Methylprednisolone

Methylprednisolone is an Anti-inflammatory and Immunosuppressive agent belonging to the pharmacological class of Corticosteroids.

Methylprednisolone has been approved to relieve symptoms and also for the treatment and maintenance of Acute respiratory distress syndrome, moderate to severe, Allergic conditions, Asthma, acute exacerbation, Chronic obstructive pulmonary disease, acute exacerbation, COVID-19, hospitalized patients, Deceased organ donor management, Giant cell arteritis, treatment, Gout, treatment, Graft-versus-host disease, acute, treatment, Immune-mediated adverse reactions associated with checkpoint inhibitor therapy, Immune thrombocytopenia, Inflammatory bowel disease, Iodinated contrast media allergic-like reaction, prevention, Multiple sclerosis, acute exacerbation, Myopathies, treatment, Nausea and vomiting of pregnancy, severe/refractory, Pneumocystis pneumonia, adjunctive therapy for moderate to severe disease, Prostate cancer, metastatic, castration resistant, Sarcoidosis, severe, acute, Systemic rheumatic disorders, organ-threatening or life-threatening, Thyroid eye disease, Warm autoimmune hemolytic anemia.

Methylprednisolone's absorption and distribution characteristics vary across different administration routes. Oral methylprednisolone demonstrates approximately 89.9% of the bioavailability observed with oral methylprednisolone acetate, while rectal administration yields only about 14.2% bioavailability. Regarding its distribution, the average volume of distribution for methylprednisolone is approximately 1.38L/kg. Methylprednisolone undergoes metabolism, primarily facilitated by enzymes like 11beta-hydroxysteroid dehydrogenases and 20-ketosteroid reductases. Elimination pathways involve both urine and faeces. In humans, methylprednisolone and its metabolites are excreted in the urine, while a study in dogs illustrated that urine elimination accounted for 25-31%, and fecal elimination constituted 44-52% of the elimination process.

The common side effects of Methylprednisolone include Weakness in muscles, Peptic ulcers, Delayed wound healing, Thinning of the skin, Redness on the face, Vertigo, Headache, Altered menstrual cycle.

Methylprednisolone is available in the form of Oral tablets ,Injectable Suspensions , Powder for injection..

Methylprednisolone is approved in Germany, Japan, Malaysia, India, the U.K., and China.

Methylprednisolone, belonging to the pharmacological class of Corticosteroids and acts as an Anti-inflammatory agent and Immunosuppressive agents.

The immediate effects of corticosteroids involve a reduction in capillary vasodilation and permeability, as well as a decrease in the migration of leukocytes to inflamed sites . The interaction between corticosteroids and the glucocorticoid receptor initiates a cascade of genetic alterations resulting in numerous downstream impacts spanning from hours to days .Glucocorticoids play a role in impeding neutrophil apoptosis and their detachment from vessel walls, dampening the activity of phospholipase A2 to curtail the production of arachidonic acid derivatives, inhibiting the action of NF-Kappa B and other transcription factors associated with inflammation, and stimulating the expression of anti-inflammatory genes such as interleukin-10 .Distinct levels of corticosteroid dosage elicit varying effects: lower doses induce anti-inflammatory responses, while higher doses exert immunosuppressive effects .Extended administration of elevated glucocorticoid doses triggers engagement with the mineralocorticoid receptor, prompting a rise in sodium levels and a decline in potassium levels .

Methylprednisolone has been approved to relieve symptoms and also for the treatment and maintenance of Acute respiratory distress syndrome, moderate to severe, Allergic conditions, Asthma, acute exacerbation, Chronic obstructive pulmonary disease, acute exacerbation, COVID-19, hospitalized patients, Deceased organ donor management, Giant cell arteritis, treatment, Gout, treatment, Graft-versus-host disease, acute, treatment, Immune-mediated adverse reactions associated with checkpoint inhibitor therapy, Immune thrombocytopenia, Inflammatory bowel disease, Iodinated contrast media allergic-like reaction, prevention, Multiple sclerosis, acute exacerbation, Myopathies, treatment, Nausea and vomiting of pregnancy, severe/refractory, Pneumocystis pneumonia, adjunctive therapy for moderate to severe disease, Prostate cancer, metastatic, castration resistant, Sarcoidosis, severe, acute, Systemic rheumatic disorders, organ-threatening or life-threatening, Thyroid eye disease, Warm autoimmune hemolytic anemia.

