Senorm (Solution) Instructions for Use

ATC Code

N05AD01 (Haloperidol)

Active Substance

Haloperidol (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antipsychotic drug (neuroleptic)

Pharmacotherapeutic Group

Psycholeptics, antipsychotic agents, butyrophenone derivatives

Pharmacological Action

Haloperidol decanoate is a long-acting antipsychotic drug. After intramuscular injection, haloperidol decanoate ester undergoes hydrolysis, leading to the gradual release of the active substance, the neuroleptic haloperidol.

The drug, by its chemical structure, belongs to the butyrophenone derivatives, exerts a central antidopaminergic action 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 neurotransmitters, reduces the permeability of presynaptic membranes, and disrupts neuronal reuptake and storage.

High antipsychotic activity is combined with a moderate sedative effect (in small doses it has an activating effect) and a pronounced antiemetic effect. It causes extrapyramidal disorders and practically has no anticholinergic action.

The sedative effect is not pronounced and is due to the blockade of α-adrenergic receptors of the brainstem reticular formation; the antiemetic effect is due to the blockade of dopamine D2 receptors of the trigger zone of the vomiting center; the hypothermic effect and galactorrhea are due to the blockade of dopamine receptors in the hypothalamus.

Long-term use is accompanied by a change in endocrine status: in the anterior pituitary lobe, the production of prolactin increases and the production of gonadotropic hormones decreases.

It is effective in patients resistant to other neuroleptic agents. It has some activating effect. In hyperactive children, it eliminates excessive motor activity, behavioral disorders (impulsivity, difficulty concentrating, aggressiveness). The therapeutic effect can last up to 6 weeks.

Pharmacokinetics

Haloperidol is 92% bound to plasma proteins. After intramuscular injection, absorption is slow and constant (due to release from the depot), the C_max of active haloperidol is reached in the serum by day 3-9 (in elderly patients – day 1), after which it decreases. T_1/2 is 3 weeks. The equilibrium plasma concentration is reached after 2-4 injections (monthly administration) and is 4-20 mg/ml (10.6-53.2 µmol/l). It easily passes through histohematic barriers, including the blood-brain barrier. It penetrates into breast milk. The pharmacokinetics of haloperidol decanoate after intramuscular injection is dose-dependent. A linear relationship was found between the administration of the drug at a dose of less than 450 mg and the achieved plasma concentration of haloperidol at this dose. Elimination from the body occurs in the form of metabolites, 60% with feces, 40% with urine.

Indications

• Maintenance therapy of chronic forms of schizophrenia in cases where previously used short-acting Haloperidol had a good therapeutic effect; especially if there is a need to use a potent neuroleptic with a mild sedative effect.

ICD codes

Dosage Regimen

Solution

Only intramuscular injections are allowed; do not administer intravenously! The single monthly dose of the drug is recommended to be injected deep into the gluteal muscles. The transition to the use of the long-acting drug is advisable in cases where the patient is constantly taking an oral antipsychotic drug (usually Haloperidol). The dose of the long-acting drug is calculated based on the orally used dose of haloperidol or another neuroleptic.

Initially, a 10-15-fold single dose of the oral drug should be administered every 4 weeks, which is usually 25-75 mg (0.5-1.5 ml) of haloperidol decanoate. The initial dose should not exceed 100 mg of haloperidol decanoate.

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

The commonly used maintenance dose, administered every 4 weeks, is 20 times the single daily oral dose of haloperidol.

Depending on the patient’s therapeutic response to haloperidol decanoate, with repeated exacerbation of the disease symptoms, additional use of oral haloperidol is possible. Doses are set individually depending on the patient’s condition. Temporary interruption of the course of treatment or more frequent administration than once every 4 weeks may be necessary. It is undesirable to inject more than 3 ml of the drug in one injection due to 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. Subsequently, depending on the patient’s condition, the dose of the drug can be increased (the interval between doses and the dose are adjusted with a frequency of at least 1 month).

Adverse Reactions

Side effects after administration of haloperidol decanoate are the same as those that may occur with the use of other dosage forms of haloperidol.

Extrapyramidal symptoms with long-term use may include tremor, muscle rigidity, bradykinesia, akathisia, acute muscle dystonia, oculogyric crisis, laryngeal dystonia (spasmodic dysphonia). Correction: anticholinergic antiparkinsonian drugs should be prescribed. However, it must be borne in mind that their constant use reduces the effectiveness of haloperidol.

Tardive dyskinesia as with the use of other antipsychotic agents, may occur with long-term use or withdrawal of the drug. It is manifested by rhythmic, involuntary movements of the muscles of the face, lips, tongue or jaw. This disorder in some patients may be residual. The disorders stop when haloperidol is resumed, when the dose is increased, or when switching to treatment with another drug. If signs of tardive dyskinesia appear, it is advisable to continue treatment with another drug.

