Special Warning : אזהרת שימוש

4.4.Special warnings and precautions for use
Warnings

- Each patient should be informed that in case of the appearance of fever, throat infection or any other infection, it is imperative to inform at once the attending physician and to control the hemogram immediately. In case of a downright modification of the latter (hyperleukocytosis, granulopenia), the administration of this treatment should be interrupted.

- Malignant syndrome: in case of unexplainable hyperthermia, it is imperative to suspend the treatment, because this sign can be one of the elements of the malignant syndrome described for neuroleptics (paleness, hyperthermia, vegetative disturbances, alteration of the conscience, muscular rigidity).
The signs of vegetative dysfunction, such as sweating and arterial instability, can precede the appearance of the hyperthermia and, consequently, constitute precocious signals.
Although this effect of neuroleptics can have an idiosyncratic origin, it seems that certain risk factors predispose to it, such as the dehydration or organic cerebral attacks.

- Lengthening of the QT interval: Neuroleptic phenothiazines may potentiate QT interval prolongation which increase the risk of onset of serious ventricular arrhythmias of the torsade de pointes type which is potentially fatal (sudden death). The levomepromazine lengthens the QT interval in a dose-dependent manner. This effect, which is known to potentiate the risk of the occurrence of grave ventricular rhythm disturbances of the torsades de pointes type, is increased due to the existence of a bradycardia, hypokalemia, a long congenital or acquired QT (association to a medicine increasing the QT interval). Therefore, it is appropriate before any administration, whenever the clinical situation permits, to make sure of the absence of factors that can be favorable for the occurrence of this rhythm disturbance: o bradycardia inferior to 55 beats per minute o hypokalemia o congenital lengthening of the QT interval o current treatment with a medicine that is susceptible to cause a marked bradycardia (< 55 beats per minute), a hypokalemia, a slowing-down of the intracardiac conduction, a lengthening of the QT interval.

- Stroke: In randomized, placebo-controlled clinical trials in elderly patients with dementia and treated with certain 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 must 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 psychosis 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 Nozinan 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. Very rare cases of potentially fatal necrotizing enterocolitis have been reported.

- It is inadvisable to use this drug in combination with alcohol, levodopa, dopamine antiparkinsonian drugs, antiparasitics likely to induce torsades de pointes, methadone, other neuroleptics and drugs likely to induce torsades de pointes (see Section 4.5).
- This medicinal product contains lactose. Its use is inadvisable in patients with galactose intolerance, Lapp lactase deficiency or glucose and galactose malabsorption syndrome (rare hereditary diseases).

- This medicinal product may be administered in patients with celiac disease. Wheat starch can contain gluten, but only traces, and is therefore considered safe for patients with celiac disease.


Precations for use
The supervision of levomepromazine treatment should be strengthened:
- in epileptics because of the possibility of the epileptogenic threshold lowering. The occurrence of convulsive attacks makes it imperative to stop the treatment.
- in elderly patients with: an elevated sensitivity to an orthostatic hypotension, sedation and extrapyramidal effects.
- a chronic constipation (risk of paralytic ileus)
- an eventual prostatic hypertrophy
- in patients – carriers of certain cardiovascular affections because of the quinidinic tachycardiac and hypotensive effects of this class of products
- in case of severe hepatic and/or renal insufficiency because of the risk of accumulation 
Hyperglycaemia

Hyperglycaemia or intolerance to glucose has been reported in patients treated with Nozinan.
Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes, who are started on Nozinan, should get appropriate glycaemic monitoring during treatment (see Section 4.8).

Levomepromazine may lower epileptic threshold (see Sections 4.5 and 4.8) and should be used with caution in epileptic patients.

Effects on Driving