Vertinex®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT VERTINEX® (VERTINEX®)

Composition:

Active substance: prochlorperazine maleate;

1 tablet contains prochlorperazine maleate 5 mg;

Excipients: lactose monohydrate, microcrystalline cellulose, maize starch, sodium croscarmellose, sodium lauryl sulfate, magnesium stearate, colloidal anhydrous silicon dioxide.

Medicinal form. Tablets.

Main physical and chemical properties: white or almost white, round, biconvex tablets, smooth on both sides.

Pharmacotherapeutic group.

Antipsychotic agents. Phenothiazine derivatives with piperazine structure. ATC code N05A B04.

Pharmacological properties.

Pharmacodynamics.

Prochlorperazine maleate is a derivative of phenothiazine.

Prochlorperazine has a broad spectrum of activity due to its inhibitory effect on the CNS, blockade of alpha-adrenergic receptors, and weak antimuscarinic effect. It inhibits dopamine and prolactin-inhibiting factor, thereby stimulating prolactin release and accelerating dopamine metabolism in the brain. There is evidence that the therapeutic effect in psychiatric conditions is due to the antagonistic action of prochlorperazine on central dopaminergic receptors.

Prochlorperazine exerts a sedative effect; however, tolerance to this effect usually develops rapidly. Prochlorperazine exhibits antiemetic and antipruritic effects and blocks the action of serotonin. In addition, prochlorperazine has a slight antihistaminic effect and weak ganglion-blocking activity. Prochlorperazine also has an inhibitory effect on the thermoregulatory center, a relaxant effect on smooth muscles, and possesses membrane-stabilizing and local anesthetic properties. The effect of prochlorperazine on the autonomic nervous system leads to vasodilation, arterial hypotension, tachycardia, xerostomia, and reduced gastric juice secretion.

Pharmacokinetics.

Prochlorperazine is well absorbed from the gastrointestinal tract but undergoes extensive presystemic metabolism in the intestinal wall. It is also actively metabolized in the liver and excreted in urine and bile. After oral administration, the plasma concentration of prochlorperazine is significantly lower than after intramuscular administration. There is no direct correlation between plasma concentrations of prochlorperazine and its metabolites and the therapeutic effect.

Prochlorperazine may be metabolized via hydroxylation and conjugation with glucuronic acid, N-oxidation, sulfur atom oxidation, and dealkylation. The elimination half-life from plasma is only several hours, but excretion of metabolites may be very prolonged. Prochlorperazine is highly bound to plasma proteins and is well distributed throughout the body; its metabolites cross the placental barrier and are excreted into breast milk. The rate of metabolism and excretion of prochlorperazine is reduced in elderly patients.

Clinical characteristics.

Indications.

Dizziness due to Ménière's syndrome, inner ear inflammation, and other causes.

Nausea and vomiting of any etiology, including migraine.

May also be used as an adjunctive medicinal product for short-term treatment of anxiety states.

Contraindications.

Known hypersensitivity to prochlorperazine or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

In case of prochlorperazine overdose, adrenaline (epinephrine) must not be administered (see section "Overdose").

The CNS depressant effect of prochlorperazine may be enhanced (additively) by alcohol, barbiturates, and other sedative agents. Respiratory depression may occur.

Anticholinergic drugs may reduce the antipsychotic effect of prochlorperazine.

The moderate anticholinergic effect of prochlorperazine may be enhanced by other anticholinergic drugs, potentially leading to constipation, heat stroke, etc.

Antacids, antiparkinsonian agents, and lithium preparations may impair absorption of prochlorperazine.

If treatment of extrapyramidal symptoms induced by neuroleptics is required, anticholinergic antiparkinsonian agents should be preferred over levodopa, since neuroleptics antagonize the antiparkinsonian effect of dopaminergic agents.

High doses of neuroleptics reduce the hypoglycemic effect of antidiabetic medicinal products; therefore, dose adjustment may be necessary.

Neuroleptic agents may enhance the hypotensive effect of most antihypertensive medicinal products, particularly alpha-adrenoblockers.

Prochlorperazine, like other phenothiazine neuroleptics, may antagonize the effects of certain drugs: amphetamine, levodopa, clonidine, guanethidine, and adrenaline.

There are data on changes in plasma concentrations of certain medicinal products (e.g., propranolol, phenobarbital), which are not of clinical significance.

Transient metabolic encephalopathy characterized by loss of consciousness for 48–72 hours has been observed during concomitant administration of prochlorperazine and desferrioxamine.

There is an increased risk of arrhythmia when prochlorperazine is used concomitantly with drugs that prolong the QT interval (including certain antiarrhythmic agents, antidepressants, and other antipsychotic drugs) and with medicinal products that disturb electrolyte balance.

There is an increased risk of agranulocytosis when prochlorperazine is used concomitantly with drugs having myelosuppressive potential (such as carbamazepine, certain antibiotics, and cytotoxic agents).

