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DRUGDEX DRUG EVALUATIONS
COSYNTROPIN
0.0 OVERVIEW
A. Cosyntropin is a synthetic tetracosapeptide corresponding to the 1st through 24th amino acid
residues of natural adrenocorticotropin hormone and which has all the activity of the natural hormone.
B. DOSING INFORMATION: Cosyntropin may be administered intramuscularly or intravenously at
an adult dose of 0.25 to 0.75 mg over 2 min/0.25 mg as an adrenal function screening test; the 0.25-mg
dose dissolved in sterile saline and injected intramuscularly is most often recommended for this purpose.
The same doses may also be administered as infusions, added to dextrose or saline solutions and
administered at a rate of 0.04 mg/hr over 6 hours. The recommended pediatric (ages 2 yrs or less) dose
for this indication is 0.125 mg.
C. PHARMACOKINETICS: Cosyntropin is absorbed only following parenteral administration; it is
inactivated when given by mouth. When cosyntropin is administered, there is a prompt rise in the plasma
hydrocortisone level because of stimulated release from the adrenal glands. Following intramuscular
injection (with normally functioning adrenals), these elevated hydrocortisone levels peak at 1 hour and
decline back to baseline levels at 4 hours. Following intramuscular injection of the long-acting zinc
phosphate or hydroxide preparations (NOT available in the USA), peak adrenally-released plasma
hydrocortisone levels occur at 8 hours and remain elevated for greater than 24 hours.
D. CAUTIONS: Cosyntropin is administered only by injection in a health care facility setting; it is
generally NOT recommended for self-injection because of the danger of serious or fatal allergic
reactions. Painful local reactions may occur if the depot preparation is not injected deep intramuscularly.
Periorbital edema, cutaneous rash, and uncomfortable dizziness have been reported. Behavioral
deterioration has been reported in infants treated with adrenocorticotropin hormone for myoclonic
encephalopathy and infantile spasms. Adverse effects seen during corticotropin therapy for infantile
spasms include excessive weight gain, diarrhea, increased susceptibility to infections due to immune
suppression, worsening of mental state with either dejection or excessive nervousness, acne, menstrual
discharges, electrolyte and calcium abnormalities, hypertension with potential intracranial hemorrhage,
transient brain shrinkage noted on CT-scans, and rarely hematuria, melena, or hematemesis.
E. CLINICAL APPLICATIONS:
1. The main use of cosyntropin is as a diagnostic test for adrenocorticotropin hormone
insufficiency; it is also sometimes used to treat ulcerative colitis and Crohn's disease.
1.0 DOSING INFORMATION
1.1 DOSAGE FORMS
A. Information on specific dosage forms can be obtained by entering a brand name or trade
name at the "Type In Topic" screen or by choosing "ProdIndx."
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1.2 STORAGE AND STABILITY
A. PARENTERAL
1. The manufacturer recommends that constituted cosyntropin solutions NOT be retained
(Prod Info Cortrosin(R), 1991).
2. When constituted with 0.9 percent sodium chloride for injection, cosyntropin is stable for
24 hours at room temperature; it is stable for up to 21 days when refrigerated at between 2 and 8
degrees centigrade under a nitrogen atmosphere (see manufacturer's recommendation above, however)
(Reynolds, 1990).
3. In solutions with a pH between 5.5 and 7.5, cosyntropin is stable for 12 hours at room
temperature.
B. PH
1. A constituted cosyntropin solution has a pH between 5.5 and 7.5.
C. SOLUBILITY
1. Cosyntropin is soluble at 1 part in 70 parts of water (Reynolds, 1990).
1.3 ADULT DOSAGE
1.3.1 NORMAL DOSE
A. PARENTERAL
1. Cosyntropin may be administered intramuscularly or intravenously in an adult dose of
0.25 to 0.75 milligram as an ADRENAL FUNCTION SCREENING TEST; the 0.25 milligram dose dissolved
in sterile saline and intramuscularly injected is most often recommended for this purpose (Olin, 1990;
Gilman et al, 1990). The same doses may also be administered as infusions, added to dextrose or saline
solutions and administered at a rate of 0.04 milligram/hour over 6 hours (Olin, 1990).
2. The usual dose of the long-acting cosyntropin depot preparation (NOT available in the
USA) for all other indications (mainly ULCERATIVE COLITIS and CROHN'S DISEASE) is an initial adult
dose of 1 milligram intramuscularly daily (Reynolds, 1990). This dosage is reduced after acute effects are
controlled to 0.5 milligram every 2 to 3 days, or 1 milligram weekly; all doses of this preparation are
injected deep intramuscularly only.
3. A solution of 0.25 milligram of cosyntropin is equivalent to corticotropin (ACTH) 25 USP
units.
4. A low-dose ACTH test (1 mcg) has been recommended in hypothalamic-pituitaryadrenal axis assessment because results of it closely correlate with those of the insulin tolerance test
while avoiding potential problems of the latter test (Rasmuson et al, 1996).
1.4 PEDIATRIC DOSAGE
1.4.1 NORMAL DOSE
A. PARENTERAL
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1. The dose for children 2 years of age or less is generally 0.125 milligram intramuscularly
or injected intravenously over 2 minutes as a DIAGNOSTIC TEST FOR CORTICOTROPIN
INSUFFICIENCY (Olin, 1990).
2. A pediatric dose of 0.25 milligram/1.73 square meters of body surface area has also
been recommended for the CORTICOTROPIN INSUFFICIENCY TEST (Reynolds, 1990).
3. The recommended dose of the long-acting cosyntropin depot preparation (NOT
available in the USA) for all other indications (usually ULCERATIVE COLITIS and CROHN'S DISEASE)
are initial daily pediatric intramuscular doses of 0.25 milligram for children aged 1 month to 2 years; 0.25
to 0.5 milligram for children aged 2 to 5 years; and 0.25 to 1 milligram for those aged 5 to 12 years. Once
the acute effects are controlled, these same doses are given at 2- to 8-day intervals as maintenance
therapy (Reynolds, 1990).
