Dexamethasone

Dexamethasone is a synthetic adrenocortical steroid (a glucocorticoid) used to treat a wide range of conditions in which inflammation or an overactive immune response is the underlying problem. It is also used as replacement therapy in adrenocortical deficiency states and as a diagnostic agent in tests of adrenal function.

Glucocorticoids occur naturally in the body (as hydrocortisone and cortisone) and are readily absorbed from the gastrointestinal tract. They cause varied metabolic effects and modify the body's immune responses to diverse stimuli. Synthetic analogs such as dexamethasone are used primarily for their anti-inflammatory effects in disorders of many organ systems. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives.

Dexamethasone first received U.S. approval in 1958.

Oral dexamethasone is used for a wide range of conditions involving inflammation or an overactive immune system, including:

• Allergic conditions — severe asthma, atopic and contact dermatitis, drug reactions, allergic rhinitis, and serum sickness, when usual treatments have not worked.
• Skin conditions — pemphigus, bullous dermatitis herpetiformis, exfoliative erythroderma, mycosis fungoides, and severe erythema multiforme (Stevens-Johnson syndrome).
• Hormone disorders — adrenal glands that don't make enough steroid hormone (although hydrocortisone or cortisone is usually preferred), congenital adrenal hyperplasia, high blood calcium caused by cancer, and nonsuppurative thyroiditis.
• Bowel conditions — flare-ups of Crohn's disease and ulcerative colitis.
• Blood disorders — autoimmune hemolytic anemia, Diamond-Blackfan anemia, pure red cell aplasia, and low platelets, including immune thrombocytopenic purpura in adults.
• Cancers — to help control symptoms in leukemia and lymphoma, and in combination with other medicines to treat multiple myeloma in adults.
• Nervous system — multiple sclerosis flare-ups, and brain swelling caused by a tumor, brain surgery, or a head injury.
• Eye conditions — uveitis, sympathetic ophthalmia, temporal arteritis, and other eye inflammation that has not responded to steroid eye drops.
• Kidney disease — nephrotic syndrome, to increase urine output and reduce protein in the urine.
• Lung conditions — sarcoidosis, eosinophilic pneumonias, berylliosis, and severe or widespread tuberculosis of the lungs, alongside TB medicines.
• Joint, muscle, and connective tissue conditions — short-term treatment of flare-ups of gout, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis, and treatment of dermatomyositis, polymyositis, systemic lupus erythematosus, and acute rheumatic carditis.
• Other uses — testing for overactive adrenal glands, trichinosis affecting the nerves or heart, and tuberculous meningitis with a blockage around the spinal cord.

• Take dexamethasone exactly as your doctor prescribes. Doses vary widely depending on the condition being treated and how you respond, so never change your dose on your own.
• Your doctor will usually start you on a higher dose and then reduce it in small steps to the lowest dose that keeps your condition under control.
• If you are taking the elixir, measure your dose with a proper measuring spoon or oral syringe, not a household spoon. Each 5 mL (one teaspoonful) contains 0.5 mg of dexamethasone and 5% alcohol.
• Do not stop taking dexamethasone suddenly. If you have been taking it for more than a few days, the dose needs to be reduced gradually. Stopping abruptly can leave your body unable to make enough of its own steroid hormones.
• Stopping after a long course can also cause a withdrawal syndrome, with muscle aches, joint pain, and a general feeling of being unwell. Tell your doctor if this happens.
• Your dose may need to be increased temporarily during periods of physical stress, such as surgery, an infection, or an injury. It may also need adjusting if your condition flares up or improves.
• Carry something that identifies you as a corticosteroid user, and tell any doctor, dentist, or other healthcare provider treating you that you are taking dexamethasone, including for several months after you stop.
• Contact your doctor straight away if you develop a fever or any other sign of infection while taking dexamethasone.
• Avoid contact with anyone who has chickenpox or measles if you have not had these illnesses. Seek medical advice without delay if you are exposed.

Serious side effects

Dexamethasone can cause the following serious side effects, particularly at higher doses and with longer treatment:

• Infections. Dexamethasone suppresses the immune system, so infections take hold more easily, spread further, and can be masked. Tuberculosis and hepatitis B can reactivate, and chickenpox and measles can be severe or even fatal in people who are not immune. Avoid in systemic fungal infections and cerebral malaria, and rule out amebiasis or Strongyloides in anyone who has spent time in the tropics.
• Vaccinations. Live vaccines must not be given at immune-suppressing doses. Other vaccines can be given, but may not work as well.
• Stopping treatment. Reduce the dose gradually. Stopping too quickly can leave the body unable to make its own steroid hormones, sometimes for months afterwards, and extra steroid may be needed during illness, injury, or surgery in that time.
• Eyes. Long-term use can cause cataracts and glaucoma with possible optic nerve damage, and makes eye infections more likely. Check eye pressure if treatment continues beyond 6 weeks.
• Heart, blood pressure, and kidneys. Can raise blood pressure and cause fluid retention with loss of potassium. Use with caution in heart failure, high blood pressure, kidney problems, or after a recent heart attack.
• Blood clots. Dexamethasone can increase the risk of developing blood clots in your veins or arteries. Your doctor may prescribe a blood thinner to help prevent this.
• Stomach and bowel. Increased risk of ulcers and perforation, and the usual warning signs may be minimal or absent. Effects are stronger in patients with cirrhosis.
• Bones and muscles. Can cause osteoporosis at any age, slow growth in children, and, at high doses, severe muscle weakness that may take months or longer to recover from.
• Mental health. Can cause insomnia, mood swings, personality changes, severe depression, and psychosis, and can worsen an existing mental health condition.
• Blood sugar and thyroid. Can raise blood glucose levels. The dose may need adjusting if thyroid status changes.
• Kaposi's sarcoma. This type of cancer has been reported in patients receiving corticosteroid therapy, most often for chronic conditions. Tell your doctor if you are diagnosed with Kaposi's sarcoma, as stopping dexamethasone may improve the condition.

Get emergency medical help if you have signs of an allergic reaction to dexamethasone: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• Signs of infection, such as fever, chills, sore throat, or a cough that will not clear
• Black, bloody, or tarry stools, or vomit that looks like coffee grounds
• Severe pain in your upper stomach spreading to your back, with nausea and vomiting
• Sudden or severe stomach pain, or a swollen, tender abdomen
• Blurred vision, eye pain, or seeing halos around lights
• Severe depression, unusual thoughts or behavior, confusion, or a seizure
• Muscle weakness, particularly in your arms and legs, or trouble breathing
• Swelling in your hands, ankles, or feet, rapid weight gain, or shortness of breath even with mild activity
• Leg cramps, an irregular or fluttering heartbeat, increased thirst or urination, or numbness and tingling. These can be signs of a low potassium level
• Severe headache, pounding in your neck or ears, or a nosebleed. These can be signs of raised blood pressure
• New or worsening pain in your hip, shoulder, back, or a long bone, or sudden pain and loss of movement in a tendon
• A persistent headache with vision changes, particularly after your dose has been reduced or stopped.

Dexamethasone can slow growth in children. Tell your doctor if your child is not growing at a normal rate while taking it.

Common side effects

Common dexamethasone side effects may include:

• Fluid retention, with swelling in your hands or ankles
• Increased appetite and weight gain
• Mood changes and trouble sleeping
• Indigestion, nausea, or stomach discomfort
• Acne, thin skin, easy bruising, stretch marks, or slow wound healing
• Increased sweating, increased body or facial hair, or thinning scalp hair
• A rounded or puffy face, and changes in where your body stores fat
• Raised blood sugar, which may mean your diabetes treatment needs adjusting
• Changes to your menstrual periods
• Headache, dizziness, or hiccups

These are not all the possible side effects of dexamethasone. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Do not take dexamethasone if you:

• Have a fungal infection affecting your whole body (a systemic fungal infection)
• Are allergic to dexamethasone or to any of the other ingredients in your tablets or the elixir.

Before taking dexamethasone, tell your doctor about all your medical conditions, including if you have ever had any of the following:

• Infections Any current infection, or one that keeps coming back Tuberculosis, or a positive TB skin test Hepatitis B, or a past hepatitis B infection. Your doctor may test you for hepatitis B before you start long-term treatment Herpes infection of the eye Threadworm (Strongyloides) infection Malaria affecting the brain Time spent in tropical countries, or diarrhea with no clear cause. Your doctor may check you for a parasite called amebiasis first Never having had chickenpox or measles, or not being vaccinated against them
• Other health conditions Heart failure, high blood pressure, or kidney problems A recent heart attack Diabetes, or high blood sugar An underactive or overactive thyroid A stomach ulcer, diverticulitis, ulcerative colitis, or recent bowel surgery Cirrhosis of the liver Glaucoma or cataracts Osteoporosis, or a higher risk of it — for example, if you are past menopause Myasthenia gravis, or another condition affecting the nerves and muscles Depression, or any other mental health condition
• Vaccinations Tell your doctor before you have any vaccine. Live vaccines should not be given while you are taking immune-suppressing doses of a corticosteroid. Other vaccines can be given, but they may not work as well as usual. If you are taking dexamethasone as replacement therapy, for example for Addison's disease, you can usually be vaccinated normally.
• Pregnancy Corticosteroids have caused birth defects, including cleft palate, in animal studies, and can cause fetal harm. Dexamethasone should only be used in pregnancy if the benefit outweighs the possible risk to the baby. If you can become pregnant, you may need to use effective birth control during treatment and for at least one month after your last dose. Babies born to mothers who took substantial doses during pregnancy should be watched closely for signs of underactive adrenal glands.
• Breastfeeding Corticosteroids taken by mouth pass into breast milk and could affect a baby's growth, interfere with the baby's own steroid production, or cause other effects. You and your doctor will need to decide whether to stop breastfeeding or stop the medicine, weighing up how important the treatment is for you. Depending on your condition and dose, you may be advised not to breastfeed during treatment and for 2 weeks after your last dose.
• Children Dexamethasone can slow growth in children, and this can happen at low doses. Children on long-term treatment should have their height monitored, along with regular checks of blood pressure, weight, and eye pressure. They should be treated with the lowest dose that works.
• Older adults Treatment is usually started at the lower end of the dose range, because kidney, liver, and heart function are more often reduced with age. Older adults may also face a higher risk of diabetes, fluid retention, and high blood pressure while taking corticosteroids.

