solution for intramuscular injection oily 50 mg/ml; dark glass ampoule 1 ml, cardboard pack 5; No. P N015065/01, 2009-05-13 from Gedeon Richter (Hungary)
Latin name
Haloperidol decanoate
Active substance
Haloperidol*(Haloperidolum)
ATX:
N05AD01 Haloperidol
Pharmacological group
Neuroleptics
Nosological classification (ICD-10)
F20 Schizophrenia
F29 Non-organic psychosis, unspecified
F91 Behavioral disorders
R41.8.0* Intellectual-mnestic disorders
R45.1 Restlessness and agitation
Release form
Solution for intramuscular administration, oily, 50 mg/ml. In a dark glass ampoule of I hydrolytic class with a breaking point, 1 ml. 5 pcs in a plastic tray. 1 plastic pallet in a cardboard box.
Compound
pharmachologic effect
pharmachologic effect- antipsychotic, neuroleptic, antiemetic.Indications of the drug
Psychomotor agitation of various origins (manic state, mental retardation, psychopathy, schizophrenia, chronic alcoholism), delusions and hallucinations (paranoid states, acute psychosis), Gilles de la Tourette syndrome, Huntington's chorea, psychosomatic disorders, behavioral disorders in old age and childhood, stuttering , long-lasting and treatment-resistant vomiting and hiccups. For haloperidol decanoate: schizophrenia (maintenance therapy).
Contraindications
Hypersensitivity, severe toxic depression of the central nervous system or coma caused by taking drugs; diseases of the central nervous system accompanied by pyramidal and extrapyramidal symptoms (including Parkinson's disease), epilepsy (the convulsive threshold may decrease), severe depressive disorders (symptoms may worsen), cardiovascular diseases with decompensation symptoms, pregnancy, breastfeeding, age up to 3 years.
Directions for use and doses
V/m, in the gluteal region.
Intended exclusively for adults, exclusively for intramuscular administration. Do not administer IV.
Doses exceeding 3 ml should be avoided to avoid an unpleasant feeling of fullness at the injection site.
Use during pregnancy and breastfeeding
Contraindicated during pregnancy.
Treatment should be stopped during treatment breast-feeding(passes into breast milk).
Side effects
From the outside nervous system and sense organs: akathisia, dystonic extrapyramidal disorders (including spasms of the muscles of the face, neck and back, tic-like movements or jerks, weakness in the arms and legs), parkinsonian extrapyramidal disorders (including difficulty speaking and swallowing, mask-like face, shuffling gait, hand tremors and fingers), headache, insomnia, drowsiness, restlessness, anxiety, agitation, agitation, euphoria or depression, lethargy, epileptic seizures, confusion, exacerbation of psychosis and hallucinations, tardive dyskinesia (see “Precautions”); visual impairment (including visual acuity), cataracts, retinopathy.
From the outside of cardio-vascular system and blood (hematopoiesis, hemostasis): tachycardia, arterial hypotension/hypertension, QT interval prolongation, ventricular arrhythmia, ECG changes; there are reports of cases sudden death, prolongation of the QT interval and heart rhythm disturbances such as “pirouette” (see “Precautions”); transient leukopenia and leukocytosis, erythropenia, anemia, agranulocytosis.
From the respiratory system: laryngospasm, bronchospasm.
From the gastrointestinal tract: anorexia, constipation/diarrhea, hypersalivation, nausea, vomiting, dry mouth, liver dysfunction, obstructive jaundice.
From the outside genitourinary system: engorgement of the mammary glands, unusual secretion of milk, mastalgia, gynecomastia, disorder menstrual cycle, urinary retention, impotence, increased libido, priapism.
From the outside skin: maculopapular and acne-like skin changes, photosensitivity, alopecia.
Others: neuroleptic malignant syndrome, accompanied by hyperthermia, muscle rigidity, loss of consciousness; hyperprolactinemia, sweating, hyperglycemia/hypoglycemia, hyponatremia.
Precautionary measures
Increased mortality in older patients with dementia-associated psychosis. According to Food and Drug Administration (FDA) 1, Antipsychotic drugs increase mortality in elderly patients when treating psychosis associated with dementia. An analysis of 17 placebo-controlled studies (lasting 10 weeks) in patients taking atypical antipsychotic drugs revealed an increase in drug-associated mortality by 1.6–1.7 times compared with patients receiving placebo. In typical 10-week controlled studies, the percentage of drug-attributable mortality was about 4.5%, compared with 2.6% in the placebo group. Although the causes of death varied, most were related to cardiovascular problems (such as heart failure, sudden death) or pneumonia. Observational studies suggest that, like atypical antipsychotics, treatment with traditional antipsychotics may also be associated with increased mortality.
Tardive dyskinesia. As with other antipsychotics, haloperidol is associated with the development of tardive dyskinesia, a syndrome characterized by involuntary movements (may occur in some patients with long-term treatment or arise after drug therapy was discontinued). The risk of developing tardive dyskinesia is higher in older patients during high-dose therapy, especially in women. Symptoms are persistent and, in some patients, irreversible: rhythmic involuntary movements of the tongue, face, mouth and jaw (for example, protrusion of the tongue, puffing out of the cheeks, puckering of the lips, uncontrolled chewing movements), sometimes they can be accompanied by involuntary movements of the limbs and torso. If tardive dyskinesia develops, discontinuation of the drug is recommended.
Dystonic extrapyramidal disorders are most common in children and young adults and at the beginning of treatment; may subside within 24–48 hours after stopping haloperidol. Parkinsonian extrapyramidal effects more often develop in older people and are detected in the first few days of treatment or during long-term therapy.
Cardiovascular effects. Cases of sudden death, QT interval prolongation and torsades de pointes have been reported in patients receiving haloperidol. Caution should be exercised when treating patients with predisposition factors to prolongation of the QT interval, incl. electrolyte imbalance (especially hypokalemia and hypomagnesemia), simultaneous use of drugs that prolong the QT interval. When treating with haloperidol, it is necessary to regularly monitor the ECG, blood count, and evaluate the level of liver enzymes. During therapy, patients should refrain from potential activities dangerous species activities requiring increased attention, quick mental and motor reactions.
Storage conditions for the drug Haloperidol decanoate
In a place protected from light, at a temperature of 15–30 °C.
Keep out of the reach of children.
- Description of the drug Haloperidol decanoate
- Composition of the drug Haloperidol decanoate
- Indications for the drug Haloperidol decanoate
- Storage conditions for the drug Haloperidol decanoate
- Shelf life of the drug Haloperidol decanoate
Release form, composition and packaging
solution for injection oily 50 mg/1 ml: amp. 5 pieces.Reg. No.: RK-LS-5-No. 010234 dated 09/06/2012 - Valid
Excipients: benzyl alcohol, sesame oil.
1 ml - dark glass ampoules (5) - cardboard packs.
Description active ingredients drug HALOPERIDOL DECANOATE. The scientific information provided is general and cannot be used to make a decision about the possibility of using a particular medicinal product. Update date: 01/14/2006
Antipsychotic drug (neuroleptic), butyrophenone derivative. It has a pronounced antipsychotic effect due to the blockade of depolarization or a decrease in the degree of excitation of dopamine neurons (reduced release) and blockade of postsynaptic dopamine D 2 receptors in the mesolimbic and mesocortical structures of the brain.
It has a moderate sedative effect due to the blockade of α-adrenergic receptors of the reticular formation of the brain stem; pronounced antiemetic effect due to blockade of dopamine D 2 receptors in the trigger zone of the vomiting center; hypothermic effect and galactorrhea caused by blockade of dopamine receptors in the hypothalamus.
Long-term use is accompanied by changes in endocrine status; in the anterior lobe of the pituitary gland, the production of prolactin increases and the production of gonadotropic hormones decreases.
Blockade of dopamine receptors in the dopamine pathways of the substantia nigra striata promotes the development of extrapyramidal motor reactions; blockade of dopamine receptors in the tuberoinfundibular system causes a decrease in the release of GH.
It has virtually no anticholinergic effect.
Eliminates persistent personality changes, delusions, hallucinations, mania, and increases interest in the environment. Effective in patients resistant to other antipsychotics. Has some activating effect. In hyperactive children, it eliminates excessive motor activity and behavioral disorders (impulsivity, difficulty concentrating, aggressiveness).
Unlike haloperidol, haloperidol decanoate is characterized by a prolonged action.
When taken orally, it is absorbed from the gastrointestinal tract by 60%. Cmax in plasma when taken orally is achieved after 3-6 hours, with intramuscular administration - after 10-20 minutes, with intramuscular administration of haloperidol decanoate - 3-9 days. Subject to first pass effect through the liver.
Protein binding is 92%. V d at equilibrium concentration is 18 l/kg. Actively metabolized in the liver with the participation of isoenzymes CYP2D6, CYP3A3, CYP3A5, CYP3A7. It is an inhibitor of the CYP2D6 isoenzyme. There are no active metabolites.
Easily penetrates histohematic barriers, including the BBB. Excreted in breast milk.
T1/2 when administered orally - 24 hours, with intramuscular administration - 21 hours, with intravenous administration - 14 hours. Haloperidol decanoate is excreted within 3 weeks.
Excreted by the kidneys - 40% and with bile through the intestines - 15%.
Acute and chronic psychotic disorders (including schizophrenia, manic-depressive, epileptic, alcoholic psychoses), psychomotor agitation of various origins, delusions and hallucinations of various origins, Huntington's chorea, mental retardation, agitated depression, behavioral disorders in old age and childhood ( including hyperreactivity in children and childhood autism), psychosomatic disorders, Tourette's disease, stuttering, long-term and treatment-resistant vomiting and hiccups, prevention and treatment of nausea and vomiting during chemotherapy.
When taken orally for adults, the initial dose is 0.5-5 mg 2-3 times / day, for elderly patients - 0.5-2 mg 2-3 times / day. Further, depending on the patient’s response to treatment, the dose is gradually increased in most cases to 5-10 mg/day. High doses (more than 40 mg/day) are used in rare cases, for a short time and in the absence of concomitant diseases. For children - 25-75 mcg/kg/day in 2-3 doses.
When administered intramuscularly to adults, the initial single dose is 1-10 mg, the interval between repeated injections is 1-8 hours; when using the depot form, the dose is 50-300 mg once every 4 weeks.
