Neomycin Sulfate, Polymyxin B Sulfate And Dexamethasone

The dosage of Dexamethasone is highly individualized and depends on the specific condition being treated, the severity of the disease, and the patient's response to therapy.

• General Inflammatory Conditions: The initial dosage typically ranges from 0.75 mg to 9 mg per day. In less severe diseases, doses lower than 0.75 mg may be sufficient, while in severe diseases, doses higher than 9 mg may be required.
• Acute Exacerbations of Multiple Sclerosis: Dosages of 16 mg daily for one week followed by 4 mg to 12 mg every other day for one month have been utilized.
• Cerebral Edema: An initial intravenous dose of 10 mg followed by 4 mg intramuscularly every six hours until the symptoms of cerebral edema subside.
• Dexamethasone Suppression Test: For the diagnosis of Cushing's syndrome, 0.5 mg is given every 6 hours for 48 hours (low-dose test) or 2 mg every 6 hours for 48 hours (high-dose test).
• COVID-19 (Hospitalized): The standard dose is 6 mg once daily (oral or IV) for up to 10 days.

Dexamethasone is used in children, but dosing must be calculated carefully, usually based on body weight or body surface area.

• General Dosing: The typical pediatric dose ranges from 0.02 to 0.3 mg/kg/day, divided into three or four doses.
• Croup (Laryngotracheobronchitis): A single dose of 0.15 mg/kg to 0.6 mg/kg is often administered to reduce airway inflammation.
• Pediatric Note: Chronic use in children can lead to growth suppression. Healthcare providers must monitor height and weight closely in pediatric patients on long-term therapy.

Renal Impairment

No specific dosage adjustments are generally required for patients with renal failure, as Dexamethasone is primarily metabolized by the liver. However, patients should be monitored for fluid retention.

Hepatic Impairment

Since Dexamethasone is metabolized by the liver, patients with severe hepatic impairment (liver disease) may experience slower clearance of the drug, leading to an increased risk of side effects. Dose reductions may be necessary based on clinical response.

Elderly Patients

In geriatric patients, the dose should be started at the lower end of the dosing range. Older adults are at a higher risk for side effects such as osteoporosis, hypertension, and glucose intolerance (diabetes).

• With Food: It is highly recommended to take Dexamethasone tablets with food or milk to minimize gastrointestinal irritation and the risk of stomach ulcers.
• Timing: If taking a single daily dose, it is often best to take it in the morning (around 8:00 AM) to mimic the body's natural circadian rhythm of cortisol production. This can help reduce the risk of insomnia.
• Consistency: Take the medication at the same time every day to maintain steady blood levels.
• Swallow Whole: Tablets should generally be swallowed whole. If using the liquid form, use a calibrated measuring device rather than a household spoon.
• Storage: Store at room temperature (68°F to 77°F) away from moisture and light. Keep out of reach of children.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular schedule. Do not double the dose to catch up. If you miss multiple doses, contact your healthcare provider for guidance.

Acute toxicity or death from a single overdose of Dexamethasone is rare. However, chronic overdose can lead to symptoms of Cushing's syndrome (moon face, buffalo hump, central obesity). Signs of acute overdose may include an exaggerated version of side effects, such as severe agitation or high blood pressure. In case of a suspected overdose, contact your local poison control center or seek emergency medical attention immediately.

> Important: Follow your healthcare provider's dosing instructions exactly. Never stop taking Dexamethasone suddenly after long-term use, as this can cause life-threatening adrenal crisis. Your doctor will provide a tapering schedule to safely reduce the dose.

Side effects are common with Dexamethasone, especially when used at high doses or for extended periods. Most common effects include:

• Increased Appetite and Weight Gain: Patients often experience a significant increase in hunger, leading to weight gain, particularly in the abdomen and face (often called 'moon face').
• Insomnia and Sleep Disturbances: Due to its stimulating effect on the central nervous system, many patients find it difficult to fall or stay asleep.
• Mood Changes: Irritability, anxiety, or a feeling of 'euphoria' (intense happiness) followed by 'crashes' are frequently reported.
• Fluid Retention: Swelling in the ankles, feet, or hands (edema) due to sodium retention.
• Upset Stomach: Mild nausea or abdominal discomfort.

• Dermatologic Changes: Thinning of the skin, easy bruising (purpura), acne, and impaired wound healing.
• Muscle Weakness: Particularly in the proximal muscles (shoulders and hips), known as steroid myopathy.
• Increased Sweating: Diaphoresis or night sweats.
• Headache and Dizziness: Often related to changes in blood pressure.

• Aseptic Necrosis: A condition where bone tissue dies due to lack of blood supply, most commonly affecting the femoral head (hip).
• Cataracts and Glaucoma: Long-term use can increase intraocular pressure or cause clouding of the lens.
• Psychosis: Severe mental health changes, including hallucinations or delusions (steroid-induced psychosis).
• Pancreatitis: Inflammation of the pancreas, characterized by severe abdominal pain.

