Cortisone

The dosage of cortisone acetate must be individualized based on the specific disease being treated and the patient's clinical response. According to clinical guidelines, the initial dosage may vary from 25 mg to 300 mg per day. In less severe conditions, lower doses may suffice, while particularly challenging cases may require higher initial amounts.

• For Adrenal Insufficiency: The typical maintenance dose is 25 mg to 37.5 mg daily, often given in divided doses (e.g., two-thirds in the morning and one-third in the late afternoon) to mimic the body's natural circadian rhythm of cortisol secretion.
• For Inflammatory Conditions (e.g., Rheumatoid Arthritis): Initial doses may range from 50 mg to 100 mg daily. Once a favorable response is noted, the healthcare provider will gradually decrease the dose to the smallest amount that maintains an adequate clinical response.
• Acute Exacerbations: In situations of high stress or acute illness, the dosage may need to be temporarily increased.

Cortisone use in children is generally reserved for endocrine replacement or severe inflammatory states. Dosing is often calculated based on body surface area or weight rather than age alone.

• Replacement Therapy: A common range is 0.7 mg/kg/day or 20 mg/m²/day, divided into three doses.
• Other Indications: The dose is determined by the severity of the condition and the child's response.

Warning: Chronic use of cortisone in children can lead to growth suppression. Pediatric patients must be monitored closely by a specialist, and the lowest effective dose should always be used for the shortest duration possible.

Renal Impairment

While the metabolites of cortisone are excreted renally, significant dosage adjustments are not typically required for patients with mild to moderate kidney disease. However, patients with severe renal impairment should be monitored for fluid retention, as cortisone has significant mineralocorticoid effects that can exacerbate edema and hypertension.

Hepatic Impairment

Because cortisone is a prodrug that requires hepatic conversion to its active form (cortisol), patients with severe liver disease (e.g., cirrhosis) may not convert the drug efficiently. In such cases, the clinical effect may be reduced, or conversely, the clearance of the active hormone may be slowed. Healthcare providers may prefer using hydrocortisone (the active form) directly in patients with significant hepatic dysfunction.

Elderly Patients

Dosage selection for an elderly patient should be cautious, usually starting at the low end of the dosing range. This population is at a higher risk for side effects such as osteoporosis, hypertension, and glucose intolerance. Regular monitoring of bone density and blood pressure is recommended.

• Administration: Take cortisone 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 recommended to take it in the morning (around 8:00 AM) to align with the body's natural steroid production. If taking multiple doses, follow the specific schedule provided by your doctor.
• Consistency: Take the medication at the same time every day to maintain steady levels in the body.
• Storage: Store at room temperature (20°C to 25°C or 68°F to 77°F) in a dry place, away from direct sunlight and moisture.

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 dosing schedule. Do not double the dose to catch up. Frequent missed doses can lead to a return of symptoms or signs of adrenal insufficiency.

Acute overdosage with cortisone rarely results in life-threatening situations. However, chronic overdosage can lead to 'Cushingoid' symptoms (e.g., moon face, weight gain, buffalo hump). In the event of an acute massive ingestion, emergency measures include gastric lavage or induced vomiting, followed by supportive care. If you suspect an overdose, contact your local poison control center or seek emergency medical attention immediately.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop taking the medication without medical guidance, as sudden discontinuation can be dangerous.

Cortisone affects nearly every system in the body, and side effects are common, especially with higher doses or prolonged use. Common effects include:

• Increased Appetite and Weight Gain: Many patients experience a significant increase in hunger, leading to weight gain, particularly in the abdomen, face ('moon face'), and back of the neck ('buffalo hump').
• Fluid Retention: Cortisone causes the body to retain salt and water, which may lead to swelling (edema) in the ankles and feet.
• Mood Changes: Patients often report feeling restless, anxious, or having trouble sleeping (insomnia). Some may experience mild euphoria or irritability.
• Digestive Issues: Indigestion, nausea, or mild stomach pain are frequent, especially if the medication is taken on an empty stomach.

