Acthrel

Corticorelin ovine triflutate is injected into a vein through an IV. A healthcare provider will give you this injection in a hospital or clinic setting.

Corticorelin ovine triflutate is usually given as a single injection for a corticorelin test. Your caregivers will need to draw at least 5 blood samples from you before and after you receive the medicine.

In most cases, the blood is tested 15 minutes before and then right before you receive the injection. These tests will give your doctor two "baseline" measurements.

After you receive corticorelin ovine triflutate, your blood will be drawn again at 15 minutes, 30 minutes, and 60 minutes after the injection. This will help your doctor determine more about your condition.

The timing of your blood tests before and after the injection is important in assuring the most accurate results from a corticorelin test. Plan to stay in the care of your healthcare providers for at least 1 hour after your injection.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

• It is used during a Cushing's syndrome test.

• If you have an allergy to corticorelin or any other part of Acthrel (corticorelin).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Acthrel® (corticorelin ovine triflutate for injection) is a sterile, nonpyrogenic, lyophilized white cake powder, containing corticorelin ovine triflutate, a trifluoroacetate salt of a synthetic peptide that is used for the determination of pituitary corticotroph responsiveness. Corticorelin ovine has an amino acid sequence identical to ovine corticotropin-releasing hormone (oCRH). Corticorelin ovine is an analogue of the naturally occurring human CRH (hCRH) peptide.  Both peptides are potent stimulators of adrenocorticotropic hormone (ACTH) release from the anterior pituitary.  ACTH stimulates cortisol production from the adrenal cortex.  The structural formula for corticorelin ovine triflutate is described below:

Ser-Gin-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Thr-Lys-Ala-Asp-Gin-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Leu-Asp-Ile-Ala-NH2∙xCF2COOH

whereas x=4 - 8.

The empirical formula of corticorelin ovine is C205H339N59O63S with a molecular weight of 4670.35 Daltons.

Acthrel® for injection is available in vials containing 100 mcg corticorelin ovine (as the trifluoroacetate), 0.88 mg ascorbic acid, 10 mg lactose, and 26 mg cysteine hydrochloride monohydrate.  Trace amounts of chloride ion may be present from the manufacturing process.  The preparation is intended for intravenous administration.

Hypersensitivity reactions have been reported with 1 mcg/kg or 100 mcg/patient and include flushing of the face, neck, and upper chest; dyspnea, wheezing, urticaria, and angioedema (involving tongue, lip and facial swelling). Subjects have also reported an urge to take a deep breath, which occurs with a timing similar to, but less frequently than, that of flushing. Higher doses (>3 mcg/kg) are associated with more prolonged flushing, tachycardia, hypotension, dyspnea, and "chest compression" or tightness. In addition, at doses of >5 mcg/kg, significant increases in heart rate and decreases in blood pressure were observed. The cardiovascular effects occurred 2-3 minutes after injection and lasted for 30-60 minutes. The facial flushing was more prolonged, lasting up to 4 hours in some subjects. All signs and symptoms could be reduced by administering the drug as a 30-second infusion instead of by bolus injection.

Total doses of up to 200 mcg of corticorelin were administered as a bolus injection to 60 men and women, including both healthy normal subjects and patients with endocrine disorders. In most cases, only minor adverse effects, such as transient flushing and feelings of dyspnea, were noted. However, a few patients with disorders of the pituitary-adrenal axis had major symptoms. One patient had a precipitous fall in blood pressure and pulse rate and developed asystole, which required resuscitation. In two patients with Cushing's disease and in one with secondary adrenal insufficiency, an "absence-like" loss of consciousness occurred, which started within a few seconds after injection of corticorelin and lasted from 10 seconds to 5 minutes. This was accompanied by a slight fall in blood pressure. One patient with a well documented seizure diathesis experienced a grand mal epileptic seizure following Acthrel® administration. The patient had discontinued anti-convulsant therapy the day of the procedure (see PRECAUTIONS - Drug Interactions).

Dosage

A single intravenous dose of Acthrel® at 1 mcg/kg is recommended for the testing of pituitary corticotrophin function. A dose of 1 mcg/kg is the lowest dose that produces maximal cortisol responses and significant (though apparently sub-maximal) ACTH responses. Doses above 1 mcg/kg are not recommended (see PRECAUTIONS and ADVERSE REACTIONS).

At a dose of 1 mcg/kg, the ACTH and cortisol responses to Acthrel® are prolonged and remain elevated for up to 2 hours. The maximum increment in plasma ACTH occurs between 15 and 60 minutes after Acthrel® administration, whereas the maximum increment in plasma cortisol occurs between 30 and 120 minutes. In a clinical study of 30 normal healthy men, the peak plasma ACTH and cortisol responses to Acthrel® administration in the early afternoon occurred at 42 ± 29 minutes and 65 ± 26 minutes (average ±SD), respectively. If a repeated evaluation using the corticorelin stimulation test with Acthrel® is needed, it is recommended that the repeat test be carried out at the same time of day as the original test because there are differences in basal levels and peak response levels following a.m. or p.m. administration to normal humans.

Administration

Acthrel® is to be reconstituted aseptically with 2 mL of Sodium Chloride injection, USP (0.9% sodium chloride), at the time of use by injecting 2 mL of the saline diluent into the lyophilized drug product cake. To avoid bubble formation, DO NOT SHAKE the vial; instead, roll the vial to dissolve the product. The sterile solution containing 50 mcg corticorelin/mL is then ready for injection by the intravenous route. The dosage to be administered is determined by the patient's weight (1 mcg corticorelin/kg). Some of the adverse effects can be reduced by administering the drug as an infusion over 30 seconds instead of as a bolus injection.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

No information provided. Please refer to the WARNINGS AND PRECAUTIONS section.

Since this medication is usually given as a single dose, you are not likely to be on a dosing schedule.

The timing of your blood tests before and after the injection is important in assuring the most accurate results from a corticorelin test. Plan to stay in the care of your healthcare providers for at least 1 hour after your injection.