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Haloperidol decanoate
Haldol decanoasTM
Description
Haldol decanoasTM contains the decanoate ester of haloperidol.
Haldol decanoasTM is available as an injectable solution.
This solution contains 70.52 mg haloperidol decanoate corresponding with 50 mg haloperidol.
The other ingredients are benzyl alcohol and sesame oil.
Properties
Pharmacodynamics
Haloperidol decanoate is an ester of haloperidol and decanoic acid, and as such, a depot neuroleptic belonging to the butyrophenones group. After intramuscular injection, haloperidol decanoate is gradually released from muscle tissue and hydrolyzed slowly into free haloperidol which enters the systemic circulation.
Haloperidol decanoate is a potent dopamine antagonist and, therefore, a very incisive neuroleptic.
In the brain, haloperidol has an incisive action on delusions and hallucinations (probably through an interaction with dopamine receptors in the mesocortical and limbic tissues) and an inhibitory effect through its activity on the basal ganglia, i.e. nigrostriatal bundles, which also underlies the extrapyramidal motor side-effects (namely dystonia, akathisia and parkinsonism).
Haloperidol presents an effective psychomotor sedative effect, which also explains the favorable effect on mania and other agitation syndromes.
A resocializing effect has been observed in emotionally withdrawn patients.
The more peripheral antidopaminergic effects explain the activity against nausea and vomiting (via the chemoreceptor-trigger zone), the relaxation of the gastro-intestinal sphincters and the increased prolactin release (through an inhibition of the activity of the prolactin inhibiting factor, PIF, at the level of the adenohypophysis).
Pharmacokinetics
Administration of haloperidol decanoate as a depot intramuscular injection results in a slow and sustained release of free haloperidol. The plasma concentrations rise gradually, usually peaking within 3-9 days after injection and falling thereafter with an apparent half-life of about 3 weeks. Steady state plasma levels are reached within 2-4 months in patients receiving monthly injections. The pharmacokinetics of haloperidol decanoate following intramuscular injections are dose-related. The relationship between dose and plasma haloperidol level is roughly linear for doses below 450 mg. It has been suggested that a plasma haloperidol concentration range from 4 µg/l to an upper limit of 20 to 25 µg/l is required for a therapeutic response. Haloperidol crosses the blood-brain barrier easily. Plasma protein binding is 92%. Haloperidol is metabolized in the liver and excreted in the urine (40%) and feces (60%). About 1% of the dose is excreted unchanged with the urine.
Indications
Haloperidol decanoate (Haldol decanoasTM) is indicated for the treatment of chronic schizophrenia and other psychoses. It is also indicated in the treatment of other mental or behavioral problems where psychomotor unrest requires maintenance treatment.
Contraindications
Comatose state; CNS depression due to alcohol or other depressant drug; Parkinson's disease; known hypersensitivity to haloperidol decanoate (Haldol decanoasTM); lesion of the basal ganglia.
Warnings and precautions
Rare cases of sudden death have been reported in psychiatric patients receiving antipsychotic drugs, including haloperidol decanoate (Haldol decanoasTM). Since QT-prolongation has been observed during haloperidol decanoate (Haldol decanoasTM) treatment, it is advised to be cautious in patients with QT-prolonging conditions (QT-syndrome, hypokalemia, drugs known to prolong QT).
It is recommended that patients being considered for haloperidol decanoate (Haldol decanoasTM) therapy be initially put on oral haloperidol to exclude the possibility of an unexpected adverse sensitivity to haloperidol.
It has been reported that seizures can be triggered by haloperidol decanoate (Haldol decanoasTM). Caution is advised in patients suffering from epilepsy and in conditions predisposing to convulsions (e.g. alcohol withdrawal and brain damage).
Thyroxin may facilitate haloperidol decanoate (Haldol decanoasTM) toxicity. Therefore, it should only be used with great caution in patients with hyperthyroidism. Antipsychotic therapy in those patients must always be accompanied by an adequate thyreostatic treatment.
As with all antipsychotic agents, haloperidol decanoate (Haldol decanoasTM) 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.
If concomitant antiparkinson medication is required, it may have to be continued for at least a couple of weeks after the last haloperidol decanoate (Haldol decanoasTM) injection because of the very long half-life of haloperidol decanoate (Haldol decanoasTM).
Interactions
In common with all neuroleptics, haloperidol decanoate (Haldol decanoasTM) can increase the central nervous system depression produced by other CNS-depressant drugs, including alcohol, hypnotics, sedatives or strong analgesics. An enhanced CNS effect, when combined with methyldopa, has been reported.
Haloperidol decanoate (Haldol decanoasTM) may antagonize the action of adrenaline and other sympathomimetic agents and reverse the blood-pressure lowering effects of adrenergic blocking agents such as guanethidine.
Haloperidol decanoate (Haldol decanoasTM) may impair the antiparkinsonian effects of levodopa.
Haloperidol decanoate (Haldol decanoasTM) inhibits the metabolization of tricyclic antidepressants, thereby increasing plasma levels of these drugs. In pharmacokinetic studies mild to moderately increased haloperidol decanoate levels have been reported when haloperidol was given concomitantly with the following drugs: quinidine, buspirone, fluoxetine. It may be necessary to reduce the haloperidol decanoate dosage.
