What are the side effects of Solumedrol (methylprednisolone)?

Solumedrol Side Effects

Solumedrol (methylprednisolone) carries significant risks including immunosuppression with increased infection susceptibility, metabolic disturbances (hyperglycemia, diabetes), neuropsychiatric effects (mood changes, insomnia, psychosis), osteoporosis, adrenal suppression, and cardiovascular complications, with severity and frequency increasing with higher doses and longer duration of therapy. 1

Immediate and Short-Term Side Effects (Days to Weeks)

Common Effects

• Mood disturbances including euphoria, insomnia, mood swings, personality changes, and severe depression occur frequently, with sleep disturbances affecting >30% of patients 2
• Facial flushing (45% of patients), headache (22%), and facial edema (18%) can occur even after single doses 3
• Hyperglycemia and worsening of diabetes are common, particularly requiring blood glucose monitoring 4, 2
• Increased appetite and weight gain often develop within the first few weeks of therapy 2
• Gastric irritation with increased risk of peptic ulcer formation 2
• Hypertension can develop or worsen quickly 2

Neuropsychiatric Effects

• Psychic derangements ranging from euphoria to frank psychotic manifestations can occur 1
• Existing emotional instability or psychotic tendencies may be aggravated 1

Serious Immunosuppression and Infection Risks

Infection Susceptibility

• Reduced resistance to new infections and exacerbation of existing infections 1
• Increased risk of disseminated infections and reactivation of latent infections 1
• Masking of infection signs, making diagnosis more difficult 1
• Infectious complications increase with increasing corticosteroid dosages 1

Specific Infection Risks

• Tuberculosis reactivation may occur in patients with latent tuberculosis or tuberculin reactivity; chemoprophylaxis should be given during prolonged therapy 1
• Varicella and measles can have serious or fatal courses in non-immune patients; prophylaxis with varicella zoster immune globulin or immunoglobulin may be indicated after exposure 1
• Hepatitis B virus reactivation can occur in carriers; screen patients before initiating immunosuppressive treatment 1
• Fungal infections may be exacerbated; avoid use in presence of systemic fungal infections unless needed to control drug reactions 1
• Amebiasis may be activated; rule out latent or active amebiasis before initiating therapy in at-risk patients 1
• Strongyloides infestation requires great care in known or suspected cases 1

Infection Prevention Recommendations

• Consider Pneumocystis jirovecii pneumonia prophylaxis for patients taking ≥20 mg prednisone equivalent for ≥4 weeks 4, 2
• Update all vaccines before starting immunosuppressive therapy 2
• Avoid live vaccines in patients already taking immunosuppressants 2

Long-Term Complications (Months to Years)

Musculoskeletal Effects

• Osteoporosis and increased fracture risk are among the most serious complications, with vertebral compression fractures occurring in up to 27% of patients 2
• Aseptic necrosis of femoral and humeral heads can develop even at moderate doses 2
• Proximal myopathy affecting diaphragmatic and intercostal muscles 4, 2
• Baseline and annual bone mineral density testing recommended for long-term therapy 2

Metabolic and Endocrine Effects

• Diabetes and glucose intolerance 4
• Adrenal axis suppression with risk of adrenal insufficiency 4
• Cushing's syndrome with redistribution of body fat, truncal obesity, moon facies, and buffalo hump occurring in 80% after two years 4, 2
• Weight gain and fluid retention 4
• Dyslipidemia increasing cardiovascular disease risk 2

Ophthalmologic Effects

• Cataracts, particularly posterior subcapsular cataracts, develop with prolonged use 4, 2
• Increased intraocular pressure and glaucoma 4, 2
• Regular eye examinations required for patients on long-term therapy 2

Gastrointestinal Effects

• Peptic ulceration risk increases, particularly with concurrent NSAID use 4
• Use cautiously in nonspecific ulcerative colitis, diverticulitis, fresh intestinal anastomoses, or active/latent peptic ulcer 1
• Proton pump inhibitor therapy recommended for GI prophylaxis in patients receiving steroids 4

