Ohm Pituitarum Complex

Dosage of Corticotropin must be highly individualized based on the disease being treated and the patient's response. According to clinical guidelines, the following are standard ranges:

• Multiple Sclerosis Exacerbations: The typical adult dose is 80 to 120 units administered intramuscularly (IM) or subcutaneously (SC) daily for 2 to 3 weeks. In some cases, a tapering schedule is used to gradually reduce the dose before discontinuation.
• Other Inflammatory/Allergic Conditions: The usual dose is 40 to 80 units every 24 to 72 hours. Your healthcare provider will adjust the dose to the lowest effective level to minimize the risk of side effects.

• Infantile Spasms: This is the primary pediatric indication. The standard recommended dose is 75 units/m² (units per square meter of body surface area) administered IM twice daily for 2 weeks. Following this 2-week period, the dose is typically tapered over another 2 weeks (e.g., 30 units/m² in the morning for 3 days, then 15 units/m² in the morning for 3 days, then 10 units/m² in the morning for 3 days, and finally 10 units/m² every other morning for 6 days).
• Other Uses: Safety and effectiveness for conditions other than infantile spasms have not been established in pediatric patients under the age of 2.

Renal Impairment

There are no specific dosage adjustment guidelines for patients with renal (kidney) impairment. However, since Corticotropin can cause fluid retention and electrolyte imbalances, patients with kidney disease should be monitored closely for worsening of their condition.

Hepatic Impairment

Specific adjustments for hepatic (liver) impairment are not established. Because the drug is metabolized by proteolytic enzymes rather than liver-specific pathways, significant changes in clearance are not typically expected, but clinical caution is advised.

Elderly Patients

In geriatric patients, the dose should be selected with caution, usually starting at the low end of the dosing range. This is due to the higher frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapies common in this population.

1. 1Preparation: Corticotropin gel should be warmed to room temperature before injection to make the solution easier to draw and inject. Do not use a microwave or hot water; simply hold the vial in your hands.
2. 2Administration Route: This medication is for intramuscular (IM) or subcutaneous (SC) use only. It must NEVER be given intravenously (IV).
3. 3Injection Site: Rotate injection sites (thigh, upper arm, or buttocks) to prevent skin issues or muscle damage. Do not inject into areas that are red, bruised, or scarred.
4. 4Technique: Use a clean, sterile needle and syringe for every dose. Your healthcare provider will demonstrate the proper technique for self-administration or administration to your child.
5. 5Storage: Store the vials in a refrigerator between 2°C to 8°C (36°F to 46°F). Keep the medication out of direct light.

If you miss a dose, contact your healthcare provider immediately for instructions. Do not double the dose to catch up. Consistency is critical, especially in the treatment of infantile spasms, to maintain therapeutic levels of the hormone.

Signs of acute overdosage may include severe fluid retention, rapid weight gain, and symptoms of Cushing's syndrome (such as a rounded face or 'moon face'). In the event of a suspected overdose, seek emergency medical attention or contact a poison control center immediately. Treatment is generally supportive, focusing on managing electrolyte imbalances and fluid status.

> 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 lead to adrenal insufficiency.

Corticotropin stimulates the production of natural steroids, and many of its side effects mimic those of long-term corticosteroid use. Common reactions include:

• Fluid Retention and Edema: Swelling in the hands, ankles, or feet due to sodium and water retention.
• Increased Appetite and Weight Gain: Often occurring rapidly after starting treatment.
• Cushingoid Features: Development of a 'moon face' (rounded face), 'buffalo hump' (fat deposit between the shoulders), and central obesity.
• Insomnia and Irritability: Difficulty sleeping and mood swings are frequently reported, especially in pediatric patients.
• Increased Blood Pressure: Hypertension (high blood pressure) is common and may require monitoring.

• Glucose Intolerance: Elevated blood sugar levels (hyperglycemia), which may unmask latent diabetes mellitus.
• Muscle Weakness: Known as steroid myopathy, affecting the proximal muscles (shoulders and hips).
• Skin Changes: Thinning of the skin, acne, and impaired wound healing.
• Electrolyte Imbalance: Specifically hypokalemia (low potassium levels), which can cause fatigue or heart palpitations.