Neuroleptic malignant syndrome (NMS) the use of haloperidol can cause NMS. A rare reaction, occurring as an idiosyncrasy, is characterized by hyperthermia, generalized muscle rigidity, autonomic lability, difficult or rapid breathing, arrhythmias, increase or decrease in blood pressure, increased sweating, urinary incontinence, epileptic seizures, and impaired consciousness of the patient. An early sign of NMS is often hyperthermia. If symptoms of NMS appear, in all cases it is necessary to interrupt treatment with antipsychotic drugs and, under conditions of careful observation, begin supportive, including detoxification, therapy.

Other side effects from the central nervous system depression, lethargy (up to a state similar to lethargy) or psychomotor agitation, insomnia or drowsiness (especially at the beginning of treatment), headache, transient memory and intellectual impairments, dizziness, motor restlessness, feelings of anxiety, fear, or euphoria, epileptic seizures of the “grand mal” type and recurrence of psychotic symptoms (development of a paradoxical reaction).

From the digestive system when used in high doses – decreased appetite, dry mouth, hyposalivation, nausea, vomiting, diarrhea or constipation, impaired liver function, up to the development of jaundice.

From the endocrine system due to the antidopaminergic action, hyperprolactinemia, galactorrhea, gynecomastia, oligo- and amenorrhea, hyper- or hypoglycemia, and decreased secretion of antidiuretic hormone may be observed.

From the cardiovascular system when used in high doses – decreased blood pressure, orthostatic hypotension, arrhythmias, tachycardia, ECG changes (QT interval prolongation).

From the hematopoietic organs transient leukopenia or leukocytosis, agranulocytosis, erythrocytopenia and a tendency to monocytosis.

Allergic reactions urticaria, anaphylaxis, photosensitization, maculopapular and acneiform skin changes, bronchospasm, laryngospasm, hyperpyrexia.

From the genitourinary system urinary retention (with prostatic hyperplasia), peripheral edema, decreased potency, increased libido, priapism.

Laboratory parameters: hyponatremia.

Other alopecia, heat stroke, weight gain, local reactions, cataract, retinopathy, blurred vision. In elderly patients, attacks of angle-closure glaucoma may be observed.

Contraindications

• Severe toxic (alcoholic or medicinal) depression of the central nervous system;
• Coma of various origins;
• Diseases of the central nervous system accompanied by pyramidal or extrapyramidal symptoms (including Parkinson’s disease);
• Depression;
• Hysteria;
• Pregnancy;
• Lactation period;
• Childhood;
• Pathological process localized in the basal ganglia;
• Previously noted hypersensitivity to the components of the drug.

With caution: decompensated cardiovascular diseases, epilepsy, angle-closure glaucoma, hepatic and/or renal insufficiency, thyrotoxicosis (with symptoms of thyrotoxicosis), cardiopulmonary and respiratory insufficiency (including in chronic obstructive pulmonary disease and acute infectious diseases), prostatic hyperplasia with urinary retention, alcoholism.

Use in Pregnancy and Lactation

Results of observation of a large number of patients showed that Haloperidol does not reliably increase the number of congenital pathologies. In isolated cases, congenital anomalies have been described against the background of the use of haloperidol during pregnancy, usually in combination with other drugs. Thus, the use of haloperidol decanoate during pregnancy is contraindicated.

Haloperidol penetrates into breast milk. In some cases, extrapyramidal disorders have been noted in newborns whose mothers took Haloperidol. Therefore, when breastfeeding, breastfeeding should be discontinued.

Use in Hepatic Impairment

With caution.

Use in Renal Impairment

With caution.

Pediatric Use

Contraindicated.

Geriatric Use

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

Special Precautions

There have been cases of sudden death in patients taking antipsychotic drugs, in particular Haloperidol. Since treatment with haloperidol in a number of patients was noted to prolong the QT interval on the ECG, the drug should be used with caution in patients at risk of QT interval prolongation (hypokalemia, simultaneous use of other drugs that can cause QT interval prolongation). If it is necessary to use haloperidol decanoate, Haloperidol should first be prescribed orally to determine possible unexpected hypersensitivity.

Since Haloperidol is metabolized in the liver, caution is required when using haloperidol in severe liver pathology. With long-term use, periodic monitoring of the blood picture and liver function is necessary.

In isolated cases, the development of convulsive syndrome has been described against the background of the use of haloperidol. Therefore, in patients with epilepsy, as well as in those patients who have increased convulsive readiness (chronic intoxication, both alcoholic and of other origin, history of traumatic brain injury, etc.), haloperidol decanoate should be prescribed with caution.

Thyroxine increases the toxicity of haloperidol, therefore Haloperidol in patients with hyperthyroidism is applicable only under the cover of adequate thyrostatic therapy.

