INDICATIONS

• Adrenal insufficiency
• TB meningitis
• ITP
• Cerebral edema (secondary to CNS toxoplasmosis)
• Numerous allergic, inflammatory, immunosuppressive conditions

• Immune reconstitution inflammatory syndrome (IRIS)
• Pneumocystis jiroveci (PCP) with PO₂<70 mm Hg or A-a gradient >35 mm Hg
• HIV-associated nephropathy (HIVAN)-limited data.
• Bacteria meningitis (esp. S. pneumoniae)
• TB pericarditis

FORMS

*Costs (rounded to the nearest dollar) are based on usual adult dosing per day, are representative of "Average Wholesale Price" (AWP), and are current within the prior three months.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

• Bacterial meninginitis (esp. pneumococcal meningitis): dexamethasone 10 mg q6h x 4d (start 15mins before or with first dose of ABx) in conjunction to ABx.
• Cerebral edema (mass effect secondary CNS toxoplasmosis): dexamethasone 4mg PO or IV q6 hrs in conjunction with toxoplasmosis treatment.
• ITP: prednisone 30-60mg/d with rapid taper to 5-10mg/d.
• PCP with PO₂<70 mm Hg or A-a gradient >35: prednisone 40mg PO bid x 5 d, then 40mg PO qd x 5 d, then 20mg/d to completion of treatment (IV methylprednisolone can be given as 75% of prednisone dose).
• TB meningitis (NEJM 2004;351:1741) grade I (Glasgow Coma Scale [GCS] of 3-15 with no focal neurologic signs): dexamethasone IV 0.3 mg/kg/d x 1 wk, then 0.2 mg/kg/d x1 wk, and then 4 wks of PO therapy (0.1 mg/kg/d for wk 3, then a total of 3 mg/d, decreasing by 1 mg/wk).
• TB meningitis (NEJM 2004;351:1741) grade II and III (GCS of 11-14 or of 15 with focal neurologic signs for grade II; and pts with grade III had a score of <10 with focal neurologic signs). Dose same as above.
• MAC immune reconstitution lymphadenitis: treat for MAC combined with NSAIDs; if sxs persist give prednisone 20-40mg/d for 4-8 wks (surgical drainage may be required for focal lesions), then slow taper.
• TB immune reconstitution syndrome: for severe reaction after TB infection: prednisone 1mg/kg/d x 1-2 wks,then taper. Continue TB and HIV therapy.
• Acute adrenal insufficiency: hydrocortisone succinate: 100mg IV q8h. Once stable change to hydrocortisone 50mg PO q8hx 6 doses then taper to 30-50mg/d in divided doses.
• Chronic adrenal insufficiency: hydrocortisone 20mg qam and 10mg qpm
• HIVAN: prednisone 60 mg/d (encouraging observational study but no prospective trials evaluating its safety and efficacy). HAART preferred.
• Relative potency of corticosteroid: prednisone 5 mg = hydrocortisone 20 mg = dexamethasone 0.5-0.75 mg
• IRIS: 40-60 mg qd

RENAL DOSING

ADVERSE DRUG REACTIONS

• Insomnia, agitation, nervousness
• Hyperglycemia
• Increased appetite
• Leukocytosis

• Hypokalemia
• Hypertension
• CNS: delirium, euphoria, hallucination
• Peptic ulcers (consider PPIs in high risk pts)
• OIs
• Osteoporosis
• Superinfection (i.e. thrush)
• Acne
• Cushing syndrome
• Lipid abnormalities
• Increase infection risk (with long term administration)

• Osteonecrosis
• Hirsutism
• Hyperpigmentation
• Skin atrophy
• Amenorrhea
• Hyperuricemia
• Hypercalcemia
• Pancreatitis
• Cataracts
• Papilledema
• Reversible myopathy

