DIPHERELINE

What it is

Diphereline is triptorelin embonate available as 3.75 mg, 11.25 mg and 22.5 mg powder for suspension. It is a powder and solvent for suspension for injection in the form of prolonged release granules. Triptorelin is a gonadotrophin releasing hormone (GnRH) agonist that inhibits gonadotrophin secretion when given continuously and in therapeutic doses.

Approved indications

— Hormone-dependent locally advanced or metastatic prostate cancer — Central precocious puberty in children 2 years and older (22.5 mg 6 month formulation only)

Dosing overview

The recommended dose of Diphereline 3.75 mg is administered once a month as a single intramuscular injection. The recommended dose of Diphereline 11.25 mg is administered every three months as a single intramuscular injection. The recommended dose of Diphereline 22.5 mg is administered every six months as a single intramuscular injection. The lyophilised microgranules are to be reconstituted using 2 mL sterile water for injection.

Key safety warnings

Initially triptorelin causes a transient increase in serum testosterone levels. As a consequence, isolated cases of transient worsening of signs and symptoms of prostate cancer may occasionally develop during the first weeks of treatment. During the initial phase of treatment, consideration should be given to the additional administration of a suitable anti-androgen to counteract the initial rise in serum testosterone levels and the worsening of clinical symptoms. Androgen deprivation therapy may prolong the QT interval. In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval, physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Diphereline. An increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratio and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and managed according to current clinical practice. The use of GnRH agonists may cause reduction in bone mineral density. Long-term androgen deprivation either by bilateral orchiectomy or administration of GnRH analogues is associated with increased risk of bone loss and may lead to osteoporosis and increased risk of bone fracture. In patients undergoing treatment with GnRH agonists, an increased risk of mood changes and depression (which may be severe and includes very rare cases of suicidal ideation or suicide attempts from post-marketing experience) was reported. Patients should be informed accordingly and treated as appropriate if symptoms occur. Patients with known depression should be monitored closely during therapy. Hyperglycaemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Monitor blood glucose and/or glycosylated haemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for the treatment of hyperglycaemia or diabetes.

Contraindications

Diphereline is contraindicated in patients with known hypersensitivity to the active substance triptorelin, GnRH, other GnRH agonist analogues or to any of the excipients. Polysorbate 80 has been observed to induce hypersensitivity reactions in some patients. Diphereline must not be administered if there are indications that the tumour is not hormone-dependent or following surgical castration. Diphereline is contraindicated in patients with spinal cord compression secondary to prostate cancer metastases. Diphereline is contraindicated in pregnancy and during lactation.

Regulatory history

The 3.75 mg and 11.25 mg formulations were first listed on the ARTG on 28 August 2006. The 22.5 mg formulation was first listed on the ARTG on 27 July 2010. The PBAC recommended listing for central precocious puberty in July 2021. This medicinal product is subject to additional monitoring in Australia due to approval of an extension of indications.