Product Name
:
DEXARELIEF
Chemical Name
:
Dexamethasone
Therapeutic Category
:
Anti-inflammatory drugs
Pharmacologic Category
:
Corticosteroid
Pharmaceutical Form
:
Ampoule
Composition
:
Dexamethasone Phosphat 8mg/2ml
Dosing
 
Dosing: Adult

Anti-inflammatory:

Oral, I.M., I.V.: 0.75-9 mg/day in divided doses every 6-12 hours

Intra-articular, intralesional, or soft tissue: 0.4-6 mg/day

Extubation or airway edema: Oral, I.M., I.V.: 0.5-2 mg/kg/day in divided doses every 6 hours beginning 24 hours prior to extubation and continuing for 4-6 doses afterwards

Antiemetic:

Prophylaxis: Oral, I.V.: 10-20 mg 15-30 minutes before treatment on each treatment day

Continuous infusion regimen: Oral or I.V.: 10 mg every 12 hours on each treatment day

Mildly emetogenic therapy: Oral, I.M., I.V.: 4 mg every 4-6 hours

Delayed nausea/vomiting: Oral: 4-10 mg 1-2 times/day for 2-4 days or

8 mg every 12 hours for 2 days; then

4 mg every 12 hours for 2 days or

20 mg 1 hour before chemotherapy; then

10 mg 12 hours after chemotherapy; then

8 mg every 12 hours for 4 doses; then

4 mg every 12 hours for 4 doses

Multiple myeloma: Oral, I.V.: 40 mg/day, days 1 to 4, 9 to 12, and 17 to 20, repeated every 4 weeks (alone or as part of a regimen)

Cerebral edema: I.V. 10 mg stat, 4 mg I.M./I.V. (should be given as sodium phosphate) every 6 hours until response is maximized, then switch to oral regimen, then taper off if appropriate; dosage may be reduced after 2-4 days and gradually discontinued over 5-7 days

Dexamethasone suppression test (depression/suicide indicator) (unlabeled use): Oral: 1 mg at 11 PM, draw blood at 8 AM the following day for plasma cortisol determination

Cushing's syndrome, diagnostic: Oral: 1 mg at 11 PM, draw blood at 8 AM; greater accuracy for Cushing's syndrome may be achieved by the following:

Dexamethasone 0.5 mg by mouth every 6 hours for 48 hours (with 24-hour urine collection for 17-hydroxycorticosteroid excretion)

Differentiation of Cushing's syndrome due to ACTH excess from Cushing's due to other causes: Oral: Dexamethasone 2 mg every 6 hours for 48 hours (with 24-hour urine collection for 17-hydroxycorticosteroid excretion)

Multiple sclerosis (acute exacerbation): Oral: 30 mg/day for 1 week, followed by 4-12 mg/day for 1 month

Treatment of shock:

Addisonian crisis/shock (eg, adrenal insufficiency/responsive to steroid therapy): I.V.: 4-10 mg as a single dose, which may be repeated if necessary

Unresponsive shock (eg, unresponsive to steroid therapy): I.V.: 1-6 mg/kg as a single I.V. dose or up to 40 mg initially followed by repeat doses every 2-6 hours while shock persists

Physiological replacement: Oral, I.M., I.V. (should be given as sodium phosphate): 0.03-0.15 mg/kg/day or 0.6-0.75 mg/m 2 /day in divided doses every 6-12 hours

Acute mountain sickness (AMS)/high altitude cerebral edema (HACE) (unlabeled use):

Prevention: Oral: 2 mg every 6 hours or 4 mg every 12 hours starting on the day of ascent; may be discontinued after staying at the same elevation for 2-3 days or if descent is initiated; do not exceed a 10 day duration (Luks, 2010). Note: In situations of rapid ascent to altitudes >3500 meters (such as rescue or military operations), 4 mg every 6 hours may be considered (Luks, 2010).