DRUG INTERACTIONS

• Vancomycin: corticosteroid decreases vancomycin CNS penetration, which may result in therapeutic failure.
• Loop diuretics: may result in additive hypokalemia with corticosteroids.
• Digoxin: monitor for toxicity secondary to corticosteroid induced hypokalemia.
• ASA: corticosteroids increases risk of gastrointestinal ulceration. Consider PPI co-administration.
• Neuromuscular blocker: may increase the risk and/or severity of myopathy resulting in prolonged flaccid paralysis. Use with caution.
• PIs and NNRTIs: dexamethasone increases CYP3A4 activity by 25% and therefore may lower serum levels of PIs and NNRTIs. Clinical significance of these potential interactions not known since there is substantial intersubject variability.
• PIs, DLV macrolides, azoles, and other CYP3A4 inhibitors: may increase serum levels of dexamethasone and methylprednisolone. Itraconazole: dexamethasone AUC increased by 3.7-fold. Methylprednisolone AUC increased by 2.5-fold but had no effect on prednisolone (Br J Clin Pharmacol. 2001;51:443-50).
• CYP3A4 enzyme inducers (i.e phenytoin, phenobarbital, NVP, EFV, and rifamycin): may increase metabolism of dexamethasone and methylprednisolone. Clinical significance unknown.
• Cholestyramine: decreased absorption of corticosteroid. Separate administration time by 4-6 hrs.
• Fluoroquinolones: may increase risk of tendon rupture. Use with caution.
• RTV: increased prednisolone AUC 30-41%. Interaction may apply to other boosted PI (PI/r). Prednisone dose adjustment may be needed with long-term co-administration of RTV.

PHARMACOLOGY

• Absorption: hydrocortisone: 96%; dexamethasone: 60-80%; prednisone: 92%; methylprednisolone: well absorbed
• Metabolism and Excretion: hydrocortisone: hepatic metabolism to inactive glucuronide and sulfates metabolites that are renally excreted; dexamethasone: metabolized via CYP3A4 with renal and biliary excretion; prednisone: reduced in the liver to prednisolone, active metabolite excreted via renal and biliary route. Methylprednisolone: reversible oxidation of the 11-hydroxyl group to active metabolite that is renally excreted.
• Protein Binding: hydrocortisone: 90%; prednisone: 65-91%
• T1/2: hydrocortisone: 1-2 hrs; dexamethasone: 2hrs; prednisone: 2.6-3.0 hrs; methylprednisolone: 2-3 hours.
• Distribution: hydrocortisone: 34L; dexamethasone: 2L/kg; prednisone: 0.4-1L/kg; methylprednisolone: 1.4L/kg

COMMENTS

References

1. Thwaites GE, Nguyen DB, Nguyen HD, et al.; Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.; N Engl J Med; 2004; Vol. 351; pp. 1741-51;
   ISSN: 1533-4406;
   PUBMED: 15496623
   Comments:Prospective randomized, double-blind, placebo-controlled trial in 545 pts found that treatment with dexamethasone associated with reduced risk of death (RR 0.69; 95%CI 0.52 to 0.92; p=0.01).
   
   
2. de Gans J, van de Beek D, European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators; Dexamethasone in adults with bacterial meningitis.; N Engl J Med; 2002; Vol. 347; pp. 1549-56;
   ISSN: 1533-4406;
   PUBMED: 12432041
   Comments:Prospective double-blind study in 301 adults with acute bacterial meningitis found that early administration of dexamethasone led to reduction in mortality (RR of death 0.48; 95% CI 0.24 to 0.96; p=0.04). In ps with pneumococcal meningitis, there were unfavorable outcomes in 26% of dexamethasone group compared with 52% of placebo group (RR 0.50; 95 %CI, 0.30 to 0.83; p=0.006). Dexamethasone should be used in pts with pneumococcal meningitis.
   
   
3. Bozzette SA, Sattler FR, Chiu J, et al.; A controlled trial of early adjunctive treatment with corticosteroids for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative Treatment Group.; N Engl J Med; 1990; Vol. 323; pp. 1451-7;
   ISSN: 0028-4793;
   PUBMED: 2233917
   Comments:Prospective double-blind, placebo-controlled trial in pts with AIDS with severe PCP found decrease in respiratory failure and improved survival with adjunctive corticosteroids. ADRs were not higher in corticosteroid treated group.