Methylprednisolone vs. prednisone: What’s the difference?

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Methylprednisolone (generic of Medrol) and prednisone (generic of Rayos) are corticosteroid medications used to treat various diseases and disorders. These drugs are synthetic compounds closely related to cortisol, a hormone produced by the body’s adrenal gland. Corticosteroids are sometimes referred to as steroids. However, they should not be confused with anabolic steroids. 

When administered in higher doses than the body would normally produce on its own, corticosteroids work through various pathways to block certain immune and inflammatory markers, such as leukotrienes, cytokines, prostaglandins, kinins, and histamines. This mechanism of action allows these drugs to be effective for treating certain respiratory diseases, allergic reactions, autoimmune disorders, and other inflammatory conditions. 

While methylprednisolone and prednisone may be used to treat the same disorders, there are some differences between the two.

What are the main differences between methylprednisolone vs. prednisone?

Methylprednisolone is a prescription medication used to treat different diseases and disorders, including asthma, ulcerative colitis, rheumatoid arthritis, and allergic reactions. Methylprednisolone is a prednisolone derivative, and its mechanism of action makes it useful in a wide variety of inflammatory and immune disorders. Methylprednisolone crosses the cellular membrane and binds to specific receptors, which blocks the production of inflammatory proteins. Cytokines, leukotrienes, and other immune response cells and proteins play a key role in the inflammatory process. Methylprednisolone is effective as both an anti-inflammatory and immunosuppressive agent.

Methylprednisolone is available as a 4 mg, 8 mg, 16 mg, and 32 mg oral tablet. The brand name of methylprednisolone tablets is Medrol. Methylprednisolone is also available as a solution that can be given as an intravenous (IV), intramuscular (IM), or intra-articular (IA) injection. Solu-Medrol is the brand name of methylprednisolone succinate that is given as an IV injection, while Depo-Medrol is the brand name of methylprednisolone acetate that is given as an IM or intra-articular injection. Methylprednisolone may be prescribed to infants, children, and adults.

Prednisone is a prescription medication that is also used to treat a variety of inflammatory and immune disorders. Prednisone is a cortisone derivative and must be metabolized by the liver into its active form, prednisolone, in order to cross the cellular membrane. Once it crosses the cellular membrane, prednisolone works similarly to methylprednisolone and other corticosteroids. It works by blocking the production of inflammatory and immune response markers.

Generic prednisone is available as a 1 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, and 50 mg oral tablet. The brand names of regular prednisone tablets, including Deltasone and Sterapred, have been discontinued in the U.S. Rayos is the brand name of prednisone delayed-release tablets, which come in strengths of 1 mg, 2 mg, and 5 mg. Prednisone is also available as a 5 mg/5 mL oral solution under the brand name Prednisone Intensol. Prednisone may be prescribed to infants, children, and adults. 

Conditions treated by methylprednisolone and prednisone

Corticosteroids, such as methylprednisolone and prednisone, are one of the most commonly prescribed types of drugs that can be used to treat numerous conditions due to their immunosuppressive and anti-inflammatory effects. 

Methylprednisolone and prednisone can be used for many of the same conditions, including rheumatic disorders (rheumatoid arthritis, psoriatic arthritis, spondylitis, and bursitis) and allergic conditions (acute allergic rhinitis, contact dermatitis, and drug sensitivity reactions). In addition, they can also be used to treat respiratory problems, such as acute flares of bronchial asthma. Other conditions that can be treated with methylprednisolone or prednisone include endocrine, collagen, hematologic, gastrointestinal, and ophthalmic disorders.

Rheumatoid arthritis

The 2021 guidelines from the American College of Rheumatology reinforce the use of the disease-modifying antirheumatic drug (DMARD) methotrexate as a first-line agent for rheumatoid arthritis. They also recommend reserving the use of corticosteroids to alleviate pain and inflammation only when necessary. The short-term use of corticosteroids, such as methylprednisolone and prednisone, may be recommended in some patients who are starting treatment with a DMARD. However, low doses of corticosteroids should be prescribed when starting DMARD treatment only when necessary to treat pain and inflammation until the effects of the DMARD kick in. 

