CORTICOTROPIN: 11,764 Adverse Event Reports & Safety Profile

Acthar Gel is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides.

The Acthar

Gel manufacturing process converts the initial porcine pituitary extract with low ACTH content into a mixture having modified porcine ACTH and other related peptide analogs solubilized in gelatin. A major component in the formulated complex mixture is N-25 deamidated porcine ACTH (1-39).

Acthar

Gel is supplied as a sterile preparation in 16% gelatin to provide a prolonged release after intramuscular or subcutaneous injection.

Acthar

Gel also contains 0.5% phenol, not more than 0.1% cysteine (added), sodium hydroxide and/or acetic acid to adjust pH and Water for Injection.

AND USAGE Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and children under 2 years of age. ( 1.1 )

Acthar

Gel is indicated for the treatment of exacerbations of multiple sclerosis in adults. ( 1.2 )

Acthar

Gel may be used for the following disorders and diseases: rheumatic ( 1.3 ); collagen ( 1.4 ); dermatologic ( 1.5 ); allergic states ( 1.6 ); ophthalmic ( 1.7 ); respiratory ( 1.8 ); and edematous state. ( 1.9 )

1.1 Infantile Spasms Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and children under 2 years of age.

1.2 Multiple Sclerosis Acthar Gel is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. Controlled clinical trials have shown Acthar Gel to be effective in speeding the resolution of acute exacerbations of multiple sclerosis. However, there is no evidence that it affects the ultimate outcome or natural history of the disease.

1.3 Rheumatic Disorders As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Psoriatic arthritis; Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); Ankylosing spondylitis.

1.4 Collagen Diseases During an exacerbation or as maintenance therapy in selected cases of: systemic lupus erythematosus, systemic dermatomyositis (polymyositis).

1.5 Dermatologic Diseases Severe erythema multiforme, Stevens-Johnson syndrome.

1.6 Allergic States Serum sickness.

1.7 Ophthalmic Diseases Severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis; iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis; anterior segment inflammation.

1.8 Respiratory Diseases Symptomatic sarcoidosis.

1.9 Edematous State To induce a diuresis or a remission of proteinuria in the nephrotic syndrome without uremia of the idiopathic type or that due to lupus erythematosus.

AND ADMINISTRATION Acthar Gel vial is for either intramuscular or subcutaneous injection. ( 2.1 )

Acthar

Gel single-dose pre-filled SelfJect injector: is for subcutaneous administration by adults only. ( 2.1 ) used to administer single doses of 40 units or 80 units only. ( 2.1 ) Infantile spasms: doses must be administered intramuscularly using the Acthar gel vial. The recommended dose is 150 U/m 2 divided into twice daily injections of 75 U/m 2 .

After

2 weeks of treatment dosing should be gradually tapered and discontinued over a 2-week period.

Acthar

Gel single-dose pre-filled SelfJect injector is not to be used for the treatment of infantile spasms ( 2.2 ) Acute exacerbations of multiple sclerosis: daily intramuscular or subcutaneous doses of 80 to 120 units for 2-3 weeks may be administered. It may be necessary to taper the dose. ( 2.3 ) Other disorders and diseases: individualize dosing depending on the disease and patient. The usual dose is 40 to 80 units given intramuscularly or subcutaneously every 24 to 72 hours. It may be necessary to taper the dose. ( 2.4 )

2.1 Important Information Acthar Gel vial is intended for either intramuscular or subcutaneous injection.

Acthar

Gel single-dose pre-filled SelfJect injector is for subcutaneous administration by adults (18 years of age and older) only. The single-dose pre-filled SelfJect injector should only be used to administer single doses of either 40 units or 80 units. For administration of doses other than 40 units or 80 units, use the Acthar Gel multi-dose vial.