2.0 PHARMACOKINETICS
2.1 ONSET AND DURATION
2.1.1 ONSET
A. INITIAL RESPONSE:
1. Adrenal insufficiency test, intramuscular: 1 hour (Reynolds, 1990)
a. When cosyntropin is administered, there is a prompt rise in the plasma
hydrocortisone level because of stimulated release from the adrenal glands. Following
intramuscular injection (with normally functioning adrenals), these elevated
hydrocortisone levels peak at 1 hour and decline back to baseline levels at 4 hours
(Reynolds, 1990).
b. Following intramuscular injection of the long-acting zinc phosphate or hydroxide
preparations (NOT available in the USA), peak adrenally-released hydrocortisone levels
occur at 8 hours (Reynolds, 1990).
2.1.2 DURATION
A. SINGLE DOSE:
1. Adrenal insufficiency test, intramuscular: Less than 4 hours (Reynolds, 1990)
a. Following intramuscular injection of the long-acting zinc phosphate or hydroxide
preparations (NOT available in the USA), peak adrenally-released hydrocortisone
levels remain elevated for greater than 24 hours (Reynolds, 1990).
2.3 ADME
2.3.1 ABSORPTION
A. BIOAVAILABILITY (F):
1. Parenteral, good (Reynolds, 1990)
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a. Cosyntropin is absorbed following parenteral administration only; it is inactivated
when given by mouth (Reynolds, 1990).
2.3.4 EXCRETION
2.3.4.1 BREAST MILK
A. BREASTFEEDING: Unknown
3.0 CAUTIONS
3.1 CONTRAINDICATIONS
A. Contraindicated in patients having had any type of allergic reaction to either natural
adrenocorticotropin hormone or cosyntropin; serious or potentially FATAL allergic reactions have
occurred, and 2 deaths have been reported in patients who had previous mild allergic reactions to
cosyntropin upon later administration of therapeutic doses (Reynolds, 1990).
3.2 PRECAUTIONS
A. The most worrisome possible side effects are serious or potentially fatal allergic reactions;
therefore, patients receiving cosyntropin should be monitored for at least one hour after administration in
a controlled setting (Reynolds, 1990) where medications and resuscitation equipment sufficient to treat
such reactions are available.
B. Painful local reactions will occur with the long-acting depot cosyntropin preparation (NOT
available in the USA) unless it is administered as a deep intramuscular injection (Burke, 1985).
C. Adverse effects seen during corticotropin therapy for infantile spasms include excessive
weight gain, diarrhea, increased susceptibility to infections due to immune suppression, worsening of
mental state with either dejection or excessive nervousness, acne, menstrual discharges, electrolyte and
calcium abnormalities, hypertension with potential intracranial hemorrhage, transient brain shrinkage
noted on computer-tomography scans, and rarely hematuria, melena, or hematemesis (Hrachovy & Frost,
1989; Fois et al, 1987; Dreifuss et al, 1986; Sorel, 1985).
3.3 ADVERSE REACTIONS
3.3.1 BLOOD
A. HEMATOLOGIC EFFECTS
1. SUBDURAL HEMATOMA and BRAIN ATROPHY occurred in an infant treated with
corticotropin for infantile spasms (Watanabe et al, 1981).
3.3.2 CARDIOVASCULAR
A. CARDIOVASCULAR EFFECTS
1. NECROTIZING ANGIITIS, CONGESTIVE HEART FAILURE, and CARDIAC
HYPERTROPHY have been associated with corticotropin administration (Prod Info
Acthar(R), 1990; Lang et al, 1984; Young et al, 1987).
B. EDEMA
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1. FLUID RETENTION is possible with corticotropin (Prod Info Acthar(R), 1990).
C. HYPERTENSION
1. Hypertension was reported in 7% (11/162) of children treated with corticotropin to
control infantile spasms. The intramuscular dose of corticotropin ranged up to 160 Units/day for 3
weeks, followed by 80 Units/day for 2 weeks, and a gradual withdrawal over the subsequent week
(Riikonen & Donner, 1980).
3.3.3 CENTRAL NERVOUS SYSTEM
A. Uncomfortable DIZZINESS has been reported with administration of the long-acting depot
cosyntropin preparation (Clemmensen & Andersen, 1984).
B. BEHAVIORAL DETERIORATION has been reported in infants treated with
adrenocorticotropin hormone or cosyntropin for myoclonic encephalopathy and infantile spasms (Rutgers
et al, 1988; Sorel, 1985).
3.3.4 ENDOCRINE/METABOLIC
A. HYPERNATREMIA
1. Hypernatremia severe enough to warrant discontinuation of cosyntropin therapy was
reported in one child treated for infantile spasms (Dreifuss et al, 1986).
B. ADRENAL HEMORRHAGE
1. Isolated cases of bilateral adrenal hemorrhage have been reported with intravenous
corticotropin infusions in patients with inflammatory bowel disease (Dunlap et al, 1989).
3.3.5 GASTROINTESTINAL
A. ULCER
1. PEPTIC ULCER, PANCREATITIS, ABDOMINAL DISTENSION, and ulcerative
ESOPHAGITIS have been associated with corticotropin injection (Prod Info Acthar(R), 1990;
Nakashima & Howard, 1977).
3.3.6 KIDNEY/GENITOURINARY
A. NEPHROTOXICITY
1. Four of 162 children with infantile spasms developed OLIGURIA and HYPERKALEMIA
associated with corticotropin administration (Riikonon & Donner, 1980).
3.3.8 OCULAR
A. OCULAR EFFECTS
1. Corticotropin may cause an increase in intraocular pressure, EXOPHTHALMOS, and
GLAUCOMA (Prod Info Acthar(R), 1990).
2. PERIORBITAL EDEMA has been reported with administration of the long-acting depot
cosyntropin preparation (Clemmensen & Andersen, 1984).
B. CATARACTS
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1. Posterior subcapsular cataracts developed in a 50-year-old female treated with
intramuscular injections of corticotropin 20 Units daily for 2.5 years (Williamson & Dalakos, 1967).
3.3.9 RESPIRATORY
A. PNEUMONIA
1. In a 16-year study of 162 children with infantile spasms treated with corticotropin,
infections, including pneumonias, were some of the most common adverse effects noted. Infections were
most frequently observed if the daily dose of corticotropin exceeded 120 Units (Riikonon &
Donner, 1980).
3.3.10 SKIN
A. DERMATOLOGIC EFFECTS
1. PETECHIAE, ECCHYMOSES, FRAGILE SKIN, ACNE, facial ERYTHEMA, increased
PERSPIRATION, and transient pain on injection and INDURATION with intramuscular or subcutaneous
injection of corticotropin have been reported (Prod Info Acthar(R), 1990).
