Pericate

/ Unipharm

This Injection is intended for use in chronic psychotic patients who require prolonged parenteral antipsychotic therapy. These patients should be previously stabilised on antipsychotic medication before considering a conversion to this product. PERICATE is for use in adults only and has been formulated to provide a one month’s therapy for most patients following a single deep intramuscular injection in the gluteal region.
This product should not be administered intravenously. As the administration of volumes greater than 3 ml are uncomfortable for the patient, such large injection volumes are not recommended. Since individual response to neuroleptic drugs is variable, dosage should be individually determined and is best initiated and titrated under close clinical supervision. The individual starting dose will depend on both the severity of the symptomatology and the amount of oral medication required to maintain the patient before starting depot treatment. It is recommended that the initial dose will be 10-15 times the previous daily dose of oral haloperidol.
For most patients, this means a starting dose ranging between 25 and 75 mg of this product. A maximum starting dose of 100 mg should not be exceeded. Depending on the individual patient’s response the dose may gradually be increased by 50 mg until an optimal therapeutic effect is obtained. The most appropriate monthly dose is often about 20 times the daily dose of oral haloperidol. During dose adjustment or episodes of exacerbation of psychotic symptoms  therapy can be supplemented with regular haloperidol.
The usual time interval between injections is four weeks. However, variation in patient response may dictate a need for adjustment of the dosing interval.
Use in elderly and in debilitated patients: It is recommended to start with low doses, for example 12.5 mg-25 mg every 4 weeks, only increasing the dose according to the patient’s respons.

Chronic schizophrenia or other mental or behavioral problems which require maintenance treatment.

Comatose state; CNS depression due to alcohol or other depressant drug; Parkinson’s disease; known hypersensitivity to this product or its excipients [contains sesame oil]; lesion of the basal ganglia.
In common with other neuroleptics, haloperidol has the potential to cause rare prolongation of the QT interval. Use of haloperidol is therefore contra-indicated in patients with clinically significant cardiac disorders e.g recent acute myocardial infarction, uncompensated heart failure, arrhythmias treated with class IA and III antiarrhythmic medicinal products, QTc interval prolongation, history of ventricular arrhythmia or Torsades de pointes clinically significant bradycardia, second or third degree heart block and uncorrected hypokalaemia.
Haloperidol should not be used concomitantly with other QT prolonging drugs.

Rare cases of sudden death have been reported in psychiatric patients receiving antipsychotic drugs, including this product. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
Cardiovascular effects: Very rare reports of QT prolongation and/or ventricular arrhythmias, in addition to rare reports of sudden death have been reported with haloperidol. They may occur more frequently with high doses and in predisposed patients As QT-prolongation has been observed during haloperidol treatment, caution is advised in patients with QTprolonging conditions (long QT-syndrome, hypokalaemia, electrolyte imbalance, drugs known to prolong QT, cardiovascular diseases, family history of QT prolongation), especially if haloperidol is given parenterally. The risk of QT prolongation and/or ventricular arrhythmias may be increased with higher doses or with parenteral use, particularly intravenous administration .
Haloperidol Decanoate must not be administered intravenously: Tachycardia and hypotension have also been reported in occasional patients.
Neuroleptic malignant syndrome: In common with other antipsychotic drugs, this product has been associated with neuroleptic malignant syndrome: a rare idiosyncratic response characterized by hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness.
Hyperthermia is often an early sign of this syndrome. Antipsychotic treatment should be withdrawn immediately and appropriate supportive therapy and careful monitoring instituted.
Tardive dyskinesia: As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or after drug discontinuation. The syndrome is mainly characterized by rhythmic involuntary movements of the tongue, face, mouth or jaw. The manifestations may be permanent in some patients. The syndrome may be masked when treatment is reinstituted, when the dosage is increased or when a switch is made to a different antipsychotic drug. Treatment should be discontinued as soon as possible.
Extrapyramidal symptoms: In common with all neuroleptics, extrapyramidal symptoms may occur, e.g. tremor, rigidity, hypersalivation bradykinesia, akathisia, acute dystonia. Antiparkinson drugs of the anticholinergic type may be prescribed as required, but should not be prescribed routinely as a preventive measure. If concomitant antiparkinson medication is required, it may have to be continued after stopping this product if its excretion is faster than that of haloperidol in order to avoid the development or aggravation of extrapyramidal symptoms. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered concomitantly with this product. Seizures/Convulsions It has been reported that seizures can be triggered by this product. Caution is advised in patients suffering from epilepsy and in conditions predisposing to convulsions (e.g., alcohol withdrawal and brain damage).
Hepatobiliary concerns: As this product is metabolized by the liver, caution is advised in patients with liver disease. Isolated cases of liver function abnormalities or hepatitis, most often cholestatic, have been reported. Endocrine system concerns Thyroxin may facilitate this product toxicity. Antipsychotic therapy in patients with hyperthyroidism should be used only with great caution and must always be accompanied by therapy to achieve a euthyroid state. Hormonal effects of antipsychotic neuroleptic drugs include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligo- or amenorrhoea. Very rare cases of hypoglycaemia and of Syndrome .of Inappropriate ADH Secretion have been reported.
Venous thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with this product and preventive measures undertaken.
Additional considerations: It is recommended that patients being considered for this product therapy be initially put on oral haloperidol to .exclude the possibility of an unexpected adverse sensitivity to haloperidol As with all antipsychotic agents, this product should not be used alone where depression is predominant. It may be combined with antidepressants to treat those conditions in which depression and psychosis coexist ,In schizophrenia, the response to antipsychotic drug treatment may be delayed. If drugs are withdrawn .recurrence of symptoms may not become apparent for several weeks or months. Caution is advised in patients with renal failure and phaeochromocytoma.
For full details see prescribing information.

