS and is 40-120 mg - is administered intravenously once, at intervals of 1 month between the procedures. With severe dermatitis in acute form (due to ivy intoxication), the patient can be relieved by a single intravenous injection at a rate of 80-120 mg (the effect occurs after 8-12 hours). In the case of the development of a contact form of dermatitis (chronic type), it may be necessary to perform repeated procedures - injections are performed at intervals of 5-10 days. With the seborrheic form of dermatitis, the disease can be controlled with weekly injections of 80 mg.

After injection of the medicine in the amount of 80-120 mg to a person with bronchial asthma, the improvement of the condition is observed after 6-48 hours, and this effect lasts for several days and can go up to 2 weeks.

In people with an allergic rhinitis, intramuscular injection of 80-120 mg of LS can reduce the manifestations of the disease (6 hours after injection). The effect is kept for several days (maximum 3 weeks).

Use in situ for local effects.

In the case of osteoarthritis and rheumatoid arthritis, the dosage size for intravenous injection depends on the degree of severity of the pathology in a person, and also on the size of its joint. In chronic diseases, the administration procedure is allowed to repeat at intervals of 1-5 (and more) weeks, taking into account the degree of improvement that was observed with the 1st injection. The following are the general sizes of standard doses for different sites of administration:

• large joint (in the shoulder, knee or ankle) - the dose limits are 20-80 mg;
• middle joint (radiocarpal or in the region of the elbows) - dosage limits within 10-40 mg mg;
• small joint (in the interphalangeal or metacarpophalangeal region, as well as in the acromioclavicular or sternoclavicular area) -dose sizes are 4-10 mg.

With bursitis. Before injection, the injection site must be completely cleaned, and infiltration should be performed with novocaine (1% solution). Next, take the needle (size 20-24), attach it to a dry syringe, and inject it into the area of the joint bag to perform aspiration of the liquid. After the end of the procedure, the needle is left in place, and the syringe is replaced with the other, the one containing the required dose of drugs. When the injection is completed, you need to get the needle and apply a small bandage to the procedure.

Other diseases: ganglion and epicondylitis with tendinitis. Taking into account the severity of the pathology, the dosage range can be 4-30 mg. In the case of relapse or chronic disease, repeated injection may be necessary.

Injections that have a local effect in dermatological pathologies. First, the area of administration is cleared (use a suitable antiseptic - for example, 70% alcohol), and then a drug injection of 20-60 mg is given. If the affected area is too large, you need to divide the dosage of 20-40 mg into separate parts, and then insert them into different places on the damaged skin. Use the medicine carefully, so as not to introduce it in an amount that can provoke depigmentation - therefore, as a result of this, powerful necrosis can develop. Often, 1-4 injections are performed. Intervals between procedures depend on the duration of improvement observed after the initial injection.

Injection into rectal area.

It was found that addition to the main treatment of Depo-Medrol at dosages equal to 40-120 mg (with the help of microclysters) or by regular instillation of the substance 3-7 times in 7 days in a period of 2+ weeks showed a good result in people with ulcerative colitis. To control the state of health of the majority of patients it is possible with the help of injections of medicines in the amount of 40 mg with water (30-300 ml).

The use of GCS in children, as well as infants and adolescents, can provoke delays in growth processes that can become irreversible. Therefore, it is required to conduct therapy with a short-term course, with the restriction of the dose size to minimally effective parameters.

Newborns, as well as children who are treated with SCS for a long period of time, are at very great risk of increasing ICP rates. The use of drugs in high doses can provoke a child's appearance of pancreatitis.

[14], [15], [16]

Use of the depot-Medrol during pregnancy

In the course of individual tests on animals, it was found that when injecting pregnant women with large doses of GCS, fetal malformations may occur.

The use of corticosteroids in pregnant animals can cause some defects in embryonic development (among them the cleft palate, delay in intrauterine growth processes, and also a negative impact on brain development and growth). There is no evidence that SCS increases the number of cases with the development of congenital malformations (eg, the wolf mouth) in humans, but with repeated administration or prolonged use during pregnancy, they can increase the likelihood of delay in the development of the fetus in the womb.

Therefore, as tests for the teratogenicity of GCS in humans have not been performed, it is recommended to use the drug (in pregnancy, lactation or in women of reproductive age) exclusively in situations where the benefits for women will be higher than the possibility of complications in the fetus / child.

Corticosteroids are able to penetrate the placental barrier. There is no effect of this substance on the birth process.

Contraindications

Among the contraindications:

• injections by epidural, intrathecal, intranasal method, as well as introduction into the eye area and other separate areas (such as the oropharynx, the skin on the skull and the winged nodule);
• infections of a general type caused by fungi;
• hypersensitivity to the active component and other components of drugs;
• Persons receiving SCS in immunosuppressive dosages can not use live or attenuated vaccines.

