Skip to Content

HRF 500MCG (POWDER FOR RECONSTITUTION FOR INJECTION)

Active substance(s): GONADORELIN

View full screen / Print PDF » Download PDF ⇩
Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
HRF 500 microgram.

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each vial contains 500 micrograms of Gonadorelin as Gonadorelin
Hydrochloride BP.

3

PHARMACEUTICAL FORM
Powder and solvent for solution for injection.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
HRF 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. HRF is also indicated for evaluating residual gonadotropic
function of the pituitary following removal of a pituitary tumour or surgery
and/or irradiation.
The HRF 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.

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/FSHRH is recommended.
Procedure:
1.

2.
3.
4.

Venous blood samples should be drawn at -15 minutes and immediately prior to
HRF administration. The LH/FSH-RH baseline is obtained by averaging the
LH/FSH-RH values of the two samples.
Administer a bolus of HRF subcutaneously or intravenously.
Draw venous blood samples at 15, 30, 45, 60 and 120 minutes after
administration.
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 HRF test should
be repeated.
The HRF 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 HRF or any of its components. 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 HRF 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 HRF 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 HRF may be blunted by
phenothiazines and dopamine antagonists which cause a rise in prolactin.

4.6

Pregnancy and lactation
HRF 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
HRF. Local swelling, occasionally with pain and pruritis at the injection site
may occur if HRF 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
HRF 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
HRF 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
HRF is supplied in a USP Type I clear glass vial with grey butyl rubber
stopper and aluminium collar. The sterile solvent is 2 ml water for injections
with 2% benzyl alcohol supplied in a Ph. Eur. Type I clear glass ampoule.

6.6

Special precautions for disposal
Preparation for single injection administration: Reconstitute 500 micrograms
vial with 2.0 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
Diamond Consultants Ltd
2 Wheeleys Road
Edgbaston
Birmingham
West Midlands
United Kingdom
B15 2LD

8

MARKETING AUTHORISATION NUMBER(S)
PL 41262/0001

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
28/03/2011

10

DATE OF REVISION OF THE TEXT
27/12/2012

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide