Methylprednisolone interactions to avoid

Methylprednisolone, generic of the brand name Medrol, is a type of corticosteroid. Not only can it improve quality of life, but it can save lives. Methylprednisolone, sometimes referred to by its shortened moniker as a “steroid,” mimics the activity of naturally occurring hormones released by the body’s adrenal gland. 

While the benefits of methylprednisolone are well-established, drug interactions with systemic corticosteroids are ubiquitous and can have profound effects if not identified and managed appropriately. Many drug interactions are related to additive adverse reaction profiles with concomitant medications with similar side effect profiles. Still, there are also interactions based on the mechanism of metabolism by the body. Some interactions go beyond medications; certain foods can also affect methylprednisolone’s effectiveness. 

Key takeaways:

• Methylprednisolone is an effective therapeutic agent to control immune responses and inflammation. However, its use can result in serious adverse effects that other medications with similar side effect profiles can compound. There is an increased risk of developing an ulcer or gastrointestinal bleeding when taken with medications like non-steroidal anti-inflammatory drugs or NSAIDs. 
• The metabolism of methylprednisolone may be impacted by other medications or foods, which can decrease the effectiveness of its use in many severe conditions. Similarly, some interactions may inhibit the metabolism of methylprednisolone, increasing circulating concentrations and, ultimately, the risk of experiencing side effects like high blood sugar and blood pressure.
• Methylprednisolone can prevent the metabolism of other medications, with the potential for serious side effects with specific medications, like warfarin and cyclosporine.
• In a methylprednisolone interaction, it is important to speak with a healthcare provider to discuss which medication should be modified since there is significant nuance in the interplay between corticosteroids and other medications. 

Methylprednisolone-drug interactions

When combined with other drugs that are known to have similar side effects,

Methylprednisolone’s most serious drug-drug interactions may occur when:

• Taken in combination with other medications known to cause similar adverse effects 
• If the other medication impacts the blood levels of methylprednisolone 
• Methylprednisolone impacts the circulating concentrations of the other medication 

These interactions include both prescription drugs and over-the-counter medications. 

Cyclosporine

Cyclosporine is an immunosuppressant agent used in multiple conditions, such as aplastic anemia, graft-versus-host disease, psoriasis, and others. One of the potential adverse effects of cyclosporine is its increased risk for seizures or convulsions; prescribing information for both cyclosporine and methylprednisolone (specifically high-dose methylprednisolone) warns that the combination may additively increase this risk. Additionally, methylprednisolone may decrease the blood levels of cyclosporine. This could significantly affect patients taking this medication to manage serious medical conditions. The exact mechanism of this interaction is not fully understood, but methylprednisolone may likely induce the activity of enzymes involved in the metabolism of cyclosporine. Due to some variation in the specific change in cyclosporine concentrations to anticipate with this combination, the general recommendation is to monitor for decreased cyclosporine concentrations when combined with methylprednisolone through blood tests. The dose of cyclosporine could then be modified, likely increased, to achieve goal levels. Similarly, when a patient is on the combination and methylprednisolone is discontinued, cyclosporine levels should be monitored closely for the need to decrease the dose without this ongoing interaction. 

Warfarin

Warfarin, a Vitamin K Antagonist, is a blood thinning medication used in cardiac conditions like atrial fibrillation (afib) and in the management of acute venous thromboembolism (VTE) -or blood clots. Inherently, use of warfarin comes with a risk of bleeding, so monitoring is regularly performed of international normalized ratio (INR) with goal ranges established based upon indication. Many medications and changes in diet can interact with warfarin, causing changes to a person’s INR, which is a measure of how long it takes blood to clot (e.g., the higher the INR, the longer it will take for clotting to occur, the more at risk of a significant bleed). When a person is on a combination of warfarin and methylprednisolone, close monitoring of the effect on the INR is recommended, with a dose adjustment of warfarin to be made accordingly (dose decrease). Several reports of patients receiving warfarin realized a significant increase in INR upon initiating corticosteroid therapy. Based on limited data and such interpatient variation in the effect, a preemptive decrease in warfarin cannot be recommended. Those on this combination should look for signs of bleeding, including nosebleeds, bloody stools, and bloody or pink urine. In the event of any sign of bleeding, seek immediate medical advice. 

