Date of approval.
Date of revision.
Haloperidol Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Warnings
Treatment of elderly patients with dementia-related psychotic disorders with atypical antipsychotics is associated with an increased risk of death. An analysis of 17 placebo-controlled clinical trials (mean duration of treatment 10 weeks) in elderly patients with dementia-related psychotic disorders found that the risk of death was 1.6-1.7 times greater in the drug-treated group than in the placebo-controlled group. In a typical 10-week controlled clinical trial, the mortality rate was approximately 4.5% in the drug-treated group and 2.6% in the placebo-controlled group. Although the causes of death varied, most deaths were due to cardiovascular disease (e.g., heart failure, sudden death) or infection (e.g., pneumonia). Observational studies have shown that, similar to atypical antipsychotics, the use of typical antipsychotics increases mortality. The results of increased mortality in observational studies may be that the characteristics of some patients using antipsychotics are unclear. Haloperidol is not approved for the treatment of dementia-related psychotic disorders (see [Precautions]).
Drug Name]
Generic Name: Haloperidol Tablets
English Name: Haloperidol Tablets
Chinese Pinyin: Fupaidingchun Pian
Ingredients
The main ingredient of this product is haloperidol.
Chemical name: 1-(4-fluorophenyl)-4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-butanone.
Chemical structure formula.
Molecular formula: C21H23ClFNO2
Molecular weight: 375.87
【Properties】.
This product is white or off-white indented tablets.
Indications】
It is used for acute and chronic schizophrenia of all types, mania, and tic and obscene syndrome. It is more effective in controlling excitement and agitation, hostility and aggressive behavior. It can also be used for cerebral organic mental disorder and geriatric mental disorder because it has less adverse effects on the cardiovascular system.
Specification
2mg
Dosage
For the treatment of schizophrenia, start with a small oral dose of 2-4mg (1-2 tablets) once, 2-3 times a day. Gradually increase to the usual dose of 10-40mg (5-20 tablets) a day and the maintenance dose of 4-20mg (2-10 tablets) a day. For the treatment of Tourette’s syndrome, 1~2mg (0.5-1 tablet) once, 2~3 times a day.
[Adverse effects].
1. Cardiovascular effects
Tachycardia, hypotension and hypertension have been reported with the administration of haloperidol. In addition, QT prolongation and/or ventricular arrhythmias have been reported in addition to ECG changes consistent with polymorphic tip-twist ventricular tachycardia, which are more likely to occur in high-dose and susceptible patients (see [Precautions]).
Cases of sudden and unexpected death have been reported with haloperidol treatment, and it is not possible to determine the role of haloperidol in the outcome of the reported cases, but the possibility of haloperidol-induced death cannot be ruled out. In addition, sudden and unexpected deaths may occur in psychiatric patients not treated with haloperidol or treated with other antipsychotic medications.
2. Central nervous system (CNS) reactions
Extrapyramidal reactions (EPS)
Extrapyramidal reactions during haloperidol administration have been frequently reported and usually occur during the first few days of treatment. Extrapyramidal reactions can be broadly classified as Parkinson’s syndrome-like symptoms, inability to sit still, or dystonia (including keratoconus and actinic crisis). Once these symptoms occur at low doses, there is a greater likelihood that they will occur at higher doses and that they will be more severe. These symptoms can be controlled by reducing the dose or by giving antiparkinsonian drugs such as benztropine mesylate or benzhexol hydrochloride. Of note, persistent extrapyramidal reactions have been reported, in which case the drug needs to be discontinued.
Dystonia
Class effect: Symptoms of abnormal muscle tone, manifested by abnormally prolonged contractions of muscle groups, may occur in those patients who are susceptible during the first few days of drug therapy. Dystonia symptoms include: muscle spasms in the neck, sometimes manifested by progressive throat tightness, dysphagia, dyspnea, and/or tongue protrusion. Once these symptoms occur at low doses of first-generation antipsychotics, there is a greater likelihood that they will be more likely to occur at higher doses and that the symptoms will be more severe. An increased risk of acute dystonia has been observed in younger male populations.
Withdrawal symptoms
Often, patients receiving short-term treatment can be abruptly discontinued from antipsychotic medications. However, some patients who require maintenance treatment experience transient symptoms of dyskinesia after abrupt discontinuation. In some cases, the movement disorder is indistinguishable from the syndrome described under “delayed-onset movement disorder” below, except for its duration. It is unclear whether tapering off antipsychotics will reduce the incidence of withdrawal symptoms, but until more evidence is available, tapering off haloperidol is recommended.
