Malasiya Product

Vertinex Tablets

Vertinex Tablets
Serrata Tablets

Ukraine Product

Serrata Tablets

Serrata Tablets

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:

When you should consult your doctor?

You should consult your doctor if you experience any of the following:
Usually the preparation is well tolerated. During a long-term usage of high doses there can be possible follow side effects:

GIT:
nausea, vomiting, heartburn, diarrhea.

CNS:
hyperexcitability of CNS, headache.

Urinary system:
formation of urinary, cystine and oxalate concernments.
Skin and subcutaneous tissue: allergic reactions.

Blood system:
It can cause erythrocyte hemolysis in patients with insufficiency of glucose-6-phosphatdehydrogenase of hematocytes.

What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

Ascozin® increases salicylates (increases a risk of crystalluria), ethynilestradiol, benzylpenicillin and tetracyclines concentrations in blood, and decreases per oral contraceptives concentration in blood. It reduces anticoagulation effect of coumarin derivatives. It improves iron drugs absorption in intestine. It increases general clearance of ethyl alcohol. Quinolone drugs, calcium chloride, salicylate, corticosteroid decrease vitamin C reserve when used for a long term. Corticosteroids (cortisone and prednisolone), which are administered in concrete diseases (arthritis, bronchial astma etc), also reduce vitamin C and zinc levels.
Concurrent usage of ascorbic acid and deferoxamine enhances tissue toxicity of iron, especially in cardiac muscle that can cause decompensation of blood circulatory system. It can be used only in 2 hours after deferoxamine injection. A long-term administration of high doses in patients, who are treated by disulfiram, inhibits disulfamide-alcohol reaction.
High doses of the preparation decrease efficacy of tricyclic depressants.

What to do if you accidentally take too much (overdose) of the medicine?

Symptoms:
nausea, vomiting, intestine spasm, diarrhea; it is possible allergic reaction, kidney dysfunction, blood pressure increase, hyperexcitability of CNS, sleep disturbance.

Treatment:
It is symptomatic.

Is it safe in pregnancy and breast-feeding?

Tell your doctor immediately if you become pregnant while taking this medication. For safety of any drug during pregnancy or breastfeeding – please consult your doctor.

Storage Conditions:

Store in a dry, protected from light place at a temperature not more than 25° C.
Keep it out of reach of children.

Drug Description

COMPOSITION:

Each uncoated tablet contains: Prochlorperazine Maleate BP……………5 mg

Indications and dosage.

INDICATIONS:
Vertigo due to Meniere's syndrome, labyrinthis and other causes, and for nausea and vomiting from whatever cause including that associated with migraine. It may also be used for schizophrenia (particularly in the chronic stage), acute mania and as an adjunct to the short-term management of anxiety;


DOSAGE:
The preparation is administered in dose of 1 tablet 2 – 3 times per day after meal.
Tablets should be swallowed without chewing, following with 1 glass of water.
Maximal daily dose is 30 mg.
The duration of the treatment course depends on the character and dynamics of pathology and is determined individually.

Side effects and drug interactions.

