Drug Class Description
LHRH analogues.

Generic Name
Goserelin - neoplastic disorders

Drug Description
Zoladex: sustained release sterile 28-day depot in a single- dose syringe applicator. Zoladex LA: sustained release sterile 12-week depot in a single-dose syringe applicator.

Presentation
Zoladex: Goserelin (as acetate) 3.6mg in a biodegradable depot. Zoladex LA: Goserelin (as acetate) 10.8mg in a biodegradable depot.

Indications
Zoladex: Prostate cancer suitable for hormone manipulation. Advanced breast cancer in pre- and peri-menopausal women suitable for hormone manipulation.Zoladex LA: Prostate cancer suitable for hormone manipulation.

Adult Dosage
Adults3.6mgOne 3.6 mg depot of Zoladex injected subcutaneously into the anterior abdominal wall, every 28 days. No dosage adjustment is necessary for patients with renal or hepatic impairment, or 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 Zoladex 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: four or eight weeks treatment. The second depot may be required for the patient with a large uterus or to allow flexible surgical timing.For women who are anaemic as a result of uterine fibroids: Zoladex 3.6 mg depot with supplementary iron may be administered for up to three months before surgery.Assisted reproduction: Zoladex 3.6 mg is administered to downregulate 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 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 retrieva l and fertilisation techniques are performed according to the normal practice of the individual clinic.ChildrenZoladex is not indicated for use in children.For correct administration of Zoladex, see instructions on the instruction card.LA 10.8mgAdult males (including the elderly): one depot of Zoladex LA injected subcutaneously into the anterior abdominal wall every 12 weeks.Children: Zoladex LA is not indicated for use in children.Renal impairment: no dosage adjustment is necessary for patients with renal impairment.Hepatic impairment: no dosage adjustment for patients with hepatic impairment.For correct administration of Zoladex, see instructions on the instruction card.

Child Dosage
Not applicable.

Contra Indications
Zoladex should not be given to patients with a known hypersensitivity to the active substance, to other LHRH analogues, or to any of the excipients of this product.Zoladex should not be used in pregnancy

Special Precautions
3.6 mgZoladex is not indicated for use in children, as safety and efficacy have not been established in this group of patients.MalesThe 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 first month of therapy. Consideration should be given to the initial use of an anti-androgen (e.g. cyproterone acetate 300 mg daily for three days before and three weeks after commencement of Zoladex) at the start of LHRH analogue therapy since this has been reported to prevent the possible sequelae of the initial rise in serum testosterone. 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 in men may cause a reduction in bone mineral density.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.FemalesThe use of LHRH agonists in women may cause a reduction in bone mineral density. Following two years treatment for early breast cancer, the average loss of bone mineral density was 6.2% and 11.5% at the femoral neck and lumbar spine respectively. This loss has been shown to be partially reversible at the one year off treatment follow-up with recovery to 3.4% and 6.4% relative to baseline at the femoral neck and lumbar spine respectively, although this recovery is based on very limited data.In patients receiving Zoladex 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.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 effect of treating benign gynaecological conditions with Zoladex for periods in excess of six months.Zoladex 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 is used with caution in assisted reproduction regimens in patients with polycystic ovarian syndrome as follicle recruitment may be increased.10.8mgZoladex LA is not indicated for use in females, since there is insufficient evidence of reliable suppression of serum estradiol. For female patients requiring treatment with goserelin, refer to the prescribing information for Zoladex 3.6 mg.Zoladex LA is not indicated for use in children, as safety and efficacy have not been established in this group of patients.The use of Zoladex LA in patients 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. Consideration should be given to the initial use of an antiandrogen (e.g. cyproterone acetate 300 mg daily for three days before, and three weeks after commencement of Zoladex) at the start of LHRH analogue therapy since this has been reported to prevent the possible sequelae of the initial rise in serum testosterone.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 in men may cause a reduction in bone mineral density.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.

Adverse Reactions
GeneralRare 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 treatment from Zoladex.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.The use of LHRH agonists may cause a reduction in bone mineral density.MalesPharmacological effects in men include hot flushes and sweating and a decrease in libido, 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.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.FemalesPharmacological effects in women include hot flushes and sweating, and loss in libido, seldom requiring withdrawal of therapy. Headaches, mood changes including depression, vaginal dryness and change in breast size have been noted. During early treatment with Zoladex some women may experience vaginal bleeding of variable duration and intensity. If vaginal bleeding occurs it is usually in the first month after starting treatment. Such bleeding probably represents oestrogen withdrawal bleeding and is expected to stop spontaneously.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 metastases have developed hypercalcaemia on initiation of therapy.Rarely, some women may enter the menopause during treatment with LHRH analogues and not resume menses on cessation of therapy. This may simply be a physiological change.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 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.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.

Manufacturer
AstraZeneca

Drug Availability
(POM)

Updated
17 June 2009