Triptorelin

General: In rare cases, treatment with GnRH agonists may reveal the presence of a previously undiagnosed gonadotroph cell pituitary adenoma. These patients may present with signs of pituitary apoplexy characterised by sudden headache, vomiting, visual impairment and ophthalmoplegia. Patients treated with GnRH agonists such as triptorelin are at increased risk of developing depression, which may be severe. Patients should be informed of this risk and treated appropriately if depressive symptoms occur. Patients with known depression should be closely monitored during therapy. Treatment with Decapeptyl should be initiated only after a thorough diagnosis (e.g. laparoscopy). Before starting triptorelin, it must be confirmed that the patient is not pregnant. Because menstruation ceases during treatment in women, the patient should inform her physician if menstruation persists. Reduction in bone mineral density Use of GnRH agonists is likely to cause a reduction in bone mineral density averaging 1% per month over a six-month treatment period. Every 10% reduction in bone mineral density is associated with an approximately two- to three-fold increase in fracture risk. Currently available data indicate that, following discontinuation of treatment, most women recover the bone mass that was lost. No specific data are available for patients with established osteoporosis or for patients with risk factors for osteoporosis (e.g. chronic alcohol abuse, smoking, long-term therapy with medicinal products that reduce bone mineral density such as anticonvulsants or corticosteroids, family history of osteoporosis, malnutrition, e.g. anorexia nervosa). Since reduction in bone mineral density is likely to pose a greater risk in these patients, treatment with triptorelin should be considered on a case-by-case basis and initiated only after careful assessment that the benefits outweigh the risks. Additional measures to counteract loss of bone mineral density should also be considered. Uterine fibroids and endometriosis At the recommended doses, triptorelin produces a sustained hypogonadotrophic amenorrhoea. If genital bleeding occurs beyond the first month of therapy, plasma estradiol levels should be measured. If these values are below 50 pg/ml, possible organic lesions should be investigated. Ovarian function resumes after discontinuation of treatment, i.e. menstrual bleeding returns 7–12 weeks after the last injection. Non-hormonal contraception should be used throughout treatment and for one month after the last injection. Since menstruation should cease during triptorelin therapy, the patient should be advised to inform her physician if regular menstruation persists. During treatment of uterine fibroids, the size of the uterus and of the fibroids should be monitored regularly, for example by ultrasound. Disproportionately rapid reduction in uterine volume relative to fibroid volume has, in several cases, resulted in bleeding and sepsis. Several cases of bleeding have been reported following treatment with GnRH analogues in patients with submucosal fibroids. Bleeding generally occurred 6–10 weeks after initiation of therapy. Assisted reproduction Down-regulation and prevention of premature LH surge Assisted reproduction is associated with an increased risk of multiple pregnancy, ectopic pregnancy and congenital malformations. These risks also apply when Decapeptyl is used as an adjunct in controlled ovarian stimulation. Administration of a GnRH agonist during controlled ovarian stimulation may increase the risk of ovarian hyperstimulation syndrome (OHSS) and ovarian cysts. In a minority of predisposed patients, particularly those with polycystic ovary syndrome, follicular recruitment induced by GnRH analogues and gonadotropins may be markedly increased. As with other GnRH analogues, cases of ovarian hyperstimulation syndrome have been reported in association with the use of triptorelin in combination with gonadotropins. In assisted reproduction, despite prolonged exposure, triptorelin is not expected to be present in the circulation at the time of embryo transfer. Ovarian hyperstimulation syndrome (OHSS) OHSS is a clinical entity distinct from uncomplicated ovarian enlargement. OHSS is a syndrome that may present with escalating degrees of severity. It comprises marked ovarian enlargement, high serum sex steroid levels and increased vascular permeability, which can result in fluid accumulation in the peritoneal, pleural and, rarely, pericardial cavities. The following symptomatology may be observed in severe cases of OHSS: abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea. Clinical evaluation may reveal hypovolaemia, haemoconcentration, electrolyte imbalance, ascites, haemoperitoneum, pleural effusion, hydrothorax, acute pulmonary distress and thromboembolic events. Excessive ovarian response to gonadotropin treatment rarely produces OHSS unless hCG is administered to trigger ovulation. Therefore, in the event of ovarian hyperstimulation, hCG administration should be withheld and the patient advised to abstain from sexual intercourse or to use barrier methods for at least 4 days. OHSS may progress rapidly (within 24 hours to several days) into a serious medical event; patients should therefore be monitored for at least 2 weeks after hCG administration. OHSS may be more severe and prolonged in the event of pregnancy. OHSS most commonly develops after discontinuation of hormonal therapy, reaching its peak 7–10 days after treatment. OHSS usually resolves spontaneously with the onset of menstruation. In the event of severe OHSS, gonadotropin therapy must be discontinued, the patient hospitalised, and specific treatment for OHSS instituted, e.g. bed rest, intravenous infusion of electrolyte or colloid solutions, or heparin. The risk of OHSS may be higher when GnRH agonists are used in combination with gonadotropins than when gonadotropins are used alone. Ovarian cysts Ovarian cysts may occur during the initial phase of treatment with GnRH agonists. These cysts are usually asymptomatic and non-functional. This medicinal product contains less than 1 mmol sodium (23 mg) per injection, that is to say essentially "sodium-free".