The peak concentration (Cmax) of methylprednisolone and its time of occurrence (Tmax) vary based on the administration route. When administered intravitreally, methylprednisolone reaches its peak concentration after approximately 2.5 hours (Tmax).

Methylprednisolone is found to be available in the form of Oral tablets, Injectable Suspensions, Powder for injection.

Methylprednisolone can be used in the following treatment:

• Acute respiratory distress syndrome, moderate to severe
• Allergic conditions
• Asthma, acute exacerbation
• Chronic obstructive pulmonary disease, acute exacerbation
• COVID-19, hospitalized patients
• Deceased organ donor management
• Giant cell arteritis, treatment
• Gout, treatment
• Graft-versus-host disease, acute, treatment
• Immune-mediated adverse reactions associated with checkpoint inhibitor therapy
• Immune thrombocytopenia
• Inflammatory bowel disease
• Iodinated contrast media allergic-like reaction, prevention
• Multiple sclerosis, acute exacerbation
• Myopathies, treatment
• Nausea and vomiting of pregnancy, severe/refractory
• Pneumocystis pneumonia, adjunctive therapy for moderate to severe disease
• Prostate cancer, metastatic, castration resistant
• Sarcoidosis, severe, acute
• Systemic rheumatic disorders, organ-threatening or life-threatening
• Thyroid eye disease
• Warm autoimmune hemolytic anemia

Methylprednisolone can help to relieve symptoms and also for the treatment and maintenance of Acute respiratory distress syndrome, moderate to severe, Allergic conditions, Asthma, acute exacerbation, Chronic obstructive pulmonary disease, acute exacerbation, COVID-19, hospitalized patients, Deceased organ donor management, Giant cell arteritis, treatment, Gout, treatment, Graft-versus-host disease, acute, treatment, Immune-mediated adverse reactions associated with checkpoint inhibitor therapy, Immune thrombocytopenia, Inflammatory bowel disease, Iodinated contrast media allergic-like reaction, prevention, Multiple sclerosis, acute exacerbation, Myopathies, treatment, Nausea and vomiting of pregnancy, severe/refractory, Pneumocystis pneumonia, adjunctive therapy for moderate to severe disease, Prostate cancer, metastatic, castration resistant, Sarcoidosis, severe, acute, Systemic rheumatic disorders, organ-threatening or life-threatening, Thyroid eye disease, Warm autoimmune hemolytic anemia.

Methylprednisolone is approved for use in the following clinical indications:

• Acute respiratory distress syndrome, moderate to severe
• Allergic conditions
• Asthma, acute exacerbation
• Chronic obstructive pulmonary disease, acute exacerbation
• COVID-19, hospitalized patients
• Deceased organ donor management
• Giant cell arteritis, treatment
• Gout, treatment
• Graft-versus-host disease, acute, treatment
• Immune-mediated adverse reactions associated with checkpoint inhibitor therapy
• Immune thrombocytopenia
• Inflammatory bowel disease
• Iodinated contrast media allergic-like reaction, prevention
• Multiple sclerosis, acute exacerbation
• Myopathies, treatment
• Nausea and vomiting of pregnancy, severe/refractory
• Pneumocystis pneumonia, adjunctive therapy for moderate to severe disease
• Prostate cancer, metastatic, castration resistant
• Sarcoidosis, severe, acute
• Systemic rheumatic disorders, organ-threatening or life-threatening
• Thyroid eye disease
• Warm autoimmune hemolytic anemia

