Pharmacological properties
Pharmacodynamics. The effect of methylprednisolone, like other glucocorticoids, is realized through interaction with steroid receptors in the cytoplasm. The steroid receptor complex is transported into the cell nucleus, binds to DNA and changes the transcription of genes for most proteins. Glucocorticoids inhibit the synthesis of many proteins, various enzymes that cause joint destruction (in rheumatoid arthritis), as well as cytokines that play an important role in immune and inflammatory reactions. Induce the synthesis of lipocortin - a key protein of the neuroendocrine interaction of glucocorticoids, which leads to a decrease in the inflammatory and immune response.
GCS, including methylprednisolone, suppress or prevent the development of tissue responses to many thermal, mechanical, chemical, infectious and immunological agents. Thus, GCS act symptomatically, reducing the symptoms of the disease without affecting the cause. The anti-inflammatory effect of methylprednisolone is at least 5 times greater than the effectiveness of hydrocortisone.
The endocrine effects of methylprednisolone are to suppress the secretion of ACTH, inhibit the production of endogenous cortisol, and with prolonged use cause partial atrophy of the adrenal cortex. A single dose of 40 mg of methylprednisolone inhibits the secretion of corticotropin for about 36 hours. They affect the metabolism of calcium, vitamin D, carbohydrate, protein and lipid metabolism, so patients taking methylprednisolone may experience an increase in blood glucose, a decrease in bone density, muscle atrophy and dyslipidemia. GCS also increase blood pressure, model behavior and mood. Methylprednisolone has practically no mineralocorticoid activity.
Pharmacokinetics. The bioavailability of oral methylprednisolone is usually more than 80%, but can decrease to 60% in the case of high doses. When methylprednisolone is taken orally, C max in blood plasma is reached after 1-2 hours. Methylprednisolone is 77% bound to plasma proteins, the binding to transcortin is insignificant. The volume of distribution is 1-1.5 l/kg. Methylprednisolone is metabolized to inactive metabolites. The average clearance is 6.5 ml/kg/min. The duration of the anti-inflammatory effect is 18-36 hours. About 5% of the drug is excreted in the urine. Methylprednisolone crosses the placenta and is excreted in breast milk. Methylprednisolone is removed by dialysis.
Indication
Primary and secondary adrenal insufficiency (in this case, the first-line drugs are hydrocortisone or cortisone, if necessary, synthetic analogues can be used in combination with mineralocorticoids; simultaneous use of mineralocorticoids is especially important for the treatment of children).
Congenital adrenal hyperplasia.
Non-purulent thyroiditis.
Hypercalcemia in cancer.
Rheumatic diseases. As an additional therapy for short-term use (to remove the patient from an acute condition or during exacerbation of the process) in the following diseases:
psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (in some cases, low-dose maintenance therapy may be required); ankylosing spondylitis; acute and subacute bursitis; acute nonspecific tendosynovitis; acute gouty arthritis; post-traumatic osteoarthritis; synovitis in osteoarthritis; epicondylitis.
Collagenoses. During the period of exacerbation or in some cases as supportive therapy for the following diseases:
systemic lupus erythematosus; systemic dermatomyositis (polymyositis); acute rheumatic carditis; polymyalgia rheumatica in giant cell arteritis.
Skin diseases:
pemphigus; bullous dermatitis herpetiformis; severe erythema multiforme (Stevens-Johnson syndrome); exfoliative dermatitis; mycosis fungoides; severe psoriasis; severe seborrheic dermatitis.
Allergic conditions. For the treatment of the following severe and allergic conditions when standard treatment is ineffective:
seasonal or perennial allergic rhinitis; serum sickness; asthma; drug allergy; contact dermatitis; atopic dermatitis.
Eye diseases. Severe acute and chronic allergic and inflammatory processes with eye damage, such as:
Allergic corneal marginal ulcers; Herpes zoster eye lesions; anterior segment inflammation; diffuse posterior uveitis and choroiditis; sympathetic ophthalmia; allergic conjunctivitis; keratitis; chorioretinitis; optic neuritis; iritis and iridocyclitis.
