Composition, form of production and packaging
Drops for oral administration as a clear, colorless solution.
1 ml
haloperidol 2 mg
Excipients: methylparahydroxybenzoate - 90 mg, propyl parahydroxybenzoate - 10 mg, lactic acid - 170 mg, purified water - 99.7 g.
30 ml - a bottle of a dropper of dark glass (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Antipsychotic agent (neuroleptic), a derivative of butyrofenone. Has a pronounced antipsychotic effect, blocks postsynaptic dopamine receptors in the mesolimbic and mesocortical structures of the brain. It inhibits the release of mediators, reducing the permeability of presynaptic membranes. High antipsychotic activity is combined with a moderate sedative effect (in small doses has an activating effect) and a pronounced antiemetic effect. Causes extrapyramidal disorders, virtually no cholinoblocking effect.
Sedative action is due to blockade of ОІ-adrenoreceptors of the reticular formation of the brainstem; 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 pituitary gland prolactin production increases and decreases - gonadotropic hormones.
Eliminates persistent personality changes, delusions, hallucinations, mania, increases interest in the environment.
PHARMACOKINETICS
Absorption if taken orally - 60%. C max in the plasma is achieved with oral administration after 3 h, after the / m introduction -10-20 min. V d - 15-35 l / kg. Binding to blood plasma proteins - 92%. Easily passes through the histohematological barriers, including the blood-brain barrier. Penetrates into breast milk.
Metabolized in the liver, subjected to the effect of "first passage" through the liver. Metabolism of haloperidol is accelerated by enzyme-inducing substances (phenobarbital, phenytoin and carbamazepine). The isoenzymes CYP2D6, CYP3A3, CYP3A5, and CYP3A7 are involved in the metabolism of haloperidol. It is an inhibitor of CYP2D6. There are no active metabolites.
T 1/2 for oral administration - 24 h (12-37 h). It is excreted with bile and urine: after ingestion with bile 15% are excreted, with urine - 40% (including 1% - unchanged).
Because of the large V d and low concentration in the blood plasma, only a very small amount of haloperidol is removed by dialysis.
INDICATIONS
- Acute psychotic syndromes accompanied by delirium, hallucinations, thinking and consciousness disorders, catatonic syndromes, delirious and other exogenous psychotic syndromes;
- chronic endogenous and exogenous psychoses (suppression of symptoms and prevention of relapses);
- psychomotor agitation;
- vomiting, stammering, with the impossibility of carrying out other therapy or resistance to treatment.
DOSING MODE
1 ml of the solution (20 drops) contains 2 mg of haloperidol; 10 drops contain 1 mg of haloperidol.
The individual dose is determined by the attending physician and depends on the clinical picture, the features of the course of the disease, the age and tolerability of the drug. The daily dose should be divided into 1-3 doses, with higher doses, more frequent intake of individual doses is possible. If the doctor has not determined the individual dose for the patient, then the following treatment regimens are usually used.
Drops for ingestion are taken during meals, dosed with a teaspoon, adding to drinks or food, or on a piece of sugar (except for patients with diabetes mellitus).
Adults . The initial dose is 0.5-1.5 mg 2-3 times / day. Then the dose is gradually increased by 0.5-2 mg / day (in resistant cases by 2-4 mg / day) until the necessary therapeutic effect is achieved. When acute symptoms are relieved in hospital, initial daily doses may be increased to 15 mg / day, in therapeutically resistant cases - higher. The maximum daily dose should not exceed 100 mg / day. The average therapeutic dose of 10-15 mg / day, with chronic forms of schizophrenia - 20-40 mg / day, in resistant cases - up to 50-60 mg / day. Supportive doses (outside the exacerbation) in outpatient settings can fluctuate - 0.5-5 mg / day.
Children older than 3 years . Treatment begins with a dose of 0.025-0.05 mg / kg body weight divided into 2-3 doses. Increase in the dose is possible up to 0.2 mg / kg of body weight.
Patients of advanced age and physically weakened patients . Treatment begins with single doses not exceeding 0.5-1.5 mg. The daily dose is not recommended to increase more than 5 mg / day.
Children, elderly patients and weakened patients do not increase their doses more than once every 3-5 days.