Neuromuscular (extrapyramidal) reactions, tachycardia, low blood pressure, mild and usually transient leukopenia and leukocytosis, hepatic changes, maculopapular and acneiform skin reactions, photosensitivity, loss of hair, anorexia, constipation, diarrhea, hypersalivation, pepsia, nausea and vomiting, dry mouth, blurred vision, urinary retention, diaphoresis and priapism, laryngospasm, bronchospasm, increased depth of respiration, visual disturbances.
For full details see prescribing information.

As with other antipsychotics, caution is advised when prescribing haloperidol with medications known to prolong the QT interval Haloperidol is metabolized by several routes, including glucuronidation and the cytochrome P450 enzyme system (particularly CYP 3A4 or CYP 2D6). Inhibition of these routes of metabolism by another drug or a decrease in CYP 2D6 enzyme activity may result in increased haloperidol concentrations and an increased risk of adverse events, including QT-prolongation. 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 CYP 3A4 or CYP 2D6 isozymes, such as, itraconazole, nefazodone buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, and promethazine. A decrease in CYP2D6 enzyme activity may result in increased haloperidol concentrations.
Increases in QTc have been observed when haloperidol was given with a combination of the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day). It may be necessary to reduce the haloperidol dosage. Caution is advised when used in combination with drugs known to cause electrolyte imbalance.
Effect of Other Drugs on Haloperidol: When prolonged treatment with enzyme-inducing drugs such as carbamazepine, phenobarbital, rifampicine ,is added to therapy, this results in a significant reduction of haloperidol plasma levels. Therefore during combination treatment, the dose or the dosage interval should be adjusted, when necessary. After stopping such drugs, it may be necessary to reduce the dosage. Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.
Effect of Haloperidol on Other Drugs: In common with all neuroleptics, this product can increase the central nervous system depression produced by other CNS-depressant drugs, including alcohol, hypnotics, sedatives or analgesics. An enhanced CNS effect when combined with methyldopa, has been reported.
This product may antagonise the action of adrenaline and other sympathomimetic agents and reverse the bloodpressure lowering effects of adrenergic blocking agents such as guanethidine. This product may impair the antiparkinsonian effects of levodopa, Haloperidol is an inhibitor of CYP 2D6. This product inhibits the metabolization of tricyclic antidepressants thereby increasing plasma levels of these drugs.
Other Forms of Interaction: In rare cases the following symptoms were reported during the concomitant use of lithium and haloperidol ,decanoate: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome brain stem disorder, acute brain syndrome and coma. Most of these symptoms were reversible. It remains unclear whether this represents a distinct clinical entity. Nonetheless, it is advised that in patients, who are treated concomitantly with lithium and this product, therapy .should be stopped immediately if such symptoms occur. Antagonism of the effect of the anticoagulant phenindione has been reported.

Pregnancy: Animal studies have demonstrated a teratogenic effect of haloperidol. Neonates exposed to antipsychotic drugs (including haloperidol) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms that may vary in severity following delivery. These symptoms in the neonates may include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory.distress, or feeding disorder. This product has shown no significant increase in fetal anomalies in large population studies. There have been isolated case reports of birth defects following fetal exposure to this product in combination with other drugs. This product should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.
Lactation: This product is excreted in breast milk. If the use is considered essential, the benefits of breastfeeding should be balanced against its potential risks. Extrapyramidal symptoms have been observed in breastfed infants of  treated women.

While overdose is less likely to occur with parenteral than with oral medication, information pertaining to oral halperidol is presented, modified only to reflect the extended duration of action of this product’s.
Symptoms: The manifestations are an exaggeration of the known pharmacological effects and adverse reactions. The most prominent symptoms are: severe extrapyramidal reactions, hypotension, and sedation. An extrapyramidal reaction is manifest by muscular rigidity and a generalised or localised tremor. Hypertension rather than hypotension is also possible. In extreme cases, the patient would appear comatose with respiratory depression, and hypotension that could be severe enough to produce a shock-like state. The risk of ventricular arrhythmias possibly associated with QT-prolongation, should be considered.
Treatment: Since there is no specific antidote, treatment is primarily supportive. For comatose patients, a patent airway should be established by use of an oropharyngeal airway or endotracheal tube. Respiratory depression may necessitate artificial respiration. Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma, or concentrated albumin, and vasopressor agents such as dopamine or noradrenaline. Adrenaline should not be used. In case of severe extrapyramidal reactions, antiparkinsonian medication of the anticholinergic type should be administered and be continued for several weeks. They must be withdrawn very cautiously as extrapyramidal symptoms may emerge ECG and vital signs should be monitored and monitoring should continue until the ECG is normal. Severe arrhythmias should be treated with appropriate anti-arrhythmic measures.