Zoladex/Zoladex LA

Zoladex/Zoladex LA

goserelin

Manufacturer:

AstraZeneca

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Goserelin acetate.
Description
Zoladex contains goserelin acetate (equivalent to 3.6 mg goserelin).
Zoladex LA contains goserelin acetate (equivalent to 10.8 mg goserelin).
Action
Pharmacology: Pharmacodynamics: Mode of action: ZOLADEX (D-Ser(But)6 Azgly10 LHRH) is a synthetic analogue of naturally occurring luteinising hormone releasing hormone (LHRH). On chronic administration ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg results in inhibition of pituitary luteinising hormone secretion leading to a fall in serum testosterone concentrations in men and serum oestradiol concentrations in women. Initially, ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg, like other LHRH agonists, may transiently increase serum testosterone concentrations in men and serum oestradiol concentrations in women.
In men by around 21 days after the first depot injection, testosterone concentrations have fallen to within the castrate range and remain suppressed with treatment every 3 months. If in exceptional circumstances repeat dosing does not occur at 3 months, data indicate that castrate levels of testosterone are maintained for up to 16 weeks in the majority of patients.
Rarely, some women may enter the menopause during treatment with LHRH analogues and do not resume menses on cessation of therapy.
Zoladex: During early treatment with ZOLADEX 3.6 mg some women may experience vaginal bleeding of variable duration and intensity. Such bleeding probably represents oestrogen withdrawal bleeding and is expected to stop spontaneously.
In women serum oestradiol concentrations are suppressed by around 21 days after the first depot injection and, with continuous treatment every 28 days, remain suppressed at levels comparable with those observed in postmenopausal women. This suppression is associated with a response in hormone dependent breast cancer, endometriosis, uterine fibroids and suppression of follicular development within the ovary. It will produce endometrial thinning and will result in amenorrhoea in the majority of patients.
ZOLADEX 3.6 mg in combination with iron has been shown to induce amenorrhoea and improve haemoglobin concentrations and related haematological parameters in women with fibroids who are anaemic. The combination produced a mean haemoglobin concentration 1g/dl above that achieved by iron therapy alone.
Zoladex LA: In women, serum oestradiol concentrations are suppressed by around 4 weeks after the first depot injection and remain suppressed until the end of the treatment period. In patients with oestradiol already suppressed by an LHRH analogue, suppression is maintained on the change of therapy to ZOLADEX LA 10.8 mg. Suppression of oestradiol is associated with a response in endometriosis and uterine fibroids and will result in amenorrhoea in the majority of patients.
During early treatment with ZOLADEX some women may experience vaginal bleeding of variable duration and intensity. Such bleeding probably represents oestrogen withdrawal bleeding and is expected to stop spontaneously.
Pharmacokinetics: ZOLADEX 3.6 mg is poorly protein bound and has a serum elimination half-life of two to four hours in subjects with normal renal function. The half-life is increased in patients with impaired renal function. For the compound given monthly in a depot formulation, this change will have minimal effect. Hence, no change in dosing is necessary in these patients. There is no significant change in pharmacokinetics in patients with hepatic failure.
Zoladex: The bioavailability of ZOLADEX 3.6 mg is almost complete. Administration of a depot every four weeks ensures that effective concentrations are maintained with no tissue accumulation.
Zoladex LA: Administration of ZOLADEX LA 10.8 mg in accordance with the dosing recommendations ensures that exposure to goserelin is maintained with no clinically significant accumulation.
Toxicology: Preclinical safety data: Following long-term repeated dosing with ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg, an increased incidence of benign pituitary tumours has been observed in male rats. Whilst this finding is similar to that previously noted in this species following surgical castration, any relevance to humans has not been established.
In mice, long term repeated dosing with multiples of the human dose produced histological changes in some regions of the digestive system manifested by pancreatic islet cell hyperplasia and a benign proliferative condition in the pyloric region of the stomach, also reported as a spontaneous lesion in this species. The clinical relevance of these findings is unknown.
Indications/Uses
Zoladex: Prostate cancer: ZOLADEX 3.6 mg is indicated in the management of prostate cancer suitable for hormonal manipulation.
Breast cancer: ZOLADEX 3.6 mg is indicated in the management of breast cancer in premenopausal and perimenopausal women suitable for hormonal manipulation.
Endometriosis: In the management of endometriosis, ZOLADEX 3.6 mg alleviates symptoms, including pain, and reduces the size and number of endometrial lesions.
Endometrial thinning: ZOLADEX 3.6 mg is indicated for the prethinning of the uterine endometrium prior to endometrial ablation or resection.
Uterine fibroids: In conjunction with iron therapy in the haematological improvement of anaemic patients with fibroids, prior to surgery.
Assisted reproduction: Pituitary down regulation in preparation for superovulation.
Zoladex LA: ZOLADEX LA 10.8 mg is indicated in the management of prostate cancer suitable for hormonal manipulation.
Endometriosis: ZOLADEX LA 10.8 mg is indicated in the management of endometriosis including alleviation of symptoms, such as pain, and reduction in the size and number of endometrial lesions.