2.2 Recommended Dosage for Infantile Spasms in Infants and Children Under 2 Years of Age In the treatment of infantile spasms, Acthar Gel must be administered intramuscularly using the Acthar gel vial. Do not use the Acthar Gel single-dose pre-filled SelfJect injector for the treatment of infantile spasms. The recommended regimen is a daily dose of 150 U/m 2 (divided into twice daily intramuscular (IM) injections of 75 U/m 2 ) administered over a 2-week period. Dosing with Acthar Gel should then be gradually tapered over a 2-week period to avoid adrenal insufficiency. The following is one suggested tapering schedule: 30 U/m 2 in the morning for 3 days; 15 U/m 2 in the morning for 3 days; 10 U/m 2 in the morning for 3 days; and 10 U/m 2 every other morning for 6 days.

Acthar

Gel is typically dosed based on body surface area (BSA). For calculation of body surface area, use the following formula: Equation Formula

2.3 Recommended Dosage for the Treatment of Acute Exacerbations in Adults with Multiple Sclerosis The recommended dose is daily intramuscular or subcutaneous doses of 80 to 120 units for 2-3 weeks for acute exacerbations. Dosage should be individualized according to the medical condition of each patient. Frequency and dose of the drug should be determined by considering the severity of the disease and the initial response of the patient. Although drug dependence does not occur, sudden withdrawal of Acthar Gel after prolonged use may lead to adrenal insufficiency or recurrent symptoms which make it difficult to stop the treatment. It may be necessary to taper the dose and increase the injection interval to gradually discontinue the medication.

2.4 Recommended Dosage for Other Indications for Adults and Children Over 2 Years of Age Dosage should be individualized according to the disease under treatment and the general medical condition of each patient. Frequency and dose of the drug should be determined by considering severity of the disease and the initial response of the patient. The usual dose of Acthar Gel is 40 to 80 units given intramuscularly or subcutaneously every 24 to 72 hours. Although drug dependence does not occur, sudden withdrawal of Acthar Gel after prolonged use may lead to adrenal insufficiency or recurrent symptoms which make it difficult to stop the treatment. It may be necessary to taper the dose and increase the injection interval to gradually discontinue the medication.

2.5 Preparation and Administration Visually inspect the liquid for particulate matter and discoloration prior to administration.

Acthar

Gel must not be injected if the solution is cloudy or contains particulate matter.

Acthar Gel

Multi-Dose Vial Warm to room temperature before using. Take caution to not over-pressurize the vial prior to withdrawing the product.

Acthar Gel

Single-Dose Pre-filled SelfJect Injector Preparation Prior to injection, remove from the refrigerator and sealed tray and allow to sit for 45 minutes to warm to room temperature.

Administration

Read the FDA-approved Instructions for Use carefully before administering. Administer by subcutaneous injection only.

Acthar

Gel single-dose pre-filled SelfJect injector is not for intramuscular injection. Inject in the upper thigh, abdomen, or back of arm. Avoid injecting within 1 inch of navel, knee, or groin area. Avoid areas with scars, tattoos, warts, birthmarks, or stretch marks, or where the skin is irritated. Rotate injection sites. Do not use the same site more than one time per week.

Acthar Gel is contraindicated: for intravenous administration. in infants under 2 years of age who have suspected congenital infections. with concomitant administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of Acthar Gel. in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, or sensitivity to proteins of porcine origin.

Acthar

Gel is contraindicated: for intravenous administration ( 4 ) in infants under 2 years of age who have suspected congenital infections ( 4 ) with concomitant administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of Acthar Gel ( 4 ) in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction, or sensitivity to proteins of porcine origin ( 4 )

REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions (5.1) ] Cushing's Syndrome and Adrenal Insufficiency Upon Withdrawal [see Warnings and Precautions (5.2) ]

Elevated Blood

Pressure, Salt and Water Retention, and Hypokalemia [see Warnings and Precautions (5.3) ]

Masking

Symptoms of Other Diseases [see Warnings and Precautions (5.5) ]

