Zoladex

Zoladex

goserelin

Manufacturer:

AstraZeneca

Distributor:

DKSH
Full Prescribing Info
Contents
Goserelin acetate.
Description
Zoladex is a sterile, white- to cream-coloured cylindrical depot in which goserelin acetate (equivalent to goserelin 3.6 mg) is dispersed in a biodegradable matrix of lactide-glycolide co-polymer. It is supplied in a single-dose SafeSystem syringe applicator with a protective sleeve in a pouch which contains a desiccant.
Action
Pharmacology: Pharmacodynamics: Mode of Action: Zoladex (D-Ser(But)6Azgly10 LHRH) is a synthetic analogue of naturally occurring LHRH. On chronic administration, Zoladex results in inhibition of pituitary LH secretion leading to a fall in serum testosterone concentrations in males and serum estradiol concentrations in females. This effect is reversible on discontinuation of therapy. Initially, Zoladex, like other LHRH agonists, may transiently increase serum testosterone concentration in men and serum estradiol concentration in women. During early treatment with Zoladex, some women may experience vaginal bleeding of variable duration and intensity. Such bleeding probably represents estrogen withdrawal bleeding and is expected to stop spontaneously.
In men by around 21 days after the 1st depot injection, testosterone concentrations have fallen to within the castrate range and remain suppressed with continuous treatment every 28 days. This inhibition leads to prostate tumor regression and symptomatic improvement in the majority of patients.
In women, serum estradiol concentrations are suppressed by around 21 days after the 1st 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 amenorrhea in the majority of patients.
Zoladex in combination with iron has been shown to induce amenorrhea and improve haemoglobin concentrations and related hematological parameters in women with fibroids who are anemic. The combination produced a mean haemoglobin concentration 1 g/dL above that achieved by iron therapy alone.
During treatment with LHRH analogues patients may enter the menopause. Rarely, some women do not resume menses on cessation of therapy.
Pharmacokinetics: The bioavailability of Zoladex is almost complete. Administration of a depot every 4 weeks ensures that effective concentrations are maintained with no tissue accumulation. Zoladex is poorly protein-bound and has a serum elimination half-life of 2-4 hrs 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.
Toxicology: Preclinical Safety Data: Following long-term repeated dosing with Zoladex, an increased incidence of benign pituitary tumors has been observed in male rats. While 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
Prostate Cancer: Management of prostate cancer suitable for hormonal manipulation.
Breast Cancer: Management of breast cancer in pre- and peri-menopausal women suitable for hormonal manipulation.
Endometriosis: In the management of endometriosis, Zoladex alleviates symptoms, including pain and reduces the size and number of endometrial lesions.
Endometrial Thinning: For the pre-thinning of the uterine endometrium prior to endometrial ablation or resection.
Uterine Fibroids: In conjunction with iron therapy in the hematological improvement of anemic patients with fibroids, prior to surgery.
Assisted Reproduction: Pituitary down-regulation in preparation for superovulation.
Dosage/Direction for Use
Adults: One 3.6-mg depot of Zoladex injected SC into the anterior abdominal wall, every 28 days.
Assisted Reproduction: Zoladex 3.6 mg is administered to down-regulate the pituitary gland, as defined by serum estradiol levels similar to those observed in the early follicular phase (approximately 150 pmol/L). This will usually take between 7 and 21 days.
When down-regulation is achieved, superovulation (controlled ovarian stimulation) with gonadotrophin is commenced. The down-regulation 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 fertilization techniques are performed according to the normal practice of the individual clinic.
No dosage adjustment is necessary for patients with renal or hepatic impairment or in the elderly.
Endometriosis should be treated for a period of 6 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 Zoladex for the treatment of endometriosis, the addition of hormone replacement therapy (a daily estrogenic agent and a progestogenic agent) has been shown to reduce bone mineral density loss and vasomotor symptoms.
Endometrial Thinning: Two depots to be administered 4 weeks apart, with surgery timed for between 0 and 2 weeks after the 2nd depot.
For women who are anemic as a result of uterine fibroids, Zoladex 3.6-mg depot with supplementary iron may be given for up to 3 months before surgery.
Children: Zoladex is not indicated for use in children. (See Use in children under Precautions.)
Overdosage
There is limited experience of overdosage in humans. In cases where Zoladex has unintentionally been re-administered 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. If overdosage occurs, this should be managed symptomatically.
Contraindications
Patients with a known hypersensitivity to Zoladex or to other LHRH analogues.