• Acute Respiratory Distress Syndrome, Moderate to Severe:
• 1-2 mg/kg/day IV divided every 6 hours for 7-14 days
• Allergic Conditions:
• 4-48 mg/day orally in divided doses, adjusted based on response
• Asthma, Acute Exacerbation:
• 40-80 mg IV once, may repeat in 1-2 days if needed
• Chronic Obstructive Pulmonary Disease, Acute Exacerbation:
• 40-80 mg IV once daily for 5-7 days
• COVID-19, Hospitalized Patients:
• Varies based on protocols, commonly 40-80 mg IV once daily for a limited duration
• Deceased Organ Donor Management:
• 15 mg/kg IV before organ retrieval
• Giant Cell Arteritis, Treatment:
• 40-60 mg/day orally, taper over weeks to months
• Gout, Treatment:
• 30-40 mg/day orally for 5-7 days
• Graft-versus-Host Disease, Acute, Treatment:
• 1-2 mg/kg/day IV divided every 6 hours
• Immune-Mediated Adverse Reactions Associated with Checkpoint Inhibitor Therapy:
• 1-2 mg/kg/day IV or orally, may be continued for weeks
• Immune Thrombocytopenia:
• 1-2 mg/kg/day IV or orally, adjust based on platelet response
• Inflammatory Bowel Disease:
• 40-60 mg/day orally, taper as clinically indicated
• Iodinated Contrast Media Allergic-Like Reaction, Prevention:
• 32 mg orally 12 and 2 hours before procedure
• Multiple Sclerosis, Acute Exacerbation:
• 1 g IV daily for 3-5 days
• Myopathies, Treatment:
• 1-2 mg/kg/day orally, taper over months
• Nausea and Vomiting of Pregnancy, Severe/Refractory:
• 10-20 mg IV daily for 2-3 days
• Pneumocystis Pneumonia, Adjunctive Therapy for Moderate to Severe Disease:
• 40 mg IV every 12 hours for 5-10 days
• Prostate Cancer, Metastatic, Castration Resistant:
• 8 mg IV every 2 weeks
• Sarcoidosis, Severe, Acute:
• 30 mg/day orally, taper over weeks to months
• Systemic Rheumatic Disorders, Organ-Threatening or Life-Threatening:
• 1-2 mg/kg/day IV or orally, adjust as needed
• Thyroid Eye Disease:
• 0.5-1 mg/kg/day orally, taper over months
• Warm Autoimmune Hemolytic Anemia:
• 1-2 mg/kg/day IV or orally, adjust based on response

Methylprednisolone is available in the following dosage forms and strengths:

• Oral tablets: 2mg, 4mg, 6mg, 8mg, 16mg, 32mg
• Injectable suspensions: 20mg/ml, 40mg/ml, 80mg/ml
• Powder for injection: 40 mg/ml, 125 mg/ml, 500 mg/ml

Oral tablets, Oral solutions, Injectable Suspensions, Powder for injection.

• Dosage Adjustments in Kidney Patients:

The understanding of Methylprednisolone's pharmacokinetics in cases of kidney impairment is not extensively defined.

• Dosage Adjustments in Hepatic Impairment Patients:

U.S. Labeling:

If ALT levels rise more than three times the upper limit of normal (ULN): Cease drug therapy and conduct an inquiry into the likely cause; if attributable to Methylprednisolone, begin an expedited drug elimination regimen and observe liver function tests weekly until they return to normal.

Canadian Labeling:

For ALT elevations ranging from 2 to 3 times the ULN: Consider lowering the maintenance dose to 10 mg taken once daily; closely monitor ALT on a weekly basis.

For persistent ALT elevations surpassing 2 times the ULN or ALT levels exceeding three times the ULN: Discontinue treatment and initiate procedures for the elimination of the drug.

• Dosage Adjustments in Pediatric Patients:

• Anaphylaxis, Adjunctive Therapy:
• Initial: 1-2 mg/kg/dose IV, may repeat as needed
• Maintenance: 0.5-1 mg/kg/dose IV every 4-6 hours
• Asthma:
• 0.5-2 mg/kg/day orally in 1-2 divided doses
• Graft-versus-Host Disease, Acute:
• 1-2 mg/kg/day IV divided every 6 hours for 3-6 days
• Immune Thrombocytopenia, Moderate to Severe Bleeding or At Risk for Severe Bleeding:
• 10-30 mg/kg/day orally in 1-3 divided doses for 1-4 weeks
• Juvenile Idiopathic Arthritis, Systemic:
• Initial: 0.5-1 mg/kg/day orally
• Maintenance: Adjust dose to lowest effective dose
• Kawasaki Disease:
• 30 mg/kg/day IV divided every 6 hours for 3-5 days
• Lupus Nephritis, Proliferative:
• 30 mg/m²/day IV divided every 6 hours for 3 days, followed by oral therapy
• Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2:
• 1-2 mg/kg/dose IV every 6 hours for 3-5 days
• Nephrotic Syndrome, Steroid Resistant:
• 2 mg/kg/day orally in 1-2 divided doses for 2-4 weeks
• Pneumocystis Pneumonia, Adjunctive Therapy for Moderate or Severe Infection:
• 1-2 mg/kg/dose IV every 6 hours for 5-10 days
• Radiocontrast Media Reaction, Prevention of Rebound Reaction:
• 1-2 mg/kg/dose IV before contrast media injection, repeat 6 and 12 hours after initial dose
• Ulcerative Colitis, Acute, Severe:

• 1-2 mg/kg/day IV divided every 6 hours for 3-5 days, then taper to oral therapy

There are no strict dietary restrictions associated with the medication. However, offering dietary guidance can contribute to optimizing patient health and mitigating potential adverse effects. Emphasize maintaining adequate calcium and vitamin D intake, especially for patients on high doses or prolonged regimens, to support bone health. Encouraging moderation of sodium intake and proper hydration can assist in managing fluid retention and blood pressure. While potassium-rich foods remain important, patients receiving higher corticosteroid doses should be mindful of their potassium consumption. Monitoring blood glucose levels is crucial for diabetic patients, necessitating balanced meal planning. Assessing protein intake and the potential need for vitamin/mineral supplementation might be beneficial. Advising on the avoidance of alcohol and caffeine, which can interact with the medication, is prudent. Addressing potential gastrointestinal issues could involve suggesting smaller, frequent meals and avoidance of triggering foods.

Molecule Methylprednisolone may be contraindicated in the following conditions:

• Methylprednisolone should not be used by individuals with a known allergy to Methylprednisolone or any of its inactive components.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows :

General Considerations:

Preservative Formulations and Benzyl Alcohol: Some formulations of methylprednisolone contain benzyl alcohol, which can be toxic when administered locally to neural tissue. Excessive exposure to benzyl alcohol, particularly in neonates and preterm infants, has been linked to toxicity, including hypotension and metabolic acidosis. Increased incidence of kernicterus and rare cases of deaths, primarily in preterm infants, have been reported due to excessive benzyl alcohol exposure. The amount of benzyl alcohol in medications is generally small compared to that in flush solutions containing it. When administering medications with this preservative, the total benzyl alcohol load should be considered. The toxic threshold of benzyl alcohol is uncertain, so practitioners should assess the combined metabolic load if patients require more than recommended dosages or other benzyl alcohol-containing medications.

Skin Changes and Atrophy: Injection Site Effects: Injection of SOLU-MEDROL can lead to skin changes, including depressions at the injection site due to dermal and subdermal alterations. To minimize dermal and subdermal atrophy, it's important not to exceed recommended doses. Avoid injecting into the deltoid muscle to prevent a high incidence of subcutaneous atrophy.

Anaphylactoid Reactions: In rare cases, patients receiving corticosteroid therapy may experience anaphylactoid reactions. These reactions should be closely monitored, as detailed in the adverse reactions section.

Stress Dosage Adjustment: When patients on corticosteroid therapy face unusual stress before, during, or after stressful situations, higher doses of rapidly acting corticosteroids may be necessary.

Cranial Trauma Study: A study involving methylprednisolone hemisuccinate, an IV corticosteroid, revealed increased mortality at both 2 weeks and 6 months in patients with cranial trauma who lacked clear indications for corticosteroid treatment. High doses of systemic corticosteroids, including SOLU-MEDROL, are not recommended for traumatic brain injury treatment.

Cardio-renal Effects:

Corticosteroid doses, especially average and large ones, can lead to elevated blood pressure, salt and water retention, and increased potassium excretion. Synthetic derivatives pose a lower risk for these effects except in large doses. Sodium restriction, potassium supplementation, and calcium excretion increase may be necessary due to these effects.

