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

Pharmacodynamics:Haloperidol - neuroleptic, belonging to the derivatives of butyrofenone. Has a pronounced antipsychotic and antiemetic effect. The effect of haloperidol is associated with blockade of central dopamine (D2) and alpha-adrenergic receptors in the mesocortical and limbic structures of the brain. Blockade of D2-receptors of the hypothalamus leads to a decrease in body temperature, galactorrhea (increased production of prolactin). The inhibition of dopamine receptors in the trigger zone of the vomiting center underlies the antiemetic effect. Interaction with the dopaminergic structures of the extrapyramidal system can lead to extrapyramidal disorders. Expressed antipsychotic activity is combined with a mild sedative effect (in small doses it has an activating effect).Strengthens the action of hypnotics, narcotic analgesics, means for general anesthesia, analgesics and other means of suppressing the function of the central nervous system.

Pharmacokinetics:Absorbed by passive diffusion, in a non-ionized form, mainly from the small intestine. Bioavailability: 60-70%. When administered orally, the maximum concentration in the blood is reached after 2-6 hours, with intramuscular - in 20 minutes. The therapeutic effect occurs at a plasma concentration of 4-20-25 mg / l. The volume of distribution is large, 7.9 + 2.5 l / kg, communication with the proteins of the shelter - 92%. Haloperidol metabolized in the liver, the metabolite is pharmacologically inactive. Also, haloperidol is subjected to oxidative N-dealkylation and glucuronprovene. The half-life from plasma after oral intake is 24 h (12-38 h), after intramuscular injection - 21 (13-36 h), after intravenous - 14 (10-19 h). It is excreted in the form of metabolites with fecal masses - 60% (including with bile - 15%), with urine - 40%, (including 1% - unchanged). Easily penetrates through gistogematicheskie barriers, incl. through placental and blood-brain, penetrates into breast milk.

Indications:

- acute and chronic psychoses accompanied by excitement, hallucinatory and delusional disorders, (schizophrenia, affective disorders, psychosomatic disorders);

- behavior disorders, personality changes (paranoid, schizoid and others), incl. and in childhood, autism, Gilles de la Tourette syndrome,

- ticks, Goettington's chorea,

- long-lasting and uncharted hiccup therapy,

- vomiting, which is not amenable to treatment with classical antiemetic drugs, including those associated with antitumor therapy,

- Premedication before surgery.

Contraindications:

- depression of the central nervous system, incl. and severe toxic oppression of the central nervous system caused by xenobiotics, coma of various origins,

- CNS diseases, accompanied by pyramidal and extrapyramidal disorders (Parkinson's disease, etc.),

- lesions of the basal ganglia,

- hypersensitivity to derivatives of butyrophenone,

- Hypersensitivity to the ingredients of the drug,

- Children's age up to 3 years,

- Depression.

Carefully:

- with decompensated cardiovascular diseases (including angina pectoris);

- if the conduction of the heart muscle is impaired;

- with severe diseases of the kidneys, liver;

- pulmonary-cardiac insufficiency (incl. with bronchial asthma and acute infections);

- epilepsy;

- convulsive conditions in the anamnesis;

- an angle-closure glaucoma;

- hyperthyroidism (thyrotoxicosis);

- hyperplasia of the prostate (urinary retention);

- active alcoholism.

Pregnancy and lactation:Haloperidol does not cause a significant increase in the number of cases of congenital malformations. Some cases of congenital defects are known when taking haloperidol concomitantly with other medications during pregnancy. The intake of haloperidol during pregnancy is only permissible if the benefit justifies the risk to which the fetus will be exposed! Haloperidol excreted in breast milk. In cases where taking haloperidol is unavoidable, the benefits of breastfeeding in relation to a potential hazard should be justified. In some cases, estradiramidal symptoms were observed in newborns whose mothers were taking haloperidol during lactation.

Dosing and Administration:

Dosage depends on the clinical response of the patient. Most often, this means a gradual increase in the dose in the acute phase of the disease, in the case of maintenance doses, a gradual dose reduction in order to ensure the lowest effective dose.High doses are used only in cases of ineffectiveness of smaller doses. The following are the average doses.

To stop psychomotor agitation in the early days haloperidol appoint intramuscularly 2.5-5 mg 2-3 times a day. either intravenously in the same dosage (the ampoule should be diluted in 10-15 ml of water for injection), the maximum daily vine: 60 mg. After achieving a stable sedative effect, they switch to taking the drug inside.

