Corticotropin
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Adrenocorticotropic Hormone (ACTH), Therapy Class:
Natural hormone, Approved Countries
The United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Corticotropin is a natural hormone belonging to the pharmacological class of Adrenocorticotropic Hormone (ACTH).
Corticotropin is approved by the FDA and is used for managing conditions such as infantile spasms in infants, multiple sclerosis exacerbations, and certain autoimmune disorders where systemic corticosteroid therapy is indicated and appropriate for treatment.
Corticotropin is not orally absorbed and is typically administered through injection. Its distribution and metabolism details are unavailable. Elimination primarily occurs via urine, with a short 15-minute elimination half-life, signifying rapid renal clearance.
The most common side effects of Corticotropin include fluid retention, increased appetite, glucose intolerance, and high blood pressure.
Corticotropin is available in the form of injectable solutions.
The molecule is available in the United States, Canada, the United Kingdom, Australia, Germany, France, Italy, Japan, India, Brazil and Mexico.
Corticotropin is a natural hormone belonging to the pharmacological class of Adrenocorticotropic Hormone (ACTH).
The anterior lobe of the pituitary gland typically produces Corticotropin. Corticotropin combines with a particular receptor on the plasma membrane of the adrenal cell to serve as a diagnostic tool (adrenocortical function). Increasing the amount of cholesterol within the mitochondria stimulates the initial reaction in synthesizing adrenal steroids (cortisol, cortisone, weak androgenic substances, and a limited quantity of aldosterone) from cholesterol in patients with normal adrenocortical function. In patients with primary adrenocortical insufficiency (Addison's disease), Corticotropin does not appreciably raise serum cortisol concentrations. Corticotropin's mode of action in the management of infantile myoclonic seizures remains unclear.
The data duration of corticotropin action usually ranges from 8 to 24 hours after administration.
The onset of Corticotropin action generally begins within an hour after administration.
The Data of Cmax and Tmax of Corticotropin has yet to be established.
Corticotropin is available in the form of injectable solutions.
Injectable solutions: Corticotropin injection is administered intramuscularly or subcutaneously. For proper use, adhere to the doctor's recommendations.
As the physician recommends, take the medication orally once daily; it can be taken with or without food as directed.
Corticotropin can be used in the following health conditions:
- Multiple sclerosis (MS)
- Infantile spasms in children below two years.
- It alleviates symptoms but doesn't cure or halt disease progression.
Management of acute exacerbations of Multiple Sclerosis (MS)
Corticotropin decreases inflammation, which helps to manage acute exacerbations of Multiple Sclerosis (MS). It helps to lessen symptom intensity and duration. When other treatments have proven ineffective or intolerable, the hormone provides relief by reducing the immune system's reaction, minimizing damage to nerve fibers, and limiting neurological impairment during MS flare-ups.
In Infantile spasms
Corticotropin administered by healthcare professionals treats infantile spasms in babies, alleviating stiffened muscles and developmental setbacks. Stimulating hormone release is crucial for this treatment, as it prevents associated complications. Its injection interacts with melanocortin receptors, impacting cell activity relevant to the condition. Additionally, it collaborates with the body's immune system, reducing inflammation in chronic inflammatory or autoimmune disorders like rheumatic disease, collagen disorders, allergies, and respiratory or ophthalmic conditions.
- Corticotropin is indicated in the management of acute exacerbations of MS, helping to reduce inflammation and shorten the duration of relapses.
- Corticotropin is also indicated in the treatment of infantile spasms (West syndrome), a rare seizure disorder in infants, where it may be effective in controlling seizures when other treatments have failed.
Parenterally: Corticotropin is available as an injectable solution and is administered intramuscularly or subcutaneously. Before use, warm the medication by removing the medication from the refrigerator and rolling the vial in your hands for a few minutes. Before using this product, check this product visually for particles or discoloration. If either is present, do not use the liquid. Cleanse the injection site thoroughly with an alcohol swab. Use a sterile needle and syringe to draw the dose from the vial. Administer the injection into the muscle or subcutaneous tissue as directed by a healthcare provider, rotating injection sites to minimize tissue irritation.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Injectable solutions: 5mL (80 units/mL)
Corticotropin is available in the form of injectable solutions.