Side Effect

Generally, adverse reactions occur at a low frequency; the most common reported adverse reactions are nervous system disorders. Immune System Disorders: Type I hypersensitivity reactions such as angioedema and urticaria. Blood and lymphatic system disorders: A mild leukopenia occurs in up to 30% of patients on prolonged high dosage. Agranulocytosis may occur rarely: it is not dose related. Endocrine: Hyperprolactinaemia which may result in galactorrhoea, gynaecomastia, amenorrhoea; impotence. Nervous system disorders: Acute dystonia or dyskinesias, usually transitory are commoner in children and young adults, and usually occur within the first 4 days of treatment or after dosage increases. Akathisia characteristically occurs after large initial doses. Parkinsonism is more common in adults and the elderly. It usually develops after weeks or months of treatment. One or more of the following may be seen: tremor, rigidity, akinesia or other features of Parkinsonism. Commonly just tremor. Tardive dyskinesia: If this occurs it is usually, but not necessarily, after prolonged or high dosage. It can even occur after treatment has been stopped. Dosage should therefore be kept low whenever possible. Insomnia and agitation may occur
. Eye disorders: Ocular changes and the development of metallic greyish-mauve coloration of exposed skin have been noted in some individuals mainly females, who have received chlorpromazine continuously for long periods (four to eight years). This could possibly happen with Vertisum. Cardiac disorders: ECG changes include QT prolongation (as with other neuroleptics), ST depression, U-Wave and T-Wave changes. Cardiac arrhythmias, including ventricular arrhythmias and atrial arrhythmias, a-v block, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest have been reported during neuroleptic phenothiazine therapy, possibly related to dosage. Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic antidepressants may predispose. There have been isolated reports of sudden death, with possible causes of cardiac origin, as well as cases of unexplained sudden death, in patients receiving neuroleptic phenothiazines. Vascular disorders: Hypotension, usually postural, commonly occurs. Elderly or volume depleted subjects are particularly susceptible; it is more likely to occur after intramuscular injection. Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs – Frequency unknown. Gastrointestinal disorders: Dry mouth may occur. Respiratory, thoracic and mediastinal disorders: Respiratory depression is possible in susceptible patients. Nasal stuffiness may occur. Hepato-biliary disorders: Jaundice, usually transient, occurs in a very small percentage of patients taking neuroleptics. A premonitory sign may be sudden onset of fever after one to three weeks of treatment followed by the development of jaundice. Neuroleptic jaundice has the biochemical and other characteristics of obstructive jaundice and is associated with obstruction of the canaliculi by bile thrombi; the frequent presence of an accompanying eosinphilia indicates the allergic nature of this phenomenon. Treatment should be withheld on the development of jaundice. Skin and subcutaneous tissue disorders: Contact skin sensitisation may occur rarely in those frequently handling preparations of certain phenothiazines. Skin rashes of various kinds may also be seen in patients treated with the drug. Patients on high dosage should be warned that they may develop photosensitivity in sunny weather and should avoid exposure to direct sunlight. General disorders and administration site conditions: Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic dysfunction and altered consciousness) may occur with any neuroleptic. Intolerance to glucose, hyperglycaemia. Pregnancy, puerperium and perinatal conditions; drug withdrawal syndrome neonatal – Frequency not known. VERT DRUG INTERACTIONS:
Adrenaline must not be used in patients overdosed with Vertisum. The CNS depressant actions of neuroleptic agents may be intensified (additively) by alcohol, barbiturates and other sedatives. Respiratory depression may occur. Anticholinergic agents may reduce the antipsychotic effect of neuroleptics and the mild anticholinergic effect of neuroleptics may be enhanced by other anticholinergic drugs, possibly leading to constipation, heat stroke, etc. Some drugs interfere with absorption of neuroleptic agents: antacids, anti-Parkinson drugs and lithium. 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 raised. The hypotensive effect of most antihypertensive drugs especially alpha adrenoceptor blocking agents may be exaggerated by neuroleptics. The action of some drugs may be opposed by phenothiazine neuroleptics; these include amfetamine, levodopa, clonidine, guanethidine and adrenaline. Increases or decreases in the plasma concentrations of a number of drugs, e.g. propranolol, phenobarbitals have been observed but were not of clinical significance. Simultaneous administration of desferrioxamine and prochlorperazine 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 neuroleptics are used concurrently with drugs with myelosuppressive potential, such as carbamazepine or certain antibiotics and cytotoxics. In patients treated concurrently with neuroleptics and lithium, there have been rare reports of neurotoxicity.

