Factrel

Lyophilized Powder in single-dose Secule® vials containing 100 mcg (NDC 0046-0507-05) and 500 mcg (NDC 0046-0509-05) gonadorelin as the hydrochloride with 100 mg lactose, USP. Each Secule vial is accompanied by one ampul containing 2 mL sterile diluent of 2% benzyl alcohol in sterile water.

DIRECTIONS

Reconstitute 100 mcg Secule® vial with 1.0 mL of the accompanying sterile diluent.

Reconstitute 500 mcg Secule® vial with 2.0 mL of the accompanying sterile diluent.

Prepare solution immediately before use. After reconstitution, store at room temperature and use within 1 day.

Discard unused reconstituted solution and diluent.

Secule® Registered trademark to designate a vial containing an injectable preparation in dry form.

Manufactured by:
Ayerst Laboratories Inc.
A Wyeth-Ayerst Company
Philadelphia, PA 19101

Factrel (gonadorelin) as a single injection is indicated for evaluating the functional capacity and response of the gonadotropes of the anterior pituitary. This single-injection test does not measure pituitary gonadotropic reserve, for which more prolonged or repeated administration may be required. The LH response is useful in testing patients with suspected gonadotropin deficiency, whether due to the hypothalamus alone or in combination with anterior pituitary failure. Factrel (gonadorelin) is also indicated for evaluating residual gonadotropic function of the pituitary following removal of a pituitary tumor by surgery and/or irradiation. In clinical studies to date, however, the single-injection test has not been useful in differentiating pituitary disorders from hypothalamic disorders. The Factrel (gonadorelin) test can be performed concomitantly with other post-treatment evaluations. The results of the Factrel (gonadorelin) test complement the clinical examination and other laboratory tests used to confirm or substantiate hypogonadotropic hypogonadism.

In cases where there is a normal response, it indicates the presence of functional pituitary gonadotropes. The single-injection test does not measure pituitary gonadotropic reserve.

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

Adults:  100 mcg dose, subcutaneously or intravenously. In females for whom the phase of the menstrual cycle can be established, the test should be performed in the early follicular phase (Days 1-7).

TEST METHODOLOGY

To determine the status of the gonadotropin secretory capacity of the anterior pituitary, a test procedure requiring seven venous blood samples for LH is recommended.

Procedure:

1. Venous blood samples should be drawn at -15 minutes and immediately prior to Factrel (gonadorelin) administration. The LH baseline is obtained by averaging the LH values of the two samples.
2. Administer a bolus of 100 mcg of Factrel (gonadorelin) subcutaneously or intravenously.
3. Draw venous blood samples at 15, 30, 45, 60, and 120 minutes after administration.
4. Blood samples should be handled as recommended by the laboratory that will determine the LH content. It must be emphasized that the reliability of the test is directly related to the inter-assay and intra-assay reliability of the laboratory performing the assay.

INTERPRETATION OF TEST RESULTS

Interpretation of the LH response to Factrel (gonadorelin) requires an understanding of the hypothalamic-pituitary physiology, knowledge of the clinical status of the individual patient, and familiarity with the normal ranges and the standards used in the laboratory performing the LH assays.

The Factrel (gonadorelin) test complements the clinical assessment of patients with a variety of endocrine disorders involving the hypothalamic-pituitary axis. In cases where there is a normal response, it indicates the presence of functional pituitary gonadotropes. The single-injection test does not determine the pathophysiological cause for the subnormal response and does not measure pituitary gonadotropic reserve.

Hypersensitivity to gonadorelin hydrochloride or any of the components.

WARNINGS

No Information Provided.

PRECAUTIONS

A.  General

Although allergic and hypersensitivity reactions have been observed with other polypeptide hormones, and rarely with multiple doses of Factrel (gonadorelin) , to date no such reactions have been reported following the administration of a single 100 mcg dose of Factrel (gonadorelin).

Antibody formation has been reported rarely after chronic administration of large doses of Factrel (gonadorelin).

B.  Drug Interactions

The Factrel (gonadorelin) test should be conducted in the absence of other drugs which directly affect the pituitary secretion of the gonadotropins. These would include a variety of preparations which contain androgens, estrogens, progestins, or glucocorticoids. The gonadotropin levels may be transiently elevated by spironolactone, minimally elevated by levodopa, and suppressed by oral contraceptives and digoxin. The response to Factrel (gonadorelin) may be blunted by phenothiazines and dopamine antagonists which cause a rise in prolactin.

C.  Carcinogenesis, Mutagenesis, Impairment of Fertility

Repetitive, high doses of Factrel (gonadorelin) may cause luteolysis and inhibition of spermatogenesis. No long-term animal studies have been done to evaluate carcinogenic potential.

D.  Pregnancy Category B

Reproduction studies have been performed in mice, rats, and rabbits at doses up to 50 times the human dose, and have revealed no evidence of harm to the fetus due to Factrel (gonadorelin). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Appropriate precautions should be taken because the effects of LH-RH on the fetus and developing offspring have not been adequately evaluated.

Nursing Mothers:   It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Factrel (gonadorelin) is administered to a nursing woman.

Pediatric Use:   Safety and effectiveness in pediatric patients have not been established.

SIDE EFFECTS

Systemic effects have been reported rarely following administration of 100 mcg of Factrel (gonadorelin).

CNS:   headache, light-headedness.

GI:   nausea, abdominal discomfort.

Dermatologic:   local swelling, occasionally with pain and pruritis, at the injection site may occur following subcutaneous administration; local and generalized skin rash have been noted after chronic subcutaneous administration.

Cardiovascular:   flushing.

Rare instances of hypersensitivity reaction (bronchospasm, tachycardia, flushing, urticaria, induration at injection site) and anaphylactic reactions have been reported following multiple-dose administration.

There has been a report of pituitary apoplexy and sudden blindness following gonadotropin-releasing hormone administration to a patient with a gonadotropin-secreting adenoma.

DRUG INTERACTIONS

The Factrel (gonadorelin) test should be conducted in the absence of other drugs which directly affect the pituitary secretion of the gonadotropins. These would include a variety of preparations which contain androgens, estrogens, progestins, or glucocorticoids. The gonadotropin levels may be transiently elevated by spironolactone, minimally elevated by levodopa, and suppressed by oral contraceptives and digoxin. The response to Factrel (gonadorelin) may be blunted by phenothiazines and dopamine antagonists which cause a rise in prolactin.

Systemic effects have been reported rarely following administration of 100 mcg of Factrel (gonadorelin).

CNS:   headache, light-headedness.

GI:   nausea, abdominal discomfort.

Dermatologic:   local swelling, occasionally with pain and pruritis, at the injection site may occur following subcutaneous administration; local and generalized skin rash have been noted after chronic subcutaneous administration.

Cardiovascular:   flushing.

Rare instances of hypersensitivity reaction (bronchospasm, tachycardia, flushing, urticaria, induration at injection site) and anaphylactic reactions have been reported following multiple-dose administration.

There has been a report of pituitary apoplexy and sudden blindness following gonadotropin-releasing hormone administration to a patient with a gonadotropin-secreting adenoma.

Factrel (gonadorelin) has been administered parenterally in doses up to 3 mg b.i.d. for 28 days without any signs or symptoms of overdosage. In case of overdosage or idiosyncrasy, symptomatic treatment should be administered as required.