Dexamethasone

BRAND NAMES:

Decadron - It contains active ingredients of dexamethasone.  It is available in the form of Elixir. It contains anti-inflammatory properties.

Hemady-It contains active ingredients of dexamethasone. It is available in the form of oral tablets. It is used to treat the myeloma.

oral concentrate (1 mg/mL), oral liquid (0.5 mg/5 mL), oral tablet (0.5 mg; 0.75 mg; 1 mg; 1.5 mg; 2 mg; 20 mg; 4 mg; 6 mg)

MECHANISM OF ACTION:

Dexamethasone impacts the body in a number of ways. It works by preventing neutrophil migration and slowing lymphocyte colony expansion. Additionally, the capillary membrane becomes less porous. Lysosomal membranes are more stable. Dexamethasone increases vitamin A concentrations in serum, suppresses prostaglandins and some cytokines, increases surfactant levels, and improves lung function. It is metabolized by the liver and eliminated primarily through the urine. 

COVID-19 produces a hyper-inflammatory response. As a result, the wide anti-inflammatory effect of glucocorticoids is most likely to explain dexamethasone's therapeutic success.

 In a clinical trial of hospitalized COVID-19 patients, dexamethasone resulted in a lower 25-day mortality than those receiving mechanical ventilation or oxygen.

PHARMACOKINETICS:

Absorption: Dexamethasone's median time to peak concentration is one hour. A high-fat, high-calorie meal reduced C max by 23% after a single 20mg dose of dexamethasone.

Distribution: A 1.5mg oral dosage of dexamethasone has a volume of distribution of 51.0L, but a 3mg intramuscular dose has a volume of 96.0L.

Metabolism: Dexamethasone is metabolized by CYP3A4. Corticosteroid 11-beta-dehydrogenase isoenzyme 2 reversibly metabolizes dexamethasone to 11-dehydrodexamethasone, which can then be converted back to dexamethasone by the same enzyme. CYP3A4 converts dexamethasone to its 6α- and 6β-hydroxy forms.

Excretion: Renal excretion of dexamethasone is less than 10% of total body clearance. Less than 10% of dexamethasone is excreted in the urine.

PHARMACODYNAMICS:

Corticosteroids have a broad therapeutic window because individuals may require dosages that exceed what the body normally generates. Patients using corticosteroids should be informed about the possibility of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections. Corticosteroids bind to the glucocorticoid receptor, reducing pro-inflammatory impulses and increasing anti-inflammatory signals. Dexamethasone's duration of action varies depending on the route.

DOSAGE AND ADMINISTRATION:

These are available in various formulations. It is available in strengths ranging from 0.5 to 6 mg as a tablet. Other administration forms are an injectable suspension or an oral solution.

• Oral tablets- 0.5mg, 0.75 mg, 1mg, 1.5mg, 2mg, 4mg, 6mg and 20mg
• Oral elixir or solution- 0.5mg/5ml
• Injection dexamethasone sodium phosphate- 4mg/ml, 20mg/5ml, 120mg/30ml,10mg/ml, 100mg/10ml 

Dexamethasone is available in both tablet and solution forms for oral administration. Take this precisely as prescribed by your physician. Do not take more or less of it, or take it more frequently than recommended by your doctor. Do not discontinue taking dexamethasone without consulting your doctor. Stopping the medicine abruptly might result in a lack of appetite, nausea, vomiting, sleepiness, disorientation, headache, fever, joint and muscular discomfort, peeling skin, and weight loss.

 DRUG INTERACTIONS:

Dexamethasone oral tablet may interact with other medications, vitamins, or herbal supplements you are taking. An interaction occurs when a substance alters how a drug works. This can be harmful or make the drug less effective.

Antibiotics- Erythromycin

Anti-fungal drugs-

• ketoconazole
• Itraconazole
• Posaconazole
• Voriconazole

Amphotericin Bis is another drug used to treat fungal infections. Using this drug with dexamethasone raises your risk of low potassium levels. This can cause muscle cramps, weakness, tiredness, and an irregular heartbeat.

Blood thinner-

• Apixaban  
• Warfarin

Cholesterol drugs- 

• Cholestyramine
• Colestipol
• Colesevelam

Diabetes drugs- 

• Pramlintide
• Metformin
• Sitagliptin
• Insulin

Diuretics-

• Bumetanide
• Furosemide
• Hydrochlorothiazides

Epilepsy drugs-

• Phenytoin
• Carbamazepine
• Phenobarbital

Heart drugs- Digoxin

HIV drugs –

• Atazanavir
• Darunavir
• Indinavir
• Ritonavir

Nonsteroidal anti-inflammatory drugs- 

• Aspirin
• Ibuprofen
• Indomethacin
• naproxen

Tuberculosis drugs-

• Rifampin
• Rifabutin

CONTRAINDICATIONS:

Using dexamethasone during pregnancy as there is an increased risk of oral cleft formation. Its use is contraindicated if patients have systemic fungal infections, hypersensitivity to dexamethasone, or cerebral malaria. Steroid use may inhibit bone formation and may lead to the formation of osteoporosis.

ADVERSE EFFECTS:

Common side effects of dexamethasone include

• Fluid retention
• Increased appetite
• Mood changes, trouble sleeping
• Skin rash
• Acene
• Headache
• Dizziness
• Nausea
• Vomiting
• Muscle tightness, weakness, or limp feeling
• Blurred vision
• Seizures
• Fast or slow heart rate

Pancreatitis-severe pain in the upper stomach spreading to your back

Low potassium level- leg cramps, constipation, increased thirst or urination

Increased blood pressure- severe headache, blurred vision, and anxiety

OVERDOSE:

An overdose of dexamethasone is not expected to produce life-threatening symptoms

• Skin thinning
• Easy bruising
• Changes in body fat
• Increased acne
• Menstrual problems

TOXICITY:

According to the manufacturer's labeling, the oral LD50 of dexamethasone in female mice is 6.5 g/kg. The intravenous formulation of dexamethasone has an LD50 of 794 mg/kg in female mice. There is no specific antidote for overdose. Therefore treatment is supportive and symptomatic.

STORAGE:

Store out of reach of children. Keep at room temperature between 20° and 25° Celsius (68° and 77° Fahrenheit).