Treatment: Oral, I.M., I.V.:

AMS: 4 mg every 6 hours (Luks, 2010)

HACE: Initial: 8 mg as a single dose; Maintenance: 4 mg every 6 hours until symptoms resolve (Luks, 2010)

Dosing: Pediatric

Antiemetic (prior to chemotherapy): Refer to individual protocols and emetogenic potential: I.V.: 10 mg/m 2 /dose every 12-24 hours on days of chemotherapy for severely emetogenic chemotherapy courses

Anti-inflammatory and/or immunosuppressant: Oral, I.M., I.V.: 0.08-0.3 mg/kg/day or 2.5-10 mg/m 2 /day in divided doses every 6-12 hours

Extubation or airway edema: Oral, I.M., I.V.: 0.5-2 mg/kg/day in divided doses every 6 hours beginning 24 hours prior to extubation and continuing for 4-6 doses afterwards

Cerebral edema: I.V.: Loading dose: 1-2 mg/kg/dose as a single dose; maintenance: 1-1.5 mg/kg/day (maximum: 16 mg/day) in divided doses every 4-6 hours, taper off over 1-6 weeks

Croup (laryngotracheobronchitis): Oral, I.M., I.V.: 0.6 mg/kg once; usual maximum dose: 16 mg (doses as high as 20 mg have been used) (Bjornson, 2004; Hegenbarth, 2008; Rittichier, 2000); a single oral dose of 0.15 mg/kg has been shown effective in children with mild-to-moderate croup (Russell, 2004; Sparrow, 2006)

Bacterial meningitis: Infants and Children >6 weeks: I.V.: 0.15 mg/kg/dose every 6 hours for the first 2-4 days of antibiotic treatment; start dexamethasone 10-20 minutes before or with the first dose of antibiotic

Physiologic replacement: Oral, I.M., I.V.: 0.03-0.15 mg/kg/day or 0.6-0.75 mg/m 2 /day in divided doses every 6-12 hours

Acute mountain sickness (AMS)/high altitude cerebral edema (HACE) (unlabeled use): Oral, I.M., I.V.: 0.15 mg/kg/dose every 6 hours; consider using for high altitude pulmonary edema because of associated HACE with this condition (Luks, 2010; Pollard, 2001)


Dosing: Geriatric

Refer to adult dosing. Use cautiously in the elderly in the smallest possible dose.


Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling; use with caution. Hemodialysis or peritoneal dialysis: Supplemental dose is not necessary.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Use
 

Primarily as an anti-inflammatory or immunosuppressant agent in the treatment of a variety of diseases including those of allergic, dermatologic, endocrine, hematologic, inflammatory, neoplastic, nervous system, renal, respiratory, rheumatic, and autoimmune origin; may be used in management of cerebral edema, chronic swelling, as a diagnostic agent, diagnosis of Cushing’s syndrome, antiemetic


Use - Unlabeled

Dexamethasone suppression test as an indicator of depression and/or risk of suicide; prevention and treatment of acute mountain sickness and high altitude cerebral edema; accelerate fetal lung maturation in patients with preterm labor

Adverse Reactions
 

Cardiovascular: Arrhythmia, bradycardia, cardiac arrest, cardiomyopathy, CHF, circulatory collapse, edema, hypertension, myocardial rupture (post-MI), syncope, thromboembolism, vasculitis

Central nervous system: Depression, emotional instability, euphoria, headache, intracranial pressure increased, insomnia, malaise, mood swings, neuritis, personality changes, pseudotumor cerebri (usually following discontinuation), psychic disorders, seizure, vertigo

Dermatologic: Acne, allergic dermatitis, alopecia, angioedema, bruising, dry skin, erythema, fragile skin, hirsutism, hyper-/hypopigmentation, hypertrichosis, perianal pruritus (following I.V. injection), petechiae, rash, skin atrophy, skin test reaction impaired, striae, urticaria, wound healing impaired

Endocrine & metabolic: Adrenal suppression, carbohydrate tolerance decreased, Cushing's syndrome, diabetes mellitus, glucose intolerance decreased, growth suppression (children), hyperglycemia, hypokalemic alkalosis, menstrual irregularities, negative nitrogen balance, pituitary-adrenal axis suppression, protein catabolism, sodium retention

Gastrointestinal: Abdominal distention, appetite increased, gastrointestinal hemorrhage, gastrointestinal perforation, nausea, pancreatitis, peptic ulcer, ulcerative esophagitis, weight gain

