Active ingredients: Haloperidol
HALDOL 1 mg tablets
HALDOL 5 mg tablets
HALDOL 2 mg / mL oral drops, solution
HALDOL 10 mg / mL oral drops, solution
HALDOL 5 mg / mL solution for injection for intramuscular use
Why is Haldol used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antipsychotic derivative of butyrophenone.
THERAPEUTIC INDICATIONS
Tablets and oral drops, solution:
Psychomotor agitation in case of:
- manic states, dementia, oligophrenia, psychopathy, acute and chronic schizophrenia, alcoholism, compulsive, paranoid, histrionic personality disorders.
Delusions and hallucinations in case of:
- acute and chronic schizophrenia, paranoia, acute mental confusion, alcoholism, (Korsakoff's syndrome), hypochondriasis, personality disorders of the paranoid, schizoid, schizotypic, antisocial type, some cases of the borderline type.
- Choreiform movements.
- Agitation, aggression and flight reactions in elderly subjects.
- Tics and stuttering.
- He retched.
- Hiccup.
- Alcohol withdrawal syndromes.
Solution for injection for intramuscular use:
Resistant forms of psychomotor excitement, acute delusional and / or hallucinatory psychosis, chronic psychosis.
The use of the product in high doses should be limited to the therapy of resistant forms of: psychomotor excitation syndromes, acute delusional and / or hallucinatory psychosis, chronic psychosis.
Contraindications When Haldol should not be used
Hypersensitivity to the active substance or to any of the excipients.
Comatose states, patients strongly depressed by alcohol or other substances active on the central nervous system, endogenous depressions without agitation, Parkinson's disease.
Asthenia, neurosis and spastic states due to lesions of the basal ganglia (hemiplegia, multiple sclerosis, etc.) Known or suspected pregnancy, breastfeeding and in the child in the first two years of life
Clinically significant heart disease (e.g. recent acute myocardial infarction, decompensated heart failure, arrhythmias treated with class Ia and III antiarrhythmic drugs).
QTc interval prolongation.
Subjects with a family history of arrhythmia or torsades de pointes
Uncorrected hypokalaemia.
Concomitant use of QTc prolonging drugs.
Precautions for use What you need to know before taking Haldol
Rare cases of sudden death have been reported in psychiatric patients treated with antipsychotic drugs, including HALDOL.
use caution in patients with cardiovascular disease or a family history of QT prolongation.
HALDOL should not be administered intravenously, as intravenous administration of haloperidol has been associated with an increased risk of QT prolongation and Torsade de Pointes. Carry out a basic ECG before starting treatment (see paragraph "Contraindications").
Monitor the ECG during therapy based on the patient's clinical condition.
During therapy, reduce dosage if QT prolongation is observed and discontinue if QTc is> 500ms.
Periodic checking of electrolytes is recommended.
Avoid concomitant therapy with other neuroleptics.
An approximately three-fold increase in the risk of cerebrovascular events was observed in randomized clinical trials versus placebo in a population of patients with dementia treated with some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk for other antipsychotics or other patient populations cannot be excluded. HALDOL should be used with caution in patients with stroke risk factors.
HALDOL should be administered with caution in the following cases:
- If the patient or someone else in their family has a history of blood clots (thrombi), as medicines like these have been associated with the formation of blood clots.
- severe cardiopathic patients, due to possible transient arterial hypotension and / or the onset of anginal pain (in this case do not use adrenaline as HALDOL can block hypertensive activity with further paradoxical reduction of pressure) and, in any case, in elderly or depressed subjects ;
- epileptic patients and those in conditions predisposing to seizures (e.g. alcohol withdrawal, brain damage), as it has been reported that HALDOL can induce seizures.
- patients with known allergies or with a history of allergic reactions to drugs or with leukopenizing conditions;
- during the manic phase of cyclical psychosis due to the possibility of a rapid change in mood towards depression;
- as haloperidol is metabolised in the liver, it is advised to administer it with caution in patients with hepatic insufficiency;
- in the case of simultaneous antiparkinsonian therapy, the latter must be continued after the suspension of HALDOL which has a longer elimination time, in order to avoid the appearance or worsening of extrapyramidal symptoms. The physician should consider the possibility of increased intraocular pressure in cases where HALDOL is administered together with anticholinergic drugs, including antiparkinson's;
- thyroxine may facilitate the toxicity of HALDOL. Therefore the product should be administered with great caution in patients with hyperthyroidism. Antipsychotic therapy in the latter should be accompanied by adequate thyrostatic treatment;
- in schizophrenia, the response to treatment with antipsychotic drugs may be delayed. Even when medications are stopped, the resumption of symptoms may not appear visible for several weeks or months;
- acute withdrawal symptoms including nausea, vomiting and insomnia have been described very rarely after abrupt withdrawal of high doses of antipsychotic drugs. Psychotic relapse can also occur, so a gradual withdrawal is recommended.
- HALDOL should not be used on its own in cases where depression is predominant. HALDOL can be associated with antidepressant drugs in conditions where depression and psychosis coexist.
The drug should be administered under the supervision of the psychiatrist.
