Triptorelin embonate

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Diphereline (Ipsen)
6 mL vials containing 3.75 mg or 11.25 mg as powder for reconstitution
Approved indication: prostate cancer
Australian Medicines Handbook section 14.3.3

Locally advanced or metastatic prostate cancer can be managed by androgen ablation. This can be achieved by orchidectomy or hormonal treatment. Several agonists of luteinising hormone releasing hormone, such as goserelin and leuprorelin, are approved for this indication. Like other agonists, triptorelin initially causes a surge in luteinising hormone concentrations, but continued use reduces pituitary secretion. This leads to reduced androgen production with testosterone concentrations falling to levels similar to those seen after orchidectomy. Patients can be given a monthly intramuscular injection (3.75 mg) or an injection of the long-acting formulation (11.25 mg) every three months. As the molecule is a synthetic peptide it is probably degraded like a protein. Clearance is reduced by hepatic or renal impairment.

A South African trial randomised 172 men with advanced prostate cancer to have monthly injections and 174 to receive the long-acting formulation. After 29 days 93% of the patients on the monthly regimen and 98% of those on the three-monthly regimen had reached the target testosterone concentration. Both regimens maintained these concentrations in most patients during the 36 weeks of the study.

Another South African trial randomised 140 men to receive monthly triptorelin and 144 to receive monthly leuprorelin. After 29 days the proportion of men with target testosterone concentrations was significantly higher with leuprorelin (99% vs 91%). By 57 days there was no significant difference.¹

The hormonal surge at the start of treatment may exacerbate symptoms, such as bone pain and bladder outflow obstruction. As treatment continues patients may complain of decreased libido, impotence, breast pain and hot flushes. Other adverse events include skeletal pain, hypertension, oedema, weight gain and pain at the injection site.

Although triptorelin has been available overseas for a few years there is little published information about its impact on survival. Although survival was not the primary end point of the comparative study, the nine-month survival rate was 97% with monthly triptorelin and 91% with leuprorelin.¹

manufacturer declined to supply data

The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Note on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).