Rare cases of neurotoxic effects have been reported with concomitant use of neuroleptics and lithium preparations.

Special precautions for use.

Prochlorperazine should not be used in patients with impaired liver or kidney function, Parkinson's disease, hypothyroidism, heart failure, pheochromocytoma, myasthenia gravis, or benign prostatic hyperplasia. Prochlorperazine is contraindicated in patients with known hypersensitivity to prochlorperazine, in patients with closed-angle glaucoma, or with a history of agranulocytosis.

Patients with epilepsy or a history of seizures should be closely monitored, as prochlorperazine may lower the seizure threshold.

Since cases of agranulocytosis have been reported during treatment with prochlorperazine, regular monitoring of complete blood count is recommended. The development of unexplained infection or fever in a patient may indicate blood dyscrasia; therefore, appropriate hematological investigations should be performed.

Treatment with prochlorperazine should be discontinued if unexplained fever occurs, as it may be a sign of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, impaired consciousness, muscle rigidity). Symptoms of autonomic dysfunction, such as hyperhidrosis and unstable blood pressure, may precede the onset of hyperthermia and serve as early signs of neuroleptic malignant syndrome. Although this syndrome may also have an idiosyncratic origin, predisposing factors include dehydration and organic brain disorders.

Since acute withdrawal symptoms (including nausea, vomiting, insomnia, extrapyramidal reactions) have been reported following abrupt discontinuation of high-dose neuroleptics, gradual withdrawal of prochlorperazine is advisable.

Like other phenothiazine neuroleptics, prochlorperazine may potentiate QT interval prolongation, increasing the risk of potentially fatal ventricular tachycardia of the torsades de pointes type (sudden death). The risk of QT interval prolongation is increased in patients with bradycardia, hypokalemia, or congenital or acquired (drug-induced) QT prolongation. Therefore, a thorough risk-benefit assessment should be performed before prescribing prochlorperazine. It is recommended to perform appropriate clinical and laboratory tests (e.g., blood biochemistry and ECG) before initiating prochlorperazine therapy, during the initial treatment phase, and as needed during treatment to rule out potential risk factors (such as heart disease, family history of QT prolongation, metabolic disorders like hypokalemia, hypocalcemia, or hypomagnesemia, history of starvation, alcohol abuse, concomitant therapy with other QT-prolonging drugs) (see also sections "Interaction with other medicinal products and other forms of interaction" and "Side effects").

Concomitant therapy with other neuroleptics should be avoided (see section "Interaction with other medicinal products and other forms of interaction").

Stroke: In randomized clinical trials conducted in elderly patients with dementia treated with certain atypical antipsychotics, a threefold increase in the risk of cerebrovascular events was observed compared to patients receiving placebo. Since the mechanism of this risk is unknown, it cannot be excluded when using other antipsychotics or in other patient populations. Prochlorperazine should be used with caution in patients with risk factors for stroke.

Like other antipsychotic agents, prochlorperazine should not be used as monotherapy when depression is the predominant symptom. However, it may be added to antidepressant therapy for the treatment of conditions where depression is combined with psychosis.

Due to the risk of photosensitization, patients taking prochlorperazine should avoid direct exposure to sunlight.

To prevent skin sensitization in individuals frequently exposed to phenothiazine derivatives, contact of the drug with the skin should be avoided (see section "Side effects").

Elderly patients.

Prochlorperazine should be used with caution in elderly patients, particularly in very hot or very cold weather, due to the potential risk of hyper- or hypothermia. Additionally, elderly patients are prone to postural hypotension. There is also an increased risk of drug-induced parkinsonism in this age group, especially after prolonged use of prochlorperazine. Since elderly patients are more sensitive to the effects of CNS-active drugs, a lower daily dose of prochlorperazine is recommended, especially at the beginning of treatment.

Increased mortality in elderly patients with dementia.

Data indicate a slightly increased risk of mortality in elderly patients with dementia treated with antipsychotic drugs. Due to insufficient data to assess the magnitude and causes of this risk, prochlorperazine should not be prescribed for the treatment of behavioral disorders associated with dementia.

Increased risk of venous thromboembolism (VTE).

Cases of VTE have been reported with the use of antipsychotic drugs. Since patients receiving antipsychotics often have risk factors for VTE, these should be identified before and during prochlorperazine therapy, and appropriate preventive measures should be taken.

Hyperglycemia or impaired glucose tolerance.

Cases of hyperglycemia or impaired glucose tolerance have been reported in patients treated with phenothiazine antipsychotics. Patients with diagnosed diabetes or individuals with risk factors for diabetes require appropriate glycemic monitoring before and during treatment with prochlorperazine.

Excipients.

The medicinal product contains lactose. If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.

Use during pregnancy or breastfeeding.

Pregnancy.

There are no adequate data on the safety of prochlorperazine use during pregnancy in humans. Prochlorperazine should be avoided during pregnancy except when the physician considers it essential. Since neuroleptics may prolong labor, administration of the drug should be discontinued until cervical dilation reaches 3–4 cm. There is a risk of adverse effects of prochlorperazine on the newborn, which may manifest as low Apgar score, lethargy, or paradoxical excitation and tremor.