[9], [10]

Side effects of the depot-Medrol

When injecting drugs in / m, the following side effects are observed:

• disturbance of the water-salt balance. In comparison with hydrocortisone or cortisone, the development of mineralocorticoid exposure is less likely when using synthetic derivatives, among which methylprednisolone acetate. As a result of this disorder, delays in fluid and salts develop, hypokalemic form of alkalosis, congestive heart failure in persons with a predisposition, blood pressure increases, and potassium loss;
• lymphatic and hematopoietic reactions: leukocytosis may develop;
• violations of cardiovascular function: there may be a rupture of the myocardium due to myocardial infarction. Possible development of thrombotic manifestations;
• manifestations from the ODA: muscle weakness, steroid form of myopathy, aseptic necrosis, osteoporosis, and vertebral fractures of compression type and fractures that have a pathological character. Also possible: muscle atrophy, ruptures in the tendon (especially Achilles), myalgia, osteonecrosis of the avascular type, arthralgia and neuropathic form of arthropathy;
• disorders in the gastrointestinal tract: ulcerative lesion, against which bleeding or perforation can be observed, and in addition pancreatitis, intestinal perforation, bleeding within the stomach and esophagitis. There may be a transient increase in moderate-type AFP, but there is no clinical syndrome. Among other manifestations of the disorder: candidiasis or ulcers inside the esophagus, flatulence, abdominal pain, dyspepsia and diarrhea;
• reactions of the hepatobiliary system: hepatitis may appear or an increase in the activity of liver enzymes (eg, ALT or AST);
• dermatological manifestations: violation of wound regeneration, thinning and weakening of the skin, as well as its atrophy, the appearance of ecchymoses with petechiae, stretch marks, acne, rashes and itching, and bruises. Erythema, urticaria, Quincke edema, skin hypopigmentation, telangiectasia and hyperhidrosis may develop;
• neurological disorders: the development of intracranial hypertension (also benign) and the appearance of seizures;
• mental disorders: there are mood swings, personal changes, a feeling of irritability, euphoria, anxiety, and also the appearance of thoughts of suicide. Insomnia and other sleep disorders, severe depression, and cognitive dysfunction (including amnesia and confusion) can develop. There may be disturbances in behavior, psychotic manifestations (hallucinations, mania and delirium, and in addition to exacerbation of schizophrenia) and dizziness. Headaches and epidural-type lipomatosis also occur;
• manifestations of the organs of the endocrine system: development of amenorrhea, hypercorticism syndrome and hirsutism. The disorder of the menstrual cycle, the delay of child growth, the suppression of the pituitary-adrenal function, the weakening of tolerance for carbohydrates, and in addition the increase in the body's need for insulin or oral hypoglycemic drugs in the presence of diabetes mellitus and signs of latent diabetes mellitus;
• Ophthalmic manifestations: long-term use of SCS can cause subcapsular cataracts of the posterior type, as well as glaucoma, which can cause damage in the optic nerve and the appearance of secondary eye infections (due to the action of viruses or fungi). There may be an increase in IOP, exophthalmos, and in addition to papilloedema, thinning of the sclera or cornea, and chorioretinopathy. People with usual eye herpes or with its location in the ocular area of the SCS are used cautiously, because there is a risk of perforation of the cornea;
• metabolic disorders and alimentary pathologies: increased appetite and a negative balance of calcium with nitrogen due to protein catabolism;
• infections or invasive diseases: infections of an opportunistic type and at the injection site, and in addition, the development of peritonitis;
• immune reactions: manifestations of intolerance (anaphylaxis);
• impairment of respiratory function: stable hiccup in case of use of large doses of SCS, relapse of latent tuberculosis;
• systemic signs: development of thromboembolism, leukocytosis or nausea;
• withdrawal syndrome: with too rapid a decrease in the dose of GCS after prolonged use, there may be adrenal insufficiency in the acute stage, lowering the level of blood pressure and death. In addition, arthralgia, runny nose, myalgia and conjunctivitis with itchy and painful skin nodes may occur, and temperature and weight may decrease.

When parenteral treatment with GCS is performed, the following disorders may appear:

• Single blindness develops (due to injection of drugs in the focus near the head or face);
• manifestations of allergy and anaphylaxis;
• hyper or hypopigmentation;
• abscess of sterile type;
• atrophy in the area of the skin with a subcutaneous layer;
• when injected into the joint, post-injection exacerbations are observed;
• A reactive arthritis similar to Charcot's arthropathy;
• Infection may occur if the sterility rules are not observed during the procedure at the site of administration.

