COMPOSITION:

Active substance: Prochlorperazine Maleate;

1 tablet contains 5 mg of Prochlorperazine Maleate;

Excipients: Lactose monohydrate, Microcrystalline Cellulose, Maize Starch, Croscarmellose sodium, Sodium lauryl Sulphate, Magnesium Stearate, Colloidal anhydrous Silica.

INDICATIONS:

Vertigo due to Meniere’s syndrome, labyrinthitis.

Nausea and vomiting from whatever cause including that associated with migraine.

It may also be used as an adjunct to the short-term management of anxiety.

DOSAGE:

Adults Prevention of nausea and vomiting.

1-2 tablets (5-10 mg) two or three times per day.

Treatment of nausea and vomiting

4 tablets (20 mg) immediately after the onset of symptoms followed if necessary by 2 more tablets (10 mg) two hours later.

Vertigo due to Meniere’s syndrome.

1 tablet (5 mg) tree times per day. If necessary, the daily dose of drug may be increased to 6 tablets (30 mg). After several weeks the daily dose may be gradually reduced to 1-2 tablets (5-10 mg).

As an adjunct to the short-term management of anxiety.

1 tablet (5 mg) 3-4 times per day at the beginning of treatment. If necessary, the daily dose of drug may be increased to 8 tablets (40 mg) taken in divided doses 3-4 times per day.

Elderly patients

Lower daily dosage of prochlorperazine is recommended for elderly patients.

ADVERSE REACTIONS:

Immune system disorders:

Angioneurotic edema, urticaria.

Blood and lymphatic system disorders: leukopenia, agranulocytosis.

Endocrine system disorders:

hyperprolactinaemia which may result in galactorrhea; gynaecomastia, amenorrhoea; impotence; glucose intolerance, hyperglycemia.

Nervous system disorders:

acute dystonia or dyskinesia; akathisia; symptoms of Parkinsonism (tremor, rigidity, akinesia or others); insomnia, agitation.

Eye disorders:

ocular changes.

Cardiac disorders:

ECG changes (QT prolongation, ST depression, U-Wave and T-Wave changes), cardiac arrhythmia (ventricular arrhythmia and atrial arrhythmia, atrioventricular block, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest), sudden death.

Vascular disorders:

hypotension, thromboembolism (including cases of pulmonary embolism), deep vein thrombosis.

Gastrointestinal disorders:

dry mouth.

Respiratory, thoracic and mediastinal disorders:

respiratory depression nasal stuffiness.

Hepatobiliary disorders:

jaundice.

Skin and subcutaneous tissue disorders:

metallic blue-purple coloration of the skin; skin rash; photosensitivity.

General disorders:

neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic dysfunction and altered consciousness).

Drug interactions:

Adrenaline must not be used in patients overdosed with Vertinex® (see section “Overdosage”).

The CNS depressant effect of Vertinex® may be intensified (additively) by alcohol, barbiturates and other sedatives. Respiratory depression may occur.

Anticholinergic agents may reduce the antipsychotic effect of Vertinex®.

The mild anticholinergic effect of Vertinex® may be enhanced by other anticholinergic drugs, possibly leading to constipation, heat stroke, etc.

Antacids, anti-Parkinson drugs and lithium may interfere with absorption of Vertinex®.

Where treatment for neuroleptic-induced extrapyramidal symptoms is required, anticholinergic Antiparkinsonian agents should be used in preference to levodopa, since neuroleptics antagonise the Antiparkinsonian action of dopaminergics.

High doses of neuroleptics reduce the response to hypoglycaemic agents, the dosage of which might have to be adjusted.

The hypotensive effect of most antihypertensive drugs especially alpha adrenoceptor blocking agents may be exaggerated by neuroleptics.

Vertinex® as well as other phenothiazine neuroleptics may suppress the action of some drugs: amphetamine, levodopa, clonidine, guanethidine and adrenaline.

There is data on changes in plasma concentrations of a number of drugs (e.g. propranolol, phenobarbital) which have no clinical significance.

Simultaneous administration of prochlorperazine and desferrioxamine has been observed to induce transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours.

There is an increased risk of arrhythmias when neuroleptics are used with concomitant QT prolonging drugs (including certain antiarrhythmics, antidepressants and other antipsychotics) and drugs causing electrolyte imbalance.

There is an increased risk of agranulocytosis when prochlorperazine is used concurrently with drugs with myelosuppressive potential (carbamazepine or certain antibiotics and cytotoxics).

In patients treated concurrently with neuroleptics and lithium, there have been rare reports of neurotoxicity.

Pregnancy and lactation:

There is inadequate evidence of safety in pregnancy; therefore Vertinex® should be avoided in pregnancy unless the potential benefits of the drug predominate the potential risks.

Since neuroleptics may prolong labour, at such time they should be withheld until the cervix is dilated 3-4 cm. There is a risk of adverse effects of prochlorperazine on the neonate which may be manifested by low Apgar score, lethargy or, on the contrary, by paradoxical hyperexcitability and tremor.

Since neonates whose mothers used antipsychotics during the third trimester of pregnancy are at risk of adverse effects including extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder) such babies should be carefully monitored.

As phenothiazine may be excreted in milk, breast feeding should be suspended during treatment.

Children:

There are no sufficient data on the use of prochlorperazine in children; therefore Vertinex® should not be given to this age group of patients.

PRECAUTIONS:

Vertinex® should be avoided in patients with liver or renal dysfunction, Parkinson’s disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis and prostate hypertrophy. Vertinex® should not be given to patients with known hypersensitivity to prochlorperazine, patients with a history of narrow angle glaucoma or agranulocytosis.

Close monitoring is required in patients with a history of epilepsy or seizures, as phenothiazine may lower the seizure threshold.

Since agranulocytosis has been reported in association with phenothiazine therapy, regular monitoring of complete blood count is recommended. In case of infection of unknown origin or fever in patient, immediate haematological investigation is necessary to identify blood dyscrasia.

It is imperative that Vertinex® treatment be discontinued in the event of fever of unknown origin, as this may be a sign of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity). Signs of autonomic dysfunction, such as hyperhidrosis and arterial blood pressure instability, may precede the onset of hyperthermia and serve as precursory symptoms of neuroleptic malignant syndrome. Although this syndrome may be idiosyncratic in origin, dehydration and organic brain disease are predisposing factors.

Since there is data on acute withdrawal symptoms, including nausea, vomiting and insomnia, extrapyramidal following the abrupt cessation of high doses of neuroleptics, gradual withdrawal of Vertinex® is appropriate.

Prochlorperazine, as well as other neuroleptic phenothiazines, may potentiate QT interval prolongation which increases the risk of onset of serious ventricular arrhythmia of the torsade de pointes type, which is potentially fatal (sudden death). The risk of QT prolongation is increased in the presence of bradycardia, hypokalaemia, and congenital or acquired (i.e. drug induced) QT prolongation. Therefore, the risk-benefit should be fully assessed before Vertinex® is prescribed. Before Vertinex® therapy and during the initial phase of treatment, and as deemed necessary during the treatment, it is recommended to perform appropriate clinical and laboratory investigations (e.g. biochemical status and ECG) to rule out possible risk factors (e.g. cardiac disease; family history of QT prolongation; metabolic abnormalities such as hypokalaemia, hypocalcaemia or hypomagnesaemia; anamnestic data on fasting, alcohol abuse; concomitant therapy with other drugs known to prolong the QT interval) (see also sections “Interaction with other medicinal products and other forms of interaction” and “Adverse reactions”).

Concomitant treatment with other neuroleptics should be avoided (see section “Interaction with other medicinal products and other forms of interaction”).

Caution should be exercised when using the drug Vertinex® in patients with risk factors for cerebrovascular accident as there is data on the increased risk of cerebrovascular complications in association with prochlorperazine therapy.

As with all antipsychotic drugs, Vertinex® should not be used alone where depression is predominant. However, it may be combined with antidepressant therapy to treat manic depressive illness.

Because of the risk of photosensitisation, patients treated with Vertinex® should avoid exposure to direct sunlight.

The drug should be used with caution in elderly patients, particularly during very hot or very cold weather due to the possible risk of hyper-, hypothermia. Besides, elderly patients are prone to postural hypotension. Also, patients in this age group have increased risk of drug-induced Parkinsonism, especially after prolonged use of the drug Vertinex®. Lower daily dose of prochlorperazine is recommended for elderly patients, especially at the beginning of treatment.

Increased Mortality in Elderly Patients with Dementia.

There is data on the increased risk of mortality in elderly patients with dementia treated with antipsychotic drugs. The drug Vertinex® is not intended for the treatment of behavioral disorders associated with dementia.

Increased risk of venous thromboembolism (VTE).

Before and during Vertinex® therapy, all possible risk factors for VTE development should be determined and, if possible, all necessary preventive measures should be taken.

Hyperglycaemia and intolerance to glucose.

Patients with diabetes mellitus or with risk factors for this disease require appropriate glycemic control before and during treatment.

The drug contains lactose. Patients with rare hereditary diseases such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use this drug.

Overdose:

Symptoms of overdosage:

Drowsiness or loss of consciousness, arterial hypotension, tachycardia, ECG changes, ventricular arrhythmia, hypothermia, extrapyramidal dyskinesia.

Treatment

First aid. Gastric lavage should be carried out if the toxic dose was taken within the previous 4 hours. Activated charcoal should be given. There is no specific antidote.

Supportive and symptomatic treatment is recommended.

Arterial hypotension. In mild cases, lifting up the patient’s upper extremities is a sufficient measure. In severe cases, infusion therapy may be necessary to correct the total volume of liquid. If fluid replacement is insufficient for correction of arterial hypotension, agents with positive isotropic effect may be used, such as dopamine.

Peripheral vasoconstrictor agents and adrenaline are not recommended.

Ventricular or supraventricular tachy-arrhythmia: Usually restoration of normal body temperature, correction of circulatory and/or metabolic disturbances is an effective measure.

If the above measures are ineffective or tachycardia is life threatening, appropriate anti-arrhythmic therapy may be considered. Avoid lidocaine and long acting anti-arrhythmic drugs.

CNS depression. Use of agents aimed at support of respiration is necessary, including assisted respiration if required.

Dystonia. In severe cases, manifestations of dystonia may be improved with intravenous or intramuscular use of procyclidine (5-10 mg) or orphenadrine (20-40 mg).

Convulsive syndrome. Intravenous diazepam is recommended.

Neuroleptic malignant syndrome. Cooling should be applied. Dantrolene sodium may be used.

Ability to influence reaction velocity while driving or operating any other mechanisms.

Patients should be warned about drowsiness during the early days of treatment. It is not recommended to drive or operate machinery.

CONTRAINDICATIONS:

Known hypersensitivity to prochlorperazine or other components of the drug.

PHARMACOLOGICAL PROPERTIES:

Pharmacotherapeutic group.

ATC code:

N05AB04. Antipsychotics. Phenothiazines with piperazine structure.

Pharmacodynamics.

Prochlorperazine maleate is a phenothiazine.

Prochlorperazine has a wide range of activity arising from its depressant actions on the CNS and its alpha-adrenergic blocking and weaker anti-muscarinic properties. It inhibits dopamine- and prolactin-release-inhibitory factor, thus stimulating the release of prolactin and increasing the metabolism of dopamine in the brain. There is evidence that the therapeutic effect in psychotic conditions is due to the antagonism of prochlorperazine to dopamine receptors in CNS.

Prochlorperazine has sedative properties but tolerance to the sedation usually develops rapidly. Prochlorperazine has anti-emetic, anti-pruritic, serotonin-blocking properties. Besides, prochlorperazine has weak antihistamine effect and slight ganglion-blocking activity. Also, prochlorperazine inhibits the heat regulating centre, has relaxing effect on smooth muscles and membrane, stabilising and local anaesthetic properties. The effect of prochlorperazine on the autonomic system produces vasodilatation, arterial hypotension tachycardia, hyposalivation and reduction of gastric secretions.

Pharmacokinetic properties.

Prochlorperazine is well absorbed from the gastrointestinal tract but is subject to considerable first pass metabolism from the gut wall. It is also extensively metabolised in the liver and is excreted in the urine and bile. Plasma concentrations following oral administration are much lower than those following intramuscular injection. There is no direct correlation between plasma concentrations of prochlorperazine and its metabolites, and therapeutic effect.

Prochlorperazine may be metabolised by hydroxylation and conjugation with glucuronic acid, N-oxidation, oxidation of the sulphur atom and dealkylation. Plasma half-life is reported to be only a few hours but elimination of the metabolites may be very prolonged. Prochlorperazine is extensively bound to plasma proteins and widely distributed in the body, its metabolites cross the placental barrier and are excreted in milk. The rate of metabolism and excretion of prochlorperazine decreases in elderly patients.

PHARMACEUTICAL CHARACTERISTICS:

General physico-chemical properties:

Film coated capsule-shaped pink tablets with etching “500” or “750” on one side.

Shelf-life:

2 years.

Storage:

Store below 25° C.

Keep out of reach of children.

Package:

10 tablets in a blister; 1 blister in a carton pack.

10 tablets in a blister; 1 blister in a carton pack; 10 carton packs in a carton box.

Conditions of supply:

On prescription.