Newborns whose mothers used antipsychotics, including prochlorperazine, during the third trimester of pregnancy are at risk of developing adverse, including serious effects, such as extrapyramidal symptoms and/or withdrawal symptoms (agitation, hypertension, hypotension, tremor, somnolence, respiratory disorders, or feeding difficulties). Such infants should be closely monitored.

Breastfeeding period.

Since prochlorperazine may pass into breast milk, breastfeeding should be discontinued during treatment.

Ability to affect reaction speed when driving or operating machinery.

Patients should be warned about drowsiness during the first days of treatment. Driving a vehicle or operating machinery is not recommended.

Dosage and Administration

The medication is intended for adults. Administer orally.

Prevention of nausea and vomiting

1-2 tablets (5-10 mg) 2-3 times daily.

Treatment of nausea and vomiting

4 tablets (20 mg) should be taken immediately after onset of symptoms; if necessary, an additional 2 tablets (10 mg) may be taken 2 hours later.

Dizziness

1 tablet (5 mg) 3 times daily. If necessary, the daily dose 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 adjunctive agent for short-term treatment of anxiety states

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

Geriatric patients

A lower daily dose of prochlorperazine is recommended for elderly patients.

Children

There is insufficient data on the use of prochlorperazine in children; therefore, Vertinex**®** should not be prescribed to this age group.

Overdose

Symptoms of overdose: drowsiness or loss of consciousness, arterial hypotension, tachycardia, ECG changes, ventricular arrhythmia, hypothermia, extrapyramidal dyskinesia.

Treatment.

First aid. If less than 6 hours have passed since ingestion of a toxic dose, gastric lavage should be performed. Induction of vomiting with medicinal agents is not recommended. Activated charcoal should be administered. There is no specific antidote. Supportive and symptomatic therapy is recommended.

Arterial hypotension. In mild cases, elevating the patient's upper limbs upward may be sufficient. In severe cases, infusion therapy may be required to correct circulating fluid volume. Pre-warmed infusion solutions should be used (to prevent hypothermia). If fluid replacement is insufficient to correct arterial hypotension, inotropic agents such as dopamine may be administered.

Peripheral vasoconstrictors and adrenaline (epinephrine) are not recommended.

Ventricular and supraventricular tachyarrhythmia. Usually, maintaining normal body temperature, correcting circulating blood volume, and/or metabolic disturbances are effective measures for managing tachyarrhythmia. If the above measures are ineffective or if the tachyarrhythmia is life-threatening, appropriate antiarrhythmic therapy should be initiated. Lidocaine or long-acting antiarrhythmic agents are not recommended.

CNS depression. Medications to support respiration should be administered, including mechanical ventilation if necessary.

Dystonia. In severe cases, dystonic symptoms may be managed with procyclidine (5-10 mg) or orphenadrine (20-40 mg) administered intravenously or intramuscularly.

Seizure syndrome. Diazepam should be administered intravenously.

Neuroleptic malignant syndrome. Physical cooling methods should be applied. Dantrolene sodium may also be used.

Adverse reactions.

Immune system disorders: Type I hypersensitivity reactions, including angioneurotic edema and urticaria.

Blood and lymphatic system disorders: leukopenia, agranulocytosis.

Endocrine system disorders: hyperprolactinemia, which may lead to galactorrhea; gynecomastia; amenorrhea; impotence; glucose intolerance; hyperglycemia.

Metabolism and nutrition disorders: syndrome of inappropriate antidiuretic hormone secretion (SIADH), hyponatremia.

Nervous system disorders: acute dystonia or dyskinesia, including oculogyric crisis; akathisia; parkinsonism symptoms (tremor, rigidity, akinesia or others); tardive dyskinesia; insomnia; anxiety agitation; seizures.

Eye disorders: ophthalmological changes.

Cardiac disorders: ECG changes (QT interval prolongation, ST segment depression, U and/or T wave changes); cardiac rhythm disorders (ventricular arrhythmia and atrial arrhythmias, atrioventricular block, ventricular tachycardia, which may lead to ventricular fibrillation or cardiac arrest); sudden death.

Vascular disorders: hypotension, venous thromboembolism (including cases of pulmonary embolism), deep vein thrombosis.

Gastrointestinal disorders: dry mouth.

Respiratory system disorders: respiratory depression, nasal congestion.

Hepatobiliary disorders: jaundice.

Skin and subcutaneous tissue disorders: metallic gray-purple skin discoloration; skin rashes; photosensitization.

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

Shelf life. 3 years.

Storage conditions.

Store at temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 1 blister in a cardboard package.

10 tablets in a blister; 1 blister in a cardboard package; 10 cardboard packages in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

KUSUM HEALTHCARE PVT LTD.

Manufacturer's address and location of business activity.

SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.