Adverse reactions : תופעות לוואי

4.8   Undesirable effects
The frequencies for adverse reactions are based on the following categories: Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from the available data)
Adverse reactions due to fluphenazine decanoate are comparatively rare and mild in the lower dosage range. Some adverse reactions occur more frequently at higher doses. Neurological symptoms are the most common in this context.
Central nervous system
Extrapyramidal motor symptoms
Early dyskinesia can occur very frequently during treatment with fluphenazine, especially in the first days and weeks. Parkinsonism and akathisia generally occur somewhat later.
Dystonia (torticollis, rigidity of the back muscles) and hyperreflexia are also possible.
Children develop extrapyramidal motor disorders even at low doses.
If early dyskinesia or parkinsonism occurs, a dose reduction or treatment with an anticholinergic antiparkinsonian agent is necessary. However, this medication should only be used if required and not given routinely. If there is a need for antiparkinsonian medication that is excreted more rapidly than fluphenazine, it may be necessary to continue this antiparkinsonian medication even after fluphenazine has been discontinued in order to prevent the occurrence or worsening of extrapyramidal motor symptoms. The potential increase in intraocular pressure with the concomitant administration of fluphenazine and anticholinergic agents, including antiparkinsonian agents, needs to be borne in mind (see section 4.5).
It is difficult to treat akathisia; a dose reduction can initially be tried, and if this is unsuccessful, a trial of treatment with sedatives, hypnotics or beta-receptor blockers can be undertaken.
Tardive dyskinesia (persistent, in many cases irreversible hyperkinetic syndromes with abnormal involuntary movements primarily involving the jaw and facial muscles, but also athetoid and ballistic movements of the limbs) may occur, mostly after longer-term and high- dose therapy or after treatment discontinuation. There is currently no established therapy for these symptoms.
It is essential to watch for the first signs of dyskinesia, primarily in the region of the tongue and orofacial muscles, and to consider stopping the neuroleptic therapy.
Tardive dyskinesia may be masked during long-term treatment with Fludecate and observed only after the end of treatment (see section 4.4).
Neuroleptic malignant syndrome
A life-threatening neuroleptic malignant syndrome (temperature above 40°C, muscle rigidity, autonomic dysregulation with palpitations and hypertension, impaired consciousness and even coma, a rise in myoglobin and creatine kinase activity (CK)) can occur during neuroleptic treatment, requiring immediate discontinuation of the medication.
The frequency of this syndrome is reported to be 0.07-2.2%.
Treatment is difficult and the following measures are recommended:
- No further administration of the medicine.
- Treatment of hyperthermia through cooling as antipyretics are potentially ineffective for a high body temperature,
- Treatment of electrolyte and fluid disturbances, cardiovascular manifestations, infections, and respiratory and renal complications,
- Therapy attempt with dantrolene infusions (3 to 10 mg/kg body weight/day) in combination with bromocriptine (7.5 to 30 mg/day orally).

Other CNS effects
Particularly at the beginning of treatment, tiredness and sedation can frequently occur, but restlessness, agitation, drowsiness, depression (especially during long-term therapy), lethargy, dizziness, headache, confused dreams, symptoms of delirium (especially during combination with anticholinergic substances), cerebral seizures, and dysregulation of body temperature (hyper- and hypothermia) are also possible as well as occasional speech, memory and sleep disorders. Isolated cases of reversible central paresis have been reported.
Changes in the EEG and cerebrospinal fluid protein may also occur during treatment withFludecate .
As occurs on other neuroleptics, psychotic processes may rarely be reactivated or exacerbated.
Cardiovascular system
Hypotension or orthostatic dysregulation and reflex acceleration of heart rate (circulatory instability) frequently occur, particularly at the beginning of treatment. ECG changes have been observed (disorders of conduction and repolarization), as well as hypertension.
Fluphenazine can prolong the QT interval in the ECG; in some instances, life-threatening torsades de pointes and even ventricular fibrillation may occur (see sections 4.4 and 4.5).
The treatment with fluphenazine should be stopped in these cases. Ventricular arrhythmias, ventricular tachycardia (rare), cardiac arrest and sudden unexplained death have been reported with medicinal products that are members of the therapeutic class of neuroleptics.
Ventricular arrhythmias may occur more frequently when high doses are administered and in predisposed patients.

Autonomic nervous system / gastrointestinal tract
Autonomic adverse reactions occur primarily at the beginning of treatment and then generally show adaptation.
Accommodation disorders, dry mouth, sweating, salivation, polyuria, high body temperature, the feeling of a blocked nose, nasal congestion, raised intraocular pressure, constipation (in some cases even paralytic ileus) and urinary retention can uncommonly occur.
Nausea, vomiting, diarrhea, loss of appetite and dyspepsia have also been uncommonly reported. These effects can usually be favorably impacted by a dose reduction or prolonged dosing interval.
Liver and bile ducts
Transient elevations of liver enzyme activities have been uncommonly reported; hepatitis (usually cholestatic) has also been very rarely reported. Jaundice can also occur.
Endocrine system
Fluphenazine decanoate can affect sexual functions (impaired sexual response, decreased libido,   erectile and ejaculatory disorders); menstrual disorders, galactorrhea and gynecomastia can occur, as well as disorders of glucose metabolism.
Like other neuroleptics, fluphenazine decanoate can lead to an increase in body weight, impaired ADH secretion and hyponatremia.
Blood and blood vessels
Hematopoietic disorders in the form of leukopenia, thrombocytopenia, eosinophilia and pancytopenia have been reported uncommonly. agranulocytosis and leg and pelvic vein thrombosis have been rarely reported.
Not known (cannot be estimated from the available data):
Cases of thromboembolic disease (including cases of pulmonary embolism and cases of deep vein thrombosis).
Pregnancy, puerperium and perinatal conditions
Not known (cannot be estimated from the available data):
Drug withdrawal syndrome in the newborn (see section 4.6).
Skin and hypersensitivity reactions
Allergic skin reactions of all severities (e.g., pruritus, erythema, urticaria, eczema, exfoliative dermatitis) and photosensitivity can occur (caution is needed if exposed to sunlight).
Respiratory symptoms, asthma and bronchopneumonia, laryngeal edema, angioneurotic edema (Quincke’s edema), anaphylactic reactions, pigmentation disorders, lupus-like syndromes and peripheral edema have been observed.
The following have also been described
Cerebral edema, retinitis pigmentosa, pigment deposits in the lens and cornea (see section 5.3).
In hospitalized psychotic patients, sudden, unexpected and unexplained deaths have occurred during phenothiazine therapy, with previous brain injury or seizures probably playing a role as predisposing factors; high doses should therefore be avoided in patients with known seizures.
Sesame oil can rarely cause severe allergic reactions.
Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health, according to the National Regulation by using an online form: https://sideeffects.health.gov.il

Additionally, you can report to Unipharm Ltd. via the following address: https://unipharm.co.il/