> Warning: Stop taking Dexamethasone and call your doctor immediately or seek emergency care if you experience any of the following:

• Anaphylaxis / Severe Allergic Reaction: Symptoms include hives, difficulty breathing, swelling of the face, lips, tongue, or throat.
• Signs of Infection: Corticosteroids suppress the immune system. Seek help for fever, chills, persistent sore throat, or wounds that will not heal. Dexamethasone can mask the signs of a serious infection.
• Severe Depression or Suicidal Thoughts: Any sudden, drastic change in mood or behavior.
• Vision Changes: Sudden blurred vision, eye pain, or seeing halos around lights.
• Gastrointestinal Bleeding: Black, tarry stools, or vomiting blood (looks like coffee grounds).
• High Blood Sugar (Hyperglycemia): Excessive thirst, frequent urination, fruity breath odor, or confusion.
• Hypokalemia (Low Potassium): Muscle cramps, irregular heartbeat, or extreme weakness.

Prolonged use of Dexamethasone (typically more than two weeks) carries significant risks:

• Osteoporosis: Steroids inhibit bone formation and increase bone resorption, leading to fragile bones and increased fracture risk. Supplemental calcium and Vitamin D are often recommended.
• Adrenal Suppression: The body stops producing its own cortisol because the synthetic Dexamethasone is providing it. This makes the body unable to respond to stress (like surgery or infection) if the drug is stopped suddenly.
• Cushingoid Features: Development of a 'buffalo hump' (fat deposit between shoulders), central obesity, and thinning of the limbs.
• Stunted Growth: In children, long-term use can permanently affect final adult height.

There are currently no FDA black box warnings specifically for Dexamethasone. However, it carries significant general warnings regarding the risk of secondary infections and the absolute necessity of tapering the dose after chronic use to avoid adrenal crisis.

Report any unusual symptoms to your healthcare provider. Keeping a daily log of your symptoms and weight can help your doctor manage your treatment effectively.

Dexamethasone is a high-potency medication that requires careful medical supervision. It can affect nearly every organ system in the body. Patients should be aware that while it is highly effective for reducing inflammation, it does not cure the underlying disease.

No FDA black box warnings for Dexamethasone. However, the FDA requires extensive labeling regarding the risks of immunosuppression and the dangers of abrupt withdrawal.

• Immunosuppression and Infection: Dexamethasone suppresses the immune system, making you more susceptible to infections (bacterial, viral, fungal, or parasitic). It can also reactivate latent infections, such as tuberculosis (TB). If you have been exposed to chickenpox or measles while taking this drug, contact your doctor immediately, as these can be fatal in immunosuppressed patients.
• Adrenal Insufficiency: Long-term use suppresses the Hypothalamic-Pituitary-Adrenal (HPA) axis. If the drug is stopped suddenly, the body cannot produce enough cortisol to function, which can lead to a life-threatening adrenal crisis (low blood pressure, shock, death).
• Cardiovascular and Renal Effects: Dexamethasone can cause sodium retention and potassium loss, leading to high blood pressure (hypertension) and congestive heart failure in susceptible individuals. Use with extreme caution in patients with a recent history of myocardial infarction (heart attack).
• Gastrointestinal Risks: There is an increased risk of gastrointestinal perforation (holes in the stomach or intestines) in patients with certain GI disorders like peptic ulcers, diverticulitis, or ulcerative colitis. This risk is significantly higher if Dexamethasone is taken with NSAIDs (like ibuprofen).
• Ophthalmic Risks: Prolonged use may produce posterior subcapsular cataracts or glaucoma with possible damage to the optic nerves.
• Psychiatric Derangements: Corticosteroids may aggravate existing emotional instability or psychotic tendencies.

Patients on long-term Dexamethasone therapy require regular monitoring, including:

• Blood Glucose: Steroids frequently cause 'steroid-induced diabetes' or worsen existing diabetes.
• Blood Pressure: Monitored at every clinic visit.
• Electrolytes: Specifically potassium and sodium levels.
• Bone Density: DEXA scans may be needed to monitor for osteoporosis.
• Eye Exams: Periodic exams to check for cataracts and glaucoma.
• Growth Monitoring: In pediatric patients, height and weight must be tracked on a growth chart.

Dexamethasone can cause dizziness, mood swings, and vision changes. Patients should determine how they react to the medication before driving or operating heavy machinery. If you feel 'jittery' or 'manic,' avoid these activities.

Alcohol should be avoided or strictly limited while taking Dexamethasone. Both alcohol and corticosteroids can irritate the stomach lining; combining them significantly increases the risk of stomach ulcers and gastrointestinal bleeding.