Uterine Fibroids: ZOLADEX LA 10.8 mg is indicated in the management of fibroids including shrinkage of lesions, improvement in the patient's haematological status and reduction of symptoms, such as pain. It can be used as an adjunct to surgery to facilitate the operative technique and reduce operative blood loss.
Dosage/Direction for Use
Caution should be taken while inserting ZOLADEX/ZOLADEX LA into the anterior abdominal wall due to the proximity of underlying inferior epigastric artery and its branches.
Use extra care when administering ZOLADEX/ZOLADEX LA to patients with a low body mass index and/or who are receiving full anticoagulation medication.
Zoladex: Adults: One 3.6 mg depot of ZOLADEX injected subcutaneously into the anterior abdominal wall, every 28 days.
Assisted reproduction: ZOLADEX 3.6 mg is administered to downregulate the pituitary gland, as defined by serum oestradiol levels similar to those observed in the early follicular phase (approximately 150 pmol/l). This will usually take between 7 and 21 days.
When downregulation is achieved, superovulation (controlled ovarian stimulation) with gonadotrophin is commenced. The downregulation achieved with a depot agonist is more consistent suggesting that, in some cases, there may be an increased requirement for gonadotrophin. At the appropriate stage of follicular development, gonadotrophin is stopped and human chorionic gonadotrophin (hCG) is administered to induce ovulation. Treatment monitoring, oocyte retrieval and fertilisation techniques are performed according to the normal practice of the individual clinic.
No dosage adjustment is necessary for patients with renal impairment.
No dosage adjustment is necessary for patients with hepatic impairment.
No dosage adjustment is necessary in the elderly.
Endometriosis should be treated for a period of six months only, since at present there are no clinical data for longer treatment periods. Repeat courses should not be given due to concern about loss of bone mineral density. In patients receiving ZOLADEX3.6 mg for the treatment of endometriosis, the addition of hormone replacement therapy (a daily oestrogenic agent and a progestogenic agent) has been shown to reduce bone mineral density loss and vasomotor symptoms.
For use in endometrial thinning; two depots to be administered 4 weeks apart, with surgery timed for between zero and two weeks after the second depot.
For women who are anaemic as a result of uterine fibroids, ZOLADEX 3.6 mg depot with supplementary iron may be given for up to three months before surgery.
Children: ZOLADEX 3.6 mg is not indicated for use in children.
Zoladex LA: Adult Men: One 10.8 mg depot of ZOLADEX LA 10.8 mg injected subcutaneously into the anterior abdominal wall, every 3 months (see Pharmacology: Pharmacodynamics under Actions).
Adult Women: One depot of ZOLADEX LA 10.8 mg injected subcutaneously into the anterior abdominal wall, every 12 weeks.
Elderly: No dosage adjustment is necessary in the elderly.
Renal Impairment: No dosage adjustment is necessary for patients with renal impairment.
Hepatic Impariment: No dosage adjustment is necessary for patients with hepatic impairment.
Children: ZOLADEX LA 10.8 mg is not indicated for use in children.
Overdosage
There is limited experience of overdosage in humans. In cases where ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg has unintentionally been readministered early, or given at a higher dose, no clinically relevant adverse effects have been seen. Animal tests suggest that no effect other than the intended therapeutic effects on sex hormone concentrations and on the reproductive tract will be evident with higher doses of ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg. If overdosage occurs, this should be managed symptomatically.
Contraindications
ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg should not be given to patients with a known hypersensitivity to the active substance, to other LHRH analogues, or to any excipients of this product.
Zoladex: ZOLADEX 3.6 mg should not be used during pregnancy or lactation. (See Use in Pregnancy & Lactation.)
Special Precautions
ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg is not indicated for use in children as safety and efficacy have not been established in this group of patients.
Injection site injury has been reported with ZOLADEX, including events of pain, haematoma, haemorrhage and vascular injury. Monitor affected patients for signs or symptoms of abdominal haemorrhage. In very rare cases, administration error results in vascular injury and haemorrhagic shock requiring blood transfusions and surgical intervention. Extra care should be taken when administering ZOLADEX 3.6 mg /ZOLADEX LA 10.8 mg to patients with a low body mass index and/or receiving full anticoagulant medications.
The use of ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg in men at particular risk of developing ureteric obstruction or spinal cord compression should be considered carefully and the patients monitored closely during the first month of therapy. If spinal cord compression or renal impairment due to ureteric obstruction are present or develop, specific standard treatment of these complications should be instituted.
The use of LHRH agonists may cause a reduction in bone mineral density. Currently available ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg data indicate a mean loss of 4.6% in vertebral bone mineral density following a six month course of treatment with progressive recovery to a mean loss compared to baseline of 2.6% six months after cessation of treatment. In patients receiving ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg for the treatment of endometriosis, the addition of hormone replacement therapy (a daily oestrogenic agent and a progestogenic agent) has been shown to reduce bone mineral density loss and vasomotor symptoms. In men, preliminary data suggest the use of a bisphosphonate in combination with an LHRH agonist may reduce bone mineral loss.