Cardiovascular Effects

• Hypertension 4
• Fluid retention 4
• Increased cardiovascular disease risk from dyslipidemia 2

Dermatologic Effects

• Dermal thinning 4
• Alopecia (with cyclophosphamide combinations) 4

Dose and Duration-Dependent Risk Factors

High-Risk Scenarios

• Doses >20 mg/day for more than 18 months lead to severe adverse effects in approximately 15% of patients 4, 2
• Duration >6 weeks significantly increases risk of adverse effects 2
• Severe adverse effects occur mainly at doses >20 mg/day for >18 months and lead to treatment discontinuation in about 15% 4

Risk Factors for Increased Complications

• Female sex associated with higher risk of glucocorticoid-related adverse events 4
• Pre-existing conditions: hypertension, diabetes, glucose intolerance, cardiovascular disease, dyslipidemia, peptic ulcer, osteoporosis, cataracts, glaucoma, chronic/recurrent infections 4
• Elderly patients require more careful monitoring and often lower doses 2
• Children at higher risk for growth suppression and have higher skin surface/body mass ratio increasing systemic absorption risk 4, 2

Special Considerations and Precautions

Pregnancy-Related Use

• Methylprednisolone 16 mg IV every 8 hours for up to 3 days can be used as last resort in severe hyperemesis gravidarum, followed by tapering over 2 weeks 4
• Slight increased risk of cleft palate when given before 10 weeks gestation; use with caution in first trimester 4

Drug Interactions

• Cyclosporine: mutual inhibition of metabolism; convulsions reported with concurrent use 1
• Phenobarbital, phenytoin, rifampin: increase methylprednisolone clearance, may require dose increases 1
• Troleandomycin, ketoconazole: inhibit metabolism, decrease clearance, requiring dose titration to avoid toxicity 1
• Aspirin: methylprednisolone may increase clearance of chronic high-dose aspirin 1
• Oral anticoagulants: variable effects; monitor coagulation indices 1

Tumor Lysis Syndrome

• Reported in patients with malignancies following systemic corticosteroid use 1
• Monitor patients at high risk (high proliferative rate, high tumor burden, high sensitivity to cytotoxic agents) closely 1

Specific Formulation Concerns

• Intrathecal methylprednisolone acetate (Depo-Medrol) is not fully safe due to neurotoxic excipients (polyethylene glycol, miripirium chloride) causing arachnoiditis, bladder dysfunction, headache, meningitis 5
• Use soluble methylprednisolone sodium succinate free from excipients instead 5

Allergic Reactions

• Rare allergic skin rashes to methylprednisolone sodium succinate have been reported; betamethasone can be substituted successfully 6

Monitoring Recommendations

Short-Term Monitoring

• Blood glucose monitoring, even during short courses 2
• Blood pressure monitoring 2
• Weight monitoring to detect rapid fluid retention 2

Long-Term Monitoring

• Bone mineral density testing at baseline and annually 2
• Regular eye examinations for cataracts and glaucoma 2
• Lipid profile monitoring 2
• Growth and development monitoring in children on prolonged therapy 1

Risk Minimization Strategies

• Use lowest effective dose for shortest duration possible 2, 1
• Consider alternate-day therapy when appropriate to reduce adrenal suppression 2
• Consider steroid-sparing agents when long-term therapy is anticipated 2
• Calcium and vitamin D supplementation to prevent osteoporosis 4, 2
• Educate patients about signs of infection and when to seek medical attention 2
• Gradual dose reduction when discontinuing to avoid adrenal insufficiency 1

Patient Education Requirements

• Warn patients on immunosuppressant doses to avoid exposure to chickenpox or measles 1
• Advise patients to seek medical advice without delay if exposed 1
• Inform about common side effects and when to report concerning symptoms 2