Haloperidol - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Haloperidol - antipsychotic agent (neuroleptic), a derivative of butyrophenone. Has a pronounced antipsychotic effect, blocks postsynaptic dopamine receptors in the mesolimbic and mesocortical structures of the brain. High antipsychotic activity is combined with a moderate sedative effect (in small doses has an activating effect) and pronounced antiemetic effect. Causes extrapyramidal disorders, almost no m-holinoblokiruyuschego action. Sedative action is due to blockade of alpha-adrenergic receptors of the reticular formation of the brain stem; antiemetic effect - blockade of dopamine D2 receptors in the trigger zone of the vomiting center; hypothermic action and galactorrhea - blockade of dopamine receptors of the hypothalamus.Prolonged reception is accompanied by a change in the endocrine status, in the anterior part of the pituitary gland prolactin production increases and -gonadotropic hormones decrease.

Pharmacokinetics:When administered intravenously, the bioavailability is 100%. With intramuscular injection, the maximum concentration (Cmax) is reached after 20 minutes. The ratio of concentration in erythrocytes to plasma concentration is 1:12. The connection with proteins is approximately 92%. The concentration of haloperidol in tissues is higher than in blood, the drug tends to accumulate in tissues. Easily penetrates through gistogematicheskie barriers, incl. through placental and blood-brain, penetrates into breast milk. Hapoperidol is metabolized in the liver, the metabolite is not active. It was found that the isoenzyme CYPZASE and / or CYP2D6 is involved in the metabolism of haloperidol. Also, haloperidol is subjected to oxidative N-dealkylation and glucuronation. The half-life from plasma after intramuscular injection is 21 h (17-25 h). Haloperidol is excreted in the form of metabolites with caloric masses - 60% (including bile 15%) and urine - 40% (including 1% - unchanged).

Indications:Kupirovanie and treatment of acute psychotic disorders, accompanied by psychomotor agitation.

Behavioral disorders, such as aggression, hyperactivity, a tendency to self-harm, in the mentally retarded and in patients with organic brain lesions.

Treatment of nausea and vomiting.

Contraindications:Hypersensitivity to haloperidol and other derivatives of butyrophenone. Behavioral disorders associated with dementia in elderly patients, oppression of the central nervous system and comatose states of any etiology; diseases of the central nervous system, accompanied by pyramidal and extrapyramidal disorders (Parkinson's disease, etc.); clinically significant heart diseases (including recently transferred acute myocardial infarction, decompensated heart failure, arrhythmias treated with antiarrhythmic drugs of IA and III class, prolongation of the QT interval, ventricular arrhythmia in the anamnesis or ventricular arrhythmia of the type "pirouette", clinically significant bradycardia, heart block II or III degree and uncorrected hypokalemia); Prolactin-dependent tumors, simultaneous administration with drugs that extend the QT interval; children's age till 18 years.

Carefully:Epilepsy, zakratougolnaya glaucoma, hepatic and / or renal failure, hyperthyroidism (with thyrotoxicosis), pulmonary-cardiac and respiratory failure (including chronic obstructive pulmonary disease and acute infectious diseases), prostatic hyperplasia with urinary retention, alcoholism , pheochromocytoma.

Pregnancy and lactation:When administered at high doses in late pregnancy, butyrofenones can cause prolonged neurologic disorders in newborns. In animal studies, the use of haloperidol during organogenesis was accompanied by the development of side effects, including intrauterine fetal death, malformations such as the "wolf mouth" and neural tube defects, as well as a decrease in brain mass and body weight, as well as behavioral disorders in offspring. The significance of these results when exposed to human therapeutic doses of haloperidol is unknown.

In newborns exposed to antipsychotics (including haloperidol) during the third trimester of pregnancy, there is a risk of developing extrapyramidal disorders and / or symptoms of the "cancellation" syndrome after childbirth.There are post-marketing reports on the incidence of agitation, hyper- and hypotension, tremor, drowsiness, respiratory distress, and eating disorders in these newborns. These complications were different in severity, and in some cases, the symptoms passed independently, and in others, additional treatment or monitoring was required.