When prolonged treatment with enzyme-inducing drugs such as carbamazepine, phenobarbital, rifampicin is added to haloperidol decanoate (Haldol decanoasTM) therapy, this results in a significant reduction of haloperidol plasma levels. Therefore, during combination treatment, the haloperidol decanoate (Haldol decanoasTM) dose or the dosage interval should be adjusted, when necessary. After stopping such drugs, it may be necessary to reduce the dosage of haloperidol decanoate (Haldol decanoasTM).
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 haloperidol decanoate (Haldol decanoasTM), therapy should be stopped immediately if such symptoms occur.
Pregnancy and lactation
Haloperidol decanoate (Haldol decanoasTM) 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 haloperidol decanoate (Haldol decanoasTM) in combination with other drugs. Haloperidol decanoate (Haldol decanoasTM) should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.
Haloperidol decanoate (Haldol decanoasTM) is excreted in breast milk. If the use of haloperidol decanoate (Haldol decanoasTM) is considered essential, the benefits of breast-feeding should be balanced against its potential risks. Extrapyramidal symptoms have been observed in breast-fed infants of haloperidol decanoate (Haldol decanoasTM) treated women.
Effects on driving ability and use of machinery
Some degree of sedation or impairment of alertness may occur, particularly with higher doses and at the start of treatment and may be potentiated by alcohol. Patients should be advised not to drive or operate machinery during treatment, until their susceptibility is known.
Dosage and administration
Haloperidol decanoate (Haldol decanoasTM) Injection is intended for use in chronic psychotic patients who require prolonged parenteral antipsychotic therapy. These patients should be previously stabilized on antipsychotic medication before considering a conversion to haloperidol decanoate (Haldol decanoasTM).
Haloperidol decanoate (Haldol decanoasTM) 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. Haldol decanoate (Haldol decanoasTM) 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 of haloperidol decanoate (Haldol decanoasTM) 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 haloperidol decanoate (Haldol decanoasTM). 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 of haloperidol decanoate (Haldol decanoasTM) is often about 20 times the daily dose of oral haloperidol. During dose adjustment or episodes of exacerbation of psychotic symptoms, haloperidol decanoate (Haldol decanoasTM) 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 response.
Adverse reactions
Any adverse reactions following the administration of haloperidol decanoate (Haldol decanoasTM) are generally those of haloperidol (Haldol).
As with all injectable medications, local tissue reactions have been reported with haloperidol decanoate (Haldol decanoasTM).
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 should not be prescribed routinely.
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 rhythmical 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.
Neuroleptic malignant syndrome
In common with other antipsychotic drugs, haloperidol decanoate (Haldol decanoasTM) has been associated with neuroleptic malignant syndrome: a rare idiosyncratic response characterized by hyperthermia, 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.
Other CNS effects
These are occasionally reported and include: depression, sedation, agitation, drowsiness, insomnia, headache, confusion, vertigo, grand mal seizures and apparent exacerbation of psychotic symptoms.
Gastro-intestinal symptoms
Nausea, vomiting and loss of appetite have been reported. Weight changes may occur.
Endocrine effects
Hormonal effects of antipsychotic neuroleptic drugs include hyperprolactinemia, which may cause galactorrhea, gynecomastia and oligo- or amenorrhea. Very rare cases of hypoglycemia and of Syndrome of Inappropriate ADH Secretion have been reported.
Cardiovascular effects
Tachycardia and hypotension have been reported in occasional patients. QT-interval prolongation and/or ventricular arrhythmias have been reported very rarely. They may occur more frequently with high doses and in predisposed patients.
Miscellaneous
There have been occasional reports of mild and usually transient decreases in blood cell counts. Agranulocytosis and thrombocytopenia have only rarely been reported, and then usually in association with other medication.
Isolated cases of liver function abnormalities or hepatitis, most often cholestatic, have been reported.
Hypersensitivity reactions such as skin rash, urticaria and anaphylaxis are exceptional.
Other side effects occasionally reported are: constipation, blurred vision, dry mouth, urinary retention, priapism, erectile dysfunction, peripheral edema, excessive perspiration or salivation and body temperature disregulation.
Overdosage
While overdosage is less likely to occur with parenteral than with oral medication, information pertaining to oral haloperidol (Haldol) is presented, modified only to reflect the extended duration of action of haloperidol decanoate (Haldol decanoasTM).
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 generalized or localized 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.
How supplied
Haloperidol decanoate (Haldol decanoasTM) 50 mg/mL is supplied in ampules of 1 mL.
Storage conditions
Store between 15 and 30°C.
Protect from light.
Keep out of reach of children.
CAUTION: Food, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.
Manufactured by:
Janssen Pharmaceutica
Beerse, Belgium
Packed by:
Interphil Laboratories, Inc.
Canlubang Industrial Estate
Bo. Pittland, Cabuyao, Laguna
For: Johnson & Johnson (Philippines), Inc.
Edison Road, Bo. Ibayo
Parañaque, Metro Manila
Exclusively distributed by:
Zuellig Pharma Corporation
Sen. Gil Puyat Avenue
Makati City
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