Methylprednisolone

Systemic glucocorticoid

ATC code: H02AB04

Brand names: Medrol, Solu-Medrol, Depo-Medrol

Updated 19 Aug 2026 · Methodology

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Chronic fatigue

Not recommended

Methylprednisolone is a systemic corticosteroid. It is prescribed for acute autoimmune crises, severe allergic reactions, cerebral edema, and severe autoimmune disease flares ( 2023, AEMPS Ficha Técnica). For chronic fatigue without a confirmed diagnosis, methylprednisolone is not indicated. The drug has serious risks on long-term use: adrenal suppression, steroid diabetes, osteoporosis with fractures, avascular bone necrosis, immunosuppression, psychiatric disturbances, cataract, and hypertension. If methylprednisolone was prescribed for fatigue, seek a second opinion immediately.

Sources

ICD-10: R53 · ICD-11: MG22

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Binds to cytoplasmic glucocorticoid receptors, inhibits phospholipase A2, reduces arachidonic acid and pro-inflammatory cytokine production. Higher anti-inflammatory potency than prednisolone at equivalent dose.

Safety

Contraindications

Hypersensitivity to methylprednisolone
Systemic fungal infections
Active viral infections (especially varicella, measles, herpes zoster)
Live vaccines at immunosuppressive doses

Serious adverse effects

Adrenal suppression and crisis on abrupt withdrawal
Severe infections due to immunosuppression
Psychosis
Avascular bone necrosis
GI perforation

Common adverse effects

Weight gain and Cushingoid features
Insomnia and mood changes
Hypertension
Hyperglycaemia
Gastritis and peptic ulcers
Osteoporosis with prolonged therapy

Uncommon adverse effects

Adrenal suppression and crisis on abrupt withdrawal
Avascular bone necrosis (especially femoral head)
Glaucoma and cataract with prolonged therapy
Severe infections due to immunosuppression
Psychosis and mood changes

Pregnancy: can you take Methylprednisolone?

AEMPS summary of product characteristics (section 4.6): methylprednisolone crosses the placenta, and there are not enough data on its use in pregnant women. Animal studies showed a higher incidence of cleft palate, and epidemiological data suggest that glucocorticoid use in the first trimester may increase the risk of cleft lip or palate. Methylprednisolone should be used in pregnancy only if the potential benefits for the mother outweigh the potential risks, including those for the fetus.

Breastfeeding: can you take Methylprednisolone?

Compatible. Hale L2. Transfers into milk in small amounts. Single pulse doses and short courses do not produce clinically meaningful infant exposure. With prolonged high-dose systemic therapy, infant growth and adrenal function are monitored.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–nutrient interactions

Grapefruit juice

Grapefruit juice can raise levels of methylprednisolone, which is broken down by CYP3A4. More steroid in the blood strengthens its effects: high glucose and blood pressure, fluid retention, insomnia, more infections. The Urbason SmPC says to avoid large amounts of grapefruit juice during treatment.

Source: AEMPS: Ficha técnica de Urbason 4 mg comprimidos (metilprednisolona) (2024)

Drug–drug interactions

8 pairs found. Sorted from critical to minor.

MajorAcetylsalicylic acidAntiplatelet agents (low dose) / NSAIDs (analgesic dose)

Mechanism

Glucocorticoids damage the gastric mucosa and suppress protective prostaglandin production. Aspirin compounds the risk of GI ulcer and bleeding.

Symptoms

Epigastric pain, nausea, heartburn. With prolonged therapy: peptic ulcer and GI bleeding risk (black stools, vomiting blood). Older patients and prior peptic ulcer disease: higher risk.

Management

Aspirin SmPCs, including those for 100 mg tablets, advise against combining aspirin with systemic glucocorticoids because together they raise the risk of ulcers and gastrointestinal bleeding (aspirin 100 mg and 500 mg SmPCs). If the combination cannot be avoided, use it with caution: tell the patient in advance about the signs of bleeding (black stools, vomiting blood, marked weakness, low blood pressure, cold sweat, abdominal pain, dizziness) and that if they appear, aspirin is stopped and they must see a doctor at once (aspirin SmPCs). The methylprednisolone SmPC also asks for patient monitoring: methylprednisolone can speed up salicylate elimination and weaken its effect (methylprednisolone SmPC). In patients on long-term high-dose aspirin, salicylate levels can rise to toxic values when methylprednisolone is withdrawn (US methylprednisolone label).