Warnings and precautions

SPECIAL WARNINGS AND PRECAUTIONS FOR USE:
Vertisum should be avoided in patients with liver or renal dysfunction, Parkinson's disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis and prostate hypertrophy. It should be avoided in patients known to be hypersensitive to phenothiazines or with a history of narrow angle glaucoma or agranulocytosis. Close monitoring is required in patients with epilepsy or a history of seizures, as phenothiazines may lower the seizure threshold. As agranulocytosis has been reported, regular monitoring of the complete blood count is recommended. The occurrence of unexplained infections or fever may be evidence of blood dyscrasia, and requires immediate haematological investigation. It is imperative that treatment be discontinued in the event of unexplained fever, as this may be a sign of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity). Signs of autonomic dysfunction, such as sweating and arterial instability, may precede the onset of hyperthermia and serve as early warning signs. Although neuroleptic malignant syndrome may be idiosyncratic in origin, dehydration and organic brain disease are predisposing factors. Acute withdrawal symptoms, including nausea, vomiting and insomnia, have very rarely been reported following the abrupt cessation of high doses of neuroleptics. Relapse may also occur, and the emergence of extrapyramidal reactions has been reported. Therefore, gradual withdrawal is advisable. In schizophrenia, the response to neuroleptic treatment may be delayed. If treatment is withdrawn, the recurrence of symptoms may not become apparent for some time. Neuroleptic phenothiazines may potentiate QT interval prolongation which increases the risk of onset of serious ventricular arrhythmias of the torsade de pointes type, which is potentially fatal (sudden death). QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalaemia, and congenital or acquired (i.e. drug induced) QT prolongation. The risk-benefit should be fully assessed before Vertisum treatment is commenced. If the clinical situation permits, medical and laboratory evaluations (e.g. biochemical status and ECG) should be performed to rule out possible risk factors (e.g. cardiac disease; family history of QT prolongation; metabolic abnormalities such as hypokalaemia, hypocalcaemia or hypomagnesaemia; starvation; alcohol abuse; concomitant therapy with other drugs known to prolong the QT interval) before initiating treatment with Vertisum and during the initial phase of treatment, or as deemed necessary during the treatment. Avoid concomitant treatment with other neuroleptics. Stroke: In randomised 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 of such risk increase is not known. An increase in the risk with other antipsychotic drugs or other populations of patients cannot be excluded. Vertisum should be used with caution in patients with stroke risk factors. As with all antipsychotic drugs, Vertisum should not be used alone where depression is predominant. However, it may be combined with antidepressant therapy to treat those conditions in which depression and psychosis coexist. Because of the risk of photosensitisation, patients should be advised to avoid exposure to direct sunlight. To prevent skin sensitisation in those frequently handling preparations of phenothiazines, the greatest care must be taken to avoid contact of the drug with the skin. It should be used with caution in the elderly, particularly during very hot or very cold weather (risk of hyper-, hypothermia). The elderly are particularly susceptible to postural hypotension. Vertisum should be used cautiously in the elderly owing to their susceptibility to drugs acting on the central nervous system and a lower initial dosage is recommended. There is an increased risk of drug-induced Parkinsonism in the elderly particularly after prolonged use. Care should also be taken not to confuse the adverse effects of Vertisum, e.g. orthostatic hypotension, with the effects due to the underlying disorder. Children: Vertisum has been associated with dystonic reactions particularly after a cumulative dosage of 0.5 mg/kg. It should therefore be used cautiously in children. Increased Mortality in Elderly people with Dementia Data from two large observational studies showed that elderly people with dementia who are treated with 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. Vertisum is not licensed for the treatment of dementia-related behavioural disturbances.Vertisum should be avoided in patients with liver or renal dysfunction, Parkinson's disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis and prostate hypertrophy. It should be avoided in patients known to be hypersensitive to phenothiazines or with a history of narrow angle glaucoma or agranulocytosis. Close monitoring is required in patients with epilepsy or a history of seizures, as phenothiazines may lower the seizure threshold. As agranulocytosis has been reported, regular monitoring of the complete blood count is recommended. The occurrence of unexplained infections or fever may be evidence of blood dyscrasia, and requires immediate haematological investigation. It is imperative that treatment be discontinued in the event of unexplained fever, as this may be a sign of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity). Signs of autonomic dysfunction, such as sweating and arterial instability, may precede the onset of hyperthermia and serve as early warning signs. Although neuroleptic malignant syndrome may be idiosyncratic in origin, dehydration and organic brain disease are predisposing factors. Acute withdrawal symptoms, including nausea, vomiting and insomnia, have very rarely been reported following the abrupt cessation of high doses of neuroleptics. Relapse may also occur, and the emergence of extrapyramidal reactions has been reported. Therefore, gradual withdrawal is advisable. In schizophrenia, the response to neuroleptic treatment may be delayed. If treatment is withdrawn, the recurrence of symptoms may not become apparent for some time. Neuroleptic phenothiazines may potentiate QT interval prolongation which increases the risk of onset of serious ventricular arrhythmias of the torsade de pointes type, which is potentially fatal (sudden death). QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalaemia, and congenital or acquired (i.e. drug induced) QT prolongation. The risk-benefit should be fully assessed before Vertisum treatment is commenced. If the clinical situation permits, medical and laboratory evaluations (e.g. biochemical status and ECG) should be performed to rule out possible risk factors (e.g. cardiac disease; family history of QT prolongation; metabolic abnormalities such as hypokalaemia, hypocalcaemia or hypomagnesaemia; starvation; alcohol abuse; concomitant therapy with other drugs known to prolong the QT interval) before initiating treatment with Vertisum and during the initial phase of treatment, or as deemed necessary during the treatment. Avoid concomitant treatment with other neuroleptics. Stroke: In randomised 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 of such risk increase is not known. An increase in the risk with other antipsychotic drugs or other populations of patients cannot be excluded. Vertisum should be used with caution in patients with stroke risk factors. As with all antipsychotic drugs, Vertisum should not be used alone where depression is predominant. However, it may be combined with antidepressant therapy to treat those conditions in which depression and psychosis coexist. Because of the risk of photosensitisation, patients should be advised to avoid exposure to direct sunlight. To prevent skin sensitisation in those frequently handling preparations of phenothiazines, the greatest care must be taken to avoid contact of the drug with the skin. It should be used with caution in the elderly, particularly during very hot or very cold weather (risk of hyper-, hypothermia). The elderly are particularly susceptible to postural hypotension. Vertisum should be used cautiously in the elderly owing to their susceptibility to drugs acting on the central nervous system and a lower initial dosage is recommended. There is an increased risk of drug-induced Parkinsonism in the elderly particularly after prolonged use. Care should also be taken not to confuse the adverse effects of Vertisum, e.g. orthostatic hypotension, with the effects due to the underlying disorder. Children: Vertisum has been associated with dystonic reactions particularly after a cumulative dosage of 0.5 mg/kg. It should therefore be used cautiously in children. Increased Mortality in Elderly people with Dementia Data from two large observational studies showed that elderly people with dementia who are treated with 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. Vertisum is not licensed for the treatment of dementia-related behavioural disturbances.

