Depo-medrol

Depo-medrol is a glucocorticoid. It belongs to the category of simple systemic corticosteroids.

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Indications Depo-medrol

Glucocorticoids are used exclusively to eliminate the symptoms of diseases. But sometimes they are used as a means of replacement therapy - for some endocrine pathologies.

Therapy for inflammatory diseases.

In rheumatic pathologies, it is used as an additional drug in supportive therapy (use of physiotherapy and kinesitherapy, as well as painkillers, etc.). It can be used for a short course of treatment (to bring the patient out of an acute condition or during an exacerbation of a chronic disease) in Bechterew's disease or psoriatic arthritis.

For the diseases described below, the medicine must be administered (if possible) by the in situ method. Among the pathologies:

• osteoarthritis of post-traumatic type;
• synovitis developing against the background of osteoarthritis or rheumatoid arthritis (this includes the juvenile type of the disease) (sometimes only supportive treatment using small doses may be required);
• bursitis in the acute or subacute stage;
• epicondylitis;
• non-specific form of tenosynovitis in the acute stage;
• acute form of arthritis of the gouty type.

For collagenoses. In some cases, it is used during an exacerbation or to maintain the patient's condition during SLE, systemic polymyositis, and also during the rheumatic form of carditis in the exacerbation stage.

Dermatological diseases: erythema multiforme in severe stage, pemphigus, exfoliative dermatitis, fungoid granuloma and Duhring's disease. In the latter case, the main drug is sulfone, and systemic GCS are used as additional drugs.

Allergic pathologies. Used as a means of control for severe allergies or those with a disabling effect that cannot be eliminated using standard medical methods. Among these:

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

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

• an eye disease that develops due to shingles;
• iridocyclitis with iritis;
• diffuse choroiditis;
• chorioretinitis;
• neuritis in the optic nerve region.

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

In case of edema, Depo-Medrol is used to stimulate the process of diuresis or induce remission in case of development of proteinuria against the background of nephrotic syndrome without development of uremia (idiopathic form or caused by SLE).

Diseases of the respiratory system:

• symptomatic respiratory sarcoidosis;
• beryllium lung disease;
• pulmonary tuberculosis of disseminated or fulminant type (used in combination with anti-tuberculosis chemotherapy procedures);
• Löffler's syndrome, which cannot be eliminated by other treatment methods;
• Mendelson syndrome.

Therapy for oncological and hematological pathologies.

Diseases of a hematological nature – hemolytic anemia (autoimmune, acquired), as well as hypoplastic type (congenital), and also erythroblastopenia or secondary thrombocytopenia (in adults).

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

Endocrine disorders.

It is used in the following cases:

• adrenal cortex insufficiency of primary or secondary type;
• the above-mentioned disease in an acute form - in this case, the main medicine is considered to be cortisone or hydrocortisone. If necessary, artificial analogues of these substances can be combined with mineralocorticoids (taking these drugs in early childhood is very important);
• congenital adrenal hyperplasia;
• hypercalcemia resulting from malignant neoplasm;
• non-purulent form of thyroiditis.

Pathologies in other systems and organs.

It is used in the tuberculous form of meningitis, which is accompanied by a threatening or subarachnoid block (in combination with appropriate chemotherapy) and trichinosis with the participation of the myocardium or nervous system. In reactions of the nervous system organs: for the treatment of exacerbated multiple sclerosis.

Use for injection directly into the lesion.

Depo-Medrol should be administered using the specified method to treat the following diseases:

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

The drug can be effective in the case of development of aponeurosis, cystic tumors or tendinosis.

Application for insertion into the rectal area.

The medicine is administered by this method to eliminate ulcerative colitis.

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Release form

Released as an injection suspension in 1 ml vials. Inside a separate package there is 1 vial.

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Pharmacodynamics

Depo-Medrol is a sterile injection suspension containing an artificial GCS – methylprednisolone acetate. The substance has long-lasting and powerful antiallergic, anti-inflammatory and immunosuppressive properties. The drug can be administered intramuscularly to achieve a long-lasting effect, and also in situ – for local therapy. The long duration of the drug’s medicinal activity is explained by the fact that its active component is released rather slowly.

The general characteristics of the active substance are similar to those of the GCS methylprednisolone, but it dissolves worse and is subject to slower metabolism, which can explain the long duration of its action.

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

The active component not only has a significant effect on immune reactions and inflammatory processes, but also affects the metabolism of fats and proteins with carbohydrates. In addition, the drug affects the functions of the central nervous system and cardiovascular system, as well as skeletal muscles.

Effects on immune responses and inflammation.