Respiratory diseases:
symptomatic sarcoidosis; Loeffler's syndrome, not amenable to other treatment methods; berylliosis; fulminant or disseminated pulmonary tuberculosis (used in combination with appropriate anti-tuberculosis chemotherapy); aspiration pneumonitis.
Hematological diseases:
idiopathic thrombocytopenic purpura in adults; secondary thrombocytopenia in adults; acquired (autoimmune) hemolytic anemia; erythroblastopenia (erythrocytic anemia); congenital (erythroid) hypoplastic anemia.
Oncological disease. As palliative therapy for the following diseases:
leukemias and lymphomas in adults; acute leukemia in children.
Diseases of the digestive tract. To bring the patient out of critical condition in the following diseases:
ulcerative colitis; regional enteritis (Crohn's disease).
Diseases of the nervous system:
multiple sclerosis in the exacerbation phase; cerebral edema caused by a brain tumor.
Diseases of other organs and systems:
tuberculous meningitis with subarachnoid block or with the threat of developing a block, in combination with appropriate anti-tuberculosis chemotherapy; trichinosis with damage to the nervous system or myocardium.
Organ transplantation.
Application
The initial dose of Metipred for adults may be 4-48 mg of methylprednisolone per day, depending on the nature of the disease. In less severe diseases, lower doses are usually sufficient, although individual patients may require higher starting doses. Higher doses may be used in diseases and conditions such as multiple sclerosis (200 mg/day), cerebral edema (200-1000 mg/day) and organ transplantation (up to 7 mg/kg/day).
If a satisfactory effect is achieved as a result of therapy, the patient should be selected for an individual maintenance dose by gradually reducing the initial dose at certain intervals until the lowest dose is established that will maintain the achieved clinical effect. It should be remembered that constant monitoring of the dosage regimen of the drug is necessary. Situations may arise in which it is necessary to adjust the dose; these include changes in the clinical condition due to the onset of remission or exacerbation of the disease, the patient's individual response to the drug, as well as the impact on the patient of stressful situations not directly related to the underlying disease, which is the subject of therapy; in the latter case, it may be necessary to increase the dose of the drug for a certain period, depending on the patient's condition. The required dose may vary and should be selected individually, depending on the nature of the disease and the patient's response to therapy.
It should be noted that the dose of the drug should be individual and based on an assessment of the course of the disease and the clinical effect.
The drug should not be discontinued suddenly, it should be done gradually.
Alternating therapy. Alternating therapy is a dosing regimen of corticosteroids in which a double daily dose of the corticosteroid is administered every other day, in the morning. The goal of this type of therapy is to achieve maximum clinical effect in a patient requiring long-term therapy while minimizing some undesirable effects, such as pituitary-adrenal axis suppression, Cushing's syndrome, corticosteroid withdrawal syndrome, and growth suppression in children.
Children. The drug is used in pediatric practice. It is necessary to carefully monitor the development and growth of children, including newborns, when using long-term therapy with corticosteroids.
In children receiving corticosteroids daily for a long time, several times a day, growth retardation may occur. Therefore, this dosage regimen should be used only for the most urgent indications. The use of alternating therapy, as a rule, makes it possible to avoid this side effect or minimize it (see APPLICATION, Alternating therapy).
Contraindication
Tuberculosis and other acute or chronic bacterial or viral infections with insufficient antibiotic and chemotherapy, systemic fungal infections. Hypersensitivity to methylprednisolone or excipients.
Side effects
When taking methylprednisolone, the same side effects develop as when taking other GCS. The duration of therapy and dosage affect the occurrence of side effects. With long-term therapy, side effects occur frequently, with a short duration of treatment - rarely.
Methylprednisolone may cause fluid and salt retention.
Because methylprednisolone in high doses causes insufficiency and atrophy of the adrenal cortex over a long period, in stressful conditions (such as surgery or infection) hypotension, hypoglycemia, and even death may develop unless the steroid dose is increased to adapt to the stressful conditions.