• Osteoporosis: Significant loss of bone density, leading to an increased risk of fractures with prolonged use.
• Cataracts and Glaucoma: Increased intraocular pressure and clouding of the lens.
• Psychosis: Severe mood disturbances, including hallucinations or intense depression.
• Hypertrophic Cardiomyopathy: In infants, the heart muscle may thicken, which usually reverses after the drug is stopped.

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

• Signs of Infection: Fever, cough, sore throat, or painful urination. Corticotropin can mask the signs of infection and weaken your immune system.
• Severe Allergic Reaction (Anaphylaxis): Hives, difficulty breathing, swelling of the face, lips, or tongue.
• Gastrointestinal Perforation: Severe abdominal pain, black or tarry stools, or vomiting blood.
• Vision Changes: Sudden blurred vision, eye pain, or seeing halos around lights.
• Congestive Heart Failure: Shortness of breath, rapid weight gain, and severe swelling.
• Adrenal Insufficiency: If the medication is stopped suddenly, symptoms like severe fatigue, dizziness, and nausea may occur.

Prolonged use of Corticotropin can lead to permanent changes in the body. These include stunted growth in children (suppression of the pituitary-gonadal axis), permanent bone loss (osteoporosis), and a persistent susceptibility to infections. Chronic use also increases the risk of developing Type 2 diabetes and cardiovascular disease due to the metabolic effects of elevated cortisol levels.

There are currently no FDA Black Box Warnings for Corticotropin. However, the FDA emphasizes the risk of serious infections and the need for careful monitoring of blood pressure and electrolytes during therapy.

Report any unusual symptoms or changes in mood/behavior to your healthcare provider immediately. Regular follow-up appointments are necessary to monitor for these side effects.

Corticotropin is a potent hormonal agent that requires diligent medical supervision. It should only be used by patients who can be monitored regularly for complications. Because it stimulates the adrenal glands, it can affect nearly every organ system in the body. Patients should be aware that this medication can suppress the immune system, making them more vulnerable to infections and potentially making infections harder to detect.

No FDA black box warnings for Corticotropin. However, clinical warnings regarding infantile spasms and MS treatment are prominent in the prescribing information.

• Infection Risk: Corticotropin can hide the symptoms of an infection. Do not start this medication if you have a systemic fungal infection. Use with caution in patients with latent tuberculosis or herpes simplex of the eye.
• Adrenal Suppression: Long-term use of Corticotropin suppresses the body's natural ability to produce ACTH. If the medication is stopped abruptly, the body may not be able to produce enough cortisol to handle stress (surgery, injury, or illness), leading to a life-threatening adrenal crisis.
• Cardiovascular and Renal Effects: The drug causes sodium and water retention and potassium loss. This can worsen heart failure, high blood pressure, or kidney disease. Monitoring of blood pressure and weight is mandatory.
• Gastrointestinal Risks: There is an increased risk of stomach ulcers and bleeding, especially when used with other drugs like NSAIDs (e.g., ibuprofen, aspirin).
• Behavioral and Mood Changes: Patients may experience euphoria, insomnia, mood swings, personality changes, or even severe depression and psychosis.
• Vaccinations: Do not receive 'live' or 'live-attenuated' vaccines while using Corticotropin. The drug's immunosuppressive effects may cause the vaccine to be ineffective or, in rare cases, cause the patient to contract the disease from the vaccine.

Your doctor will order regular tests to ensure the medication is working safely:

• Blood Pressure: Checked at every visit.
• Electrolytes: Monitoring for low potassium and high sodium.
• Blood Glucose: Regular checks for hyperglycemia, especially in diabetic patients.
• Growth Monitoring: In children, height and weight must be tracked closely to detect growth suppression.
• Eye Exams: Periodic checks for cataracts and glaucoma if used long-term.
• Echocardiograms: Recommended for infants to monitor for heart muscle thickening.

Corticotropin may cause dizziness, blurred vision, or mood changes. Do not drive or operate heavy machinery until you know how this medication affects you.

Alcohol should be avoided or strictly limited. Alcohol increases the risk of stomach irritation and gastrointestinal bleeding when taking hormonal therapies like Corticotropin. It can also worsen the mood-altering effects of the drug.

NEVER stop taking Corticotropin suddenly. Your doctor will provide a tapering schedule to slowly lower the dose over several days or weeks. This allows your adrenal glands to resume their natural function. Sudden withdrawal can cause 'steroid withdrawal syndrome,' characterized by joint pain, weakness, and severe fatigue.