Haloperidol should be used during pregnancy only as a last resort if the expected benefit to the mother exceeds the potential risk to the fetus. The dose and duration of treatment should be as low and short as possible, respectively.

Haloperidol excreted in breast milk: In cases where haloperidol is unavoidable, breastfeeding should be abolished. In some cases, extrapyramidal symptoms have been observed in newborns whose mothers have been taking haloperidol during lactation.

Dosing and Administration:Intramuscularly, intravenously.

The dose of the drug for all indications is set individually under the supervision of a doctor. To determine the initial dose, the age of the patient, the severity of the symptoms and the previous response to neuroleptics should be taken into account.Elderly patients who are weakened and who have previously experienced adverse reactions to antipsychotics may need a lower dose of haloperidol, the initial dose for such patients should be half the usual dose for adults and then be gradually adjusted to achieve an optimal response to therapy.

In case of liver failure, the dose should be reduced. Haloperidol should be administered at the lowest clinically effective dose.

Schizophrenia, psychosis, mania, hypomania, mental disorders or behavioral disorders, psychomotor agitation, agitation, violent or dangerous impulsive behavior, organic brain damage: a dose of 5 mg is administered until symptom control is reached every hour or up to a maximum dose of 20 mg / day.

For the treatment of nausea and vomiting: 1-2 mg.

Parenteral administration should be as short as possible, followed by a transition to oral administration.

Side effects:The frequency of side effects is presented in the following gradation: very often (≥1/10), often (from ≥1/100 to <1/10), infrequently (from ≥1/1000 to <1/100), rarely (from ≥1/10000 to <1/1000), the frequency is unknown (can not be estimated from available data).

From the side of the blood and lymphatic system: infrequently, leukopenia; frequency unknown - agranulocytosis, neutropenia, pancytopenia, thrombocytopenia.

From the immune system: infrequently - hypersensitivity reactions; frequency unknown - anaphylactic reactions, toxic epidermal necrolysis, Stevens-Johnson syndrome.

From the endocrine system: rarely - hyperprolactinaemia; frequency is unknown - inadequate secretion of antidiuretic hormone.

Metabolic and nutritional disorders: frequency is unknown - hypoglycemia.

Mental disorders: very often - agitation, insomnia; often depression, psychotic disorders; infrequently - confusion, decrease and loss of libido, anxiety.

From the nervous system: very often - extrapyramidal disorders, hyperkinesia, headache; late dyskinesia, oculogyric crisis, dystonia, dyskinesia, akathisia, bradykinesia, hypokinesia, hypertonia, drowsiness, masky face, tremor, dizziness; infrequently - cramps, parkinsonism, akinesia, rigidity as a "cogwheel", sedation, involuntary muscle contracture; rarely - motor disability, malignant neuroleptic syndrome, nystagmus.

From the side of the organ of vision: often - impaired vision; infrequently - indistinctness of visual perception.

From the cardiovascular system: often - lowering blood pressure, orthostatic hypotension; infrequently - tachycardia; ventricular fibrillation, arrhythmia of the type "pirouette", ventricular tachycardia, extrasystole; frequency is unknown (when taking antipsychotic drugs) - venous thromboembolism, including pulmonary embolism, deep vein thrombosis.

From the gastrointestinal tract: often - constipation, dry mouth, increased salivation; nausea, vomiting.

From the respiratory system: infrequently - odishika; rarely - bronchospasm; frequency is unknown - laryngeal edema, laryngospasm.

From the side of the liver: often - the deviation of indicators of "liver" enzymes; infrequently - hepatitis, jaundice; frequency unknown - acute liver failure, cholestasis.

From the skin and subcutaneous tissue: often - skin rash; infrequently, reactions of photosensitization, urticaria, pruritus, hyperhidrosis; frequency unknown - leukocytoclastic vasculitis, exfoliative vasculitis.

From the musculoskeletal system: infrequently - torticollis, muscle rigidity, muscle spasm, stiff musculature of the skeletal muscles; rarely - trismus, muscle twitching.

From the side of the kidneys and urinary tract: often - urinary retention.

