Acthrel

Name: Acthrel

What is Acthrel (corticorelin ovine triflutate)?

Corticorelin ovine triflutate is a man-made form of a hormone that occurs naturally in the body.

Corticorelin ovine triflutate is used as part of a medical test in people with Cushing's syndrome. Cushing syndrome is caused by high levels of cortisol (a steroid hormone produced by the adrenal gland).

Corticorelin ovine triflutate is also used to help your doctor determine why your body is producing too much of its own cortisol.

Corticorelin ovine triflutate may also be used for purposes not listed in this medication guide.

Acthrel (corticorelin ovine triflutate) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your caregiver right away if you have:

  • chest pain or pressure, fast heart rate;

  • trouble breathing, feeling like you can't get enough air;

  • severe redness or warmth in your face; or

  • a light-headed feeling, like you might pass out.

Common side effects may include:

  • flushing (warmth, redness, or tingly feeling) in your face, neck, or chest.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Commonly used brand name(s)

In the U.S.

  • Acthrel

Available Dosage Forms:

  • Powder for Solution

Therapeutic Class: Diagnostic Agent

How is this medicine (Acthrel) best taken?

Use Acthrel as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as a shot into a vein.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Chest pain or pressure or a fast heartbeat.
  • Very bad dizziness or passing out.
  • Shortness of breath.
  • Wheezing.
  • Flushing.

Indications and Usage for Acthrel

Acthrel® is indicated for use in differentiating pituitary and ectopic production of ACTH in patients with ACTH-dependent Cushing's syndrome.

Differential Diagnosis

There are two forms of Cushing's syndrome:

  1. ACTH-dependent (83%), in which hypercortisolism is due either to pituitary hypersecretion of ACTH (Cushing's disease) resulting from an adenoma (40%, usually microadenomas) or nonadenomatous hyperplasia, possibly of hypothalamic origin (28%), or to hypercortisolism that is secondary to ectopic secretion of ACTH (15%) and,

  2. ACTH- independent (17%), in which hypercortisolism is due to autonomous cortisol secretion by an adrenal tumor (9% adenomas, 8% carcinomas).

After the establishment of hypercortisolism consistent with the presence of Cushing's syndrome, and following the elimination of autonomous adrenal hyperfunction as its cause, the corticorelin test is used to aid in establishing the source of excessive ACTH secretion.

The corticorelin stimulation test helps to differentiate between the etiologies of ACTH-dependent hypercortisolism as follows:

1. High basal plasma ACTH plus high basal plasma cortisol (20 - 40 mcg/dL). Acthrel® injection (1 mcg/kg) results in:
  1. Increased plasma ACTH levels
  2. Increased plasma cortisol levels
    Diagnosis: Cushing's disease (ACTH of pituitary origin)
2 High basal plasma ACTH (may be very high) plus high basal plasma cortisol (20 - 40 mcg/dL). Acthrel® injection (1 mcg/kg) results in:
  1. Little or no response of plasma ACTH levels
  2. Little or no response of plasma cortisol levels
Diagnosis: Ectopic ACTH syndrome

Test Methodology

To evaluate the status of the pituitary-adrenal axis in the differentiation of a pituitary source from an ectopic source of excessive ACTH secretion, a corticorelin test procedure requires a minimum of five blood samples.

Procedure
  1. Venous blood samples should be drawn 15 minutes before and immediately prior to Acthrel® administration. The ACTH baseline is obtained by averaging the values of the two samples.

  2. Administer Acthrel® as an intravenous infusion over a 30 to 60- second interval at a dose of 1 mcg/kg body weight. Higher doses are not recommended (see PRECAUTIONS and ADVERSE REACTIONS).

  3. Draw venous blood samples at 15, 30, and 60 minutes after administration.

  4. Blood samples should be handled as recommended by the laboratory that will determine their ACTH content. It is extremely important to recognize that the reliability of the Acthrel® test is directly related to the inter-assay and intra-assay variability of the laboratory performing the assay.

Cortisol determinations may be performed on the same blood samples for the same time points as outlined above. The blood sample handling precautions noted for ACTH should be followed for cortisol.