Abrupt withdrawal of long-term steroid therapy may cause withdrawal syndrome. The severity of symptoms depends on the degree of atrophy of the adrenal cortex. In mild cases, the following symptoms may occur: headache, nausea, abdominal pain, dizziness, loss of appetite, mood swings, weakness and fever. In severe cases, mental disorders and increased intracranial pressure may occur. Fatalities have been reported after abrupt withdrawal of glucocorticoid therapy. In patients with rheumatic diseases, pseudorheumatism may develop upon discontinuation of therapy.
In isolated cases, post-steroid panniculitis has been reported upon discontinuation of therapy. The appearance of firm, burning, red subcutaneous nodules has been reported, which appear approximately 2 weeks after discontinuation of therapy and disappear spontaneously.
Methylprednisolone can cause allergic and anaphylactic reactions.
The frequency of adverse reactions is classified as follows: very common (≥1/10); common (≥1/100, 1/10); uncommon (≥1/1000, 1/100); rare (≥1/10,000, 1/1000); very rare (1/10,000); frequency unknown (cannot be determined from the available data).
Immune system disorders: often - increased sensitivity to infections, masking of symptoms of infection; rarely - allergic and anaphylactic reactions.
Anaphylactoid reactions, possible suppression of reactions during skin tests.
Endocrine system disorders: often - suppression of endogenous secretion of ACTH and cortisol (with prolonged use), Cushing's syndrome, worsening or development of diabetic conditions. Metabolic acidosis, impaired glucose tolerance, increased need for insulin or oral antidiabetic agents in diabetes mellitus, increased appetite (which may lead to weight gain). Hypopituitarism.
Disturbances of water and electrolyte balance: often - hypokalemia, sodium retention. Hypokalemic alkalosis.
Mental disorders: infrequently - mood disorders, increased concentration, depression, mania, psychosis, insomnia.
Euphoria, delusions, exacerbation of schizophrenia, psychotic behavior, affective disorder (including affective lability, psychological dependence, suicidal thoughts), personality changes, mood swings, confusion, abnormal behavior, anxiety, irritability, amnesia, cognitive disorder.
Nervous system disorders: rarely - dementia, increased intracranial pressure (with optic disc edema (benign intracranial hypertension)), epileptic seizures.
Convulsions, neuropathic arthropathy, arthralgia, myalgia.
From the side of the organs of hearing and vestibular apparatus: vertigo.
Disorders of the organ of vision: infrequently - increased intraocular pressure, glaucoma, cataract.
Exophthalmos, thinning of the sclera and cornea.
Cardiovascular system disorders: infrequently - hypertension, thrombosis. Congestive heart failure (in patients with a predisposition to its development), embolism, myocardial rupture in the area of a previous myocardial infarction.
Respiratory, thoracic and mediastinal disorders: rarely - hiccups.
Digestive system disorders: rarely - gastric ulcer, pancreatitis. Peptic ulcer (with possible perforation and bleeding), intestinal perforation, gastric bleeding, ulcerative esophagitis, bloating, esophagitis, abdominal pain, diarrhea, dyspepsia, nausea.
Hepatobiliary disorders: rarely - increased liver enzymes.
Skin and subcutaneous tissue disorders: often - slowed regeneration, skin atrophy, the appearance of hematomas and atrophic skin stripes (striae), acne, hirsutism, ecchymoses, purpura; rarely - allergic dermatitis, contact dermatitis, Quincke's edema. Kaposi's sarcoma, erythema, itching, urticaria, rash, hyperhidrosis, telangiectasias, petechiae.
Musculoskeletal and connective tissue disorders: common: atrophy, myopathy, muscle weakness, osteoporosis; rare: aseptic osteonecrosis, tendon rupture. Pathological fractures.
Injury, poisoning and procedural complications: spinal compression fracture.
Infections and infestations: infections, opportunistic infections, relapse of latent tuberculosis.
Reproductive system and breast disorders: irregular menstruation.
