Lundbeck Limited

Section 4.9 has been revised with the addition of the highlighted text:

Overdosage may cause somnolence, or even coma, extrapyramidal symptoms, convulsions, hypotension, shock, hyper-or hypothermia.  ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular arrhythmias have been reported when administered in overdose together with drugs known to affect the heart. Treatment is symptomatic and supportive, with measures aimed at supporting the respiratory and cardiovascular systems.  The following specific measures may be employed if required.

-    anticholinergic antiparkinson drugs if extrapyramidal symptoms occur.

-     sedation (with benzodiazepines) in the unlikely event of agitation or excitement or convulsions.

-     noradrenaline in saline intravenous drip if the patient is in shock.  Adrenaline must not be given.

The changes affect Sections 4.1, 4.2, 4.4 and 4.8 of the SPC. The changes to Sections 4.4 and 4.8 of the SPC are to implement changes required by the Pharmacovigilance Working Party (PhVWP) for antipsychotic drugs.

Section 4.1 Therapeutic indications

Addition of:

Use of Depixol should be restricted to those stabilised on oral therapy.

Section 4.2 Posology and method of administration

Addition of:

Reduced renal function

Flupentixol has not been studied in renal impairment. Increased cerebral sensitivity to antipsychotics has been noted in severe renal impairment (see section 4.4).

Reduced hepatic function

Flupentixol has not been studied in hepatic impairment. It is extensively metabolised by the liver and particular caution should be used in this situation and serum level monitoring is advised (see section 4.4). Depixol should be initiated at low doses orally to check for tolerability before switching to the depot formulation.

Section 4.4 Special warnings and precautions for use

Addition of:

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Depixol and preventive measures undertaken.

Increased Mortality in Elderly people with Dementia

Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.
Depixol is not licensed for the treatment of dementia-related behavioural disturbances.

Section 4.8 Undesirable effects

Addition of:

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs- Frequency unknown.

Section 4.5 Interaction with other medicinal products and other forms of interaction

Addition of:

Relevant classes include:

• class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)

• some antipsychotics (e.g. thioridazine)

• some macrolides (e.g. erythromycin)

• some antihistamines

• some quinolone antibiotics (e.g. moxifloxacin)

Deletion of:

Relevant classes include:

• class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)

• some antipsychotics (e.g. thioridazine)

• some macrolides (e.g. erythromycin)

• some antihistamines (e.g. terfenadine, astemizole)

• some quinolone antibiotics (e.g. gatifloxacin, moxifloxacin)

For further information contact: Lundbeck Medical Information, email: ukmedicalinformation@lundbeck.com

Tel: 01908 638972.

Section 4.3 addition of - Hypersensitivity to the active substance or to any of the excipients (see section 6.1).

Circulatory collapse, depressed level of consciousness due to any cause (e.g. intoxication with alcohol, barbiturates or opiates), coma

Section 4.8 revision of section

Section 4.5: Addition of: “Increases in the QT interval related to antipsychotic treatment may be exacerbated by the co‑administration of other drugs known to significantly increase the QT interval.  Co-administration of such drugs should be avoided.  Relevant classes include:

• class Ia and III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide)
• some antipsychotics (e.g. thioridazine)
• some macrolides (e.g. erythromycin)
• some antihistamines (e.g. terfenadine, astemizole)
• some quinolone antibiotics (e.g. gatifloxacin, moxifloxacin)

The above list is not exhaustive and other individual drugs known to significantly increase QT interval (e.g. cisapride, lithium) should be avoided.
Drugs known to cause electrolyte disturbances such as thiazide diuretics (hypokalaemia) and drugs known to increase the plasma concentration of flupentixol should also be used with caution as they may increase the risk of QT prolongation and malignant arrythmias (see section 4.4).
Section 4.8: Addition of: “As with other drugs belonging to the therapeutic class of antipsychotics, rare cases of QT prolongation, ventricular arrythmias - ventricular fibrillation, ventricular tachycardia, Torsade de Pointes and sudden unexplained death have been reported for flupentixol decanoate (see section 4.4).
Section 4.9, Addition of: “ECG changes, QT prolongation, Torsade de Pointes, cardiac arrest and ventricular arrhythmias have been reported when administered in overdose together with drugs known to affect the heart.