• Dermatologic Changes: Thinning of the skin, easy bruising (purpura), and slow wound healing. Some patients may develop acne or increased facial hair growth (hirsutism).
• Musculoskeletal Weakness: Muscle weakness (steroid myopathy), particularly in the thighs and shoulders, can occur.
• Glucose Intolerance: Cortisone can raise blood sugar levels, which may require adjustments in medication for patients with diabetes.
• Increased Sweating: Night sweats or general hyperhidrosis.

• Ocular Changes: Development of cataracts (posterior subcapsular) or increased intraocular pressure (glaucoma).
• Aseptic Necrosis: A rare but serious condition where bone tissue dies due to lack of blood supply, most commonly affecting the femoral head (hip).
• Psychosis: Severe mental health changes, including hallucinations or profound depression.

> Warning: Stop taking Cortisone and call your doctor immediately if you experience any of these serious symptoms:

• Signs of Infection: Steroids mask the symptoms of infection. Seek help for fever, persistent sore throat, or chills.
• Anaphylaxis: Severe allergic reactions including hives, difficulty breathing, or swelling of the face, lips, and tongue.
• Gastrointestinal Bleeding: Black, tarry stools, or vomiting blood (looks like coffee grounds).
• Severe Hypertension: Blurred vision, severe headache, or pounding in the neck or ears.
• Adrenal Insufficiency: If you stop the drug too quickly, you may experience severe fatigue, dizziness, fainting, and joint pain.
• Pancreatitis: Severe pain in the upper stomach spreading to the back, often accompanied by nausea and vomiting.

Prolonged use of cortisone (typically more than 2-3 weeks) carries significant risks that require careful management by a healthcare provider:

• Osteoporosis: Cortisone inhibits calcium absorption and bone formation, significantly increasing the risk of fractures. Bone density scans and calcium/vitamin D supplementation are often required.
• HPA Axis Suppression: The body stops producing its own natural cortisol. If the drug is stopped suddenly, the body cannot react to stress, leading to a life-threatening adrenal crisis.
• Cushing’s Syndrome: A hormonal disorder caused by prolonged exposure to high levels of cortisol, characterized by central obesity, thin skin, and high blood pressure.
• Immunosuppression: Long-term use makes the body more susceptible to 'opportunistic' infections (fungal, viral, or unusual bacterial infections).

No FDA black box warnings currently exist for Cortisone Acetate. However, the FDA requires extensive 'Precautions' and 'Warnings' sections on the label regarding the risk of secondary infection and the dangers of abrupt withdrawal.

Report any unusual symptoms to your healthcare provider immediately. Regular follow-ups are essential to monitor for these potential adverse effects.

Cortisone is a potent medication that requires careful medical supervision. One of the most critical safety points is that you must never stop taking cortisone suddenly if you have been on it for more than a few days. Abrupt discontinuation can lead to acute adrenal insufficiency, a medical emergency where the body cannot produce enough cortisol to maintain vital functions like blood pressure. Symptoms of adrenal crisis include severe vomiting, diarrhea, low blood pressure (hypotension), and loss of consciousness.

There are no FDA black box warnings for Cortisone. However, the clinical warnings regarding HPA axis suppression and masking of infections are treated with similar clinical gravity by healthcare professionals.

• Infection Risk: Cortisone suppresses the immune system. This can make you more likely to get infections or make any current infection worse. It can also reactivate 'latent' infections like tuberculosis (TB). If you have a history of TB or positive skin tests, your doctor must monitor you closely.
• Cardiovascular and Renal Effects: Because cortisone causes sodium and water retention and potassium loss, it can lead to high blood pressure and congestive heart failure in susceptible patients. It should be used with extreme caution in patients with a history of hypertension or heart disease.
• Gastrointestinal Risk: There is an increased risk of developing stomach ulcers or perforations, especially when cortisone is used alongside NSAIDs (like ibuprofen or aspirin). Patients with a history of peptic ulcers or ulcerative colitis should be monitored closely.
• Ocular Effects: Prolonged use may result in glaucoma with damage to the optic nerves and may favor the establishment of secondary ocular infections due to fungi or viruses.
• Vaccinations: While on cortisone, you should not receive 'live' vaccines (such as the MMR or chickenpox vaccine). The drug's immunosuppressive effect may cause the vaccine to be ineffective or, in rare cases, cause the disease the vaccine is intended to prevent.