Dose Adjustment in Adult Patients:
Adrenal responsiveness 40–80 unit IM/SC verified every 24–72 hours.
Acute Exacerbations of Multiple Sclerosis: 80–120 units of IM qDay for two to three weeks.
Nephrotic Syndrome
induces diuresis or a remission of proteinuria in cases of nephrotic syndrome without idiopathic or lupus erythematosus-related uremia.
IM/SC every 1-3days 40-80 units
While using Corticotropin, adhere to dietary restrictions such as avoiding excessive grapefruit juice consumption due to potential interactions. Limit alcohol intake as it may exacerbate side effects. Use caution with nitrates to prevent possible hypotension. Additionally, maintain a balanced diet and discuss any potential interactions with other medications or supplements to ensure safe and effective treatment while on Corticotropin therapy.
For children with epilepsy, a ketogenic diet, low in carbs and high in fats, shifts energy generation to fat utilization instead of glucose. Adolescents and adults benefit from the Atkins (high fat and controlled carbohydrates) diet, balancing high fat and controlled carbohydrates.
The dietary restriction should be individualized as per patient requirements.
Corticotropin may be contraindicated in the following conditions: -
- Sensitivity to porcine proteins
- Children under two years old who may have congenital infections.
- IV administration
- Coadministration of immunosuppressive dosages of Corticotropin together with live or live-attenuated vaccinations
- Infants <2 years are suspected of congenital infections.
- Scleroderma
- Osteoporosis
- Systemic fungal infections
- Ocular herpes simplex
- Recent surgery
- Active/history of peptic ulcer
- CHF, HTN
- Infections: There is a raised chance of developing a new disease and a worsening, spreading, or reactivating an old one. Infection signs can go undetected.
- Chronic Adrenal Insufficiency: After treatment ends, monitor for the consequences of hypothalamic-pituitary axis suppression.
- After receiving long-term therapy, Cushing's syndrome may develop. Assess any symptoms or signs.
- Hyperkalemia, Retention of Salt and Water, and Elevated Blood Pressure: Monitor high potassium and sodium levels and your blood pressure.
- Immunization: Patients receiving immunosuppressive dosages should not receive live or live-attenuated vaccinations.
- Symptoms of Other Underlying Diseases or Disorders Being Disguised. Patients should be evaluated for any indications of hidden underlying diseases or illnesses.
- Gastric ulcers and bleeding are possible side effects of gastrointestinal perforation. Patients with specific gastrointestinal problems are more likely to get a perforation. Symptoms and signs can be masked. Monitor for bleeding and perforation symptoms.
- Behavioural and Mood Disorders: These could include psychosis, profound depression, mood swings, personality changes, euphoria, and insomnia. It's the potential to make preexisting conditions worse.
- Comorbid Conditions: Treatment for myasthenia gravis and diabetes may make symptoms worse.
- Effects on the Eyes: Monitor for glaucoma, infections, and cataracts.
- Immunogenicity Potential: Long-term neutralizing antibody treatment may cause endogenous ACTH activity to decrease.
- When used by patients who have liver cirrhosis or hypothyroidism, the effects could be exacerbated.
- Adverse Effects on Physical Development and Growth: Monitor pediatric patients receiving long-term therapy.
- Reduced Bone Density: Patients receiving long-term therapy should be evaluated for osteoporosis.
- Embryocidal effect when used throughout pregnancy. Advise women that there could be a risk to the unborn.
Alcohol Warning
It is unsafe to consume Corticotropin with alcohol.
Breast Feeding Warning
It is most likely safe to use corticotropin during nursing. There isn't much evidence on humans to support the drug's potential risks to the unborn child.
Pregnancy Warning
Generally, not advised to be used in pregnancy. However, if used benefits should overweigh the risk.
Food Warning
Limit grapefruit and alcohol, and adopt good balanced diet.
The adverse reactions related to Corticotropin can be categorized as
- Common Adverse Effects: Edema, hypertension.
- Less Common Adverse Effects: Psychotic disorder, disorders of the skin, and peptic ulcer disease.
- Rare Adverse Effects: Immune hypersensitivity reactions and muscle weakness.
alcohol and Reports
Reactions at the injection location
Reduced tolerance to carbohydrates (infants exclusively), hirsutism, and irregular menstruation
Ulcerative esophagitis, abdominal distention, and pancreatitis (adult only)
Adults only experience headaches, vertigo, subdural hematomas, intracranial haemorrhages, and irreversible brain shrinkage (typically caused by hypertension) in babies.