Overdosage and Contraindications

Overdose:
Symptoms of phenothiazine overdosage include drowsiness or loss of consciousness, hypotension, tachycardia, ECG changes, ventricular arrhythmias and hypothermia. Severe extrapyramidal dyskinesias may occur. If the patient is seen sufficiently soon (up to 6 hours) after ingestion of a toxic dose, gastric lavage may be attempted. Pharmacological induction of emesis is unlikely to be of any use. Activated charcoal should be given. There is no specific antidote. Treatment is supportive. Generalised vasodilatation may result in circulatory collapse; raising the patient's legs may suffice. In severe cases, volume expansion by intravenous fluids may be needed; infusion fluids should be warmed before administration in order not to aggravate hypothermia. Positive inotropic agents such as dopamine may be tried if fluid replacement is insufficient to correct the circulatory collapse. Peripheral vasoconstrictor agents are not generally recommended. Avoid the use of adrenaline. Ventricular or supraventricular tachy-arrhythmias usually respond to restoration of normal body temperature and correction of circulatory or metabolic disturbances. If persistent or life threatening, appropriate anti-arrhythmic therapy may be considered. Avoid lidocaine and, as far as possible, long acting anti-arrhythmic drugs. Pronounced central nervous system depression requires airway maintenance or, in extreme circumstances, assisted respiration. Severe dystonic reactions usually respond to procyclidine (5-10 mg) or orphenadrine (20-40 mg) administered intramuscularly or intravenously. Convulsions should be treated with intravenous diazepam. Neuroleptic malignant syndrome should be treated with cooling. Dantrolene sodium may be tried.

CONTRAINDICATIONS:
Known hypersensitivity to prochlorperazine or to any of the other ingredients.

Clinical pharmacology.

PHARMACOLOGICAL PROPERTIES:

Pharmacotherapeutic Group: Antipsychotic
ATC Code: N05AB04
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. The turnover of dopamine in the brain is increased. There is evidence that the antagonism of central dopaminergic function is related to the therapeutic effect in psychotic conditions. Prochlorperazine has sedative properties but tolerance to the sedation usually develops rapidly. Prochlorperazine has antiemetic, anti-pruritic, serotonin-blocking, and weak antihistamine properties and slight ganglion-blocking activity. It inhibits the heat regulating centre, can relax smooth muscle and has membrane stabilising and hence local anaesthetic properties. Its actions on the autonomic system produce vasodilatation, hypotension and tachycardia. Salivary and gastric secretions are reduced. PHARMACOKINETIC PROPERTIES: Prochlorperazine is well absorbed from the GI 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, and are subject to wide inter-subject variation. There is no simple 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, widely distributed in the body (it crosses the blood/brain barrier) and its metabolites cross the placental barrier and are excreted in milk. The rate of metabolism and excretion decreases in old age.

Shelf-life:
3 years.

Storage:
Store below 300C in dry place. Protect from light..

Package:
№10:
10 tablets are in a strip, 1 strip is in a carton box;

№10x10:
10 tablets are in a strip, 1 strip is in a carton box, 10 packs in a carton pack;

№10x3:
Tablets
Aluminium-PVC/PVDC blister packs of 10 tablets. 1 or 10 such blisters are packed in a

№30:
30 tablets are in a blister or in a strip, 1 blister or strip is in a carton box.

Conditions of supply:
By prescription.

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare
D-158A, OKHLA,INDUSTRIAL AREA,
PHASE-I, NEW DELHI,
Pin 110020
INDIA
Tel: 011-41005147, 011-40514919
Fax: +91-11-40527575

Drug Description

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 and dosage.

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.

Side effects and drug interactions.

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.

Warnings and precautions

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.

Overdosage and Contraindications

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.

Clinical pharmacology.

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 physic-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.

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