2. A cutaneous RASH was noted in one patient treated with the long-acting depot
cosyntropin preparation when used in combination with chlorpromazine for prophylaxis against cisplatin
chemotherapy-induced nausea and vomiting (Colbert et al, 1983).
B. ERYTHEMA MULTIFORME
1. Exudative erythema multiforme developed following a single dose of corticotropin
(Soloshenko & Brailovskii, 1975).
C. SKIN DISCOLORATION
1. Pigmentation of the skin has occasionally been associated with corticotropin
administration (Levantine & Almeyda, 1973).
3.3.11 MUSCULOSKELETAL
A. MUSCULOSKELETAL EFFECTS
1. Prolonged administration of corticotropin can cause MUSCLE WEAKNESS, MUSCLE
WASTING, VERTEBRAL COMPRESSION FRACTURES, or FRACTURES of the long bones.
These are due to PROTEIN CATABOLISM (Prod Info Acthar(R), 1990; Gilman et al, 1990).
2. Painful local reactions will occur with the long-acting depot cosyntropin preparation
(NOT available in the USA) unless it is administered as a deep intramuscular injection (Burke, 1985).
B. OSTEONECROSIS
1. ASEPTIC NECROSIS of the femur developed 9 months after a 23-year-old multiple
sclerosis patient had been treated with a total of 1070 Units of corticotropin over a 16-day period (Good,
1974).
C. OSTEOPOROSIS
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1. In a 16-year study of 162 children with infantile spasms treated with corticotropin, 2
children developed osteoporosis (Riikonon & Donner, 1980).
3.3.12 OTHER
A. HYPERSENSITIVITY
1. ANAPHYLAXIS and hypersensitivity reactions can develop with corticotropin. The risk is
increased with prolonged administration (Prod Info Acthar(R), 1990; Shapiro, 1972). Cosyntropin was
successfully administered to a patient with an immediate cutaneous reaction to
porcine corticotropin (Lee et al, 1987).
2. The most worrisome possible side effects of cosyntropin are serious or potentially fatal
ALLERGIC REACTIONS; therefore, patients receiving cosyntropin should be monitored for at
least one hour after administration in a controlled setting where medications and resuscitation
equipment sufficient to treat such reactions are available (Reynolds, 1990).
B. OVERDOSE See POISINDEX(R) Management "CORTICOSTEROIDS"
C. SUPERINFECTIONS - GASTROINTESTINAL
1. In a 16-year study of 162 children with infantile spasms treated with corticotropin,
INFECTIONS, including those of the gastrointestinal tract, were some of the most common adverse
effects noted. Infections were most frequently observed if the daily dose of corticotropin exceeded 120
Units (Riikonon & Donner, 1980).
3.4 TERATOGENICITY/EFFECTS IN PREGNANCY
A. TERATOGENICITY
1. Natural corticotropin is classified as U.S. Food and Drug Administration's Pregnancy
Category C (Prod Info Acthar(R), 1990). Cosyntropin would most likely be similarly classified. See Drug
Consult reference: "PREGNANCY RISK CATEGORIES"
3.5 DRUG INTERACTIONS
3.5.1 DRUG-DRUG COMBINATIONS
A. TUBERCULIN
1. Summary: Reactivity to a tuberculin skin test may be depressed or suppressed for as
long as five to six weeks in patients receiving systemic corticosteroids (Prod Info Tubersol(R), 1995).
2. Adverse Effect: decreased reactivity to tuberculin
3. Clinical Management: Clinicians should be alerted to corticosteroid use in patients
receiving tuberculin skin tests. Further evaluation of the patient may be warranted if the
immunosuppression caused by corticosteroid use is thought to result in a false-negative test.
4. Severity: minor
5. Onset: delayed
6. Documentation: poor
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7. Probable Mechanism: immunosuppression
B. VACCINES
1. Summary: As a general rule, live-attenuated viral or bacterial vaccines should not be
administered to patients who are immunosuppressed as a result of large amounts of corticosteroids
(more than 10 mg of prednisone or equivalent for more than two weeks). However, an inadequate
response to inactivated vaccines may also occur with immunsuppression due to large doses of steroids.
Low- to moderate-dose short-term systemic corticosteroid therapy (less than 14 days), topical steroid
therapy, long-term alternative-day treatment with low to moderate doses of short-acting systemic steroids,
and intra-articular, bursal, or tendon injections of corticosteroids should not be considered
contraindications to vaccine administration (CDC, 1989). Likewise, doses of steroids given as
replacement therapy, such as in Addison's disease, are not considered immunosuppressive
(Grabenstein, 1990). The exact interval between discontinuing immunosuppressives and regaining the
ability to respond to individual vaccines is not known. Estimates vary from three months to one year
(Anon, 1991).
2. Adverse Effect: an inadequate immunological response to the vaccine
3. Clinical Management: If possible, delay the administration of vaccines, especially live
viral or bacterial types, in persons immunosuppressed with large doses of corticosteroids. However, the
clinical judgment of the responsible physician should prevail.
4. Severity: moderate
5. Onset: delayed
6. Documentation: fair
7. Probable Mechanism: suppression of the immune system
3.5.4 INTRAVENOUS ADMIXTURES
3.5.4.1 COMPATIBILITIES - SOLUTIONS
A. DEXTROSE SOLUTIONS
1. Dextrose solutions (recommended for the dilution of cosyntropin; conditions not
specified) (Trissel, 1990)
B. SODIUM CHLORIDE
1. Sodium chloride 0.9% (may be used for the reconstitution of cosyntropin to a
concentration of 25 IU/mL; reconstituted solution is stable for 24 hours at room temperature or 3 weeks
under refrigeration; may be used to further dilute cosyntropin, final concentration not stated, and solution
is stable for 12 hours at room temperature provided that pH of the solution is between 5.5 and 7.5)
(Kirschenbaum & Latiolais, 1976)
3.5.4.3 INCOMPATIBILITIES - SOLUTIONS
A. BLOOD
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1. Blood (may inactivate cosyntropin) (Trissel, 1990)
2. For More Information:
See Drug Consult reference: "BLOOD IV COMPATIBILITIES"
B. PLASMA
1. Plasma (may inactivate cosyntropin) (Trissel, 1990)
4.0 CLINICAL APPLICATIONS
4.1 MONITORING PARAMETERS
4.1.1 THERAPEUTIC
A. PHYSICAL EXAMINATION
1. The most worrisome possible side effects are serious or potentially fatal allergic
reactions; therefore, patients receiving cosyntropin should be monitored for at least one hour after
administration in a controlled setting where medications and resuscitation equipment sufficient to
treat such reactions are available (Reynolds, 1990).