Adults

The initial oral dosage varies from 0.75 mg to 9 mg a day, depending on the disease being treated. For multiple myeloma, the recommended dosage is 20 mg or 40 mg once daily on specific days.

• Dosage varies and must be individualized to the condition and the patient's response
• Once the patient responds, reduce in small steps to the lowest dose that keeps the condition controlled
• Adjust the dose if the disease flares or remits, if response changes, or during surgery, infection, or injury. A temporary increase may be needed
• Withdraw gradually, not abruptly, after more than a few days of treatment.

Acute exacerbations of multiple sclerosis

Daily doses of 30 mg of dexamethasone for a week, followed by 4 mg to 12 mg every other day for one month, have been shown to be effective.

Acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders

The following schedule, combining parenteral and oral therapy, is suggested.

This schedule is designed to ensure adequate therapy during acute episodes while minimizing the risk of overdosage in chronic cases.

Dexamethasone suppression tests

Tests for Cushing's syndrome. Give 1 mg of dexamethasone orally at 11:00 p.m. Blood is drawn for plasma cortisol determination at 8:00 a.m. the following morning. For greater accuracy, give 0.5 mg of dexamethasone orally every 6 hours for 48 hours, with 24-hour urine collections made for determination of 17-hydroxycorticosteroid excretion.

Test to distinguish Cushing's syndrome due to pituitary ACTH excess from Cushing's syndrome due to other causes. Give 2 mg of dexamethasone orally every 6 hours for 48 hours, with 24-hour urine collections made for determination of 17-hydroxycorticosteroid excretion.

Children

In pediatric patients, the initial dose may vary depending on the specific disease being treated. The range of initial doses is 0.02 mg/kg/day to 0.3 mg/kg/day in three or four divided doses (0.6 mg/m2/day to 9 mg/m2/day).

Corticosteroid dose equivalents

The following equivalent milligram dosages apply only to oral or intravenous administration. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

Call your doctor for advice if you miss a dose of dexamethasone. Do not take a double dose to make up for the one you missed. Dexamethasone doses vary widely between patients and are often reduced step by step, so the right thing to do depends on your dose and how long you have been taking it.

Seek emergency medical attention, or call the Poison Help line at 1-800-222-1222.

A single accidental overdose of dexamethasone is not expected to cause life-threatening symptoms, and treatment is aimed at supporting you and relieving any symptoms. Taking high doses over a long period is a different matter, and can lead to:

• Thin, fragile skin and easy bruising
• Changes in where the body stores fat, particularly the face, neck, back, and waist
• Acne, increased body or facial hair, and thinning scalp hair
• Muscle weakness and loss of muscle
• Thinning of the bones (osteoporosis)
• Menstrual changes, reduced interest in sex, and problems with erections
• Raised blood sugar and raised blood pressure.

• Live vaccines. Do not have a live vaccine while you are taking immune-suppressing doses of dexamethasone. Live vaccines include measles, mumps and rubella (MMR), polio, rotavirus, typhoid, yellow fever, chickenpox (varicella), and shingles (zoster). Other vaccines can be given, but they may not protect you as well as usual. Tell your doctor you are taking a steroid before you have any vaccination.
• Contact with infections. Try to avoid close contact with people who are unwell. Dexamethasone suppresses your immune system, so infections can take hold more easily, spread further, and be harder to spot.
• Chickenpox and measles. If you have never had chickenpox or measles, avoid anyone who has them. These illnesses can be severe or even fatal in people taking steroids. Contact your doctor straight away if you are exposed. Preventive treatment is available.
• Alcohol. Drinking alcohol while taking dexamethasone may add to the risk of stomach irritation and bleeding. Ask your doctor whether alcohol is safe for you. Note that the elixir itself contains 5% alcohol.