For intravenous administration, a single dose is 0.5-50 mg, the frequency of administration and the dose for repeated administration depend on the indications and clinical situation.
Maximum doses: when taken orally for adults - 100 mg/day;
From the side of the central nervous system: headache, insomnia, anxiety, feelings of anxiety and fear, euphoria, agitation, drowsiness (especially at the beginning of treatment), akathisia, depression or euphoria, lethargy, epileptic attack, development of a paradoxical reaction (exacerbation of psychosis, hallucinations);
From the cardiovascular system: when used in high doses - arterial hypotension, tachycardia, arrhythmia, ECG changes (increased QT interval, signs of ventricular flutter and fibrillation).
From the outside digestive system: when used in high doses - loss of appetite, dry mouth, hyposalivation, nausea, vomiting, constipation or diarrhea, liver dysfunction, including the development of jaundice.
From the hematopoietic system: rarely - mild and temporary leukopenia, leukocytosis, agranulocytosis, slight erythropenia and a tendency to monocytosis.
From the outside endocrine system: gynecomastia, pain in mammary glands, hyperprolactinemia, menstrual irregularities, decreased potency, increased libido, priapism.
From the side of metabolism: hyper- and hypoglycemia, hyponatremia;
From the side of the organ of vision: impaired visual acuity, cataracts, retinopathy, accommodation disorders.
Allergic reactions: rarely - skin rash, bronchospasm, laryngospasm, hyperpyrexia.
Dermatological reactions: maculopapular and acne-like skin changes;
Effects due to cholinergic action: dry mouth, hyposalivation, urinary retention, constipation.
Diseases of the central nervous system, accompanied by symptoms of extrapyramidal disorders, depression, hysteria, coma of various etiologies; severe toxic depression of the central nervous system caused by drugs. Pregnancy, lactation. Childhood up to 3 years. Increased sensitivity to haloperidol and other butyrophenone derivatives.
Use during pregnancy and breastfeeding
Haloperidol is contraindicated during pregnancy and lactation.
IN experimental studies in some cases, teratogenic and fetotoxic effects were detected. Haloperidol is excreted in breast milk. It has been shown that the concentrations of haloperidol in breast milk sufficient to cause sedation and impairment motor functions in an infant.
Use with caution when cardiovascular diseases with symptoms of decompensation, myocardial conduction disorders, an increase in the QT interval or the risk of an increase in the QT interval (including hypokalemia, simultaneous use with drugs that can increase the QT interval); for epilepsy; angle-closure glaucoma; hepatic and/or renal failure; with thyrotoxicosis; pulmonary-cardiac and respiratory failure(including for COPD and acute infectious diseases); with hyperplasia prostate gland with urinary retention; for chronic alcoholism; simultaneously with anticoagulants.
If tardive dyskinesia develops, it is necessary to gradually reduce the dose of haloperidol and prescribe another drug.
There are reports of the possibility of symptoms of diabetes insipidus, exacerbation of glaucoma, and a tendency (with long-term treatment) to the development of lymphomonocytosis during haloperidol therapy.
Elderly patients usually require a lower initial dose and a more gradual dose titration. This group of patients is characterized by a high probability of developing extrapyramidal disorders. To identify early signs For tardive dyskinesia, careful monitoring of the patient is recommended.
During treatment with antipsychotics, the development of NMS is possible at any time, but most often it occurs soon after the start of therapy or after transferring a patient from one antipsychotic drug to another, during combination treatment with another psychotropic drug, or after increasing the dose.
During the treatment period, avoid drinking alcohol.
Impact on the ability to drive vehicles and operate machinery
During the period of use of haloperidol, you should refrain from engaging in potentially hazardous activities that require increased attention and high speed of psychomotor reactions.
When used simultaneously with drugs that have a depressant effect on the central nervous system, ethanol may increase central nervous system depression, respiratory depression and hypotensive effects.
With the simultaneous use of drugs that cause extrapyramidal reactions, the frequency and severity of extrapyramidal effects may increase.
When used simultaneously medicines, having anticholinergic activity, it is possible to enhance the anticholinergic effects.
When used simultaneously with anticonvulsants there may be a change in the type and/or frequency of epileptiform seizures, as well as a decrease in the concentration of haloperidol in the blood plasma; with tricyclic antidepressants (including desipramine) - the metabolism of tricyclic antidepressants decreases, the risk of developing seizures increases.
With simultaneous use, haloperidol potentiates the effect of antihypertensive drugs.
When used simultaneously with beta-blockers (including propranolol), severe arterial hypotension is possible. With the simultaneous use of haloperidol and propranolol, a case of severe arterial hypotension and cardiac arrest.
With simultaneous use, a decrease in the effect of indirect anticoagulants is observed.
When used simultaneously with lithium salts, the development of more pronounced extrapyramidal symptoms is possible due to increased blockade of dopamine receptors, and when used in high doses, irreversible intoxication and severe encephalopathy are possible.
When used simultaneously with venlafaxine, it is possible to increase the concentration of haloperidol in the blood plasma; with guanethidine - it is possible to reduce the hypotensive effect of guanethidine; with isoniazid - there are reports of increased concentrations of isoniazid in the blood plasma; with imipenem - there are reports of transient arterial hypertension.
When used simultaneously with indomethacin, drowsiness and confusion are possible.
When used simultaneously with carbamazepine, which is an inducer of microsomal liver enzymes, it is possible to increase the rate of metabolism of haloperidol. Haloperidol may increase plasma concentrations of carbamazepine. Symptoms of neurotoxicity may occur.
With simultaneous use, the therapeutic effect of levodopa and pergolide may be reduced due to blockade of dopamine receptors by haloperidol.
When used simultaneously with methyldopa, sedation, depression, dementia, confusion, and dizziness are possible; with morphine - myoclonus may develop; with rifampicin, phenytoin, phenobarbital - a decrease in the concentration of haloperidol in the blood plasma is possible.
When used concomitantly with fluvoxamine, there are limited reports of a possible increase in the concentration of haloperidol in the blood plasma, which is accompanied by toxic effects.
When used simultaneously with fluoxetine, the development of extrapyramidal symptoms and dystonia is possible; with quinidine - an increase in the concentration of haloperidol in the blood plasma; with cisapride - prolongation of the QT interval on the ECG.
When used simultaneously with epinephrine, it is possible to “pervert” the pressor effect of epinephrine, and as a result of this, the development of severe arterial hypotension and tachycardia.
Dosage form"type="checkbox">
Dosage form
Oily solution for injection, 50 mg/ml
Compound
1 ml of the drug contains
active substance – haloperidol decanoate 70.52 mg (equivalent to 50 mg haloperidol)
excipients: benzyl alcohol, sesame oil for injection, refined.
Description
A transparent solution of yellow or greenish-yellow color.
Pharmacotherapeutic group
Antipsychotic drugs. Butyrophenone derivatives. Haloperidol.
ATX code N05AD01
Pharmacological properties"type="checkbox">
Pharmacological properties
Pharmacokinetics
Haloperidol decanoate is an ester of haloperidol and decanoic acid.
When administered intramuscularly, slow hydrolysis occurs
release of haloperidol, then enters the systemic circulation.
After intramuscular administration, the maximum concentration of haloperidol in the blood plasma is reached on days 3–9, after which it decreases. The half-life is approximately 3 weeks. With regular monthly administration, a stable concentration of the drug in the blood plasma is established after 2–4 months. Pharmacokinetics when administered intramuscularly is dose-dependent. At doses below 450 mg, there is a direct relationship between the dose and the concentration of haloperidol in the blood plasma. To achieve a therapeutic effect, the required concentration of haloperidol in blood plasma ranges from 4 to 20–25 mcg/l. Haloperidol penetrates the blood-brain barrier. The drug is 92% bound to blood plasma proteins, excreted from the body in the form of metabolites, 60% - with feces, 40% - with urine.
Pharmacodynamics
Haloperidol decanoate belongs to the neuroleptics - butyrophenone derivatives. Haloperidol is an antagonist of central dopamine receptors and is a strong antipsychotic.
Haloperidol decanoate is used in the treatment of hallucinations and delusions, due to the direct blockade of central dopamine receptors (acts on mesocortical and limbic structures), affects basal ganglia(nigrostriatal system). It has a pronounced calming effect during psychomotor agitation, and is effective against mania and other agitations.
The limbic activity of haloperidol results in a sedative effect. Impact on the basal ganglia causes extrapyramidal adverse reactions(dystonia, akathisia, parkinsonism).
Severe peripheral antidopamine activity is accompanied by the development of nausea and vomiting (irritation of chemoreceptors), relaxation of the gastrointestinal sphincter and increased release of prolactin (blocks the prolactin-inhibiting factor in the adenohypophysis).
Indications for use
Treatment of schizophrenia and prevention of relapse
Other psychoses, especially paranoid
Mental and behavioral problems that occur with psychomotor agitation and require long-term treatment.
Directions for use and doses
The drug is intended exclusively for adults and exclusively for intramuscular administration! Do not administer intravenously!
Haloperidol decanoate should be administered by intramuscular injection deep into the muscle using a special needle, preferably 2-2.5 inches long, with a diameter of at least 21G. Local reactions and leakage of drug from the injection site can be reduced by using a proper injection technique, such as the Z-technique. As with all injections of oil solutions, it is important to ensure that the needle is not in the lumen of the vein by aspirating the contents before injecting. Doses exceeding 3 ml should be avoided to avoid an unpleasant feeling of fullness at the injection site.
The recommended initial dose is 50 mg once every four weeks, if necessary, the dose is increased to 300 mg with dose increments of 50 mg once every four weeks. If clinical circumstances dictate that biweekly dosing is preferred, these doses should be halved.
Typically, the maintenance dose corresponds to 20 times daily dose Haloperidol for oral administration. If the symptoms of the underlying disease return during the dose selection period, treatment with Haloperidol decanoate can be supplemented with Haloperidol for oral administration.
Typically, injections are given every 4 weeks, however, due to large individual differences in effectiveness, more frequent use of the drug may be required.
In patients who have previously received maintenance therapy with oral antipsychotics, a rough guideline for the starting dose of Haloperidol decanoate is as follows: 500 mg of chlorpromazine per day is equivalent to 100 mg of Haloperidol decanoate once a month.
