H.P. ACTHAR
-
corticotropin injection
Questcor Pharmaceuticals
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H.P. Acthar Gel (REPOSITORY CORTICOTROPIN INJECTION) U.S. Pat. No. 2,992,165DESCRIPTION
H.P. Acthar Gel (Repository Corticotropin Injection) is a highly
purified sterile preparation of the adrenocorticotropic hormone in
16 percent gelatin to provide a prolonged release after intramuscular
or subcutaneous injection. Also contains 0.5 percent phenol, not more
than 0.1 percent cysteine (added), sodium hydroxide and/or acetic acid to
adjust pH and water for injection, q.s.
ACTH is a 39 amino acid peptide with the following chemical formula:
H-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-
1 2 3 4 5 6 7 8 9 10
Lys-Pro-Val-Gly-Lys-Lys-Arg-Arg-Pro-Val-
11 12 13 14 15 16 17 18 19 20
Lys-Val-Try-Pro-Asp-Gly-Ala-Glu-Asp-Gln-
21 22 23 24 25 26 27 28 29 30
Leu-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe-OH
31 32 33 34 35 36 37 38 39
ACTH stimulates the adrenal cortex to secrete cortisol, corticosterone,
aldosterone, and a number of weakly androgenic
substances. Although ACTH does stimulate secretion of aldosterone,
the rate is relatively independent. Prolonged administration of large
doses of ACTH induces hyperplasia and hypertrophy of the adrenal
cortex and continuous high output of cortisol, corticosterone and
weak androgens. The release of ACTH is under the influence of the
nervous system via the corticotropin regulatory hormone released
from the hypothalamus and by a negative corticosteroid feedback
mechanism. Elevated plasma cortisol suppresses ACTH release.
The trophic effects of ACTH on the adrenal cortex are not understood
beyond the fact that they appear to be mediated by cyclic AMP.
ACTH rapidly disappears from the circulation following its intravenous
administration; in man the plasma half-life is about 15
minutes.
The maximal effects of a trophic hormone on a target organ are
achieved when optimal amounts of hormone are acting continuously.
Thus, a fixed dose of ACTH will demonstrate a linear increase in
adrenocortical secretion with increasing duration for the infusion.
INDICATIONS AND USAGE
H.P. Acthar Gel (Repository Corticotropin Injection) is indicated for
diagnostic testing of adrenocortical function.
H.P. Acthar Gel (Repository Corticotropin Injection) has limited
therapeutic value in those conditions responsive to corticosteroid
therapy; in such cases, corticosteroid therapy is considered to be
the treatment of choice. H.P. Acthar Gel (Repository Corticotropin
Injection) may be employed in the following disorders:
ENDOCRINE DISORDERS: Nonsuppurative thyroiditis; Hypercalcemia
associated with cancer.
NERVOUS SYSTEM DISEASES: Acute exacerbations of multiple
sclerosis.
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; Acute and subacute bursitis; Acute
nonspecific tenosynovitis; Acute gouty arthritis; Post-traumatic
arthritis; Synovitis of osteoarthritis; Epicondylitis.
COLLAGEN DISEASES: During an exacerbation or as maintenance
therapy in selected cases of:
Systemic lupus erythematosus; Systemic dermatomyositis (polymyositis);
Acute rheumatic carditis.
DERMATOLOGIC DISEASES: Pemphigus; Bullous dermatitis
herpetiformis; Severe erythema multiforme (Stevens-Johnson
syndrome); Exfoliative dermatitis; Severe psoriasis; Severe
seborrheic dermatitis; Mycosis fungoides.
ALLERGIC STATES: Control of severe or incapacitating allergic
conditions intractable to adequate trials of conventional treatment:
Seasonal or perennial allergic rhinitis; Bronchial asthma; Contact
dermatitis; Atopic dermatitis; Serum sickness.
OPHTHALMIC DISEASES: Severe acute and chronic allergic and
inflammatory processes involving the eye and its adnexa such as:
Allergic conjunctivitis; Keratitis; Herpes zoster ophthalmicus; Iritis
and iridocyclitis; Diffuse posterior uveitis and choroiditis; Optic
neuritis; Sympathetic ophthalmia; Chorioretinitis; Anterior segment
inflammation; Allergic corneal marginal ulcers.
RESPIRATORY DISEASES: Symptomatic sarcoidosis; Loeffler’s
syndrome not manageable by other means; Berylliosis; Fulminating
or disseminated pulmonary tuberculosis when used concurrently
with antituberculous chemotherapy; Aspiration pneumonitis.
HEMATOLOGIC DISORDERS: Acquired (autoimmune) hemolytic
anemia; Secondary thrombocytopenia in adults; Erythroblastopenia
(RBC anemia); Congenital (erythroid) hypoplastic anemia.