Asthma

Inhaled corticosteroids, such as fluticasone, budesonide, and mometasone, are often recommended to help control and manage asthma symptoms. Inhaled corticosteroids are different from systemic corticosteroids like methylprednisolone and prednisone and are usually prescribed with other inhaled medications, such as long-acting beta-agonists. However, for acute exacerbations or worsened symptoms of asthma, a short course of systemic corticosteroids may be prescribed to reduce inflammation in the airways. For example, a healthcare provider may prescribe 40 to 50 mg of prednisone daily for five to seven days. 

Multiple sclerosis

Acute exacerbations, also known as episodes or relapses, can occur in people with multiple sclerosis. Acute symptoms can peak over one to two weeks and negatively affect quality of life. A short-term course of high-dose corticosteroids is the first-line treatment for relapses. A healthcare provider may recommend a high dose of IV methylprednisolone followed by a tapered-dose regimen of oral prednisone. However, due to the possible side effects of high-dose corticosteroids, treatment should be tailored according to the severity of symptoms and the person’s overall condition.  

Inflammatory bowel disease

Inflammatory bowel disease (IBD) may refer to ulcerative colitis or Crohn’s disease and often involves inflammation of the gastrointestinal tract. Flare-ups can cause  diarrhea and persistent abdominal pain. Treatments for IBD may include aminosalicylates, immunosuppressants, and corticosteroids. A short-term course of corticosteroids, such as methylprednisolone or prednisone, may help alleviate IBD symptoms quickly but should only be used short-term. 

COVID-19

Some studies have found that systemic corticosteroids, such as methylprednisolone, are associated with a lower risk of death with COVID-19. Compared with placebo, systemic corticosteroids were associated with a lower 28-day all-cause mortality. 

The following table, while extensive, may not list every use of these two medications. Please consult with your healthcare provider for more information on indications of use.

Is methylprednisolone or prednisone more effective?

There are many ways to compare methylprednisolone and prednisone due to their wide range of uses. However, treatment with corticosteroids is limited to short-term use in inflammatory diseases, especially for severe and acute worsening of inflammation. 

In terms of potency, methylprednisolone is slightly stronger than prednisone. When comparing doses of methylprednisolone and prednisone, 4 mg of methylprednisolone is equivalent to 5 mg of prednisone. However, when doses are adjusted and monitored for treatment responses, both drugs can be similarly effective. One corticosteroid may be preferred over another, depending on the condition being treated.

Unlike prednisone, methylprednisolone is available as an injection. With an injection, methylprednisolone can be administered in a precise dose and a controlled manner. For example, methylprednisolone can be administered directly into an affected joint as an intra-articular injection in people with arthritis. One study found that injections of methylprednisolone may help relieve knee osteoarthritis for up to 24 weeks

While methylprednisolone injections may be better for joint pain relief, prednisone may be preferred for other conditions. One study compared the effectiveness of intravenous methylprednisolone to that of oral prednisone for acute asthma exacerbations in children. Two treatment groups were randomized to receive either 30 mg of intravenous methylprednisolone or 30 mg of oral prednisone. Both groups received albuterol, and researchers evaluated symptomatic relief, peak expiratory flow (PEF), and pulse oximetry readings. Readings were taken for each group at two, four, and six hours after beginning treatment. There were no clinically or statistically significant differences at each interval between the two groups. However, researchers concluded that oral prednisone might be a better choice due to lower costs and a less traumatic administration. 

Treatment with corticosteroids should always be used under the guidance of a healthcare provider. As with other corticosteroids, treatment with methylprednisolone and prednisone should be limited to the lowest effective dose for the shortest possible duration. Long-term use of corticosteroids is associated with an increased risk of adverse effects. 