Other drugs may interact with dexamethasone, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. Medications that may interact with dexamethasone include:

• CYP3A4 inducers (for example, barbiturates, phenytoin, carbamazepine, rifampin) may enhance the metabolism of corticosteroids and require the corticosteroid dosage to be increased.
• CYP3A4 inhibitors (for example, erythromycin, ketoconazole, itraconazole, clarithromycin, ritonavir, cobicistat-containing products) may increase plasma concentrations of dexamethasone and the risk of systemic corticosteroid side effects. Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, and can itself inhibit adrenal corticosteroid synthesis and cause adrenal insufficiency during corticosteroid withdrawal.
• CYP3A4 substrates (for example, indinavir, erythromycin) may have increased clearance and decreased plasma concentrations when given with dexamethasone.
• Aminoglutethimide may diminish adrenal suppression by corticosteroids.
• Amphotericin B injection and potassium-depleting agents (for example, diuretics): observe closely for hypokalemia. Cases of cardiac enlargement and congestive heart failure have been reported with concomitant amphotericin B and hydrocortisone.
• Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance.
• Anticholinesterases may produce severe weakness in patients with myasthenia gravis; if possible, withdraw anticholinesterase agents at least 24 hours before starting corticosteroid therapy.
• Oral anticoagulants: co-administration with warfarin usually inhibits the response to warfarin, although reports conflict. Monitor coagulation indices frequently.
• Antidiabetic agents: corticosteroids may increase blood glucose concentrations, so dosage adjustments may be required.
• Antitubercular drugs: serum concentrations of isoniazid may be decreased.
• Cholestyramine may increase the clearance of corticosteroids.
• Cyclosporine: increased activity of both cyclosporine and corticosteroids may occur; convulsions have been reported with concurrent use.
• Digitalis glycosides: patients may be at increased risk of arrhythmias due to hypokalemia.
• Ephedrine may enhance the metabolic clearance of corticosteroids, requiring an increase in corticosteroid dosage.
• Estrogens, including oral contraceptives, may decrease the hepatic metabolism of certain corticosteroids and increase their effect.
• Indomethacin has been reported to cause false-negative results in the dexamethasone suppression test, so results should be interpreted with caution in these patients.
• NSAIDs, including aspirin: concomitant use increases the risk of gastrointestinal side effects. Aspirin should be used cautiously with corticosteroids in hypoprothrombinemia, and the clearance of salicylates may be increased.
• Phenytoin: post-marketing reports describe both increases and decreases in phenytoin levels with dexamethasone, leading to altered seizure control.
• Skin tests: corticosteroids may suppress reactions.
• Thalidomide: use cautiously, as toxic epidermal necrolysis has been reported with concomitant use.
• Vaccines: patients may exhibit a diminished response to toxoids and live or inactivated vaccines. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine vaccination should be deferred until corticosteroid therapy is discontinued if possible.

This is not a complete list. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Tablets. Dexamethasone tablets, USP are supplied in a range of strengths. Products covered by the labeling reviewed here include:

• 0.25 mg tablets — orange, pentagonal, 6 mm, scored, imprinted "083" (inactive ingredients: anhydrous lactose, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, stearic acid, FD&C Yellow #6)
• 4 mg tablets — pale yellow, round, side-notched, functional score on one side, debossed "S2" on the other
• 6 mg tablets — light blue, round, side-notched, functional score on one side, debossed "S3" on the other

Inactive ingredients of the 4 mg and 6 mg tablets are corn starch, D&C yellow 10 (4 mg), FD&C blue 1 (6 mg), lactose monohydrate, and magnesium stearate.

Elixir. Dexamethasone elixir, USP 0.5 mg per 5 mL is a pink-red raspberry-flavored liquid supplied in 237 mL (8 fl oz) bottles. Each 5 mL (one teaspoonful) contains 0.5 mg dexamethasone, benzoic acid 0.1% as a preservative, and 5% alcohol. Inactive ingredients are artificial raspberry flavor, citric acid, edetate disodium, FD&C Red #40, propylene glycol, purified water, saccharin sodium, and sorbitol solution.

• Tablets: store at 20°C to 25°C (68°F to 77°F) and protect from moisture. Keep in the original tightly closed, light-resistant container.
• Elixir: store at 25°C (77°F); brief exposure to 15°C to 30°C (59°F to 86°F) is acceptable. Keep the bottle tightly closed and do not freeze.

Keep all medicines out of the reach of children.