Laboratory tests: decreased carbohydrate tolerance, increased urinary calcium levels.
General disorders: often - growth retardation in children, edema. Increased fatigue, general weakness, impaired recovery.
Withdrawal symptoms include vomiting, lethargy, joint pain, desquamation, myalgia, weight loss and/or hypotension, weakness, lethargy, rhinitis, conjunctivitis, painful skin nodules with itching. These effects are believed to be related to the sudden change in GCS concentration rather than to their low levels.
During corticosteroid therapy, an increase in the total number of leukocytes is noted, while the number of eosinophils, monocytes and lymphocytes decreases. The mass of lymphoid tissue decreases. During methylprednisolone therapy, the risk of kidney stones increases, and a slight increase in the level of leukocytes and erythrocytes in the urine is possible.
Blood clotting may increase, hyperlipidemia may develop, and the risk of atherosclerosis and vasculitis may occur. Sperm quality may deteriorate, and amenorrhea may occur.
Special instructions
Methylprednisolone, like other corticosteroids, can lead to exacerbation of some underlying diseases.
GCS should be used with caution and under medical supervision in patients with hypertension, congestive heart failure, mental disorders, diabetes mellitus, pancreatitis, with gastrointestinal diseases (ulcer disease, local ileitis, ulcerative colitis (or other inflammatory diseases of the intestinal tract) or diverticulitis with an increased risk of bleeding and perforation), osteoporosis, glaucoma. Patients with blood clotting disorders should be under close medical supervision. It is also necessary to exercise caution when prescribing the drug to patients who have recently suffered a myocardial infarction, with epilepsy, recent anastomoses and renal failure.
When using GCS, the diagnosis of the latent period of hyperparathyroidism, as well as complications from the gastrointestinal tract, is difficult, since the pain syndrome is reduced.
With the simultaneous use of methylprednisolone and anticoagulants, the risk of gastric ulcer and bleeding increases. GCS can also reduce the effects of anticoagulants. Thus, the dosage regimen of anticoagulants must necessarily be accompanied by monitoring of prothrombin time, namely the international normalized ratio.
Immunosuppressive effects and increased susceptibility to infections. GCS may increase susceptibility to infections and mask some symptoms of infections, in addition, new infections may develop against the background of corticosteroid therapy. When using GCS, resistance to infections may decrease and the body's inability to localize infection may develop. Infections caused by any pathogen, including viruses, bacteria, fungi, protozoa or helminths of any localization in the body, may be associated with the use of GCS as monotherapy or in combination with other immunosuppressants that affect cellular, humoral immunity or neutrophil function. These infections can be both mild and severe, and in some cases - fatal. With increasing doses of GCS, the frequency of infectious complications increases.
Patients taking medications that suppress the immune system are more susceptible to infections than healthy people. Chickenpox and measles, for example, can have more serious or even fatal consequences in unimmunized children or adults taking corticosteroids.
In addition, corticosteroids should be used with great caution in patients with confirmed or suspected parasitic infections, such as strongyloidiasis (infection with hookworm). In such patients, immunosuppression induced by corticosteroids can lead to strongyloidiasis hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal septicemia caused by gram-negative microorganisms.
There is no consensus on the role of corticosteroids in the treatment of patients with septic shock. Early studies reported both positive and negative effects of corticosteroids in this clinical setting. Later studies have suggested that corticosteroids as adjunctive therapy may be beneficial in patients with septic shock who have adrenal insufficiency. However, routine use of these drugs in patients with septic shock is not recommended. A systematic review of studies after short courses of high-dose corticosteroids in such patients concluded that there is no evidence to support such use. However, a meta-analysis and one review have shown that longer (5–11 days) courses of low-dose corticosteroids may be associated with reduced mortality, particularly in patients with vasopressor-dependent septic shock.
The use of live or live attenuated vaccines in patients receiving corticosteroids in immunosuppressive doses is contraindicated. Patients receiving corticosteroids in immunosuppressive doses can be vaccinated using killed or inactivated vaccines, but their response to such vaccines may be reduced. These immunization procedures can be performed in patients receiving corticosteroids in non-immunosuppressive doses.