Sources

Pair details →Acetylsalicylic acid →

MajorBupropionOther antidepressants (NDRI)

Mechanism

Methylprednisolone (a systemic glucocorticoid) modestly lowers the seizure threshold and induces CYP3A4. Bupropion also lowers the seizure threshold. Combined action raises the risk of episodes, particularly in patients with prior epilepsy or eating disorders.

Symptoms

Seizures (generalised tonic-clonic or focal). In patients without prior epilepsy: isolated episodes; with epilepsy: more frequent seizures. Agitation, anxiety possible.

Management

Avoid the combination in patients with prior epilepsy or eating disorders. If unavoidable, do not increase bupropion dose and discontinue methylprednisolone as soon as possible. Alternative antidepressants without seizure threshold reduction: sertraline, escitalopram.

Sources

FDA: Wellbutrin (bupropion hydrochloride) prescribing information (2017)

Pair details →Bupropion →

MajorCiprofloxacinFluoroquinolone antibacterials

Mechanism

Fluoroquinolones, including ciprofloxacin, can cause tendinitis and tendon rupture, most often of the Achilles tendon. The risk is higher in older patients, in renal impairment, after solid organ transplantation and in patients who take corticosteroids at the same time (ciprofloxacin SmPC). Methylprednisolone itself very rarely causes tendon rupture, for example of the Achilles tendon (methylprednisolone SmPC). The US Food and Drug Administration () label specifies age over 60 and adds strenuous physical activity and previous tendon disorders as risk factors (ciprofloxacin FDA label). A second mechanism is metabolic: some corticosteroids are cleared by the CYP3A4 enzyme (methylprednisolone SmPC), and the FDA classes ciprofloxacin as a moderate CYP3A inhibitor (FDA list), so methylprednisolone levels may rise.

Symptoms

Pain, swelling and inflammation of the Achilles tendon, less often of tendons in the shoulder, hand or biceps, sometimes on both sides, up to tendon rupture (ciprofloxacin labels). Symptoms can start within 48 hours of starting ciprofloxacin and as late as several months after the course ends (ciprofloxacin SmPC).

Management

The ciprofloxacin SmPC says concomitant use of corticosteroids should be avoided because of the risk of tendinitis and tendon rupture (ciprofloxacin SmPC). The methylprednisolone SmPC also advises avoiding CYP3A inhibitors unless the benefit outweighs the higher risk of systemic corticosteroid adverse effects, and monitoring the patient for them if the combination is used (methylprednisolone SmPC); the US Food and Drug Administration () classes ciprofloxacin as a moderate CYP3A inhibitor (FDA list). Ciprofloxacin is generally not given to patients who have had tendon disorders with a quinolone before (ciprofloxacin SmPC). Warn the patient about the symptoms: at the first sign of tendinitis, such as painful swelling or inflammation, stop ciprofloxacin at once and immobilise the affected limb, and do not use corticosteroids if there are signs of tendinopathy (ciprofloxacin SmPC).

Sources

Pair details →Ciprofloxacin →

MajorClarithromycinMacrolide antibiotic

Mechanism

Methylprednisolone is broken down in the liver by CYP3A4, and clarithromycin inhibits this enzyme. A considerable rise in methylprednisolone blood levels has been observed with clarithromycin (methylprednisolone SmPC). Higher levels increase the risk of systemic corticosteroid adverse effects (methylprednisolone SmPC).

Symptoms

Moon face, central obesity, abdominal striae, high blood pressure, high blood glucose (Cushing's syndrome). After prolonged combined use and abrupt withdrawal, adrenal insufficiency with low blood pressure and weakness may occur.

Management

Avoid the combination unless the benefit outweighs the risk of systemic corticosteroid adverse effects: the methylprednisolone SmPC sets this rule for all CYP3A4 inhibitors and names clarithromycin separately as a drug that considerably raises methylprednisolone levels (methylprednisolone SmPC). If the combination is needed, monitor the patient closely for systemic corticosteroid adverse effects throughout the clarithromycin course (methylprednisolone SmPC; clarithromycin SmPC). The US Food and Drug Administration () advises titrating the methylprednisolone dose to avoid steroid toxicity when drugs that slow its clearance are added (methylprednisolone FDA label).

Sources

Pair details →Clarithromycin →

MajorKetoconazoleSystemic antimycotics. Imidazole derivatives

Mechanism

Ketoconazole strongly blocks CYP3A4 – the main methylprednisolone metabolic route. Methylprednisolone plasma levels rise 2- to 3-fold. Risk of iatrogenic Cushing's syndrome and adrenal insufficiency on withdrawal.

