LUCRIN DEPOT

What it is

LUCRIN DEPOT contains leuprorelin acetate. It is supplied as a prefilled dual chamber syringe consisting of powder for injection and diluent. LUCRIN DEPOT is available in five adult formulations: 1-Month 7.5 mg, 3-Month 22.5 mg, 4-Month 30 mg, and 6-Month 45 mg. A paediatric formulation, LUCRIN DEPOT Paediatric 30 mg, is also available. The powder for injection is a white lyophilised powder that becomes a milky suspension once reconstituted.

Approved indications

— Palliative treatment of metastatic or locally advanced prostate cancer. — Treatment of children with central precocious puberty.

Dosing overview

LUCRIN DEPOT 1-Month 7.5 mg is administered as one injection every 4 weeks. LUCRIN DEPOT 3-Month 22.5 mg is administered as one injection every 12 weeks. LUCRIN DEPOT 4-Month 30 mg is administered as one injection every 16 weeks. LUCRIN DEPOT 6-Month 45 mg is administered as one injection every 24 weeks. LUCRIN DEPOT Paediatric 30 mg is administered once every three months as a single intramuscular injection. All formulations are administered as intramuscular injections.

Key safety warnings

In men with prostate cancer, LUCRIN DEPOT causes an initial increase in serum testosterone levels during the first week of treatment, which may lead to transient worsening of symptoms or temporary bone pain. Isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. Co-initiating a non-steroidal anti-androgen with leuprorelin acetate has proven benefit in reducing flare reactions in at-risk patients such as those with metastatic vertebral lesions or at risk of cord compression. Postmarketing reports of convulsions have been observed in patients on leuprorelin acetate therapy, including in the female and paediatric populations, patients with a history of seizures, epilepsy, cerebrovascular disorders, or central nervous system anomalies or tumours, and in patients on concomitant medications associated with convulsions such as bupropion and SSRIs. Delayed hypersensitivity reactions including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis have been very rarely reported postmarketing in association with leuprorelin acetate therapy; discontinue future therapy at first signs or symptoms of a delayed hypersensitivity reaction. Androgen deprivation therapy, including GnRH agonists, may be associated with an increased risk of metabolic changes such as hyperglycaemia, diabetes, hyperlipidaemia, and non-alcoholic fatty liver disease; patients at increased risk should be monitored for signs and symptoms of metabolic syndrome including lipids, blood glucose and glycosylated haemoglobin. Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with GnRH agonists in men; the risk appears low and should be evaluated along with cardiovascular risk factors when determining treatment, and patients should be monitored for symptoms suggestive of cardiovascular disease. Pseudotumour cerebri or idiopathic intracranial hypertension has been reported in paediatric patients receiving leuprorelin acetate; patients should be monitored for signs and symptoms including headache, papilloedema, and visual changes, referred to an ophthalmologist if indicated, and leuprorelin acetate permanently discontinued if confirmed.

Contraindications

LUCRIN DEPOT is contraindicated in patients with known hypersensitivity to GnRH, GnRH agonists, leuprorelin acetate, similar nonapeptides or any of the excipients. Although not expected to be relevant to the approved indications, LUCRIN DEPOT is contraindicated when the patient is pregnant or may become pregnant due to its embryotoxic effects. LUCRIN DEPOT should not be administered to a nursing mother, as it is not known whether leuprorelin acetate is excreted into human milk.

PBS listing

The 7.5 mg strength is listed on the PBS with restriction status, ex-manufacturer price A$232.55. The 22.5 mg strength is listed on the PBS with restriction status, ex-manufacturer price A$625.45. The 4-Month 30 mg strength is listed on the PBS with restriction status, ex-manufacturer price A$833.55. The paediatric 30 mg (3-month) formulation is listed on the PBS with two items, restriction status, ex-manufacturer price A$624.70. The 45 mg strength is listed on the PBS with restriction status, ex-manufacturer price A$1249.40.

Regulatory history

The 7.5 mg, 3-Month 22.5 mg, and 4-Month 30 mg formulations were first listed on the ARTG on 8 April 2005. The 6-Month 45 mg formulation was first listed on the ARTG on 12 May 2015. The paediatric 30 mg formulation was first listed on the ARTG on 13 October 2014. An AusPAR was issued on 30 July 2010 for approval of a new 30 mg 6-month strength formulation (Lucrin XL Depot). In March 2016, the PBAC recommended amending the PBS listings for leuprorelin for the treatment of locally advanced or metastatic prostate carcinoma and central precocious puberty from Authority Required to Restricted Benefit.