PERCUTALGINE

Commonly known as decadron, dexamethasone acetate is a glucocorticosteroid previously marketed in the USA for the treatment of inflammatory respiratory, allergic, autoimmune, and other conditions. 2, 4, 5 Developed in 1957, dexamethasone is structurally similar to other corticosteroids such as hydrocortisone and prednisolone.

Dexamethasone acetate has largely been replaced by dexamethasone phosphate and continues to be administered for a large variety of inflammatory conditions.

Recently, dexamethasone has been a drug of interest in the treatment of COVID-19.

In a

June 16 2020 press release highlighting early results of a clinical trial, Randomized Evaluation of COVID-19 Therapy (RECOVERY), it was reported that dexamethasone reduced COVID-19 deaths by approximately one-fifth and one-third in patients on oxygen therapy and mechanical ventilation, respectively.

Dexamethasone was therefore recommended as a life-saving treatment for COVID-19 patients experiencing severe respiratory symptoms.

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Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids that are readily absorbed from the gastrointestinal tract.

Glucocorticoids cause varied metabolic effects.

In addition, they modify the body's immune responses to diverse stimuli.

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have sodium-retaining properties, are used as replacement therapy in adrenocortical deficiency states.

Their synthetic analogs, including dexamethasone, are primarily used 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 of hydrocortisone.

Target Actions Organism A Glucocorticoid receptor agonist Humans U Annexin A1 agonist Humans U Nitric oxide synthase, inducible negative modulator Humans U Nuclear receptor subfamily 0 group B member 1 stimulator Humans U Nuclear receptor subfamily 1 group I member 2 agonist Humans.

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Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy See ADVERSE REACTIONS.

Increased dosage of rapidly acting corticosteroids is indicated in patients on corticosteroid therapy subjected to any unusual stress before, during, and after the stressful situation.

Average and large doses of corticosteroids can cause elevation of blood pressure, sodium and water retention, and increased excretion of potassium.

These effects are less likely to occur with the synthetic derivatives except when used in large doses.

Dietary salt restriction and potassium supplementation may be necessary.

All corticosteroids increase calcium excretion.

Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients.

Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for corticosteroid insufficiency after withdrawal of treatment.

Adrenocortical insufficiency may result from too rapid withdrawal of corticosteroids and may be minimized by gradual reduction of dosage.

This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted.

If the patient is receiving steroids already, dosage may have to be increased.

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients.

Changes in thyroid status of the patient may necessitate adjustment in dosage.

Infections General: Patients who are on corticosteroids are more susceptible to infections than are healthy individuals.

There may be decreased resistance and inability to localize infection when corticosteroids are used.

Infection with any pathogen (viral, bacterial, fungal, protozoan or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents.

These infections may be mild to severe.

With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.

Corticosteroids may also mask some signs of current infection.

Infections: Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control life-threatening drug reactions.

There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.

Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, Toxoplasma.

It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea.

Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation.

In such patients, corticosteroid.

• induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Corticosteroids should not be used in cerebral malaria.

The use of corticosteroids in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen.

If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur.

During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Ki l ed or inactivated vaccines may be administered.

However, the response to such vaccines cannot be predicted.

Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison's disease.

Viral infections

Chickenpox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids.

In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure.

The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known.

If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated.

If exposed to measles, prophylaxis with immune globulin (IG) may be indicated.

If chickenpox develops, treatment with antiviral agents should be considered.

Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses.

The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes.

Corticosteroids should not be used in active ocular herpes simplex.

Infections](#warnings) and patients with known hypersensitivity to the product and its consituents.

The initial dosage varies from 0.75 to 9 mg a day depending on the disease being treated.

It Should Be Emphasized That Dosage Requirements Are Variable And Must Be Individualized On The Basis Of The Disease Under Treatment And The Response Of The Patient.

After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage that maintains an adequate clinical response is reached.

Situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient's individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment.

In this latter situation it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient's condition.

If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

In the treatment of acute exacerbations of multiple sclerosis, daily doses of 30 mg of dexamethasone for a week followed by to 12 mg every other day for one month have been shown to be effective.

