Source: FDA, National Drug Code (US) Revision Year: 2021
Acthar Gel is contraindicated:
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)].
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.
Treatment with Acthar Gel can cause hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing’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 [see Patient Counseling Information (17)].
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 in adults and infants by tapering of the dose when discontinuing treatment.
Signs or symptoms of Cushing’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.
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, congestive heart failure, or renal insufficiency.
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.
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.
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.
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.
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.
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.
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.
There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver.
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.
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.
The following clinically significant adverse reactions are described elsewhere in the labeling:
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.
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/m2 twice daily n=122, (%) | 150 U/m2 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* | 20 | 46 |
| Investigations | ||
| Weight gain | 1 | 3 |
| Metabolism and nutrition disorders | ||
| Increased appetite | 0 | 5 |
| Decreased appetite | 3 | 3 |
| Nervous system disorders | ||
| Convulsion† | 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 |
* Specific infections that occurred at ≥2% were candidiasis, otitis media, pneumonia and upper respiratory tract infections.
† 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.
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.
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 responses have presented as dizziness, nausea, and anaphylaxis (anaphylactic shock, hypotension, respiratory compromise, urticaria, edema).
Necrotizing angitis (adults only), congestive heart failure, atrial fibrillation, and palpitations.
Skin thinning (adults only), facial erythema, and increased sweating (adults only).
Decreased carbohydrate tolerance (infants only), hirsutism, and menstrual irregularities.
Pancreatitis (adults only), abdominal distention, and ulcerative esophagitis.
Injection site reaction and asthenic conditions (including fatigue, malaise, asthenia, and lethargy).
Abscess.
Blood glucose increased.
Hypokalemic alkalosis (infants only) and fluid retention (including peripheral swelling).
Muscle weakness and vertebral compression fractures (infants only).
Headache (adults only), vertigo (adults only), subdural hematoma, intracranial hemorrhage (adults only), and reversible brain shrinkage (usually secondary to hypertension) (infants only).
Insomnia.
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:
Impaired wound healing, petechiae and ecchymoses, and suppression of skin test reactions.
Negative nitrogen balance due to protein catabolism and alteration in glucose tolerance.
Loss of muscle mass and aseptic necrosis of femoral and humeral heads.
Increased intracranial pressure with papilledema, (pseudo-tumor cerebri) usually after treatment, and subdural effusion.
Exophthalmos.
Formal drug-drug interaction studies have not been performed.
Acthar Gel may accentuate the electrolyte loss associated with diuretic therapy.
Based on Acthar Gel’s pharmacological effect of stimulating an endogenous steroid response [see Clinical Pharmacology ( 12.1)], Acthar Gel may cause fetal harm when administered to a pregnant woman. The published literature on systemic corticosteroid use during pregnancy, which may be relevant, suggests potential concerns. Intrauterine growth restriction, decreased birth weight, and preterm birth have been reported with maternal use of corticosteroids; however, the underlying maternal condition may also contribute to these risks. Hypoadrenalism has also been reported in infants after high-dose and/or long-term use of corticosteroids during pregnancy (see Clinical Considerations). The potential adverse developmental effects of Acthar Gel have not been adequately assessed in animals.
The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Hypoadrenalism has been reported in infants born to mothers treated with systemic corticosteroids during pregnancy. Infants born to mothers treated with Acthar Gel should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly [see Warnings and Precautions (5.2)].
There are no available data on the presence of corticotropin in either human or animal milk, the effects on the breastfed infant, or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Acthar Gel and any potential adverse effects on the breastfed infant from Acthar Gel or from the underlying maternal condition.
Acthar Gel is indicated as monotherapy for the treatment of infantile spasms in infants and children less than 2 years of age. Both serious and other adverse reactions can occur in this population [see Warnings and Precautions (5) and Adverse Reactions (6.1)].
The efficacy of Acthar Gel for the treatment of infantile spasms in infants and children less than 2 years of age was evaluated in a randomized, single blinded (video EEG interpreter blinded) clinical trial and an additional active control supportive trial [see Clinical Studies (14)]. A responding patient was defined as having both complete cessation of spasms and elimination of hypsarrhythmia.
Safety in the pediatric population for infantile spasms was evaluated by retrospective chart reviews and data from non-sponsor conducted clinical trials [see Adverse Reactions (6.1)]. While the types of adverse reactions seen in infants and children under 2 years of age 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. Effects on growth are of particular concern [see Warnings and Precautions (5.12)]. Serious adverse reactions observed in adults may also occur in children [see Warnings and Precautions (5)].
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