Interpretation of Test Results

The interpretation of the ACTH and cortisol responses following Acthrel® administration requires a knowledge of the clinical status of the individual patient, understanding of hypothalamic-pituitary-adrenal physiology, and familiarity with the normal hormonal ranges and the standards used by the laboratory that performs the ACTH and cortisol assays.

Cushing's Disease

The results of challenge with corticorelin injection have been reported in approximately 300 patients with Cushing's disease. Although the ACTH and cortisol responses were variable, a hyper-response to corticorelin was seen in a majority of patients, despite high basal cortisol levels. This response pattern indicates an impairment of the negative feedback of cortisol on the pituitary. Patients with pituitary-dependent Cushing's disease tested with corticorelin do not show the negative correlation between basal and stimulated levels of ACTH and cortisol that is found in normal subjects. A positive correlation between basal ACTH levels and maximum ACTH increments after corticorelin administration has been found in Cushing's disease patients.

Ectopic ACTH Secretion

Patients with Cushing's syndrome due to ectopic ACTH secretion (N=32) were found to have very high basal levels of ACTH and cortisol, which were not further stimulated by corticorelin. However, there have been rare instances of patients with ectopic sources of ACTH that have responded to the corticorelin test.

SUMMARY OF ACTH RESPONSES IN PATIENTS WITH HIGH BASAL CORTISOL
  High ACTH Response Low ACTH Response
High Basal ACTH Cushing's Disease Ectopic ACTH Secretion

CUSHING'S DISEASE ACTH RESPONSES
(mean of 181 patients)
Basal ACTH 63 ± 72 pg/mL (mean ± SD)
Peak ACTH 189 ± 262 pg/mL (mean ± SD)
Mean of individual change from baseline + 227%

ECTOPIC ACTH SECRETION RESPONSES
(mean for 31 patients)
Basal ACTH 266 ± 464 pg/mL (mean ± SD)
Peak ACTH 276 ± 466 pg/mL (mean ± SD)
Mean of individual change from baseline + 15%

False negative responses to the corticorelin test in Cushing's disease patients occur approximately 5 to 10% of the time, which may lead the clinician to an incorrect diagnosis of ectopic production of ACTH at that frequency (see INDICATIONS AND USAGE, Differential Diagnosis).

PRINCIPAL DISPLAY PANEL - 100 mcg Vial Label

100 mcg
Acthrel®
(corticorelin ovine triflutate for injection)

NDC 55566-0302-1

Contains 100 mcg corticorelin ovine (as the trifluoroacetate),
10 mg lactose, 0.88 mg ascorbic acid, and 26 mg cysteine
hydrochloride monohydrate. Sterile. For intravenous use only.
Reconstitute with sodium chloride injection immediately prior
to use. Protect from light. Rx only. Dosage: See package insert.
Store at refrigerator temperature 2° to 8°C (36° to 46°F).

Manufactured for:
Ferring Pharmaceuticals Inc.
Parsippany, NJ 07054

6010–06
Made in Germany

LOT:
EXP:

2008052635

Acthrel 
corticorelin ovine triflutate injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:55566-0302
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Corticorelin ovine triflutate (Corticorelin) Corticorelin ovine 100 ug  in 2 mL
Inactive Ingredients
Ingredient Name Strength
Ascorbic Acid 0.88 mg  in 2 mL
LACTOSE, UNSPECIFIED FORM  
Cysteine Hydrochloride  
Product Characteristics
Color WHITE Score     
Shape Size
Flavor Imprint Code
Contains     
Packaging
# Item Code Package Description
1 NDC:55566-0302-1 1 VIAL, GLASS in 1 CARTON
1 2 mL in 1 VIAL, GLASS
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA020162 05/23/1996
Labeler - Ferring Pharmaceuticals Inc. (103722955)
Establishment
Name Address ID/FEI Operations
Rentschler Biotechnologie GmbH 332952766 MANUFACTURE(55566-0302), PACK(55566-0302)
Revised: 09/2016   Ferring Pharmaceuticals Inc.

Corticorelin Pregnancy Warnings

Animal studies have not been conducted. There are no controlled data in human pregnancy. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if clearly needed. US FDA pregnancy category: C

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