Antiallergenic, anti-inflammatory and immunosuppressive effects lead to the development of the following actions:

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

A dosage of 4.4 mg of methylprednisolone acetate (or 4 mg of the substance methylprednisolone) has an anti-inflammatory effect similar to that of 20 mg of hydrocortisone. Methylprednisolone has weak mineralocorticoid properties (the value of 200 mg of the component methylprednisolone is equal to 1 mg of the substance deoxycorticosterone).

Effects on carbohydrate and protein metabolism.

Glucocorticoids have a catabolic effect on protein metabolism. The amino acids released during this process are converted in the liver into glycogen with glucose (with the participation of gluconeogenesis). Glucose absorption in peripheral tissues decreases, which can result in the development of glucosuria with hyperglycemia (this is especially true for people with a tendency to develop diabetes mellitus).

Impact on fat metabolism processes.

The medicine has lipolytic properties, which are most clearly manifested in the limbs. It also has a lipogenetic effect, which is most clearly manifested in the head with the neck and sternum. As a result of these processes, there is a redistribution of existing fat reserves.

The peak of its medicinal activity of GCS is reached later than its maximum values in the blood are observed. This allows us to conclude that the most pronounced properties of the drug are more likely to develop due to changes in enzymatic activity, rather than due to the direct effect of the drug.

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Pharmacokinetics

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

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

After intramuscular injections in the amount of 40 mg/ml, after approximately 7.3±1 hour, the peak serum level of the substance is 1.48±0.86 μg/100 ml. The half-life is 69.3 hours. With a single administration of the drug in the amount of 40-80 mg, the duration of the suppression of the HPA system can be 4-8 days.

When the drug is administered intra-articularly (40 mg intra-articularly into both knee joints – 80 mg in total), its peak plasma level is about 21.5 mcg/100 ml and occurs after 4-8 hours. Diffusion helps the substance to penetrate from the joint into the circulatory system (in a period of about 7 days). This indicator is confirmed by the duration of the process of suppression of the HPA system, as well as the serum level of the active component of the drug.

The substance methylprednisolone undergoes hepatic metabolism in amounts similar to cortisol. Its main breakdown products are 20-beta-hydroxymethylprednisolone together with 20-beta-hydroxy-6-alpha-methylprednisone. The breakdown products are mainly excreted in the urine in the form of sulfates with glucuronides, as well as compounds of the unconjugated type. Such conjugation reactions occur mainly in the liver, and to a small extent in the kidneys.

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Dosing and administration

The medicine is administered intramuscularly or intrasacral, and also intrabursally or periarticularly, into the area of soft tissue or the site of the disease and into the rectum.

Use to achieve systemic effects.

The size of the intramuscular dosage depends on the severity of the pathology. To obtain a long-term effect, the weekly dosage is calculated by multiplying the daily oral dosage by 7, and then administered as a single injection.

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

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

For people with adrenogenital syndrome, a single injection of 40 mg of the drug is usually prescribed, administered at intervals of 2 weeks.

For maintenance treatment, individuals with rheumatoid arthritis are administered a dose of 40-120 mg of the drug once a week.

The standard dosage for people with dermatological lesions is reduced in the case of a systemic course using GCS and is 40-120 mg - administered intramuscularly once with intervals of 1 month between procedures. In severe acute dermatitis (due to ivy intoxication), the patient's condition can be alleviated with a single intramuscular injection of 80-120 mg (the effect occurs after 8-12 hours). In the case of contact dermatitis (chronic type), repeated procedures may be necessary - injections are performed at intervals of 5-10 days. In the case of seborrheic dermatitis, the disease can be controlled with weekly injections of 80 mg.

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

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

In situ use for local effects.

In osteoarthritis and rheumatoid arthritis - the dosage size for intravenous injection depends on the severity of the pathology in a person, as well as the size of his joint. In chronic diseases, the injection procedures are allowed to be repeated at intervals of 1-5 (or more) weeks, taking into account the degree of improvement observed with the 1st injection. Below are the general sizes of standard doses for different injection sites:

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

For bursitis. Before the injection, the injection area must be completely cleaned, and infiltration must be performed using novocaine (1% solution). Next, take a needle (size 20-24), attach it to a dry syringe, and insert it into the joint capsule to perform fluid aspiration. After the procedure, leave the needle in place, and replace the syringe with another one - one that contains the required dose of the drug. After the injection, remove the needle and apply a small bandage to the procedure site.

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

Injections that have a local effect on dermatological pathologies. First, the injection area is cleaned (use a suitable antiseptic - for example, 70% alcohol), and then the drug is injected in the amount of 20-60 mg. If the affected area is too large, it is necessary to divide the dosage of 20-40 mg into separate parts, and then inject them into different places on the damaged skin. The drug should be used carefully so as not to inject it in an amount that can provoke depigmentation - because as a result, severe necrosis can develop. Often 1-4 injections are performed. The intervals between procedures depend on the duration of the improvement observed after the initial injection.

