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

Pharmacodynamics:Haloperidol decanoate is an antipsychotic drug of prolonged action. After intramuscular injection from the ester of haloperidol decanoate by hydrolysis, a gradual release of the active ingredient, a haloperidol antileptic, occurs.

The drug for chemical structure refers to derivatives of butyrofenone, has a central antidofaminergic effect and is a highly effective neuroleptic. It 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, violates the reverse neuronal capture and deposition.High antipsychotic activity is combined with a moderate sedative effect (in small doses has an activating effect) and pronounced antiemetic effect. Causes extrapyramidal disorders, virtually no cholinoblocking effect.

Sedative action is not expressed, due to blockade of alpha-adrenergic receptors 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.

Effective in patients resistant to other neuroleptic drugs. Has some activating effect. In hyperactive children, eliminates excessive motor activity, behavioral disorders (impulsivity, difficulty concentrating, aggressiveness).

The therapeutic effect can last up to 6 weeks.

Pharmacokinetics:The drug is 92% bound to blood plasma proteins.After intramuscular administration, absorption is slow and constant (due to release from the depot), the maximum concentration of active haloperidol is reached in the blood serum by 3-9 days (in elderly patients - 1 day), and then decreases. The half-life of this dosage form is 3 weeks. Equilibrium plasma concentration is achieved after 2-4 injections (monthly administration) and is 4-20 mg / ml (10.6-53.2 μmol / L). Easily passes through the histohematological barriers, including the hemoencephalic barrier (BBB). Penetrates into breast milk. The pharmacokinetics of haloperidol decanoate after intramuscular administration is dose-dependent. Between the administration of the drug in a dose of less than 450 mg and the level of haloperidol achieved in this plasma, a linear dependence is revealed. Excretion from the body occurs in the form of metabolites, 60% with feces, 40% with urine.

Indications:Supportive therapy for chronic forms of schizophrenia in cases where the previously used haloperidol had a good therapeutic effect; especially if there is a need for a strong neuroleptic with a little sedative effect.

Contraindications:The previously noted increased sensitivity to the components of the drug.Inhibition of central nervous system toxic (alcoholic or drug-induced) genesis in severe, coma various genesis, central nervous system diseases accompanied by pyramidal or extrapyramidal symptoms (including Parkinson's disease), depression, hysteria, pregnancy, lactation, children age. Pathological process with localization in the region of the basal ganglia.

Carefully:Diseases of the cardiovascular system decompensation, epilepsy, angle-closure glaucoma, liver and / or kidney failure, hyperthyroidism (s thyrotoxicosis phenomena), pulmonary heart and respiratory failure (including chronic obstructive pulmonary disease and acute infectious diseases) , hyperplasia of the prostate with a delay of urine, alcoholism.

Pregnancy and lactation:Pregnancy and lactation. The results of monitoring a large number of patients showed that haloperidol reliably does not increase the number of congenital pathologies. In some cases, congenital anomalies are described against the background of haloperidol during pregnancy, usually in combination with other drugs. In this way, haloperidol can be prescribed during pregnancy only if the expected benefits unambiguously exceed the possible teratogenic effect. Haloperidol penetrates into the mother's milk. In some cases, extrapyramidal disorders have been noted in newborns whose mother has been taking haloperidol. Therefore, when breastfeeding haloperidol should also be appointed with a careful assessment of the relationship between the expected effect and the possible risk.

Dosing and Administration:Only intramuscular injections are allowed, do not inject intravenously! A single monthly dose of the drug is recommended to be injected deep into the gluteal muscles.

The transition to the use of long-acting drugs is appropriate in cases where the patient constantly takes an oral antipsychotic drug (as a rule, haloperidol). Calculation of the dose of the long-acting drug is carried out using the oral dosage of haloperidol or another neuroleptic.

Initially, every 10 to 10 times a single dose of the oral preparation should be given every 4 weeks, which is usually 25-75 mg (0.5-1.5 ml) Haloperidol decanoate. The initial dose should not exceed 100 mg Haloperidol decanoate.

Further, depending on the therapeutic response, the dose of the drug can be increased gradually by 50 mg, until the optimal effect is achieved.

The usual maintenance dose, administered every 4 weeks, is 20 times the one-day oral dose of haloperidol.

Depending on the therapeutic response of the patient to Haloperidol decanoate, with the repeated increase in the symptoms of the disease, additional use of haloperidol is possible orally. Dosages are set individually depending on the patient's condition. It may be necessary to temporarily interrupt the course of treatment or more frequent than once in 4 weeks, the administration of the drug. It is not desirable to administer more than 3 ml of the drug in one injection because of the risk of discomfort in the patient.

In elderly and debilitated patients, lower initial doses should be used - 12.5-25 mg once every 4 weeks. Later, depending on the patient's condition, the dose of the drug can be increased (the interval between doses and dosage is adjusted at a frequency of at least 1 month).

