Active ingredients: Haloperidol
SERENASE 1 mg tablets
SERENASE 5 mg tablets
SERENASE 10 mg tablets
SERENASE 2 mg / ml oral drops, solution
SERENASE 10 mg / ml oral drops, solution
SERENASE 2 mg / 2 ml solution for injection for intramuscular use
SERENASE 5 mg / 2 ml solution for injection for intramuscular use
Why is Serenase used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antipsychotic derivative of butyrophenone.
THERAPEUTIC INDICATIONS
Tablets and oral drops, solution:
Psychomotor agitation in case of:
- Manic states, dementia, oligophrenia, psychopathy, acute and chronic schizophrenia, alcoholism, compulsive, paranoid, histrionic personality disorders.
Delusions and hallucinations in case of:
- Acute and chronic schizophrenia, paranoia, acute mental confusion, alcoholism (Korsakoff's Syndrome), hypochondriasis, personality disorders of the paranoid, schizoid, schizotypic, antisocial type, some cases of the borderline type.
- Choreiform movements.
- Agitation, aggression and flight reactions in elderly subjects.
- Tics and stuttering.
- He retched.
- Hiccup.
- Alcohol withdrawal syndromes.
Solution for injection for intramuscular use:
Resistant forms of psychomotor excitement, acute delusional and / or hallucinatory psychosis, chronic psychosis.
The use of the product in high doses should be limited to the therapy of resistant forms of: psychomotor excitation syndromes, acute delusional and / or hallucinatory psychosis, chronic psychosis.
In the treatment of intense pain generally in association with narcotic analgesics.
Contraindications When Serenase should not be used
Hypersensitivity to the active substance or to any of the excipients.
Comatose states, patients strongly depressed by alcohol or other substances active on the central nervous system, endogenous depressions without agitation, Parkinson's disease.
Asthenia, neurosis and spastic states due to lesions of the basal ganglia (hemiplegia, multiple sclerosis, etc.).
Known or suspected pregnancy, lactation and in children.
Clinically significant heart disease (e.g. recent acute myocardial infarction, decompensated heart failure, arrhythmias treated with class IA and III antiarrhythmic drugs).
QTc interval prolongation.
Subjects with a family history of arrhythmia or torsades de pointes.
Uncorrected hypokalaemia.
Concomitant use of QTc prolonging drugs.
Precautions for use What you need to know before taking Serenase
Rare cases of sudden death have been reported in psychiatric patients treated with antipsychotic drugs, including SERENASE.
Use with caution in patients with cardiovascular disease or a family history of QT prolongation.
SERENASE should not be administered intravenously as intravenous administration of haloperidol has been associated with an increased risk of QT prolongation and Torsade de Pointes. Perform a basic ECG before starting treatment (see "Contraindications" section).
Monitor the ECG during therapy based on the patient's clinical condition.
During therapy, reduce dosage if QT prolongation is observed and discontinue if QTc is> 500ms.
Periodic checking of electrolytes is recommended.
Avoid concomitant therapy with other neuroleptics.
An approximately three-fold increase in the risk of cerebrovascular events was observed in randomized clinical trials versus placebo in a population of patients with dementia treated with some atypical antipsychotics. The mechanism of this increased risk is unknown.
An increased risk for other antipsychotics or other patient populations cannot be excluded. SERENASE should be used with caution in patients with stroke risk factors.
SERENASE should be administered with caution in the following cases:
- if the patient or someone else in their family has a history of blood clots (thrombi), as medicines like these have been associated with the formation of blood clots
- severe cardiopathic patients, due to possible transient arterial hypotension and / or the onset of anginal pain (in this case do not use adrenaline as SERENASE can block hypertensive activity with further paradoxical reduction of pressure) and, in any case, in elderly or depressed subjects
- epileptic patients and those who are predisposed to seizures (e.g. alcohol withdrawal, brain damage), as SERENASE has been reported to induce seizures
- patients with known allergies or with a history of allergic reactions to drugs or with leukopenizing conditions
- during the manic phase of cyclical psychosis due to the possibility of a rapid change in mood towards depression
- since haloperidol is metabolised in the liver, it is advised to administer it with caution in patients with hepatic insufficiency
- in the case of simultaneous antiparkinsonian therapy, the latter should be continued after the suspension of SERENASE, which has a longer clearance time, in order to avoid the appearance or worsening of extrapyramidal symptoms. The doctor should consider the possibility of an increase intraocular pressure when SERENASE is given together with anticholinergic drugs, including antiparkinson's
- thyroxine can facilitate the toxicity of SERENASE. Therefore the product should be administered with great caution in patients with hyperthyroidism. Antipsychotic therapy in the latter should be accompanied by adequate thyrostatic treatment
- in schizophrenia, the response to treatment with antipsychotic drugs may be delayed. Even when medications are stopped, the resumption of symptoms may not appear visible for several weeks or months
- acute withdrawal symptoms including nausea, vomiting and insomnia have been described very rarely after abrupt withdrawal of high doses of antipsychotic drugs. Psychotic relapse can also occur, so a gradual withdrawal is recommended
- SERENASE should not be used on its own in cases where depression is predominant. SERENASE can be combined with antidepressant drugs in conditions where depression and psychosis coexist.