The approximate equivalent for transfer of patients previously receiving maintenance therapy with fluphenazine decanoate or flupenthixol decanoate is as follows: 25 mg fluphenazine decanoate once every 2 weeks or 40 mg flupenthixol decanoate once every two weeks is equivalent to 100 mg of Haloperidol decanoate once a month.
The dose should be adjusted according to individually due to significant individual differences in response. Dose selection should be carried out under strict medical supervision of the patient.
Patients with severe symptoms, or patients who require large doses of oral medications for maintenance therapy, will require higher doses of Haloperidol decanoate. However, experience with the clinical use of Haloperidol decanoate in doses greater than 300 mg per month is limited.
Side effects"type="checkbox">
Side effects
Very common (≥1/10)
Agitation, insomnia, headache
Extrapyramidal symptoms: tremor, rigidity, drooling, bradykinesia, acute dystonia, laryngeal dystonia (in such cases, anticholinergic drugs can be used, however, in no case for prophylactic purposes, since they reduce the effectiveness of Haloperidol decanoate)
Hyperkinesia
Often (from ≥1/100 to<1/10)
Depression, psychotic symptoms
Tardive dyskinesia, characterized by involuntary rhythmic twitching of the muscles of the tongue, face, mouth or chin, uncontrolled chewing movements, uncontrolled movements of the arms and legs (resumption of therapy, increasing the dose, replacing the drug with another antipsychotic drug can mask the syndrome; if these phenomena develop, treatment should be discontinued, As soon as possible)
Dystonia, akathisia, dyskinesia, bradykinesia, hypokinesia, hypertonicity, mask-like face, tremor
Drowsiness, dizziness
Visual impairment, oculogyric crisis
Arterial hypotension, orthostatic hypotension
Constipation, dry mouth, increased salivation, nausea, vomiting
Rash, injection site reactions
Urinary retention, erectile dysfunction
Weight gain, weight loss
Abnormal liver function tests
Uncommon (≥1/1000 to<1/100)
Leukopenia
Hypersensitivity, photosensitivity reaction, urticaria, itching, hyperhidrosis
Confusion, decreased libido, loss of libido, motor agitation
Blurred vision, cataracts, retinopathy, in elderly patients an attack of angle-closure glaucoma
Tachycardia, shortness of breath
Hepatitis, jaundice
Muscle rigidity, cogwheel rigidity, involuntary muscle contractions, muscle spasms, joint stiffness, torticollis
Amenorrhea, dysmenorrhea, galactorrhea, breast pain or discomfort
Gait disturbance, hyperthermia, peripheral edema
Seizures, parkinsonism, akinesia, sedation
Rarely (from ≥1/10000 to<1/1000)
Hyperprolactinemia
Neuroleptic malignant syndrome, motor dysfunction, nystagmus
Bronchospasm
Trismus, muscle twitching
Menorrhagia, menstrual irregularities, sexual dysfunction
Prolongation of the QT interval on the electrocardiogram
Unknown (cannot be estimated from available data)
Agranulocytosis, neutropenia, pancytopenia, thrombocytopenia
Anaphylactic reaction
Laryngeal edema, laryngospasm
Inappropriate ADH secretion, gynecomastia, priapism
Hypoglycemia
Ventricular tachycardia, ventricular fibrillation, ventricular tachycardia of the pirouette type, extrasystole, QT interval prolongation, cardiac arrest (these effects are more often observed when using high doses of haloperidol and in predisposed patients).
Acute liver failure, cholestasis
Leukocytoclastic vasculitis, exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome
Withdrawal syndrome in newborns
Sudden death,
Facial edema, hypothermia, abscess at the injection site
Cases of venous thromboembolic complications, including cases of pulmonary embolism and cases of deep vein thrombosis.
Contraindications
Hypersensitivity to any of the components of the drug
Coma
Central nervous system depression caused by drugs or alcohol
Diseases of the central nervous system accompanied by pyramidal and extrapyramidal symptoms (including Parkinson's disease)
Pathological process localized in the basal ganglia region
Recent acute myocardial infarction, decompensated heart failure,
Arrhythmias treated with class IA and III antiarrhythmic drugs, prolongation of the QT interval, concomitant use with drugs that prolong the QT interval
History of ventricular arrhythmia and/or ventricular tachycardia of the torsade de pointes type, clinically significant bradycardia, II-III degree heart block and uncorrected hypokalemia
Children and teenagers up to 18 years of age
Pregnancy and lactation
Drug interactions
Concomitant use of haloperidol with drugs that may prolong the QT interval may increase the risk of developing ventricular arrhythmias, including torsade de pointes (TdP). Therefore, the simultaneous use of these drugs is not recommended (see section Contraindications).
Examples of these drugs are certain antiarrhythmic drugs, such as class 1A (eg, quinidine, disopyramide, procainamide) and class III (eg, amiodarone, sotalol, and dofetilide), certain antimicrobials (sparfloxacin, moxifloxacin, IV erythromycin), tricyclic antidepressants (eg, amitriptyline), some tetracyclic antidepressants (eg, maprotiline), other antipsychotics (eg, phenothiazines, pimozide, and sertindole), some antihistamines (eg, terfenadine), cisapride, bretylium, and some antimalarials such as quinine and mefloquine.
Concomitant use of drugs that disrupt electrolyte balance may increase the risk of developing ventricular arrhythmia and is not recommended. Diuretics, especially those causing hypokalemia, should be avoided; if necessary, potassium-sparing diuretics are preferred.
Haloperidol is metabolized by several pathways, including glucuronidation and the cytochrome P450 enzyme system (particularly CYP 3A4 or CYP 2D6). Inhibition of these metabolic pathways by another drug or reduction in CYP2D6 enzyme activity may result in increased haloperidol concentrations and an increased risk of adverse events, including QT prolongation. When haloperidol was co-administered with drugs characterized as substrates or inhibitors of CYP 3A4 or CYP 2D6 isoenzymes, such as itraconazole, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine and promethazine, mild to moderately increased concentrations of haloperidol were observed. A decrease in the activity of the CYP2D6 enzyme may lead to increased concentrations of haloperidol. When haloperidol was used in combination with metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day), prolongation of the QT interval and extrapyramidal symptoms were observed. A dose reduction of haloperidol may be required.
Effect of other drugs on haloperidol
When long-term treatment with enzyme-inducing drugs such as carbamazepine, phenobarbital and rifampicin is prescribed in addition to therapy with haloperidol decanoate, this leads to a significant decrease in haloperidol plasma concentrations. Therefore, when carrying out combination therapy, if necessary, the dose of Haloperidol decanoate should be adjusted. After discontinuation of such drugs, it may be necessary to reduce the dose of Haloperidol decanoate.
Sodium valproate, a drug known as a glucuronidation inhibitor, does not affect plasma concentrations of haloperidol.
Effect of haloperidol on other drugs
Like all antipsychotics, Haloperidol decanoate may potentiate the central nervous system depression caused by other CNS depressants including alcohol, hypnotics, sedatives, or potent analgesics. The combined use of haloperidol decanoate with them can lead to respiratory depression.
When used simultaneously with methyldopa, an increased effect on the central nervous system may be observed.
Haloperidol decanoate may antagonize the actions of epinephrine and other sympathomimetics and reverse the hypotensive effects of blockers such as guanithidine.
Haloperidol decanoate may reduce the antiparkinsonian effects of levodopa.
Haloperidol is a CYP2D6 inhibitor. Haloperidol decanoate inhibits the metabolism of tricyclic antidepressants, thereby increasing plasma concentrations of these drugs.
Other forms of interaction
In rare cases, an encephalopathy-like syndrome has been reported with the combined use of lithium and haloperidol. It is controversial whether these cases represent a distinct entity or whether they are in fact cases of neuroleptic malignant syndrome and/or manifestations of lithium toxicity. Symptoms of encephalopathy-like syndrome include confusion, disorientation, headache, poor balance and drowsiness. One report demonstrating asymptomatic EEG abnormalities during combination treatment suggested the use of EEG monitoring. When combined therapy with lithium and haloperidol, haloperidol should be administered at the lowest effective dose, and lithium concentrations should be monitored and maintained below 1 mmol/L. If symptoms of encephalopathy-like syndrome occur, treatment should be discontinued immediately.
Antagonism has been reported regarding the action of the anticoagulant phenindione.
Taking into account the decrease in the seizure threshold, an increase in the dose of anticonvulsants may be necessary.
special instructions
Treatment should begin with oral Haloperidol and then proceed to injections of the drug Haloperidol decanoate to identify unexpected adverse reactions. Parenteral administration of the drug Haloperidol decanoate should be carried out under the close supervision of a physician (especially in elderly patients); when a therapeutic effect is achieved, it should be switched to oral administration.
Cases of sudden death have been reported in patients with mental disorders receiving antipsychotic drugs, including haloperidol.
Elderly patients with psychosis due to dementia
Elderly patients with psychosis due to dementia receiving antipsychotic drugs are at increased risk of death. Causes of death vary, with most deaths being cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia).
Cardiovascular effects
Very rare cases of QT prolongation and/or ventricular arrhythmia have been reported with the use of haloperidol. They may occur more frequently when high doses are used and in predisposed patients.
Before initiating treatment, the benefit-risk ratio of haloperidol should be fully assessed and patients should be closely monitored (ECG and plasma potassium) with risk factors for ventricular arrhythmia such as heart disease, family history of sudden death and/or prolongation of the ventricular arrhythmia. QT interval, uncorrected electrolyte disturbances, subarachnoid hemorrhage, fasting or alcohol abuse, especially in the initial phase of treatment, to obtain stable plasma concentrations.
At higher doses or when used parenterally, especially when administered intravenously, the risk of QT prolongation and/or ventricular arrhythmias may be increased.
Haloperidol decanoate should not be administered intravenously.
Before treatment, it is recommended that all patients undergo a baseline ECG recording, especially elderly patients and patients with a personal or family history of heart disease or cardiac pathology identified during clinical examination. During treatment, the need for ECG monitoring should be assessed individually (for example, when increasing the dose). During treatment, if the QT interval is prolonged, the dose of the drug should be reduced, and if the QT interval is prolonged by more than 500 ms, haloperidol should be discontinued.
When using some atypical antipsychotic drugs, there is a 3-fold increase in the risk of developing cerebrovascular adverse events. The mechanism for this increased risk is unknown. An increased risk cannot be excluded with the use of other antipsychotic drugs or in other patient groups.