The use of corticosteroids in active tuberculosis should be limited to cases of fulminant or disseminated tuberculosis, in which cases corticosteroids are used in combination with appropriate anti-tuberculosis chemotherapy. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin test deviations, treatment should be carried out under close medical supervision, since exacerbation of the disease is possible. With prolonged corticosteroid therapy, such patients should be prescribed chemoprophylactic drugs.
There is a risk of tuberculosis recurrence and complications from chickenpox and herpes zoster.
Cases of Kaposi's sarcoma have been reported in patients receiving corticosteroid therapy. In such cases, discontinuation of corticosteroid therapy may result in clinical remission.
Blood and lymphatic system: Acetylsalicylic acid and NSAIDs in combination with corticosteroids should be used with caution.
Immune system: Allergic reactions (e.g. angioedema) may develop.
With abrupt withdrawal of corticosteroids, acute adrenal insufficiency may develop, which can be fatal. Adrenal insufficiency caused by the use of the drug can be minimized by gradually reducing the dose. This type of relative insufficiency may persist for several months after discontinuation of therapy, therefore, if stressful situations arise during this period, hormone therapy should be resumed. Since mineralocorticoid secretion may be impaired, electrolytes and/or mineralocorticoids should be administered simultaneously. Since corticosteroids can cause or exacerbate Cushing's syndrome, their use should be avoided in patients with Cushing's disease.
There is a more pronounced effect of GCS on patients with hypothyroidism.
Metabolism and nutrition: Corticosteroids, including methylprednisolone, may increase blood glucose levels, worsen the condition of patients with pre-existing diabetes mellitus, and predispose patients to diabetes mellitus on long-term corticosteroid use.
Mental disorders. When using GCS, various mental disorders are possible: from euphoria, insomnia, mood swings, personality changes to severe depression with psychotic manifestations. In addition, while taking GCS, pre-existing emotional instability and a tendency to psychotic reactions may increase.
Potentially serious psychiatric disorders may develop with systemic corticosteroids (see Adverse Reactions). Symptoms usually occur within a few days or weeks of initiating therapy. Most reactions resolve after dose reduction or discontinuation of the drug, although specific treatment may be required. Psychiatric reactions have been reported with discontinuation of corticosteroids; the frequency is unknown. Patients/caregivers should be advised to seek medical advice if the patient develops any psychiatric disorder, particularly if they suspect that they are depressed or have suicidal thoughts. Patients/caregivers should be alert to possible psychiatric disorders that may occur during or immediately after tapering or discontinuing systemic steroids.
If a patient receiving steroid therapy is exposed to an unusual stressor, it is necessary to increase the dose of fast-acting steroids before, during, and after the stressful situation.
Nervous system disorders: In patients with convulsions, as well as myasthenia gravis, corticosteroids should be used with caution.
Organ of vision. In case of eye damage caused by the herpes simplex virus, corticosteroids should be used with caution, as corneal perforation is possible.
Prolonged use of corticosteroids may cause posterior subcapsular cataracts and nuclear cataracts (especially in children), exophthalmos, or increased intraocular pressure, which can lead to glaucoma with possible damage to the optic nerve. Patients using corticosteroids are at increased risk of developing secondary eye infections caused by fungi and viruses.
Cardiac disorders: In patients with chronic heart failure, systemic corticosteroids should be used with caution and only when absolutely necessary.
Vascular disorders: In patients with hypertension, corticosteroids should be used with caution.
Gastrointestinal tract. There is no consensus on whether it is GCS that cause the development of gastric ulcer during therapy. However, glucocorticoid therapy can mask the symptoms of peptic ulcer, so perforation or bleeding may occur without pronounced pain.
GCS should be prescribed with caution in nonspecific ulcerative colitis, if there is a risk of perforation, abscess formation or other purulent infection; in diverticulitis; in the case of recently performed intestinal anastomoses; in active or latent peptic ulcer disease.