The drug should be administered under the supervision of the psychiatrist.
SERENASE 2 mg / 2 ml solution for injection for intramuscular use
SERENASE 5 mg / 2 ml solution for injection for intramuscular use
The patient should consult his doctor to be instructed on the most correct method of administering the drug.
SERENASE in ampoule formulation must be administered intramuscularly.
Interactions Which drugs or foods can change the effect of Serenase
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Do not administer concomitantly with QT prolonging drugs such as some class IA antiarrhythmics (e.g. quinidine, disopyramide and procainamide) and class III (e.g. amiodarone, sotalol), some antihistamines, other antipsychotics and some antimalarials (e.g. quinine and mefloquine) and also moxifloxacin. This list is to be considered only indicative and not exhaustive.
Mild to moderate increases in haloperidol concentrations have been reported in pharmacokinetic studies when administered with drugs such as itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, serthaline, chlorpromazine and promethazine. QTc increases were observed when haloperidol was administered in combination with the metabolic inhibitors ketoconazole (400 mg / day) or paroxetine (20 mg / day). In this case, the haloperidol dose may need to be reduced.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Concomitant use of diuretics, particularly those that can cause hypokalaemia, should be avoided.
The combination with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects of interaction. Like all neuroleptics, SERENASE can enhance the CNS depressant action of other drugs including alcohol, hypnotics, sedatives or strong analgesics. An enhancement of these effects has also been reported when combined with methyldopa.
SERENASE may decrease the antiparkinsonian effects of levodopa.
SERENASE inhibits the metabolism of tricyclic antidepressants, increasing their plasma levels.
Chronic treatment with enzymatic activators such as carbamazepine, phenobarbital, rifampicin, in combination with SERENASE causes a significant reduction in plasma levels of haloperidol; therefore, in case of concomitant treatment, the dose of SERENASE should be appropriately corrected. After stopping these drugs, the dosage of SERENASE may need to be reduced.
In rare cases, the following symptoms have been reported during concomitant use of lithium and SERENASE: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, brain stem disorders, acute brain syndrome and coma. Most of these symptoms were Reversible. It remains controversial whether these symptoms are related to co-administration or whether they are the manifestation of a distinct clinical episode. Nevertheless, it is recommended that, in patients treated concomitantly with SERENASE and lithium, therapy is immediately discontinued if these appear. symptoms SERENASE can antagonize the action of adrenaline and other sympathomimetic agents and reverse the hypotensive effects of adrenergic agents such as guanethidine.
An "antagonistic action on" the effect of the anticoagulant phenindione has been reported.
Warnings It is important to know that:
Neuroleptic Malignant Syndrome
A potentially fatal symptom complex called Neuroleptic Malignant Syndrome has been reported during treatment with antipsychotic drugs. Clinical manifestations of this syndrome are: hyperpyrexia, muscle stiffness, akinesia, vegetative disorders (irregularities in the pulse and blood pressure, sweating, tachycardia, arrhythmias); changes in consciousness which can progress to stupor and coma. The treatment of the S.N.M. it consists in immediately suspending the administration of antipsychotic drugs and other non-essential drugs and in instituting intensive symptomatic therapy (particular care must be taken to reduce hyperthermia and correct dehydration). If the resumption of antipsychotic treatment is deemed essential, the patient should be carefully monitored.
