Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2022 Publisher: Takeda UK Limited, 1 Kingdom Street, London, W2 6BD, United Kingdom
Treatment of central precocious puberty (girls under 9 years of age, boys under 10 years of age) (See Section 5.1).
The usual recommended dose is 11.25 mg presented as a three month depot injection and administered as a single subcutaneous injection at intervals of three months. The majority of patients will respond to this dosage. PROSTAP 3 therapy should not be discontinued when remission or improvement occurs. As with other drugs administered regularly by injection, the injection site should be varied periodically.
Response to PROSTAP 3 therapy should be monitored by clinical parameters and by measuring prostate-specific antigen (PSA) serum levels. Clinical studies with leuprorelin acetate have shown that testosterone levels increased during the first 4 days of treatment in the majority of non-orchidectomised patients. They then decreased and reached castrate levels by 2-4 weeks. Once attained, castrate levels were maintained as long as drug therapy continued. If a patient’s response appears to be sub-optimal, then it would be advisable to confirm that serum testosterone levels have reached or are remaining at castrate levels. Transient increases in acid phosphatase levels sometimes occur early in the treatment period but usually return to normal or near normal values by the 4th week of treatment.
In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of castrate-resistant prostate cancer. Reference should be made to relevant guidelines.
The recommended dose is 11.25 mg administered as a single intramuscular injection every 3 months for a period of 6 months only. Treatment should be initiated during the first 5 days of the menstrual cycle.
In women receiving GnRH analogues for the treatment of endometriosis, the addition of hormone replacement therapy (HRT – an estrogen and progestogen) has been shown to reduce bone mineral density loss and vasomotor symptoms. Therefore if appropriate, HRT should be co-administered with PROSTAP 3 taking into account the risks and benefits of each treatment.
The recommended dose is 11.25 mg administered as a single subcutaneous injection every 3 months.
The recommended dose is 11.25 mg administered as a single subcutaneous injection every 3 months in combination with tamoxifen or an aromatase inhibitor.
In women receiving chemotherapy, leuprorelin should be commenced after completion of chemotherapy, once pre-menopausal status has been confirmed (see section 4.4).
The recommended treatment duration for adjuvant treatment in combination with other hormonotherapy is up to 5 years.
Treatment with leuprorelin must be initiated at least 6-8 weeks before starting aromatase inhibitor treatment. A minimum of one injection of PROSTAP 3 should be administered before commencement of aromatase inhibitor treatment.
Ovarian suppression should be confirmed by low blood concentrations of FSH and estradiol prior to starting aromatase inhibitor treatment and measurements should be repeated every three months during combination therapy with leuprorelin and an aromatase inhibitor (see Section 4.4).
During treatment with an aromatase inhibitor, leuprorelin must not be interrupted to avoid rebound increases in circulating estrogens in premenopausal women.
PROSTAP 3 should not be used for preservation of ovarian function (see Section 5.1).
As for adults.
The treatment of children with leuprorelin acetate should be under the overall supervision of the paediatric endocrinologist.
The dosing scheme needs to be adapted individually.
The recommended starting dose is dependent on the body weight.
1 ml (11.25 mg leuprorelin acetate) suspension of 130.0 mg sustained-release microcapsules in 1 ml vehicle solution are administered every 3 months as a single subcutaneous injection.
In these rare cases the following dosage should be administered according to the clinical activity of the central precocious puberty:
0.5 ml (5.625 mg leuprorelin acetate) suspension of 130.0 mg sustained-release microcapsules in 1 ml vehicle solution are administered every 3 months as a single subcutaneous injection.
The remainder of the suspension should be discarded. The child’s weight gain should be monitored.
Depending on the activity of the central precocious puberty, it may be necessary to increase the dosage in the presence of inadequate suppression (clinical evidence e.g. spotting or inadequate gonadotropin suppression in the LHRH test). The minimaleffective 3-monthly dose to be administered should then be determined by means of the LHRH test.
Sterile abscesses at the injection site often occurred when leuprorelin acetate was administered intramuscularly at higher than the recommended dosages. Therefore, in such cases, the medicinal product should be administered subcutaneously (see 4.4).
It is recommended to use the lowest volumes possible for injections in children in order to decrease the inconvenience which is associated with the intramuscular/subcutaneous injection.
The duration of treatment depends on the clinical parameters at the start of treatment or during the course of treatment (final height prognosis, growth velocity, bone age and/or bone age acceleration) and is decided by the treating paediatrician together with the legal guardian and, if appropriate, the treated child. The bone age should be monitored during treatment at 6-12 month intervals.
In girls with bone maturation of older than 12 years and boys with bone maturation of older than 13 years discontinuation of treatment should be considered taking into account the clinical parameters.
In girls, pregnancy should be excluded before the start of treatment. The occurrence of pregnancy during treatment cannot be generally excluded. In such cases, medical advice should be sought.
Note: The administration interval should be 90 ± 2 days in order to prevent the recurrence of precocious puberty symptoms.
PROSTAP 3 should be prepared, reconstituted and administered only by healthcare professionals who are familiar with these procedures.
The pre-filled syringe of PROSTAP 3 microsphere powder should be reconstituted immediately prior to administration by subcutaneous or intramuscular injection.
To prepare for injection, screw the plunger rod into the end stopper until the end stopper begins to turn.
Remember to check if the needle is tight by twisting the needle cap clockwise. Do not overtighten.
Holding the syringe upright, release the diluents by SLOWLY PUSHING the plunger until the middle stopper is at the blue line in the middle of the barrel.
NOTE: Pushing the plunger rod quickly or over the blue line will cause leakage of the suspension from the needle.
Gently tap the syringe on the palm keeping the syringe upright to thoroughly mix the particles to form a uniform suspension. The suspension will appear milky.
NOTE: Avoid hard tapping to prevent the generation of bubbles.
Remove the needle cap and advance the plunger to expel the air from the syringe.
At the time of injection, check the direction of the safety device (with round mark face up) and inject the entire contents of the syringe. Inject the entire contents of the syringe subcutaneously or intramuscularly as you would for a normal injection
Withdraw the needle from the patient. Immediately activate the safety device by pushing the arrow forward with the thumb or finger until the device is fully extended and a CLICK is heard or felt.
NOTE: The suspension settles out very quickly following reconstitution and therefore the product should be mixed and used immediately.
No case of overdose has been reported.
In animal studies, doses of up to 500 times the recommended human dose resulted in dyspnoea, decreased activity and local irritation at the injection site. In cases of overdose, the patients should be monitored closely and management should be symptomatic and supportive.
3 years unopened.
Once reconstituted with sterile solvent, the suspension should be administered immediately.
Do not store above 25°C.
Do not refrigerate or freeze.
Store in the original container in order to protect from light.
One dual chamber pre-filled syringe containing 11.25 mg leuprorelin acetate powder in the front chamber and 1 ml of Sterile Solvent in the rear chamber.
1 × 23 gauge syringe needle fitted with safety device.
1 x syringe plunger.
Prepare the injectable suspension at the time of use and, after reconstituting, use immediately. Always ensure the safety device to prevent needle-stick injury is deployed after injection. Any unused product or waste material should be disposed of in accordance with local requirements.
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