Hepatobiliary system. There is an increase in the severity of the effects of GCS in patients with cirrhosis of the liver.
Musculoskeletal: Cases of acute myopathy have been reported with high doses of corticosteroids, most commonly in patients with neuromuscular disorders (e.g. myasthenia gravis) or in patients receiving anticholinergic agents such as neuromuscular blocking agents (e.g. pancuronium). Generalized acute myopathy may involve the eye and respiratory muscles and result in quadriparesis. Elevated creatine kinase may occur. Clinical improvement or recovery may take several weeks to several years after discontinuation of corticosteroids.
Osteoporosis is a common (but rarely diagnosed) side effect associated with long-term use of high-dose corticosteroids.
During long-term therapy with Metipred, it is necessary to consider the appointment of bisphosphonates in patients with osteoporosis or in the presence of risk factors for its development. The risk of osteoporosis can be minimized by adjusting the dose of Metipred, reducing it to the minimum therapeutic level.
The simultaneous use of fluoroquinolones and corticosteroids increases the risk of tendon damage.
Research results. When using hydrocortisone or cortisone in medium and high doses, an increase in blood pressure, salt and water retention, and increased potassium excretion are possible. These effects are less common with the use of synthetic derivatives of these drugs, except when high doses are used. A diet with limited salt intake and potassium supplements are recommended. All GCS increase calcium excretion.
Injury, poisoning and procedural complications: Systemic corticosteroids should not be used in high doses in the treatment of patients with traumatic brain injury.
Other. The drug contains lactose monohydrate, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not use this medicine.
Since the occurrence of complications in the treatment of GCS depends on the dose of the drug and the duration of therapy, in each case, a careful assessment of the ratio of the benefit of using the drug and the potential risk should be carried out when determining both the dose and duration of treatment, and the choice of the regimen of use - daily or intermittent course.
When treating with corticosteroids, the minimum dose that provides a sufficient therapeutic effect should be prescribed, and when dose reduction becomes possible, it should be carried out gradually.
Carcinogenic, mutagenic and reproductive effects. The drug has no carcinogenic or mutagenic effects, nor has it had any adverse effects on reproductive functions.
With prolonged use in children, growth retardation is possible, so it is necessary to limit yourself to taking minimum doses according to certain indicators for the shortest possible period.
Treatment of elderly patients should be carried out with caution, since elderly people are more susceptible to side effects that may occur when taking GCS, such as stomach ulcers, osteoporosis, and skin atrophy.
Use during pregnancy or breastfeeding
The results of animal studies have shown that the administration of high doses of corticosteroids to females can lead to fetal malformations.
Despite the results of animal studies, the possibility of harm to the fetus when this drug is used during pregnancy is unlikely. Studies of the effect of GCS on human reproductive function have not been conducted. Since there is no adequate evidence of the safety of GCS when used in pregnant women, these drugs should be prescribed during pregnancy only if absolutely necessary.
Some corticosteroids readily cross the placental barrier. In one retrospective study, mothers taking corticosteroids reported an increased incidence of low birth weight in their infants. Although adrenal insufficiency is rare in infants exposed to corticosteroids in utero, infants born to mothers who received relatively high doses of corticosteroids during pregnancy should be closely monitored for signs of adrenal insufficiency.
The effect of corticosteroids on the course and outcomes of labor is unknown.
When prescribing corticosteroids during pregnancy and breastfeeding or to women planning pregnancy, the benefit of the drug for the mother and the potential risk to the fetus should be carefully assessed.
GCS are excreted in breast milk. GCS excreted in breast milk may inhibit growth and affect endogenous GCS production in breastfed infants. Since adequate studies on the effects of GCS on human reproduction have not been conducted, this drug should be used in nursing mothers only if the benefit of the drug outweighs the potential risk to the infant.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug usually does not affect the reaction speed when driving or using other mechanisms, but there is a risk of mood disorders, which may affect the ability to drive or operate other mechanisms.