HALDOL 5 mg / mL solution for injection for intramuscular use
The patient should consult his doctor to be instructed on the most correct method of administering the drug.
HALDOL in ampoule formulation should be administered intramuscularly.
Interactions Which drugs or foods can modify the effect of Haldol
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Do not administer concomitantly with QT prolonging drugs such as some class Ia antiarrhythmics (e.g. quinidine, disopyramide and procainamide) and class III (e.g. amiodarone, sotalol), some antihistamines, other antipsychotics and some antimalarials (e.g. quinine and mefloquine) and also moxifloxacin. This list is to be considered only indicative and not exhaustive
Mild to moderate increases in haloperidol concentrations have been reported in pharmacokinetic studies when administered with drugs such as itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, serthaline, chlorpromazine and promethazine. QTc increases were observed when haloperidol was administered in combination with the metabolic inhibitors ketoconazole (400 mg / day) or paroxetine (20 mg / day). In this case, the haloperidol dose may need to be reduced.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Concomitant use of diuretics, particularly those that can cause hypokalaemia, should be avoided.
The combination with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects of interaction. Like all neuroleptics, HALDOL can enhance the CNS depressant action of other drugs including alcohol, hypnotics, sedatives or strong analgesics. An enhancement of these effects has also been reported when combined with methyldopa.
HALDOL may decrease the antiparkinsonian effects of levodopa.
HALDOL inhibits the metabolism of tricyclic antidepressants, increasing their plasma levels.
l chronic treatment with enzymatic activators such as carbamazepine, phenobarbital, rifampicin, in combination with HALDOL causes a significant reduction in plasma levels of haloperidol; therefore, in case of concomitant treatment, the dose of HALDOL should be appropriately corrected. After stopping these drugs, the dosage of HALDOL may need to be reduced.
In rare cases, the following symptoms have been reported during concomitant use of lithium and HALDOL: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, brain stem disorders, acute brain syndrome and coma. Most of these symptoms were Reversible. It remains controversial whether these symptoms are related to co-administration or whether they are the manifestation of a distinct clinical episode. Nevertheless, it is recommended that, in patients treated concomitantly with HALDOL and lithium, therapy is immediately discontinued if these appear. symptoms.
HALDOL can antagonize the action of adrenaline and other sympathomimetic agents and reverse the hypotensive effects of adrenergic agents such as, for example, guanethidine.
An "antagonistic action on" the effect of the anticoagulant phenindione has been reported
Warnings It is important to know that:
Neuroleptic malignant syndrome
A potentially fatal symptom complex called Neuroleptic Malignant Syndrome has been reported during treatment with antipsychotic drugs. Clinical manifestations of this syndrome are: hyperpyrexia, muscle stiffness, akinesia, vegetative disorders (irregularities in the pulse and blood pressure, sweating, tachycardia, arrhythmias); changes in consciousness which can progress to stupor and coma. The treatment of the S.N.M.it consists in immediately suspending the administration of antipsychotic drugs and other non-essential drugs and in instituting intensive symptomatic therapy (particular care must be taken to reduce hyperthermia and correct dehydration). If the resumption of antipsychotic treatment is deemed essential, the patient should be carefully monitored.
With the use of some major neuroleptics, including HALDOL, the occurrence of cases of bronchopneumonia has been reported, probably favored by dehydration due to reduced sensation of thirst, haemoconcentration and reduced pulmonary ventilation; the appearance of such symptoms, especially in the elderly, requires prompt and adequate therapy.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
HALDOL is contraindicated in pregnancy and breastfeeding.
The following symptoms have been observed in newborn babies of mothers who have taken conventional or atypical antipsychotics including HALDOL during the last trimester (last three months of pregnancy): shaking, muscle stiffness and / or weakness, sleepiness, agitation, breathing problems and difficulty in food intake. If your child shows any of these symptoms, contact your doctor.
Effects on ability to drive and use machines
HALDOL can cause sedation and reduced attention, especially with higher doses and at the beginning of treatment; these effects can be enhanced by alcohol. Patients should be advised not to drive or operate machinery during treatment until their reactivity to the drug is ascertained.
Safety data available in the pediatric population indicate a risk of extrapyramidal symptoms, including tardive dyskinesia and sedation. No long-term safety data are available.
Important information about some of the ingredients of HALDOL
HALDOL tablets contain lactose and the 1 mg tablets also contain sucrose. If your doctor has diagnosed an intolerance to some sugars, contact your doctor before taking this medicine.
HALDOL oral drops contain para-hydroxybenzoates. They can cause allergic reactions (even delayed)
Dosage and method of use How to use Haldol: Dosage
The suggested posologies are only indicative as the dosage is strictly individual and varies according to the patient's response. This means that in the acute phase a progressive increase in doses is often necessary, followed by a gradual reduction in the maintenance phase, in order to establish the minimum effective dose. High doses should only be given to patients who have responded poorly to lower doses.
ADULTS
1) As a neuroleptic
acute phase: acute episodes of schizophrenia, delirium tremens, paranoia, acute confusion, Korsakoff's syndrome, acute paranoia: 5 mg for intramuscular use to be repeated every hour until adequate symptom control is achieved and in any case up to a maximum of 20 mg / day.