Never stop taking Dexamethasone abruptly. If you have taken the drug for more than a few days, your doctor will provide a 'tapering' schedule. This involves slowly reducing the dose over weeks or months to allow your adrenal glands to 'wake up' and start producing natural cortisol again. Withdrawal symptoms can include fever, muscle pain, joint pain, and malaise.

> Important: Discuss all your medical conditions, especially any history of tuberculosis, diabetes, high blood pressure, or mental health issues, with your healthcare provider before starting Dexamethasone.

• Live Vaccines: Dexamethasone suppresses the immune response. Administering live or live-attenuated vaccines (such as MMR, Varicella, or the Flumist) to a patient on immunosuppressive doses of Dexamethasone is contraindicated. The vaccine may replicate uncontrollably, leading to the very disease it was meant to prevent.
• Desmopressin: Use with Dexamethasone can increase the risk of severe water retention and low blood sodium (hyponatremia).

• NSAIDs (Nonsteroidal Anti-inflammatory Drugs): Taking Dexamethasone with aspirin, ibuprofen (Advil/Motrin), naproxen (Aleve), or celecoxib significantly increases the risk of gastrointestinal ulcers and bleeding. If the combination is necessary, a proton pump inhibitor (PPI) like omeprazole may be prescribed for stomach protection.
• Warfarin and Anticoagulants: Dexamethasone can either increase or decrease the blood-thinning effects of warfarin. Close monitoring of the INR (International Normalized Ratio) is required.
• Antidiabetic Agents: Because Dexamethasone increases blood sugar, the doses of insulin or oral diabetes medications (like metformin or glipizide) usually need to be increased.
• Potassium-Depleting Agents: Diuretics like furosemide (Lasix) or hydrochlorothiazide can cause severe potassium loss when combined with Dexamethasone, leading to heart arrhythmias.

• CYP3A4 Inducers: Drugs like phenytoin, carbamazepine, and rifampin speed up the metabolism of Dexamethasone, making it less effective. The Dexamethasone dose may need to be increased.
• CYP3A4 Inhibitors: Drugs like ketoconazole, erythromycin, and ritonavir slow down the metabolism of Dexamethasone, increasing its concentration in the blood and the risk of toxicity.
• Digoxin: Increased risk of digitalis toxicity due to potential potassium loss.

• Grapefruit Juice: While the effect is less pronounced than with other drugs, grapefruit juice can potentially inhibit the metabolism of Dexamethasone, leading to higher levels in the body.
• Sodium (Salt): High salt intake can worsen the fluid retention and high blood pressure caused by Dexamethasone. A low-sodium diet is often recommended.
• Calcium and Vitamin D: Dexamethasone interferes with calcium absorption. Increasing intake of calcium-rich foods (dairy, leafy greens) or supplements is often necessary to protect bone health.

• St. John's Wort: This herbal supplement induces CYP3A4 and can significantly reduce the effectiveness of Dexamethasone.
• Echinacea: May interfere with the immunosuppressive effects of Dexamethasone.
• Licorice Root: Can increase the risk of potassium loss and fluid retention.

• Skin Tests: Dexamethasone may suppress reactions to skin tests (such as allergy tests or TB tests), leading to false-negative results.
• Thyroid Function Tests: May decrease levels of TSH and T4, complicating the diagnosis of thyroid disorders.

For each major interaction, the clinical consequence is usually either a loss of therapeutic effect or an increase in steroid-related toxicity. Management strategies include dose adjustment, increased monitoring, or choosing alternative therapies.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers.

There are specific circumstances where Dexamethasone must NEVER be used due to the risk of life-threatening complications:

• Systemic Fungal Infections: Corticosteroids can worsen fungal infections (like candidiasis or aspergillosis) by suppressing the immune system's ability to fight them. They should not be used unless specific antifungal therapy is also being administered and the benefits outweigh the risks.
• Known Hypersensitivity: If a patient has had a previous severe allergic reaction (anaphylaxis) to Dexamethasone or any component of the formulation.
• Cerebral Malaria: Studies have shown that steroids are not beneficial and may be harmful in the treatment of cerebral malaria.
• Administration of Live Vaccines: As noted in interactions, the immunosuppressed state makes live vaccines dangerous.

In these conditions, healthcare providers must perform a careful risk-benefit analysis before prescribing Dexamethasone:

• Active Tuberculosis (TB): Unless it is fulminating or disseminated TB where steroids are used with antituberculous drugs.
• Ocular Herpes Simplex: Due to the risk of corneal perforation.
• Peptic Ulcer Disease: High risk of causing or worsening stomach holes/bleeding.
• Severe Hypertension or Heart Failure: Risk of worsening fluid overload.
• Diabetes Mellitus: Steroids make blood sugar control extremely difficult.
• Osteoporosis: Steroids will further decrease bone mineral density.
• Psychosis: May trigger a relapse of severe mental health symptoms.