Delayed-onset movement disorder
As with all antipsychotics, haloperidol is associated with persistent dyskinesia. Delayed dyskinesia is a syndrome of potentially irreversible, involuntary movement disorders that may occur in some patients on long-term treatment or after discontinuation of medication. Older patients (especially women) receiving high doses of therapy appear to be at greater risk. These symptoms are persistent and irreversible for some patients. The syndrome is characterized by rhythmic involuntary movements of the tongue, face, mouth, and jaw (e.g., tongue protrusion, cheek swelling, mouth wrinkling, masticatory movements). It may sometimes be accompanied by involuntary movements of the limbs and trunk.
There is no definitive treatment for tardive dyskinesia; anti-Parkinsonian medications usually do not relieve the symptoms of the syndrome. If symptoms of tardive dyskinesia develop, it is recommended that all antipsychotic medications be discontinued. If treatment is resumed, or if the dose is adjusted, or if treatment is switched to other antipsychotic medications, the symptoms of tardive dyskinesia may be masked.
It has been reported that tiny tongue wriggles may be an early sign of delayed-onset movement disorder and may not progress to full syndrome if the medication is discontinued at this time.
Other central nervous system (CNS) reactions
Insomnia, irritability, anxiety, euphoria, agitation, sleepiness, depression, drowsiness, headache, confusion, vertigo, grand mal seizures, worsening of psychotic symptoms including hallucinations and catatonic behavioral states (these states may be associated with anticholinergic withdrawal and/or treatment).
Systemic: Neuroblocker malignant syndrome (NMS), high fever, and heat shock have been reported with haloperidol (see [Precautions]).
Hematologic: Slight and transient leukopenia and leukocytosis, slight decrease in red blood cell count, anemia, or lymphocytosis. Granulocyte deficiency occurs rarely with haloperidol and only in combination with other drugs.
Liver: impaired liver function and/or jaundice.
Skin: maculopapular rash, acne, photosensitivity, and alopecia.
Endocrine system: breast overflow, breast swelling, breast pain, irregular menstruation, feminization of the male breast, impotence, increased libido, hyperglycemia, hypoglycemia and hyponatremia.
Gastrointestinal system: anorexia, constipation, diarrhea, excessive salivation, indigestion, nausea and vomiting.
Autonomic reactions: dry mouth, blurred vision, urinary retention, sweating and abnormal penile erection.
Respiratory: laryngospasm, bronchospasm and increased depth of breathing.
Other: cataracts, retinopathy and visual disturbances.
3. Post-marketing events
Hyperammonemia was reported in a five-and-a-half-year-old child with guanosineemia, an inherited disorder of ammonia excretion, following the use of haloperidol.
[Contraindication
Basal ganglion lesions, Parkinson’s disease, Parkinson’s syndrome, those with severe central nervous depression, myelosuppression, glaucoma, myasthenia gravis and those with hypersensitivity to this product.
[Precautions].
Increased mortality in elderly patients with dementia-related psychosis
Treatment of elderly patients with dementia-related psychotic disorders with atypical antipsychotics increases the risk of death. An analysis of 17 placebo-controlled clinical trials (mean treatment duration 10 weeks) in elderly patients with dementia-related psychotic disorders found that the risk of death was 1.6-1.7 times greater in the drug-treated group than in the placebo-controlled group. In a typical 10-week controlled clinical trial, the mortality rate was approximately 4.5% in the drug-treated group and 2.6% in the placebo-controlled group. Although the causes of death varied, most deaths were due to cardiovascular disease (e.g., heart failure, sudden death) or infection (e.g., pneumonia). Observational studies have shown that, similar to atypical antipsychotics, the use of typical antipsychotics increases mortality. The results of increased mortality in observational studies may be that the characteristics of some patients using antipsychotics are unclear. Haloperidol is not approved for the treatment of dementia-related psychotic disorders (see [cautionary note]).
Cardiovascular Effects
Cases of sudden death, QT prolongation, and tip-twist ventricular tachycardia have been reported in patients treated with haloperidol. Administration of higher than recommended doses of haloperidol increases the risk of QT prolongation and tip-twisting ventricular tachycardia. Cases have been reported even in the absence of predisposing factors, and special caution is advised when treating other QT-prolonging conditions, including electrolyte disorders [especially hypokalemia and hypomagnesemia], administration of drugs known to prolong QT, underlying heart rate abnormalities, hypothyroidism, and familial long QT syndrome.