In oral administration, doses between 2 and 20 mg / day could be administered either as a single dose or as divided doses.
chronic phase: chronic schizophrenia, chronic alcoholism, chronic personality disorders: for oral administration: 1-3 mg three times a day. in relation to the individual response.
However, the maximum daily dose should not exceed 20 mg.
2) In the control of psycho-motor agitation
acute phase: mania, dementia, alcoholism, personality and behavioral disorders, hiccups, choreiform movements, tics, stammering:
5 mg for intramuscular use to be repeated every hour until adequate symptom control is achieved and in any case up to a maximum of 20 mg per day
chronic phase: for oral administration: from 0.5 mg-1 mg three times a day up to 2-3 mg three times a day depending on the individual response.
3) As a hypnotic for oral administration: 2-3 mg in a single dose, in the evening before going to bed.
4) As an antiemetic
in vomiting of central origin: 5 mg for intramuscular use
In the prophylaxis of postoperative vomiting: 2.5 - 5 mg for intramuscular use at the end of the operation.
SENIOR CITIZENS
In the treatment of elderly patients, the posology must be carefully established by the doctor, who will have to evaluate a possible reduction of the dosages indicated above.
Pediatric population
The safety and efficacy of haloperidol have not been established in the pediatric population.
Overdose What to do if you have taken too much Haldol
Symptoms:
The manifestations of overdose are those deriving from an exaltation of the known pharmacological effects and adverse reactions. The main symptoms are: intense extrapyramidal reactions, hypotension and sedation. An extrapyramidal reaction manifests itself with muscle stiffness and generalized or localized tremor.
In extreme cases, the patient may manifest a comatose state with respiratory depression and severe arterial hypotension, leading to a shock-like state. The risk of ventricular arrhythmias possibly associated with prolongation of the QT interval of the electrocardiogram should also be considered.
Treatment:
There is no specific antidote. Treatment is primarily supportive. Activated charcoal can be given.
In comatose patients, a patent airway should be established by tracheostomy or intubation. Respiratory depression may require artificial respiration. The ECG and vital signs should be monitored until the ECG is restored to normal.
Severe arrhythmias should be treated with appropriate antiarrhythmic measures.
Hypotension and circulatory collapse can be treated by intravenous infusion of fluids, plasma or concentrated albumin or the use of vasopressor agents such as dopamine or noradrenaline. Adrenaline should not be used as it may cause severe hypotension in the presence of HALDOL
In case of severe extrapyramidal reactions, antiparkinsonian drugs (eg benztropine mesylate: 1-2 mg im or iv) should be administered parenterally.
In case of accidental ingestion / intake of an excessive dose of HALDOL, notify your doctor immediately or go to the nearest hospital.
IF ANY DOUBT ABOUT THE USE OF HALDOL, ASK YOUR DOCTOR OR PHARMACIST
Side Effects What are the side effects of Haldol
Like all medicines, HALDOL can cause side effects, although not everybody gets them.
Side effects reported by patients taking HALDOL are listed below:
- Nervous system disorders: extrapyramidal disorders, hyperkinesia, tremor, hypertonia, dystonia, somnolence, bradykinesia, dizziness, akathisia, dyskinesia, hypokinesia, tardive dyskinesia, motor dysfunction, involuntary muscle contractions, neuroleptic malignant syndrome, nystagmus, parkinsonism, sedation headache.
- Eye disorders: vision disturbances, oculogyric crisis, blurred vision.
- Gastrointestinal disorders: constipation, dry mouth, salivary hypersecretion, vomiting, nausea.
- Vascular disorders: orthostatic hypotension, hypotension.
- Reproductive system and breast disorders: erectile dysfunction, amenorrhea, feeling of discomfort in the breast, breast pain, galactorrhea, dysmenorrhea, sexual dysfunction, menstrual disorders, menorrhagia, priapism, gynecomastia.
- Investigations: weight gain, prolonged QT electrocardiogram, weight decrease.
- Endocrine disorders: hyperprolactinaemia, inappropriate secretion of the antidiuretic hormone.
- Psychiatric disorders: decreased libido, loss of libido, agitation, psychotic disorders, confusional state, depression, insomnia.
- Cardiac disorders: tachycardia, torsade de pointes (torsade de pointes), ventricular fibrillation, ventricular tachycardia, extrasystole.
- Musculoskeletal and connective tissue disorders: trismus, stiff neck, muscle stiffness, muscle spasms, musculoskeletal pain, muscle contractions.
- General disorders and administration site conditions: gait disturbances, sudden death, face edema, edema, hyponatremia, hyperthermia.
- Disorders of the haemolifopoietic system: agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, neutropenia.
- Immune system disorders: anaphylactic reaction, hypersensitivity.
- Nutrition and metabolism disorders: hypoglycemia.
- Respiratory, thoracic and mediastinal disorders: bronchospasm, laryngospasm, laryngeal edema, dyspnoea.
- Hepatobiliary disorders: acute liver failure, hepatitis, cholestasis, jaundice, liver function test abnormalities.
- Skin and subcutaneous tissue disorders: leukocytoclastic vasculitis, exfoliative dermatitis, urticaria, photosensitivity reactions, rash, pruritus, hyperhidrosis.