Genitourinary: Altered (increased or decreased) spermatogenesis

Hepatic: Hepatomegaly, transaminases increased

Local: Postinjection flare (intra-articular use), thrombophlebitis

Neuromuscular & skeletal: Arthropathy, aseptic necrosis (femoral and humoral heads), fractures, muscle mass loss, myopathy (particularly in conjunction with neuromuscular disease or neuromuscular-blocking agents), neuropathy, osteoporosis, parasthesia, tendon rupture, vertebral compression fractures, weakness

Ocular: Cataracts, exophthalmos, glaucoma, intraocular pressure increased

Renal: Glucosuria

Respiratory: Pulmonary edema

Miscellaneous: Abnormal fat deposition, anaphylactoid reaction, anaphylaxis, avascular necrosis, diaphoresis, hiccups, hypersensitivity, impaired wound healing, infections, Kaposi's sarcoma, moon face, secondary malignancy

Contraindications
 
Hypersensitivity to dexamethasone or any component of the formulation; systemic fungal infections, cerebral malaria
Warnings / Precautions Drug
 

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercorticism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections.

• Immunosuppression: Prolonged use of corticosteroids may also increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Exposure to chickenpox should be avoided; corticosteroids should not be used to treat ocular herpes simplex. Corticosteroids should not be used for cerebral malaria or viral hepatitis. Close observation is required in patients with latent tuberculosis and/or TB reactivity; restrict use in active TB (only in conjunction with antituberculosis treatment).

• Kaposi's sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi's sarcoma (case reports); if noted, discontinuation of therapy should be considered.

• Myopathy: Acute myopathy has been reported with high dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.

• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Pre-existing psychiatric conditions may be exacerbated by corticosteroid use.

Disease-related concerns:

• Adrenal insufficiency: Dexamethasone does not provide adequate mineralocorticoid activity in adrenal insufficiency (may be employed as a single dose while cortisol assays are performed). The lowest possible dose should be used during treatment; discontinuation and/or dose reductions should be gradual.

• Cardiovascular disease: Use with caution in patients with HF; long-term use has been associated with fluid retention and hypertension.

• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, peptic ulcer, ulcerative colitis) due to perforation risk.

• Head injury: Increased mortality was observed in patients receiving high-dose I.V. methylprednisolone. High-dose corticosteroids should not be used for the management of head injury.

• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.

• Myocardial infarction (MI): Use with caution following acute MI; corticosteroids have been associated with myocardial rupture.

• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Consider routine eye exams in chronic users.

• Osteoporosis: Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.

• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.

• Seizure disorders: Use with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.

• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Special populations:

• Elderly: Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly in the smallest possible effective dose for the shortest duration.

• Pediatrics: May affect growth velocity; growth should be routinely monitored in pediatric patients.

Other warnings/precautions:

• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.

Interactions
 

Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Risk X: Avoid combination

Aminoglutethimide: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy

Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Risk C: Monitor therapy

Antacids: May decrease the bioavailability of Corticosteroids (Oral). Management: Consider separating doses by 2 or more hours. Budesonide enteric coated tablets could dissolve prematurely if given with drugs that lower gastric acid, with unknown impact on budesonide therapeutic effects. Risk D: Consider therapy modification

Antidiabetic Agents: Corticosteroids (Systemic) may diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy

Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy

Apixaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban. Risk X: Avoid combination

Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification

ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double the oral aripiprazole dose and closely monitor clinical response. Reduce the oral aripiprazole dose to 10-15 mg/day if the inducer is discontinued. Avoid use of CYP3A4 inducers for more than 14 days with extended-release injectable aripiprazole. Risk D: Consider therapy modification

Asparaginase (E. coli): May increase the serum concentration of Dexamethasone (Systemic). This is thought to be due to an asparaginase-related decrease in hepatic proteins responsible for dexamethasone metabolism. Risk C: Monitor therapy

Asparaginase (Erwinia): May increase the serum concentration of Dexamethasone (Systemic). This is thought to be due to an asparaginase-related decrease in hepatic proteins responsible for dexamethasone metabolism. Risk C: Monitor therapy

Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Risk X: Avoid combination

Barbiturates: May decrease the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Bedaquiline: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline. Risk X: Avoid combination