Symptoms

Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia (Cushing's syndrome). With prolonged combination and abrupt withdrawal: adrenal insufficiency risk with hypotension and weakness.

Management

Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed, halve the methylprednisolone dose.

Sources

Pair details →Ketoconazole →

MajorRitonavirHIV protease inhibitor / pharmacokinetic booster

Mechanism

Ritonavir is the most potent CYP3A4 inhibitor available – the main methylprednisolone metabolic route. Methylprednisolone plasma levels rise 5- to 10-fold. High risk of iatrogenic Cushing's syndrome and severe adrenal insufficiency on withdrawal.

Symptoms

Management

Avoid the combination. Alternative glucocorticoid: hydrocortisone (less CYP3A4-dependent) or inhaled/topical routes (no systemic effect). If methylprednisolone is needed, reduce 5-fold and keep the course as short as possible. Taper over several weeks on withdrawal because of suppressed adrenal cortex.

Sources

Pair details →Ritonavir →

ModerateAmlodipineCalcium channel blockers (dihydropyridines)

Mechanism

Similar to amlodipine + prednisolone. Methylprednisolone causes sodium retention via mineralocorticoid effect, reducing amlodipine's antihypertensive action.

Symptoms

Gradual blood pressure rise 2–4 weeks after starting the glucocorticoid. In heart failure: oedema, weight gain.

Management

For short methylprednisolone courses, no adjustment. For prolonged systemic therapy, increase amlodipine or add a diuretic (hydrochlorothiazide, indapamide) with blood pressure monitoring every 2 weeks.

Sources

FDA: Norvasc (amlodipine) prescribing information (2017)

Pair details →Amlodipine →

ModerateBisoprololSelective beta-adrenergic blockers

Mechanism

Methylprednisolone causes sodium and water retention via mineralocorticoid effect, reducing the antihypertensive effect of the beta-blocker.

Symptoms

Gradual blood pressure rise 2–4 weeks after starting the glucocorticoid. In heart failure: oedema, weight gain.

Management

For short methylprednisolone courses (up to 7 days), no adjustment. For prolonged systemic therapy, increase bisoprolol or add a diuretic (hydrochlorothiazide, indapamide) with blood pressure monitoring every 2 weeks.

Sources

FDA: Bisoprolol tablet (Micro Labs Limited) – Prescribing Information (2016)

