methylprednisolone (Rx)

Frequency Not Defined

Acne

Adrenal suppression

Amenorrhea

Delayed wound healing

Delirium

Diabetes mellitus

Edema

Emotional instability

Erythema

Fluid retention

GI perforation

Glucose intolerance

Growth suppression (children)

Hallucinations

Headache

Hepatomegaly

Hepatitis

Hypokalemic alkalosis

Increased transaminases

Insomnia

Leukocytosis

Menstrual irregularity

Myopathy

Neuritis

Osteoporosis

Peptic ulcer

Perianal pruritus

Pituitary adrenal axis suppression

Protein catabolism

Pseudotumor cerebri (on withdrawal)

Psychosis

Sodium and water retention

Seizure

Tachycardia

Ulcerative esophagitis

Urticaria

Vasculitis

Vertigo

Weight gain

Contraindications

Untreated serious infections

Documented hypersensitivity to drug or components (eg, lactose monohydrate from cow milk)

Intrathecal administration

Systemic fungal infection (except intra-articular injection in localized joint conditions)

IM route is contraindicated in idiopathic thrombocytopenic purpura

Premature infants (formulations containing benzyl alcohol only)

Traumatic brain injury (high doses)

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids

Cautions

Use with caution in cirrhosis, ocular herpes simplex, hypertension, diverticulitis, hypothyroidism, myasthenia gravis, peptic ulcer disease, osteoporosis, ulcerative colitis, psychotic tendencies, renal insufficiency, pregnancy, diabetes mellitus, history of seizure disorders, multiple sclerosis, thromboembolic disorders, myocardial infarction

Long-term treatment: Risk of osteoporosis, myopathy, delayed wound healing

Minimal mineralocorticoid activity

Use in septic shock or sepsis syndrome not proven effective and may increase mortality in some patients including patients with elevated serum creatinine and patients who develop secondary infections

Clearance of corticosteroids may increase in hyperthyroid patients and decrease in hypothyroid ones; dose adjustments may be necessary

Patients receiving corticosteroids should avoid chickenpox or measles-infected persons if unvaccinated

Latent tuberculosis may be reactivated (patients with positive tuberculin test should be monitored)

Some suggestion (not fully substantiated) of slightly increased cleft palate risk if corticosteroids are used in pregnancy

May cause hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing syndrome, or hyperglycemia

Prolonged corticosteroid use may result in elevated IOP, glaucoma, or cataracts

Killed or inactivated vaccines may be administered; however, the response to such vaccines cannot be predicted

Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy in physiologic doses (eg, for Addison’s disease)

Injection may result in dermal and/or subdermal changes forming depressions in the skin at injection site; to minimize incidence of dermal and subdermal atrophy, care must be exercised not to exceed recommended doses in injections; avoid injection into deltoid muscle due to high incidence of subcutaneous atrophy

Increased dosage of rapidly acting corticosteroids indicated in patients on corticosteroid therapy subjected to any unusual stress before, during, and after the stressful situation

Not for use in the treatment of traumatic brain injury

Average and large doses of corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium; dietary salt restriction and potassium supplementation may be necessary; all corticosteroids increase calcium excretion

Drug induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage; relative insufficiency may persist for months after discontinuation of therapy; therefore, in situation of stress occurring during that period, hormone therapy should be reinstituted

Rarely, high doses of cyclically pulsed intravenous methylprednisolone (usually for the treatment of exacerbations of multiple sclerosis at doses of 1 g/day) can induce a toxic form of acute hepatitis; discontinue therapy if it occurs; since recurrence has occurred after re-challenge, avoid use in patients with a history of toxic hepatitis caused by methylprednisolone

With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases; corticosteroids may also mask some signs of current infection; corticosteroids may exacerbate systemic fungal infections and should not be used in presence of such infections unless needed to control drug reactions; latent amebiasis or active amebiasis should be ruled out before initiating corticosteroid therapy patients who have spent time in tropics or patients with unexplained diarrhea