Bile Acid Sequestrants: May decrease the absorption of Corticosteroids (Oral). Risk C: Monitor therapy

Boceprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Boceprevir. Management: Avoid strong CYP3A4 inducers with boceprevir when possible, and closely monitor response to boceprevir if such a combination cannot be avoided. Carbamazepine, phenytoin, phenobarbital, rifampin, and St. John's wort are considered contraindicated. Risk D: Consider therapy modification

Bosutinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib. Risk X: Avoid combination

Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy

Cabozantinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib. Risk X: Avoid combination

Calcitriol: Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May decrease the metabolism of Corticosteroids (Systemic). Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy

Caspofungin: Inducers of Drug Clearance may decrease the serum concentration of Caspofungin. Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m 2 , up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Risk D: Consider therapy modification

Cobicistat: Dexamethasone (Systemic) may decrease the serum concentration of Cobicistat. Risk C: Monitor therapy

Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy

Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Risk X: Avoid combination

CycloSPORINE (Systemic): May increase the serum concentration of Dexamethasone (Systemic). Dexamethasone (Systemic) may decrease the serum concentration of CycloSPORINE (Systemic). Dexamethasone (Systemic) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification

CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Dabigatran Etexilate. Management: Avoid concurrent use of dabigatran with p-glycoprotein inducers when possible. Closely monitor for decreased levels/effects of dabigatran if concomitantly administering p-glycoprotein inducers, particularly strong inducers. Risk X: Avoid combination

Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Deferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy

Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Risk X: Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification

Elvitegravir: Dexamethasone (Systemic) may decrease the serum concentration of Elvitegravir. Risk C: Monitor therapy

Enzalutamide: CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide. Risk X: Avoid combination

Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Risk X: Avoid combination

Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane U.S. product labeling recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. The Canadian product labeling does not recommend a dose adjustment with concurrent use of strong CYP3A4 inducers. Risk D: Consider therapy modification

Fluconazole: May decrease the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Risk D: Consider therapy modification

Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse drug reactions, consider increasing gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers. Carefully monitor clinical response and development of adverse reactions. Risk D: Consider therapy modification

GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Consider increasing the guanfacine dose by 2-fold when adding a strong CYP3A4 inducer. Titrate the guanfacine dose up to a max of 8 mg/day when starting guanfacine in a patient who is taking a strong CYP3A4 inhibitor. Risk D: Consider therapy modification

Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Management: Consider avoiding CYP3A4 inducing herbs in order to avoid therapeutic failure of the substrate. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Risk D: Consider therapy modification

Ifosfamide: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Risk C: Monitor therapy

Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Risk D: Consider therapy modification

Indacaterol: May enhance the hypokalemic effect of Corticosteroids (Systemic). Risk C: Monitor therapy

Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Risk C: Monitor therapy

Ivacaftor: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor. Risk X: Avoid combination

Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m 2 to 60 mg/m 2 (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider therapy modification

Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk X: Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification

Lenalidomide: Dexamethasone (Systemic) may enhance the thrombogenic effect of Lenalidomide. Risk D: Consider therapy modification

Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy

Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Risk X: Avoid combination

Macrolide Antibiotics: May decrease the metabolism of Corticosteroids (Systemic). Exceptions: Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification

Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with Clcr less than 30 mL/min. Risk D: Consider therapy modification

Mifepristone: May diminish the therapeutic effect of Corticosteroids (Systemic). Mifepristone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (e.g., for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Risk X: Avoid combination

Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Risk D: Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Risk D: Consider therapy modification

NIFEdipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine. Management: Consider alternatives to nifedipine for patients who are using strong CYP3A4 inducers. At least one specific brand of nifedipine (Adalat CC) lists this combination as contraindicated. Risk D: Consider therapy modification

Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Risk X: Avoid combination

Nisoldipine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine. Risk X: Avoid combination

NSAID (COX-2 Inhibitor): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). Risk C: Monitor therapy

NSAID (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of NSAID (Nonselective). Risk C: Monitor therapy

Pazopanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib. Risk X: Avoid combination