Pair details →Bisoprolol →

Label mentions44 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorCobicistat
«- Inhibidores de CYP3A: se espera que el tratamiento concomitante con inhibidores de CYP3A, incluyendo medicamentos que contienen cobicistat, aumente el riesgo de reacciones adversas sistémicas. Se…»
AEMPS, section 4.5 · Open on CIMA
Majorinhibidores del CYP3A4class named in the label
«- Inhibidores de CYP3A: se espera que el tratamiento concomitante con inhibidores de CYP3A, incluyendo medicamentos que contienen cobicistat, aumente el riesgo de reacciones adversas sistémicas. Se…»
AEMPS, section 4.5 · Open on CIMA
MajorKetoconazole
«- Inhibidores enzimáticos (ketoconazol): posible aumento de las concentraciones plasmáticas de corticoide.»
AEMPS, section 4.5 · Open on CIMA
MajorKetoconazole
«Drug Interactions: The pharmacokinetic interactions listed below are potentially clinically important. Mutual inhibition of metabolism occurs with concurrent use of cyclosporine and…»
FDA, section 7 · Open on DailyMed
MajorPhenobarbital
«Drug Interactions: The pharmacokinetic interactions listed below are potentially clinically important. Mutual inhibition of metabolism occurs with concurrent use of cyclosporine and…»
FDA, section 7 · Open on DailyMed
MajorPhenytoin
«Drug Interactions: The pharmacokinetic interactions listed below are potentially clinically important. Mutual inhibition of metabolism occurs with concurrent use of cyclosporine and…»
FDA, section 7 · Open on DailyMed
ModerateAmphotericin B
«- Anfotericina B: posible aumento de la hipopotasemia, con riesgo de toxicidad. Se deben vigilar los niveles plasmáticos de potasio.»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantsclass named in the label
«Drug Interactions: The effect of methylprednisolone on oral anticoagulants is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with…»
FDA, section 7 · Open on DailyMed
Moderateantidiabéticosclass named in the label
«- Antidiabéticos: los glucocorticoides puedenreducir el efecto hipoglucemiante de los antidiabéticos. Los pacientes tratados con antidiabéticos pueden precisar un ajuste de la dosis.»
AEMPS, section 4.5 · Open on CIMA
ModerateCiclosporin
«Se ha comunicado posible reducción del metabolismo hepático del corticoide. Estudios similares han evidenciado un aumento de las concentraciones plasmáticas mínimas de ciclosporina. Hay evidencias…»
AEMPS, section 4.5 · Open on CIMA
Moderatedigitálicosclass named in the label
«- Glucósidos cardiotónicos (digitálicos): la acción de los digitálicos puede estar potenciada por una hipopotasemia potencial con aumento de la toxicidad cardiaca. Se debe vigilar al paciente.»
AEMPS, section 4.5 · Open on CIMA
ModerateDiltiazem
«- Diltiazem: inhibición del metabolismo de la metilprednisolona (CYP3A4) e inhibición de la glicoproteína-P. Aumento de los niveles plasmáticos de metilprednisolona con posible potenciación de su…»
AEMPS, section 4.5 · Open on CIMA
Moderatediuréticosclass named in the label
«- Diuréticos: puede ocurrir un aumento de la excreción de potasio, es decir, puede producirse una posible potenciación de la toxicidad por aumento de la hipopotasemia. Se deben vigilar los niveles…»
AEMPS, section 4.5 · Open on CIMA
Acetylsalicylic acid
«Antiinflamatorios no esteroideos (p. ej., ácido acetilsalicílico, indometacina) y alcohol: pueden incrementar el riesgo de hemorragia gastrointestinal.»
AEMPS, section 4.5 · Open on CIMA
AINEclass named in the label
«Antiinflamatorios no esteroideos (p. ej., ácido acetilsalicílico, indometacina) y alcohol: pueden incrementar el riesgo de hemorragia gastrointestinal.»
AEMPS, section 4.5 · Open on CIMA
anticoagulantesclass named in the label
«- Derivados de la cumarina: el efecto anticoagulante puede reducirse, haciéndose necesario un control de los índices de coagulación.»
AEMPS, section 4.5 · Open on CIMA
anticonceptivos hormonalesclass named in the label
«- Estrógenos (p. ej., anticonceptivos orales): el empleo concomitante de estrógenos puede alterar el metabolismo de los corticoides incluida la metilprednisolona. Las necesidades de corticoides…»
AEMPS, section 4.5 · Open on CIMA
antiepilépticosclass named in the label
«- Inductores enzimáticos (carbamazepina, antiepilépticos como fenitoína, barbitúricos o primidona, rifampicina, rifabutina): algunos corticoides son metabolizados por el CYP3A4, por lo que los…»
AEMPS, section 4.5 · Open on CIMA
barbitúricosclass named in the label
«- Inductores enzimáticos (carbamazepina, antiepilépticos como fenitoína, barbitúricos o primidona, rifampicina, rifabutina): algunos corticoides son metabolizados por el CYP3A4, por lo que los…»
AEMPS, section 4.5 · Open on CIMA
bloqueantes neuromuscularesclass named in the label
«- Relajantes musculares no despolarizantes: puede prolongarse la relajación (ver sección 4.8).»
AEMPS, section 4.5 · Open on CIMA
Carbamazepine
«- Inductores enzimáticos (carbamazepina, antiepilépticos como fenitoína, barbitúricos o primidona, rifampicina, rifabutina): algunos corticoides son metabolizados por el CYP3A4, por lo que los…»
AEMPS, section 4.5 · Open on CIMA
Clarithromycin
«- Claritromicina, eritromicina: se ha observado un considerable aumento de las concentraciones plasmáticas de metilprednisolona.»
AEMPS, section 4.5 · Open on CIMA
Erythromycin
«- Claritromicina, eritromicina: se ha observado un considerable aumento de las concentraciones plasmáticas de metilprednisolona.»
AEMPS, section 4.5 · Open on CIMA
Hydrocortisone
«- Algunos informes describen que prednisona e hidrocortisona antagonizan el bloqueo neuromuscular en pacientes con insuficiencia corticosuprarrenal tratados con pancuronio.»
AEMPS, section 4.5 · Open on CIMA
Phenytoin
«- Inductores enzimáticos (carbamazepina, antiepilépticos como fenitoína, barbitúricos o primidona, rifampicina, rifabutina): algunos corticoides son metabolizados por el CYP3A4, por lo que los…»
AEMPS, section 4.5 · Open on CIMA
Prednisone
«Anticolinesterasa (neostigmina, piridostigmina): descritos casos de antagonismo del efecto de los anticolinesterasa, con depresión muscular. Los efectos no revirtieron con inhibidores de la…»
AEMPS, section 4.5 · Open on CIMA
relajantes muscularesclass named in the label
«- Relajantes musculares no despolarizantes: puede prolongarse la relajación (ver sección 4.8).»
AEMPS, section 4.5 · Open on CIMA
Rifabutin
«- Inductores enzimáticos (carbamazepina, antiepilépticos como fenitoína, barbitúricos o primidona, rifampicina, rifabutina): algunos corticoides son metabolizados por el CYP3A4, por lo que los…»
AEMPS, section 4.5 · Open on CIMA
Rifampicin
«- Inductores enzimáticos (carbamazepina, antiepilépticos como fenitoína, barbitúricos o primidona, rifampicina, rifabutina): algunos corticoides son metabolizados por el CYP3A4, por lo que los…»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