SIDE EFFECT
When applying 1-2 mg / day, undesirable effects are not expressed and are transient. When higher doses are used, the incidence of adverse reactions increases.
From the side of the nervous system: headache, dizziness, insomnia or drowsiness (especially at the beginning of treatment), anxiety, anxiety, arousal, fear, akathisia, euphoria, depression, lethargy, epileptic seizures, development of paradoxical reaction - exacerbation of psychosis and hallucinations; with prolonged treatment - extrapyramidal disorders, incl. late dyskinesia (smacking lips and lips, inflating cheeks, quick and wormlike movements of the tongue, uncontrolled chewing movements, uncontrolled movements of the hands and feet), late dystonia (rapid blinking or spasms of the eyelids, unusual facial expression, unusual body position, uncontrollable curving neck movements, torso, arms and legs), malignant neuroleptic syndrome (shortness or rapid breathing, tachycardia, arrhythmia, hyperthermia, increase or decrease in blood pressure, increased sweating, incontinence, muscle -lingual rigidity, seizures, loss of consciousness).
From the side of the cardiovascular system: when applied in high doses - reduced blood pressure, orthostatic hypotension, arrhythmia, tachycardia, changes in the ECG (prolongation of the QT interval, flutter and ventricular fibrillation).
On the part of the respiratory system: violation of the rhythm of breathing, dyspnea, pneumonia (bronchopneumonia).
On the part of the digestive system: when used in high doses - a decrease in appetite, dryness of the oral mucosa, hypo-salivation, nausea, vomiting, diarrhea, constipation, impaired liver function, jaundice.
From the hematopoiesis: transient leukopenia or leukocytosis, agranulocytosis, erythropenia, monocytosis.
On the part of the genitourinary system: urinary retention (with prostatic hyperplasia), peripheral edema, pain in the mammary glands, gynecomastia, hyperprolactinaemia, menstrual cycle disorder, decreased potency, increased libido, priapism.
From the sense organs: cataract, retinopathy, blurred vision.
Allergic reactions: maculopapular changes in the skin, acne, photosensitivity reactions, bronchospasm, laryngospasm, hyperpyrexia.
Laboratory indicators: hyponatremia, hyperglycemia, hypoglycemia.
Other: alopecia, heat stroke, weight gain.
CONTRAINDICATIONS
- coma of different genesis;
- children under the age of 3;
- Pregnancy;
- lactation period;
- severe oppression of the central nervous system on the background of intoxication with xenobiotics;
- CNS diseases, accompanied by pyramidal or extrapyramidal symptoms (including Parkinson's disease);
- hypersensitivity to haloperidol and / or other derivatives of butyrofenone or other excipients of the drug.
Carefully
Acute intoxication with alcohol, opioid analgesics, sleeping pills or psychotropic drugs, depressing the central nervous system; hepatic and renal insufficiency;hypokalemia; bradycardia; prolongation of the QT interval (including the syndrome of congenital extension of the QT interval) or a predisposition to this is a simultaneous intake of drugs that can promote the development of hypokalemia; other clinically significant violations from the heart (in particular, violations of intracardiac conduction, arrhythmia); prolactin-dependent tumors (eg, breast tumors); severe arterial hypotension or orthostatic dysregulation; endogenous depression;diseases of the hematopoiesis system; malignant neuroleptic syndrome in the anamnesis; organic brain diseases and epilepsy; hyperthyroidism.
Particular caution is required in patients with neurological symptoms of damage to the subcortical structures of the brain and a lower threshold of convulsive readiness (in anamnesis or on the background of discontinuation of alcohol intake). Haloperidol reduces the threshold of convulsive activity, so convulsions of the "grandmal" type can be observed. Patients with epilepsy should be treated with haloperidol only if anticonvulsant therapy continues.
Haloperidol should not be used in severe depressive conditions. With concomitant depression and psychosis, haloperidol should be combined with antidepressants.
Because thyroxin may contribute to an increase in the incidence of adverse effects associated with taking haloperidol, patients with hyperthyroidism should not receive haloperidol treatment, except when accompanied by adequate antithyroid therapy.