Haloperidol should be used with caution in patients with risk factors for stroke.
Neuroleptic malignant syndrome
Like other antipsychotics, haloperidol has been associated with neuroleptic malignant syndrome: a rare idiosyncratic reaction characterized by hyperthermia, generalized muscle rigidity, autonomic instability, and altered consciousness. Hyperthermia is often an early sign of this syndrome. If symptoms of neuroleptic syndrome are detected, treatment with haloperidol should be immediately discontinued and appropriate supportive therapy and careful monitoring of the function of vital organs and systems should be initiated.
Tardive dyskinesia
As with all antipsychotic drugs, some patients may develop tardive dyskinesia, which is characterized by involuntary rhythmic movements of the tongue, face, mouth or chin, during long-term therapy or after discontinuation of the drug. In some patients, these manifestations may be permanent. The syndrome may be masked by restarting therapy, increasing the dose, or changing the drug to another antipsychotic drug. Treatment should be discontinued as soon as possible.
Extrapyramidal symptoms
As with all antipsychotic drugs, extrapyramidal symptoms such as tremor, rigidity, hypersalivation, bradykinesia, akathisia and acute dystonia may occur.
If necessary, antiparkinsonian drugs of the anticholinergic type may be prescribed, but should not be prescribed as a preventive measure. If concomitant antiparkinsonian treatment is necessary, it should be continued after discontinuation of the drug Haloperidol decanoate, if its elimination occurs faster than the elimination of Haloperidol decanoate, in order to avoid the development or exacerbation of extrapyramidal symptoms. The doctor should be aware of the possible increase in intraocular pressure when using anticholinergic drugs, including antiparkinsonian drugs, used simultaneously with Haloperidol decanoate.
Seizures
Haloperidol may cause seizures. Caution is recommended in patients with epilepsy and conditions that precipitate seizures (eg, alcohol withdrawal and brain damage).
Disorders of the liver and biliary tract
Since Haloperidol decanoate is metabolized in the liver, caution is recommended in patients with impaired liver function. Isolated cases of liver dysfunction or hepatitis, most often of the cholestatic type, have been reported.
Endocrine system disorders
Thyroxine may increase the toxicity of Haloperidol decanoate. Therefore, it should be used with great caution in patients with hyperthyroidism.
Antipsychotic (neuroleptic) drugs can cause hyperprolactinemia, which can cause the development of galactorrhea, gynecomastia and oligo- or amenorrhea. Very rare cases of hypoglycemia and syndrome of inappropriate antidiuretic hormone (ADH) secretion have also been reported.
Venous thromboembolic complications
Cases of venous thromboembolic complications (VTE) have been reported with the use of antipsychotic drugs. Since patients treated with antipsychotic drugs often have acquired risk factors for the development of VTE, all possible risk factors for the development of VTE should be identified before and during treatment with haloperidol and preventive measures taken.
Additional factors
As with all antipsychotic drugs, if depression predominates, Haloperidol decanoate should not be used as monotherapy. It can be prescribed simultaneously with antidepressants to treat diseases that combine depression and psychosis.
In schizophrenia, the response to treatment with antipsychotic drugs may be delayed. Likewise, when medications are discontinued, symptoms may not recur for several weeks or months.
Haloperidol decanoate contains 15 mg/ml benzyl alcohol.
Caution must be exercised when performing heavy physical work or taking a hot bath (heat stroke may develop due to suppression of central and peripheral thermoregulation in the hypothalamus).
During treatment, you should not take “anti-cold” over-the-counter medications (anticholinergic effects and the risk of heat stroke may increase).
Exposed skin should be protected from excess solar radiation due to the increased risk of photosensitivity.
Treatment is stopped gradually to avoid withdrawal syndrome. Antiemetic effects may mask signs of drug toxicity and make it difficult to diagnose conditions in which nausea is the first symptom.
Pregnancy and lactation
Haloperidol decanoate does not significantly increase the incidence of malformations. In a few isolated cases, congenital malformations have been observed when haloperidol decanoate was used concomitantly with other drugs during fetal development. Haloperidol decanoate passes into breast milk. In some cases, the development of extrapyramidal symptoms in infants was observed when the drug was taken by a nursing mother.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
In the initial period of treatment and when using high doses of Haloperidol decanoate, it is prohibited to drive a car or perform work associated with potentially dangerous mechanisms; sedation of varying degrees of severity and impaired concentration may occur. In the future, the degree of prohibition is determined based on the individual reaction of the patient.
Overdose
Symptoms: extrapyramidal reactions (in the form of muscle rigidity and general or localized tremor), decreased or increased blood pressure, sedation. In exceptional cases, the development of a coma with respiratory depression and arterial hypotension. Possible prolongation of the QT interval with the development of ventricular arrhythmias.
Treatment: symptomatic, there is no specific antidote. An open airway should be ensured using an oropharyngeal or endotracheal tube; if respiratory depression occurs, artificial ventilation may be required. Vital functions and ECG are monitored until they are completely normalized, severe arrhythmias are treated with appropriate antiarrhythmic drugs; with a decrease in blood pressure and vascular insufficiency - intravenous administration of plasma or a concentrated solution of albumin and dopamine, or norepinephrine as a vasopressor. The administration of (adrenaline) epinephrine is unacceptable, because As a result of interaction with Haloperidol decanoate, it can cause extreme hypotension. For severe extrapyramidal symptoms, administer antiparkinsonian anticholinergic drugs (for example, 1-2 mg benztropine mesylate intravenously or intramuscularly) for several weeks (symptoms may return after discontinuation of these drugs).
Conditions for dispensing from pharmacies
On prescription
Name and country of the manufacturing organization
JSC "Gedeon Richter"
1103 Budapest, st. Dymroyi 19-21, Hungary
Solution, 50 mg/ml:
- Active substance: haloperidol decanoate 70.52 mg (corresponds to 50 mg of haloperidol);
- Excipients;
- benzyl alcohol - 15 mg;
- sesame oil - up to 1 ml.
In a dark glass ampoule of I hydrolytic class with a breaking point, 1 ml. 5 pcs in a plastic tray. 1 plastic pallet in a cardboard box.
Description of the dosage form
Oily solution for intramuscular administration.
pharmachologic effect
Haloperidol decanoate is an ester of haloperidol and decanoic acid. When administered intramuscularly, slow hydrolysis releases haloperidol, which then enters the systemic circulation. Haloperidol decanoate is a butyrophenone-derived antipsychotic. Haloperidol is a strong antagonist of central dopamine receptors and is a strong neuroleptic.
Haloperidol is highly effective in the treatment of hallucinations and delusions, due to the direct blockade of central dopamine receptors (probably acts on mesocortical and limbic structures), and affects the basal ganglia (nigrostria). It has a pronounced calming effect during psychomotor agitation, and is effective against mania and other agitations.
The limbic activity of the drug manifests itself in a sedative effect; effective as an additional remedy for chronic pain.
Impact on the basal ganglia causes extrapyramidal reactions (dystonia, akathisia, parkinsonism).
In socially withdrawn patients, social behavior is normalized.
Severe peripheral antidopamine activity is accompanied by the development of nausea and vomiting (irritation of chemoreceptors), relaxation of the gastroduodenal sphincter and increased release of prolactin (blocks the prolactin-inhibiting factor in the adenohypophysis).
Pharmacokinetics
Absorption and distribution.
The Cmax of haloperidol released from the haloperidol depot after intramuscular injection is reached after 3-9 days. With regular monthly administration, the saturation stage in plasma is reached after 2-4 months. Pharmacokinetics with intramuscular administration is dose-dependent. At doses below 450 mg, there is a direct relationship between the dose and plasma concentration of haloperidol. To achieve a therapeutic effect, a plasma concentration of haloperidol of 20-25 mcg/l is required.
Haloperidol easily penetrates the BBB. Plasma protein binding - 92%.
Excretion.
T1/2 about 3 weeks. Excreted through the intestines (60%) and kidneys (40%, including 1% unchanged).
Instructions
IM, in the gluteal region.
Intended exclusively for adults, exclusively for intramuscular administration. Do not administer i.v.
Doses exceeding 3 ml should be avoided to avoid an unpleasant feeling of fullness at the injection site.
Indications for use: Haloperidol decanoate
Chronic schizophrenia and other psychoses, especially when treatment with rapid-acting haloperidol has been effective and an effective, moderately sedative antipsychotic is needed.
Other disorders of mental activity and behavior that occur with psychomotor agitation and require long-term treatment.
Contraindications for use of Haloperidol decanoate
- Coma;
- CNS depression caused by drugs or alcohol;
- Parkinson's disease;
- damage to the basal ganglia;
- hypersensitivity to the components of the drug.
With caution: decompensated diseases of the cardiovascular system (including angina pectoris, intracardiac conduction disorders, prolongation of the QT interval or a predisposition to this - hypokalemia, simultaneous use of other drugs that can cause prolongation of the QT interval), epilepsy, angle-closure glaucoma, liver and/or renal failure, hyperthyroidism (with symptoms of thyrotoxicosis), pulmonary-cardiac and respiratory failure (including in COPD and acute infectious diseases), prostatic hyperplasia with urinary retention, alcoholism.
Haloperidol decanoate Use in pregnancy and children
Prescribing the drug during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus.
Haloperidol Decanoate is excreted in breast milk. Prescribing the drug during breastfeeding is possible only if the expected benefit to the mother outweighs the potential risk to the baby. In some cases, the development of extrapyramidal symptoms in infants was observed when the drug was taken by a nursing mother.
Contraindicated for children.
Haloperidol decanoate Side effects
Side effects that develop during treatment with Haloperidol Decanoate are due to the action of haloperidol.
It is possible to develop local reactions associated with intramuscular administration of the drug.
From the nervous system: headache, insomnia or drowsiness (especially at the beginning of treatment), anxiety, anxiety, agitation, fears, akathisia, euphoria or depression, lethargy, epileptic attacks, development of a paradoxical reaction - exacerbation of psychosis and hallucinations; with long-term treatment - extrapyramidal disorders, incl. tardive dyskinesia (smacking and wrinkling of the lips, puffing out of the cheeks, rapid and worm-like movements of the tongue, uncontrolled chewing movements, uncontrolled movements of the arms and legs), tardive dystonia (frequent blinking or spasms of the eyelids, unusual facial expression or body position, uncontrolled bending movements of the neck, torso , arms and legs) and neuroleptic malignant syndrome (difficulty or rapid breathing, tachycardia, arrhythmia, hyperthermia, increased or decreased blood pressure, increased sweating, urinary incontinence, muscle rigidity, epileptic seizures, loss of consciousness).