2. The clinical disappearance of spasms and normalization (flattening) of the
electroencephalogram should be monitored; a temporary worsening of the behavioral state (either
dejected or hyperirritable) does NOT indicate the need to discontinue therapy (Sorel, 1985).
4.1.2 TOXIC
A. PHYSICAL EXAMINATION
1. The most worrisome possible side effects are serious or potentially fatal allergic
reactions; therefore, patients receiving cosyntropin should be monitored for at least one hour after
administration in a controlled setting where medications and resuscitation equipment sufficient to
treat such reactions are available (Reynolds, 1990).
4.2 PATIENT INSTRUCTIONS
A. HOW TO TAKE THIS MEDICATION
1. Cosyntropin is administered only by injection in a health care facility setting; it is generally
NOT recommended for self-injection because of the danger of serious or fatal allergic reactions
(Reynolds, 1990).
B. POSSIBLE SIDE EFFECTS FROM THIS MEDICATION
1. The most worrisome possible side effects are serious or potentially fatal allergic reactions;
therefore, patients receiving cosyntropin should be monitored for at least one hour after administration in
a controlled setting (Reynolds, 1990) where medications and resuscitation equipment sufficient to treat
such reactions are available.
2. Periorbital edema, cutaneous rash, and uncomfortable dizziness have been reported with
administration of the long-acting depot cosyntropin preparation (Clemmensen & Andersen, 1984; Colbert
et al, 1983).
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C. STORAGE INSTRUCTIONS FOR THIS MEDICATION
1. When constituted with 0.9 percent sodium chloride for injection, cosyntropin is stable for
24 hours at room temperature; it is stable for up to 21 days when refrigerated at between 2 and 8
degrees centigrade under a nitrogen atmosphere (Reynolds, 1990). Constituted solutions of pH 5.5 to 7.5
are stable for 12 hours at room temperature.
2. However, the manufacturer recommends that constituted solutions not be retained (Prod
Info Cortrosyn(R), 1991).
4.3 PLACE IN THERAPY
A. While cosyntropin may be used for any indication for which natural adrenocorticotropin
hormone (ACTH) is utilized (refer to corticotropin drug evaluation for more information), it is usually
restricted to use as a diagnostic testing agent for the investigation of corticotropin insufficiency, and
sometimes for the treatment of ulcerative colitis or Crohn's disease (Reynolds, 1990).
B. In much of the literature, it is unclear whether natural ACTH or cosyntropin was administered
for a large variety of indications including diagnosis of corticotropin insufficiency, acute gout, GuillainBarre' syndrome, control of infantile spasms (West's syndrome) and childhood seizures, Bell's palsy,
multiple sclerosis, rheumatic diseases, vitiligo, myasthenia gravis, herpes zoster, asthma and status
asthmaticus, ulcerative colitis, diagnosis of Sheehan's syndrome, adjunct to smoking cessation,
schizophrenia, hay fever, myoclonic encephalopathy, acute inflammatory polyneuropathy, and prevention
of peripheral neuropathy, nausea, and vomiting during cisplatin chemotherapy.
4.4 MECHANISM OF ACTION/PHARMACOLOGY
A. MECHANISM OF ACTION
1. Cosyntropin is a synthetic tetracosapeptide corresponding to the 1st through 24th amino
acid residues of natural adrenocorticotropin hormone and which has all the activity of the natural
hormone to stimulate release of corticoid hormones by the adrenal gland (Reynolds, 1990; Gilman et al,
1990; Prod Info Cortrosyn(R), 1991).
2. While cosyntropin may be used for any indication for which natural ACTH is utilized (refer
to corticotropin drug evaluation for more information), it is usually restricted to use as a diagnostic testing
agent for the investigation of corticotropin insufficiency and occasionally for the treatment of ulcerative
colitis or Crohn's disease (Reynolds, 1990).
4.5 THERAPEUTIC USES
A. ASTHMA
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective;
pediatric, possibly effective
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DOCUMENTATION: Adult, fair; pediatric, fair
2. SUMMARY: Adrenocorticotropin hormone (ACTH) has improved respiratory status in
adults with status asthmaticus and children with asthma, although it does not appear to protect against
subclinical lung changes in asthmatic children.
3. ADULT:
a. Adrenocorticotropin hormone (ACTH) 40 Units (equivalent to 0.4 milligram of
cosyntropin) was given intravenously every 8 hours in addition to corticosteroids and aminophylline in 15
patients with STATUS ASTHMATICUS not responsive to intensive standard therapy (Sarkar et al, 1985).
Improvement was noted in 48 to 72 hours, and more invasive measures such as intubation and muscle
paralysis were avoided. The authors speculated that a pharmacologic effect of ACTH was responsible for
the noted improvement in respiratory status, as the adrenal cortex would be expected to be suppressed
from the large doses of corticosteroids already administered when ACTH was added to the regimen.
4. PEDIATRIC:
a. In a 5-year follow-up study of 21 children aged 6 to 17 years with severe bronchial
asthma treated with systemic corticosteroids and/or adrenocorticotropin hormone (ACTH) (preparation(s)
and doses not specified) for at least 2 years, subjective improvement and a decreased need for corticoid
and bronchodilator therapy was noted in this group, despite the fact that progressive subclinical
bronchial obstructive changes and hyperinflation of the lungs were found on pulmonary function testing
(Oberger & Engstrom, 1981). These findings suggest that corticoid (including ACTH) therapy may be
beneficial in severe CHILDHOOD ASTHMA, but may not prevent progression of lung changes. As no
control group with a similar severity of asthma was compared, it cannot be said whether or not corticoid
therapy may potentially attenuate the severity of the noted lung changes.
B. BELL'S PALSY
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
2. SUMMARY: In a comparison study of 28 patients with Bell's palsy, of the 7 patients who
received adrenocorticotropin hormone (preparation and dose not stated) 4 (57%) had full recovery and 2
(28%) had partial recovery (Al-Husaini et al, 1986).