NSAIDs

Methylprednisolone, and other corticosteroids, should be taken in combination with corticosteroids cautiously as both drug classes independently increase the risk of gastrointestinal adverse effects. When taken together, the risk is further increased. Corticosteroid use has been associated with the development of gastrointestinal ulceration, and its use has been identified as a significant risk factor for gastrointestinal complications when combined with NSAIDs. Both corticosteroids and NSAIDs have been found to cause gastrointestinal injury through multiple mechanisms, including direct irritant effects on the protective layer of the GI tract, impairment of protective mechanisms such as suppression of gastric prostaglandin production, and reduced blood flow which interferes with the body’s repair response. The interaction is severe enough that prescribing information for many NSAIDs warns against the concomitant use of corticosteroids in a Food and Drug Administration (FDA) issued Medication Guide. It is best to avoid this combination of medications entirely. However, short courses of combination therapy are likely to be safe. Similar monitoring for signs and symptoms of bleeding as with warfarin should occur. 

NSAIDs are a class of medications which include: 

• Diclofenac
• Etodolac
• Ibuprofen
• Indomethacin
• Ketorolac
• Meloxicam
• Nabumetone
• Naproxen
• Sulindac

Desmopressin

Desmopressin, also referred to as DDAVP, is a medication employed for numerous serious medical conditions, one of which is due to reversible causes of low blood levels of an important electrolyte-sodium. This condition is known as hyponatremia. Sodium is critical for maintaining appropriate fluid balance and blood pressure, and very low sodium levels can result in fatigue, confusion, seizures, and even a coma. Corticosteroids may enhance the hyponatremic effect of desmopressin, and this combination is contraindicated in the prescribing information of desmopressin. After discontinuing the steroid, desmopressin initiation should be delayed for approximately three days (depending upon the corticosteroid). 

Estrogen Derivatives

Estrogen derivatives encompass contraceptives for birth control and estrogens for hormone replacement therapy. This class of medication may increase the blood levels of corticosteroids, such that individuals receiving both an estrogen derivative and a corticosteroid should be monitored for increased effects and toxicities of the steroid. Side effects to monitor for include muscle pain or weakness, high blood pressure, thin skin, impaired wound healing, and altered mental status. Similarly, suppose an individual receives both medications at a stable (symptom-controlled) dose, and the estrogen derivative is discontinued or the dose is decreased. In that case, the individual should be monitored for decreased corticosteroid effects. The mechanism of these interactions is not entirely understood. Still, it may be related to an estrogen-induced change in steroid metabolism or the ability of the steroid to bind to certain proteins to have its effect.

Estrogen derivatives include but are not limited to: 

• Cyproterone and ethinyl estradiol
• Drospirenone and estradiol
• Estradiol and norethindrone
• Estradiol
• Estradiol and levonorgestrel
• Estradiol and norgestimate
• Estrogens, conjugated
• Ethinyl estradiol
• Mestranol

Quinolones

Quinolones are a class of antibiotics used to manage infections caused by various bacteria. Quinolones are an excellent resource in our antibiotic armamentarium. Still, they are independently associated with many significant side effects, much so that the FDA has issued guidance regarding their use. Quinolones should be reserved for select populations to treat serious, complicated infections for which less toxic alternatives may exist. For example, older patients, transplant recipients, and patients on long-term corticosteroid use should generally avoid quinolones since they are at an increased risk of experiencing their more serious adverse effects of developing tendon ruptures, peripheral neuropathy, or central nervous system implications. Those with multiple baseline risk factors, such as age greater than 60 and on chronic methylprednisolone, are at even higher risk of these serious side effects if a quinolone antibiotic is also prescribed. Any individual receiving quinolone antibiotics and methylprednisolone should monitor themselves closely for new-onset tendon or joint pain, and if such develops, contact a healthcare professional to receive guidance on the next steps. It may be crucial to discontinue quinolone. Still, given the nature of its indication in treating acute bacterial infections, it will likely need to be immediately replaced with an alternative option.