In patients whose psychopathological disorders include symptoms of a depressive syndrome, Haloperidol should be administered in combination with antidepressants. If it is necessary to simultaneously carry out antiparkinsonian therapy for the patient, then after the introduction of the last dose of haloperidol decanoate, treatment with these drugs should be continued for some time, because the elimination of the antiparkinsonian drug from the body occurs faster than that of haloperidol decanoate, a long-acting drug.

Caution should be exercised when performing heavy physical work, taking a hot bath (heat stroke may develop due to suppression of central and peripheral thermoregulation in the hypothalamus).

During treatment, over-the-counter “cold” medicines should not be taken (anticholinergic effects may be enhanced and the risk of heat stroke may increase).

Open areas of the skin should be protected from excessive solar radiation due to an increased risk of photosensitization.

Treatment should be discontinued gradually to avoid the occurrence of withdrawal syndrome.

The antiemetic effect may mask signs of drug toxicity and complicate the diagnosis of conditions whose first symptom is nausea.

Before prescribing the prolonged form, the patient should first be switched from any other neuroleptic to Haloperidol (to prevent unexpected hypersensitivity to haloperidol).

Influence on the ability to drive vehicles and mechanisms

In the initial period of treatment, you should not drive a car or work in conditions of increased risk of injury. Subsequently, the degree of restrictions is determined individually. During the use of the drug, you should not drink alcoholic beverages.

Overdose

Symptoms of haloperidol decanoate overdose are similar to those observed with the use of other dosage forms of haloperidol.

If an overdose of haloperidol decanoate is suspected, the prolonged nature of the drug’s action should be taken into account.

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

In severe cases, a coma may occur, with respiratory depression against the background of severe arterial hypotension. The possibility of developing ventricular arrhythmias with QT interval prolongation should be considered.

Treatment there is no specific antidote. Symptomatic therapy: in a coma, support of the respiratory system function is necessary, if necessary, connection to a ventilator. Monitoring of ECG and other vital functions of the body is necessary. For the treatment of severe arterial hypotension or circulatory insufficiency, intravenous administration of a sufficient volume of fluid, plasma or concentrated albumin solution, as well as the appointment of vasopressor agents (norepinephrine or dopamine) is necessary. Epinephrine is strictly prohibited in these cases! In combination with haloperidol, it can cause severe arterial hypotension). For severe extrapyramidal symptoms, it is necessary to use antiparkinsonian agents and central anticholinergics parenterally. Hemodialysis is ineffective.

Drug Interactions

The drug is capable of enhancing the effect of agents that depress the central nervous system – alcohol, sedative and hypnotic drugs, as well as narcotic analgesics. Simultaneous administration of haloperidol with these drugs can lead to respiratory depression. In combination with methyldopa, it enhances the effect of the latter on the central nervous system, increases the risk of mental disorders (including disorientation in space, slowing and difficulty in thinking processes).

Reduces the antiparkinsonian effect of levodopa and other anticonvulsants (haloperidol lowers the seizure threshold).

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

Pharmacokinetic studies have revealed an increase, moderate or moderate in severity, in the level of haloperidol in the blood serum with the combined use of haloperidol with the following drugs: quinidine, buspirone, fluoxetine. If it is necessary to combine them, a reduction in the dose of haloperidol may be required.

With long-term use of drugs that have the properties of inducers of liver microsomal enzymes (carbamazepine, rifampicin, phenobarbital, etc.), the concentration of haloperidol in the blood decreases. Therefore, if it is necessary to use them together, an increase in the dose of haloperidol may be required. In case of subsequent withdrawal of therapy with these drugs, the advisability of reducing the dose of haloperidol should be taken into account.

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

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

Haloperidol reduces the effectiveness of the use of antihypertensive agents from the group of adrenergic blockers.

Weakens the vasoconstrictive effect of dopamine, phenylephrine, norepinephrine, ephedrine and epinephrine (blockade of alpha-adrenergic receptors by haloperidol can lead to a perversion of the action of epinephrine and to a paradoxical decrease in blood pressure).

Enhances the action of peripheral anticholinergics and most hypotensive agents (reduces the effect of guanethidine due to its displacement from alpha-adrenergic neurons and suppression of its uptake by these neurons).

Prevents the suppression of insulin release by diazoxide. When used simultaneously with bupropion, it lowers the seizure threshold and increases the risk of major epileptic seizures.

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

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

Amphetamines reduce the antipsychotic effect of haloperidol, which in turn reduces their psychostimulant effect (blockade of alpha-adrenergic receptors by haloperidol).

M-cholinoblocking, antihistamine (first generation), and antidyskinetic agents: may enhance the m-cholinoblocking effect of haloperidol and reduce its antipsychotic action (dose adjustment may be required).

Concomitant use with drugs that cause extrapyramidal reactions increases the frequency and severity of extrapyramidal disorders.

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

Storage Conditions

Store in a light-protected place, out of reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.