On the part of the reproductive system and mammary glands: often erectile dysfunction; infrequently - amenorrhea, dysmenorrhea, galactorrhea, pain and discomfort in the dairy / mammary glands; menorrhagia, menstrual disorders, sexual dysfunction; frequency unknown - gynecomastia, priapism.

General violations and violations at the place of introduction: infrequent - gait disturbance, hyperthermia, edema; frequency unknown - sudden death, face swelling, hypothermia, withdrawal syndrome in newborns.

Laboratory indicators: often - increase or decrease in body weight, prolongation of the QT interval on the ECG.

Overdose:

Symptoms: characterized by an increase in the severity of known pharmacological and side effects. The most important signs of an overdose: severe extrapyramidal disorders, hypotension, severe inhibition. Extrapyramidal disorders manifest themselves in the form of rigidity of muscles, general or local tremor of muscles. Arterial hypertension can develop more often than hypotension. In some cases, a comatose state with respiratory depression with pronounced arterial hypotension is possible.It can be so heavy that it can lead to shock. It is necessary to take into account the possibility of developing ventricular arrhythmia with an elongation of the QT interval.

Treatment: There is no specific antidote, symptomatic therapy should be given. In a comatose state, support for the function of the respiratory system, the introduction of an orotracheal or endotracheal tube is necessary. With respiratory depression, it may be necessary to carry out mechanical ventilation. It is necessary to monitor the ECG and vital parameters of hemodynamics before ECG normalization. With severe arterial hypotension or circulatory insufficiency, intravenous administration of a sufficient volume of fluid, blood plasma or concentrated albumin, as well as the introduction of vasopressor drugs (dopamine or norepinephrine) is performed. Do not use epinephrine, since in combination with haloperidol it can cause severe arterial hypotension. In severe extrapyramidal disorders, parenteral antiparkinsonian agents (benztropine mesilate for adults 1-2 mg intravenously or intramuscularly) are used.The abolition of these drugs should be carried out with caution, since a sharp cessation of their administration may lead to a relapse of extrapyramidal disorders.

Interaction:

Simultaneous use of drugs that cause electrolyte imbalance, requires increased caution - the risk of developing ventricular arrhythmias may increase. The use of diuretics that cause hypokalemia, it is recommended to avoid and give preference to potassium-sparing diuretics.

Haloperidol potentiates the inhibitory effect on the central nervous system of antihypertensive drugs, narcotic analgesics, hypnotics, tricyclic antidepressants, agents for general anesthesia, alcohol. The simultaneous administration of haloperidol with these drugs can lead to respiratory depression. With simultaneous use with antiparkinsonian drugs (levodopa and others), the therapeutic effect of the ethics of medicines may be reduced because of the antagonistic effect on the dopaminergic structures.

When used with methyldopa, development of disorientation, difficulty and slowing down of thinking processes is possible.

Haloperidol can reduce the intensity of the action of epinephrine and other sympathomimetics, cause a "paradoxical" reduction in arterial pressure and tachycardia when combined.

Strengthens the action of peripheral m-holinoblokatorov and most antihypertensives (reduces the effect of guanetidine due to its displacement from alpha-adrenergic neurons and suppression of its capture by these neurons). When combined with anticonvulsants (including barbiturates and other inducers of microsomal oxidation), the doses of the latter should be increased, haloperidol reduces the threshold of convulsive activity.

In addition, the serum concentrations of haloperidol may decrease. In particular, with the simultaneous use of tea or coffee, the action of haloperidol may weaken.

Haloperidol may reduce the effectiveness of indirect anticoagulants, so when combined, the dose of the latter should be adjusted.

Haloperidol slows the metabolism of tricyclic antidepressants and monoamine oxidase (MAO) inhibitors, which increases their plasma concentration and toxicity.

With simultaneous use with bupropion reduces the epileptic threshold and increases the risk of epileptic seizures.

With the simultaneous administration of haloperidol with fluoxetine, quinidine, buspirone, the risk of side effects on the central nervous system increases, especially extrapyramidal reactions. If necessary, the dose of haloperidol should be reduced at the same time. Inhibitors or substrates of the isoenzyme CYPZA4 and CYP2D6, such as, itraconazole, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, promethazine can increase the concentration of haloperidol in blood plasma. The decrease in the activity of the isoenzyme CYP2D6 can lead to an increase in the concentration of haloperidol. Cases of prolongation of the QT interval and extrapyramidal symptoms have been reported in the case of simultaneous use of haloperidol with ketoconazole (400 mg / day) and paroxetine (20 mg / day). Haloperidol dose adjustment may be required.