For elderly patients: 0.5-1.5 mg (0.1-0, 3ml solution), the maximum daily dose: 5 mg (1ml solution).

For children older than 3 years, the dose is 0.025-0.05 mg per day, divided into 2 doses. The maximum daily dose: 0.1 5 mg / kg.

On average, the therapeutic dose is 10-15 mg / day, with chronic forms of schizophrenia - 20-40 mg / day, if necessary, the dose can be increased to 50-60 mg / day.

The average duration of treatment: 2-3 months.

Supporting doses (without exacerbation): from 0.5-0.75 mg to 5 mg / day (dose is reduced gradually).

Children 3-12 years old (with a body weight of 15-40 kg): 0.025-0.05 mg per kilogram of body weight per day 2-3 times a day, increasing the dose no more often than every 5-7 days, to a daily dose of 0 , 15 mg / kg.

In case of behavioral disorders, Tourette's syndrome: 0,05 mg / kg / day, dividing by 2-3 doses and increasing the dose no more often than every 5-7 days to 3 mg / day.

With autism: 0.025-0.05 mg / kg / day.

Older patients and weakened patients are prescribed 1 / 3-1 / 2 of the usual dose for adults, the dose is increased no more often than every 2-3 days.

As an antiemetic, appoint inwards for 1.5-2.5 mg.

Side effects:

At low daily doses (an average of 3-5 mg) haloperidol, usually, well tolerated, side effects are not expressed. At higher doses, side effects develop more often. The most frequent reactions are from the nervous system:

From the side of the central nervous system: extrapyramidal disorders of varying severity. Most patients have transient akineto-rigid syndrome, oculogic crises, akathisia, dystonic phenomena.

Perhaps the development of neuroleptic malignant syndrome (NZS), one of the first signs of which is an increase in body temperature.

The state of anxiety, anxiety, agitation, depression, seizures of epilepsy, the development of a paradoxical reaction - exacerbation of psychotic disorders.

With long-term administration of haloperidol, it is possible to develop late dyskinesias, especially in elderly patients and patients with organic deficiency of the central nervous system, so doses for this category of patients should be reduced.

At the beginning of therapy, there may be lethargy, drowsiness or insomnia, headache that occurs after the appointment of correctors (anti-Parkinsonian drugs).

From the cardiovascular system: arrhythmia, tachycardia, when using high doses - lowering blood pressure; orthostatic hypotension, lability of blood pressure, very rarely ECG changes (prolongation of QT interval, signs of flutter and ventricular fibrillation at high doses and in case of predisposition).

From the organs of blood and blood: Transient leukopenia or leukocytosis. erythropenia, lymphomonocytosis, rarely - agranulocytosis.

From the side of the liver: increased activity of "liver" transaminases, jaundice.

From the skin: allergic reactions, rash, toxicodermia, dry skin. photosensitization. hyperfunction of the sebaceous glands.

From the digestive tract: anorexia, dyspepsia, dry mouth, sometimes hypersalivation, nausea. vomiting. constipation. diarrhea.

From the endocrine system: dysmenorrhea, frigidity, gynecomastia, pain in the mammary glands, galactorrhea, impotence, increased libido, priapism, weight gain.

From the genitourinary system: retention of urine (for example, with hyperplasia of the prostate gland), peripheral edema.

Other: increased fatigue, decreased thirst, heat stroke, alopecia, hyponatremia, hyper- or hypoglycemia.

Overdose:

In case of an overdose of the drug, the appearance of acute neuroleptic reactions, listed above, is possible. Symptoms: muscle stiffness, tremor, drowsiness, decrease, sometimes high blood pressure, in severe cases - coma, respiratory depression, shock, prolongation of the QT interval with ventricular arrhythmia.

Particularly should alarm the increase in body temperature, which may be one of the symptoms of malignant neuroleptic syndrome. In severe cases of overdose, various forms of impaired consciousness can be observed, including coma, convulsive reactions.