- Pregnancy, puerperium and perinatal conditions: tremor, muscle stiffness and / or weakness, drowsiness, agitation, breathing problems and difficulty in eating have been observed in infants of mothers who have taken conventional or atypical antipsychotics including HALDOL during the last trimester (the last three months of pregnancy).
Possible side effects
- Blood clots (thrombi) in the veins particularly in the legs (symptoms include swelling, pain and redness in the legs), which can travel through blood vessels in the lungs causing chest pain and difficulty breathing. If you notice any of these symptoms, please contact your doctor immediately.
Additional important information
- In older people with dementia, a small increase in the number of deaths has been reported for those patients taking antipsychotics compared with those not taking them.
- Elderly patients with dementia who require treatment with HALDOL to control their behavior may have an increased risk of death compared to not being treated.
- If you have had episodes of irregular heartbeat (palpitations, dizziness, fainting), high fever, muscle stiffness, fast breathing, abnormal sweating or decreased mental alertness, contact your doctor immediately. Your body may be reacting inappropriately to the medicine
- Rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been observed with HALDOL and other drugs of the same class.
Very rare cases of sudden death.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
"Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly through the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting side effects you can help provide more information on the safety of this medicine. "
Expiry and Retention
Expiry: see the expiry date indicated on the package.
WARNING: do not use the medicine after the expiry date indicated on the package. The expiry date refers to the product in intact packaging, correctly stored.
storage
Store at a temperature not exceeding 25 ° C.
Vials: keep away from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
How to open the bottle of drops
HALDOL is available in 30ml bottles with dropper device and child resistant closure. To open, push the plastic cap down firmly, then unscrew. After removing the cap, pour the required number of drops using the dropper
COMPOSITION
HALDOL 1 mg tablets
One tablet contains:
Active ingredient: haloperidol 1 mg. Excipients: lactose, corn starch, sucrose, hydrogenated cottonseed oil, talc.
HALDOL 5 mg tablets
One tablet contains:
Active ingredient: haloperidol 5 mg. Excipients: lactose, indigo carmine (E 132), corn starch, hydrogenated cottonseed oil, talc.
HALDOL 2 mg / mL oral drops, solution
One mL of solution contains:
Active ingredient: haloperidol 2 mg. Excipients: lactic acid, methyl para-hydroxybenzoate, purified water.
HALDOL 10 mg / mL oral drops, solution
One mL of solution contains:
Active ingredient: haloperidol 10 mg. Excipients: lactic acid, methyl parahydroxybenzoate, propyl parahydroxybenzoate, purified water.
HALDOL 5 mg / mL solution for injection for intramuscular use
One mL contains:
Active ingredient: haloperidol 5 mg. Excipients: lactic acid, water for injections.
PHARMACEUTICAL FORM AND CONTENT
30 tablets of 1 mg
30 tablets of 5 mg
30 mL oral drops 2 mg / mL
30 mL oral drops 10 mg / mL
5 ampoules of 1 mL solution for injection for intramuscular use 5 mg / mL.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
HALDOL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 mg tablets
One tablet contains:
Active ingredient: Haloperidol 1 mg
Excipient: lactose
5 mg tablets
One tablet contains:
Active ingredient: Haloperidol 5 mg
Excipient: lactose
2 mg / ml oral drops, solution
One milliliter contains:
Active ingredient: Haloperidol 2 mg
Excipients: methyl-para-hydroxybenzoate, propyl-para-hydroxybenzoate
5 mg / ml solution for injection for intramuscular use
One milliliter contains:
Active ingredient: Haloperidol 5 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets
Oral drops, solution
Solution for injection for intramuscular use
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Tablets and oral drops, solution:
Psychomotor agitation in case of:
- manic states, dementia, oligophrenia, psychopathy, acute and chronic schizophrenia, alcoholism, compulsive, paranoid, histrionic personality disorders.
Delusions and hallucinations in case of:
- acute and chronic schizophrenia, paranoia, acute mental confusion, alcoholism (Korsakoff's Syndrome), hypochondriasis, personality disorders of the paranoid, schizoid, schizotypic, antisocial type, some cases of the borderline type;
- Choreiform movements;
- Agitation, aggression and flight reactions in elderly subjects;
- Tics and stuttering;
- He retched;
- Hiccup;
- Alcohol withdrawal syndromes.
Solution for injection for intramuscular use:
Resistant forms of psychomotor excitement, acute delusional and / or hallucinatory psychosis, chronic psychosis.
The use of the product in high doses should be limited to the therapy of resistant forms of: psychomotor excitation syndromes, acute delusional and / or hallucinatory psychosis, chronic psychosis.
04.2 Posology and method of administration
The suggested posologies are only indicative as the dosage is strictly individual and varies according to the patient's response. This means that in the acute phase a progressive increase in doses is often necessary, followed by a gradual reduction in the maintenance phase, in order to establish the minimum effective dose. High doses should only be given to patients who have responded poorly to lower doses.
HALDOL in ampoule formulation should be administered intramuscularly (see section 4.4 Special warnings and precautions for use).