Delayed-onset movement disorder syndrome
Delayed dyskinesia syndrome may occur in patients treated with antipsychotics. Although the syndrome appears to be most prevalent in older adults (especially older women), it is difficult to rely on prevalence estimates to predict which patients are likely to develop the syndrome during the initial phase of antipsychotic treatment. Whether there are differences in the likelihood of antipsychotic medications causing delayed-onset dyskinesia is unclear.
The risk and incidence of delayed-onset movement disorder syndrome increases with duration of therapy and cumulative dose and is irreversible. However, delayed-onset dyskinesia syndrome can occur in a few cases when treated with small doses and short courses of therapy.
There is no definitive treatment for delayed-onset dyskinesia syndrome, but the syndrome can be partially or fully resolved after discontinuation of medication. Antipsychotic medication itself can suppress (or partially suppress) the signs and symptoms of tardive dyskinesia syndrome, thereby masking its course. The mechanism of action for the suppression of symptoms in the long-term course of the late-onset movement disorder syndrome is unclear.
Given these considerations, antipsychotic medications should be prescribed to minimize the occurrence of delayed-onset movement disorder syndrome. Chronic antipsychotic medication is generally given only to patients with chronic conditions that are 1) known to respond to antipsychotics and 2) for which no other equally effective, but potentially less harmful, treatment is available. For patients requiring long-term treatment, the lowest possible dose and shortest possible course of treatment should be used to achieve satisfactory clinical outcomes. Continuation of treatment should be evaluated periodically.
Patients on antipsychotics who develop signs and symptoms of delayed dyskinesia may be considered for treatment interruption. However, some patients may require continued antipsychotic treatment (see [Adverse Reactions]).
Neuroblocker malignant syndrome (NMS)
Neuroblocker malignant syndrome (NMS) is a potentially life-threatening disorder that can be caused by antipsychotic medications. Clinical manifestations include hyperthermia, muscle tonicity, altered mental status (including catatonic psychiatric symptoms) and autonomic dysregulation (irregular pulse rate or blood pressure, tachycardia, sweating and arrhythmias). Other signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
The diagnostic evaluation of neural blocker malignant syndrome is more complex. In giving the diagnosis, it is important to distinguish it from signs and symptoms of severe medical illness (e.g., pneumonia, systemic infections, etc.) and untreated or inadequately treated extrapyramidal reactions (EPS). It is also important to distinguish from toxic reactions to central antiparasympathetic effects, heat shock, drug fever, and primary CNS disease.
Management of NMS includes 1) immediate discontinuation of antipsychotics and other medications that are unnecessary for concurrent treatment, 2) intensive symptomatic treatment and clinical monitoring, and 3) special management of other serious complications. There is no consensus on whether to provide special management for non-severe NMS.
If patients still require antipsychotic medication after recovery from NMS, careful consideration should be given and close monitoring should be performed to prevent relapse.
High fever and heat shock unrelated to the above syndrome have been reported with the application of haloperidol.
Falls
Haloperidol can cause drowsiness, postural hypotension, motor and sensory instability, which can lead to falls that can result in fractures or other injuries. For patients whose own illness, symptoms or medication may exacerbate these effects, risk assessment should be performed at the time of initiation of antipsychotic treatment and repeatedly during the patient’s long-term use of antipsychotic therapy.
Other
Numerous cases of bronchopneumonia, some of them fatal, have occurred following the use of antipsychotics, including haloperidol. It is hypothesized that drowsiness and decreased thirst due to central depression may lead to dehydration, hemoconcentration, and decreased pulmonary ventilation. Once these signs and symptoms are noticed, especially in the elderly, prompt medical treatment should be sought.
Reduced serum cholesterol and/or skin and eye changes have been reported in patients receiving chemotherapy and have not been reported with haloperidol.
Haloperidol may impair the mental and/or physical abilities required for specific operations, such as operating machinery or motor vehicles. Patients need to be warned accordingly.
Concomitant use of haloperidol with alcohol should be avoided due to possible superimposed effects and hypotension.
Leukopenia, neutropenia and granulocyte deficiency
Cases of leukopenia/neutropenia have been reported in clinical trials and post-marketing studies of antipsychotic drugs, including haloperidol, and granulocyte deficiency (including fatal cases) has also been reported.