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

• Blood Pressure: Monitored at every visit to check for steroid-induced hypertension.
• Blood Glucose: Particularly in patients with diabetes or pre-diabetes, as steroids increase insulin resistance.
• Electrolytes: Periodic checks of serum potassium and sodium levels.
• Bone Mineral Density (BMD): To screen for the early onset of osteoporosis.
• Ophthalmic Exams: Yearly checks for cataracts and glaucoma if therapy is prolonged.
• Growth Monitoring: In pediatric patients to ensure the drug is not causing significant growth delays.

Cortisone generally does not interfere with the ability to drive or operate machinery. However, some patients may experience dizziness, blurred vision, or significant mood swings. If you experience these side effects, avoid these activities until you know how the medication affects you.

Alcohol should be used with caution while taking cortisone. Both alcohol and cortisone can irritate the stomach lining; combining them significantly increases the risk of gastrointestinal bleeding and peptic ulcers. Additionally, alcohol can complicate the management of blood sugar levels, which are already affected by cortisone.

When it is time to stop taking cortisone, your doctor will provide a tapering schedule. This involves gradually reducing the dose over weeks or even months. This gives your adrenal glands time to 'wake up' and resume natural hormone production. If you experience severe fatigue, joint pain, or weakness during the taper, contact your doctor immediately.

> Important: Discuss all your medical conditions, including history of depression, heart disease, or infections, with your healthcare provider before starting Cortisone.

• Live Attenuated Vaccines: Taking cortisone with live vaccines (e.g., Yellow Fever, Live Flu Mist) is contraindicated in immunosuppressed doses. The vaccine may cause a systemic infection because the body cannot mount an adequate immune response.
• Desmopressin: Using cortisone with desmopressin can increase the risk of water intoxication and severely low sodium levels (hyponatremia).

• NSAIDs and Aspirin: Combining cortisone with nonsteroidal anti-inflammatory drugs (like ibuprofen, naproxen, or celecoxib) significantly increases the risk of gastrointestinal ulceration and bleeding. If you must take both, your doctor may prescribe a 'proton pump inhibitor' to protect your stomach.
• Warfarin and Anticoagulants: Cortisone can unpredictably increase or decrease the blood-thinning effects of warfarin. Frequent monitoring of the INR (International Normalized Ratio) is required.
• Antidiabetic Agents: Since cortisone increases blood glucose, the effectiveness of insulin or oral diabetes medications (like metformin or glyburide) may be reduced. Doses of these medications often need to be increased during steroid therapy.
• Amphotericin B and Diuretics: When taken with 'potassium-wasting' diuretics (like furosemide or hydrochlorothiazide) or Amphotericin B, cortisone can lead to dangerously low potassium levels (hypokalemia), which can affect heart rhythm.

• CYP3A4 Inducers: Drugs like rifampin, phenytoin, and carbamazepine can speed up the metabolism of cortisone, making it less effective. The dose of cortisone may need to be increased.
• CYP3A4 Inhibitors: Drugs like ketoconazole, erythromycin, and ritonavir can slow the metabolism of cortisone, increasing the risk of side effects.
• Oral Contraceptives: Estrogens can increase the levels of transcortin, which may increase the half-life of cortisone and enhance its effects.

• Sodium/Salt: High salt intake can worsen the fluid retention and high blood pressure caused by cortisone. A low-sodium diet is often recommended.
• Grapefruit Juice: While more significant with other steroids, grapefruit juice can potentially inhibit the metabolism of corticosteroids, leading to higher levels in the blood.
• Dairy/Calcium: Cortisone interferes with calcium absorption. Increasing intake of calcium-rich foods is often encouraged to protect bone health.