From the cardiovascular system: when used in high doses - decreased blood pressure, orthostatic hypotension, arrhythmias, tachycardia, ECG changes (prolongation of the QT interval, signs of flutter and ventricular fibrillation).
From the digestive system: when used in high doses - loss of appetite, dry mouth, hyposalivation, nausea, vomiting, diarrhea or constipation, impaired liver function, up to the development of jaundice.
From the hematopoietic system: rarely - transient leukopenia or leukocytosis, agranulocytosis, erythropenia and a tendency to monocytosis.
From the urinary system: urinary retention (with prostatic hyperplasia), peripheral edema.
From the reproductive system and mammary gland: pain in the mammary glands, gynecomastia, hyperprolactinemia, menstrual irregularities, decreased potency, increased libido, priapism.
From the organ of vision: cataracts, retinopathy, blurred vision.
Metabolism: hyperglycemia, hypoglycemia, hyponatremia.
From the skin and subcutaneous tissues: maculopapular and acne-like skin changes, photosensitivity.
Allergic reactions: rarely - bronchospasm, laryngospasm.
Other: alopecia, weight gain.
Drug interactions
Increases the severity of the depressant effect on the central nervous system of ethanol, tricyclic antidepressants, opioid analgesics, barbiturates and hypnotics, and general anesthesia.
Enhances the effect of peripheral m-anticholinergic drugs and most antihypertensive drugs (reduces the effect of guanethidine due to its displacement from α-adrenergic neurons and suppression of its uptake by these neurons).
It inhibits the metabolism of tricyclic antidepressants and MAO inhibitors, thereby increasing (mutually) their sedative effect and toxicity.
When used simultaneously with bupropion, it reduces the epileptic threshold and increases the risk of grand mal seizures.
Reduces the effect of anticonvulsants (lowering the seizure threshold with haloperidol).
Weakens the vasoconstrictor effect of dopamine, phenylephrine, norepinephrine, ephedrine and epinephrine (blockade of α-adrenergic receptors by haloperidol, which can 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, it increases the risk of developing mental disorders (including disorientation in space, slowing down and difficulty thinking).
Amphetamines reduce the antipsychotic effect of haloperidol, which in turn reduces their psychostimulant effect (blockade of α-adrenergic receptors by haloperidol).
Anticholinergic, antihistamine (1st generation) and antiparkinsonian drugs can enhance the m-anticholinergic effect of haloperidol and reduce its antipsychotic effect (dose adjustment may be required).
Long-term use of carbamazepine, barbiturates and other inducers of microsomal oxidation reduces the concentration of haloperidol in plasma.
In combination with lithium preparations (especially in high doses), the development of encephalopathy (can cause irreversible neurointoxication) and increased extrapyramidal symptoms is possible.
When taken simultaneously with fluoxetine, the risk of developing side effects from the central nervous system, especially extrapyramidal reactions, increases.
When used simultaneously with drugs that cause extrapyramidal reactions, it increases the frequency and severity of extrapyramidal disorders.
Drinking strong tea or coffee (especially in large quantities) reduces the effect of haloperidol.
Dosage of Haloperidol decanoate
Adults: Patients on long-term treatment with oral antipsychotics (mainly haloperidol) may be advised to switch to depot injections. The dose should be adjusted on an individual basis due to significant individual differences in response. Dose selection should be carried out under strict medical supervision of the patient. The choice of the initial dose is carried out taking into account the symptoms of the disease, its severity, the dose of haloperidol or other antipsychotics prescribed during previous treatment.
At the beginning of treatment, it is recommended to prescribe doses 10-15 times higher than the dose of oral haloperidol every 4 weeks, which usually corresponds to 25-75 mg of haloperidol decanoate (0.5-1.5 ml). The maximum initial dose should not exceed 100 mg.
Depending on the effect, the dose can be increased stepwise by 50 mg until the optimal effect is obtained. Typically the maintenance dose corresponds to 20 times the daily dose of oral haloperidol. If symptoms of the underlying disease return during dose titration, treatment with haloperidol decanoate can be supplemented with oral haloperidol. Typically, injections are given every 4 weeks, but due to large individual differences in effectiveness, more frequent use of the drug may be required.
Overdose
The use of depot injections of the drug Haloperidol Decanoate is associated with a lower risk of overdose than oral administration of haloperidol. Symptoms of an overdose of Haloperidol Decanoate and haloperidol are the same. If an overdose is suspected, the longer action of the former should be taken into account.
Symptoms: development of known pharmacological effects and side effects in a more pronounced form. The most dangerous symptoms are extrapyramidal reactions, decreased blood pressure, and sedation. Extrapyramidal reactions manifest themselves in the form of muscle rigidity and general or localized tremor. More often it is possible to increase blood pressure rather than decrease it. In exceptional cases, the development of a coma with respiratory depression and arterial hypotension, turning into a shock-like state. Possible prolongation of the QT interval with the development of ventricular arrhythmias.
Treatment: there is no specific antidote. Airway patency during the development of a coma is ensured using an oropharyngeal or endotracheal tube; in case of respiratory depression, mechanical ventilation may be required. Monitor vital functions and ECG (until it is completely normalized), treat severe arrhythmias with appropriate antiarrhythmic drugs; with reduced blood pressure and circulatory arrest - intravenous administration of fluid, plasma or concentrated albumin and dopamine or norepinephrine as a vasopressor. The administration of epinephrine is unacceptable, because as a result of interaction with the drug Haloperidol Decanoate, blood pressure may increase significantly, which will require immediate correction. For severe extrapyramidal symptoms, administration of antiparkinsonian drugs with anticholinergic action for several weeks (symptoms may return after discontinuation of these drugs).
Precautionary measures
In several cases, sudden death occurred in psychiatric patients receiving antipsychotic drugs.
If you are predisposed to prolongation of the QT interval (long QT syndrome, hypokalemia, use of drugs that prolong the QT interval), caution should be exercised during treatment due to the risk of prolongation of the QT interval.
Treatment should begin with oral haloperidol and only then proceed to injections of the drug Haloperidol Decanoate to identify unexpected adverse reactions.
If liver function is impaired, caution must be exercised, because the drug is metabolized in the liver.
With long-term treatment, regular monitoring of liver function and blood counts is necessary.
In isolated cases, Haloperidol Decanoate has caused convulsions. Treatment of patients with epilepsy and conditions predisposing to seizures (eg, head trauma, alcohol withdrawal) requires caution.
Thyroxine increases the toxicity of the drug. Treatment with Haloperidol Decanoate in patients suffering from hyperthyroidism is permissible only with appropriate thyreostatic treatment.
In case of simultaneous presence of depression and psychosis or in case of dominance of depression, Haloperidol Decanoate is prescribed together with antidepressants.
When antiparkinsonian therapy is carried out simultaneously after the end of treatment with Haloperidol Decanoate, it should be continued for several more weeks due to the faster elimination of antiparkinsonian drugs.
The drug Haloperidol Decanoate is an oil solution for intramuscular administration, therefore it is prohibited to administer it intravenously.
During treatment with the drug, it is prohibited to drink alcohol. In the future, the degree of prohibition is determined based on the individual reaction of the patient.
At the beginning of treatment with the drug and especially when used in high doses, a sedative effect of varying severity may occur with a decrease in attention, which can be aggravated by alcohol intake.
Caution must be exercised when performing heavy physical work or taking a hot bath (heat stroke may develop due to suppression of central and peripheral thermoregulation in the hypothalamus).
During treatment, you should not take “anti-cold” over-the-counter medications (anticholinergic effects and the risk of heat stroke may increase).
Exposed skin should be protected from excess solar radiation due to the increased risk of photosensitivity.
Treatment is stopped gradually to avoid withdrawal syndrome.
Influence on the ability to drive vehicles and operate machinery.
At the beginning of treatment with Haloperidol Decanoate, it is prohibited to drive a car or perform work associated with an increased risk of injury and/or requiring increased concentration.
pharmacodynamics. Mechanism of action. Haloperidol decanoate is an ester of haloperidol and decanoic acid, a long-acting antipsychotic drug that belongs to butyrophenone derivatives. After injection of haloperidol, decanoate is gradually released from muscle tissue and slowly hydrolyzed, turning into free haloperidol, which enters the systemic circulation.
Haloperidol is a powerful central antagonist of type 2 dopamine receptors; in recommended doses, it has low α 1 -antiadrenergic activity and does not have an antihistamine or anticholinergic effect.
Pharmacodynamic effects. Haloperidol suppresses delusions and hallucinations by blocking dopaminergic signaling pathways in the mesolimbic structures. The central antidopaminergic action occurs in the basal ganglia (nigrostriatal ganglia). Haloperidol effectively eliminates psychomotor agitation, which explains its beneficial effect in mania and other syndromes accompanied by agitation.
The effect on the basal ganglia probably underlies unwanted extrapyramidal movement disorders (dystonia, akathisia, parkinsonism).
The antidopaminergic effect of haloperidol on lactotroph cells of the anterior pituitary gland causes hyperprolactinemia, which occurs due to the elimination of tonic inhibition of prolactin secretion mediated by dopamine.
Clinical researches. In clinical studies, patients were reported to be treated with oral haloperidol before switching to haloperidol decanoate. Sometimes patients were previously treated with another oral antipsychotic drug.
Pharmacokinetics
Absorption. After injection of haloperidol decanoate, there is a slow and constant release of free haloperidol from the depot. The concentration of haloperidol in the blood plasma increases gradually, reaching a maximum, usually 3-9 days after injection.
With regular monthly administration, the saturation stage in the blood plasma is reached after 2-4 months.
Distribution. Plasma protein binding in adult patients averages about 88-92%. The degree of binding to plasma proteins is characterized by high intersubject variability. Haloperidol is rapidly distributed in various tissues and organs, as evidenced by the large volume of distribution (average value 8-21 l/kg after i.v. administration). Haloperidol easily penetrates the BBB. It also crosses the placenta and is detected in breast milk.