Patients who are allergic to other corticosteroids (such as prednisone, methylprednisolone, or hydrocortisone) may also be allergic to Dexamethasone. This is known as cross-sensitivity. While not always the case, healthcare providers should exercise caution and may perform a skin patch test if a steroid allergy is suspected.

> Important: Your healthcare provider will evaluate your complete medical history, including any dormant infections or chronic conditions, before prescribing Dexamethasone. Always be honest about your health history to ensure your safety.

Dexamethasone is classified as FDA Pregnancy Category C. This means that animal studies have shown adverse effects on the fetus (such as cleft palate and intrauterine growth restriction), but there are no adequate, well-controlled studies in humans.

• First Trimester: Some data suggest a slightly increased risk of oral clefts if used in early pregnancy.
• Late Pregnancy: Use near term may lead to hypoadrenalism in the newborn, requiring the infant to be monitored for adrenal insufficiency after birth.
• Clinical Use: Dexamethasone is sometimes specifically used in pregnancy to help mature the lungs of a fetus at risk of preterm birth (antenatal steroids).

Dexamethasone is excreted into breast milk and could potentially suppress the infant's growth or interfere with their natural corticosteroid production.

• Low Dose: Short-term, low-dose use is generally considered compatible with breastfeeding.
• High Dose: If high doses are required, the healthcare provider may recommend monitoring the infant's growth or considering alternative feeding methods. The risk-benefit ratio must be discussed with a pediatrician.

Dexamethasone is approved for use in children for various conditions, including croup and certain leukemias.

• Growth Suppression: The most significant concern is the suppression of linear growth. Children on long-term therapy must have their height and weight monitored frequently.
• Infections: Children may be at higher risk for severe complications from common childhood illnesses like chickenpox while on Dexamethasone.

Elderly patients are more susceptible to the side effects of Dexamethasone.

• Osteoporosis: Older adults, especially post-menopausal women, are at very high risk for steroid-induced fractures.
• Diabetes and Hypertension: These conditions are more common in the elderly and are easily exacerbated by steroids.
• Cognitive Effects: Older adults may be more prone to 'steroid psychosis' or confusion.
• Dosing: Doctors typically start at the lowest possible dose for the shortest duration.

While Dexamethasone is not primarily cleared by the kidneys, renal impairment can lead to increased fluid retention. Patients with kidney disease must be monitored for edema and electrolyte imbalances. Dexamethasone is not significantly removed by hemodialysis.

The liver is the primary site of Dexamethasone metabolism. In patients with severe liver disease (e.g., cirrhosis), the drug remains in the system longer, increasing the risk of systemic toxicity. Dose adjustments are often based on the severity of the liver impairment and the patient's clinical response.

> Important: Special populations require individualized medical assessment. Never share your medication with others, especially those in these sensitive groups.

Dexamethasone is a synthetic glucocorticoid receptor agonist. Its primary action is to bind to the glucocorticoid receptor (GR) in the cytoplasm. The resulting complex translocates to the nucleus, where it binds to DNA and modulates gene expression. This results in the inhibition of pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-alpha) and the induction of anti-inflammatory proteins (Annexin A1). It also inhibits the enzyme phospholipase A2, which reduces the release of arachidonic acid, the precursor to inflammatory prostaglandins and leukotrienes.

• Dose-Response: Dexamethasone exhibits a linear dose-response relationship regarding its anti-inflammatory effects.
• Onset of Action: For oral administration, effects usually begin within 1 to 2 hours. For IV administration, the onset is rapid (minutes).
• Duration: It is a 'long-acting' steroid with a biological effect lasting 36 to 72 hours, significantly longer than its plasma half-life.
• Tolerance: While true 'tolerance' is rare, the underlying disease may become less responsive to steroids over time, requiring higher doses.

| Parameter | Value |

|---|---|

| Bioavailability | 70% - 90% |

| Protein Binding | ~77% (Primarily Albumin) |

| Half-life (Plasma) | 1.8 - 3.5 hours |

| Biological Half-life | 36 - 72 hours |

| Tmax (Oral) | 1 - 2 hours |

| Metabolism | Hepatic (CYP3A4) |

| Excretion | Renal (8%), Fecal (Minimal) |

• Molecular Formula: C22H29FO5
• Molecular Weight: 392.46 g/mol
• Solubility: Practically insoluble in water; sparingly soluble in acetone, ethanol, and chloroform.
• Structure: It is a fluorinated steroid. The presence of the fluorine atom at the 9-alpha position significantly increases its glucocorticoid activity while minimizing mineralocorticoid (salt-retaining) activity.

Dexamethasone is classified as a Corticosteroid [EPC] and a Glucocorticoid. Related medications include Prednisone, Methylprednisolone, and Betamethasone. Within this class, Dexamethasone is distinguished by its high potency and long duration of action.