• St. John's Wort: This herbal supplement induces CYP3A4 enzymes and may reduce the effectiveness of cortisone.
• Licorice Root: Natural licorice contains glycyrrhizic acid, which can increase the side effects of cortisone, particularly potassium loss and high blood pressure.
• Echinacea: May interfere with the immunosuppressive effects of cortisone.

Cortisone can affect the results of several clinical tests:

• Skin Tests: It can suppress reactions to skin tests (like the TB skin test or allergy tests), leading to false-negative results.
• Thyroid Function: It may decrease TSH levels and affect the results of thyroid function tests.
• Nitroblue Tetrazolium Test: May produce false-negative results for bacterial infections.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. A complete medication review is the best way to prevent dangerous interactions.

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

1. 1Systemic Fungal Infections: Cortisone suppresses the immune system's ability to fight fungi. In the presence of a systemic fungal infection (like candidiasis or aspergillosis), steroids can allow the infection to spread uncontrollably throughout the body.
2. 2Known Hypersensitivity: If a patient has had a documented severe allergic reaction (anaphylaxis) to cortisone acetate or any of the inactive ingredients in the tablet, the drug is strictly contraindicated.
3. 3Cerebral Malaria: Clinical trials have shown that steroids are not beneficial and may actually be harmful in the treatment of cerebral malaria.

In these conditions, the healthcare provider will perform a careful risk-benefit analysis, as the drug may exacerbate the underlying problem:

• Active Peptic Ulcer Disease: Because cortisone thins the stomach lining and increases acid production, it can cause an existing ulcer to bleed or perforate.
• Diverticulitis: There is an increased risk of intestinal perforation in patients with active diverticulitis.
• Recent Intestinal Anastomoses: Steroids can delay the healing of surgical connections in the bowel.
• Psychosis or Severe Affective Disorders: Cortisone can trigger acute psychotic episodes or severe depression in patients with a history of mental health conditions.
• Osteoporosis: Since cortisone actively breaks down bone, its use in patients with already fragile bones must be very carefully managed.
• Herpes Simplex Keratitis: Use of steroids can lead to corneal perforation in patients with this specific eye infection.

Patients who are allergic to other corticosteroids (such as hydrocortisone, prednisone, or triamcinolone) may also be allergic to cortisone. This is known as cross-sensitivity. If you have had a reaction to any 'steroid' medication in the past, it is vital to inform your prescribing physician before starting cortisone.

> Important: Your healthcare provider will evaluate your complete medical history, including any dormant infections or chronic conditions, before prescribing Cortisone to ensure it is safe for you.

Cortisone is classified by the FDA as Pregnancy Category C. This means that animal reproduction studies have shown an adverse effect on the fetus (such as cleft palate), but there are no adequate and well-controlled studies in humans.

• First Trimester: Some data suggest a slightly increased risk of oral clefts if steroids are used early in pregnancy.
• Late Pregnancy: Use of high doses can lead to fetal adrenal suppression. Infants born to mothers who received substantial doses of cortisone during pregnancy should be carefully observed for signs of hypoadrenalism (low blood pressure, electrolyte imbalances).
• Clinical Use: Cortisone is only used during pregnancy if the potential benefit justifies the potential risk to the fetus, such as in life-threatening maternal conditions.

Cortisone is excreted into human breast milk. While low doses typically do not have a significant effect on the nursing infant, high doses of systemic corticosteroids could potentially interfere with the infant's natural corticosteroid production or cause other unwanted effects.

• Recommendation: Mothers taking high doses of cortisone should consult with their doctor about whether to continue breastfeeding or switch to a different medication. Often, waiting 3-4 hours after a dose before breastfeeding can minimize the amount of drug the infant receives.

Cortisone is used in children, but with significant caution.

