Triftazin-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRIFTAZIN-DARNITSA (TRIFTAZIN-DARNITSA)

Composition:

Active substance: trifluoperazine;

1 ml of solution contains 2 mg of trifluoperazine hydrochloride;

Excipients: sodium citrate, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear colorless or slightly yellowish liquid.

Pharmacotherapeutic group.

Antipsychotic agents. Piperazine derivatives of phenothiazine.

ATC code N05A B06.

Pharmacological properties.

Pharmacodynamics.

Triftazin-Darnytsia is an antipsychotic agent (neuroleptic) and a piperazine derivative of phenothiazine. It exerts antipsychotic, sedative, antiemetic, cataleptic, hypotensive, hypothermic, and weak anticholinergic effects, as well as action against hiccups.

The antipsychotic effect is associated with blockade of D2-dopaminergic receptors in the mesolimbic and mesocortical systems, blockade of α-adrenergic receptors in the central nervous system (CNS), and increased release of hypothalamic and pituitary hormones.

Sedative effect develops due to blockade of adrenergic receptors in the reticular formation of the brainstem.

The antiemetic effect is related to blockade of peripheral and central D2-dopaminergic receptors and blockade of vagus nerve endings in the gastrointestinal tract.

Hypothermic effect arises from blockade of dopaminergic receptors in the hypothalamus.

Sedative effects and influence on the autonomic nervous system are weaker compared to other phenothiazine derivatives, whereas extrapyramidal and antiemetic effects are stronger.

Pharmacokinetics.

After intramuscular administration, the drug undergoes a "first-pass" effect through the liver. It binds strongly to plasma proteins, with a binding rate of 95%. Time to reach maximum plasma concentration (Tmax) is 1–2 hours. The drug penetrates the blood-brain barrier and is excreted into breast milk. It is intensively metabolized in the liver; metabolites are pharmacologically inactive. The elimination half-life (T1/2) is 15–30 hours. Metabolites are excreted from the body via bile and kidneys. Weak dialysis occurs due to high plasma protein binding.

Clinical characteristics.

Indications.

Psychotic disorders, including schizophrenia.

Contraindications.

Hypersensitivity to the components of the medicinal product or to other phenothiazine derivatives. Decompensated heart failure. Marked arterial hypotension. Central nervous system (CNS) depression. Coma of any etiology. Progressive systemic diseases of the brain and spinal cord. Angina pectoris. Breast cancer. Closed-angle glaucoma. Renal and hepatic dysfunction, liver damage. Peptic ulcer of the stomach and duodenum during exacerbation. Epilepsy. Parkinson's disease. Disorders of the central respiratory control mechanism (especially in children). Reye's syndrome. Cachexia. Pheochromocytoma. Prolactin-dependent tumor. Myxedema. Benign prostatic hyperplasia. Blood disorders associated with impaired hematopoiesis. Pregnancy or breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Medicinal products that suppress central nervous system functions (anesthetic agents, opioid analgesics, barbiturates, anxiolytics, ethanol, and ethanol-containing preparations) – enhance the effect of the medicinal product, increase CNS depression, and suppress respiration.

CYP1A2 inducers (carbamazepine, phenobarbital, rifampicin, aminoglutethimide) – reduce the concentration and effect of Triftazin-Darnytsia.

CYP1A2 inhibitors (amiodarone, ciprofloxacin, fluvoxamine, ketoconazole, norfloxacin, ofloxacin, rofecoxib) – increase the concentration and effect of Triftazin-Darnytsia.

α-adrenoblockers – enhance the hypotensive effects of the medicinal product.

Levodopa and phenamines – reduce the effect of the medicinal product.

Antiepileptic drugs – when used concomitantly, the efficacy of antiepileptic drugs may be reduced.

Antithyroid agents – increased risk of agranulocytosis.

Astemizole, disopyramide, erythromycin, procainamide – increased risk of tachycardia.

Tricyclic antidepressants, maprotiline, MAO inhibitors – possible prolongation and intensification of sedative and anticholinergic effects of Triftazin-Darnytsia.

Lithium preparations – possible exacerbation of extrapyramidal symptoms and early signs of lithium intoxication.

Adrenomimetics and sympathomimetics – concomitant use may lead to paradoxical reduction in blood pressure.

Mutual enhancement of effects occurs with concomitant use of ethanol.

Anticonvulsants – possible reduction in seizure threshold.

Medicinal products that cause extrapyramidal reactions (metoclopramide) – possible increase in frequency and severity of extrapyramidal disorders.

Antihypertensive drugs – possible development of orthostatic arterial hypotension.

Prochlorperazine – prolonged loss of consciousness may occur.

The medicinal product may reduce the vasoconstrictive effect of ephedrine and epinephrine, enhance anticholinergic effects of other medicinal products, and inhibit the action of amphetamines, levodopa, clonidine, guanethidine.

Bromocriptine – phenothiazines inhibit the ability of bromocriptine to reduce serum prolactin concentration.