Treatment: discontinuation of therapy with neuroleptics, with ingestion - against maintenance therapy, gastric lavage, Activated carbon, if the consciousness is not darkened and there is no soma, seizures. If breathing is depressed, artificial ventilation may be required. With hypotension and collapse - intravenously,To maintain circulation, plasma or concentrated albumin, dopamine, or norepinephrine as an invoker. Epinephrine in these cases it is strictly forbidden to apply, as it can provoke extreme hypotension! For relief of extrapyramidal symptoms - central antiparkinsonian preparations of anticholinergic action (for example, 1-2 mg of benzthropin mesylate intravenously or intramuscularly). Their cancellation should be done with caution. Intravenously injected diazepam, glucose solution, nootropics, B and C vitamins. Dialysis is ineffective.

There is no specific antidote.

Interaction:

Haloperidol enhances the oppressive effects of opioid analgesics, hypnotics, tricyclic antidepressants, agents for general anesthesia, alcohol on the central nervous system.

With simultaneous use with antiparkinsonian drugs (levodopa and others), the therapeutic effect of these agents may decrease 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 weaken the action of epinephrine (epinephrine) and other sympathomimetics, cause a "paradoxical" reduction in arterial pressure and tachycardia when combined.

Strengthens the action of peripheral M-holinoblokatorov and most antihypertensive drugs (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 can 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 MAO inhibitors, which increases their plasma levels and increases 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, the risk of side effects on the central nervous system increases. especially extrapyramidal reactions.

With concomitant administration with lithium, especially in high doses, can cause irreversible neurointoxication, as well as enhance extrapyramidal symptoms.

With simultaneous reception with amphetamines, the antipsychotic effect of haloperidol and the psychostimulatory effect of amphetamines are reduced as a result of 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:

Parenteral administration should be carried out under the strict supervision of a physician, especially in the case of elderly and children. When the therapeutic effect is achieved, the oral form of treatment should be switched.

Because the haloperidol may cause prolongation of the QT interval, caution should be exercised if there is a risk of prolongation of QT (QT syndrome, hypokalemia, drugs causing prolongation of the RT interval), especially with parenteral administration.

In connection with the metabolism of haloperidol in the liver, it is important to exercise caution when prescribing it to patients with impaired hepatic function.

There are cases of development of seizures caused by haloperidol. Patients with epilepsy and patients, in conditions predisposing to the development of convulsive syndrome (alcoholism, brain trauma), the drug should be used with extreme caution. When lactose intolerance should be taken into account that 1.5 mg tablet contains 157 mg of lactose, 5 mg tablet - 153.5 mg.

With severe physical exertion, taking a hot bath, care must be taken because of the possible development of a heat stroke as a result of ineffective central and peripheral thermoregulation of the hypothalamus due to taking the drug.

You should warn the patient about the need to avoid taking medications against colds that are acquired without a prescription, because it is possible to enhance the anticholinergic effects of haloperidol and the development of a heat stroke.

During treatment, patients should regularly monitor ECG, blood formulas, hepatic samples.

For relief of extrapyramidal disorders, antiparkinsonian agents (cyclodol, etc.), nootropics, vitamins are prescribed; their use continues after haloperidol withdrawal, if they are excreted from the body more quickly than haloperidol to avoid extrapyramidal symptoms.

The severity of extrapyramidal disorders is associated with a dose, often, with a decrease in dose, they can decrease or disappear.

In a number of cases, signs of neurological disorders are observed when the drug is withdrawn after a long course of treatment, so haloperidol should be abolished, gradually reducing the dose.

With the development of tardive dyskinesia should not abruptly cancel the drug; a gradual dose reduction is recommended.

Protect open areas of the skin from excessive sunlight due to the increased risk of photosensitization in such cases.

The antiemetic effect of haloperidol can mask the signs of drug toxicity and make it difficult to diagnose conditions, the first symptom of which is nausea.

While taking haloperidol, alcohol is not allowed.

Effect on the ability to drive transp. cf. and fur:During the reception of haloperidol it is prohibited to drive vehicles, service mechanisms and perform other types of work requiring increased concentration of attention.

Form release / dosage:Solution for intravenous and intramuscular injection 5 mg / 1 ml.

Packaging:1 ml of the drug in an ampoule of colorless glass I hydrolytic class. 5 ampoules in contour plastic packaging. 1 contour plastic packaging together with instructions for use in a cardboard bundle.

Storage conditions:Store at a temperature of 15-30 ° C, protected from light, out of reach of children.

Shelf life:5 years. Do not use the product after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013574 / 02

Date of registration:09.08.2011

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Information update date: & nbsp09.08.2011

Illustrated instructions

Instructions

Haloperidol-Richter (Haloperidol-Richter)