Cardiovascular Caution: The use of corticosteroids should be approached with caution in patients with recent myocardial infarctions due to a potential association with left ventricular free wall rupture.

Endocrine Impact: Chronic corticosteroid use can lead to hypothalamic-pituitary adrenal (HPA) axis suppression, Cushing’s syndrome, and hyperglycemia. Monitoring for these conditions is recommended.

Corticosteroid Discontinuation: Reversible HPA axis suppression, with a risk of glucocorticosteroid insufficiency after treatment withdrawal, can occur. Gradual dosage reduction helps mitigate secondary adrenocortical insufficiency. In stress situations during the post-discontinuation period, hormone therapy should be reinstituted.

Infections and Immunosuppression:

Corticosteroid users are more susceptible to infections and might not exhibit typical symptoms. Infections can range from mild to severe or fatal. Increasing corticosteroid doses raises the risk of infection. Corticosteroids may also mask signs of ongoing infections.

Fungal Infections: Corticosteroids should be used cautiously in the presence of systemic fungal infections. Concomitant use with substances like amphotericin B and hydrocortisone has been linked to cardiac enlargement and congestive heart failure.

Pathogen Considerations: Latent diseases may be activated or worsened due to corticosteroid use. Careful assessment is required before initiating corticosteroid therapy in patients with tropical exposure or unexplained diarrhea. Strongyloides infestations also demand caution due to potential severe complications.

Cerebral Malaria and Tuberculosis: Corticosteroids should not be used in cerebral malaria and should be restricted in active tuberculosis cases, unless for specific management in conjunction with antituberculous regimen.

Vaccination and Viral Infections:

Live vaccines are contraindicated in patients receiving immunosuppressive corticosteroid doses. Caution is necessary in patients with limited exposure to chicken pox and measles. Special considerations apply to these situations.

Neurologic, Ophthalmic, and Other Precautions:

Intrathecal administration has been linked to severe medical events. Ocular concerns include cataracts, glaucoma, and secondary ocular infections. Corticosteroids should not be used in active ocular herpes simplex.

Additional Precautions: Sensitivity to heat, gradual dose reduction, and careful monitoring of conditions under treatment are crucial. Risk/benefit assessment, caution in cardiac and renal conditions, endocrine adjustments, and patient education about discontinuation and exposure avoidance should be practiced.

It is advised to exercise caution when consuming alcohol while using Methylprednisolone. Alcohol consumption may interact with Methylprednisolone and exacerbate its potential side effects. Alcohol and Methylprednisolone both have the potential to affect the liver. Combining the two could increase the risk of liver-related complications.

Corticosteroids administered systemically are detectable in human breast milk and have the potential to hinder growth, disrupt the body's natural corticosteroid production, or trigger other undesirable outcomes. Given the possibility of significant adverse effects in breastfeeding infants due to corticosteroids, it is essential to deliberate whether to sustain breastfeeding while taking the medication or to cease its use, considering the medication's significance to the mother.

Pregnancy Category C

Research has demonstrated the teratogenic potential of corticosteroids across various species, evident when doses comparable to those prescribed for humans were administered. Investigations involving pregnant mice, rats, and rabbits, in which corticosteroids were introduced, have revealed a heightened occurrence of cleft palate in the offspring. In the context of pregnancy, no comprehensive and well-controlled studies involving pregnant women have been conducted. Consequently, corticosteroids should be employed during pregnancy only if the potential benefits outweigh the potential risks to the developing fetus. Newborns born to mothers who received corticosteroids during pregnancy should undergo vigilant monitoring for indications of hypoadrenalism.

When consuming food alongside the use of methylprednisolone, there are certain considerations to bear in mind to ensure optimal effectiveness and minimize potential risks. While there isn't a specific "food warning" associated with methylprednisolone, it's advised to take the medication with a meal or snack to reduce the likelihood of stomach discomfort or irritation. However, it's important to avoid grapefruit and its juice, as they can interact with the medication and lead to increased levels in the body, potentially intensifying side effects. Additionally, since methylprednisolone can cause fluid retention and elevated blood pressure, moderating sodium intake by limiting high-sodium foods can be beneficial. Monitoring potassium-rich foods, like bananas and oranges, is advised to maintain electrolyte balance.