Gastrointestinal

Perforation and Bleeding [see Warnings and Precautions (5.6) ] Behavioral and Mood Disturbances [see Warnings and Precautions (5.7) ]

Ophthalmic

Effects [see Warnings and Precautions (5.9) ]

Immunogenicity

Potential [see Warnings and Precautions (5.10) ]

Negative

Effects on Growth and Physical Development [see Warnings and Precautions (5.12) ] Decrease in Bone Density [see Warnings and Precautions (5.13) ] Commonly reported postmarketing adverse reactions for Acthar Gel include injection site reaction, asthenic conditions (including fatigue, malaise, asthenia and lethargy), fluid retention (including peripheral swelling), insomnia, headache, and blood glucose increased. ( 6.2 ) The most common adverse reactions (5% or greater in the recommended twice daily dosing group) for the treatment of infantile spasms are increased risk of infections, convulsions, hypertension, irritability, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mallinckrodt at 1-800-844-2830 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse

Reactions in Infants and Children Under 2 Years of Age While the types of adverse reactions seen in infants and children under age 2 treated for infantile spasms are similar to those seen in older patients, their frequency and severity may be different due to the very young age of the infant, the underlying disorder, the duration of therapy and the dosage regimen. Below is a summary of adverse reactions specifically tabulated from source data derived from retrospective chart reviews and clinical trials in children under 2 years of age treated for infantile spasms. The number of patients in controlled trials at the recommended dose was too few to provide meaningful incidence rates or to permit a meaningful comparison to the control groups. The most common adverse reactions (5% or greater in the recommended twice daily dosing group) for the treatment of infantile spasms are increased risk of infections, convulsions, hypertension, irritability, and pyrexia. TABLE: Incidence (%) of Adverse Reactions Occurring in ≥2% of Infants and Children Under 2 Years of Age Treated with Acthar Gel Adverse Reactions Recommended 75 U/m 2 twice daily n=122, (%) 150 U/m 2 once daily n=37 (%) Cardiac disorders Cardiac Hypertrophy 3 0 Endocrine disorders Cushingoid 3 22 Gastrointestinal disorders Diarrhea 3 14 Vomiting 3 5 Constipation 0 5 General disorders and administration site conditions Irritability 7 19 Pyrexia 5 8 Infections and infestations Infection Specific infections that occurred at ≥2% were candidiasis, otitis media, pneumonia and upper respiratory tract infections. 20 46 Investigations Weight gain 1 3 Metabolism and nutrition disorders Increased appetite 0 5 Decreased appetite 3 3 Nervous system disorders Convulsion In the treatment of infantile spasms, other types of seizures/convulsions may occur because some patients with infantile spasms progress to other forms of seizures (for example, Lennox-Gastaut Syndrome). Additionally, the spasms sometimes mask other seizures and once the spasms resolve after treatment, the other seizures may become visible. 12 3 Respiratory, thoracic and mediastinal disorders Nasal Congestion 1 5 Skin and subcutaneous tissue disorders Acne 0 14 Rash 0 8 Vascular disorders Hypertension 11 19 These adverse reactions may also be seen in adults and children over 2 years of age when treated for other purposes and with different doses and regimens.

6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of Acthar Gel. Because adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Allergic Reactions

Allergic responses have presented as dizziness, nausea, and anaphylaxis (anaphylactic shock, hypotension, respiratory compromise, urticaria, edema).

Cardiovascular

Necrotizing angitis (adults only), congestive heart failure, atrial fibrillation, and palpitations.

Dermatologic

Skin thinning (adults only), facial erythema, and increased sweating (adults only).

Endocrine

Decreased carbohydrate tolerance (infants only), hirsutism, and menstrual irregularities.

Gastrointestinal

Pancreatitis (adults only), abdominal distention, and ulcerative esophagitis.

General

Disorders and Administration Site Conditions Injection site reaction and asthenic conditions (including fatigue, malaise, asthenia, and lethargy). Infections and Infestations Abscess.