Simultaneous use of haloperidol with drugs that extend the QT interval, for example, antiarrhythmic drugs IА (incl. quinidine, disopyramide, procainamide) and III (incl. amiodarone, sotalol, dofetilide) class, some antimicrobial (sparfloxacin, moxifloxacin, erythromycin intravenously), tricyclic antidepressants (incl. amitriptyline), some tetracyclic antidepressants (incl. maprotiline), other neuroleptics (including phenothiazines, pimozide, sertindole), some antihistamines (including terfenadine), cisapride, brethium tosilate, some antimalarial (including quinine, mefloquine) increases the risk of developing ventricular arrhythmia, including arrhythmia of the "pirouette" type. Therefore, their joint reception is not recommended (this list is not exhaustive).

Long-term combined use of haloperidol with drugs that are inducers of liver enzymes (carbamazepine, rifampicin, phenobarbital , etc.), leads to a decrease in the concentration of haloperidol in the blood plasma. If it is necessary to combine them, an increase in the dose of haloperidol may be required, but after the inducer of the liver enzymes has been withdrawn, it is necessary to reduce the dose of haloperidol.

When used simultaneously with lithium salts, especially in high doses, can cause irreversible neurointoxication, and also enhance extrapyramidal symptoms. If the above condition occurs in patients taking both lithium and haloperidol, therapy should be immediately canceled.

With simultaneous reception with amphetamines, the antipsychotic effect of haloperidol and the psychostimulatory effect of amphetamines are reduced, owing to the blockade of alpha-adrenergic receptors by haloperidol.

Haloperidol can reduce the effect of bromocriptine. Anticholinergic, antihistamines (1 generation), antiparkinsonian drugs can enhance anticholinergic side effects and reduce the antipsychotic effect of haloperidol.

Thyroxine may increase the toxicity of haloperidol. With hyperthyroidism haloperidol can be prescribed only with the simultaneous carrying out of appropriate thyreostatic therapy.

With simultaneous use with anticholinergic drugs may increase intraocular pressure.

Special instructions:

Malignant neuroleptic syndrome: when antipsychotic drugs were used, the occurrence of malignant neuroleptic syndrome was reported (characterized by hyperthermia, generalized rigidity of muscles, vegetative lability, impaired consciousness of the patient and elevated level of CK in blood plasma).Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If these symptoms occur, discontinue antipsychotic medication immediately and begin appropriate maintenance therapy (eg, intravenous dantrolene infusion).

Extrapyramidal symptoms: with long-term use can mark the signs characteristic of neuroleptics - tremor, rigidity of muscles, bradykinesia, akathisia, acute muscular dystonia or laryngeal dystonia. In these cases, it is possible to prescribe antiparkinsonian preparations of anticolinergic action, but not in the order of preventive therapy, since their use reduces the effectiveness of haloperidol.

Late dyskinesia: as with the use of other antipsychotics, prolonged use of haloperidol or its withdrawal may cause tardive dyskinesia. This syndrome is characterized by an involuntary rhythmic twitching of the tongue, face, mouth or jaw. In some patients these signs are constantly noted. The syndrome can be masked when the course of therapy is resumed,increase the dose of haloperidol or prescribe another antipsychotic drug. When signs of late dyskinesia, it is advisable to interrupt the course of therapy as soon as possible. Rhythmic random jerking of the tongue can be an early sign of tardive dyskinesia. Cancellation of treatment at this early stage can prevent the development of this syndrome.