The adverse reactions related to Methylprednisolone can be categorized as follows:

Common

• Increased appetite
• Weight gain
• Fluid retention (swelling in extremities)
• Elevated blood pressure
• Mood changes (e.g., irritability)
• Difficulty sleeping
• Acne
• Indigestion
• Nausea

Less Common

• Headache
• Dizziness
• Fatigue
• Muscle weakness
• Thinning of the skin
• Easy bruising
• Slow wound healing
• Changes in menstrual cycle

Rare

• Allergic reactions (skin rash, itching, swelling)
• Glaucoma (increased eye pressure)
• Cataracts
• Osteoporosis (bone thinning)
• Adrenal insufficiency (particularly with long-term use)
• Increased susceptibility to infections
• Blood disorders (e.g., low red blood cells, low white blood cells)
• Gastrointestinal bleeding or ulceration
• Aseptic necrosis of bone (bone tissue death)
• Intracranial hypertension (increased pressure in the skull)

The clinically relevant drug interactions of Methylprednisolone is briefly summarized here:

Aminoglutethimide Interaction:

Aminoglutethimide can counteract the adrenal suppression caused by corticosteroids.

Amphotericin B and Potassium-Depleting Agents:

When corticosteroids are administered alongside potassium-depleting agents like amphotericin B and diuretics, close monitoring is essential to detect the development of hypokalemia. Cases have been reported where concomitant use of amphotericin B and hydrocortisone led to cardiac enlargement and congestive heart failure.

Antibiotics and Corticosteroids:

Macrolide antibiotics may reduce the clearance of corticosteroids, necessitating attention to potential drug interactions involving hepatic enzymes.

Anticholinesterases and Corticosteroids:

In patients with myasthenia gravis, simultaneous use of anticholinesterase agents and corticosteroids may induce severe Weakness. Ideally, anticholinesterase agents should be discontinued at least 24 hours before initiating corticosteroid therapy.

Oral Anticoagulants and Corticosteroids:

Co-administration of corticosteroids and warfarin usually results in decreased response to warfarin. Monitoring of coagulation parameters is advised to maintain the desired anticoagulant effect.

Antidiabetic Agents and Corticosteroids:

Due to the potential elevation of blood glucose levels by corticosteroids, adjustments in antidiabetic agent dosages might be necessary.

Antitubercular Drugs and Corticosteroids:

Corticosteroid use may lead to decreased serum concentrations of isoniazid.

Cholestyramine Interaction:

Cholestyramine can enhance the clearance of corticosteroids.

Cyclosporine and Corticosteroids:

Concurrent use of cyclosporine and corticosteroids may heighten the activity of both drugs, potentially causing convulsions.

Digitalis Glycosides and Corticosteroids:

Patients on digitalis glycosides may face an increased risk of arrhythmias due to corticosteroid-induced hypokalemia.

Estrogens and Corticosteroids:

Estrogens, including oral contraceptives, might reduce the hepatic metabolism of specific corticosteroids, intensifying their effects.

Hepatic Enzyme Inducers and Inhibitors:

Drugs like barbiturates, phenytoin, carbamazepine, rifampin, ketoconazole, and macrolide antibiotics can influence the metabolism of corticosteroids, either increasing or decreasing their concentrations.

Ketoconazole and Corticosteroids:

Ketoconazole can significantly reduce the metabolism of certain corticosteroids, elevating the risk of corticosteroid-related side effects.

Nonsteroidal Anti-Inflammatory Agents (NSAIDs) and Corticosteroids:

Co-administration of aspirin or other NSAIDs with corticosteroids increases the likelihood of gastrointestinal side effects. Aspirin should be used cautiously with corticosteroids in cases of hypoprothrombinemia.

Skin Tests and Corticosteroids:

Corticosteroids can suppress reactions to skin tests.

Vaccines and Corticosteroids:

Extended corticosteroid therapy can lead to reduced responses to vaccines and toxoids, as well as potential amplification of replication for organisms found in live attenuated vaccines. Routine vaccination should ideally be postponed until corticosteroid therapy is discontinued, if possible.