The effect of GCS on the speed of reaction when driving vehicles or working with other mechanisms has not been systematically evaluated. After treatment with GCS, side effects such as dizziness, vertigo, visual disturbances, fatigue may occur. In this case, patients should not drive vehicles or other mechanisms.
Interactions
CYP 3A4 inhibitors - Drugs that inhibit CYP 3A4 activity tend to decrease hepatic clearance and increase plasma concentrations of drugs that are CYP 3A4 substrates, such as methylprednisolone. In the presence of a CYP 3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity. CYP 3A4 inhibitors include grapefruit juice, macrolide antibiotics (troleandomycin).
CYP 3A4 inducers - drugs that stimulate CYP 3A4 activity, as a rule, increase hepatic clearance, which leads to a decrease in plasma concentrations of drugs - CYP 3A4 substrates. With the simultaneous use of these drugs, an increase in the dose of methylprednisolone may be required to achieve the desired result. Such drugs include the antibiotic, anti-tuberculosis agent - rifampicin; anticonvulsants - phenobarbital, phenytoin.
CYP 3A4 substrates - the presence of another CYP 3A4 substrate may lead to inhibition or induction of the hepatic clearance of methylprednisolone, requiring appropriate dose adjustment. It is possible that adverse reactions associated with the use of one of these drugs as monotherapy will be more likely when they are used simultaneously. These include immunosuppressants - cyclophosphamide, tacrolimus.
CYP 3A4 inducers and substrates - anticonvulsants: carbamazepine.
CYP 3A4 inhibitors and substrates - antiemetics: aprepitant, fosaprepitant; antifungals: itraconazole, ketoconazole; calcium channel blockers: diltiazem; contraceptives (oral): ethinyl estradiol/norethindrone; macrolide antibiotics: clarithromycin, erythromycin.
Immunosuppressants - cyclosporine:
When cyclosporine is used concomitantly with methylprednisolone, there may be mutual inhibition of metabolism, resulting in increased plasma concentrations of one or both of these drugs. Therefore, it is possible that adverse events associated with the use of one of these drugs as monotherapy will be more likely when they are used concomitantly; seizures have been reported with the simultaneous use of methylprednisolone and cyclosporine.
Antiviral drugs - HIV protease inhibitors:
Protease inhibitors such as indinavir and ritonavir may lead to increased plasma concentrations of corticosteroids;
GCS can induce the metabolism of HIV protease inhibitors, resulting in a decrease in their plasma concentrations.
Anticholinesterase agents: in patients with myasthenia gravis, the use of corticosteroids and anticholinesterase agents may cause muscle weakness.
Anticoagulants (oral): The effect of methylprednisolone on oral anticoagulants is variable and may result in either increased or decreased effects of oral anticoagulants when used concomitantly. Coagulation parameters should be monitored regularly to ensure the desired anticoagulant effect.
Anticholinergics. GCS may interfere with the effects of anticholinergics:
Cases of acute myopathy have been reported with the simultaneous use of high-dose corticosteroids and anticholinergics that block neuromuscular transmission (see Precautions);
Antagonism of the neuromuscular blocking effects of pancuronium and vecuronium has been reported in patients receiving corticosteroids. This interaction is expected for all competitive neuromuscular blocking agents.
Salicylates and other nonsteroidal anti-inflammatory drugs: Concomitant use of salicylates, indomethacin and other nonsteroidal anti-inflammatory drugs may increase the incidence of gastrointestinal bleeding and ulcers. Methylprednisolone may increase the clearance of acetylsalicylic acid with prolonged use in high doses, which may lead to a decrease in plasma salicylate levels or an increased risk of salicylate intoxication when methylprednisolone is discontinued. Acetylsalicylic acid and nonsteroidal anti-inflammatory drugs in combination with corticosteroids should be used with caution in the treatment of patients with hypoprothrombinemia.
Hypoglycemic drugs: methylprednisolone may partially suppress the hypoglycemic effect of oral hypoglycemic agents and insulin.
Enzyme inducers, such as barbiturates, phenytoin, pyrimidone, carbamazepine, and rifampin
