Posology : מינונים

4.2. Posology and Method of Administration                                                                            haloperidol concentrations have been reported when haloperidol was given concomitantly with drugs                                                                                                                                          5.2. Pharmacokinetic Properties
Vascular Disorders: Hypotension; Orthostatic hypotension
PERICATE Injection is intended for use in chronic psychotic patients who require prolonged parenteral                 characterized as substrates or inhibitors of CYP 3A4 or CYP 2D6 isozymes, such as, itraconazole, nefazodone,                                                                                                                               Absorption
Musculoskeletal and Connective Tissue Disorders: Trismus; Torticollis; Muscle spasms; Musculoskeletal
antipsychotic therapy. These patients should be previously stabilised on antipsychotic medication before              buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, and                                                                                                                                    Administration of haloperidol decanoate as a depot intramuscular injection results in a slow and sustained stiffness; Muscle twitching
considering a conversion to PERICATE.                                                                                 promethazine. A decrease in CYP2D6 enzyme activity may result in increased haloperidol concentrations.                                                                                                                                     release of free haloperidol. The plasma concentrations rise gradually, usually peaking within 3 to 9 days after Reproductive System and Breast Disorders: Amenorrhoea; Galactorrhoea; Menstrual disorder; Erectile
PERICATE is for use in adults only and has been formulated to provide a one month’s therapy for most patients         Increases in QTc have been observed when haloperidol was given with a combination of the metabolic inhibitors                                                                                                                              injection. The pharmacokinetics of haloperidol decanoate following intramuscular injections are dose-related. dysfunction; Breast discomfort; Breast pain; Dysmenorrhoea; Menorrhagia
following a single deep intramuscular injection in the gluteal region. PERICATE should not be administered            ketoconazole (400 mg/day) and paroxetine (20 mg/day). It may be necessary to reduce the haloperidol dosage.                                                                                                                                The relationship between dose and plasma haloperidol level is roughly linear for doses below 450 mg. General Disorders and Administration Site Conditions: Gait disturbance
intravenously. As the administration of volumes greater than 3 ml are uncomfortable for the patient, such large       Caution is advised when used in combination with drugs known to cause electrolyte imbalance.                                                                                                                                               Distribution
injection volumes are not recommended.                                                                                Effect of Other Drugs on Haloperidol                                                                                                                                                                                                       Haloperidol crosses the blood-brain barrier easily. Plasma protein binding is 92%.
Postmarketing Data
Since individual response to neuroleptic drugs is variable, dosage should be individually determined and is           When prolonged treatment with enzyme-inducing drugs such as carbamazepine, phenobarbital, rifampicine                                                                                                                                      Metabolism
Adverse events first identified as ADRs during postmarketing experience with haloperidol are included in Tables
best initiated and titrated under close clinical supervision. The individual starting dose will depend on both        is added to PERICATE therapy, this results in a significant reduction of haloperidol plasma levels. Therefore,                                                                                                                             Haloperidol is metabolized by several routes including the cytochrome P450 enzyme system (particularly CYP 3. The postmarketing review was based on review of all cases including haloperidol and haloperidol decanoate
the severity of the symptomatology and the amount of oral medication required to maintain the patient before          during combination treatment, the PERICATE dose or the dosage interval should be adjusted, when necessary.                                                                                                                                 3A4 or CYP 2D6) and glucuronidation.
containing products. In each table, the frequencies are provided according to the following convention:
starting depot treatment.                                                                                             After stopping such drugs, it may be necessary to reduce the dosage of PERICATE.                                                                                                                                                           Elimination
Very common ≥1/10
It is recommended that the initial dose of PERICATE be 10-15 times the previous daily dose of oral haloperidol.       Sodium valproate, a drug known to inhibit glucuronidation, does not affect haloperidol plasma concentrations.                                                                                                                              After reaching peak plasma concentrations, levels fall with an apparent half-life of about 3 weeks. Haloperidol Common ≥1/100 to <1/10
For most patients, this means a starting dose ranging between 25 and 75 mg of PERICATE. A maximum starting            Effect of Haloperidol on Other Drugs                                                                                                                                                                                                       is excreted in the urine (40%) and faeces (60%). About 1% of the dose is excreted unchanged with the urine. Uncommon ≥1/1,000 to <1/100
dose of 100 mg should not be exceeded.                                                                                In common with all neuroleptics, PERICATE can increase the central nervous system depression produced by                                                                                                                                   Multiple-Dose Pharmacokinetics
Rare ≥1/10,000 to <1/1,000
Depending on the individual patient’s response the dose may gradually be increased by 50 mg until an optimal          other CNS-depressant drugs, including alcohol, hypnotics, sedatives or analgesics. An enhanced CNS effect,                                                                                                                                 Steady state plasma levels are reached within 2 to 4 months in patients receiving monthly injections. Very rare <1/10,000, including isolated reports
therapeutic effect is obtained. The most appropriate monthly dose of PERICATE is often about 20 times the             when combined with methyldopa, has been reported.                                                                                                                                                                                          Therapeutic Concentrations
In Table 3, ADRs are presented by frequency category based on spontaneous reporting rates
daily dose of oral haloperidol. During dose adjustment or episodes of exacerbation of psychotic symptoms,             PERICATE may antagonise the action of adrenaline and other sympathomimetic agents and reverse the blood-                                                                                                                                   It has been suggested that a plasma haloperidol concentration range from 4 μg/l to an upper limit of 20 to 25 PERICATE therapy can be supplemented with regular haloperidol.                                                        pressure lowering effects of adrenergic blocking agents such as guanethidine.                                                                                                                                                              μg/l is required for a therapeutic response.
Table 3: Adverse Drug Reactions Identified During Postmarketing Experience with Haloperidol (oral, solution,
The usual time interval between injections is four weeks. However, variation in patient response may dictate a        PERICATE may impair the antiparkinsonian effects of levodopa.
or decanoate) by Frequency Category Estimated From Spontaneous Reporting Rates
need for adjustment of the dosing interval.                                                                           Haloperidol is an inhibitor of CYP 2D6. PERICATE inhibits the metabolization of tricyclic antidepressants,                                                                                                                                 5.3. Preclinical Safety Data
thereby increasing plasma levels of these drugs.                                                                       Blood and Lymphatic System Disorders                                                                                Nonclinical data reveal no special hazards for humans based on conventional studies of local tolerability, repeat
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          Other Forms of Interaction                                                                                             Very rare                         Agranulocytosis, Pancytopenia, Thrombocytopenia, Leukopenia,                      dose toxicity, genotoxicity and carcinogenicity. In rodents, haloperidol administration showed a decrease in according to the patient’s response.                                                                                  In rare cases the following symptoms were reported during the concomitant use of lithium and haloperidol                                                 Neutropenia                                                                       fertility, limited teratogenicity as well as embryo-toxic effects.
decanoate: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome,                Immune System Disorders                                                                                             Haloperidol has been shown to block the cardiac hERG channel in several published studies in vitro. In a