The following are the side effects involving Methylprednisolone:

• Weakness in muscles
• Peptic ulcers
• Delayed wound healing
• Thinning of the skin
• Redness on the face
• Vertigo
• Headache
• Altered menstrual cycle
• Elevated eye pressure
• Nausea
• Vomiting
• Heartburn
• Dizziness
• Sleep disturbances
• Changes in appetite
• Excessive sweating
• Development of acne
• Retention of bodily fluids
• Swelling in the abdominal area
• High blood pressure
• Reactions at injection sites (pain, redness, swelling)

The use of Methylprednisolone should be prudent in the following group of special populations:

Pregnancy:

Pregnancy Category C

Research has demonstrated the teratogenic potential of corticosteroids across various species, evident when doses comparable to those prescribed for humans were administered. Investigations involving pregnant mice, rats, and rabbits, in which corticosteroids were introduced, have revealed a heightened occurrence of cleft palate in the offspring. In the context of pregnancy, no comprehensive and well-controlled studies involving pregnant women have been conducted. Consequently, corticosteroids should be employed during pregnancy only if the potential benefits outweigh the potential risks to the developing fetus. Newborns born to mothers who received corticosteroids during pregnancy should undergo vigilant monitoring for indications of hypoadrenalism.

Lactation

Corticosteroids administered systemically are detectable in human breast milk and have the potential to hinder growth, disrupt the body's natural corticosteroid production, or trigger other undesirable outcomes. Given the possibility of significant adverse effects in breastfeeding infants due to corticosteroids, it is essential to deliberate whether to sustain breastfeeding while taking the medication or to cease its use, considering the medication's significance to the mother.

Pediatric

Certain formulations of this product incorporate benzyl alcohol as a preservative (as described in the product's description section). It's essential to carefully inspect vials to ascertain the specific formulation in use. Benzyl alcohol, which is a constituent of this product, has been linked to severe adverse events and even fatalities, particularly among pediatric patients. The occurrence of the "gasping syndrome," characterized by symptoms like central nervous system depression, metabolic acidosis, gasping respirations, and elevated levels of benzyl alcohol and its byproducts in the bloodstream and urine, has been associated with benzyl alcohol dosages exceeding 99 mg/kg/day in neonates and low-birth-weight neonates. Additional manifestations might encompass gradual neurological decline, seizures, intracranial bleeding, blood-related irregularities, skin deterioration, liver and kidney failure, low blood pressure, slow heart rate, and cardiovascular collapse.

While typical therapeutic doses of this product result in benzyl alcohol levels significantly lower than those linked to the "gasping syndrome," the minimum quantity of benzyl alcohol at which toxicity becomes a concern remains uncertain. Premature and low-birth-weight infants, along with individuals receiving high doses, might face a higher likelihood of encountering toxicity. Medical professionals administering this product or other medications containing benzyl alcohol should factor in the cumulative daily metabolic burden of benzyl alcohol from all sources.

The efficacy and safety of corticosteroids in the pediatric population are founded on the well-established course of action that corticosteroids follow, a pattern comparable in both pediatric and adult groups. Published research offers substantiating evidence of corticosteroid efficacy and safety in treating pediatric patients for conditions such as nephrotic syndrome (for ages >2 years) and aggressive lymphomas and leukemias (for ages >1 month). Other pediatric applications of corticosteroids, like severe Asthma and wheezing, rely on well-conducted trials in adults, premised on the assumption that the progression of these diseases and their underlying pathophysiology bear significant resemblance across both age groups.

The adverse effects of corticosteroids in pediatric patients mirror those seen in adults . Similar to adults, pediatric patients should be vigilantly monitored, with regular assessments of blood pressure, weight, height, intraocular pressure, and clinical evaluations to detect infections, psychosocial issues, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients undergoing corticosteroid treatment in any form, including systemic administration, may experience reduced growth velocity. This impact on growth has been observed even at low systemic doses and in cases without evident suppression of the HPA axis, indicated by basal cortisol plasma levels and cosyntropin stimulation tests. As such, growth velocity can be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used HPA axis function tests. Thus, the linear growth of pediatric patients under corticosteroid treatment should be carefully monitored, and the potential growth effects of extended treatment should be weighed against the clinical benefits achieved and the availability of alternative treatments. To minimize the potential impact on growth, pediatric patients should be titrated to the lowest effective dose possible.