Risk factors for leukopenia/neutropenia include a preexisting low white blood cell count (WBC) and a history of leukopenia/neutropenia-inducing medications. Patients with a low white blood cell count (WBC) or taking leukopenia/neutropenia-inducing drugs should have their complete blood count (CBC) monitored frequently during the first few months of dosing and haloperidol should be discontinued as soon as a decline in white blood cell count (WBC) occurs in the absence of other causative factors.
Patients with neutropenia should be closely monitored for fever or other signs of infection and promptly treated. Haloperidol should be discontinued in patients with severe neutropenia (absolute neutrophil count <1000 / mm 3) until the white blood cell count (WBC) returns to normal.
Haloperidol should be used with caution in patients with
Severe cardiovascular disease with possible transient hypotension and/or exacerbation of angina pectoris. Vasopressin should be used when hypotension occurs and epinephrine should be avoided because haloperidol may have a reversal of adrenergic effects and further lower blood pressure. Instead, meprobamate, phenylephrine, or norepinephrine should be used.
Patients with a history of seizures or EEG abnormalities requiring antiepileptic drug therapy should be given concomitantly with appropriate anticonvulsant therapy, if necessary, because haloperidol may lower the threshold for convulsions.
Known allergy, or history of drug allergy.
Patients receiving anticoagulant therapy in whom an instance of interference between an anticoagulant (fexofenadine) and it has occurred.
If concomitant antiparkinsonian medication is required, it is necessary to continue the antiparkinsonian medication after discontinuation of haloperidol due to differences in excretion rates, and extra-pyramidal reactions may occur if both are discontinued. Remember that when anticholinergic drugs (including antiparkinsonian drugs) are given concomitantly with haloperidol, they may increase intraocular pressure.
Similar to other antipsychotics, haloperidol may potentiate the effects of central nervous system (CNS) depressants, such as narcotics, opioids, and alcohol.
In a study of 12 patients with schizophrenia given haloperidol and rifampin together, plasma haloperidol levels decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale improved from baseline. In another five schizophrenic patients given haloperidol and rifampin, discontinuation of rifampin resulted in a mean 3.3-fold increase in haloperidol concentrations. Therefore, patients treated with haloperidol need to be carefully monitored for clinical status if rifampin is given or discontinued.
When haloperidol is used to treat periodic disorder mania, mood may rapidly turn to depression.
Patients with thyrotoxicosis may experience severe neurotoxicity (rigidity, inability to walk or talk) when treated with antipsychotic medications, including haloperidol.
Antipsychotic drugs raise prolactin levels, and long-term use leads to persistently elevated prolactin levels. Tissue culture experiments have shown that about one-third of human breast cancers are prolactin-dependent, and the patient’s prior breast cancer needs to be taken into account when prescribing. The clinical significance of elevated serum prolactin levels is not known for most patients, although cases such as breast discharge, amenorrhea, gynecomastia, and impotence have been reported. Increased mammary tumors have been found in rodent studies following long-term antipsychotic drug use. To date, neither clinical nor epidemiological studies have found an association between long-term antipsychotic drug use and mammary tumorigenesis; the available evidence is limited and inconclusive at this time.
[For pregnant and lactating women].
Non-teratogenic effects
In late pregnancy, newborns exposed to antipsychotics are at risk for extrapyramidal and/or withdrawal symptoms after delivery. Agitation, hypertonia, hypotonia, tremor, lethargy, respiratory distress, and feeding disorders have been reported in such neonates. These complications vary in severity and in some cases the symptoms are self-limiting, while in other cases the neonate requires intensive care unit support and long-term hospitalization.
Haloperidol should be used in pregnancy only when the potential benefit outweighs the potential risk to the fetus.
Well-controlled studies have not been performed in pregnant women. However, cases of limb deformities have been reported and observed after the use of haloperidol and other drugs in the first trimester of pregnancy. However, a causal relationship has not been established in these cases. Since such experience does not exclude the possibility of fetal impairment with haloperidol, the drug should be used in women between pregnancies or possible pregnancies only if the benefit clearly outweighs the potential risk to the fetus. Breastfeeding should be discontinued during drug treatment.
For children]
Refer to the adult dose and reduce the dosage as appropriate.
Use in the elderly
The dose should be started in small doses and increased slowly to avoid extrapyramidal reactions and delayed dyskinesia.
Drug Interaction】 1.
1. When combined with ethanol or other CNS depressants, the central depressant effect is enhanced. Due to possible superimposed effects and hypotension, concomitant use of haloperidol with alcohol should be avoided.