ADULTS
1) As a neuroleptic
acute phase : acute episodes of schizophrenia, delirium tremens, paranoia, acute confusion, Korsakoff's syndrome, acute paranoia.
5-10 mg I.M. to be repeated every hour until adequate symptom control is achieved and in any case up to a maximum of 60 mg / day.
In oral administration it may be necessary to double the above doses
chronic phase : chronic schizophrenia, chronic alcoholism, chronic personality disorders.
For oral administration: 1-3 mg three times a day, up to 10-20 mg three times a day depending on the individual response.
2) In the control of psycho-motor agitation
acute phase : mania, dementia, alcoholism, personality and behavioral disorders, hiccups, choreiform movements, tics, stuttering: 5-10 mg I.M.
chronic phase :
For oral administration: from 0.5-1 mg three times a day up to 2-3 mg three times a day depending on the individual response.
3) As a hypnotic:
For oral administration: 2-3 mg in a single dose, in the evening before bedtime.
4) As an antiemetic:
In vomiting of central origin: 5 mg I.M.
In the prophylaxis of postoperative vomiting: 2.5-5 mg I.M. at the end of the intervention.
SENIOR CITIZENS
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Pediatric population
The safety and efficacy of haloperidol have not been established in the pediatric population.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Comatose states, patients strongly depressed by alcohol or other substances active on the central nervous system, endogenous depressions without agitation, parkinson's disease, asthenia, neurosis and spastic states due to lesions of the basal ganglia (hemiplegia, multiple sclerosis, etc. ).
Clinically significant heart disease (e.g. recent acute myocardial infarction, decompensated heart failure, arrhythmias treated with class Ia and III antiarrhythmic drugs).
QTc interval prolongation.
Subjects with a family history of arrhythmia or torsades de pointes.
Uncorrected hypokalaemia.
Concomitant use of QTc prolonging drugs.
Known or suspected pregnancy, breastfeeding and in the child in the first two years of life.
04.4 Special warnings and appropriate precautions for use
Perform a basic ECG before starting treatment (see section 4.3).
Monitor the ECG during therapy based on the patient's clinical condition.
During therapy, reduce dosage if QT prolongation is observed and discontinue if QTc is> 500ms.
Periodic checking of electrolytes is recommended.
Avoid concomitant therapy with other neuroleptics.
Rare cases of sudden death have been reported in psychiatric patients treated with antipsychotic drugs, including HALDOL.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Patients treated with antipsychotic drugs often have acquired risk factors for VTE; therefore all possible risk factors for VTE must be identified before and during HALDOL therapy and preventive measures undertaken.
Increased mortality in older people with dementia
Data from two large observational studies have shown that the risk of death is slightly increased in older people with dementia treated with antipsychotics than in untreated people. There are insufficient data to accurately estimate the magnitude of the risk and the cause of the increased risk is not known.
HALDOL is not licensed for the treatment of dementia-related behavioral disorders.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs show an increased risk of death. Analysis of seventeen placebo-controlled clinical trials (10-week modal duration), predominantly in patients receiving atypical antipsychotic drugs, revealed a 1.6- to 1.7-fold increased risk of death in drug-treated patients. compared with placebo. In a 10-week controlled clinical trial with a typical drug, the mortality rate was approximately 4.5% in drug-treated patients compared to approximately 2.6% in the drug-treated group. placebo. Although the causes of death varied, most deaths appeared to be cardiovascular (e.g. heart failure, sudden death) or infectious (e.g. pneumonia). Observational studies suggest that, like atypical antipsychotics, treatment with conventional antipsychotics may increase mortality. In this context, it is unclear whether the increased mortality observed in observational studies can be attributed to antipsychotics or conversely to some characteristics of patients.
Cardiovascular effects
Cases of QT interval prolongation and / or ventricular arrhythmias, in addition to rare cases of sudden death, have been reported very rarely with haloperidol and may occur more frequently with high drug doses and in predisposed patients.
Since QT interval prolongation has been observed during HALDOL therapy, caution is recommended in patients with conditions predisposing to QT prolongation (prolonged QT syndrome, hypokalaemia, electrolyte imbalance, drugs that cause QT prolongation. , cardiovascular disease, family history of QT prolongation) especially if HALDOL is administered parenterally (see section 4.5).
The risk of QT interval prolongation and / or ventricular arrhythmias may increase with high doses (see sections 4.8 and 4.9) or when the medicinal product is administered parenterally.
HALDOL should not be administered intravenously, as intravenous administration of haloperidol has been associated with an increased risk of QT prolongation and Torsade de Pointes.
Tachycardia and hypotension have also been reported in occasional patients.
Neuroleptic malignant syndrome
Like other antipsychotic drugs, HALDOL has also been associated with neuroleptic malignant syndrome: a rare and idiosyncratic response characterized by hyperthermia, generalized muscle rigidity, autonomic instability, altered state of consciousness. Hyperthermia is often an early symptom of this syndrome. Antipsychotic treatment should be discontinued immediately and appropriate supportive care and careful monitoring instituted.