Propranolol, sulfadoxine – increase the plasma concentration of Triftazin-Darnytsia.

Polypeptide antibiotics – concomitant use may cause paralysis of respiratory muscles.

Tramadol – additive hypotensive effect is observed.

Valproic acid – concomitant use leads to increased plasma concentration of valproic acid.

The medicinal product may reduce the effect of oral anticoagulants.

Concomitant use with medicinal products that prolong the QT interval (antiarrhythmics, non-sedating antihistamines, antimalarials, cisapride, diuretics, tricyclic antidepressants) increases the risk of ventricular arrhythmias with phenothiazine derivatives.

Use with caution when co-administered with antituberculosis antibacterial agents.

Special precautions for use.

Use with caution in patients with glaucoma (contraindicated in closed-angle glaucoma), cardiovascular diseases, hepatic or renal dysfunction, cerebrovascular or respiratory disorders, jaundice, Parkinson's disease, myasthenia gravis, urinary retention, or paralytic ileus.

Patients receiving this medicinal product for prolonged periods require careful monitoring to enable early detection of signs of tardive dyskinesia, ocular changes, blood disorders, hepatic dysfunction, or disturbances in cardiac conduction.

If symptoms of tardive dyskinesia or neuroleptic malignant syndrome occur, the drug should be discontinued. Clinical manifestations of neuroleptic malignant syndrome may include hyperthermia, muscle rigidity, altered mental status and consciousness, autonomic instability (irregular pulse, fluctuating blood pressure, tachycardia, excessive sweating, cardiac arrhythmia). Diagnosis of this syndrome is particularly difficult in patients with severe underlying conditions (e.g. pneumonia, systemic infection, etc.). Differential diagnosis is required in patients with CNS pathology, drug-induced fever, heat stroke, or central anticholinergic toxicity. Encephalopathic syndrome (weakness, lethargy, fever, tremor, confusion, extrapyramidal symptoms, leukocytosis, elevated enzyme levels, blood urea nitrogen, and blood glucose) has been reported in some patients receiving combined therapy with lithium; in some cases irreversible brain damage has developed. Therefore, careful monitoring for early signs of neurological toxicity is essential, and treatment should be discontinued immediately upon appearance of such symptoms.

This medicinal product should be prescribed to patients with Reye’s syndrome, urinary retention, chronic respiratory disorders, or vomiting only after careful assessment of the benefit-risk ratio.

For treatment of non-psychotic anxiety, trifluoperazine should generally be prescribed only after trying alternative medications (e.g. benzodiazepines) that lack some of the adverse effects associated with trifluoperazine.

Withdrawal syndrome characterized by nausea, vomiting, sweating, and insomnia has been described. Recurrence of psychotic symptoms and emergence of movement disorders (akathisia, dystonia, dyskinesia) are also possible. Therefore, discontinuation of the drug should be carried out gradually.

Elderly patients are more prone to developing arterial hypotension and neuromuscular reactions; close monitoring is required during treatment. The lower end of the dosage range is usually sufficient for most elderly patients. Dosage should be adjusted according to individual response and modified appropriately. Doses should be increased gradually in these patients. Use of this medicinal product in elderly patients may lead to the development of irreversible dyskinesia.

Use of phenothiazine derivatives in elderly patients with dementia may increase the risk of fatal outcomes.

Use under extreme conditions may be dangerous, as phenothiazines may impair thermoregulation. Exposure to direct sunlight should be avoided.

The duration of treatment with this medicinal product should not exceed 12 weeks, as prolonged use may lead to the development of persistent tardive dyskinesia, which may be irreversible.

If hypersensitivity reactions occur (including jaundice, pathological blood changes), phenothiazines should not be re-administered.

Concomitant use with sedatives, anesthetics, tranquilizers, or alcohol may lead to increased sedation.

Alcohol consumption is not recommended during treatment with this medicinal product.

The effect of phenothiazines on the vomiting center may mask symptoms of overdose with other medicinal products.

Regular eye examinations are recommended for patients undergoing long-term phenothiazine therapy.

Use with caution in patients with acute infection or leukopenia.

After parenteral administration, patients should remain lying on their back for 30 minutes under blood pressure monitoring.

Important information on excipients.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially "sodium-free".

Use during pregnancy or breastfeeding.

This medicinal product is contraindicated during pregnancy. If treatment is necessary, breastfeeding should be discontinued.

Effect on ability to drive or operate machinery.

During treatment with this medicinal product, patients should refrain from driving vehicles or engaging in potentially hazardous activities requiring high psychomotor reaction speed.

Dosage and Administration.

Administer intramuscularly. The initial dose for adults is 1–2 mg. Repeat administration should be performed every 4–6 hours; more frequent injections may lead to accumulation phenomena. The usual daily dose is 6 mg; in exceptional cases, up to 10 mg.

In depressive-hallucinatory and depressive-delirious states, Triptazine-Darnytsia should be used concomitantly with antidepressants.