2. Combination of this product with amphetamine may reduce the effect of the latter.
3. When combined with barbiturates or other anticonvulsants: it may alter the seizure form; it does not potentiate the anticonvulsants.
4. When combined with anti-hypertensive drugs, it can produce severe hypotension.
5. When combined with anticholinergic drugs, it may increase intraocular pressure.
6. Combination of this product with epinephrine may result in a decrease in blood pressure due to the blocking of alpha receptors and the predominance of beta receptor activity.
7. When this product is used in combination with lithium salts, neurotoxicity and brain damage need to be observed.
Encephalopathy syndrome (characterized by weakness, lethargy, fever, tremors and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) followed by irreversible brain injury has occurred in a small number of patients receiving lithium and haloperidol combination therapy. The causal relationship between these events and the combination of lithium and haloperidol is unclear. However, patients receiving the combination should be closely monitored for early signs of neurotoxicity and treatment should be discontinued immediately if such signs occur.
8. The combination of this product with methyldopa may produce impaired consciousness, slowed thinking, and disorientation.
9. Combination of this product with carbamazepine may decrease the blood concentration and diminish the effect of this product.
10. Drinking tea or coffee may reduce the absorption of this product and decrease the efficacy.
Drug overdose
Clinical manifestations
Usually, the symptoms of overdose are an amplification of known pharmacological effects and adverse reactions, the most prominent of which are 1) severe extrapyramidal reactions, 2) hypotension, and 3) sedation. Patients may experience coma accompanied by respiratory depression and hypotension severe enough to produce a shock-like state. Extrapyramidal reactions are manifested by muscle weakness or rigidity and generalized or localized tremor, which manifests as akinetic or tremulous type, respectively. Hypertension rather than hypotension occurs in 2-year-old children due to accidental overdose. The risk of ECG changes associated with tip-twisting ventricular tachycardia should be considered (see [Adverse Reactions]).
Treatment
Gastric lavage or emetic should be performed immediately, followed by administration of activated charcoal. Since no specific antagonist is available, supportive therapy is primarily used. A patent airway must be established through the use of an oropharyngeal airway or tracheal intubation, and in cases of prolonged coma, through tracheostomy. Respiratory depression can be relieved by artificial respiration and mechanical ventilators. Hypotension and circulatory collapse may be relieved by intravenous fluids, plasma or albumin concentrate, and vasopressors (e.g., meprobamate, phenylephrine, and norepinephrine); epinephrine should be avoided. If severe extrapyramidal reactions are identified, antiparkinsonian medication should be given. Monitoring of ECG and vital signs, especially signs of QT prolongation or arrhythmia, should be continued until the ECG is normal. Appropriate antiarrhythmic measures should be taken for severe arrhythmias.
Pharmacology and Toxicology
It is an antipsychotic of the butylphenyl group, and its antipsychotic effect is related to the blocking of dopamine receptors in the brain and promoting the conversion of dopamine in the brain, which has good anti-hallucinatory delusions and anti-excitation and agitation effects.
Pharmacokinetics]
Fast oral absorption, plasma protein binding rate of about 92%, bioavailability of 40%-70%, oral 3-6 hours to peak blood concentration, half-life (t1/2) of 21 hours. It is metabolized by the liver, and about 40% of a single oral dose is excreted in the urine within 5 days, of which 1% is the prodrug and the active metabolite is reduced haloperidol. About 15% is excreted by bile and the rest is excreted by kidney.
Storage】Store under light and seal.
Package】 High-density polyethylene bottle, 100 tablets/bottle.
Expiration date】 18 months
Execution Standard
Approval number】 State Drug Administration H33020585
[Drug Marketing Licensee
Company Name: Ningbo Da Hong Ying Pharmaceutical Co.
Registered Address: No. 396, Mingzhu Road, Ningbo Science and Technology Park, Ningbo, Zhejiang, China
Postal Code: 315040
Contact: 0574-87053888; 0574-87053826
Fax number: 0574-87053856; 0574-87053808
Web address: http://www.dhypharm.com
Manufacturer
Company name: Ningbo Da Hong Ying Pharmaceutical Co.
Address: No. 396, Mingzhu Road, Ningbo Science and Technology Park, Ningbo, Zhejiang, China
Postal Code: 315040
Contact：0574-87053888；0574-87053826
Fax number: 0574-87053856; 0574-87053808
Web address: http://www.dhypharm.com