Side effects:

Adverse events after administration Haloperidol decanoate The same, which can occur when using other forms of haloperidol. Extrapyramidal symptoms With long-term use may occur tremor, rigidity of muscles, bradykinesia, akathisia, acute muscular dystonia, oculogic crisis, laryngeal dystonia (spastic dysphonia).

Correction: antiparkinsonian preparations of anticholinergic action should be prescribed. However, it must be borne in mind that their constant use reduces the effectiveness of haloperidol.

Late dyskinesia As with other antipsychotics, it can occur with prolonged use or withdrawal of the drug. It is manifested by rhythmic movements of muscles of the face, lips, tongue or jaw area that can not be controlled by volitional control. This disorder in some patients may be characterized by residual events. Disorders cease with the resumption of haloperidol, with increasing doses or when switching to treatment with another drug. When signs of late dyskinesia, it is advisable to continue treatment with another drug.

Malignant neuroleptic syndrome (CNS) The use of haloperidol can cause CNS. A rare reaction that arises in the idiosyncrasy type is characterized by hyperthermia, generalized rigidity of the muscles, vegetative lability, shortness of breath or rapid breathing, arrhythmias, increased or decreased blood pressure (BP), increased sweating, urinary incontinence, epileptic seizures, and impaired consciousness. The early sign of the NSA is often hyperthermia. When symptoms of NSA appear in all cases, it is necessary to interrupt treatment with antipsychotics and, under careful monitoring, begin supporting, including detoxification therapy.

Other side effects from the CNS Depression, inhibition (up to a state similar to lethargy) or psychomotor agitation, insomnia or drowsiness (especially at the beginning of treatment), headache, coming mild-intellectual disorders, dizziness, motor anxiety, anxiety, fear, or euphoria, epileptic seizures type "grand mal" and the resumption of psychotic symptoms (the development of a paradoxical reaction).

Digestive system When used in high doses - decreased appetite, dry mouth, hypo-salivation, nausea, vomiting, diarrhea or constipation, impaired liver function, until the development of jaundice.

Endocrine system Because of the antidopaminic effect, hyperprolactinemia, galactorrhea, gynecomastia, oligo- and amenorrhea can be observed. Rarely, hyper-or hypoglycemia and a decrease in the secretion of antidiuretic hormone. The cardiovascular system When used in high doses - reduced blood pressure, orthostatic hypotension, arrhythmias, tachycardia, changes in the electrocardiogram (ECG) (prolongation of the QT interval).

On the part of the organs of hematopoiesis Rarely - temporary leukopenia or leukocytosis, agranulocytosis, erythropenia and a tendency to monocytosis.

Allergic reactions In particular, hives, anaphylaxis, photosensitization, maculopapular and acne-like skin changes, rarely - bronchospasm, laryngospasm, hyperpyrexia.

From the genitourinary system Urinary retention (with hyperplasia

prostate gland), peripheral edema, decreased libido, priapism. Laboratory indicators Hyponatremia.

Other side effects Alopecia, heat stroke, weight gain, local reactions, cataract, retinopathy, blurred vision. In the elderly, patients may experience attacks of closed-angle glaucoma.

Overdose:Overdose Symptoms Haloperidol decanoate are similar to those observed when other forms of haloperidol are used. If there is a suspicion of overdose Haloperidol decanoate should take into account the prolonged nature of the drug.

The most important signs of an overdose are: severe extrapyramidal disorders (muscle rigidity, muscle hypertension is possible, general or localized tremor), arterial hypo-, sometimes hypertension, a state of severe inhibition.

In extreme cases, a comatose state may occur, with respiratory depression on the background of severe arterial hypotension.

It is necessary to take into account the possibility of developing ventricular arrhythmias with an elongation of the QT interval.

Treatment of overdose: there is no specific antidote. Symptomatic therapy:

In comatose state, support of the respiratory system function is necessary, if necessary, connection to the artificial respiration apparatus.It is necessary to monitor the ECG and other vital functions of the body.

To treat severe arterial hypotension or circulatory insufficiency, intravenous injection of a sufficient volume of fluid, blood plasma or concentrated albumin solution, and the appointment of vasopressor drugs (norepinephrine or dopamine) is necessary.

In these cases, epinephrine is strictly forbidden!

In combination with haloperidol, it can cause severe arterial hypotension. In case of severe extrapyramidal symptoms, it is necessary to use parenterally anti-Parkinsonics and central holinoblokatory. Dialysis is ineffective.

Interaction:The drug is able to enhance the effect of drugs that depress the central nervous system - alcohol, sedatives and hypnotics, as well as narcotic analgesics. The simultaneous administration of haloperidol with these drugs can lead to respiratory depression. In combination with methyldopa enhances the effect of the latter on the central nervous system, increases the risk of developing mental disorders (including disorientation in space, slowing down and obstructing thinking processes).Reduces the antiparkinsonian effect of levodopa and other anticonvulsants (reduction of the convulsive threshold by haloperidol).

Haloperidol inhibits the metabolism of tricyclic antidepressants and monoamine oxidase inhibitors, so that their level in the blood plasma may increase, with an increase in anticholinergic action, and toxicity, including. in relation to the cardiovascular system.