Use in pregnancy & lactation: Although reproductive toxicology in animals gave no evidence of teratogenic potential, Zoladex should not be used in pregnancy as there is a theoretical risk of abortion or fetal abnormality if LHRH agonists are used during pregnancy. Potentially fertile women should be examined carefully before treatment to exclude pregnancy. Nonhormonal 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 that there is no causal association between Zoladex and any subsequent abnormalities of oocyte development or pregnancy and outcome.
The use of Zoladex during breastfeeding is not recommended.
Special Precautions
Males: The use of Zoladex in men at particular risk of developing ureteric obstruction or spinal cord compression should be considered carefully and the patients monitored closely during the 1st 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.
Females: The use of LHRH agonists in women may cause a loss of bone mineral density. Currently available Zoladex data indicate a mean loss of 4.6% in vertebral bone mineral density following a 6-month course of treatment with progressive recovery to a mean loss compared to baseline of 2.6% 6 months after cessation of treatment. In patients receiving Zoladex for the treatment of endometriosis, the addition of hormone replacement therapy (a daily estrogenic agent and a progestogenic agent) has been shown to reduce bone mineral density loss and vasomotor symptoms.
Zoladex 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.
Currently, there are no clinical data on the effects of treating benign gynecological conditions with Zoladex for periods in excess of 6 months.
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 down-regulation achieved with a depot agonist may lead, in some cases, to an increased requirement of 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.
Effects on the Ability to Drive or Operate Machinery: There is no evidence that Zoladex results in the impairment of these activities.
Use in children: Zoladex is not indicated for use in children as safety and efficacy have not been established in this group of patients.
Use In Pregnancy & Lactation
Although reproductive toxicology in animals gave no evidence of teratogenic potential, Zoladex should not be used in pregnancy as there is a theoretical risk of abortion or fetal abnormality if LHRH agonists are used during pregnancy. Potentially fertile women should be examined carefully before treatment to exclude pregnancy. Nonhormonal 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 that there is no causal association between Zoladex and any subsequent abnormalities of oocyte development or pregnancy and outcome.
The use of Zoladex during breastfeeding is not recommended.
Side Effects
General: Rare incidences of hypersensitivity reactions which may include some manifestations of anaphylaxis have been reported.
Arthralgia has been reported. Non-specific paraesthesias have been reported. Skin rashes have been reported which are generally mild, often regressing without discontinuation of therapy.
Changes in blood pressure, manifest as hypotension or hypertension, have been occasionally observed in patients administered Zoladex. The changes are usually transient, resolving either during continued therapy or after cessation of therapy with Zoladex. Rarely, such changes have been sufficient to require medical intervention, including withdrawal of Zoladex treatment.
As with other agents in this class, very rare cases of pituitary apoplexy have been reported following initial administration.
Occasional local reactions include mild bruising at the subcutaneous injection site.
Males: Pharmacological effects in men include hot flushes and sweating and a decrease in potency, seldom requiring withdrawal of therapy. Breast swelling and tenderness have been noted infrequently. Initially, prostate cancer patients may experience a temporary increase in bone pain, which can be managed symptomatically. Isolated cases of ureteric obstruction and spinal cord compression have been recorded.
The use of LHRH agonists in men may cause a loss of bone mineral density.
Females: Pharmacological effects 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. Initially, breast cancer patients may experience a temporary increase in signs and symptoms, which can be managed symptomatically. In women with fibroids, degeneration of fibroids may occur. Rarely, breast cancer patients with bony metastases have developed hypercalcemia on initiation of therapy.
In Assisted Reproduction: 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 down-regulation 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.
Follicular and luteal ovarian cysts have been reported to occur following LHRH therapy. Most cysts are asymptomatic, non-functional, varying in size and resolve spontaneously.
Drug Interactions
None known.
Caution For Usage
Instructions for Use, Handling and Disposal: Use as directed by the prescriber. 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
SafeSystem depot inj 3.6 mg x 1's.
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