Coverage and cost comparison of methylprednisolone vs. prednisone

Methylprednisolone is a generic medication that is typically covered by commercial insurance plans and Medicare. A six-day course of 21 of the 4 mg strength tablets, also known as the Medrol Dosepak, can cost around $40. With a methylprednisolone coupon from SingleCare, you may be able to get methylprednisolone at a discounted price.

Prednisone is also a generic medication typically covered by commercial insurance plans and Medicare. The average retail price of prednisone is around $12 for 10 of the 20 mg tablets. You may be able to get a typical supply of generic prednisone tablets for less than $4 with a SingleCare prednisone coupon.

It is important to note that for certain disease states, corticosteroids may not be covered under Medicare prescription drug benefits but may be covered under Medicare Part B. Your pharmacist can provide more information on coverage. The cost of the medication may also vary depending on the pharmacy location and dosage prescribed. 

Common side effects of methylprednisolone vs. prednisone

Methylprednisolone and prednisone are chemically similar. They both fall under the glucocorticoid category of corticosteroids and share the same potential side effects, which can affect various systems of the body. Severe side effects are typically associated with long-term treatment and high doses.

Cardiovascular side effects  

Glucocorticoids are known to cause fluid and electrolyte imbalances, which may lead to sodium and fluid retention, high blood pressure, and, in some cases, congestive heart failure.   

Musculoskeletal side effects  

Methylprednisolone and prednisone may also lead to myopathy, or muscle weakness and loss of muscle mass. Myopathy usually occurs in the legs and arms but is often reversible after discontinuing the steroid.  

Gastrointestinal side effects  

Glucocorticoids are known to affect the gastrointestinal system and may cause nausea, vomiting, or abdominal bloating. More serious gastrointestinal side effects include inflammation of the stomach lining (gastritis), stomach ulcers, and gastrointestinal bleeding.   

Infections 

Steroids may slow the healing of wounds. The immunosuppressive effects of corticosteroids can lead to an increased risk of bacterial, fungal, viral, or parasitic infections, especially with long-term treatment. Infections can range from mild to life-threatening, and the risk of infections may be greater in older people and people taking other immunosuppressants.   

Growth suppression  

Prolonged use of methylprednisolone and prednisone may slow the growth of children. The use of corticosteroids should be limited to as short a duration as possible to achieve remission of symptoms.  

Blood sugar levels  

Glucocorticoids may impair the body’s response to insulin. Patients on long-term steroid therapy may be up to four times more likely to develop diabetes. Patients who depend on injectable insulin or other antidiabetic drugs for blood sugar control may have to increase their dosage of antidiabetic agents while on steroids. It is not uncommon for well-controlled diabetics to see a rise in their blood sugar even on a short-term course of steroids.  

Adrenal suppression  

Taking steroids can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to a decreased production of some of the body’s natural hormones. Discontinuing steroid treatment may then lead to withdrawal and symptoms of adrenal insufficiency, including fatigue, nausea, vomiting, and headaches.   

Mental health disturbances  

Steroids like methylprednisolone and prednisone may cause psychiatric side effects, such as depression, mood swings, insomnia, and even psychosis. The risk of these side effects is greater in people on long-term steroid treatment and children. These side effects may occur during the first week of steroid treatment but usually resolve after stopping treatment. 

The following table is not intended to be a comprehensive list of side effects. Please consult your pharmacist or physician for a complete list of all side effects.

Frequency is not based on data from a head-to-head trial. This may not be a complete list of adverse effects that can occur. Please refer to your doctor or healthcare provider to learn more.

Source: DailyMed (Methylprednisolone), DailyMed (Prednisone)

Drug interactions of methylprednisolone and prednisone

CYP3A4 inducers and inhibitors

Methylprednisolone and prednisone are substrates of the cytochrome P450 (CYP) 3A4 enzyme. The CYP3A4 enzyme in the liver is responsible for the metabolism of many drugs. Combining drugs that affect the CYP3A4 enzyme with methylprednisolone or prednisone may lead to drug interactions.