Biotransformation. Haloperidol undergoes active metabolism in the liver. The main pathways of metabolism of haloperidol in the human body are glucuronidation, reduction to ketones, oxidative N-dealkylation and the formation of pyridinium metabolites. It is believed that the metabolites of haloperidol do not significantly affect its activity, but about 23% of the drug is metabolized by reduction, and the reverse conversion of the reduced metabolite of haloperidol to haloperidol cannot be completely excluded. Cytochrome P450 isoenzymes CYP 3A4 and CYP 2D6 are involved in the metabolism of haloperidol. Inhibition or induction of the CYP3A4 enzyme or inhibition of the CYP2D6 enzyme may affect the metabolism of haloperidol. A decrease in the activity of the CYP2D6 enzyme may lead to increased concentrations of haloperidol.
Removal. The final half-life of haloperidol after administration of haloperidol decanoate averages 3 weeks. This is longer than with other dosage forms, where T ½ of haloperidol averages 24 hours after administration and 21 hours after administration.
The estimated clearance of haloperidol after extravascular administration is 0.9-1.5 l/h/kg and is reduced in poor CYP2D6 metabolizers. Decreased CYP2D6 enzyme activity may result in increased haloperidol concentrations. Intersubject variability (coefficient of variation,%) of haloperidol clearance in patients with schizophrenia was 44% in a population pharmacokinetic analysis. After administration of haloperidol, 21% of the dose is excreted in feces and 33% in urine. Less than 3% of the dose is excreted unchanged in the urine.
Linearity/nonlinearity. The pharmacokinetics of haloperidol after intravenous injections of haloperidol decanoate is dose-dependent. When administering doses<450 мг между дозой и концентрацией галоперидола в плазме крови наблюдается почти линейная зависимость.
Special patient groups
Elderly patients. The concentration of haloperidol in the blood plasma of elderly patients is higher than in young adult patients when using the same dose. The results of small clinical studies indicate low clearance and a longer half-life of haloperidol in elderly patients. These results are consistent with the range of observed variations in the pharmacokinetic parameters of haloperidol. Dose adjustment of haloperidol is recommended when used in elderly patients (see APPLICATION).
Kidney failure. The effect of renal failure on the pharmacokinetics of haloperidol has not been studied. About a third of the dose of haloperidol is excreted in the urine, mainly in the form of metabolites. Less than 3% of the dose is excreted unchanged in the urine.
Haloperidol metabolites do not significantly affect the activity of haloperidol, although reverse conversion of the reduced haloperidol metabolite to haloperidol cannot be completely ruled out. Although renal impairment should not affect the elimination of haloperidol to a clinically significant extent, caution is recommended when treating patients with impaired renal function, especially in cases of severe renal impairment, due to the prolonged half-life of haloperidol and its reduced metabolite and the potential for accumulation (see APPLICATION).
Due to the large volume of distribution of haloperidol and its binding to plasma proteins, very small amounts of the drug can be removed by dialysis.
Liver failure. The effect of hepatic impairment on the pharmacokinetics of haloperidol has not been studied. However, hepatic impairment may have a significant effect on the pharmacokinetics of haloperidol because it is extensively metabolized in the liver. For patients with impaired liver function, it is recommended to adjust the dose and take safety precautions (see APPLICATION and SPECIAL INSTRUCTIONS).
Relationship between pharmacokinetics and pharmacodynamics
Therapeutic concentrations. According to published data from numerous clinical studies, the therapeutic effect in most patients with acute or chronic forms of schizophrenia is achieved at a plasma concentration of the drug of 1-10 ng/ml. Some patients may require higher concentrations of the drug due to the high intersubjective variability in the pharmacokinetic parameters of haloperidol.
In patients with first-episode schizophrenia treated with short-acting haloperidol dosage forms, therapeutic response can be achieved at concentrations of at least 0.6-3.2 ng/mL. Binding of 60-80% D 2 receptors better ensures the achievement of a therapeutic response with minimal extrapyramidal symptoms. On average, haloperidol concentrations in this range can be achieved using doses of 1-4 mg/day.
Due to the high intersubjective variability in the pharmacokinetic parameters of haloperidol and the concentration dependence of the effect, it is recommended to select an individual dose of haloperidol decanoate based on the patient's response to treatment. It is necessary to consider the time after dose change to achieve a new stable plasma concentration of haloperidol and the additional time for the manifestation of a therapeutic response. In some cases, it may be advisable to measure the concentration of haloperidol in the blood.
Cardiovascular effects. Risk of prolongation of the interval Q-Tc increases with increasing dose and concentration of haloperidol in the blood plasma.
Extrapyramidal symptoms. Extrapyramidal symptoms may develop when the drug is used in the therapeutic dose range, although their frequency tends to increase when used in doses exceeding the therapeutic dose.
INDICATIONS
maintenance therapy for schizophrenia and schizoaffective disorders in adult patients whose condition has stabilized while taking oral haloperidol.
APPLICATION
initiation of treatment and dose titration should be carried out under close supervision.
Dosage. The individual dose will depend on both the severity of symptoms and the current dosage of haloperidol. The lowest effective dose should always be used.
The initial dose of haloperidol decanoate is set based on the multiple increase in the daily dose of haloperidol; There are no specific recommendations for switching from other antipsychotic drugs (see PHARMACOLOGICAL PROPERTIES).
Adults (ages 18+)
Table 1. Dosing recommendations for haloperidol decanoate for adult patients (18 years and older)
|
The dose of haloperidol decanoate for most patients is 25-150 mg |
| Continuation of treatment
The most effective dose usually ranges from 50-200 mg. If it is necessary to administer doses of 200 mg once every 4 weeks, it is recommended to evaluate the individual benefit-risk ratio. The maximum dose of 300 mg once every 4 weeks should not be exceeded as safety concerns outweigh the clinical benefit of treatment |
| Dosing interval |
|
The total total dose of haloperidol in the two dosage forms should not exceed the corresponding maximum oral haloperidol dose of 20 mg/day |
Special patient groups
Elderly patients
Table 2. Haloperidol decanoate dosing recommendations for elderly patients
| Switching from haloperidol |
| Continuation of treatment
The most effective dose is usually 25-75 mg. Doses exceeding 75 mg every 4 weeks should only be given to patients who have tolerated higher doses and only after re-evaluation of the patient's individual benefit-risk balance. |
| Dosing interval
Typically the interval between injections is 4 weeks. Dosing interval adjustment may be required (depending on individual patient response) |
| Additional use of haloperidol in another dosage form
Additional treatment with haloperidol in a different dosage form may be required when switching to haloperidol decanoate treatment, for dose adjustment, or during exacerbation of episodes of psychotic symptoms (depending on the individual patient's response). The total total dose of haloperidol in the two dosage forms should not exceed the respective maximum haloperidol dose of 5 mg/day or the previously prescribed dose of oral haloperidol that the patient received during long-term therapy with oral haloperidol. |
Kidney failure. The effect of renal failure on the pharmacokinetics of haloperidol has not been studied.
Dose adjustment is not recommended, but caution should be used when treating patients with renal impairment. Patients with severe renal impairment may require a lower initial dose followed by dose increases in smaller increments and at longer intervals than in patients with normal renal function (see PHARMACOLOGICAL PROPERTIES).
Liver failure. The effect of hepatic impairment on the pharmacokinetics of haloperidol has not been studied.
Since haloperidol undergoes active metabolism in the liver, it is recommended to reduce the initial dose by 2 times and increase it in smaller increments and at longer intervals than in patients with normal liver function (see SPECIAL INSTRUCTIONS and PHARMACOLOGICAL PROPERTIES).
Use in children. The safety and effectiveness of haloperidol decanoate in children and adolescents (under 18 years of age) have not been established. No data available.
Mode of application. The drug is intended for intramuscular administration only! Do not administer IV!
Haloperidol decanoate is used as a single intramuscular injection deep into the gluteal muscle. It is recommended to alternate the gluteal muscles. It is undesirable to administer the drug in a dose whose volume exceeds 3 ml in order to avoid the unpleasant sensation of bloating at the injection site.
Children. Parenteral use of haloperidol decanoate in children (under 18 years of age) is contraindicated!
CONTRAINDICATIONS
- hypersensitivity to the active substance or any excipient of the drug;
- coma;
- inhibition of central nervous system activity;
- Parkinson's disease;
- dementia with Lewy bodies (DLB);
- progressive supranuclear palsy;
- extended interval QT-s or congenital long interval syndrome Q-T;
- recent acute myocardial infarction;
- uncompensated heart failure;
- history of ventricular arrhythmia or ventricular tachycardia of the torsade de pointes type;
- uncorrected hypokalemia;
- concomitant treatment with drugs that prolong the interval Q-T(see INTERACTIONS).
SIDE EFFECTS
According to the results of summary safety data obtained in clinical trials, the most frequently reported adverse events were: extrapyramidal disorders (14%), tremor (8%), parkinsonism (7%), muscle rigidity (6%) and somnolence (5%) .
In table 3 side effects are listed:
- identified in clinical studies of haloperidol decanoate;
- identified in clinical studies of haloperidol (in other dosage forms) and associated with the active substance;
- identified during the post-registration period of use of haloperidol decanoate and haloperidol.
The frequency of adverse reactions was assessed in clinical or epidemiological studies of haloperidol decanoate according to the following classification: very often (≥1/10), often (≥1/100 -<1/10), нечасто (≥1/1000 — <1/100), редко (≥1/10 000 — <1/1000), очень редко (<1/10 000), частота неизвестна (невозможно оценить по доступным данным).
Adverse reactions are presented by organ system and in order of decreasing severity.
