Each mL contains 5 mg of Haloperidol, BP.
Inactives: Lactic acid, Sodium hydroxide.
Pharmacology: Pharmacodynamics: Haloperidol is a member of the butyrophenone class of neuroleptic drugs. The antipsychotic, anti-anxiety and anti-emetic effects of haloperidol have been well demonstrated. Although the precise mechanism of action has not been elucidated, antagonism of dopamine-mediated synaptic neurotransmission appears to be an important action of haloperidol and may be the primary action through which the antipsychotic and extrapyramidal neurologic effects are mediated.
Within the autonomic nervous system, haloperidol displays weak anticholinergic activities. Orthostatic hypotension that is mediated by a combination of central actions and peripheral alpha-adrenergic blockade occurs less frequently during treatment with haloperidol in comparison with other antipsychotic therapy. Haloperidol binds to opiate receptors.
Pharmacokinetics: Haloperidol is well absorbed from the intramuscular sites. Variable bioavailability is likely due to the extent of first-pass hepatic metabolism. Metabolism is by oxidative dealkylation. The elimination half-life is approximately 20 hours. Haloperidol extensively bound to plasma proteins, is widely distributed throughout the body and crosses the blood-brain barrier. Metabolites of haloperidol appear to be inactive and excretion occurs via urine and faeces.
Haloperidol Injection is indicated for use in the treatment of schizophrenia.
Haloperidol injection is indicated for the control of tics and vocal utterances of Tourette's Disorder.
To determine the initial dosage, consideration should be given to the patient's age, severity of illness, previous response to other antipsychotic drugs, and any concomitant medication or disease state. Debilitated or geriatric patients, as well as those with a history of adverse reactions to antipsychotic drugs, may require less haloperidol. The optimal response in such patients is usually obtained with more gradual dosage adjustments and at lower dosage levels.
Parenteral medication, administered intramuscularly in doses of 2 to 5 mg, is utilized for prompt control of the acutely agitated schizophrenic patient with moderately severe to very severe symptoms. Depending on the response of the patient, subsequent doses may be given, administered as often as every hour, although 4 to 8 hour intervals may be satisfactory. The maximum dose is 20 mg/day.
Switchover Procedure: An oral form should supplant the injectable as soon as practicable. In the absence of bioavailability studies establishing bioequivalence between these two dosage forms the following guidelines for dosage are suggested. For an initial approximation of the total daily dose required, the parenteral dose administered in the preceding 24 hours may be used. Since this dose is only an initial estimate, it is recommended that careful monitoring of clinical signs and symptoms, including clinical efficacy, sedation, and adverse effects, be carried out periodically for the first several days following the initiation of switchover. In this way, dosage adjustments, either upward or downward, can be quickly accomplished. Depending on the patient's clinical status, the first oral dose should be given within 12-24 hours following the last parenteral dose.
In general, the symptoms of overdosage would be an exaggeration of known pharmacologic effects and adverse reactions, the most prominent of which would be: 1) severe extrapyramidal reactions, 2) hypotension, or 3) sedation. Since there is no specific antidote, treatment is primarily supportive.
Haloperidol Injection is contraindicated in severe toxic central nervous system depression or comatose states from any cause and in individuals who are hypersensitive to this drug or have Parkinson's disease.
Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Haloperidol Injection is not approved for the treatment of patients with dementia-related psychosis.
Cardiovascular Effects: HALOPERIDOL INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION. lf Haloperidol Injection is administered intravenously, the ECG should be monitored for QT prolongation and arrhythmias
Tardive Dyskinesia: A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs.
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Geriatric Use: Prevalence of tardive dyskinesia appears to be highest among the elderly, especially elderly women. Also, the pharmacokinetics of haloperidol in geriatric patients generally warrants the use of lower doses.
Pregnancy: Pregnancy Category C: Haloperidol should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Lactation: Since haloperidol is excreted in human breastmilk, infant should not be nursed during drug treatment with haloperidol.
General Disorders and Administration Site Conditions:
Injection Site Reaction
Tachycardia, hypotension, and hypertension have been reported. QT-prolongation and/or ventricular arrhythmias have also been reported, in addition to ECG pattern changes compatible with the polymorphous configuration of Torsades de Pointes, and may occur more frequently with high doses and in predisposed patients.
Extrapyramidal disorder; Hyperkinesia; Headache, Tardive dyskinesia; Oculogyric Crisis; Dystonia; Dyskinesia; Akathisia; Bradykinesia; Hypokinesia; Hypertonia; Somnolence; Masked Facies, Tremor; Dizziness.
Constipation; Dry mouth; salivary hypersecretion; Nausea; Vomiting.
Skin and subcutaneous tissue disorders:
Pharmacodynamic Interactions: Since QT-prolongation has been observed during haloperidol treatment, caution is advised when prescribing to patient with QT-prolongation conditions (long QT-syndrome, hypokalemia, electrolyte imbalance) or to patients receiving medications known to prolong the QT-interval or known to cause electrolyte imbalance.
If concomitant antiparkinson medication is required, it may have to be continued after haloperidol is discontinued because of the difference in excretion rates.
As with other antipsychotic agents, it should be noted that haloperidol may be capable of potentiating CNS depressants such as anesthetics, opiates and alcohol.
Ketoconazole is a potent inhibitor of CYP3A4. Increases in QTc have been observed when haloperidol was given in combination with the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day). It may be necessary to reduce the haloperidol dosage.
Pharmacokinetic Interactions: The Effect of Other Drugs on Haloperidol: Haloperidol is metabolized by several routes, including the glucuronidalion and the cytochrome P450 enzyme system. Inhibition of these routes of metabolism by another drug may result in increased haloperidol concentrations and potentially increase the risk of certain adverse events, including QT-prolongation.
Drugs Characterized as Substrates, Inhibitors or Inducers of CYP3A4, CYP2D6 or Glucuronidation: In pharmacokinetic studies, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs characterized as substrates or inhibitors of CYP3A4 or CYP2D6 isoenzymes, such as, itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fiuvoxamine, quinidine, fiuoxetine, sertraline, chlorpromazine, and promethazine.
When prolonged treatment (1 to 2 weeks) with enzyme-inducing drugs such as rifampin or carbamazepine is added to haloperidol therapy, this results in a significant reduction of haloperidol plasma levels.
Rifampin: In a study of 12 schizophrenic patients coadministered oral haloperidol and rifampin, plasma haloperidol levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other schizophrenic patients treated with haloperidol and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in haloperidol concentrations.
Carbamazepine: In a study in 11 schizophrenic patients co-administered haloperidol and increasing doses of carbamazepine, haloperidol plasma concentrations decreased linearly with increasing carbamazepine concentrations. Thus, careful monitoring of clinical status is warranted when enzyme inducing drugs such as rifampin or carbamazepine are administered or discontinued in haloperidol-treated patients. During combination treatment, the haloperidol dose should be adjusted, when necessary. After discontinuation of such drugs, it may be necessary to reduce the dosage of haloperidol.
Valproate: Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.
Store in a dry place below 30°C. Protect from light.
N05AD01 - haloperidol ; Belongs to the class of butyrophenone derivatives antipsychotics.
Soln for inj (for IM only, type I clear glass ampoule) 5 mg/mL x 1 mL x 5's.