PREGNANCY AND LACTATION
The use of haloperidol-ratopharm during pregnancy is contraindicated. Before starting treatment, a pregnancy test should be performed. During treatment with the drug, it is necessary to use effective methods of contraception. Haloperidol excreted in breast milk. The use of haloperidol-ratopharm during the period of breastfeeding is contraindicated.
APPLICATION FOR CHILDREN
Children older than 3 years . Treatment begins with a dose of 0.025-0.05 mg / kg body weight divided into 2-3 doses. Increase in the dose is possible up to 0.2 mg / kg of body weight.
Children up to 3 years of the drug is contraindicated.
APPLICATION IN ELDERLY PATIENTS
Patients of advanced age and physically weakened patients . Treatment begins with single doses not exceeding 0.5-1.5 mg. The daily dose is not recommended to increase more than 5 mg / day.
SPECIAL INSTRUCTIONS
If, especially in the first three months of treatment, fever, gingivitis and stomatitis, pharyngitis, purulent sore throat and flu-like symptoms occur, consult a doctor immediately.
You should avoid self-medication analgesics.
Before starting treatment with haloperidol, patients need to perform a general blood test (including differential counting of blood cells and platelets), ECG and electroencephalogram. If abnormalities are detected, haloperidol can be used only in absolute indications and subject to mandatory control studies of general blood counts. Before treatment, correction of hypokalemia is necessary.
In patients with organic brain damage, arteriosclerotic cerebrovascular diseases and endogenous depression in the treatment of haloperidol requires special care.
Due to the fact that in elderly patients and patients with concomitant diseases of the cardiovascular system there may be disturbances of intracardiac conduction, regular monitoring of cardiac activity is recommended against the background of therapy. In patients with pheochromocytoma, renal insufficiency, heart failure, or cerebral insufficiency against the background of haloperidol therapy, hypotensive reactions may develop, so careful monitoring is required for such patients.
Although the prevalence of late dyskinesias has not been adequately studied, older patients (especially older women) tend to develop this condition. The risk of developing tardive dyskinesia, especially the irreversible type, increases with the duration of treatment and with the use of antipsychotic doses. Late dyskinesia can develop after short-term treatment in low doses. Antipsychotic treatment at the beginning can mask the symptoms of primary late dyskinesia. Symptoms may appear after the drug is discontinued. Care must be taken when performing heavy physical work, taking a hot bath (it is possible to develop a heat stroke due to the suppression of central and peripheral thermoregulation in the hypothalamus).
During treatment, do not take "cold" non-prescription drugs (possibly increasing m-cholinoblocking effects and the risk of heat stroke).
It is necessary to protect the exposed areas of the skin from excessive solar radiation due to the increased risk of photosensitivity reactions.
Treatment is stopped gradually to avoid the occurrence of the "withdrawal" syndrome.
An antiemetic effect can mask the signs of drug toxicity and make it difficult to diagnose these conditions, the first symptom of which is nausea.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment period it is necessary to avoid (especially at the first stages of treatment) or to be cautious when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Because of the wide therapeutic index, intoxication usually develops only in cases of severe overdose. Symptoms of overdose:
- severe extrapyramidal disorders: acute dyskinetic or dystonic symptoms, glossopharyngeal syndrome, spasm of the eye, spasms of the larynx, pharynx;
- drowsiness, sometimes coma, agitation and confusion with delirium;
- less often - epileptic seizures;
- Hyperthermia or hypothermia;
- Cardiovascular system: decreased or increased blood pressure, tachycardia or bradycardia, changes in ECG, such as prolongation of PQ and QT intervals, flutter and ventricular fibrillation, cardiovascular failure;
- rarely - m-cholinoblocking effects: blurred vision, an attack of increased intraocular pressure, intestinal paresis, urinary retention;
- rarely - respiratory complications: cyanosis, respiratory depression, respiratory failure, aspiration, pneumonia.
Treatment is symptomatic and supportive, in accordance with the general principles of treatment of overdose, while the following circumstances must be taken into account.
Attempts to induce vomiting may be hindered by the antiemetic effect of antipsychotics. Because of rapid absorption, gastric lavage is recommended only in cases of early diagnosis of an overdose. Forced diuresis and dialysis are of little effect.