Geriatric Use

Comprehensive clinical investigations did not encompass a significant quantity of individuals aged 65 and above, precluding the ability to ascertain potential variations in their responses relative to younger participants. Prior clinical observations have not revealed notable discrepancies in reactions between elderly patients and their younger counterparts. When considering dosage for elderly patients, a prudent approach is advised, often involving initiation at the lower end of the dosing spectrum. This strategy acknowledges the heightened likelihood of diminished hepatic, renal, or cardiac function among the elderly, as well as the greater prevalence of concurrent health conditions or additional medication regimens.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Methylprednisolone.

In cases of acute overdose, the approach to treatment involves providing supportive and symptomatic therapy. When faced with chronic overdose situations, particularly in the presence of serious conditions necessitating ongoing corticosteroid treatment, adjustments to the corticosteroid dosage might be made temporarily. Alternatively, a regimen of treatment on alternate days could also be implemented.

Pharmacodynamics:

Corticosteroids operate by binding to the glucocorticoid receptor, thereby inhibiting signals that trigger inflammation while simultaneously promoting the transmission of anti-inflammatory signals, as noted in reference 5. These compounds exhibit a wide therapeutic range, allowing for the administration of doses that exceed the body's natural production levels, as emphasized by the same source. However, individuals prescribed corticosteroids should be provided with thorough counseling about potential risks. This includes the likelihood of hypothalamic-pituitary-adrenal axis suppression and an increased susceptibility to infections, as cautioned in the same reference.

Pharmacokinetics:

Absorption

Bioavailability of Methylprednisolone

● Oral methylprednisolone exhibits 89.9% of the bioavailability found in oral methylprednisolone acetate, while rectal methylprednisolone displays only 14.2% of this bioavailability.

● Intravitreal administration of methylprednisolone results in a Tmax of 2.5 hours, indicating the time to peak concentration.

● Approximately 1/10 of the dosage administered orally or via intravenous route of methylprednisolone eventually reaches the vitreous humor.

● Detailed data on the absorption characteristics of methylprednisolone are not readily accessible.

Volume of Distribution

● The average volume of distribution for methylprednisolone stands at 1.38L/kg.

Protein Binding

● In plasma, methylprednisolone binds to proteins at a rate of 76.8%, with insignificant binding to corticosteroid binding protein.1

● Human serum albumin in plasma serves as the binding site for methylprednisolone.

Metabolism

● The primary enzymatic mediation of methylprednisolone's metabolism is attributed to 11beta-hydroxysteroid dehydrogenases and 20-ketosteroid reductases.

Metabolites

● The products formed through the metabolism of methylprednisolone include several metabolites: M13, M15, M14, M7, M10, M9, M4, M5, M6, M2, M3, M1, M11, M12, and M8.

Route of Elimination

● Human urine has been found to collect both methylprednisolone and its metabolites.

● Studies conducted on dogs indicate that 25-31% of elimination occurs through urine, while 44-52% takes place through feces.

1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011856s103s104lbl.pdf
2. https://www.pfizer.ca/en/our-products/solu-medrol-methylprednisolone-sodium-succinate-injection-usp
3. https://www.webmd.com/drugs/2/drug-6470/methylprednisolone-oral/details
4. https://go.drugbank.com/drugs/DB00959
5. https://www.drugs.com/methylprednisolone.html
6. https://my.clevelandclinic.org/health/drugs/19300-methylprednisolone-Oral tablets, Oral solutions ,Injectable Suspensions , Powder for injection.
7. https://www.pfizer.ca/en/our-products/medrol-methylprednisolone
8. https://reference.medscape.com/drug/medrol-medrol-dosepak-methylprednisolone-342746
9. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011153s075lbl.pdf
10. https://www.rxlist.com/a-methapred-drug.htm