SALVACYL Powder and solvent for prolonged-release suspension for injection Ref.[27669] Active ingredients: Triptorelin

Treatment with Salvacyl should be considered on an individual basis and only be initiated if the benefits of treatment outweigh the risk following a very careful appraisal.

Initially triptorelin causes a transient increase in serum testosterone levels. During the initial phase of treatment, the patient should be closely monitored by the treating psychiatrist and consideration should be given to the additional administration of a suitable anti-androgen to counteract the initial rise in serum testosterone levels in order to control possible increase in sexual drive, if considered appropriate.

Following treatment interruption, there is a risk of an increased sensitivity to the restored testosterone, which can lead to a highly increased sexual drive. For this reason, the addition of an adequate anti-androgen before stopping Salvacyl treatment should be considered.

Once the castration levels of testosterone have been achieved by the end of the first month, they are maintained for as long as the patient receives their injection every twelve weeks.

The evaluation of the treatment effect is essentially clinical. A clinical assessment of the treatment effect should be done regularly, e.g. before each 3-month injection of triptorelin. Serum testosterone levels may be measured in case there is any doubt of treatment effect, which could be related to compliance with triptorelin treatment or to a technical problem with the injection.

Caution is required in patients treated with anti-coagulants, due to the potential risk of haematomas at the site of injection.

Administration of triptorelin in therapeutic doses results in suppression of the pituitary gonadal system. Normal function is usually restored after treatment is discontinued. Diagnostic tests of pituitary gonadal function conducted during treatment and after discontinuation of therapy with a GnRH agonist may therefore be misleading.

Long term androgen deprivation either by bilateral orchidectomy or administration of GnRH analogues is associated with increased risk of bone loss and may lead to osteoporosis and increased risk of bone fracture. Preliminary data suggest that the use of a bisphosphonate in combination with a GnRH agonist may reduce bone mineral loss. Particular caution is necessary in patients with additional risk factors for osteoporosis (e.g. chronic alcohol abuse, smokers, long-term therapy with drugs that reduce bone mineral density, e.g. anticonvulsants or corticoids, family history of osteoporosis, malnutrition).

Bone mineral density may be assessed before the start of treatment and may be followed regularly during the treatment.

In order to prevent the treatment-related bone loss, lifestyle modification including smoking cessation, moderation of alcohol consumption and regular weight bearing exercise are recommended. Adequate dietary calcium and vitamin D intake should also be maintained.

Rarely, treatment with GnRH analogues may reveal the presence of a previously unknown gonadotroph cell pituitary adenoma. These patients may present with a pituitary apoplexy characterised by sudden headache, vomiting, visual impairment and ophthalmoplegia.

Increased lymphocyte count has been reported with patients undergoing GnRH analogue treatment. This secondary lymphocytosis is apparently related to GnRH induced castration and seems to indicate that gonadal hormones are involved in thymic involution.

There is an increased risk of incident depression (which may be severe) in patients undergoing treatment with GnRH agonists, such as triptorelin. Patients should be informed accordingly and treated as appropriate if symptoms occur. Patients with known depression should be monitored closely during therapy.

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 (see section 4.5) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Salvacyl.

In addition, from epidemiological data, it has been observed that patients may experience metabolic changes (e.g. glucose intolerance), or an increased risk of cardiovascular disease during androgen deprivation therapy. However, prospective data did not confirm the link between treatment with GnRH analogues and an increase in cardiovascular mortality. Patients at high risk for metabolic or cardiovascular diseases should be carefully assessed before commencing treatment and adequately monitored during androgen deprivation therapy.

Salvacyl contains less than 1 mmol (23 mg) sodium per dose, i.e. essentially ‘sodium-free’.

When triptorelin is co-administered with drugs affecting pituitary secretion of gonadotropins, caution should be exercised and it is recommended that the patient’s hormonal status be supervised.

Since androgen deprivation treatment may prolong the QT interval, the concomitant use of Salvacyl with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics, etc. should be carefully evaluated (see section 4.4).

Salvacyl is not indicated for use in females.

Animal studies have shown effects on reproductive parameters (see section 5.3).

No studies on the effects on the ability to drive and use machines have been performed. However, the ability to drive and use machines may be impaired should the patient experience dizziness, somnolence and visual disturbances being possible undesirable effects of treatment.

As seen with other GnRH agonist therapies or after surgical castration, the most commonly observed adverse events related to triptorelin treatment were due to its expected pharmacological effects. These effects include hot flushes and erectile dysfunction (observed in 10% of the patients). With the exception of hypersensitivity reactions (rare) and injection site pain (<5%), all adverse events are known to be related to testosterone changes. The long-term use of synthetic GnRH analogues may be associated with increased bone loss and may lead to osteoporosis and increases the risk of bone fracture.

The following adverse reactions considered as at least possibly related to triptorelin treatment were reported in clinical studies performed in men suffering from advanced prostate cancer and in healthy male volunteers. Most of these events are known to be related to biochemical or surgical castration.

The frequency of the adverse reactions is classified as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10000 to <1/1000); not known (cannot be estimated from the available data).

^* This frequency is based on class-effect frequencies common for all GnRH agonists.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.