Infants may experience hypokalemic alkalosis and fluid retention, which includes peripheral oedema.
Development of antibodies and loss of stimulatory effect
Blood sugar levels increased.
Palpitations, atrial fibrillation, and necrotizing angiitis (adults only)
Adults only: facial erythema, thinning skin, and increased perspiration
Suppression of skin test reactions
Hyperpigmentation
Increased perspiration and facial erythema (adults only)
Fractures from compression (only in newborns)
Insomnia
Delayed healing of wounds
Weight gain
Ecchymoses and petechiae
Acne
Abscess
Overpigmentation
Anaphylaxis (including urticaria, oedema, hypotension, anaphylactic shock, and respiratory impairment)
The clinically relevant drug interactions of Corticotropin are briefly summarized here.
- Anticoagulants (Warfarin, Heparin): Corticotropin can alter anticoagulant effectiveness, potentially leading to increased or decreased clotting, necessitating regular monitoring and dosage adjustments.
- Immunosuppressants: Increased immunosuppression might result from concurrent administration of Corticotropin with other immunosuppressants, potentially leading to an increased risk of infections. Careful monitoring for infections and adjustments in immunosuppressive therapy might be necessary.
- Diuretics (Furosemide, Hydrochlorothiazide): Interaction with diuretics can lead to electrolyte imbalances, notably potassium loss or hypokalemia, impacting cardiovascular health. Monitoring electrolyte levels becomes crucial.
- Antidiabetic Agents (Insulin, Oral Hypoglycemics): Corticotropin can elevate blood glucose levels, potentially reducing the efficacy of antidiabetic medications. Regular monitoring of blood sugar levels and dosage adjustments are essential.
- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Concurrent use may increase the risk of gastrointestinal ulceration or bleeding due to their combined effects on the stomach lining. Caution and monitoring for signs of bleeding are recommended.
- Vaccines (Live or Live-Attenuated): Corticotropin's immunosuppressive action might reduce the effectiveness of live vaccines or potentiate vaccine-related adverse effects. Avoiding live vaccines while on immunosuppressive doses is recommended.
The common side effects of Corticotropin include:-
Reaction at the injection location
Physical weakness, exhaustion, and low energy
Seizures
Increased blood pressure
Irritability
Fever
Insomnia, or trouble falling asleep
Increased risk of infection
Headache
Fluid retention is the build-up of fluid in bodily cavities and tissues.
Changes in glucose tolerance or elevated blood sugar levels
Behavioural and mood changes
Increased appetite
Weight gain
- Pregnancy
Pregnancy Category C (FDA): Use caution if the benefits outweigh the risks.
Corticotropin has been shown to have an embryocidal effect.
There aren't enough reliable, well-controlled research on pregnant women. During pregnancy, Corticotropin should only be taken if the possible advantages outweigh the potential risks to the developing foetus.
- Nursing Mothers
It is unknown if this medication is eliminated in human milk. Given that many medicines are excreted in human milk and that Corticotropin can cause severe adverse reactions in nursing infants, it is essential to weigh the risks and benefits to the mother when deciding whether to stop treating a nursing mother.
- Pediatric Use
In children under two years old, Corticotropin is approved for use as a monotherapy to treat infantile spasms.
Data
Clinical trials evaluated its effectiveness by defining response as total cessation of spasms and elimination of hypsarrhythmia. Non-sponsor studies and retrospective chart reviews were used in safety evaluations of the pediatric population. Regarding age, underlying diseases, length of therapy, and dosage, adverse reactions can differ in frequency and severity, even though they are similar to those seen in older patients. Among the significant issues with children are growth effects, which include severe adverse reactions that have been seen in adults.
Dosage adjustment in pediatric
Anti-Inflammatory/Immunosuppressive
0.8 UI/kg/day IM or 25 UI/m²/day divided into 12-24 hour periods.
Under two years old: Infantile spasms (West syndrome) Two weeks of 75 units/m² IM BID, followed by a two-week taper.
