Adverse reactions : תופעות לוואי

4.8    Undesirable effects

The safety of haloperidol was evaluated in 284 haloperidol-treated patients who participated in 3 placebo-controlled clinical studies and in 1295 haloperidol-treated patients who participated in 16 double-blind active comparator-controlled clinical studies.

Based on pooled safety data from these clinical studies, the most commonly reported adverse reactions were: extrapyramidal disorder (34%), insomnia (19%), agitation (15%), hyperkinesia (13%), headache (12%), psychotic disorder (9%), depression (8%), weight increased (8%), tremor (8%), hypertonia (7%), orthostatic hypotension (7%), dystonia (6%) and somnolence (5%).

In addition, the safety of haloperidol decanoate was evaluated in 410 patients who participated in 3 comparator studies (1 comparing haloperidol decanoate versus fluphenazine and 2 comparing the decanoate formulation to oral haloperidol), 9 open label studies and 1 dose response study.

Table 4 lists adverse reactions as follows:

•      Reported in clinical studies with haloperidol.
•      Reported in clinical studies with haloperidol decanoate and relate to the active moiety.
•      From postmarketing experience with haloperidol and haloperidol decanoate.

Adverse reaction frequencies are based on (or estimated from) clinical trials or epidemiology studies with haloperidol, and classified using the following convention:

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.

The adverse reactions are presented by System Organ Class and in order of decreasing seriousness within each frequency category.



Table 4: Adverse reactions

System                                          Adverse Reaction
Organ Class
Frequency
Very        Common       Uncommon                Rare             Not known Common
Blood and                                     Leukopenia                             Pancytopenia lymphatic                                                                            Agranulocytosis system                                                                               Thrombocytopeni disorders                                                                            a Neutropenia
Immune                                        Hypersensitivit                        Anaphylactic system                                        y                                      reaction disorders
Endocrine                                                       Hyperprolactinaem    Inappropriate disorders                                                       ia                   antidiuretic hormone secretion
Metabolic                                                                            Hypoglycaemia and nutritional disorders
Psychiatric        Agitation    Psychotic    Confusional disorders          Insomnia     disorder     state
Depression   Loss of libido
Libido decreased
Restlessness
Nervous            Extrapyramid Tardive      Convulsion          Neuroleptic         Akinesia system             al disorder  dyskinesia   Parkinsonism        malignant           Cogwheel disorders          Hyperkinesia Akathisia    Sedation            syndrome            rigidity Headache     Bradykinesia Muscle              Motor dysfunction   Masked facies Dyskinesia   contractions        Nystagmus
Dystonia     involuntary
Hypokinesia
Hypertonia
Dizziness
Somnolence
Tremor
Eye disorders                   Oculogyric   Vision blurred crisis
Visual disturbance
Cardiac                                      Tachycardia                             Ventricular disorders                                                                            fibrillation Torsade de pointes
Ventricular tachycardia
Extrasystoles
Vascular                        Hypotension disorders                       Orthostatic hypotension

System                                         Adverse Reaction
Organ Class
Frequency
Very      Common        Uncommon              Rare            Not known Common
Respiratory,                                Dyspnoea          Bronchospasm        Laryngeal thoracic and                                                                      oedema mediastinal                                                                       Laryngospasm disorders
Gastrointestin                Vomiting al disorders                  Nausea
Constipation
Dry mouth
Salivary hypersecretio n
Hepatobiliary                 Liver         Hepatitis                             Acute hepatic disorders                     function test Jaundice                              failure abnormal                                            Cholestasis
Skin and                      Rash          Photosensitivit                       Angioedema subcutaneous                                y reaction                            Dermatitis tissue                                      Urticaria                             exfoliative disorders                                   Pruritus                              Leukocytoclastic Hyperhidrosis                         vasculitis

Musculoskelet                               Torticollis     Trismus               Rhabdomyolysis al and                                      Muscle rigidity Muscle twitching connective                                  Muscle spasms tissue                                      Musculoskelet disorders                                   al stiffness
Renal and                     Urinary urinary                       retention disorders
Pregnancy,                                                                        Drug withdrawal puerperium                                                                        syndrome and perinatal                                                                     neonatal (see conditions                                                                        section 4.6) Reproductive                  Erectile      Amenorrhoea       Menorrhagia         Priapism system and                    dysfunction   Galactorrhoea     Menstrual           Gynaecomastia breast                                      Dysmenorrhoe      disorder disorders                                   a                 Sexual
Breast pain       dysfunction
Breast discomfort
General                                     Hyperthermia                          Sudden death disorders and                               Oedema                                Face oedema administratio                               Gait                                  Hypothermia n site                                      disturbance conditions
Investigations                Weight                          Electrocardiogram increased                       QT prolonged
Weight decreased


Electrocardiogram QT prolonged, ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), torsade de pointes and sudden death have been reported with haloperidol.

Class effects of antipsychotics

Cardiac arrest has been reported with antipsychotics.
Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis, have been reported with antipsychotics. The frequency is unknown.

Reporting of suspected adverse reactions

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