NEOPLASTIC DISEASES: For palliative management of: Leukemias
and lymphomas in adults; Acute leukemia of childhood.
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.
GASTROINTESTINAL DISEASES: To tide the patient over a critical
period of the disease in: Ulcerative colitis; Regional enteritis.
MISCELLANEOUS: Tuberculous meningitis with subarachnoid
block or impending block when used concurrently with appropriate
antituberculous chemotherapy; Trichinosis with neurologic or
myocardial involvement.
CONTRAINDICATIONS
Corticotropin is contraindicated 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, hypertension, or sensitivity to proteins of
porcine origin.
Treatment of conditions listed within the INDICATIONS section (see
above) is contraindicated when they are accompanied by primary
adrenocortical insufficiency or adrenocortical hyperfunction.
Intravenous administration of corticotropin is contraindicated.
WARNINGS
Chronic administration of corticotropin may lead to adverse
effects which are not reversible. Corticotropin may only suppress
symptoms and signs of chronic diseases without altering the natural
course of the disease. H.P. Acthar Gel (Repository Corticotropin
Injection) should not be administered for treatment until adrenal
responsiveness has been verified with the route of administration
which will be utilized during treatment, intramuscularly or
subcutaneously. A rise in urinary and plasma corticosteroid
values provides direct evidence of a stimulatory effect. Prolonged
administration of corticotropin increases the risk of hypersensitivity
reactions. Although the action of corticotropin is similar to that of
exogenous adrenocortical steroids, the quantity of adrenocorticoid
may be variable. In patients who receive prolonged corticotropin
therapy, the additional use of rapidly acting corticosteroids before,
during, and after an unusual stressful situation is indicated.
Prolonged use of corticotropin may produce posterior subcapsular
cataracts and glaucoma with possible damage to the optic nerves.
Corticotropin may mask some signs of infection, and new infections
including those of the eye due to fungi or viruses may appear during
its use. There may be decreased resistance and inability to localize
infection when corticotropin is used.
Corticotropin can cause elevation of blood pressure, salt and
water retention, and increased excretion of potassium. Dietary
salt restriction and potassium supplementation may be necessary.
Corticotropin increases calcium excretion.
While on corticotropin therapy, patients should not be vaccinated
against smallpox. Other immunization procedures should be
undertaken with caution in patients who are receiving corticotropin,
especially when high doses are administered because of the
possible hazards of neurological complications and lack of antibody
response.
PRECAUTIONS
1. General
Corticotropin injection should be used in the lowest dose for
the shortest period of time to accomplish the therapeutic goal.
Corticotropin should be used for treatment only when the disease
is intractable to non-steroid treatment.
There is an enhanced effect in patients with hypothyroidism and
in those with cirrhosis of the liver. Sensitivity to porcine protein
should be considered before starting therapy and during the
course of treatment should symptoms arise.
When an infection is present, appropriate antibiotic therapy
should be given. Patients with latent tuberculosis should be
observed closely, and if therapy is prolonged, chemoprophylaxis
should be instituted.
Psychic symptoms may appear with use of corticotropin or preexisting
symptoms may be enhanced. These may range from
mood alteration to a psychotic state.
Patients with a secondary disease may have that disease
worsened. Caution should be used when prescribing corticotropin
in patients with diabetes, renal insufficiency, diverticulitis, and
myasthenia gravis.
Corticotropin often acts by suppressing symptoms without
altering the course of the underlying disease. Since complications
with corticotropin use are dependent on the dose and duration of
treatment, a risk/benefit decision must be made in each case.
Suppression of the pituitary adrenal axis occurs following
prolonged therapy which may be slow in returning to normal.
Patients should be protected from the stress of trauma or surgery
by the use of corticosteroids during the period of stress.
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.
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. The studies do show
that relatively high doses of ACTH are necessary to demonstrate
a significant effect. (See DOSAGE AND ADMINISTRATION
section).
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.
Aspirin should be used cautiously in conjunction with corticotropin
in hypoprothrombinemia.
2. Drug Interactions
Corticotropin may accentuate the electrolyte loss associated with
diuretic therapy.
3. 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 Pregnancy warning below.
Pregnancy Class C: Corticotropin has been shown to have an
embryocidal effect. There are no adequate and well-controlled
studies in pregnant women. Corticotropin should be used during
pregnancy only if the potential benefit justifies the potential risk
to the fetus.
5. Nursing Mothers
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
corticotropin, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the
importance of the drug to the mother.