• Growth Suppression: The primary concern is the suppression of linear growth. Pediatricians must monitor height and weight frequently.
• Dosing: Dosing should be kept to the lowest possible level, and alternate-day therapy is sometimes used to reduce growth-related side effects.
• Infections: Children on cortisone are at high risk for severe complications from common childhood illnesses like chickenpox or measles. If a child is exposed to these viruses while on cortisone, medical attention should be sought immediately for prophylactic treatment (e.g., VZIG).

Elderly patients are more susceptible to the adverse effects of cortisone.

• Bone Health: The risk of steroid-induced osteoporosis and resulting hip or spinal fractures is significantly higher in patients over 65.
• Cardiovascular Risk: Older adults are more likely to experience fluid retention and hypertension.
• Polypharmacy: The elderly often take multiple medications, increasing the risk of drug-drug interactions.
• Cognitive Effects: There is a higher incidence of 'steroid psychosis' or confusion in the geriatric population.

In patients with kidney disease, the primary concern is the mineralocorticoid effect of cortisone. Sodium retention can lead to worsening edema and high blood pressure. While the dose itself may not need adjustment based on GFR, the patient's fluid status and electrolytes must be monitored more frequently than in patients with normal renal function.

Because cortisone is a prodrug that requires the liver to convert it to active cortisol, patients with severe liver impairment (Child-Pugh Class C) may experience reduced efficacy. Furthermore, the liver is responsible for clearing the active hormone. In cirrhosis, the half-life of cortisol may be prolonged, leading to an increased risk of toxicity. Healthcare providers often prefer using hydrocortisone in these patients.

> Important: Special populations require individualized medical assessment and more frequent monitoring to ensure safety.

Cortisone acetate is a synthetic glucocorticoid with both glucocorticoid and mineralocorticoid properties. At the molecular level, it acts as an agonist for the glucocorticoid receptor (GR). Once the prodrug cortisone is converted to cortisol by the enzyme 11β-hydroxysteroid dehydrogenase type 1, it binds to the GR in the cytoplasm. This complex translocates to the nucleus, where it alters gene transcription. Specifically, it inhibits the transcription of pro-inflammatory genes (like those for COX-2 and various cytokines) and promotes the transcription of anti-inflammatory genes (like Lipocortin-1, which inhibits Phospholipase A2). This dual action effectively shuts down the inflammatory cascade at multiple points.

The pharmacodynamic effects of cortisone are wide-reaching. Beyond its anti-inflammatory effects, it stimulates gluconeogenesis (the creation of glucose), promotes protein breakdown (catabolism), and causes the redistribution of body fat. It also decreases the number of circulating lymphocytes and eosinophils while increasing the number of erythrocytes and neutrophils. The onset of action for oral cortisone is relatively fast (1-2 hours for peak blood levels), but because it works via gene expression, the full clinical effect may take several hours or even days to manifest.

| Parameter | Value |

|---|---|

| Bioavailability | 80% to 90% |

| Protein Binding | 90% (Primarily to Transcortin and Albumin) |

| Half-life (Plasma) | 0.5 to 2 hours (Cortisol) |

| Biological Half-life | 8 to 12 hours |

| Tmax | 1 to 2 hours |

| Metabolism | Hepatic (Conversion to Cortisol, then conjugation) |

| Excretion | Renal (>90% as inactive metabolites) |

• Molecular Formula: C23H30O6 (Cortisone Acetate)
• Molecular Weight: 402.48 g/mol
• Solubility: Practically insoluble in water; sparingly soluble in alcohol and chloroform.
• Structure: It is a pregnane (21-carbon) steroid with a 1,4-diene-3,20-dione structure and a 21-acetate group. The presence of the 11-keto group distinguishes it from hydrocortisone (which has an 11-beta-hydroxy group).

Cortisone belongs to the therapeutic class of Corticosteroids, specifically the sub-class of Glucocorticoids. Related medications include Hydrocortisone (the active form), Prednisone (more potent, less salt retention), and Dexamethasone (long-acting, very potent). Within the hierarchy of steroids, cortisone is considered a short-acting agent with a high degree of mineralocorticoid activity compared to newer synthetic analogs.