STABLON Coated tablet Ref.[7676] Active ingredients: Tianeptine

• Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self-harming and suicidality (suicidal behaviour). This risk persists until a significant remission has been obtained. Clinical improvement may not be obtained until after several weeks of treatment, and so patients must be closely monitored until this improvement has been achieved. Clinical experience shows that the risk of suicide can increase during the very early stages of recovery. Patients with a history of suicidal behaviour or expressing significant suicidal thoughts before starting the treatment face a higher risk of the onset of suicidal thoughts or suicidal behaviour, and must be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of the use of antidepressants in adults displaying psychiatric disorders has revealed an increase in the risk of suicidal behaviour in patients under 25 years of age who were being treated with antidepressants compared to those receiving a placebo. Careful monitoring of patients, and particularly of high-risk patients, must accompany use of this medication, particularly at the beginning of treatment and at times of dose changes. The patients (and their family and friends) must be alerted to the need to monitor for the onset of clinical worsening, the appearance of suicidal thoughts/behaviour or any abnormal change of behaviour, and to seek medical advice immediately if such symptoms present.
• As with any psychotropic drug, the intake of alcohol should be avoided during the treatment with tianeptine.
• If general anaesthesia is necessary, the anaesthetist should be informed of the treatment, and the drug stopped 24 or 48 hours prior to surgery.
• In an emergency, surgery may be performed without an intervening wash-out period; peroperative monitoring should be performed.
• Do not exceed the recommended doses.
• Abuse/dependence and withdrawal syndrome:
  • If there is a history of drug dependence or alcohol dependence, the patients must be kept under very close surveillance in order to avoid any increase in dosage.
  • After discontinuation of treatment with tianeptine, withdrawal symptoms have been observed in some patients. The following events have been observed: anxiety, muscle pain, abdominal pain, insomnia, joint pain. When the treatment is started, the patient should be informed on the risk of withdrawal syndrome at discontinuation.
  • If the treatment is to be interrupted the dosage should be gradually reduced over a period of 7 to 14 days in order to reduce the risk of withdrawal reactions (see section 4.2).
• The combination with MAOIs is unadvisable: a wash-out period of two weeks is necessary between treatment with MAOIs and treatment with tianeptine. A wash-out period of only 24 hours is required when replacing tianeptine with an MAOI.
• Hyponatraemia: Hyponatraemia probably due to a syndrome of inappropriate anti-diuretic hormone secretion (SIADH) has been reported with the use of tianeptine. The majority of cases were reported in the elderly, especially when coupled with a recent history of, or condition pre-disposing to, altered fluid balance. Caution should be exercised in patients at increased risk for hyponatraemia, such as elderly, cirrhotic, or dehydrated patients or those treated with diuretics.
• Due to the sucrose content, this medicinal product is contraindicated for patients with fructose intolerance, glucose and galatose malbsorption syndrome or sucrase-isomaltase deficiency (rare inherited diseases).

Level of sodium: This medicine contains less than 1 mmol sodium (23 mg) per coated-tablet, i.e. essentially ‘sodium-free’.

Use in children and adolescents: Tianeptine is not recommended in the treatment of depression in patients under 18 years of age since safety and efficacy of tianeptine have not been established in this age group. In clinical trials among children and adolescents treated with other antidepressants, suicide-related behaviour (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed compared to those treated with placebo.

Unadvisable combinations

With irreversible MAOIs inhibitors (ipronazide): risk of cardiovascular collapse or paroxysmal hypertension, hyperthermia, convulsions, death.

Pregnancy

In a peri- and postnatal study, increased post-implantation and postnatal losses were observed in rats at a maternotoxic dose (see section 5.3). There are no or limited data (less than 300 pregnancy outcomes) from the use of tianeptine in pregnant women.

Therefore, it is preferable not to use tianeptine during pregnancy whatever the term.

It is preferable to maintain a balanced maternal psychic equilibrium throughout pregnancy. If tianeptine is necessary to ensure this balance, treatment should be initiated or continued at the necessary dose throughout pregnancy and if possible as monotherapy and the pharmacological profile of the molecule should be taken into account when monitoring the newborn baby.

Breast-feeding

Dysgalactia in the dams was observed in rats at a maternotoxic dose (see section 5.3). Tricyclic antidepressants are excreted into breast milk, and thus breast feeding is not recommended during treatment.

Fertility

In rats, a fertility study showed decreased reproductive performances (increase in pre-implantation losses) at a maternotoxic dose (see section 5.3).

In humans, no clinical data are available.

Some patients may experience diminished alertness. The attention of drivers and machine-operators should thus be drawn to the risk of somnolence with this product.

Summary of safety profile

Side effects reported with tianeptine in clinical trials are of mild intensity. They consist mainly in nausea, constipation, abdominal pain, somnolence, headaches, dry mouth and dizziness.

Tabulated list of adverse reactions

The following adverse reactions have been reported during clinical trials and/or post marketing use with tianeptine and are ranked using the following frequency: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (≥1/100,000 to <1/10,000); not known (cannot be estimated from the available data).

^* Post-marketing experience

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 ADR Reporting Website: www.medicinesauthority.gov.mt/adrportal.

Not applicable.