Investigations

Blood glucose increased.

Metabolic

Hypokalemic alkalosis (infants only) and fluid retention (including peripheral swelling).

Musculoskeletal

Muscle weakness and vertebral compression fractures (infants only).

Neurological

Headache (adults only), vertigo (adults only), subdural hematoma, intracranial hemorrhage (adults only), and reversible brain shrinkage (usually secondary to hypertension) (infants only).

Psychiatric Disorders

Insomnia.

6.3 Possible Additional Steroidogenic Effects Based on steroidogenic effects of Acthar Gel certain adverse events may be expected due to the pharmacological effects of corticosteroids. The adverse events that may occur but have not been reported for Acthar Gel are: Dermatologic Impaired wound healing, petechiae and ecchymoses, and suppression of skin test reactions.

Metabolic

Negative nitrogen balance due to protein catabolism and alteration in glucose tolerance.

Musculoskeletal

Loss of muscle mass and aseptic necrosis of femoral and humeral heads.

Neurological

Increased intracranial pressure with papilledema, (pseudo-tumor cerebri) usually after treatment, and subdural effusion.

Ophthalmic

Exophthalmos.

AND PRECAUTIONS The adverse effects of Acthar Gel are related primarily to its steroidogenic effects. Not all of the adverse events described below have been seen after treatment with Acthar Gel, but they might be expected to occur because they are steroidogenic effects [see Adverse Reactions (6.3) ] . Infections: Increased susceptibility to new infection and increased risk of exacerbation, dissemination or reactivation of latent infections. Signs and symptoms of infection may be masked. ( 5.1 )

Adrenal

Insufficiency after Prolonged Therapy: Monitor for effects of hypothalamic-pituitary-adrenal axis suppression after stopping treatment. ( 5.2 ) Cushing's Syndrome: May occur after prolonged therapy. Monitor for signs and symptoms. ( 5.2 )

Elevated Blood

Pressure, Salt and Water Retention, and Hypokalemia: Monitor blood pressure and sodium and potassium levels. ( 5.3 ) Masking of Symptoms of Other Underlying Disease/Disorders: Monitor patients for signs of other underlying disease/disorders that may be masked. ( 5.5 )

Gastrointestinal

Perforation and Bleeding: There is a risk for gastric ulcers and bleeding. There is an increased risk of perforation in patients with certain GI disorders. Signs and symptoms may be masked. Monitor for signs of perforation and bleeding. ( 5.6 ) Behavioral and Mood Disturbances: May include euphoria, insomnia, mood swings, personality changes, severe depression and psychosis. Existing conditions may be aggravated. ( 5.7 )

Comorbid

Diseases: Symptoms of diabetes and myasthenia gravis may be worsened with treatment. ( 5.8 )

Ophthalmic

Effects: Monitor for cataracts, infections and glaucoma. ( 5.9 )

Immunogenicity

Potential: Neutralizing antibodies with chronic administration may lead to a loss of endogenous ACTH activity. ( 5.10 ) Use in Patients with Hypothyroidism or Liver Cirrhosis: May result in an enhanced effect. ( 5.11 )

Negative

Effects on Growth and Physical Development: Monitor pediatric patients on long term therapy. ( 5.12 ) Decrease in Bone Density: Monitor for osteoporosis in patients on long term therapy. ( 5.13 )

5.1 Infections Acthar Gel may increase the risks related to infections with any pathogen, including viral, bacterial, fungal, protozoan or helminthic infections. Patients with latent tuberculosis or tuberculin reactivity should be observed closely, and if therapy is prolonged, chemoprophylaxis should be instituted.