Tapering schedule
30 units/m² of IM qAM for three days, 15 units/m² of IM qAM for three days, 10 units/m² of IM qAM for three days, and 10 units/m² every other morning for six days.
Nephrotic Syndrome
causes diuresis or a remission of proteinuria in cases of nephrotic syndrome without idiopathic or lupus erythematosus-related uremia
Less than two years: Not proven to be safe or effective.
40–80 units per two years SC/IM q1-3days.
Dose Adjustment in Kidney Impairment Patients:
Mild-to-severe: Adjust Corticotropin dosage cautiously, considering the extent of renal dysfunction.
Dose Adjustment in Hepatic Impairment Patients:
Hepatic impairment: No dosage adjustment is required.
Signs and Symptoms
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Corticotropin.
Overconsumption of Corticotropin could lead to increased blood pressure, fluid retention, electrolyte imbalance, and potential manifestations of Cushing's syndrome, including weight gain and muscle weakness.
Management
There is no specific antidote or treatment for excessive Corticotropin intake, so treatment typically involves symptomatic and supportive measures. Addressing hypertension may require antihypertensive agents. Electrolyte imbalances should be corrected as needed. Monitoring for signs of Cushing's syndrome, including weight gain, muscle weakness, and other steroid-related symptoms, is essential. If ingestion is recent, induction of vomiting or gastric lavage may be considered alongside activated charcoal to reduce further absorption. In severe cases with cardiovascular compromise, vasopressor support might be necessary. Due to its short half-life, supportive measures primarily focus on managing symptoms and monitoring potential complications continuously.
When corticotropin overdose is suspected or proven, it is essential to seek medical assistance immediately to reduce the risk of side effects and successfully treat symptoms.
Pharmacodynamics:
Corticotropin stimulates the primary cell surface ACTH receptors on adrenocortical cells. Corticotropin activates the adrenal gland's cortex, increasing the production of corticosteroids, mostly glucocorticoids and androgens, which are sex hormones. In numerous organisms, Corticotropin and the circadian rhythm are connected.
Pharmacokinetics:
Absorption
Corticotropin is swiftly absorbed when administered intramuscularly, with an approximate duration of 8-15 hours for absorption.
Distribution
Not Available
Metabolism
Not Available
Elimination
Its elimination predominantly occurs through urine. Despite its swift absorption, the drug has a short elimination half-life, lasting around 15 minutes, indicating a relatively brief duration of action within the body before clearance through the renal system.
- Zhang H, Zhou JJ, Shao JY, Sheng ZF, Wang J, Zheng P, Kang X, Liu Z, Cheng ZJ, Kline DD, Li DP. Hypothalamic Corticotropin-Releasing Hormone Contributes to Hypertension in Spontaneously Hypertensive Rats. J Neurosci. 2023 Jun 14;43(24):4513-4524. doi: 10.1523/JNEUROSCI.2343-22.2023. Epub 2023 May 9. PMID: 37160364; PMCID: PMC10278672.
- O'Kane M, Murphy EP, Kirby B. The role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory disease. Exp Dermatol. 2006 Mar;15(3):143-53. doi: 10.1111/j.1600-0625.2006.00382.x. PMID: 16480421.
- Slominski A. On the role of the corticotropin-releasing hormone signalling system in the aetiology of inflammatory skin disorders. Br J Dermatol. 2009 Feb;160(2):229-32. doi: 10.1111/j.1365-2133.2008.08958.x. PMID: 19187344; PMCID: PMC2649670.
- Chrousos GP, Calabrese JR, Avgerinos P, Kling MA, Rubinow D, Oldfield EH, Schuermeyer T, Kellner CH, Cutler GB Jr, Loriaux DL, et al. Corticotropin releasing factor: basic studies and clinical applications. Prog Neuropsychopharmacol Biol Psychiatry. 1985;9(4):349-59. doi: 10.1016/0278-5846(85)90187-3. PMID: 2999871.
- KD Tripathi. [link]. Seventh Edition. New Delhi, India: Jaypee Brothers Medical Publishers; 2013: Page No 243-244
- https://pubchem.ncbi.nlm.nih.gov/compound/Corticotropin
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/008372s057lbl.pdf
- https://www.acthar.com/Static/pdf/Acthar-PI.pdf
Published on: 28 Nov 2023 10:18 AM GMT