Perampanel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Perampanel. Management: Avoid use of perampanel with strong CYP3A inducers other than enzyme-inducing antiepileptic drugs (EIAEDs). Increase perampanel starting dose to 4 mg/day when used with EIAEDs such as phenytoin, carbamazepine, or oxcarbazepine. Risk X: Avoid combination

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Risk C: Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

Pomalidomide: P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Pomalidomide. Risk X: Avoid combination

Ponatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ponatinib. Risk X: Avoid combination

Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Avoid concomitant use of praziquantel with strong CYP3A4 inducers. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Risk X: Avoid combination

Primidone: May decrease the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy

Quinolone Antibiotics: May enhance the adverse/toxic effect of Corticosteroids (Systemic). Risk of tendon-related side effects, including tendonitis and rupture, may be enhanced. Risk C: Monitor therapy

Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination

Regorafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib. Risk X: Avoid combination

Rifamycin Derivatives: May increase the metabolism of Corticosteroids (Systemic). Risk C: Monitor therapy

Rilpivirine: Dexamethasone (Systemic) may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination

Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Risk X: Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk D: Consider therapy modification

RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Risk X: Avoid combination

Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy

SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Risk X: Avoid combination

SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing sunitinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination

Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification

Telaprevir: May increase the serum concentration of Corticosteroids (Systemic). Corticosteroids (Systemic) may decrease the serum concentration of Telaprevir. Management: Concurrent use of telaprevir and systemic corticosteroids is not recommended. When possible, consider alternatives. If used together, employ extra caution and monitor closely for excessive corticosteroid effects and diminished telaprevir effects. Risk D: Consider therapy modification

Telaprevir: Corticosteroids may decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Corticosteroids. Management: Concurrent use of telaprevir and systemic corticosteroids is not recommended. When possible, consider alternatives. If used together, employ extra caution and monitor closely for excessive corticosteroid effects and diminished telaprevir effects. Risk D: Consider therapy modification

Thalidomide: Dexamethasone (Systemic) may enhance the dermatologic adverse effect of Thalidomide. Dexamethasone (Systemic) may enhance the thrombogenic effect of Thalidomide. Risk D: Consider therapy modification

Thiazide Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide Diuretics. Risk C: Monitor therapy

Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Risk X: Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or other non-disease modifying antirheumatic drugs (non-DMARDs) is permitted, and this warning seems to particularly focused on more potent immunosuppressants. Risk X: Avoid combination

Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Risk X: Avoid combination

Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Risk X: Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Risk D: Consider therapy modification

Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Risk X: Avoid combination

Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Risk C: Monitor therapy

VinCRIStine (Liposomal): CYP3A4 Inducers (Strong) may decrease the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination

Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Risk C: Monitor therapy

Pregnancy
 
Pregnancy Risk Factor

C

Pregnancy Implications Adverse events have been observed with corticosteroids in animal reproduction studies. Dexamethasone crosses the placenta; and is partially metabolized to an inactive metabolite by placental enzymes. Due to its positive effect on stimulating fetal lung maturation, the injection is often used in patients with premature labor (24-34 weeks gestation). Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts; adverse events in the fetus/neonate have been noted in case reports following large doses of systemic corticosteroids during pregnancy.
Lactation
 

Excretion in breast milk unknown/use caution

Breast-Feeding Considerations

Corticosteroids are excreted in human milk; information specific to dexamethasone has not been located.

Monitoring Parameters
 

Hemoglobin, occult blood loss, serum potassium, glucose, growth in children

Reference Range

Dexamethasone suppression test, overnight: 8 AM cortisol <6 mcg/100 mL (dexamethasone 1 mg); plasma cortisol determination should be made on the day after giving dose

Mechanism of Action
 
Decreases inflammation by suppression of neutrophil migration, decreased production of inflammatory mediators, and reversal of increased capillary permeability; suppresses normal immune response. Dexamethasone's mechanism of antiemetic activity is unknown.
Pharmacodynamics / Kinetics
 

Onset of action: Acetate: Prompt

Duration of metabolic effect: 72 hours; acetate is a long-acting repository preparation

Metabolism: Hepatic

Half-life elimination: Normal renal function: 1.8-3.5 hours; Biological half-life: 36-54 hours

Time to peak, serum: Oral: 1-2 hours; I.M.: ~8 hours

Excretion: Urine and feces