Analeptics are contraindicated, because against the background of the use of haloperidol because of lowering the threshold of convulsive readiness, there is a tendency to develop epileptic seizures. If severe extrapyramidal symptoms develop, antiparkinsonian drugs should be used, for example, biperiden IV; may require the use of anti-Parkinsonics for several weeks. Patients in a coma undergo intubation. Spasm of pharyngeal muscles can complicate intubation; in this case, the use of short-acting muscle relaxants is possible.
In patients with symptoms of intoxication, the parameters of the ECG and the basic functional indices of the body must be constantly monitored until their normalization. With arterial hypotension, due to the increase in paradoxical effects, adrenaline drugs (epinephrine (adrenaline)) should not be used, which affect blood circulation; Instead, drugs like norepinephrine (for example, continuous drip infusions of norepinephrine (norepinephrine)) or angiotensinamide should be used. Beta-adrenomimetics should be avoided because they cause increased vasodilation.
Hypothermia is treated with slow warming. Infusion solutions for use in patients with hypothermia should be heated.
If fever is severe, antipyretic agents should be used, if necessary, ice baths.
M-holinoblokirujushchie signs can be stopped by application of physostigmine (1-2 mg iv) (if necessary to repeat); The use in standard daily practice is not recommended due to the severe undesirable effects of this drug.
Anticonvulsant drugs are used to treat repeated epileptiform seizures, provided that it is possible to perform artificial ventilation, since there is a risk of respiratory depression.
DRUG INTERACTION
The simultaneous administration of eionol and haloperidol can enhance the effect of alcohol and lead to arterial hypotension.
Increases the severity of the inhibitory effect on the CNS ethanol, tricyclic antidepressants, opioid analgesics, barbiturates and other hypnotics, funds for general anesthesia.
Strengthens the action of peripheral m-holinoblokatorov and most hypotensive drugs (reduces the effect of guanetidine due to its displacement from alpha-adrenergic neurons and suppression of its capture by these neurons).
It inhibits the metabolism of tricyclic antidepressants and MAO inhibitors, while their (mutually) sedative effect and toxicity increase.
With simultaneous use with bupropion reduces the epileptic threshold and increases the risk of major epileptic seizures.
Reduces the effect of anticonvulsants (lowering the threshold of convulsive activity with haloperidol).
Weaken the vasoconstrictive effect of dopamine, phenylephrine, norepinephrine, ephedrine and epinephrine (blockade of? -adrenoceptors with haloperidol, may lead to a distortion of the action of epinephrine and a paradoxical decrease in blood pressure).
Reduces the effect of antiparkinsonian drugs (antagonistic effect on dopaminergic structures of the central nervous system).
Changes (may increase or decrease) the effect of anticoagulants.
Reduces the effect of bromocriptine (dose adjustment may be required).
When used with methyldopa increases the risk of developing mental disorders (including disorientation in space, slowing down and obstructing thinking processes).
Amphetamines reduce the antipsychotic effect of haloperidol, which, in turn, reduces their psychostimulatory effect (haloperidol blockade of? -adrenoceptors).
M-anticholinergic drugs, blockers of histamine H 1 receptors I and antidiskineticheskie generation drugs may enhance m-anticholinergic effect of haloperidol and reduce its antipsychotic effects (may require dose correction).
Long-term use of carbamazepine, barbiturates and other inducers of microsomal oxidation reduces the concentration of haloperidol in plasma.
While the use of lithium drugs (particularly in high dosage) may encephalopathy (may cause irreversible neurointoxications) and strengthening extrapyramidal symptoms.
When concomitantly with fluoxetine increases the risk of side effects from the CNS, especially extrapyramidal reactions.
With simultaneous use with drugs that cause extrapyramidal reactions, increases the frequency and severity of extrapyramidal disorders.
The use of strong tea or coffee (especially in large quantities) reduces the effect of haloperidol.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Store at a temperature not exceeding 25 В° C. Keep out of the reach of children. Shelf life - 5 years.
After opening the bottle drug suitable for use to 6 months. Do not use after the expiration date printed on the package.