CYP3A4 inducers, such as carbamazepine, phenytoin, and rifampin, can increase the metabolism of corticosteroids and potentially decrease the effects of corticosteroids. CYP3A4 inhibitors, such as ketoconazole, erythromycin, and ritonavir, can decrease the metabolism of corticosteroids and lead to an increased risk of corticosteroid side effects. The dosage of corticosteroids may need to be adjusted when taking drugs that affect the CYP3A4 enzyme. 

Immunosuppressants

Corticosteroids are commonly used in patients who are also on other immunosuppressive agents. Controlling the body’s immune response in organ transplantation and certain autoimmune disorders may require the use of more than one immunosuppressive agent. However, the blood levels of immunosuppressive agents, such as tacrolimus and cyclosporine, and corticosteroids may be altered when these drugs are combined. For example, combining methylprednisolone or prednisone with certain immunosuppressive agents may lead to increased serum concentrations of methylprednisolone or prednisone. Taking corticosteroids with immunosuppressants may also increase the risk of infections. 

There have been incidences of convulsions or seizures reported with the concurrent use of cyclosporine and methylprednisolone. The use of corticosteroids with cyclosporine may need to be avoided or monitored. 

Antidiabetic agents

Corticosteroids may increase blood sugar levels. Therefore, the dosage of antidiabetic agents may need to be adjusted when taking corticosteroids. 

Blood thinners

Corticosteroids can increase or decrease the effects of blood thinning drugs, such as anticoagulants and antiplatelet agents. Blood coagulation laboratory values may need to be monitored when combining blood thinners with corticosteroids.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Taking corticosteroids with NSAIDs may lead to an increased risk of gastrointestinal side effects. In addition, corticosteroids can alter the clearance of aspirin from the body. In other words, taking corticosteroids with aspirin may lead to decreased salicylate levels, and subsequent discontinuation of corticosteroid treatment may increase the risk of salicylate toxicity.  

Potassium-depleting agents

Loop diuretics can help manage fluid status in the body but can also decrease potassium levels. Because corticosteroids can also decrease potassium levels, combining methylprednisolone or prednisone with other potassium-depleting agents, such as loop diuretics or amphotericin B, may lead to an excessive loss of potassium or hypokalemia. Low potassium levels could have negative effects on cardiac function. Patients who take corticosteroids with potassium-depleting agents should have their electrolyte status monitored closely.

This table is not a list of all possible drug interactions. Please consult a healthcare provider for other possible drug interactions. 

Warnings of methylprednisolone and prednisone

Contraindications

Methylprednisolone and prednisone should be avoided in people with systemic fungal infections. Taking methylprednisolone or prednisone may increase the risk of worsened systemic fungal infections. 

These corticosteroids should also be avoided in people with known or suspected allergies to any of their ingredients. Seek immediate medical attention if signs or symptoms of an allergic reaction develop, such as rash, hives, swelling of the face or throat, or difficulty breathing. 

Corticosteroids, especially in high doses, can inhibit the body’s ability to produce antibodies when vaccinations are given. Therefore, vaccines may not be effective in patients who are also taking steroids. Live vaccines, such as smallpox, should not be given to patients undergoing corticosteroid therapy. Patients taking immunosuppressive agents are also at an increased risk of infection from live vaccines.

Warnings

Corticosteroids may mask signs of an infection and slow the discovery of new infections. Corticosteroids may also worsen or increase the risk of latent infection, such as latent tuberculosis or latent amebiasis. 

Methylprednisolone and prednisone may increase blood pressure and salt and water retention. Corticosteroids should be used with caution in people with heart failure, high blood pressure, and kidney problems. 

The use of corticosteroids may increase the risk of gastrointestinal ulcers and perforations. People with a history of perforations, gastrointestinal inflammation, and ulcers should use corticosteroids with caution. 