A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes mellitus. Consideration should therefore be given to monitoring blood glucose.
ZOLADEX 3.6 mg/ZOLADEX LA should be used with caution in women with known metabolic bone disease.
ZOLADEX may cause an increase in uterine cervical resistance, which may result in difficulty in dilating the cervix.
Cardiovascular Diseases: Increased risk of myocardial infarction and sudden cardiac death has been reported in association with use of GnRH analogs in men. Monitor for cardiovascular disease and manage according to current clinical practice.
Zoladex: Currently, there are no clinical data on the effects of treating benign gynaecological conditions with ZOLADEX for periods in excess of six months.
Androgen deprivation therapy may prolong the QT interval. In patients with a history of or who have risk factors for QT prolongation and in patients receiving concomitant medicinal products that may prolong the QT interval physicians should assess the benefit risk ratio including the potential for Torsade de Pointes prior to initiating ZOLADEX.
Assisted Reproduction:
ZOLADEX 3.6 mg should only be administered as part of a regimen for assisted reproduction under the supervision of a specialist experienced in the area.
As with other LHRH agonists, there have been reports of ovarian hyperstimulation syndrome (OHSS) associated with the use of ZOLADEX 3.6 mg, in combination with gonadotrophin. It has been suggested that the downregulation achieved with a depot agonist may lead, in some cases, to an increased requirement for gonadotrophin. The stimulation cycle should be monitored carefully to identify patients at risk of developing OHSS because its severity and incidence may be dependent on the dose regimen of gonadotrophin. Human chorionic gonadotrophin (hCG) should be withheld, if appropriate.
It is recommended that ZOLADEX 3.6 mg be used with caution in assisted reproduction regimens in patients with polycystic ovarian syndrome as follicle recruitment may be increased.
Zoladex LA: In women, ZOLADEX LA 10.8 mg is only indicated for use in endometriosis and fibroids. For female patients requiring treatment with goserelin for other conditions, refer to previously mentioned text.
Time to return of menses after cessation of therapy with ZOLADEX LA 10.8mg may be prolonged in some patients.
There is no experience of the use of hormone replacement therapy in women receiving ZOLADEX LA 10.8 mg.
Effects on ability to drive or operate machinery: There is no evidence that ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg results in impairment of ability to drive or operate machinery.
Use In Pregnancy & Lactation
Pregnancy: Zoladex: Although reproductive toxicology in animals gave no evidence of teratogenic potential, ZOLADEX 3.6 mg should not be used in pregnancy as there is a theoretical risk of abortion or foetal abnormality if LHRH agonists are used during pregnancy. Potentially fertile women should be examined carefully before treatment to exclude pregnancy. Non hormonal methods of contraception should be employed during therapy and in the case of endometriosis until menses are resumed.
Pregnancy should be excluded before ZOLADEX 3.6 mg is used for assisted reproduction. The clinical data from use in this setting are limited but the available evidence suggests there is no causal association between ZOLADEX 3.6 mg and any subsequent abnormalities of oocyte development or pregnancy and outcome.
Zoladex LA: ZOLADEX LA 10.8 mg should not be used in pregnancy as there is a theoretical risk of abortion or foetal abnormality if LHRH agonists are used during pregnancy. Potentially fertile women should be examined carefully before treatment to exclude pregnancy. Non hormonal methods of contraception should be employed during therapy until menses resume (see Precautions).
Lactation: The use of ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg during breast feeding is not recommended.
Adverse Reactions
The following frequency categories for adverse drug reactions (ADRs) were calculated based on reports from ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg clinical trials and post-marketing sources. (See Tables 1 and 2.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Zoladex LA: Pharmacological effects of ZOLADEX treatment in women include hot flushes and sweating, and a change in libido, seldom requiring withdrawal of therapy. Headaches, mood changes including depression, vaginal dryness and change in breast size have been noted infrequently. In women with fibroids, degeneration of fibroids may occur.
As with other LHRH agonists, there have been reports of ovarian cyst formation.
Drug Interactions
Since androgen deprivation treatment may prolong the QT interval, the concomitant use of ZOLADEX with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de Pointes should be carefully evaluated.
Caution For Usage
Instructions for use, handling and disposal: Use as directed by the prescriber. Use extra care when administering ZOLADEX 3.6 mg/ZOLADEX LA 10.8 mg to patients with a low body mass index and/or who are receiving full anticoagulation medication.
Use only if pouch is undamaged. Use immediately after opening pouch.
Dispose of the syringe in an approved sharps collector.
Storage
Do not store above 25°C.
ATC Classification
L02AE03 - goserelin ; Belongs to the class of gonadotropin releasing hormone analogues. Used in endocrine therapy.
Presentation/Packing
Zoladex: Depot inj (pre-filled syringe) 3.6 mg x 1's.
Zoladex LA: Depot inj (pre-filled syringe) 10.8 mg x 1's.
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