In psychiatric practice, patients who received antipsychotics, including haloperidol, cases of sudden death were reported. Since the prolongation of the QT interval on the ECG is possible during haloperidol treatment, the benefit / risk ratio in the use of the drug in patients with circulatory disease, the occurrence of a sudden death and / or prolongation of the QT interval in the history, especially with parenteral application of haloperidol, should be evaluated. Before the start of therapy, it is necessary to perform ECG monitoring (see the section "Contraindications"). In the treatment code, the need for ECG monitoring should be determined individually. In patients with subarachnoidal hemorrhage, fasting,alcohol abusers and having uncorrected electrolyte disturbances, ECG and potassium levels should be monitored closely, especially in the initial phase of treatment until equilibrium concentrations in the blood plasma are reached. Violation of the balance of electrolytes may increase the risk of developing ventricular arrhythmias, so regular monitoring of the electrolyte level is recommended, especially in patients taking diuretics. During therapy, the dose should be reduced in the case of an extended QT interval, and haloperidol - cancel immediately if the QT interval exceeds 500 ms. Haloperidol should be used with extreme caution in patients who are "slow metabolizers" CYP2D6, as well as using cytochrome P450 inhibitors.

Simultaneous use with other antipsychotics should be avoided.

Care must be taken when using haloperidol in liver failure. With prolonged use of the drug, periodic monitoring of the blood picture and liver function is necessary. Patients with epilepsy, as well as patients with increased predisposition to convulsive conditions (chronic intoxication of both alcoholic and other genesis, traumatic brain injury in the past, etc.) haloperidol should be administered with caution.

Care should be taken when using haloperidol in patients with renal insufficiency and pheochromocytoma.

Thyroxine increases the toxicity of haloperidol, so patients with hyperthyroidism should only use it under the cover of adequate thyreostatic therapy.

Patients with schizophrenia respond to antipsychotic therapy with a delay. After the end of treatment with haloperidol, the symptoms appear again only after a few weeks or months. The sudden cessation of the course of therapy with antipsychotic drugs, especially when used in high doses, can cause withdrawal symptoms (nausea, vomiting, insomnia), as well as relapse of the disease, so the drug must be canceled, gradually lowering the dose.

Patients who, in psychopathological disorders, are depressed and psychotic, haloperidol should be taken in combination with antidepressants.

If there is a need for simultaneous therapy with haloperidol and antiparkinsonian drugs, after haloperidol withdrawal, the use of an antiparkinsonian drug should be continued to prevent an increase in the severity of extrapyramidal symptoms, especially if the rate of removal of the antiparkinsonian agent is higher.It should be borne in mind that the combined use of haloperidol and anticholinergic drugs (including anti-Parkinsonics) may lead to increased intraocular pressure.

When using antipsychotic drugs, cases of venous thromboembolism were reported. Because patients receiving treatment with antipsychotic drugs often note acquired risk factors for venous thromboembolism, which should be identified before treatment begins; In the treatment of haloperidol it is necessary to take preventive measures.

There was an increased mortality in elderly people with dementia. In elderly people with dementia who received antipsychotic drugs, they noted a slightly increased risk of death compared with those who did not receive treatment. Data to provide an accurate measure of the magnitude of the risk and the reason for its increase is not enough. Haloperidol It is not indicated for the treatment of behavioral disorders against the background of dementia in the elderly.

During therapy with the drug, you should avoid drinking alcohol. At the beginning of therapy with haloperidol,and especially when used in high doses, sedation of varying degrees and decreased attention, the severity of which increases with the use of alcoholic beverages, may occur.

Effect on the ability to drive transp. cf. and fur:During the treatment period, it is necessary to refrain from driving transport and practicing other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection 5 mg / ml.

Packaging:1 ml per ampoule of colorless or light-shielding neutral glass with a colored break ring or with a colored dot and a notch or without a kink ring, a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding can additionally be applied to the ampoules.

5 ampoules per circuit cell packaging made of polyvinylchloride film and aluminum foil foil or polymer film, or without foil and without film.Or 5 ampoules are placed in a prefabricated form (tray) made of cardboard for consumer containers with cells for packing ampoules.

One or two contour squares or cardboard trays, together with an instruction for use and a scarifier or knife, ampoule, or without a scarifier and a knife ampullum, are placed in a cardboard package (bundle).

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002603

Date of registration:26.08.2014 / 24.08.2015

Expiration Date:26.08.2019

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp13.03.2017

Illustrated instructions

Instructions

Haloperidol (Haloperidol)