Lowest possible dose should be used to control condition under treatment; when reduction in dosage possible, reduction should be gradual

Risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used

Kaposi’s sarcoma reported in patients receiving corticosteroid therapy, most often for chronic conditions; discontinuation of therapy may result in clinical improvement

Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not affect the ultimate outcome or natural history of the disease

Psychic derangements may appear when corticosteroids used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations; also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids

Give consideration to potential for hypersensitivity reactions to cow’s milk ingredients in Solumedrol; if appropriate, stop administration of injection solution Solumedrol and treat patient’s condition accordingly; alternative treatments, including use of corticosteroid formulations that do not contain ingredients produced from cow’s milk, should be considered for acute allergy management

Increased incidence of scleroderma reported in patients with systemic sclerosis; use caution

Epidural injection

• Serious neurologic events, some resulting in death, have been reported with epidural injection
• Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke
• These serious neurologic events have been reported with and without use of fluoroscopy
• Safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use

Methylprednisolone preserved with benzyl alcohol

• Methylprednisolone preserved with benzyl alcohol should not be administered to neonates, infants, pregnant women, or breastfeeding women
• Benzyl alcohol is associated with serious adverse events and death, particularly in pediatric patients (gasping syndrome, characterized by CNS depression, metabolic acidosis, and gasping respirations)

Pregnancy category: C

Lactation: Drug enters milk; use with caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Potent glucocorticoid with minimal to no mineralocorticoid activity

Modulates carbohydrate, protein, and lipid metabolism and maintenance of fluid and electrolyte homeostasis

Controls or prevents inflammation by controlling rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at cellular level

Absorption

Onset: 1-2 hr (PO); 4-8 days (IM); 1 week (intra-articular)

Duration: 30-36 hr (PO); 1-4 weeks (IM)

Peak plasma time: 31 min (IV)

Distribution

Vd: 0.7-1.5 L/kg

Metabolism

Extensively metabolized in liver

Elimination

Half-life: 3-3.5 hr

Dialyzable: Hemodialysis, slightly

Total body clearance: 16-21 L/hr

Excretion: Urine (mainly, as metabolites), feces (minimally)

IV Compatibilities

Solution: D5/0.5 NS, D5/NS, D5W, LR, NS

Additive: Chloramphenicol sodium succinate, cimetidine, clindamycin, dopamine, granisetron, heparin, norepinephrine, penicillin G potassium, ranitidine, theophylline, verapamil

Syringe: Diatrizoate meglumine, diatrizoate meglumin/diatrizoate sodium, granisetron, iohexol, iopamidol, iothalamate meglumine, ioxalate meglumine/ioxalate sodium, metoclopramide

Y-site (partial list): Acyclovir, amifostine, amiodarone, cisplatin, dopamine, enalaprilat, famotidine, heparin, inamrinone, linezolid, meperidine, metronidazole, midazolam, morphine, sodium bicarbonate

IV Incompatibilities

Additive: Aminophylline(?), calcium gluconate, cytarabine(?), glycopyrrolate, metaraminol, nafcillin, penicillin G sodium

Syringe: Doxapram

Y-site: Allopurinol, amsacrine, ciprofloxacin, cisatracurium(?), diltiazem(?), etoposide phosphate, fenoldopam, filgrastim, gemcitabine, heparin/hydrocortisone(?), ondansetron, paclitaxel, potassium chloride(?), propofol, sargramostim, vinorelbine, vitamins B and C(?)

IV/IM Preparation

Reconstitute for IM/IV injection with BWI containing 0.9% benzyl alcohol

IV Administration

Inject directly into vein or into tubing of running IV

Injection: Administer over at least 1 minute

Infusion: Further dilute reconstituted mixture with D5W, NS, D5/NS, or other compatible solution

Push: Administer over 10-20 minutes