Tardive dyskinesia
As with all antipsychotic drugs, tardive dyskinesia may occur in some patients on long-term therapy or after discontinuation of therapy. This syndrome is mainly characterized by involuntary rhythmic movements of the tongue, face, mouth or jaw. Manifestations may be permanent in some patients. The syndrome may be masked by resuming treatment, increasing the dose or switching to another antipsychotic. Treatment should be stopped as soon as possible.
Extrapyramidal symptoms
As with all neuroleptics, extrapyramidal symptoms may arise, eg tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia.
Anticholinergic antiparkinsonian drugs may be prescribed if necessary, but should not be used routinely as a preventative measure. If concomitant treatment with antiparkinsonian drugs is necessary it should be continued after discontinuation of HALDOL, if their excretion is faster than that of HALDOL, in order to avoid the development or aggravation of extrapyramidal symptoms. The physician should consider what is possible. increased intraocular pressure due to anticholinergic drugs, including antiparkinsonian agents, when administered concomitantly with HALDOL.
Safety data available in the pediatric population indicate a risk of extrapyramidal symptoms, including tardive dyskinesia and sedation. No long-term safety data are available.
Seizures / Convulsions
The onset of seizures triggered by HALDOL has been reported. Caution is advised in epileptic patients and in conditions predisposing to seizures (eg alcohol withdrawal and brain damage).
Hepatobiliary effects
As HALDOL is metabolised by the liver, caution is recommended in patients with liver disease. There have been isolated reports of abnormal liver function or hepatitis, most often cholestatic.
Effects on the endocrine system
Thyroxine can facilitate the toxicity of HALDOL. Antipsychotic therapy in patients with hyperthyroidism should only be undertaken with great caution and should always be accompanied by therapy to achieve a euthyroid state.
The hormonal effects of neuroleptic antipsychotics include hyperprolactinaemia, which can cause galactorrhea, gynaecomastia, and oligo- or amenorrhea. Very rare cases of hypoglycaemia and ADH Inappropriate Secretion Syndrome have been reported.
Additional considerations
In schizophrenia, the response to antipsychotic drug treatment may be delayed. Even if the drugs are stopped, the resumption of symptoms may not appear visible for several weeks or months. Acute withdrawal symptoms including nausea, vomiting and insomnia have been described very rarely after abrupt withdrawal of high doses of antipsychotic drugs. Psychotic relapse can also occur, so a gradual withdrawal is recommended. As with all antipsychotics, HALDOL should not be used alone in cases where depression is predominant. HALDOL can be associated with antidepressant drugs in conditions where depression and psychosis coexist.
Important information about some of the ingredients
The tablets contain Lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
The 1 mg tablets also contain sucrose: patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
As with other antipsychotics, use caution when prescribing haloperidol along with other drugs that induce QT interval prolongation.
Haloperidol follows several metabolic pathways including glucuronidation and the cytochrome P450 system (particularly CYP 3A4 or CYP2D6). Inhibition of these metabolic pathways by another drug or a decrease in the enzymatic activity of CYP 2D6 may cause increased haloperidol concentration and an increased risk of adverse events including QT prolongation.
Mild to moderate increases in haloperidol concentration have been reported in pharmacokinetic studies when co-administered with substrates or inhibitors of CYP 3A4 or CYP 2D6 isoenzymes such as itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, serthal chlorpromazine and promethazine. A decrease in CYP 2D6 enzyme activity may cause increased concentrations of haloperidol. Increases in QTc have been observed when haloperidol was administered with a combination of the metabolic inhibitors ketoconazole (400 mg / day) and paroxetine (20 mg / day). die). In this case it may be necessary to reduce the haloperidol dose.
Caution should be used when administering haloperidol in combination with drugs that can cause electrolyte imbalance.
Effects of other drugs on haloperidol
When prolonged treatment with enzyme inducers such as carbamazepine, phenobarbital, rifampicin is added to HALDOL therapy, a significant decrease in plasma haloperidol levels may occur. Therefore, during the combined treatment, the dose of HALDOL should be adjusted if necessary. After discontinuation of such drugs it may be necessary to reduce the dosage of HALDOL.
Sodium valproate, a drug known as a glucuronidation inhibitor, does not affect the plasma levels of haloperidol.
Effects of haloperidol on other drugs
Like all neuroleptics, HALDOL may enhance the CNS depressant action of other drugs, including alcohol, hypnotics, sedatives, or strong analgesics.
An enhancement of these effects has also been reported when combined with methyldopa.
HALDOL can antagonize the action of adrenaline and other sympathomimetic agents and reverse the hypotensive effect of adrenergic blocking agents, such as eg guanethidine.
HALDOL may decrease the antiparkinsonian effects of levodopa.
Haloperidol is a CYP 2D6 inhibitor.
Do not administer concomitantly with QT prolonging drugs such as some class Ia antiarrhythmics (e.g. quinidine, disopyramide and procainamide) and class III (e.g. amiodarone, sotalol), some antihistamines, other antipsychotics and some antimalarials (e.g. quinine and mefloquine) and also moxifloxacin.
This list is to be considered only indicative and not exhaustive.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Concomitant use of diuretics, particularly those that can cause hypokalaemia, should be avoided.
HALDOL inhibits the metabolism of tricyclic antidepressants, thereby increasing their plasma levels.