5.2 Cushing&apos;s Syndrome and Adrenal Insufficiency Upon Withdrawal Treatment with Acthar Gel can cause hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing&apos;s syndrome. These conditions should be monitored especially with chronic use. Suppression of the HPA may occur following prolonged therapy with the potential for adrenal insufficiency after withdrawal of the medication. Patients should be monitored for signs of insufficiency such as weakness, hyperpigmentation, weight loss, hypotension and abdominal pain. The symptoms of adrenal insufficiency in infants treated for infantile spasms can be difficult to identify. The symptoms are non-specific and may include anorexia, fatigue, lethargy, weakness, excessive weight loss, hypotension and abdominal pain. It is critical that parents and caregivers be made aware of the possibility of adrenal insufficiency when discontinuing Acthar Gel and should be instructed to observe for, and be able to recognize, these symptoms <span class="opacity-50 text-xs">[see Patient Counseling Information (17) ]</span> . The recovery of the adrenal gland may take from days to months so patients should be protected from the stress (e.g., trauma or surgery) by the use of corticosteroids during the period of stress. The adrenal insufficiency may be minimized by tapering of the dose when discontinuing treatment. Signs or symptoms of Cushing&apos;s syndrome may occur during therapy but generally resolve after therapy is stopped. Patients should be monitored for these signs and symptoms such as deposition of adipose tissue in characteristics sites (e.g., moon face, truncal obesity), cutaneous striae, easy bruisability, decreased bone mineralization, weight gain, muscle weakness, hyperglycemia, and hypertension.

5.3 Elevated Blood Pressure, Salt and Water Retention, and Hypokalemia Acthar Gel can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium and calcium. Dietary salt restriction and potassium supplementation may be necessary. Caution should be used in the treatment of patients with hypertension or renal insufficiency.

Acthar

Gel is contraindicated in patients with congestive heart failure [see Contraindications (4) ] .

5.4 Vaccination Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar Gel. Killed or inactivated vaccines may be administered; however, the response to such vaccines can not be predicted. Other immunization procedures should be undertaken with caution in patients who are receiving Acthar Gel, especially when high doses are administered, because of the possible hazards of neurological complications and lack of antibody response.

5.5 Masking Symptoms of Other Diseases Acthar Gel often acts by masking symptoms of other diseases/disorders without altering the course of the other disease/disorder. Patients should be monitored carefully during and for a period following discontinuation of therapy for signs of infection, abnormal cardiac function, hypertension, hyperglycemia, change in body weight and fecal blood loss.

5.6 Gastrointestinal Perforation and Bleeding Acthar Gel can cause GI bleeding and gastric ulcer. There is also an increased risk for perforation in patients with certain gastrointestinal disorders. Signs of gastrointestinal perforation, such as peritoneal irritation, may be masked by the therapy. Use caution where there is the possibility of impending perforation, abscess or other pyogenic infections, diverticulitis, fresh intestinal anastomoses, and active or latent peptic ulcer.

5.7 Behavioral and Mood Disturbances Use of Acthar Gel may be associated with central nervous system effects ranging from euphoria, insomnia, irritability (especially in infants), mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated. These effects are reversible once Acthar Gel therapy is stopped.

5.8 Comorbid Diseases Patients with a comorbid disease may have that disease worsened. Caution should be used when prescribing Acthar Gel in patients with diabetes and myasthenia gravis.

5.9 Ophthalmic Effects Prolonged use of Acthar Gel may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves and may enhance the establishment of secondary ocular infections due to fungi and viruses.

5.10 Immunogenicity Potential Acthar Gel is immunogenic. Limited available data suggest that a patient may develop antibodies to Acthar Gel after chronic administration and loss of endogenous ACTH and Acthar Gel activity. Prolonged administration of Acthar Gel may increase the risk of hypersensitivity reactions. Cases of anaphylaxis have been reported in the postmarketing setting. Use in patients with sensitivity to porcine protein is contraindicated, and the possibility of sensitivity should be considered during the course of treatment should symptoms arise.

5.11 Use in Patients with Hypothyroidism or Liver Cirrhosis There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver.