Disorders arising from the use of contraindicated methods of injection:

• intrathecal method: the occurrence of vomiting, seizures, headaches, nausea and sweating. In addition, the development of Dupree's disease, arachnoiditis with meningitis and paraplegia, and with it an intestinal / urinary function disorder, as well as sensitivity and cerebrospinal fluid;
• extradural method: loss of sphincter control and divergence of wound edges;
• intranasal route: persistent or transient visual disorders (eg, blindness), the onset of a runny nose and other allergic symptoms.

[11], [12], [13]

Overdose

There is no information on the development of acute intoxication due to the use of methylprednisolone acetate.

With frequent repeated injections of Depo-Medrol (daily or several times per week) over a long period of time, the development of hypercorticoid syndrome is possible.

Interactions with other drugs

Among the appropriate interactions.

In the treatment of pulmonary tuberculosis of disseminated or fulminant type or tubercular form of meningitis (accompanied by a threatening or subarachnoidal block), it is permitted to combine methylprednisolone with appropriate anti-tuberculosis drugs.

In the process of therapy in cancer pathologies (including lymphoma with leukemia), the medication is often combined with an alkylating drug, Vinca rosea alkaloid, and antimetabolite.

Among inappropriate interactions.

GKS can increase the clearance of salicylates in the kidneys. As a result, the serum salicylate values may decrease with increasing their toxic properties upon cancellation of GCS.

Macrolide antibiotics, among which ketoconazole with erythromycin, are able to slow the metabolic processes of GCS. To prevent intoxication, you need to adjust the dosage size of GCS.

Combination with rifampicin, primidon and phenylbutazone, and in addition to carbamazepine and barbiturates, as well as with phenytoin and rifabutin, can lead to induction of metabolism or a decrease in the efficacy of GCS.

When combined with GCS, the response to anticoagulants may increase / decrease. As a consequence, it is required to monitor the coagulation indicators.

The GCS can increase the insulin requirement or the need for oral hypoglycemic drugs in people with diabetes mellitus. The combination of a drug with diuretics of the thiazide type increases the likelihood of reducing the body's tolerance for glucose.

Combination with ulcerogenic drugs (such as NSAIDs and salicylates) may increase the likelihood of ulcers in the digestive tract.

If hypoprothrombinemia is present, it is necessary to combine aspirin with GCS cautiously.

The use of the drug together with cyclosporine sometimes led to the appearance of seizures. The combination of these drugs caused mutual oppression of the exchange processes. It is possible that convulsions or negative manifestations associated with the separate use of these medicines may become more frequent when combined.

The combination with quinolones increases the likelihood of tendonitis.

Combination with inhibitors of the substance cholinesterase (among them pyridostigmine or neostigmine) can cause a myasthenic crisis.

The required effect of antidiabetic agents (among them insulin), hypotensive drugs and diuretics is inhibited by corticosteroids. Potentiation of hypokalemic properties of acetazolamide, diuretic thiazide or loop type, as well as carbenoxolone is observed.

Combination with antihypertensive drugs may contribute to a partial loss of control over the increase in blood pressure, because the mineralocorticoid effect of GCS can increase blood pressure.

Simultaneous use together with GCS potentiates toxic properties of cardiac glycosides, as well as related drugs. This is due to the fact that the mineralocorticoid action of GCS can cause potassium excretion.

The substance of methotrexate can affect the effectiveness of methylprednisolone - by providing a synergistic effect on the condition of the pathology. With this in mind, it is possible to reduce the dosage of GCS.

The active component of Depot-Medrol is able to partially inhibit the properties of neuromuscular blocking drugs (such as pancuronium).

The drug is able to potentiate a reaction to sympathomimetics (eg, salbutamol). As a result, the effectiveness of these agents increases and their toxicity may increase.

Methylprednisolone is a substrate of the hemoprotein enzyme P450 (CYP). It undergoes a metabolism in which the enzyme CYP3A participates. Element CYP3A4 is the dominant enzyme of the most common CYP subtype within the adult liver. This component is a catalyst for steroid 6-β-hydroxylation and the main stage of the first stage of the metabolism of internal and artificial GCS. A number of other compounds are also substrates of the element CYP3A4. Individual components (like other drugs) cause a change in the metabolic processes of the GCS, activating or slowing the isoenzyme CYP3A4.

Storage conditions

Depot-Medrol should be kept out of reach of small children. Do not freeze the suspension. The temperature level is not more than 25 ° С.

[17], [18]

Shelf life

Depot-Medrol can be used in the period of 5 years since the release of the medicine.

[19], [20], [21], [22]