3. ADULT:
a. In this study, an unfavorable outcome was associated with a delay of more than 24
hours in beginning treatment. A high titer for rubella was also associated with treatment failure or only
partial recovery in the 4 patients whose treatment was delayed (Al-Husaini et al, 1986). Of the 21 patients
treated with oral prednisone at a dose of 60 milligrams daily for 6 days with doses then tapered over 4
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days, complete recovery occurred in 12 (57%), partial recovery was noted in 7 (33%), and there were 2
treatment failures.
C. CORTICOTROPIN INSUFFICIENCY DIAGNOSTIC TEST
FDA Labeled Indication
1. OVERVIEW:
FDA APPROVAL: Adult, yes; pediatric, yes
EFFICACY: Adult, effective; pediatric, effective
DOCUMENTATION: Adult, good; pediatric, good
2. SUMMARY: The smallest recommended doses of the regular cosyntropin preparation
have resulted in maximal adrenal stimulation (Olin, 1990). The long-acting zinc phosphate or hydroxide
cosyntropin preparation is not used initially for this test (Reynolds, 1990).
3. ADULT:
a. Plasma cortisol concentrations are measured immediately before and exactly 30
minutes after intramuscular or intravenous injection of 0.25 milligram (adults) of cosyntropin (Olin, 1990;
Reynolds, 1990; Burke, 1985). Alternatively, a single plasma cortisol sample can be drawn at 45 minutes
after injection (Burke, 1985). Better results may be obtained by intravenous infusion of 0.04 milligram of
cosyntropin in a dextrose or saline solution per hour over 6 hours (Olin, 1990). Normal adrenal function is
indicated by an increase in the plasma cortisol concentration of at least 70 micrograms/liter (200
nanomoles/liter) (Reynolds, 1990). A measured plasma cortisol level of 20 micrograms/deciliter (550
nanomoles/liter) at any time after cosyntropin injection rules out adrenal insufficiency of any etiology
(Burke, 1985). In a patient with Sheehan's syndrome, infusion of 0.25 milligram of cosyntropin over 8
hours produced a rise in serum cortisol from 1 to 23 micrograms/milliliter (Giustina et al, 1985).
b. If a test with the regular preparation is equivocal, then an adult dose of 1 milligram of
the long-acting cosyntropin depot preparation (NOT available in the USA) may be given intramuscularly
and plasma cortisol levels measured (Reynolds, 1990; Burke, 1985). The usual adult dose of long-acting
depot cosyntropin is 1 to 2 milligrams (Burke, 1985). Normal adrenal function is indicated by a steady
increase of plasma cortisol levels to between 1,000 and 1,800 nanomoles/Liter by 5 hours after
cosyntropin administration (Reynolds, 1990). Peak plasma cortisol levels in normal individuals occur at 4
to 6 hours after cosyntropin administration, and may be 30 micrograms/deciliter (900 nanomoles/Liter) or
greater (Burke, 1990). Some cases of secondary adrenal failure may be detected in the depot
cosyntropin test, as the long-acting preparation may stimulate some function in a "sleepy" adrenal,
manifested as an increased plasma cortisol in a sample obtained at 12 to 24 hours after depot
cosyntropin administration (Burke, 1985).
c. Secondary adrenocortical insufficiency cannot be excluded by a lack of plasma cortisol
response at 12 to 24 hours after depot cosyntropin administration; a prolonged stimulation test is required
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(Burke, 1985). The prolonged depot cosyntropin test consists of administration of 3 separate deep
intramuscular injections of the long-acting preparation (NOT available in the USA) at 48-hour intervals in a
dose of 1 milligram. Plasma cortisol levels are obtained at 24 hours after each injection. Nearly all
patients with adrenocorticotropin hormone deficiency will have some increase in plasma cortisol levels by
the 6th day; those with Addison's disease will have NO response (Burke, 1985).
d. A low-dose ACTH test (1 mcg) has been recommended in hypothalamic-pituitaryadrenal axis assessment because results of it closely correlate with those of the insulin tolerance test
while avoiding potential problems of the latter test (Rasmuson et al, 1996).
4. PEDIATRIC:
a. Plasma cortisol concentrations are measured immediately before and exactly 30
minutes after intramuscular or intravenous injection of 0.125 milligram (0.25 milligram per 1.73 square
meters of body surface area) (children aged 2 years or less) of cosyntropin (Olin, 1990; Reynolds, 1990;
Burke, 1985). Alternatively, a single plasma cortisol sample can be drawn at 45 minutes after injection
(Burke, 1985). In one reported case, a 6-month-old child was successfully tested with 0.25 milligram
intravenously and found to have secondary adrenocortical insufficiency (Carey, 1985).
D. GOUT - ACUTE
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
2. SUMMARY: In one study adrenocorticotropin hormone effectively reduced acute gout
pain.
3. ADULT:
a. In a comparison study of adrenocorticotropin hormone (ACTH) versus oral
indomethacin for the treatment of acute gouty attacks, a single intramuscular injection of ACTH at a dose
of 40 Units (equivalent to 0.4 milligram of cosyntropin) produced no side effects and significantly
lessened the interval to relief of pain when compared to oral indomethacin at a dose of 50 milligrams 4
times daily until pain subsided (Axelrod & Preston, 1988). A number of gastrointestinal and
neuropsychological side effects were reported in the indomethacin group.
E. HAY FEVER
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
14
2. SUMMARY: In a study of 14 patients with hay fever, a dose of 200 Units of corticotropin
was superior to a dose of 80 Units (doses given every two weeks) in producing symptomatic relief
(equivalent doses of cosyntropin, 2 milligrams and 0.8 milligram) (Parr & Davies, 1980). No placebo
controls were compared in this study.
F. INFANTILE SPASMS
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Pediatric, effective
DOCUMENTATION: Pediatric, good
2. SUMMARY: Corticotropin, both natural and synthetic, have been considered efficacious
for the treatment of infantile spasms (WEST'S SYNDROME) (Hrachovy & Frost, 1989; De Negri et al, 1988;
Fois et al, 1987; Dreifuss et al, 1986; Sorel, 1985). However, adverse effects can be severe, and some
children develop other seizure disorders after control of infantile spasms.