Quinolones include:

• Delafloxacin (Bexdala)
• Ciprofloxacin (Cipro)
• Levofloxacin (Levaquin)
• Moxifloxacin (Avelox)

CYP3A4 inducers

Many methylprednisolone drug interactions occur due to medications referred to as “CYP3A4 inducers”-which are medications that increase the activity of a common enzyme (cytochrome P450) involved in the metabolism of many medications, including corticosteroids. CYP3A4 inducers are ubiquitous and rev up the enzyme to varying degrees. Strong CYP3A4 inducers include anticonvulsant medications like phenobarbital, phenytoin, and carbamazepine. These medications will decrease the blood levels of methylprednisolone, which may necessitate dose increases of the steroid, but minimally close monitoring for reduced steroid efficacy. Depending upon the indication for the corticosteroid, this interaction could have a significant impact-including increased asthma exacerbations for those with steroid-dependent asthma, for example. 

Other strong CYP3A4 inducers include: 

• Rifampin
• Ketoconazole

Moderate CYP3A4 inducers include:

• Diltiazem
• Erythromycin
• Medications for fungal infections, such as fluconazole, isavuconazole, and posaconazole
• Letermovir
• Verapamil

It’s important to note that these lists are not all-inclusive. Always check with a healthcare professional for any drug-drug interactions. 

Diabetes medications

One of the unintended side effects of corticosteroid use is that it increases the body’s glucose production. For patients with diabetes and on related medications, this may render their blood glucose control suboptimal while receiving corticosteroids. The mechanism by which corticosteroids are responsible for glucose intolerance is like that of Type 2 diabetes via increased insulin resistance. 

Diabetes drug classes and medications include but are not limited to:

Biguanides 

• Metformin
• Riomet
• Glumetza

Sulfonylureas 

• Glimepiride
• Glyburide
• Glipizide

Alpha glucosidase inhibitors

• Acarbose
• Precose
• Glyset
• Miglitol

Amylin analogues 

• Pramlintide

Meglitinides 

• Repaglinide
• Nateglinide
• Starlix

Thiazolidinediones 

• Actos
• Actoplus Met
• Duetact
• Oseni
• Pioglitazone

Dipeptidyl peptidase-4 (DPP-4) inhibitors 

• Sitagliptin
• Saxagliptin
• Linagliptin

Sodium-glucose co-transporter-2 (SGLT2) inhibitors 

• Ertugliflozin
• Dapagliflozin 
• Canagliflozin 
• Empagliflozin

Incretin mimetics 

• Exenatide
• Semaglutide
• Dulaglutide
• Liraglutide)

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists 

• Rybelsus
• Ozempic
• Victoza
• Saxenda
• Tirzepatide
• Trulicity

Antihypertensives (ACE inhibitors and ARBs)

Combining corticosteroids with antihypertensives like Angiotensin Converting Enzyme inhibitors (ACE-inhibitors) or Angiotensin II Receptor Blockers (ARBs) may result in antagonistic activity. Methylprednisolone and other systemic corticosteroids are known to increase blood pressure, so adding it to a patient already requiring ACE inhibitors or ARBs for hypertension may reduce the ability of the blood pressure medications to control high blood pressure. The mechanism by which corticosteroids increase blood pressure is through the promotion of fluid retention. If a person with hypertension requires a course of methylprednisolone, their blood pressure should be monitored more closely for the duration of the steroid course. Minor modifications to the antihypertensive dose may be required, and the dose would then need to be re-evaluated upon completion of the steroid course. 

Angiotensin-converting enzyme inhibitors (ACE-inhibitors) include:

• Benazepril 
• Captopril
• Enalapril 
• Fosinopril
• Lisinopril 
• Quinapril 
• Ramipril 
• Trandolapril 

Angiotensin II receptor blockers (ARBs) include: 

• Azilsartan 
• Candesartan 
• Irbesartan 
• Losartan
• Olmesartan 
• Telmisartan 
• Valsartan 

Diuretics (Loop and Thiazide Diuretics)

An important side effect of methylprednisolone is its effect on serum electrolytes like potassium. There are several contributing mechanisms to this side effect. Both loop diuretics and thiazide diuretics are also known to cause potassium wasting, so concurrent therapy with corticosteroids may be additive. Frequent monitoring of serum potassium is recommended in patients on this combination therapy, and potassium supplementation may be necessary. Symptoms of hypokalemia (low potassium) may not always be apparent, so it’s important to keep up with any recommended laboratory monitoring by a medical professional. Often, symptoms associated with hypokalemia are not apparent until the level is severe and may cause an abnormal heart rhythm (arrhythmia).