Injection into the rectal area.

It was found that the use of Depo-Medrol in addition to the main treatment in dosages equal to 40-120 mg (using microclysters), or by regular instillation of the substance - 3-7 times per 7 days for a period of 2+ weeks, showed good results in people with ulcerative colitis. The health of most patients can be monitored using injections of the drug 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 growth retardation, which may become irreversible. Therefore, it is necessary to conduct therapy in a short course, with the dose size limited to the minimum effective indicators.

Newborns and children who are treated with GCS for a long period of time are at very high risk of increased ICP. The use of drugs in high doses can provoke pancreatitis in a child.

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Use Depo-medrol during pregnancy

In the course of individual animal tests, it was found that when pregnant women are injected with large doses of GCS, the fetus may develop developmental defects.

The use of corticosteroids in pregnant animals may cause some birth defects (including cleft palate, intrauterine growth retardation, and adverse effects on brain development and growth). There is no evidence that corticosteroids increase the incidence of birth defects (e.g., cleft palate) in humans, but with repeated or prolonged use during pregnancy they may increase the likelihood of fetal growth retardation.

Since tests regarding the teratogenicity of GCS in humans have not been performed, it is recommended to use the drug (during pregnancy, lactation or in women of reproductive age) only in situations where the benefit to the woman will be higher than the possible risk of complications in the fetus/child.

Corticosteroids are able to penetrate the placental barrier. No effect of this substance on the process of labor is observed.

Contraindications

Among the contraindications:

• injections by epidural, intrathecal, intranasal methods, as well as administration into the eye area and other individual areas (such as the oropharynx, scalp and pterygopalatine ganglion);
• general infections caused by fungi;
• hypersensitivity to the active component and other components of the drug;
• Persons receiving GCS in immunosuppressive doses cannot use live or attenuated vaccines.

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Side effects Depo-medrol

When injecting drugs intramuscularly, the following side effects are observed:

• water-salt imbalance disorder. In comparison with hydrocortisone or cortisone, the development of mineralocorticoid effects is less likely when using synthetic derivatives, including methylprednisolone acetate. As a result of this disorder, fluid and salt retention, hypokalemic alkalosis, congestive heart failure in predisposed individuals develop, blood pressure increases, and potassium loss is observed;
• reactions of the lymph and hematopoietic system: development of leukocytosis is possible;
• Cardiovascular dysfunction: myocardial rupture may occur due to myocardial infarction. Thrombotic manifestations may develop;
• manifestations from the musculoskeletal system: muscle weakness, steroid myopathy, aseptic necrosis, osteoporosis, as well as vertebral compression fractures and fractures of a pathological nature. Also possible: muscle atrophy, tendon ruptures (especially Achilles), myalgia, avascular osteonecrosis, arthralgia and neuropathic arthropathy;
• Gastrointestinal disorders: ulcerative lesions, which may result in bleeding or perforation, as well as pancreatitis, intestinal perforation, bleeding inside the stomach, and esophagitis. A transient increase in moderate ALP levels is possible, but no clinical syndrome is observed. Other manifestations of the disorder include candidiasis or ulcers inside the esophagus, flatulence, abdominal pain, dyspepsia, and diarrhea;
• reactions of the hepatobiliary system: hepatitis may develop or the activity of liver enzymes may increase (for example, ALT or AST);
• dermatological manifestations: impaired wound regeneration, thinning and weakening of the skin, as well as its atrophy, the appearance of ecchymosis with petechiae, stretch marks, acne, rashes and itching, as well as bruises. Erythema, urticaria, Quincke's edema, skin hypopigmentation, telangiectasia and hyperhidrosis may develop;
• neurological disorders: development of intracranial hypertension (also benign) and the appearance of seizures;
• Mental disorders: mood swings, personality changes, irritability, euphoria, anxiety, and suicidal thoughts are observed. Insomnia and other sleep disorders, severe depression, and cognitive dysfunction (including amnesia and confusion) may develop. Behavioral disturbances, psychotic manifestations (including hallucinations, mania, and delusions, as well as exacerbation of schizophrenia), and dizziness are possible. Headaches and epidural lipomatosis also occur;
• manifestations of the endocrine system: development of amenorrhea, hypercorticism syndrome and hirsutism. Menstrual cycle disorders, delayed growth in children, suppression of the pituitary-adrenal function, weakening of tolerance to carbohydrates, as well as an increase in the body's need for insulin or oral hypoglycemic drugs in the presence of diabetes mellitus and signs of latent diabetes mellitus;
• ophthalmologic manifestations: prolonged use of GCS can cause posterior subcapsular cataract, as well as glaucoma, which can provoke damage to the optic nerves and the appearance of secondary eye infections (due to the action of viruses or fungi). An increase in IOP, exophthalmos, and in addition papilloedema, thinning of the sclera or cornea, as well as chorioretinopathy may be observed. People with common ocular herpes or when it is located in the periorbital area, GCS are used with caution, because there is a risk of corneal perforation;
• metabolic disorders and alimentary pathologies: increased appetite and negative calcium-nitrogen balance due to protein catabolism;
• infections or invasive diseases: opportunistic infections and at the injection site, as well as the development of peritonitis;
• immune reactions: manifestations of intolerance (anaphylaxis);
• respiratory dysfunction: persistent hiccups in case of using high doses of GCS, relapse of latent tuberculosis;
• systemic symptoms: development of thromboembolism, leukocytosis or nausea;
• Withdrawal syndrome: if the dose of GCS is reduced too quickly after prolonged use, acute adrenal insufficiency, decreased blood pressure and death may occur. In addition, arthralgia, rhinitis, myalgia and conjunctivitis with itchy and painful skin nodules may occur, as well as a decrease in temperature and weight.