3. PEDIATRIC:
a. In 39 children aged 2 months to 9 years undergoing treatment with corticotropin
(preparation not specified) at a dose of 0.025 milligram/kilogram as daily injections for two weeks and
then tapering, for a variety of seizure disorders including infantile spasms, Doppler ultrasound studies
of cerebral blood flow revealed a significant decrease in the average maximal blood velocity and
maximal end-diastolic blood velocity in the internal carotid artery. These values were already decreased
by 30 minutes after the first corticotropin injection, and were only nearly returned to baseline 24 hours
later when the next dose was administered. The changes became minimal after one week of corticotropin
therapy, and gradually increased to baseline levels after 8 weeks of treatment (Futagi et al, 1988).
b. Thirty-three children (8 with idiopathic disease; 5 with secondary disease) were treated
with a regimen of 2 Units of adrenocorticotropin hormone/kilogram of body weight for 10 days followed by
10 Units/kilogram on alternate days for a further 20 days (Fois et al, 1987). In 5 of the 8 children with
idiopathic disease, 5 had complete clinical and electroencephalogram normalization. In children with
secondary disease, 2 had complete normalization and 15 others improved. The only side effects noted
were frequent hyperirritability, moderate weight gain, and diarrhea.
c. One dosing regimen for the long-acting depot cosyntropin preparation (NOT available
in the USA) for a 6-month-old, approximately 8-kilogram child is to begin with 0.1 milliliter (0.1 milligram)
injected intramuscularly for 4 days, increasing the dosage by 0.1 milliliter (0.1 milligram) per day every 4
days until the spasms cease and electroencephalogram flattens; the dose required to bring about these
changes is considered the plateau dose and should be continued daily for one month. After one month of
daily intramuscular injections of the plateau dose, the daily dose is gradually reduced by 0.1-milliliter (0.1
milligram) increments until treatment is concluded over about 2-1/2 to 3 months. Shorter treatment
15
regimens carry the danger of recidivism. In primary cases where there is no pre-existing brain lesion, a
total cure (with the exception of minor psychomotor difficulties) may be expected in about 80 percent of
patients if corticotropin therapy is begun within 6 weeks of the onset of the illness. In children 1.5 to 5
years of age, the long-acting cosyntropin preparation (NOT available in the USA) may be added to oral
therapy with hydrocortisone during the first month of treatment at a dose of between 0.5 milliliter (0.5
milligram) to 1 milliliter (1 milligram) intramuscularly between 1 and 3 times weekly depending on the
child's age (Sorel, 1985).
d. Forty-eight children less than 2 years of age with infantile spasms were studied to
compare 4 weeks of treatment with corticotropin at a daily intramuscular dose of 40 Units (equivalent to
0.4 milligram of cosyntropin per day) with nitrazepam at a dose of between 0.2 and 0.4
milligram/ kilogram/day (maximum dose 1 milligram) given in two divided doses (Dreifuss et al, 1986).
There was no significant difference between the two treatment groups in the reduction of spasm
frequency; both resulted in a significant decrease in this parameter. However, although there were more
side effects noted with nitrazepam, those seen with corticotropin were more severe and necessitated
discontinuation of therapy in 6 cases.
e. In a double-blind crossover study of low-dose corticotropin (20 to 30 Units/day;
equivalent to 0.2 to 0.3 milligram of cosyntropin/day) versus prednisone 2 milligrams/day, both given for 2
to 6 weeks, no major difference in electroencephalogram (EEG) improvement or stopping the spasms
was demonstrated; about 60 to 70 percent of children responded to either one or the other medication.
No graded responses were noted in this study; control of the spasms was either all or none, and the
therapy could be discontinued once control was achieved. Patients who continued to have spasms had
relative normalization of the EEG, calling into question the usefulness of this test for monitoring the
response to therapy. In this study, the overall long-term prognosis was poor; only 5 percent of the
children had a normal outcome and 69 percent had severe to very severe neurological impairment. This
may have been due to the inclusion of greater numbers of children with pre-existing brain lesions. Early
treatment was NOT associated with a better outcome in this study. About half of patients with infantile
spasms develop other types of seizures once the spasms stop (Hrachovy & Frost, 1989).
G. MULTIPLE SCLEROSIS SYMPTOMS
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
2. SUMMARY: Although corticotropin has been said to be "well accepted in the symptomatic
treatment of multiple sclerosis" (Kiessling, 1987), dexamethasone at tapered doses beginning at 8
milligrams/day for 7 days was more effective in one study (Milanese et al, 1989) and methylprednisolone
16
at an intravenous dose of 1 gram/day for 3 days was equally efficacious (Thompson et al, 1989) in
producing symptomatic relief.
3. ADULT:
a. In another study of 55 patients, 2 weeks of bed rest was equally efficacious as bed rest
plus depot cosyntropin therapy (1 milligram intramuscularly daily for 5 days and then tapered)
(Hoogstraten et al, 1987). However, some authors have stated that corticotropin (including cosyntropin) is
superior to corticosteroids in the symptomatic treatment of multiple sclerosis and may have fewer side
effects, particularly in patients with diabetes or hypertension (Poser, 1989). Suggested mechanisms of
action of cosyntropin in multiple sclerosis include direct regulation of antibody response, direct effect on
neural function (possibly acting as a neurotransmitter), interaction with corticotropin receptors on
lymphocytes, or binding to opioid receptors (Poser, 1989; Troiano et al, 1989; Davis & Stefoski, 1988).
The effects of cosyntropin in multiple sclerosis appear to be cumulative, with little or no response noted
before 5 or 6 injections are given (Poser, 1989).
b. A study of 15 patients thought to have multiple sclerosis who received 40 Units of
adrenocorticotropin hormone daily (equivalent to 0.4 milligram of cosyntropin) had a decrease in
dysphoria and a significant decrease in total mood scores by the 3rd day of treatment; a comparison
group (2 patients with multiple sclerosis; 6 with various dermatological conditions) given oral prednisone
in an average daily dose of 51 milligrams (followed by dose tapering to an average daily dose of 30
milligrams on day 10) had similar effects, but a difference was not noted until day 7 of prednisone
treatment (Cameron et al, 1985).
H. MYOCLONIC ENCEPHALOPATHY
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Pediatric, ineffective
DOCUMENTATION: Pediatric, poor
2. SUMMARY: Two infants with mycolonic encephalopathy did not benefit from treatment with
adrenocorticotropin hormone.
