Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Fludecate must be used only after a rigorous benefit-risk assessment and with special caution in
• Hepatic and renal impairment.
• Pheochromocytoma.
• Hypotension, Hypertension, Orthostatic Dysregulation, Bradycardia, Hypokalemia.
• Congenital long QT syndrome or family history of QT syndrome or other clinically significant cardiac disorders (especially coronary heart disease, conduction disorders, arrhythmias).
• Concomitant treatment with medicinal products that also prolong the QT interval on the ECG or that can cause hypokalemia or other electrolyte disturbances (see section 4.5).
• History of organic brain disorders and epileptic seizures.
• Suspected or neurologically recognizable subcortical brain injury.
• Depressive disorder.
• Chronic respiratory conditions and asthma.
• Severe quantitative impairment of consciousness, e.g., somnolence.
• Glaucoma, pyloric stenosis, prostatic hyperplasia, urinary retention.
• Patients exposed to high temperatures.
• Use of organophosphate insecticides.
• Concomitant treatment with other neuroleptics should be avoided (see section 4.5).
Children and adolescents
There are insufficient studies on the efficacy and tolerability of fluphenazine in children and adolescents. Fludecate should therefore only be prescribed in children over the age of 12 and adolescents after careful assessment of the benefit-risk ratio.
Tardive dyskinesia
Although the prevalence of tardive dyskinesia has not yet been sufficiently researched, it appears that elderly patients, in particular elderly women, are particularly predisposed to it.
The risk of tardive dyskinesia, and especially the risk of irreversibility, presumably increases with the length of treatment and level of the neuroleptic dose. However, tardive dyskinesia can also occur even after a short period of treatment and using low doses. Neuroleptic treatment itself can initially mask the symptoms of incipient tardive dyskinesia. After discontinuation of the medication, the tardive dyskinesia then becomes obvious. There is currently no established therapy for these symptoms.

Increased mortality in elderly patients with dementia disorders
The data from two large observational studies showed that elderly patients with dementia disorders treated with conventional (typical) antipsychotics have a slightly increased risk of mortality compared with those not treated with antipsychotics. The available study data do not allow the exact extent of this risk to be stated and the reason for the increased risk is not known.
Fluphenazine decanoate is not indicated for the treatment of behavioral disorders associated with dementia disorders.
Increased risk of adverse cerebrovascular events
In randomized, placebo-controlled clinical studies in patients with dementia who were treated with some atypical antipsychotics, there was noted to be an approximately three-fold increased risk of adverse cerebrovascular events. The mechanism leading to this increase in risk is not known. It is not possible to rule out this effect also occurring with the use of other antipsychotics or in other patient groups. Fluphenazine decanoate should therefore be used with caution in patients at increased risk of stroke.

Risk of thromboembolism
Cases of venous thromboembolism (VTE) have been reported in association with the use of antipsychotics. As patients treated with antipsychotics frequently have acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with fluphenazine decanoate and preventive measures taken.

Special caution is required in patients with organic brain damage arteriosclerotic cerebrovascular disorders, and a tendency to seizures (in the medical history, e.g., in the context of alcohol withdrawal) as fluphenazine lowers the seizure threshold. The occurrence of seizures is more likely, especially with high doses in the begining of treatment, rapid increase in doses and abrupt discontinuation of high doses. Patients with epilepsy should be treated with Fludecate only if anticonvulsant therapy is being used concomitantly.
In disorders of the basal ganglia, Fludecateshould only be used in exceptional cases and the treatment should be stopped if symptoms worsen. In patients with depression, Fludecate should only be used in conjunction with an antidepressant as Fludecate can worsen symptoms of depression. Fludecate must not be used in severe depressive disorders (see section 4.5).
Patients with pheochromocytoma, renal failure, heart failure or cerebral insufficiency develop more frequently hypotensive reactions due to fluphenazine administration and should therefore be carefully monitored.
Neuroleptics result in increased prolactin secretion. Experiments in tissue cultures in vitro suggest that approximately a third of breast tumors are prolactin-dependent. Although there are not yet any informative clinical or epidemiological studies available, caution is advised if there is a relevant history.
The blood count (including differential and platelet count) should be checked prior to treatment with Fludecate Treatment with Fludecate must not take place if the blood counts are abnormal (see sections 4.3 and 4.8).
After intitating treatment the blood count (including differential count) should be checked weekly for a period of four months. If the results obtained are normal, the interval between checks can then be lengthened. If the white cell count falls rapidly, especially to values below 3000/mm3, or if other blood count abnormalities occur, treatment with tricyclic neuroleptics should be stopped immediately and replaced by other forms of treatment.
Intensive care measures should be implemented if necessary. The blood count must be monitored until it has returned to normal.
The patient should be instructed not to self-medicate with analgesics/antibiotics if he/she develops ahigh temperature, inflammation of the gums or oral mucosa, sore throat, purulent tonsillitis or flu-like symptoms, especially if these symptoms occur within the first three months after starting treatment with the drug, but instead to consult his/her attendant physician immediately.
Body weight, blood glucose and serum lipid levels, and dental status should be monitored at regular intervals.
Renal and hepatic function should be monitored at regular intervals during therapy.
Conduction disorders may occur, especially in elderly patients and patients with pre-existing heart damage. The circulatory status (including an ECG recording) should be monitored at regular intervals during therapy, and a baseline ECG should be available for subsequent monitoring of any changes.
Pre-existing hypokalemia should be corrected before initiate treatment.
The possibility of the occurrence of neuroleptic malignant syndrome (high body temperature, muscle rigidity, impaired consciousness, autonomic nervous system instability) exists with all neuroleptics. The symptoms are often misdiagnosed as catatonia. As further administration of a neuroleptic can be life-threatening in this situation, the differential diagnosis is extremely important (including medication history, examination for muscle rigidity, high body temperatureand elevation of blood creatine kinase activity, elevation of myoglobin in the blood and urine). Cases with a fatal outcome are particularly prevalent among patients with a pre-existing organic brain syndrome, intellectual impairment and opiate or alcohol dependence. The symptoms may persist in a dose-dependent manner (corresponding to the treatment intervals) for a considerable time after the IM injection (forundesirable effects, see section 4.8).
The doses must be adjusted in hepatic or renal impairment. Special caution is required, especially in elderly patients, because of increased sensitivity. The anticholinergic adverse reactions are frequently more pronounced. Elderly patients may develop extrapyramidal adverse reactions, even at low doses. The frequency of tardive dyskinesia is increased . The sedative effect is alsomore pronounced in elderly patients. Hypotension may occur more frequently among elderly.

Excipients of Fludecate
Fludecate contains 15 mg benzyl alcohol, which may cause allergic reactions. Fludecate must be used with caution in patients with renal or hepatic impairment, or in patients who are pregnant or breast feeding, because of the risk of accumulation and toxicity (metabolic acidosis).

Effects on Driving

4.7   Effects on ability to drive and use machines
Even when used correctly, Fludecate can alter the ability to react to such an extent that the ability to drive or use machines is compromised. This applies even more so in conjunction with alcohol. Therefore patients should completely avoid driving vehicles, using machines or undertaking other dangerous activities, at least during the first phase of treatment. In each specific case, the decision is made by the attendant physician taking into account the individual response and relevant dosage.