The drug should be avoided, or used with caution, in patients with liver dysfunction or cardiac disease. The hypotensive effects of Levomepromazine should be taken into account when it is administered to patients with cardiac disease and the elderly or debilitated. Patients receiving large initial doses should be kept in bed. As with other neuroleptics, cases of QT interval prolongation have been reported with levomepromazine very rarely. Consequently, and if the clinical situation permits, absence of the following risk factors for onset of this type of arrhythmia should be verified prior to administration:
- Bradycardia or 2nd or 3rd degree heart block.
- Metabolic abnormalities such as hypokalaemia, hypocalcaemia or hypomagnesaemia.
- Starvation or alcohol abuse.
- A history of QT interval prolongation, ventricular arrhythmias or Torsades de Pointes.
- A family history of QT interval prolongation.
- Concomitant neuroleptics
- Ongoing treatment with another drug(s) liable to induce marked bradycardia, electrolyte imbalance, slowed intracardiac conduction or prolonged QT interval.
Prior to initiation of treatment with levomepromazine, it may be appropriate to consider an ECG with measurement of serum calcium, magnesium and potassium levels. Periodic serum electrolyte levels should be monitored and corrected if necessary, especially during long-term chronic usage. An ECG may be appropriate to assess the QT interval whenever dose escalation is proposed and when the maximum therapeutic dose is reached.
Stroke: In randomized clinical trials versus placebo performed in a population of elderly patients with dementia and treated with certain atypical antipsychotic drugs, a 3-fold increase of the risk of cerebrovascular events has been observed. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Levomepromazine should be used with caution in patients with risk factors for stroke.
Increased Mortality in Elderly people with Dementia Data from two large observational studies showed that elderly people with dementia who are treated with conventional (Typical) 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. Levomepromazine is not licensed for the treatment of dementia-related behavioural disturbances.
Venous thromboembolism: 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 Nozinan and preventive measures undertaken.
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 Levomepromazine, should get appropriate glycaemic monitoring during treatment .
Drug interactions
Cytochrome P450 2D6 Metabolism: Levomepromazine and its non-hydroxylated metabolites are reported to be potent inhibitors of cytochrome P450 2D6. Co-administration of levomepromazine and drugs primarily metabolised by the cytochrome P450 2D6 enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic or adverse effects of those drugs. There is an increased risk of arrhythmias when neuroleptics are used with drugs that prolong the QT interval such as certain class 1A and III antiarrhythmics (such as quinidine, disopyramide, procainamide, amiodarone, sotalol and dofetilide), certain antimicrobials (such as sparfloxacin, moxifloxacin and erythromycin IV), tricyclic antidepressants (e.g. amitriptyline), tetracyclic antidepressants (e.g. maprotiline), other neuroleptics (e.g. phenothiazines, pimozide and sertindole), antihistamines (e.g. terfenadine), cisapride, bretylium and antimalarials (e.g. quinine and mefloquine). The anticholinergic effect of neuroleptics may be enhanced by other anticholinergic drugs. Avoid concomitant neuroleptics and any other drugs that may cause electrolyte imbalance. Diuretics, in particular those causing hypokalemia, should be avoided but, if necessary, potassium-sparing diuretics are preferred. Simultaneous administration of desferrioxamine and prochlorperazine has been observed to induce a transient metabolic encephalopathy, characterised by loss of consciousness for 48 to 72 hours. It is possible that this may occur with Levomepromazine since it shares many of the pharmacological activities of prochlorperazine. Adrenaline (epinephrine) must not be used in patients overdosed with neuroleptics. Alcohol should be avoided.