Table 3
| Organ system class | Adverse reactions | ||||
|---|---|---|---|---|---|
| Frequency | |||||
| Often | Often | Infrequently | Rarely | Frequency unknown | |
| Blood and lymphatic system | Pancytopenia, agranulocytosis, thrombocytopenia, leukopenia, neutropenia | ||||
| The immune system | Anaphylactic reactions, hypersensitivity | ||||
| Endocrine system | Impaired ADH secretion, hyperprolactinemia | ||||
| Metabolism and nutrition | Hypoglycemia | ||||
| Mental disorders | Depression, insomnia | Psychotic disorders, agitation, confusion, loss of libido, decreased libido, anxiety | |||
| Nervous system | Extrapyramidal symptoms | Akathisia, parkinsonism, masked face, tremor, somnolence, sedation | Akinesia, dyskinesia, dystonia, cogwheel rigidity, hypertonicity, headache | Neuroleptic malignant syndrome, tardive dyskinesia, convulsions, bradykinesia, hyperkinesia, hypokinesia, dizziness, involuntary muscle contraction, incoordination, nystagmus | |
| Organ of vision | Oculogyric crisis, blurred vision, visual impairment | ||||
| Heart disorders | Tachycardia | Ventricular fibrillation, ventricular tachycardia of the pirouette type, ventricular tachycardia, extrasystole | |||
| Vascular disorders | Arterial hypotension, orthostatic hypotension | ||||
| Respiratory system, chest organs and mediastinum | Laryngeal edema, bronchospasm, laryngospasm, shortness of breath | ||||
| Gastrointestinal tract | Constipation, dry mouth, increased salivation | Nausea, vomiting | |||
| Acute liver failure, hepatitis, cholestasis, jaundice, abnormal liver function tests | |||||
| Skin and subcutaneous tissue | Angioedema, exfoliative dermatitis, leukocytoclastic vasculitis, photosensitivity reaction, urticaria, itching, rash, increased sweating | ||||
| Musculoskeletal and connective tissue disorders | Muscle stiffness | Rhabdomyolysis, torticollis, trismus, muscle spasm, muscle cramp, musculoskeletal stiffness | |||
| Kidneys and urinary tract | Urinary retention | ||||
| Impact on the course of pregnancy, postpartum and perinatal periods | Withdrawal syndrome in the newborn (see. ) | ||||
| Reproductive system and mammary glands | Sexual dysfunction | Priapism, amenorrhea, galactorrhea, dysmenorrhea, menorrhagia, erectile dysfunction, gynecomastia, menstrual irregularities, breast pain, breast discomfort | |||
| General disorders or disorders at the injection site | Reaction at the injection site | Sudden death, facial swelling, edema, hyperthermia, hypothermia, gait disturbance, injection site abscess | |||
| Laboratory indicators | Weight gain | Interval extension Q-T on ECG, weight loss | |||
Interval extension Q-T, ventricular tachycardia of the pirouette type; Ventricular arrhythmia, including ventricular fibrillation, ventricular tachycardia, and sudden death, have been reported in patients taking haloperidol.
Specific effects of antipsychotic drugs. Cases of cardiac arrest, venous thromboembolism, including pulmonary embolism and deep vein thrombosis have been reported with the use of antipsychotic drugs. The frequency of their occurrence is unknown.
Reporting suspected adverse reactions. Reporting suspected adverse reactions during post-marketing surveillance is important. This makes it possible to control the benefit/risk ratio when using medications. Healthcare professionals should report any suspected adverse reactions.
SPECIAL INSTRUCTIONS
increased mortality in elderly patients with dementia. Isolated cases of sudden death have been reported in patients with mental disorders taking antipsychotics, including haloperidol (see ADVERSE EFFECTS).
Elderly patients with psychosis due to dementia who are receiving antipsychotic drugs have an increased risk of death. An analysis of 17 placebo-controlled studies (modal duration 10 weeks) involving patients taking atypical antipsychotics showed that the risk of death in treated patients was 1.6-1.7 times higher than the risk of death in patients receiving placebo. In a 10-week controlled study, the death rate was about 4.5% in treated patients and about 2.6% in the placebo group. Although causes of death varied, most deaths were cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia). Observational studies suggest that the use of haloperidol in elderly patients is also associated with increased mortality. This association may be more pronounced with haloperidol than with atypical antipsychotics, is clearly evident in the first 30 days after the start of treatment and persists for at least 6 months. How much of this depends on the drug used and how much depends on patient characteristics has not yet been clarified.
Haloperidol decanoate is not indicated for the treatment of behavioral disorders associated with dementia.
Effect on the cardiovascular system. Isolated cases of interval prolongation have been reported with the use of haloperidol. Q-Tс and/or ventricular arrhythmia, except for rare reports of sudden death (see CONTRAINDICATIONS and SIDE EFFECTS). The risk of these disorders increases with the use of high doses of the drug, in the case of high concentrations in the blood plasma, if the patient has a tendency to such disorders, as well as with intravenous administration.
Haloperidol decanoate should not be administered intravenously.
Caution is recommended when used in patients with bradycardia, heart disease, prolongation of the interval Q-Tс family history or history of heavy alcohol abuse. Caution is also necessary when treating patients with potentially high plasma concentrations of the drug (see SPECIAL INSTRUCTIONS: Poor Metabolizers of the CYP 2D6 Enzyme).
An ECG is recommended before treatment with haloperidol. During treatment, the need for regular ECG should be assessed in order to detect prolongation of the interval Q-Tс and ventricular arrhythmias in all patients. It is recommended to reduce the dose if the interval prolongs Q-Tс during treatment. If the duration Q-Tс exceeds 500 ms, haloperidol should be discontinued.
Electrolyte imbalances, such as hypokalemia and hypomagnesemia, increase the risk of developing ventricular arrhythmias and should be corrected before initiating treatment with haloperidol. Therefore, preliminary and periodic monitoring of electrolyte concentrations is recommended.
Tachycardia and hypotension (including orthostatic hypotension) have also been reported (see ADVERSE EFFECTS). Caution is recommended when prescribing haloperidol to patients with arterial hypotension or orthostatic hypotension.
Cerebrovascular disorders. In randomized, placebo-controlled clinical trials in patients with dementia, some atypical antipsychotics were associated with an approximately 3-fold increased risk of cerebrovascular adverse events.
Surveillance studies that compared the incidence of stroke in elderly patients receiving any antipsychotic drug with those not taking such medications found an increased incidence of stroke in group 1. The risk of stroke increases with all butyrophenones, including haloperidol. The mechanism by which this risk increases is unknown. An increased risk in other patient groups cannot be excluded. Haloperidol decanoate should be used with caution in patients with risk factors for stroke.
Neuroleptic malignant syndrome. The use of haloperidol has been associated with the development of neuroleptic malignant syndrome, a rare idiosyncratic reaction characterized by hyperthermia, generalized rigidity, autonomic lability, impaired consciousness and increased levels of CPK in the blood serum. An early sign of this syndrome is often hyperthermia. Treatment with antipsychotic drugs should be immediately interrupted and appropriate supportive therapy should be initiated under close monitoring.
Tardive dyskinesia. Tardive dyskinesia may occur in some patients with long-term use or discontinuation of the drug. The syndrome is mainly characterized by involuntary rhythmic movements of the tongue, face, mouth or jaw. In some patients, these manifestations may be permanent. The syndrome may be masked when resuming the course of therapy, increasing the dose, or switching to another antipsychotic drug. If signs of tardive dyskinesia occur, therapy with antipsychotic drugs, including haloperidol, should be discontinued as soon as possible.
Extrapyramidal symptoms. Extrapyramidal symptoms such as tremor, rigidity, hypersalivation, bradykinesia, akathisia and acute dystonia may occur with the use of antipsychotic drugs.
The use of haloperidol is associated with the development of akathisia, which is characterized by subjectively unpleasant or anxious restlessness and the need to be constantly on the move, often accompanied by the inability to sit or stand still. Most often, akathisia develops during the first few weeks of treatment. For patients with such symptoms, increasing the dose may be harmful.
Acute dystonia may occur during the first few days of haloperidol treatment, but later onset or development after dose increases have also been reported. Symptoms of dystonia may include torticollis, facial grimace, spasm of the masticatory muscles (trismus), tongue protrusion, and abnormal eye movements, including oculogyric crisis. Male and younger patients are at higher risk of developing such reactions. The development of acute dystonia may require discontinuation of the drug.
If necessary, anti-parkinsonian drugs with anticholinergic effects can be prescribed, but their use in routine practice as a preventive measure is not recommended. If concomitant antiparkinsonian treatment is necessary, it should be continued after discontinuation of the drug Haloperidol decanoate, since the elimination of antiparkinsonian drugs occurs faster than the elimination of haloperidol decanoate in order to avoid the development or exacerbation of extrapyramidal symptoms. When combined with haloperidol decanoate, anticholinergic drugs, including antiparkinsonian drugs, must be aware of the possible increase in intraocular pressure.
Seizures/convulsions. It has been reported that the use of haloperidol may cause seizures. Treatment of patients with epilepsy or patients with an increased tendency to seizures (for example, alcohol withdrawal syndrome or traumatic brain injury) requires caution.
Disorders of the liver and biliary tract. Since the metabolism of the drug occurs in the liver, dose adjustment and precautions are recommended when treating patients with liver failure (see APPLICATION and PHARMACOLOGICAL PROPERTIES). Isolated cases of liver dysfunction or hepatitis, most often cholestatic, have been reported (see SIDE EFFECTS).
From the endocrine system. Thyroxine increases the toxicity of haloperidol. Antipsychotic drugs should be used with caution in patients with hyperthyroidism and only in combination with therapy aimed at achieving a euthyroid state.
Hormonal effects of antipsychotics include hyperprolactinemia, which may cause galactorrhea, gynecomastia, and oligo- or amenorrhea (see ADVERSE EFFECTS).
Tissue culture studies suggest that prolactin may stimulate the growth of human breast tumor cells. Although clinical and epidemiological studies have not demonstrated a clear association between the use of antipsychotic drugs and breast cancer in humans, caution is advised when treating patients with a relevant medical history. In patients with pre-existing hyperprolactinemia and in patients with possible prolactin-dependent tumors, Haloperidol decanoate should be used with caution.
Cases of hypoglycemia and syndrome of inappropriate ADH secretion have been reported very rarely (see ADVERSE EFFECTS).
Venous thromboembolism. Cases of venous thromboembolism (VTE) have been reported with the use of antipsychotic drugs. Since acquired risk factors for the development of VTE are often observed in patients treated with antipsychotic drugs, all possible risk factors for the development of VTE should be identified before and during treatment with haloperidol and preventive measures should be taken.
Start of treatment. Patients planning to be treated with haloperidol decanoate should first take oral haloperidol to reduce the likelihood of unpredictable adverse sensitivity to haloperidol.
Patients with depression. It is not recommended to use Haloperidol decanoate as monotherapy in patients with predominant symptoms of depression. It can be combined with antidepressants to treat conditions that are characterized by a combination of depression and psychosis (see INTERACTIONS).