> Important: Discuss all your medical conditions, including a history of ulcers, heart disease, or mental health issues, with your healthcare provider before starting Corticotropin.

• Live Vaccines: (e.g., MMR, Varicella, Yellow Fever). Corticotropin suppresses the immune system, which can lead to a severe or fatal reaction to live virus vaccines. The vaccine will also likely fail to provide immunity.
• Systemic Fungal Infections: Corticotropin should not be used in patients with systemic fungal infections as it can worsen the infection and lead to disseminated disease.

• Diuretics (Water Pills): Drugs like furosemide or hydrochlorothiazide can cause the body to lose potassium. When taken with Corticotropin, the risk of severe hypokalemia (dangerously low potassium) increases, which can lead to heart rhythm problems.
• Amphotericin B: This antifungal medication also depletes potassium; combining it with Corticotropin significantly elevates the risk of cardiac arrhythmias.
• Antidiabetic Agents: Corticotropin increases blood sugar levels. Patients taking insulin or oral diabetes medications (like metformin or glipizide) will likely need their doses adjusted to maintain glycemic control.
• NSAIDs and Salicylates: Taking aspirin, ibuprofen, or naproxen with Corticotropin increases the risk of developing stomach ulcers and gastrointestinal bleeding.

• Anticonvulsants: Certain seizure medications (like phenytoin or carbamazepine) may increase the clearance of corticosteroids, potentially reducing the effectiveness of Corticotropin.
• Anticoagulants: Corticotropin can alter the body's response to blood thinners like warfarin. Close monitoring of the INR (International Normalized Ratio) is required to prevent bleeding or clotting complications.
• Oral Contraceptives: Estrogens may increase the levels of cortisol-binding globulin, which can change the amount of active cortisol produced in response to Corticotropin.

• Sodium (Salt): High salt intake can worsen the fluid retention and high blood pressure caused by Corticotropin. Patients are often advised to follow a low-sodium diet.
• Potassium-Rich Foods: Your doctor may recommend increasing your intake of potassium (e.g., bananas, spinach) to counteract the potassium-wasting effects of the medication.
• Grapefruit: While not as significant as with other drugs, grapefruit can occasionally interfere with the metabolism of steroids; consult your doctor before consuming large amounts.

• St. John's Wort: May induce enzymes that speed up the breakdown of steroids, potentially lowering the drug's efficacy.
• Licorice Root: Contains glycyrrhizic acid, which can mimic some effects of steroids and worsen potassium loss and high blood pressure.
• Echinacea: May interfere with the immunosuppressive goals of Corticotropin therapy.

Corticotropin can interfere with several diagnostic tests:

• Skin Tests: It may suppress reactions to allergy skin tests.
• Thyroid Function Tests: It may decrease levels of TSH (Thyroid Stimulating Hormone).
• Urine Tests: It can cause false results in tests for urinary 17-ketosteroids.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking to prevent dangerous interactions.

Corticotropin must NEVER be used in the following circumstances:

1. 1Systemic Fungal Infections: The drug's immunosuppressive properties allow fungal infections to spread unchecked throughout the body.
2. 2Scleroderma: In patients with scleroderma, Corticotropin has been associated with an increased risk of renal crisis (sudden kidney failure and severe high blood pressure).
3. 3Recent Surgery: Because it impairs wound healing, it should not be used immediately following major surgery.
4. 4Known Hypersensitivity: If you have had a previous allergic reaction to porcine (pig) proteins or any component of the Corticotropin injection, you must not use this drug.
5. 5Ocular Herpes Simplex: Use is contraindicated due to the risk of corneal perforation.
6. 6Congestive Heart Failure: In severe cases where fluid retention would be life-threatening.
7. 7Uncontrolled Hypertension: High blood pressure that is not managed with medication.

Your healthcare provider will perform a careful risk-benefit analysis if you have:

• Diabetes Mellitus: Due to the risk of severe hyperglycemia.
• Osteoporosis: Because the drug causes further bone loss.
• Diverticulitis or Peptic Ulcer: Due to the risk of intestinal perforation.
• Myasthenia Gravis: Initial treatment may temporarily worsen muscle weakness.
• Psychiatric Disorders: Especially a history of depression or psychosis, which the drug can exacerbate.