Other forms of interaction
In rare cases, the following symptoms have been reported during concomitant use of lithium and HALDOL: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, brain stem disorders, acute brain syndrome and coma. Most of these symptoms were Reversible It remains controversial whether these symptoms are related to co-administration or whether they are the manifestation of a distinct clinical episode.
Nevertheless, it is recommended that, in patients treated concomitantly with HALDOL and lithium, therapy is stopped immediately if these symptoms appear.
An "antagonistic action on" the effect of the anticoagulant phenindione has been reported.
04.6 Pregnancy and lactation
Animal studies have shown a teratogenic effect of haloperidol (see section 5.3).
Infants exposed to conventional or atypical antipsychotics including HALDOL during the third trimester of pregnancy are at risk for side effects including extrapyramidal or withdrawal symptoms which may vary in severity and duration after birth. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, food intake disturbances. Infants should therefore be closely monitored.
Not to be used in case of confirmed or presumed pregnancy, nor during breastfeeding.
04.7 Effects on ability to drive and use machines
HALDOL can cause sedation and reduced attention, especially with higher doses and at the beginning of treatment; these effects can be enhanced by alcohol. Patients should be advised not to drive or operate machinery during treatment until their reactivity to the drug is ascertained.
04.8 Undesirable effects
Clinical trial data
Data from Double-Blind Placebo Controlled Studies - Adverse Drug Reactions Reported at ≥ 1% Incidence
The safety of HADOL (2-20 mg / day) was evaluated in 566 subjects (including 284 treated with HALDOL and 282 with placebo) participating in 3 double-blind placebo-controlled clinical trials, two in the treatment of schizophrenia and the third in the treatment of bipolar disorder.
Adverse drug reactions (ADRs) reported by ≥ 1% of subjects treated with HALDOL in these studies are shown in Table 1.
Table 1. Adverse Drug Reactions Reported by ≥ 1% of HALDOL-Treated Subjects Participating in 3 Double-Blind HALDOL Clinical Trials in Parallel to Placebo.
Active Controlled Clinical Trial Data - Adverse Drug Reactions Reported at ≥ 1% Incidence
Sixteen double-blind, active-controlled clinical trials were selected to determine the incidence of ADRs. In these 16 studies 1295 subjects were treated with HALDOL at a dose of 1-45 mg / day for the treatment of schizophrenia.
The ADRs reported by ≥ 1% of HALDOL-treated subjects observed in these studies are shown in Table 2.
Table 2. Adverse Drug Reactions Reported by ≥ 1% of HALDOL-Treated Subjects in 16 Double-Blind Controlled Clinical Trials of HALDOL
Data from placebo and active controlled clinical trials - Adverse drug reactions reported at incidence
Additional ADRs that occurred in
Table 3. Adverse drug reactions reported by
Postmarketing data
The first adverse events identified as ADRs during the postmarketing experience with haloperidol are included in Table 4. The post-marketing review is based on the review of all cases in which the active part of haloperidol (HALDOL and HALDOL DECANOAS) was administered. In each table the frequencies are provided according to the following convention:
In Table 4 ADRs are shown by frequency class based on spontaneous reporting rate.
Table 4. Adverse drug reactions during postmarketing experience with haloperidol (oral, solution or decanoate) reported by frequency category estimated from spontaneous reporting rates
Rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been observed with HALDOL and other drugs of the same class.
Very rare cases of sudden death.
Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis, have been reported with antipsychotic drugs - Frequency not known.
04.9 Overdose
Symptoms:
The manifestations of overdose are those deriving from an exaltation of the known pharmacological effects and adverse reactions. The main symptoms are: intense extrapyramidal reactions, hypotension and sedation. An extrapyramidal reaction manifests itself with muscle stiffness and generalized or localized tremor.
In extreme cases, the patient may manifest a comatose state with respiratory depression and severe arterial hypotension, leading to a shock-like state. The risk of ventricular arrhythmias possibly associated with prolongation of the QT interval of the electrocardiogram should also be considered.
Treatment:
There is no specific antidote. Treatment is mainly supportive but gastric lavage or induction of vomiting is still recommended (unless the patient is sedated, comatose or convulsing) followed by the administration of activated charcoal.
In comatose patients, a patent airway should be established by tracheostomy or intubation. Respiratory depression may require artificial respiration. The ECG and vital signs should be monitored until the ECG is restored to normal.
Severe arrhythmias should be treated with appropriate antiarrhythmic measures.
Hypotension and circulatory collapse can be treated by intravenous infusion of fluids, plasma or concentrated albumin or the use of vasopressor agents such as dopamine or noradrenaline. Adrenaline should not be used as it may cause severe hypotension in the presence of HALDOL.
In case of severe extrapyramidal reactions, anti-parkinson drugs (eg benztropine mesylate: 1-2 mg IM or IV) should be administered parenterally.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antipsychotic, derivative of butyrophenone.
ATC code: N05AD01
Haloperidol is a neuroleptic belonging to the group of butyrophenones. Haloperidol is a potent dopamine antagonist; it has similar affinity for all dopamine receptor subtypes: it is therefore a non-selective dopaminergic antagonist. The drug also has antagonistic activity towards α-adrenergic receptors, while it does not exhibit antihistaminergic or anticholinergic activity.
