Included as part of the PRECAUTIONS section.
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 might be expected to occur [see
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
Cushing’s Syndrome And Adrenal Insufficiency Upon
Treatment with Acthar Gel can cause
hypothalamic-pituitary-axis (HPA) 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 INFORMATION].
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.
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, 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.
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.
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
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.
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
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. Sensitivity to porcine protein should be considered before starting
therapy and during the course of treatment should symptoms arise.
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.
Negative Effects On Growth And Physical Development
Long-term use of Acthar Gel may have negative effects on
growth and physical development in children. 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 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.
Use In Pregnancy
Acthar Gel has been shown to have an embryocidal effect.
Apprise women of potential harm to the fetus [see Use In Specific
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Adequate and well-controlled studies have not been done
in animals. Human use has not been associated with an increase in malignant
disease [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Use In Specific Populations
Pregnancy Class C: Acthar Gel has been shown to have an
embryocidal effect. There are no adequate and well-controlled studies in
pregnant women. Acthar Gel should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
It is not known whether this drug is excreted in human
milk. Because many drugs are excreted in human milk and because of the
potential for serious adverse reactions in nursing infants from Acthar Gel, when
treating a nursing mother, a decision should be made whether to discontinue
nursing or to discontinue the drug, considering the risk and benefit to the
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 in this population are discussed in
Warnings and Adverse Reactions in Infants and Children Under 2 Years of Age
AND PRECAUTIONS and ADVERSE REACTIONS].
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]. 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]. 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]. Serious
adverse reactions observed in adults may also occur in children [see WARNINGS