Zoladex LA 10.8 Injection

Indications

• Locally advanced prostate cancer
• Metastatic prostate cancer
• Adjuvant treatment to radiotherapy in prostate cancer
• Neoadjuvant treatment prior to radiotherapy in high-risk prostate cancer
• Advanced breast cancer
• Oestrogen-receptor-positive early breast cancer
• Endometriosis
• Uterine fibroids

Dosage

Children: Paediatric dosing information should be referred to in the BNF for Children as specific doses are not

Adults: For adults, the standard dosage is 3.6 mg administered subcutaneously every 28 days.

Mechanism of action

Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered. It initially stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but with chronic administration, it leads to down-regulation of gonadotropin-releasing hormone receptors. This results in sustained suppression of LH and serum testosterone levels, ultimately causing regression of hormone-sensitive tissues.

Pharmacodynamics

Upon administration, goserelin causes an initial increase in serum LH and FSH levels, which is followed by a sustained decrease in gonadotropins and serum testosterone levels. This pharmacodynamic effect effectively mimics surgical castration, as testosterone levels can fall to castrate levels approximately 21 days after the initiation of therapy. Studies have shown that goserelin can lead to the regression of hormone-sensitive tumors.

Pharmacokinetics

Goserelin is administered as a subcutaneous depot formulation, with pharmacokinetics evaluated in both male and female healthy volunteers. Following a single or multiple doses, goserelin reaches peak serum concentrations, and its effects on gonadotropin suppression are maintained over the duration of therapy. The drug exhibits a sustained release profile, contributing to its effectiveness in long-term treatment settings.

Contra-indications

• Hypersensitivity to goserelin or any of its components
• Pregnancy
• Breastfeeding
• Unhealed lesions from dental or oral surgery

Adverse effects

• Abdominal discomfort
• Altered smell sensation
• Alopecia
• Anxiety
• Appetite change
• Constipation
• Diarrhoea
• Dizziness
• Drowsiness
• Dry eye
• Dysuria
• Fatigue
• Feeling of pressure behind the eyes
• Hypercalcaemia (on discontinuation)
• Increased risk of fracture
• Menopausal symptoms
• Muscle weakness
• Nausea
• Oedema
• Palpitations
• Sexual dysfunction
• Skin reactions
• Vision disorders
• Vomiting
• Weight changes
• QT interval prolongation
• Hyperhidrosis
• Memory loss
• Embolism and thrombosis
• Second primary malignancy
• Osteonecrosis of the jaw
• Atypical femur fracture

Precautions

• Caution in patients with a history of pituitary tumors
• Monitor for symptoms of hypercalcaemia
• Ensure effective non-hormonal contraception during treatment
• Consider temporary interruption of treatment in cases of osteonecrosis of the jaw

Pregnancy

Avoid in pregnancy. Pregnancy should be excluded before treatment initiation.

Breast-feeding

Avoid during breastfeeding.

Storage

Store in a refrigerator (2 to 8 degrees Celsius). Protect from light.

Formulations

• Goserelin acetate 3.6 mg depot injection (Zoladex®)

Mechanism of action

Goserelin is a synthetic decapeptide analogue of LHRH. Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. The result is sustained suppression of LH and serum testosterone levels. Zoladex is a synthetic decapeptide analogue of LHRH. Zoladex acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. Following initial administration, ZOLADEX causes an initial increase in serum-luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels with subsequent increases in serum levels of testosterone. Chronic administration of Zoladex leads to sustained suppression of pituitary gonadotropins, and serum levels of testosterone consequently fall into the range normally seen in surgically castrated men approximately 21 days after initiation of therapy. This leads to accessory sex organ regression. In animal and in in vitro studies, administration of goserelin resulted in the regression or inhibition of growth of the hormonally sensitive dimethylbenzanthracene (DMBA)-induced rat mammary tumor and Dunning R3327 prostate tumor. In clinical trials using Zoladex 3.6 mg with follow-up of more than 2 years, suppression of serum testosterone to castrate levels has been maintained for the duration of therapy.

Pharmacodynamics

The pharmacokinetics of goserelin have been determined in both male and female healthy volunteers and patients. In these studies, goserelin was administered as a single 250µg (aqueous solution) dose and as a single or multiple 3.6 mg depot dose by subcutaneous route.