The drug's effect on delirium and hallucinations is believed to be linked to dopaminergic antagonism in the mesocortical and limbic regions.
Antagonism in the basal ganglia is probably the cause of the extrapyramidal motor side effects (dystonia, akathisia and parkinsonism).
Haloperidol has an effective psychomotor sedative effect which contributes to the favorable action on mania and other agitation syndromes.
Haloperidol has also been shown to be useful in the treatment of chronic pain, an effect possibly due to limbic action.
The more peripheral anti-dopaminergic effects explain the activity against nausea and vomiting (antagonism at the level of chemoreceptor trigger zone, CTZ), the increased release of prolactin (through the antagonism towards the inhibition activity, mediated by dopamine, of the release of prolactin by the adenohypophysis) and the relaxation of the gastrointestinal sphincters.
05.2 Pharmacokinetic properties
Absorption
After oral administration, the bioavailability of the drug is 60-70% of the administered dose; maximum plasma concentrations are reached between 2 and 6 hours. After intramuscular administration, the peak concentration is reached after 20 minutes.
Distribution
Haloperidol easily crosses the blood-brain barrier. The drug is 92% bound to plasma proteins. The steady-state volume of distribution (Vdss) is high (7.9 ± 2.5 L / kg)
Metabolism
Haloperidol is metabolised by several pathways, including the cytochrome P450 enzyme system (particularly CYP 3A4 or CYP 2D6) and glucuronidation.
Elimination
The terminal plasma half-life (terminal elimination) is on average 24 hours (12 ÷ 38 hours) after oral administration and 21 hours (13 ÷ 36 hours) after intramuscular administration
Excretion occurs via the faecal (60%) and urinary (40%) routes. Approximately 1% of the ingested dose is excreted as unchanged drug in the urine
Therapeutic concentrations
It has been suggested that the therapeutic response is achieved with a range of haloperidol plasma concentrations between 4 mcg / l and 20-25 mcg / l.
05.3 Preclinical safety data
Non-clinical data based on conventional studies of repeated dose toxicity, genotoxicity and carcinogenicity did not reveal any particular hazard for humans.
In rodents the administration of haloperidol has shown a decrease in fertility and limited teratogenic and embryotoxic effects.
In several published studies in vitro, haloperidol has shown the ability to block the cardiac hERG channel.
In some studies conducted in vivo In animal models, intravenous haloperidol administration caused significant QTc prolongation, at doses equal to 0.3 mg / kg iv, showing a peak blood concentration Cmax 3 to 7 times higher than the effective plasma concentration of 4- 20 ng / ml obtained in man.
These intravenously administered doses that cause QTc interval prolongation did not cause arrhythmias. In some studies a higher dose of 1 to 5 mg / kg administered intravenously caused QTc prolongation and / or ventricular cardiac arrhythmias. a peak plasma concentration Cmax 19 to 68 times greater than the effective plasma concentrations in humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
1 mg tablets: lactose, corn starch, sucrose, hydrogenated sunflower seed oil, talc.
5 mg tablets: lactose, indigo carmine (E132), corn starch, sunflower seed oil, talc
Oral drops, solution 2 mg / ml: lactic acid, methyl-para-hydroxybenzoate, purified water.
Solution for injection for intramuscular use: lactic acid, water for injections.
06.2 Incompatibility
Not relevant
06.3 Period of validity
Tablets:
1mg: 3 years
5mg: 5 years
Oral drops, solution: 5 years
Solution for injection for intramuscular use: 5 years
06.4 Special precautions for storage
Store at a temperature not exceeding 25 ° C
Solution for injection for intramuscular use: keep away from light.
06.5 Nature of the immediate packaging and contents of the package
HALDOL 30 tablets of 1 mg in PVC / Aluminum blister
HALDOL 30 tablets of 5 mg in PVC / Aluminum blister
HALDOL bottle 30 ml oral drops, solution 2 mg / ml in HPDE bottle with dropper in LPDE.
HALDOL 5 ampoules of 1 ml solution for injection for intramuscular use 5 mg / ml in amber yellow Type I glass ampoules.
06.6 Instructions for use and handling
Oral drops, solution:
HALDOL is available in 30ml bottles with dropper device and child resistant closure. To open, push the plastic cap down firmly, then unscrew. After removing the cap, pour the required number of drops using the dropper.
Solution for injection for intramuscular use:
Break the vials as indicated below.
07.0 MARKETING AUTHORIZATION HOLDER
- Janssen-Cilag SpA
Via M. Buonarroti, 23
20093 Cologno Monzese (MI)
08.0 MARKETING AUTHORIZATION NUMBER
HALDOL 1 mg tablets: 30 tablets 025373010
HALDOL 5 mg tablets: 30 tablets 025373034
HALDOL 2 mg / ml oral drops, solution: bottle of 30 ml 025373059
HALDOL 5 mg / ml solution for injection for intramuscular use: 5 ampoules of 1 ml 025373073
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
07.06.1984 / May 2010
10.0 DATE OF REVISION OF THE TEXT
January 2014