Pharmacokinetic studies revealed an increase in moderate or moderate severity, the level of haloperidol in the blood serum, when combined with haloperidol, the following drugs: quinidine, buspirone, fluoxetine. If they need to be combined, a dose reduction of haloperidol may be required.

With prolonged use of drugs that have the properties of inducers of liver enzymes (carbamazepine, rifampicin, phenobarbital and others) the concentration of haloperidol in the blood decreases. Therefore, if necessary, their combined use may require an increase in the dose of haloperidol. In the case of subsequent withdrawal of therapy with these drugs should be borne in mind the advisability of reducing the dose of haloperidol.

In rare instances, the joint application of haloperidol and lithium salts were observed following disorders: phenomenon encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, brain stem symptoms, coma. In most cases, these disorders are reversible. The reason for their manifestation in this situation is unclear. If these disorders occur, haloperidol should be discontinued immediately.

Haloperidol changes (may increase or decrease) the effect of anticoagulants.

Haloperidol reduces the effectiveness of the use of antihypertensive drugs from the group of adrenoblockers.

, Decreases the vasoconstrictor action of dopamine, phenylephrine, norepinephrine, epinephrine and ephedrine (alpha adrenoceptor blockade galoperid scarlet, can lead to distortion of the action of epinephrine and a paradoxical decrease in blood pressure).

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).

Prevents the suppression of diazoxide release of insulin. With simultaneous use with bupropion reduces the epileptic threshold and increases the risk of major epileptic seizures.

Reduces the effect of antiparkinsonian drugs (antagonistic effect on dopaminergic structures of the central nervous system).

Reduces the effect of bromocriptine (dose adjustment may be required).

Amphetamines reduce antipsychotic effect of haloperidol, which, in turn, reduces their inducing effect (haloperidol blockade of alpha-adrenoceptors).

Anticholinergic, antihistamine (I generation) and antidiskinetic agents of the agent can enhance the M-cholinolytic effect of haloperidol and reduce its antipsychotic effect (dose adjustment may be required).

With simultaneous use with drugs that cause extrapyramidal reactions, increases the frequency and severity of estropyramide disorders.

The use of strong tea or coffee (especially in large quantities) reduces the effect of haloperidol.

Special instructions:

There are isolated cases of sudden death of patients taking antipsychotic drugs, in particular haloperidol. Since haloperidol some patients observed lengthening QT interval on the ECG, the drug should be used with caution in patients in whom there is a risk lengthening QT interval (hypokalemia, concurrent use of other drugs that can cause elongation of the interval). If it is necessary to use Haloperidol decanoate, you must first assign haloperidol orally, to determine a possible unexpected hypersensitivity.

Due to haloperidol is metabolized in the liver, caution is needed in the application of haloperidol in severe hepatic pathology. With prolonged use, periodic monitoring of the blood picture and liver function is necessary. In some cases, the development of the phenomena of convulsive syndrome is described against the background of the use of haloperidol. Therefore patients with epilepsy and those patients who have an increased convulsive readiness (chronic intoxication as alcohol and other genesis, craniocerebral trauma history, etc.) Haloperidol decanoate should be administered with caution.

Thyroxine increases haloperidol toxicity, so haloperidol in patients with hyperthyroidism is only applicable under the cover of adequate thyreostatic therapy.

Patients who have a picture of psychopathological disorders, there are phenomena of depressive syndrome, haloperidol should be administered in combination with antidepressants. If there is a need for simultaneous administration of antiparkinsonian therapy to a patient, then after the last dose Haloperidol decanoate treatment with these drugs should continue for some time, since the removal of the antiparkinsonian drug from the body occurs faster than Haloperidol decanoate - a product of prolonged action.

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, it is not necessary to take "anti-cold" OTC medicines (possibly intensifying anticholinergic effects and the risk of heat stroke).

Protect open areas of the skin from excessive sunlight due to the increased risk of photosensitivity.

Treatment is stopped gradually to avoid the occurrence of withdrawal syndrome.

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

Before the appointment of the prolonged form, the patient should first be transferred from any other antipsychotic to haloperidol (prevention of unexpected hypersensitivity to haloperidol).

During the use of the drug, you should not drink alcohol.

Effect on the ability to drive transp. cf. and fur:In the initial period of treatment, you can not drive a car or work in conditions of increased risk of injury. Subsequently, the degree of restrictions is determined on an individual basis.

Form release / dosage:Solution for intramuscular administration (oily).

Packaging:1 ml of preparation in ampoule from brown glass I of hydrolytic class with a point for the fault. 5 ampoules in contour plastic packaging. 1 contour plastic packaging together with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C, in a place protected from light. Keep out of the reach of children!

Shelf life:5 years.Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015065 / 01

Date of registration:13.05.2009 / 17.03.2015

Expiration Date:Unlimited

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

Manufacturer: & nbsp

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp17.03.2015

Illustrated instructions

Instructions

Haloperidol decanoate (Haloperidol decanoate)