3. PEDIATRIC:
a. In two patients aged 15 and 20 months with myoclonic encephalopathy (KINSBOURNE
SYNDROME) exhibiting myoclonus, opsoclonus, ataxia, and irritability, treatment with adrenocorticotropin
hormone (ACTH) 40 Units daily (equivalent to 0.4 milligram of cosyntropin) was associated with a
behavior deterioration to extreme dullness and depression which lasted for 3 to 4 weeks despite
improvement in the signs of the presenting disease. When prednisone was substituted for the ACTH, a
striking improvement in the behavioral state was noted; both patients had relatively normal neurological
development with slight disturbances a few years later (Rutgers et al, 1988).
17
I. NAUSEA AND VOMITING
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, effective
DOCUMENTATION: Adult, fair
2. SUMMARY: The combination of cosyntropin and chlorpromazine before cisplatin
administration effectively diminished nausea and vomiting in one study.
3. ADULT:
a. A combination of chlorpromazine in a dose of 50 milligrams injected intramuscularly 30
minutes before cisplatin administration and the long-acting cosyntropin depot preparation injected
intramuscularly 24 and 12 hours, and immediately before cisplatin administration at 1 milligram per dose,
decreased the incidence of VOMITING and duration of nausea compared to placebo plus
chlorpromazine given in a similar regimen (Colbert et al, 1983). Of the 19 patients who received
cosyntropin plus chlorpromazine in this study, 8 had no nausea or vomiting at all, compared with only one
patient in the placebo-plus-chlorpromazine group.
J. PERIPHERAL NEUROPATHY PREVENTION
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
2. SUMMARY: In a double-blind, randomized, placebo-controlled study of 55 women
receiving cisplatin chemotherapy for ovarian cancer, concomitant administration of an
adrenocorticotropin hormone analogue (Org 2766) in a dose of 1 milligram every three weeks prevented
or attenuated the development of CISPLATIN-INDUCED PERIPHERAL NEUROPATHY (van der Hoop et
al, 1990). With an Org 2766 dose of 0.25 milligram every three weeks concomitantly with cisplatin, the
protective effects were less prominent.
K. POLYNEUROPATHY - INFLAMMATORY
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, poor
2. SUMMARY: In one study of acute INFLAMMATORY POLYNEUROPATHY, intramuscular
administration of adrenocorticotropin hormone 100 Units daily for 10 days (equivalent to 1 milligram of
cosyntropin) did not produce any immediate improvement, but was associated with shortening of the
disease duration; paradoxically, the duration of hospitalization was longer in the corticotropin-treated
18
patients compared to untreated controls (Hughes et al, 1981).
L. SCHIZOPHRENIA
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
2. SUMMARY: In a single case, a teenaged girl with schizophrenia improved in mental state
on 6 occasions after having received corticotropin injections.
3. ADULT:
a. A single case was reported of a teenaged girl with schizophrenia that failed to respond
to therapy with a wide variety of standard antipsychotic medications, psychotherapy, and
electroconvulsive therapy (ECT) who had improvement in mental state beginning 2 hours after injection of
1 milligram of corticotropin (preparation not specified) that lasted for 2 days on 6 separate occasions
(Salimi-Eshkevari, 1983). This patient had previously had an improved mental state while being treated
with prednisolone, apparently for an unrelated condition.
M. SEIZURES
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Pediatric, possibly effective
DOCUMENTATION: Pediatric, fair
2. SUMMARY: In one study 55% of children with myoclonic/akinetic seizures benefited from
daily treatment with cosyntropin, while children with other kinds of seizures did not respond.
3. PEDIATRIC:
a. Seventeen children with intractable seizures other than infantile spasms were treated
with corticotropin at a starting dose of 3 to 6 Units/kilogram/day (equivalent of 0.03 to 0.06 milligram of
cosyntropin daily), tapered to the same dose every other day in the second week of therapy, for an
average duration of 5.9 weeks (Dooley et al, 1989). In 5 (55.6 percent) of the 8 children with
myoclonic/akinetic seizures, a remission of seizures lasting at least one year was noted; none of the 9
children with intractable generalized clonic or complex partial seizures responded to this therapy (Dooley
et al, 1989). No serious side effects were noted in this study.
N. SHINGLES
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
19
2. SUMMARY: Both chickenpox and shingles (ZOSTER) are caused by VARICELLA-ZOSTER
INFECTION. The primary infection is called chickenpox. After the primary infection, the virus may persist
in a latent form. Activation of the virus results in shingles (zoster) (Peter et al, 1988).
3. ADULT:
a. The long-acting cosyntropin depot preparation (NOT available in the USA) at a dose of
1 milligram, three times weekly for a total of 7 injections, produced a decrease in analgesic consumption
and subjective pain scores during the first 4 days when compared to placebo and prednisone in a group
of 60 patients with HERPES ZOSTER; the development of postherpetic neuralgia was not affected,
although the groups may have been too small to detect a significant difference (Clemmensen &
Andersen, 1984). The healing process of vesicle and crust formation was also not affected by
cosyntropin therapy in this study.
O. SMOKING CESSATION
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
2. SUMMARY: Corticotropin has been used to suppress the symptoms of NICOTINE
WITHDRAWAL SYNDROME as an adjunctive therapy in smoking cessation programs, and has been said
to increase the possibility of long-term tobacco abstinence (Targovnik, 1989).
3. ADULT:
a. In a small case series of patients treated with 3 injections of adrenocorticotropin
hormone at doses of 160 Units, 80 Units, and 40 Units at 3-day intervals (equivalent to cosyntropin doses
of 1.6 milligrams, 0.8 milligram, and 0.4 milligram), complete cigarette abstinence or an 80 to 90 percent
decrease in the number of cigarettes smoked daily was seen in 13 of 15 patients (McElhaney, 1989). No
placebo controls were compared in this study.
P. ULCERATIVE COLITIS
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, possibly effective
DOCUMENTATION: Adult, fair
2. SUMMARY: Cosyntropin appears to benefit patients with ulcerative colitis who have not
previously been treated with corticosteroids.