Corticotropin used in the United States is typically derived from porcine (pig) pituitary glands. Patients with a known allergy to pork or pork products may experience cross-allergic reactions, ranging from mild rashes to life-threatening anaphylaxis. Always inform your doctor of any food or animal allergies.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Corticotropin to ensure it is safe for you.

Corticotropin is classified as FDA Pregnancy Category C. This means that animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well-controlled studies in humans.

• Risks: Prolonged use during pregnancy may lead to fetal adrenal insufficiency or low birth weight.
• Clinical Use: Corticotropin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not typically used for fertility treatments.

It is not known whether Corticotropin is excreted in human milk. However, because many drugs are excreted in milk and because of the potential for serious adverse reactions in nursing infants (such as growth suppression), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

• Approved Use: Corticotropin is specifically approved for the treatment of infantile spasms in infants and children under 2 years of age.
• Growth Effects: Long-term use in children can lead to permanent growth suppression. Height and weight must be monitored at every clinical visit.
• Heart Health: There is a risk of hypertrophic cardiomyopathy (thickening of the heart muscle) in infants. Regular echocardiograms are often recommended during treatment.
• Bone Health: Children are at risk for decreased bone mineral density.

Clinical studies of Corticotropin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

• Risks: Elderly patients are at a significantly higher risk for developing hypertension, edema, and osteoporosis while on this medication.
• Polypharmacy: Older adults are more likely to be taking medications that interact with Corticotropin, such as diuretics or NSAIDs. Dose selection should be cautious.

Patients with renal insufficiency should be monitored closely. Corticotropin causes the body to hold onto salt and water, which can lead to edema (swelling) and worsen kidney function. While the drug itself is not primarily cleared by the kidneys, its physiological effects can be dangerous for those with pre-existing kidney disease.

In patients with cirrhosis or other forms of liver disease, there may be an enhanced effect of the steroids produced by Corticotropin. This is because the liver is responsible for metabolizing the cortisol produced by the adrenals. If the liver is not functioning well, cortisol levels may stay high for longer, increasing the risk of side effects.

> Important: Special populations require individualized medical assessment and frequent monitoring by a specialist.

Corticotropin is an 39-amino acid peptide that acts as a potent agonist at the Melanocortin Receptor 2 (MC2R), located primarily in the zona fasciculata of the adrenal cortex. Binding to MC2R activates the G-protein-coupled receptor, which stimulates the enzyme adenylate cyclase. This increases intracellular levels of cyclic AMP (cAMP), which in turn activates protein kinase A (PKA). PKA facilitates the transport of cholesterol into the mitochondria via the Steroidogenic Acute Regulatory (StAR) protein. Once inside the mitochondria, cholesterol is converted to pregnenolone, the precursor for cortisol, aldosterone, and adrenal androgens.

The primary pharmacodynamic effect of Corticotropin is the rapid increase in plasma cortisol levels. Onset of adrenal stimulation occurs within minutes of injection, but the therapeutic anti-inflammatory effects take longer to manifest. In the treatment of infantile spasms, the exact mechanism is not fully understood but is thought to involve the suppression of corticotropin-releasing hormone (CRH) in the brain, which may reduce neuronal excitability. Tolerance to the adrenal-stimulating effects is rare, but the body's response can be limited by the maximum secretory capacity of the adrenal glands.

| Parameter | Value |

|---|---|

| Bioavailability | High (via IM/SC injection) |

| Protein Binding | Minimal (acts as a free peptide) |

| Half-life | ~15 minutes (plasma); 12-24 hours (biological effect) |

| Tmax | 3 to 12 hours (for cortisol stimulation) |

| Metabolism | Proteolytic degradation in various tissues |

| Excretion | Minimal renal excretion of intact peptide |

• Molecular Formula: C210H314N56O57S (for human ACTH)
• Molecular Weight: ~4541.1 g/mol
• Solubility: Soluble in water and physiological saline.
• Structure: A single-chain polypeptide containing 39 amino acids. The first 24 amino acids are identical across species and are responsible for the biological activity.

Corticotropin is classified as an Adrenocorticotropic Hormone [EPC]. It is unique among hormonal therapies because it acts as a trophic hormone (a hormone that stimulates another endocrine gland). Related medications include synthetic ACTH analogs like Cosyntropin, which is primarily used for diagnostic testing (the ACTH stimulation test) rather than long-term therapy.