MajorCobicistat
«Established and Other Potentially Significant Interactions: Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone triamcinolone ↓…»
FDA, section 7 · Open on DailyMed
MajorDarunavir
«Established and Other Potentially Significant Drug Interactions: Corticosteroids: dexamethasone (systemic) Corticosteroids primarily metabolized by CYP3A: eg. betamethasone budesonide ciclesonide…»
FDA, section 7 · Open on DailyMed
ModerateClarithromycin
«Interacciones basadas en CYP3A: Se pueden considerar ajustes de dosis y cuando sea posible, las concentraciones séricas de los fármacos metabolizados principalmente por CYP3A se deben controlar de…»
AEMPS, section 4.5 · Open on CIMA
ModerateClarithromycin
«DRUG INTERACTIONS: Alfentanil Bromocriptine Cilostazol Methylprednisole Vinblastine Phenobarbital St. John’s Wort Use With Caution There have been spontaneous or published reports of CYP3A based…»
FDA, section 7 · Open on DailyMed
ModerateDiltiazem
«Corticosteroides (metilprednisolona): inhibición del metabolismo de metilprednisolona (CYP3A4) y de la P-glucoproteína: Debe vigilarse al paciente cuando se inicie el tratamiento con…»
AEMPS, section 4.5 · Open on CIMA
ModerateErythromycin
«La eritromicina es un inhibidor de la CYP3A4 y la proteína transportadora glucoproteína P. Es difícil predecir el alcance de la inhibición de los distintos sustratos del CYP3A4. Por lo tanto, no…»
AEMPS, section 4.5 · Open on CIMA
ModerateRitonavir
«Established and Other Potentially Significant Drug Interactions: Systemic/Inhaled/Nasal/Ophthalmic Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone…»
FDA, section 7 · Open on DailyMed
ModerateTacrolimus
«Effects of Other Drugs on Tacrolimus: Mild or Moderate CYP3A Inducers Methylprednisolone, prednisone May decrease tacrolimus whole blood trough concentrations. Monitor tacrolimus whole blood trough…»
FDA, section 7 · Open on DailyMed
Azithromycin
«Recomendación relativa a la administración conjunta: No se observaron cambios clínicamente significativos en la exposición de azitromicina o de los medicamentos administrados conjuntamente en los…»
AEMPS, section 4.5 · Open on CIMA
Ciclosporin
«Fármacos que aumentan los niveles de ciclosporina: Es de esperar que todos los inhibidores del CYP3A4 y/o gp-P aumenten los niveles de ciclosporina. Ejemplos son: nicardipino, metoclopramida…»
AEMPS, section 4.5 · Open on CIMA
Itraconazole
«Antivirales para uso sistémico: Metilprednisolona 16 mg»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Methylprednisolone used for?

Methylprednisolone is evaluated for the following indications with varying evidence strength: Chronic fatigue (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Methylprednisolone?

Common side effects of Methylprednisolone (≥ 1 in 100): Weight gain and Cushingoid features, Insomnia and mood changes, Hypertension, Hyperglycaemia, Gastritis and peptic ulcers, Osteoporosis with prolonged therapy. See the Safety section for uncommon and serious reactions.

Is Methylprednisolone safe during pregnancy?

Is Methylprednisolone compatible with breastfeeding?

Who should not take Methylprednisolone?

Methylprednisolone is contraindicated in: Hypersensitivity to methylprednisolone; Systemic fungal infections; Active viral infections (especially varicella, measles, herpes zoster); Live vaccines at immunosuppressive doses. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 11/21/2024
FDA / DailyMedLabel dated 06/22/2026

Other drugs in this group

Betamethasone, Deflazacort, Dexamethasone, Fludrocortisone, Hydrocortisone, Prednisolone, Prednisone