Treatment with Triptazine-Darnytsia must be strictly individualized depending on the course of the disease. The duration of treatment should not exceed 12 weeks.

Children.

The use of this medicinal product in children is not recommended due to limited clinical experience.

Overdose.

Overdose manifests as dyskinesia, dysarthria, drowsiness and stupor, extrapyramidal disorders, involuntary muscle contractions, arterial hypotension or hypertension, cardiac arrhythmias, seizures, electrocardiogram changes, fever, autonomic disturbances, dry mouth, intestinal obstruction. In severe cases, coma may occur.

Treatment. Treatment is symptomatic and supportive. In case of respiratory depression, perform artificial ventilation of the lungs and oxygen therapy. Correct acid-base balance and fluid-electrolyte balance, and apply forced diuresis.

Adverse Reactions

Eye disorders: Accommodation paresis, retinopathy, lens and corneal clouding, visual disturbances, conjunctivitis.

Gastrointestinal disorders: Dry mouth, hypersalivation, anorexia, bulimia, nausea, vomiting, diarrhea, constipation, gastralgia, intestinal paresis, trismus, tongue protrusion.

Hepatobiliary and biliary tract disorders: Cholestatic jaundice, hepatotoxicity, hepatitis.

Renal and urinary disorders: Decreased potency, ejaculation disorders, priapism, urinary retention, oliguria, micturition disorders.

Endocrine system disorders: Hypo- or hyperglycemia, glucosuria, menstrual cycle disturbances (dysmenorrhea, amenorrhea), gynecomastia, weight gain, galactorrhea, breast pain, libido disorders, hyperprolactinemia.

Nervous system disorders: Headache, drowsiness, dizziness, lethargy, insomnia, akathisia, dystonic extrapyramidal reactions (which may include neck muscle spasms, torticollis, back muscle extension possibly progressing to opisthotonus, carpopedal spasm, trismus, swallowing difficulties, oculogyric crisis, tongue protrusion; these symptoms disappear within several hours or 24–48 hours after discontinuation of the drug), pseudoparkinsonism (mask-like face, drooling, "pill-rolling" movements, cogwheel rigidity, shuffling gait), tardive dyskinesia (symptoms may be irreversible, characterized by rhythmic involuntary movements of the tongue, mouth, jaw (e.g., tongue protrusion, cheek puffing, perioral wrinkling, chewing movements), tardive dystonia, involuntary limb movements (limb movements may be the sole manifestation of tardive dyskinesia), tardive dysamnesia, neuroleptic malignant syndrome, mental indifference, delayed response to external stimuli, akinetic-rigid phenomena, hyperkinesia, tremor, autonomic disturbances, tardive dyskinesia of facial muscles, dystonia, thermoregulation disorders, increased fatigue, consciousness disturbances, muscle rigidity, seizures.

Cardiovascular system disorders: Tachycardia, decreased blood pressure (orthostatic hypotension), cardiac arrhythmias, ECG changes (prolonged QT interval, flattened T wave), angina attacks, ventricular arrhythmia resembling torsades de pointes, cardiac arrest.

Blood and lymphatic system disorders: Thrombocytopenia, agranulocytosis, anemia (hemolytic, aplastic), pancytopenia, leukopenia, thrombocytopenic purpura, eosinophilia.

Immune system disorders: Allergic reactions, including rash, urticaria, angioedema, anaphylactic shock.

Skin and subcutaneous tissue disorders: Photodermatitis, skin redness, skin depigmentation, exfoliative dermatitis.

Musculoskeletal and connective tissue disorders: Myasthenia.

General disorders and administration site reactions: Weakness, edema.

Laboratory findings: False-positive pregnancy tests, false-positive phenylketonuria tests.

Adverse reactions typical of phenothiazines: Hypothermia, night terrors, depression, hypercholesterolemia, hyperpyrexia, brain edema, generalized and partial seizures, prolonged CNS effects of opioids, analgesics, antihistamines, barbiturates, alcohol, atropine, heat, organophosphorus insecticides, nasal congestion, adynamic intestinal obstruction, intestinal atony, miosis, mydriasis, reactivation of psychotic processes, catatonic-like states, liver function disturbances, jaundice, biliary stasis, irregular menstruation, pruritus, eczema, asthma, epinephrine effect, increased appetite, lupus-like syndrome, skin pigmentation, epithelial keratopathy, lens and corneal deposits, sudden fatal outcome, asphyxia, injection site reactions including pain and irritation.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after drug registration is an important procedure. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national reporting system.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibility.

Solutions of trifluoperazine and other phenothiazine derivatives are incompatible with barbiturate solutions, carbonate solutions, and Ringer's solution (precipitate formation).

Should not be administered in the same syringe with other medicinal products.

Packaging.

1 ml in a vial; 5 vials in a blister pack; 2 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnitsya".

Manufacturer's address and location of manufacturing activities.

13 Borispilska Street, Kyiv, 02093, Ukraine.