Levomepromazine maleate INN (methotrimeprazine maleate BAN) 25mg per tablet.

Tablets.

Nozinan is a neuroleptic with indications in psychiatry and general medicine, particularly in terminal illness. Clinically it is more sedative and more potent than chlorpromazine in the management of psychotic conditions and in the relief of severe chronic pain. Psychiatry As an alternative to chlorpromazine in schizophrenia especially when it is desirable to reduce psychomotor activity. General medicine Alone, or together with appropriately modified doses of analgesics and narcotics, in the relief of severe pain and accompanying anxiety and distress.

Dosage varies with the condition under treatment and the individual response of the patient.

1. Terminal illness

Nozinan tablets 25mg may be substituted for the injection if oral therapy is more convenient, the dosage being 12.5mg to 50mg every 4 to 8 hours.

Elderly

No specific dosage recommendations.

2. Psychiatric conditions

Adults

Ambulant patients: initially the total daily oral dose should not exceed 25mg to 50mg usually divided into 3 doses; a larger portion of the dosage may be taken at bedtime to minimise diurnal sedation. The dosage is then gradually increased to the most effective level compatible with sedation and other side effects.

Bed patients: initially the total daily oral dosage may be 100mg to 200mg, usually divided into 3 doses, gradually increased to 1g daily if necessary. When the patient is stable attempts should be made to reduce the dosage to an adequate maintenance level.

Children are very susceptible to the hypotensive and soporific effects of levomepromazine. It is advised that a total daily oral dosage of 1½ tablets should not be exceeded. The average effective daily intake for a ten year old is ½ to 1 tablet.

It is not advised to give levomepromazine to ambulant patients over 50 years of age unless the risk of a hypotensive reaction has been assessed.

Safety in pregnancy has not been established.

There are no absolute contraindications to the use of Nozinan in terminal care.

The drug should be avoided, or used with caution, in patients with liver dysfunction or cardiac disease.

The hypotensive effects of Nozinan 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 2^nd or 3^rd 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.

• Ongoing treatment with another drug liable to induce marked bradycardia, hypokalaemia, slowed intracardiac conduction or prolonged QT interval.

It is recommended, as part of the initial evaluation in patients to be treated with levomepromazine, that an ECG is performed with measurement of serum calcium, magnesium and potassium levels. Periodic serum electrolyte levels should be monitored and corrected especially when long-term chronic usage is anticipated. An ECG should be repeated to assess the QT interval whenever dose escalation is proposed and when the maximum therapeutic dose is reached.

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 antiarrhythmics, antidepressants and other antipsychotics. If these drugs are co-administered this should be done with ECG monitoring.

The anticholinergic effect of neuroleptics may be enhanced by other anticholinergic drugs.

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 Nozinan 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

Somnolence and asthenia are frequent side effects. Dry mouth is encountered occasionally. Hypotension may occur, especially in elderly patients. A raised ESR may occasionally be encountered. Agranulocytosis has been reported, as have photosensitivity and allergic skin reactions.

Parkinsonian-like reactions may occur in patients receiving prolonged high dosage. Jaundice is a rare side effect. Other adverse effects common to phenothiazine neuroleptics may be seen, such as heat stroke in hot and humid conditions, constipation that may become severe leading to paralytic ileus, neuroleptic malignant syndrome and rare cases of cardiac rhythm disturbances and prolongation of the QT interval.

Very rarely cases of Torsades de Pointes have been reported, treatment of which should include discontinuation of levomepromazine and correction of hypoxia, electrolyte abnormalities and acid base disturbances.

Necrotizing enterocolitis which can be fatal, has been very rarely reported in patients treated with levomepromazine. Priapism has also been very rarely reported.

Link Pharmaceuticals Ltd

POM