3. ADULT:
a. A group of 66 hospitalized patients with exacerbations of ulcerative colitis were studied
in a prospective, double-blind trial of intravenous hydrocortisone (300 milligrams/day) or corticotropin
20
(120 Units/day; equivalent to 1.2 milligrams/day of cosyntropin) (Meyers et al, 1983). In this study,
corticotropin was more effective in producing a remission in patients who had not been previously treated
with corticosteroids, while hydrocortisone was more effective in patients who had previously received
corticosteroid therapy.
b. In an editorial commenting on the above study, it was noted that a randomized clinical
trial of corticotropin versus placebo in the treatment of exacerbations of ulcerative colitis has never been
done, although corticotropin has widespread acceptance as a therapeutic agent for this indication.
There is evidence that while corticotropin or oral cortisone have equivalent activity in patients
experiencing a first attack of ulcerative colitis, adrenocorticotropin hormone may be more effective in
patients having a relapse. However, corticotropin should not be considered for those patients already
receiving oral corticosteroid therapy (Peppercorn, 1983).
4.6 COMPARATIVE EFFICACY AND EVALUATION WITH OTHER SIMILAR THERAPEUTIC AGENTS
A. CORTICOTROPIN
1. GOUT
a. In a comparison study of adrenal corticotropic hormone (ACTH) versus oral indomethacin
for the treatment of acute gouty attacks, a single intramuscular injection of ACTH at a dose of 40 Units
(equivalent to 0.4 milligram of cosyntropin) produced no side effects and significantly lessened the
interval to relief of pain when compared to oral indomethacin at a dose of 50 milligrams 4 times daily
until pain subsided (Axelrod & Preston, 1988). A number of gastrointestinal and neuropsychological
side effects were reported in the indomethacin group.
2. INFANTILE SPASMS
a. In a double-blind crossover study of low-dose corticotropin (20 to 30 Units/day; equivalent
to 0.2 to 0.3 milligram of cosyntropin/day) versus predisone 2 milligrams/day, both given for 2 to 6 weeks,
no major difference in electroencephalogram improvement or stopping the spasms was demonstrated;
about 60 to 70 percent of children responded to either one or the other medication. No graded
responses were noted in this study; control of the spasms was either all or none, and the therapy could
be discontinued once control was achieved. Patients who continued to have spasms had relative
normalization of the electroencephalogram, calling into question the usefulness of this test for monitoring
the response to therapy (Hrachovy & Frost, 1989).
b. Four weeks of treatment with corticotropin at a daily intramuscular dose of 40 Units
(equivalent to 0.4 milligram of cosyntropin per day) were compared with nitrazepam at a dose of between
0.2 and 0.4 milligram/kilogram/day (maximum dose 1 milligram) given in two divided doses in 48 children
less than 2 years of age with infantile spasms. There was no significant difference between the two
treatment groups in the reduction of spasm frequency; both resulted in a significant decrease in this
21
parameter. However, although there were more side effects noted with nitrazepam, those seen with
corticotropin were more severe and necessitated discontinuation of therapy in 6 cases (Dreifuss et al,
1986).
3. MULTIPLE SCLEROSIS
a. Although corticotropin has been said to be "well accepted in the symptomatic treatment of
multiple sclerosis" (Kiessling, 1987), dexamethasone at tapered doses beginning at 8 milligrams/day for 7
days was more effective in one study (Milanese et al, 1989) and methylprednisolone at an intravenous
dose of 1 gram/day for 3 days was equally efficacious (Thompson et al, 1989) in producing symptomatic
relief.
b. A study of 15 patients thought to have multiple sclerosis who received 40 Units of ACTH
daily (equivalent to 0.4 milligram of cosyntropin) had a decrease in dysphoria and a significant decrease
in total mood scores by the 3rd day of treatment; a comparison group (2 patients with multiple sclerosis;
6 with various dermatological conditions) given oral prednisone in an average daily dose of 51 milligrams
(followed by dose tapering to an average daily dose of 30 milligrams on day 10) had similar effects, but
a difference was not noted until day 7 of prednisone treatment (Cameron et al, 1985).
c. Some authors have stated that corticotropin (including cosyntropin) is superior to
corticosteroids in the symptomatic treatment of multiple sclerosis and may have fewer side effects,
particularly in patients with diabetes or hypertension (Poser, 1989).
d. When used for the symptomatic treatment of multiple sclerosis, remarkably fewer side
effects have been noted with cosyntropin compared to natural corticotropin (ACTH) (Poser, 1989).
4. PHARMACOLOGY
a. Cosyntropin is a synthetic tetracosapeptide corresponding to the 1st through 24th amino
acid residues of natural adrenocorticotropin hormone (ACTH) and has all the activity of the natural
hormone; it increases the rate of excretion of corticoid hormones by the adrenal gland (Olin, 1990;
Reynolds, 1990; Prod Info Cortrosyn(R), 1991). While cosyntropin may be used for any indication for
which natural ACTH is utilized, it is usually restricted to diagnostic testing for corticotropin insufficiency
and occasionally is used for ulcerative colitis or Crohn's disease (Reynolds, 1990).
B. METHYLPREDNISOLONE
1. EMESIS - CHEMOTHERAPY-INDUCED
a. Methylprednisolone and cosyntropin (tetracosactrin) demonstrate equivalent antiemetic
activity in breast cancer patients receiving epirubicin, 5-fluorouracil, and cyclophosphamide (FEC).
Intravenous 40 mg or intramuscular cosyntropin 0.5 mg were administered to 97 patients just prior to
chemotherapy. Objectively, the results were NOT significantly different; however, more patients
subjectively preferred cosyntropin (Bonneterre et al, 1991).
22
C. PREDNISONE
1. SHINGLES
a. GENERAL INFORMATION: Both chickenpox and shingles (ZOSTER) are caused by
VARICELLA-ZOSTER INFECTION. The primary infection is called chickenpox. After the primary
infection, the virus may persist in a latent form. Activation of the virus results in shingles (zoster)
(Peter et al, 1988).
b. The long-acting cosyntropin depot preparation (NOT available in the USA) at a dose of 1
milligram, three times weekly for a total of 7 injections, produced a decrease in analgesic consumption
and subjective pain scores during the first 4 days when compared to placebo and prednisone in a group
of 60 patients with herpes zoster; the development of postherpetic neuralgia was not affected, although
the groups may have been too small to detect a significant difference (Clemmensen & Andersen, 1984).
The healing process of vesicle and crust formation was also not effected by cosyntropin therapy in this
study.
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Original publication: 12/90
Most recent revision: 12/97