Loop diuretics include:

• Bumetanide
• Ethacrynic acid 
• Furosemide 
• Torsemide 

Thiazide diuretics include:

• Chlorothiazide 
• Chlorthalidone 
• Hydrochlorothiazide
• Metolazone 

Methylprednisolone-food interactions

Corticosteroids are known to increase appetite, which can result in increased caloric intake. For some, this side effect can be challenging to control. Those requiring a short burst of steroid therapy may not be significantly impacted. Others requiring chronic or long-term steroids may experience lasting effects on weight gain. Coupling this with methylprednisolone’s ability to cause increased blood glucose, individuals can get into serious trouble. Usually, the higher the dose of the steroid and the longer the treatment is required, the more difficult this side effect is to manage. Eating small, frequent meals of high nutritional value should be encouraged to curb this side effect and increase the sensation of satiety. 

Methylprednisolone and grapefruit 

Grapefruit and its juice interact with many prescription drugs. It is known through scientific studies to inhibit an important enzyme in the metabolism of many medications, known as cytochrome P450 3A4 or CYP3A4. CYP3A4 plays a role in metabolizing more than 65% of all drugs. When grapefruit juice inhibits the action of the enzyme, more of the drug is available to remain in the blood and throughout the body. This interaction is present between methylprednisolone and grapefruit juice, with studies demonstrating that high amounts of grapefruit juice increase blood levels of methylprednisolone. Persons who regularly consume grapefruit juice and go on to take methylprednisolone should be aware of this interaction and monitor themselves for increased side effects related to the steroid. 

Other methylprednisolone interactions

In those receiving high doses of corticosteroids, generally defined as systemic (as opposed to topical or inhaled) doses equivalent to more than 2 mg/kg or 20 mg/day of prednisone for more than two weeks, live vaccines should not be administered. The Advisory Committee on Immunization Practices (ACIP) states that this dose or duration-equivalent steroid use is sufficient to suppress the immune system, such that the administration of live vaccines increases the risk of vaccine-associated infection. ACIP recommendations also state vaccination with live vaccines should be avoided until after systemic corticosteroids have been discontinued for a minimum of one month, and those individuals who have received a live vaccine should avoid initiating systemic corticosteroids for at least one month after receipt of the live vaccine. 

Examples of live vaccines include:

• Measles, mumps, and rubella (MMR) vaccines
• Measles, mumps, rubella, and varicella (MMRV) vaccines
• Rotavirus vaccines
• Smallpox vaccines
• Varicella (Chickenpox) vaccines 

Methylprednisolone and caffeine 

Methylprednisolone and caffeine do not interact with one another in the traditional sense, but one should use caution when combining the two. Like caffeine, methylprednisolone and other steroids can cause stimulant-life effects, such as the sensation of anxiety or an overall jitteriness. Those who are particularly sensitive to the effects of caffeine should exercise caution if also taking steroids, as those effects may be additive. Experiencing a rapid heart rate or light-headedness would be symptoms that should give pause to put down that extra cup of coffee if placed on a corticosteroid. 

Methylprednisolone and medical conditions

There are many medical conditions and scenarios in which corticosteroids should be avoided. Myasthenia gravis (MG) is a disorder in which muscle weakness occurs in those muscles over which we typically have voluntary control. This can result in limitations with ambulation, vision problems, inability to talk, and even breathing issues. Corticosteroids are known to cause exacerbations of MG, so they should only be used in patients with MG under the careful eye of a medical professional. 

Long-term use of methylprednisolone and other steroids can induce serious medical conditions, including osteoporosis, glaucoma, cataracts, and thyroid dysfunction. 

How to minimize methylprednisolone interactions

Always carry a complete list of medications, including supplements, on your person. Any time you’re inquiring about medical advice, provide this list so that a thorough review and drug information assessment can be performed to minimize the risk of drug interactions. Anytime you start a new medication, and new signs or symptoms arise, however mild they might be, it is best to review them with your healthcare professional. 

When to talk to a healthcare provider about methylprednisolone interactions

This article is not a complete list of methylprednisolone interactions. Be mindful of the risk of additive side effects and direct drug interactions when corticosteroids are combined with prescription and over-the-counter medications. Communicate directly with a healthcare professional anytime you begin taking methylprednisolone so that a comprehensive review of interactions between medications, diet, and conditions occurs to ensure a proper monitoring plan is put in place.