5.12 Negative Effects on Growth and Physical Development Long-term use of Acthar Gel may have negative effects on growth and physical development in pediatric patients. Changes in appetite are seen with Acthar Gel therapy, with the effects becoming more frequent as the dose or treatment period increases. These effects are reversible once Acthar Gel therapy is stopped. Growth and physical development of pediatric patients on prolonged therapy should be carefully monitored.

5.13 Decrease in Bone Density Decrease in bone formation and an increase in bone resorption both through an effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function may occur. These, together with a decrease in the protein matrix of the bone (secondary to an increase in protein catabolism) and reduced sex hormone production, may lead to inhibition of bone growth in children and adolescents and to the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (i.e., postmenopausal women) before initiating therapy, and bone density should be monitored in patients on long term therapy.

PRECAUTIONS General Patients with latent tuberculosis or tuberculin reactivity who receive corticotropin should be closely observed as reactivation of the disease may occur. During prolonged corticotropin therapy, these patients should receive chemoprophylaxis. Skin testing should be performed prior to treatment of all patients with suspected sensitivity to porcine protein. Immediately following intramuscular or subcutaneous administration of corticotropin all patients should be observed carefully for sensitivity reactions. Relative adrenocortical insufficiency induced by prolonged corticotropin therapy may be minimized by gradual reduction of corticotropin dosage. This type of insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress during that period, hormone therapy should be reinstituted. There is an enhanced effect of corticotropin in patients with hypothyroidism and in those with cirrhosis. The lowest possible dosage of corticotropin should be used to control the condition under treatment, and when reduction in dosage is possible the reduction should be gradual. Corticotropin should be administered for treatment only when the disease is intractable to more conventional therapy. Corticotropin should be adjunctive and not the sole therapy in the treatment of a disease. Since maximal corticotropin stimulation of the adrenals may be limited during the first few days of treatment, other drugs should be administered when an immediate therapeutic effect is desirable. When infection is present appropriate anti-infective therapy should be administered during corticotropin and following discontinuation of corticotropin therapy. Treatment of acute gouty arthritis should be limited to a few days. Since rebound attacks may occur when corticotropin is discontinued, conventional concomitant therapy should be administered during corticotropin treatment, and for several days after it is stopped. Psychic derangements may appear when corticotropin is used, ranging from euphoria, insomnia, mood swings, personality changes, and depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticotropin. Corticotropin should be used with caution in patients with diabetes, abscess, pyogenic infections, diverticulitis, renal insufficiency, and myasthenia gravis. Growth and development of infants and children on prolonged corticotropin therapy should be carefully observed. Although controlled clinical trials have shown ACTH to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that it affects the ultimate outcome or natural history of the disease. Since complications of treatment with ACTH are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment.

Drug Interactions

Aspirin should be used cautiously in conjunction with corticotropin in hypoprothrombinemia.

Pregnancy

Since fetal abnormalities have been observed in experimental animals, use of this drug in pregnancy, nursing mothers, or women of childbearing potential requires that the potential benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticotropin during pregnancy should be carefully observed for signs of hypoadrenalism.

INTERACTIONS Formal drug-drug interaction studies have not been performed.

Acthar

Gel may accentuate the electrolyte loss associated with diuretic therapy.

Acthar

Gel may accentuate electrolyte loss associated with diuretics. ( 7 )

ACTIVE INGREDIENTS (HPUS*): Equal amounts of: Adrenal Gland 10X, Adrenocorticotrophin 10X, Cerebrum 14X, Liver Gland 10X, Pituitarum Posterium Gland 10X, Placenta 8X, Thyroidinum 8X. ​*The letters "HPUS" indicate that the components in this product are officially monographed in the Homeopathic Pharmacopeia of the United States.

INACTIVE INGREDIENTS: Ethanol Alcohol 15% (Non-GMO, Kosher Certified, Corn, Gluten, Allergen Free), Purified Water, Vegetable Glycerin 15%.