indication

Injection: for the treatment of endocrine disorders, rheumatic D=disorders, collagen diseases, dermatologic diseases, allergic statesc, ophthalmic diseases, gastrointestinal diseases, respiratory diseases, hematologic disorders, neoplastic diseases, edematous states, cerebral edema.
Ophthalmic ointment and solution: for the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe.
Ophthalmic solution only: for the treatment of steroid responsive inflammatory conditions of the external auditory meatus
Topic cream: for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses
Oral aerosol: for the treatment of bronchial asthma and related corticosteroid responsive bronchospastic states intractable to adequate trial of conventional therapy
Intranasal aerosol: for the treatment of allergic ot inflammatory nasal conditions, and nasal polyps

pharmacology

Dexamethasone and its derivatives, dexamethasone sodium phosphate and dexamethasone acetate, are synthetic glucocorticoids. Used for its antiinflammatory or immunosuppressive properties and ability to penetrate the CNS, dexamethasone is used alone to manage cerebral edema and with tobramycin to treat corticosteroid-responsive inflammatory ocular conditions.

mechanism of action

Dexamethasone is a glucocorticoid agonist. Unbound dexamethasone crosses cell membranes and binds with high affinity to specific cytoplasmic glucocorticoid receptors. This complex binds to DNA elements (glucocorticoid response elements) which results in a modification of transcription and, hence, protein synthesis in order to achieve inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, suppression of humoral immune responses, and reduction in edema or scar tissue. The antiinflammatory actions of dexamethasone are thought to involve phospholipase A₂ inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

toxicity

Oral, rat LD₅₀: >3 gm/kg. Signs of overdose include retinal toxicity, glaucoma, subcapsular cataract, gastrointestinal bleeding, pancreatitis, aseptic bone necrosis, osteoporosis, myopathies, obesity, edemas, hypertension, proteinuria, diabetes, sleep disturbances, psychiatric syndromes, delayed wound healing, atrophy and fragility of the skin, ecchymosis, and pseudotumor cerebri.

biotransformation

Hepatic.

absorption

80-90%

half life

36-54 hours

drug interactions

Acenocoumarol: The corticosteroid, dexamethasone, alters the anticoagulant effect, acenocoumarol.

Acetylsalicylic acid: The corticosteroid, dexamethasone, may decrease the effect of the salicylate, acetylsalicylic acid.

Ambenonium: The corticosteroid, dexamethasone, may decrease the effect of the anticholinesterase, ambenonium.

Aminoglutethimide: Aminoglutethimide may decrease the effect of dexamethasone.

Amobarbital: The barbiturate, amobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Anisindione: The corticosteroid, dexamethasone, alters the anticoagulant effect of anisindione.

Aprepitant: Aprepitant may increase the effect and toxicity of dexamethasone.

Aprobarbital: The barbiturate, aprobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Butabarbital: The barbiturate, butabarbital, may decrease the effect of the corticosteroid, dexamethasone.

Butalbital: The barbiturate, butalbital, may decrease the effect of the corticosteroid, dexamethasone.

Butethal: The barbiturate, butethal, may decrease the effect of the corticosteroid, dexamethasone.

Dabigatran etexilate: P-Glycoprotein inducers such as dexamethasone may decrease the serum concentration of dabigatran etexilate. This combination should be avoided.

Dicumarol: The corticosteroid, dexamethasone, alters the anticoagulant effect of dicumarol.

Dihydroquinidine barbiturate: The barbiturate, dihydroquinidine barbiturate, may decrease the effect of the corticosteroid, dexamethasone.

Edrophonium: The corticosteroid, dexamethasone, may decrease the effect of the anticholinesterase, edrophonium.

Ethotoin: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, dexamethasone.

Fosphenytoin: The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, dexamethasone.

Heptabarbital: The barbiturate, heptabarbital, may decrease the effect of the corticosteroid, dexamethasone.

Hexobarbital: The barbiturate, hexobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Imatinib: Dexamethasone may decrease levels of imatinib.

Magnesium salicylate: The corticosteroid, dexamethasone, may decrease the effect of magnesium salicylate.

Mephenytoin: The enzyme inducer, mephenytoin, may decrease the effect of the corticosteroid, dexamethasone.

Methohexital: The barbiturate, methohexital, may decrease the effect of the corticosteroid, dexamethasone.

Methylphenobarbital: The barbiturate, methylphenobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Midodrine: Increased arterial pressure

Neostigmine: The corticosteroid, dexamethasone, may decrease the effect of the anticholinesterase, neostigmine.

Pentobarbital: The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Phenobarbital: The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Phenytoin: The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, dexamethasone.

Primidone: The barbiturate, primidone, may decrease the effect of the corticosteroid, dexamethasone.

Pyridostigmine: The corticosteroid, dexamethasone, may decrease the effect of the anticholinesterase, pyridostigmine.

Quinidine barbiturate: The barbiturate, quinidine barbiturate, may decrease the effect of the corticosteroid, dexamethasone.

Rifampin: The enzyme inducer, rifampin, may decrease the effect of the corticosteroid, dexamethasone.

Salsalate: The corticosteroid, dexamethasone, may decrease the effect of the salicylate, salsalate.

Secobarbital: The barbiturate, secobarbital, may decrease the effect of the corticosteroid, dexamethasone.

Sunitinib: Possible decrease in sunitinib levels

Tacrine: Tacrine and Dexamethasone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.

Talbutal: The barbiturate, talbutal, may decrease the effect of the corticosteroid, dexamethasone.

Telithromycin: Co-administration may cause decreased Telithromycin and increased Dexamethasone plasma concentrations. Consider alternate therapy.

Temsirolimus: Dexamethasone may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

Thalidomide: Increased risk of dermatologic adverse effects and venous thromboembolic events (VTE). Consider VTE prophylaxis during concomitant therapy and monitor for adverse dematologic effects.

Tramadol: Dexamethasone may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.

Trazodone: The CYP3A4 inducer, Dexamethasone, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Dexamethasone is initiated, discontinued or dose changed.

Vecuronium: Vecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Dexamethasone. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of dexamethasone by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of dexamethasone if voriconazole is initiated, discontinued or dose changed.

Warfarin: The corticosteroid, dexamethasone, alters the anticoagulant effect of warfarin.