Dexamethasone

Article Author:
Donavon Johnson
Article Editor:
Steve Bhimji
Updated:
10/27/2018 12:31:32 PM
PubMed Link:
Dexamethasone

Indications

Dexamethasone has a wide variety of uses in the medical field. As a treatment, dexamethasone has been useful in the treatment of acute exacerbations of multiple sclerosis, allergies, cerebral edema, inflammation, and shock. Patients with conditions such as asthma, atopic and contact dermatitis, and drug hypersensitivity reactions have benefited from the use of dexamethasone.

In endocrinology, dexamethasone has been found useful as a test for Cushing syndrome. This test begins with a low dose test. There are 2 versions of this test: the standard two-day test and the overnight test. With the standard test, 0.5 mg oral dose of dexamethasone is given every 6 hours for 2 days. Six hours after the final dose is given serum cortisol levels are measured. The overnight test begins with a 1 mg oral dose of dexamethasone at 11:00 pm with a second 1 mg oral dose at midnight. The following morning, serum cortisol levels are tested between 8:00 am and 9:00 am. The test is read as a positive screening test for Cushing syndrome if the final cortisol reading is high, signaling that the more specific confirmative high dose dexamethasone suppression test should be ordered. The high dose dexamethasone suppression test has three forms: the standard 2-day test, the overnight test, and the intravenous (IV) test. With all 3 versions of the test, baseline serum cortisol levels need to be determined before commencing with the test. Baseline serum can be measured with a 24-hour urinary free cortisol test. The standard 2-day test uses 2 mg of oral dexamethasone given every 6 hours for 2 days. During the 2-day exam, urine is collected and tested for free cortisol and 6 hours after the final dose of dexamethasone; blood is drawn to measure the serum cortisol level. The overnight test begins with an 8 mg oral dose of dexamethasone at 11:00 pm. The following morning between 8:00 am, and 9:00 am, serum cortisol is measured. The IV test is the shortest of the test. One milligram of dexamethasone is given via continuous intravenous infusion per hour for 7 hours. Serum cortisol is measured at the end of 7 hours.

Off-label indications are as follows. Dexamethasone is used in the treatment of chemotherapy-induced nausea and vomiting. It is used in the prevention and treatment of altitude sickness. It has also been used in the treatment of spinal cord compression due to metastases in oncological cases.

Mechanism of Action

Dexamethasone is a potent glucocorticoid with very little, if any, mineralocorticoid activity. Dexamethasone’s effect on the body is seen in a variety of ways. It has been shown to work is by suppressing migration of neutrophils and decreasing lymphocyte colony proliferation. It has been shown that capillary membrane becomes less permeable as well. Lysosomal membranes have increased stability. There are higher concentrations of vitamin A compounds in the serum, and prostaglandin and some cytokines (interleukin-1, interleukin-12, interleukin-18, tumor necrosis factor, interferon gamma, and granulocyte-macrophage colony stimulating factor) are inhibited. Increased levels of surfactant and improved pulmonary circulation have also been shown with dexamethasone use. Dexamethasone is metabolized by the liver and excreted in the urine mainly. Dexamethasone has a half-life of approximately 3 hours.

Administration

Dexamethasone is available in various formulations. As a tablet, it is available in strengths ranging from 0.5 mg to 6 mg. Other forms of administration are as an injectable suspension or as an oral solution.

  • In the treatment of inflammation, it is advised to begin with low doses of 0.75 mg/day, which may be titrated to 9 mg/day, with dosing divided into 2 to 4 doses throughout the day. This applies to intravenous, intramuscular, and oral administrations. Less may be used when directly administered to the lesion or tissue with dosing ranging from 0.2 to 6 mg per day.
  • For the treatment of acute multiple sclerosis exacerbations, 30 mg oral daily doses taken for seven days is recommended followed by 1 month of 4 to 12 mg oral daily doses.
  • As cerebral edema may be a life-threatening condition, aggressive treatment is necessary. It is recommended that 10 mg of intravenous dexamethasone be administered followed by 4 mg of intramuscular administration given every 6 hours. In this instance, it is necessary to titrate down over 7 days to discontinue dexamethasone therapy.
  • In the treatment of circulatory shock, it is advised to administer 1 to 6 mg/kg of intravenous dexamethasone as a one-time bolus. This regiment may be substituted for 40 mg given intravenously every 2 to 6 hours as needed. Treatment with high dose dexamethasone is not recommended beyond 2 to 3 days.
  • Allergic reactions have been shown to improve with a 6-day regiment beginning with 4 to 8 mg intramuscular injection on the first day. This is followed by oral doses on days 2 to 6 beginning with 1.5 mg every 12 hours for days 2 and 3, 0.75 mg every 12 hours for the third day, and finally 0.75 mg daily for days 5 and 6. The patient should appropriately be titrated down by day 7 with no dosing necessary on day 7.

Adverse Effects

Although dexamethasone is generally well tolerated, it does have its drawbacks as a medication. Most frequent adverse effect reported by patients is the presence of insomnia after use. Some other frequent adverse effects reported by patients include acne, indigestion, weight gain, increased appetite, anorexia, nausea, vomiting, acne, agitation, and depression. There have been reports of adrenal suppression, arrhythmias, spermatogenic changes, glaucoma, hypokalemia, pulmonary edema, pseudotumor cerebri, and increased intracranial pressure.

Contraindications

Dexamethasone use is contraindicated if patients have systemic fungal infections, hypersensitivity to dexamethasone, or cerebral malaria. It is also contraindicated to administer live or live-attenuated vaccines during the use of dexamethasone as the immune system is being suppressed and will less like form a strong enough immune response placing the patient at risk. It is still okay to administer killed or inactivated vaccines although it should be noted that immune response may be attenuated and it is unpredictable if immunity with developing as a result.

In patients with cirrhosis, diverticulitis, myasthenia gravis, renal insufficiency, or ulcerative diseases such as peptic ulcer disease or ulcerative colitis, it is important to use caution when prescribing dexamethasone. It is also recommended to use dexamethasone with caution during pregnancy as there is an increased risk of oral cleft formations. It has been shown that large doses can increase blood pressure. In patients with recent myocardial infarction, it is advised to proceed with caution as an increase in free wall rupture of the left ventricle has been reported with use of dexamethasone. Suppression of the hypothalamus pituitary adrenal axis (HPA axis) occurs with use, and therefore rapid withdrawal of dexamethasone is not recommended. It is important to gradually increase and/or decrease any corticosteroid due to its effect on the HPA axis.

Latent diseases such as fungal (Candida, Cryptococcus, Pneumocystis), parasitic (Toxoplasmosis, Amebiasis, Strongyloides), and bacterial (Mycobacterium, Nocardia) infections may become active due to suppression of the immune system.

Steroid use may inhibit bone formation and may lead to the formation of osteoporosis. Caution should be taken when prescribing dexamethasone to populations at higher risk for osteoporosis.