When performing parenteral treatment with GCS, the following disorders may occur:

• blindness develops occasionally (due to injection of drugs into the lesion 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 the subcutaneous layer;
• when injected into the joint, post-injection exacerbations are observed;
• reactive arthritis similar to Charcot arthropathy;
• If the rules of sterility are not followed during the procedure, infections may appear at the injection site.

Disorders resulting from the use of contraindicated injection methods:

• intrathecal route: the appearance of vomiting, convulsions, headaches, nausea and sweating. In addition, the development of Dupre's disease, arachnoiditis with meningitis and paraplegia, and along with this, a disorder of intestinal/urinary function, as well as sensitivity and cerebrospinal fluid;
• extradural method: loss of control over the sphincter and divergence of the wound edges;
• intranasal route: permanent or transient visual disturbances (eg, blindness), the appearance of a runny nose and other allergic symptoms.

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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 a week) over a long period of time, the development of hypercorticism syndrome is possible.

Interactions with other drugs

Among the suitable interactions.

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

During therapy for oncological pathologies (including lymphoma and leukemia), the drug is often combined with an alkylating agent, the alkaloid Vinca rosea, and an antimetabolite.

Among inappropriate interactions.

GCS can enhance the clearance of salicylates within the kidneys. As a result, a decrease in serum salicylate levels may be observed with an increase in their toxic properties when GCS is discontinued.

Macrolide antibiotics, including ketoconazole with erythromycin, can slow down the processes of GCS metabolism. To prevent intoxication, it is necessary to adjust the dosage of GCS.

Combination with rifampicin, primidone and phenylbutazone, as well as with carbamazepine and barbiturates, as well as with phenytoin and rifabutin, may lead to induction of metabolism or a decrease in the effectiveness of GCS.

When combined with GCS, the response to anticoagulants may increase/decrease. As a result, it is necessary to monitor coagulation parameters.

GCS agents can increase insulin requirements or the need for oral hypoglycemic drugs in people with diabetes. Combination of the drug with thiazide-type diuretics increases the likelihood of decreased glucose tolerance.

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

In the presence of hypoprothrombinemia, aspirin should be combined with GCS with caution.

The use of the drug together with cyclosporine sometimes led to the occurrence of convulsions. The combination of these drugs caused mutual inhibition of metabolic processes. It is possible that convulsions or negative manifestations associated with the separate use of these drugs may increase in frequency when they are combined.

Combination with quinolones increases the likelihood of tendonitis.

Combination with cholinesterase inhibitors (including pyridostigmine or neostigmine) may cause myasthenic crisis.

The required effect of antidiabetic agents (including insulin), hypotensive drugs and diuretics is inhibited by corticosteroids. In this case, potentiation of the hypokalemic properties of acetazolamide, thiazide or loop diuretics, and 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 levels.

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

The substance methotrexate is able to influence the effectiveness of methylprednisolone - exerting a synergistic effect on the condition of the pathology. Taking this into account, it is possible to reduce the dosage of GCS.

The active component of Depo-Medrol is capable of partially inhibiting the properties of drugs that block neuromuscular transmission (such as pancuronium).

The drug can potentiate the reaction to sympathomimetics (for example, salbutamol). As a result, the effectiveness of these drugs increases and their toxicity may increase.

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

Storage conditions

Depo-Medrol should be kept out of the reach of small children. Do not freeze the suspension. The temperature level should not exceed 25°C.

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Shelf life

Depo-Medrol can be used for a period of 5 years from the date of release of the drug.

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