Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

Special Warnings

•   All patients must be advised that if they experience fever, sore throat or any other infection, they should inform their treating physician immediately and undergo a complete blood count.
Treatment with this drug should be discontinued if any marked changes (hyperleucocytosis, granulocytopenia) are observed in the blood count.

•   Neuroleptic malignant syndrome : if unexplained fever occurs, treatment must imperatively be discontinued since this may be one of the symptoms of the malignant syndrome reported with neuroleptic drugs ( pallor, hyperthermia, autonomic disorders ,consciousness disorders, muscle rigidity)
Signs of autonomic dysfunction, such as perspiration and changes in arterial blood pressure, may occur before hyperthermia and thus constitute early warning signs.
Although this effect of neuroleptics may be idiosyncratic in origin, there may be predisposing risk factors, such as dehydration and organic brain damage.

•   Prolonged QT interval: neuroleptics of the phenothiazine class can cause dose-dependent prolongation of the QT interval. This effect, which is known to increase the risk of serious ventricular arrhythmias, particularly torsades de pointes, is enhanced in patients with bradycardia, hypokalemia and congenital or acquired QT prolongation (when neuroleptics are taken with a medicinal product prolonging the QT interval) (see Section     4.8).

Consequently, before administering the drug, and if the clinical situation permits, patients should be checked for the following risk factors that may promote this type of arrhythmia:
−   bradycardia of less than 55 beats per minute,
−   hypokalemia,
−   congenital QT interval prolongation,
−   ongoing treatment with a drug likely to induce marked bradycardia (less than 55 beats per minute), hypokalemia, delayed intracardiac conduction or QT interval prolongation (see Sections 4.3 and 4.5).

Except in emergencies, it is recommended that an ECG be performed as part of the initial evaluation of patients due to receive treatment with a neuroleptic agent.

•   Stroke: in randomized, placebo-controlled clinical trials in elderly patients with dementia and treated with atypical antipsychotics, a higher risk of stroke was observed versus placebo. The reason for this increased risk is unknown. Increased risk with other antipsychotics or in other patient populations cannot be ruled out. This drug should be used with caution in patients with risk factors for stroke.

•   Elderly patients with dementia: the risk of mortality increases in elderly patients suffering from dementia-related psychotic disorders and treated with antipsychotic drugs.

Analysis of 17 placebo-controlled studies (mean duration of 10 weeks), conducted in patients mainly taking atypical antipsychotic drugs showed that the risk of mortality increased 1.6 to 1.7-fold in patients treated with these medicinal products versus placebo.

After a mean treatment period of 10 weeks, the risk of mortality was 4.5% in the treated patient group versus 2.6% in the placebo group.

Although the causes of death varied in the clinical trials with the atypical antipsychotic drugs, the majority of deaths appeared to be either cardiovascular (e.g. heart failure, sudden death) or infectious (e.g. pneumonia).

Epidemiological studies suggest that treatment with conventional antipsychotic drugs may increase mortality, as is the case for atypical antipsychotic drugs.

The respective contribution of the antipsychotic drug and patient characteristics to the increase in mortality found in the epidemiological studies is unclear.

•   Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotic drugs often present acquired risk factors for VTE, any potential risk factors for VTE must be identified before and during treatment with Neuleptil, and preventive measures should be taken (see Section 4.8).

•   Except in special cases, this drug should not be administered to patients with Parkinson's disease.

•   The onset of paralytic ileus, which may be manifested by distension and abdominal pain, should be treated as an emergency.

•   Use of this drug is not recommended in combination with levodopa and antiparkinsonian dopamine agonists (see Section 4.5).

•   Patients are strongly advised not to drink alcoholic beverages or to take medicines containing alcohol during treatment.

Neuleptil drops

•   In children, an annual clinical examination to assess learning capacities is recommended due to the cognitive effects of the drug. Dosage should be adjusted on a regular basis depending on the child's clinical status.
Use in children under 6 years of age is reserved for exceptional circumstances in a specialized setting.
•   This medicinal product contains sucrose. Its use in patients with fructose intolerance, glucose and galactose malabsorption syndrome or sucrase-isomaltase deficiency is not recommended.

This drug contains 12% v/v ethanol (alcohol); i.e. 96.9 mg of ethanol in 40 drops or 1 ml of solution, which is equivalent to 2.4 ml of beer or 1 ml of wine for this dose. Use of this drug is dangerous in alcoholics and should be weighed in pregnant or breast-feeding women, in high-risk populations such as patients with hepatic insufficiency or epilepsy.

Precautions for use

Monitoring of treatment with pericyazine must be intensified in the following cases:
• Epileptic patients, as periciazine may lower the seizure threshold. Treatment must be discontinued if seizures occur,
• Elderly patients with : o greater susceptibility to postural hypotension, sedation and extrapyramidal effects, o chronic constipation (risk of paralytic ileus),
o possible prostatic hypertrophy.

•   Patients with certain cardiovascular disease due to the quinidine-like, tachycardia- inducing and hypotensive effects of this class of drugs.
•   Patients with severe hepatic and/or renal insufficiency, due to the risk of accumulation.

Cases of hyperglycemia or glucose intolerance and onset or exacerbation of diabetes have been reported in patients treated with phenothiazines (see Section 4.8).
Patients treated with antipsychotics including Neuleptil require clinical monitoring and monitoring of laboratory test results as per the current recommendations. Diabetic patients or those with risk factors for diabetes should be particularly closely monitored.

Effects on Driving

4.7 Effects on ability to drive and use machines

The attention of patients, particularly drivers and machine operators, should be drawn to the risk of drowsiness associated with this medicine especially at the beginning of treatment.