1. Name Of The Medicinal Product
Gonadorelin 100 micrograms powder and solvent for solution for injection
HRF 100 microgram
2. Qualitative And Quantitative Composition
Each vial contains 100 micrograms of gonadorelin as gonadorelin hydrochloride.
3. Pharmaceutical Form
Powder and solvent for solution for injection.
4. Clinical Particulars
4.1 Therapeutic Indications
Gonadorelin as a single injection is indicated for evaluating the functional capacity and response of the gonadotropes of the anterior pituitary. The LH/FSH-RH response is used in testing patients with suspected gonadotropin deficiency, whether due to the hypothalamus alone or in combination with anterior pituitary failure. Gonadorelin injection is also indicated for evaluating residual gonadotropic function of the pituitary following removal of a pituitary tumour or surgery and/or irradiation.
The 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 patho-physiological cause for the subnormal response and does not measure pituitary gonadotropic reserve.
4.2 Posology And Method Of Administration
Route of administration
For subcutaneous and intravenous administration.
Adults and Elderly
100 micrograms, 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).
Children
Do not use in children under one year as the diluent contains 2% benzyl alcohol.
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/FSH-RH is recommended.
Procedure:
1. Venous blood samples should be drawn at -15 minutes and immediately prior to gonadorelin administration. The LH/FSH-RH baseline is obtained by averaging the LH/FSH-RH values of the two samples.
2. Administer a bolus of 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/FSH-RH content. It must be emphasised 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/FSH-RH response 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/FSH-RH assays.
Curves provided represent the LH/FSH-RH response curves after administration in normal subjects. The normal LH/FSH-RH response curves were established between the 10th percentile (B line) and 90th percentile (A line) of all LH/FSH-RH responses in normal subjects analysed from the results of clinical studies.
Individual patient responses should be plotted on the appropriate curve. A subnormal response in patients is defined as three or more LH/FSH-RH values which fall below the B line of the normal LH/FSH-RH response curve.
In cases where there is a blunted or borderline response, the gonadorelin test should be repeated.
The gonadorellin 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 patho-physiological cause for the subnormal response and does not measure pituitary gonadotropic reserve.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Known or suspected pregnancy.
Do not use in children under one year of age as diluent contains 2% benzyl alcohol.
4.4 Special Warnings And Precautions For Use
Although allergic and hypersensitivity reactions have been observed with other polypeptide hormones, to date no such reactions have been encountered following the administration of a single 100 micrograms dose of gonadorelin used for diagnostic purposes. Rare instances of hypersensitivity reactions have been reported. Therefore, patients treated by intermittent pulsatile therapy in whom re-administration is considered, particularly by the intravenous route, should be carefully observed. Administration during the follicular phase of a normal cycle may result in premature ovulation and appropriate measures are advised to prevent an unwanted pregnancy in these circumstances.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
The gonadorelin test should be conducted in the absence of other drugs which directly affect the pituitary secretion of gonadotropins. These would include a variety of preparations which contain androgens, oestrogens, progestogens or glucocorticoids. The gonadotropin levels may be transiently elevated by spironolactone, minimally elevated by methyldopa, and suppressed by oral contraceptives and digoxin. The response to gonadorelin may be blunted by phenothiazines and dopamine antagonists which cause a rise in prolactin.
4.6 Pregnancy And Lactation
Gonadorelin should not be administered to pregnant women or nursing mothers.
4.7 Effects On Ability To Drive And Use Machines
None known.
4.8 Undesirable Effects
Systemic complaints such as headache, nausea, light headedness, abdominal discomfort and flushing have been reported rarely following administration of gonadorelin. Local swelling, occasionally with pain and pruritis at the injection site may occur if gonadorelin is administered subcutaneously. Local and generalised skin rash have been noted after chronic subcutaneous administration.
Thrombophlebitis with septicaemia, mild and severe, has been reported in isolated cases at the site of intravenous injection. Rare instances of hypersensitivity reaction (bronchospasm, tachycardia, flushing, urticaria, swelling, itching and redness of the face, eyelids and lips, induration at injection site) have been reported following multiple-dose administration of large doses. Antibody formation has also been reported rarely after chronic administration of large doses.
4.9 Overdose
Gonadorelin has been administered parenterally in doses up to 3 mg bd for 28 days without any signs or symptoms of overdosage. In cases of overdosage or idiosyncrasy, symptomatic treatment should be administered as required.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Gonadorelin stimulates the synthesis of follicle stimulating hormone and luteinising hormone in the anterior lobe of the pituitary as well as their release.
5.2 Pharmacokinetic Properties
Gonadorelin is rapidly hydrolysed in plasma and excreted in urine with a half life of about 4 minutes.
5.3 Preclinical Safety Data
Not applicable.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Lactose monohydrate USP
Solvent:
Benzyl alcohol BP
Water for injections BP
6.2 Incompatibilities
Gonadorelin should not be mixed with any other substance.
6.3 Shelf Life
Unopened: 48 months
After reconstitution: 24 hours
6.4 Special Precautions For Storage
Store below 25°C.
6.5 Nature And Contents Of Container
Gonadorelin is supplied in a USP Type I clear glass vial with grey butyl rubber stopper and aluminium collar. The sterile solvent is 5 ml water for injections with 2% benzyl alcohol supplied in a Ph.Eur. Type I clear glass ampoule.
6.6 Special Precautions For Disposal And Other Handling
Preparation for single injection administration: Reconstitute 100 micrograms vial with 1.0 ml of the accompanying sterile solvent of 2 % benzyl alcohol. Prepare solution immediately before use. After reconstitution, refrigerate and use within 1 day. Discard unused reconstituted solution and solvent.
7. Marketing Authorisation Holder
Intrapharm Laboratories Limited
Kidwells Park House
Kidwells Park Drive
Maidenhead
Berkshire SL6 8AQ
United Kingdom
8. Marketing Authorisation Number(S)
PL 17509/0005.
9. Date Of First Authorisation/Renewal Of The Authorisation
Date of first authorisation: 25 May 2001
Date of latest renewal: 26 June 2004
10. Date Of Revision Of The Text
11 March 2010.
11 DOSIMETRY
IF APPLICABLE
12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS
IF APPLICABLE
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