In pediatric patients, the initial dose of dexamethasone may vary depending on the specific disease entity being treated.

The range of initial doses is 0.02 to 0.3 mg/kg/day in three or four divided doses (0.6 to 9 mg/m2bsa/day).

For the purpose of comparison, the fo ll owing is the equivalent mi lli gram dosage of the various corticosteroids: Dexamethasone, 1.5 Methylprednisolone, 8 Prednisone, 10 Triamcinolone, 8 Prednisolone, 10 Betamethasone, 1.5 Hydrocortisone, 40 Paramethasone, 4 Cortisone, 50 These dose relationships apply only to oral or intravenous administration of these compounds.

When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

In acute, self-limited allergic disorders or acute exacerbations of chronic allergic disorders, the following dosage schedule combining parenteral and oral therapy is suggested: Dexamethasone sodium phosphate injection, 4 mg per mL First Day 1 or 2 mL, intramuscularly Dexamethasone tablets, 0.75 mg Second Day 4 tablets in two divided doses Third Day 4 tablets in two divided doses Fourth Day 2 tablets in two divided doses Fifth Day 1 tablet Sixth Day 1 tablet Seventh Day No treatment Eighth Day Follow-up visit This schedule is designed to ensure adequate therapy during acute episodes, while minimizing the risk of overdosage in chronic cases.

In cerebral edema, dexamethasone sodium phosphate injection is generally administered initially in a dosage of 10 mg intravenously followed by 4 mg every six hours intramuscularly until the symptoms of cerebral edema subside.

Response is usually noted within to 24 hours and dosage may be reduced after two to four days and gradually discontinued over a period of five to seven days.

For pal l iative management of patients with recurrent or inoperable brain tumors, maintenance therapy with either dexamethasone sodium phosphate injection or dexamethasone tablets in a dosage of 2 mg two or three times daily may be effective.

Tests 1.

Tests for

Cushing’s syndrome Give 1.0 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.

Twenty-four hour urine co l ections are made for determination of 17-hydroxycorticosteroid excretion. 2.

Test to distinguish

Cushing’s syndrome due to pituitary ACTH excess from Cushing’s syndrome due to other causes.

Give 2.0 mg of dexamethasone orally every 6 hours for 48 hours.

Twenty-four hour urine co l ections are made for determination of 17-hydroxycorticosteroid excretion.

USP, 1.5 mg are supplied as white, round shaped tablets debossed “702” on one side and bisected on the opposite side.

The bisect on the tablet provides for a functional scoring of the tablet to ensure accurate breaking.

They are available in bottles of

Bottles of 21 Tablets NDC: 80425-0346-01 Bottles of 27 Tablets NDC: 80425-0346-02 Bottles of 49 Tablets NDC: 80425-0346-03 Bottles of 60 Tablets NDC: 80425-0346-04 Store and Dispense Store at 20° to 25°C (68° to 77°F) .

Protect from moisture.

Dispense in a we l -closed, light-resistant container as defined in the USP/NF.

Cal l your doctor for medical advice about side effects.

Distributed by

Key Therapeutics Flowood, MS 39232 Questions: 981-8332 Rev. 07/2023.

Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose.

Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring.

There are no adequate and well-controlled studies in pregnant women.

Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.

Because of the potential for serious adverse reactions in nursing infants from corticosteroids, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

The efficacy and safety of corticosteroids in the pediatric population are based on the we l -established course of effect of corticosteroids, which is similar in pediatric and adult populations.

Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (patients >2 years of age), and aggressive lymphomas and leukemias (patients >1 month of age).

Other indications for pediatric use of corticosteroids, e.g., severe asthma and wheezing, are based on adequate and we l -controlled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations.

The adverse effects of corticosteroids in pediatric patients are similar to those in adults See ADVERSE REACTIONS.

Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis.

Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity.

This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels).

Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function.

The linear growth of pediatric patients treated with corticosteroids should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of treatment alternatives.

In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose.

Clinical studies did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.

Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

In particular, the increased risk of diabetes mellitus, fluid retention and hypertension in elderly patients treated with corticosteroids should be considered.