6. Pediatric Use
Prolonged use of corticotropin in children will inhibit skeletal
growth. If use is necessary, it should be given intermittently and
the child carefully observed.
ADVERSE REACTIONS
Fluid and electrolyte disturbances:
Sodium retention; fluid retention; potassium loss; hypokalemic
alkalosis; calcium loss.
Musculoskeletal:
Muscle weakness; steroid myopathy; loss of muscle mass;
osteoporosis; vertebral compression fractures; aseptic necrosis of
femoral and humeral heads; pathologic fracture of long bones.
Gastrointestinal:
Peptic ulcer with possible perforation and hemorrhage; pancreatitis;
abdominal distention; ulcerative esophagitis.
Dermatologic:
Impaired wound healing; thin fragile skin; petechiae and ecchymoses;
facial erythema; increased sweating; suppression of skin
test reactions; acne; hyperpigmentation.
Cardiovascular:
Hypertension; necrotizing angiitis; congestive heart failure.
Neurological:
Convulsions; increased intracranial pressure with papilledema,
(pseudo-tumor cerebri) usually after treatment; headache; vertigo.
Endocrine:
Menstrual irregularities; development of Cushingoid state; suppression
of growth in children; secondary adrenocortical and
pituitary unresponsiveness, particularly in times of stress, as in
trauma, surgery or illness; decreased carbohydrate tolerance;
manifestations of latent diabetes mellitus; increased requirements
for insulin or oral hypoglycemic agents in diabetics; hirsutism.
Ophthalmic:
Posterior subcapsular cataracts; increased intraocular pressure;
glaucoma with possible damage to optic nerve; exophthalmos.
Metabolic:
Negative nitrogen balance due to protein catabolism.
Allergic reactions:
Especially in patients with allergic responses to proteins manifesting
as dizziness, nausea and vomiting, shock, skin reactions.
Miscellaneous:
Abscess; prolonged use of ACTH may result in antibodies to it and
resulting loss of stimulatory effect.
Drug Abuse and Dependence:
Although drug dependence does not occur, sudden withdrawal of
corticotropin after prolonged use may lead to recurrent symptoms
which make it difficult to stop. It may be necessary to taper the
dose and increase the injection interval to gradually discontinue the
medication.
OVERDOSAGE
An acute overdose would present no different adverse reactions.
DOSAGE AND ADMINISTRATION
Standard tests for verification of adrenal responsiveness to
corticotropin may utilize as much as 80 units as a single injection
or one or more injections of a lesser dosage. Verification tests
should be performed prior to treatment with corticotropins. The
test should utilize the route(s) of administration proposed for
treatment. Following verification, 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, plasma and
urine corticosteroid levels and the initial response of the patient.
Only gradual change in dosage schedules should be attempted,
after full drug effects have become apparent.
The chronic administration of more than 40 units daily may be
associated with uncontrollable adverse effects.
When reduction in dosage is indicated this should be done gradually
by either reducing the amount of each injection, administering
injections at longer intervals or by a combination of both of the
above. During reduction of dosage careful consideration should be
given to the disease being treated, the general medical conditions
of the patient and the duration over which corticotropin was
administered.
The usual dose of H.P. Acthar Gel (Repository Corticotropin
Injection) is 40-80 units given intramuscularly or subcutaneously
every 24-72 hours.
In the treatment of acute exacerbations of multiple sclerosis
daily intramuscular doses of 80-120 units for 2-3 weeks may be
administered.
Preparation: H.P. Acthar Gel (Repository Corticotropin Injection)
should be warmed to room temperature before using.
product.
HOW SUPPLIED
H.P. Acthar Gel
(Repository Corticotropin Injection)
Presentation NDC
5 mL multi-dose vial 63004-7731-1
containing 80 USP
Units per mL
Storage: Store H.P. Acthar Gel (Repository Corticotropin Injection)
under refrigeration between 2 degrees -8 degrees C (36 degrees -46 degrees F).
Product is stable for the period indicated on the label when stored
under the conditions described.
Rev. 10/01 No. 1350 PL065/Rev.01
Manufactured for Questcor Pharmaceuticals, Inc.
Questcor Pharmaceuticals, Inc.
3260 Whipple Road
Union City, CA 94587 USA
phone (800) 411-3065
(510) 400-0700
fax (510) 400-0799
only
PM 210 Rev.02 01/06
| H.P. ACTHAR
corticotropin injection |
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| NDA | NDA008372 | 09/09/2005 | 02/24/2010 |
| Labeler - Questcor Pharmaceuticals (625130828) |
| Registrant - Cangene Biopharma (050783398) |
| Establishment | |||
| Name | Address | ID/FEI | Operations |
| Cangene Biopharma | 050783398 | manufacture | |