Slow enzyme metabolizersCYP2D6. Haloperidol decanoate should be used with caution in patients with poor cytochrome P450 (CYP) 2D6 metabolism and concomitant use of CYP3A4 inhibitors.
Excipients: Haloperidol decanoate. Haloperidol decanoate injection contains 15 mg/ml benzyl alcohol, which may cause anaphylactic reactions.
Haloperidol decanoate, solution for injection, contains sesame oil. Sesame oil has very rarely caused severe allergic reactions.
Use during pregnancy and lactation
Pregnancy. According to data on the use of haloperidol in pregnant women (more than 400 pregnancy results with a known outcome), there is no evidence of teratogenicity or feto-/neonatal toxicity. However, there are isolated reports of cases of congenital developmental defects during the use of haloperidol in combination with other drugs during pregnancy. Animal studies have demonstrated toxic effects on reproductive function. It is recommended to avoid the use of haloperidol decanoate during pregnancy.
Newborns whose mothers took antipsychotic drugs (including haloperidol) during the third trimester of pregnancy are at risk of developing adverse reactions, including extrapyramidal symptoms and/or withdrawal symptoms after delivery, which may vary in severity and duration. Agitation, hypertension, hypotension (increased or decreased muscle tone), tremor, somnolence, respiratory distress, or digestive disturbances have been reported. Therefore, careful monitoring of the condition of newborns should be carried out.
Lactation. Haloperidol decanoate passes into breast milk. Small amounts of haloperidol have been detected in the plasma and urine of newborns whose mothers received haloperidol. There is insufficient information about the effects of haloperidol on breastfed infants. The decision to discontinue breastfeeding or discontinue therapy with haloperidol decanoate must be made taking into account the benefits of breastfeeding for the child and the benefits of treatment for the woman.
Fertility. Haloperidol increases prolactin levels. Hyperprolactinemia may inhibit the synthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus, resulting in decreased gonadotropin secretion. This may suppress reproductive function as a result of inhibition of the synthesis of sex steroids in the gonads of women and men (see SPECIAL INSTRUCTIONS).
The ability to influence reaction speed when driving vehicles or other mechanisms. Haloperidol decanoate has a moderate effect on the ability to drive a car and perform work associated with an increased risk of injury. Sedation or difficulty concentrating may occur, especially when using high doses and early in treatment. These phenomena may intensify with alcohol consumption. Patients are advised to refrain from driving and performing work involving an increased risk of injury while being treated with haloperidol until their response to the drug is known.
INTERACTIONS
interaction studies were conducted with adults only.
Effect on the cardiovascular system. Haloperidol decanoate is contraindicated in combination with drugs that prolong the interval Q-Tс(see CONTRAINDICATIONS).
Examples of such drugs are:
- class IA antiarrhythmic drugs: (disopyramide, quinidine);
- class III antiarrhythmic drugs (amiodarone, dofetilide, dronedarone, ibutilide, sotalol);
- some antidepressants (citalopram, escitalopram);
- some antibiotics (azithromycin, clarithromycin, erythromycin, levofloxacin, moxifloxacin, telithromycin);
- other antipsychotics (phenothiazine derivatives, sertindole, pimozide, ziprasidone);
- some antifungals (pentamidine);
- some antimalarials (halofantrine);
- some drugs that affect the gastrointestinal tract (dolasetron);
- some medicines used to treat cancer (toremifene, vandetanib);
- some other medicines (bepredil, methadone).
The simultaneous use of drugs that cause electrolyte imbalance requires caution (see SPECIAL INSTRUCTIONS).
Medicines that may increase plasma concentrations of haloperidol. Haloperidol is metabolized in several ways (see PHARMACOLOGICAL PROPERTIES). The main pathway is glucuronidation and reduction to ketones. Also involved in metabolism is the cytochrome P450 enzyme system, especially CYP 3A4 and to a lesser extent CYP 2D6. Inhibition of these metabolic pathways by another drug or reduction in CYP2D6 enzyme activity may result in increased haloperidol concentrations. An additive effect of suppressing the activity of CYP 3A4 and reducing the activity of the CYP 2D6 enzyme is possible. Given limited and sometimes conflicting information, the potential increase in haloperidol plasma concentrations when coadministered with a CYP3A4 and/or CYP2D6 enzyme inhibitor may be as high as 20% to 40%, although increases of up to 100% have been reported in some cases. Examples of medicinal products that may increase haloperidol plasma concentrations (based on clinical experience or drug-drug interaction mechanisms) include:
- CYP 3A4 enzyme inhibitors: alprazolam, fluvoxamine, indinavir, itraconazole, ketoconazole, nefazodone, posaconazole, saquinavir, verapamil, voriconazole;
- CYP 2D6 enzyme inhibitors: bupropion, chlorpromazine, duloxetine, paroxetine, promethazine, sertraline, venlafaxine;
- combined inhibitors of CYP 3A4 and CYP 2D6 isoenzymes: fluoxetine, ritonavir;
- drugs with an unknown mechanism of action - buspirone.
This list is not exhaustive.
Increasing the concentration of haloperidol in blood plasma may increase the risk of adverse events, including prolongation of the interval Q-Tc(see SPECIAL INSTRUCTIONS). Interval extension Q-Tc observed when haloperidol was used in combination with metabolic inhibitors - ketoconazole (400 mg/day) and paroxetine (20 mg/day).
Patients taking haloperidol in combination with such drugs are advised to monitor for symptoms of increased or prolonged pharmacological action of haloperidol and, if necessary, reduce the dose of haloperidol decanoate.
Medicines that may reduce plasma concentrations of haloperidol. Concomitant use of haloperidol with strong inducers of the CYP3A4 isoenzyme may gradually lead to a decrease in the plasma concentration of haloperidol to such an extent that the effectiveness of haloperidol may be reduced. Examples of such drugs are carbamazepine, phenobarbital, phenytoin, rifampicin, St. John's wort (Hypericum perforatum).
The list is not exhaustive.
Enzyme induction is possible after just a few days of treatment. Maximum enzyme induction is usually observed after approximately 2 weeks and may persist for the same period of time after discontinuation of drug therapy. When using CYP 3A4 enzyme inducers simultaneously, it is recommended to monitor the patient and, if necessary, increase the dose of Haloperidol decanoate. After discontinuation of the CYP3A4 inducer, the concentration of haloperidol may gradually increase, therefore, it may be necessary to reduce the dose of Haloperidol decanoate.
It is known that sodium valproate suppresses glucuronidation, but does not affect the concentration of haloperidol in blood plasma.
Effect of haloperidol on other drugs. Haloperidol may potentiate the effects of CNS depressants, including alcohol, hypnotics, sedatives and potent analgesics. An enhanced effect on the central nervous system was also noted when combined with methyldopa.
Haloperidol may antagonize the effects of epinephrine (adrenaline) and other sympathomimetic drugs (eg, stimulants such as amphetamines) and result in alterations in the antihypertensive effects of blockers such as guanethidine.
Haloperidol may reduce the effects of levodopa and other dopamine agonists.
Haloperidol is a CYP2D6 inhibitor. Haloperidol decanoate inhibits the metabolism of tricyclic antidepressants (for example, imipramine, desipramine), thereby increasing their concentration in the blood plasma.
Other forms of interaction. In rare cases, the following symptoms have been observed with concomitant use of lithium and haloperidol: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, acute cerebral syndrome and coma. Most of these symptoms are reversible. Whether these symptoms are a manifestation of a specific nosological form has not been clarified.
Haloperidol has been reported to antagonize the anticoagulant phenindione.
OVERDOSE
with parenteral use of haloperidol, overdose is observed less frequently than with oral administration of the drug. The following data are based on oral haloperidol.
Symptoms. In general, a manifestation of an overdose of haloperidol is the development of its known pharmacological effects and adverse reactions in a more pronounced form. The most pronounced are severe extrapyramidal symptoms, arterial hypotension and sedation. Extrapyramidal reactions manifest themselves as muscle rigidity and general or localized tremor. Hypertension may often occur instead of hypotension.
In exceptional cases, a coma with respiratory depression and arterial hypotension may develop, which can be quite severe, with the development of a shock-like state.
The risk of developing ventricular arrhythmia, possibly associated with prolongation of the interval, should be considered Q-Tс.
Treatment. There is no specific antidote. Treatment should be symptomatic.
Patency of the airway of a comatose patient is ensured using an oropharyngeal or endotracheal tube; if respiratory depression occurs, artificial ventilation may be required.
With reduced blood pressure and circulatory failure, it is necessary to administer a sufficient amount of fluid, plasma or concentrated albumin, as well as the use of vasopressors - dopamine or norepinephrine. Epinephrine should not be used as it may cause extreme hypotension through interaction with haloperidol.
For severe extrapyramidal disorders, it is recommended to use antiparkinsonian drugs, the effect of which lasts for several weeks. Antiparkinsonian drugs should be discontinued very carefully, as extrapyramidal symptoms may return.
STORAGE CONDITIONS
at a temperature not exceeding 25 °C in the original packaging to protect from exposure to light.
Date added: 01/27/2020
© Compendium 2019
Prices HALOPERIDOL DECANOATE in cities of Ukraine
Vinnitsa 289.01 UAH/pack.
HALOPERIDOL DECANOATE ..... 254.99 UAH/pack.
« PHARMACY BAM»
Vinnitsa, Khmelnitskoe highway, 108A, tel.: +380981858361
Dnieper 263.45 UAH/pack.
HALOPERIDOL DECANOATE solution d/in. 50 mg/ml amp. 1 ml No. 5, Gedeon Richter ..... 242.85 UAH/pack.
« PHARMACIES OF THE MEDICAL ACADEMY»
Dnepr, ave. Gagarina Yuria, 8A, tel.: +380563769472
Zhytomyr 268.63 UAH/pack.
HALOPERIDOL DECANOATE solution d/in. 50 mg/ml amp. 1 ml No. 5, Gedeon Richter ..... 266 UAH/pack.
« PHARMACY WHOLESALE PRICES»
Zhytomyr, st. Kyiv, 7/4, tel.: +380800505911
Zaporozhye 285.47 UAH/pack.
HALOPERIDOL DECANOATE solution d/in. 50 mg/ml amp. 1 ml No. 5, Gedeon Richter ..... 266 UAH/pack.
« PHARMACY WHOLESALE PRICES»
Zaporozhye, st. Sedova, 1, tel..