Osteoporosis is a potential adverse effect of corticosteroids, as corticosteroids can decrease bone density and increase the rate of bone loss. People at risk of osteoporosis, such as postmenopausal women, should avoid long-term corticosteroid treatment. 

Prolonged use of methylprednisolone and prednisone may lead to cataracts and glaucoma, among other eye problems. People with a history of eye disorders should use corticosteroids with caution. 

Methylprednisolone and prednisone may alter the results of skin tests or other allergy tests. For the most accurate results, steroid therapy should be stopped days before undergoing allergy tests. 

Pregnancy

There are limited well-controlled studies of corticosteroids in pregnant women. However, animal studies suggest that corticosteroids may cause birth defects in infants. The use of corticosteroids during pregnancy should only be recommended when it is clear the benefit outweighs any risks. Infants born to mothers who used corticosteroids during pregnancy should be observed for hypoadrenalism.

Steroids should only be administered for as short a duration as possible to achieve the desired effects. If long-term use of steroids is medically necessary, the steroids should be prescribed at the lowest effective dose.

Frequently asked questions about methylprednisolone vs. prednisone

What is methylprednisolone?

Methylprednisolone is a synthetic corticosteroid used to treat a variety of inflammatory and autoimmune disorders. It is available as an oral tablet and IV, IM, or intra-articular injection. The most common treatment duration for oral therapy with a Medrol Dosepak is six days. Brand names of the injectable form of methylprednisolone include Solu-Medrol and Depo-Medrol. 

What is prednisone?

Prednisone is a synthetic corticosteroid that is metabolized by the liver to its active form, prednisolone. Like other corticosteroids, it is used to treat many inflammatory and autoimmune diseases. Prednisone is available as an oral tablet and oral solution. Prednisone for short-term corticosteroid treatment usually entails a five-day regimen.

Are methylprednisolone and prednisone the same?

Although they are both steroids that work in similar ways, methylprednisolone and prednisone are not the same. Prednisone must be metabolized to its active form, prednisolone, in order to have an effect on the body. In addition, methylprednisolone is slightly more potent than prednisone. A dose of 4 mg of methylprednisolone is equivalent to 5 mg of prednisone.

Is methylprednisolone or prednisone better?

Methylprednisolone and prednisone can help reduce inflammation and treat various conditions when the right doses are given. Methylprednisolone may be better when intra-articular injections are needed. However, oral formulations may be preferred over injectable formulations for certain diseases due to lower costs and ease of administration. Methylprednisolone is slightly stronger than prednisone. 

Can I use methylprednisolone or prednisone while pregnant?

Methylprednisolone and prednisone are in pregnancy risk category C. In other words, there are no controlled human studies proving the medication is safe during pregnancy. However, animal studies suggest these corticosteroids may cause fetal harm. These medications should only be used when the benefit clearly outweighs the risk.

Can I use methylprednisolone or prednisone with alcohol?

Alcohol is metabolized by the liver. Chronic consumption of alcohol may affect the body’s ability to metabolize prednisone into its active form. Alcohol and corticosteroids can also affect blood sugar levels, blood pressure, the immune system, and the gastrointestinal system, especially with long-term use of alcohol or corticosteroids. Alcohol use is best minimized during courses of steroid treatment.

Is methylprednisolone a strong steroid?

While methylprednisolone is approximately 25% more potent than prednisone, it is only one-fifth the potency of other glucocorticoids, such as dexamethasone or betamethasone. However, methylprednisolone is about five times more potent than hydrocortisone.

How long does it take methylprednisolone to start working? / Is methylprednisolone fast acting?

Methylprednisolone has a rapid onset. It reaches its peak effect within one to two hours after an oral dose and within one hour of an intravenous dose. It is metabolized by the liver into inactive metabolites, which are excreted in the urine. The average half-life of methylprednisolone following IV administration is around three hours, while the average half-life of methylprednisolone following oral administration is around two hours.