With the use of some major neuroleptics, including SERENASE, the occurrence of cases of bronchopneumonia has been reported, probably favored by dehydration due to reduced sensation of thirst, haemoconcentration and reduced pulmonary ventilation; the appearance of such symptoms, especially in the " elderly, requires prompt and adequate therapy.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine. SERENASE is contraindicated in pregnancy and during lactation.
The following symptoms have been observed in newborn babies of mothers who have taken conventional or atypical antipsychotics, including SERENASE, during the last trimester (last three months of pregnancy): shaking, muscle stiffness and / or weakness, sleepiness, agitation, breathing problems and difficulty in food intake. If your child shows any of these symptoms, contact your doctor.
Effects on ability to drive and use machines
SERENASE can cause sedation and reduced attention, especially with higher doses and at the beginning of treatment; these effects can be enhanced by alcohol. Patients should be advised not to drive or operate machinery during treatment until their reactivity to the drug is ascertained.
Warnings about some of the ingredients of SERENASE
SERENASE tablets contain lactose. If your doctor has diagnosed an intolerance to some sugars, contact your doctor before taking this medicine. SERENASE oral drops contain parahydroxybenzoates. They can cause allergic reactions (including delayed). SERENASE 2 mg / 2 ml solution for injection contains parahydroxybenzoates. They can cause allergic reactions (even delayed) and, exceptionally, bronchospasm.
Dosage and method of use How to use Serenase: Dosage
The suggested posologies are only indicative as the dosage is strictly individual and varies according to the patient's response. This means that in the acute phase a progressive increase in doses is often necessary, followed by a gradual reduction in the maintenance phase, in order to establish the minimum effective dose. High doses should only be given to patients who have responded poorly to lower doses.
ADULTS
1. As a neuroleptic
acute phase: acute episodes of schizophrenia, delirium tremens, paranoia, acute confusion, Korsakoff's syndrome, acute paranoia: 5 mg for intramuscular use to be repeated every hour until adequate symptom control is achieved and in any case up to a maximum of 20 mg / day. In oral administration, doses between 2 and 20 mg / day could be administered either as a single dose or as divided doses.
chronic phase: chronic schizophrenia, chronic alcoholism, chronic personality disorders: for oral administration: 1-3 mg three times a day, depending on the individual response.
However, the maximum daily dose should not exceed 20 mg.
2. In the control of psycho-motor agitation
acute phase: mania, dementia, alcoholism, personality and behavioral disorders, hiccups, choreiform movements, tics, stuttering: 5 mg for intramuscular use to be repeated every hour until adequate symptom control is achieved and in any case up to a maximum of 20 mg / day
chronic phase: for oral administration: from 0.5-1 mg three times a day up to 2-3 mg three times a day, depending on the individual response.
3. As a hypnotic
for oral administration: 2-3 mg in a single dose, in the evening before bedtime.
4. As an antiemetic
in vomiting of central origin: 5 mg for intramuscular use
In the prophylaxis of postoperative vomiting: 2.5-5 mg for intramuscular use at the end of the operation.
SENIOR CITIZENS
In the treatment of elderly patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Overdose What to do if you have taken too much Serenase
Symptoms:
The manifestations of overdose are those deriving from an exaltation of the known pharmacological effects and adverse reactions. The main symptoms are: intense extrapyramidal reactions, hypotension and sedation. An extrapyramidal reaction manifests itself with muscle stiffness and generalized or localized tremor. In extreme cases, the patient may manifest a comatose state with respiratory depression and severe arterial hypotension, leading to a shock-like state. The risk of ventricular arrhythmias possibly associated with prolongation of the QT interval of the electrocardiogram should also be considered.
Treatment:
There is no specific antidote. Treatment is primarily supportive. Activated charcoal can be given. In comatose patients, a patent airway should be established by tracheostomy or intubation. Respiratory depression may require artificial respiration. The ECG and vital signs should be monitored until the ECG is restored to normal.
Severe arrhythmias should be treated with appropriate antiarrhythmic measures.
Hypotension and circulatory collapse can be treated by intravenous infusion of fluids, plasma or concentrated albumin or the use of vasopressor agents such as dopamine or noradrenaline. Adrenaline should not be used as it may cause severe hypotension in the presence of SERENASE. In case of severe extrapyramidal reactions, anti-parkinson drugs (eg benztropine mesylate: 1-2 mg im or iv) should be administered parenterally.
In case of accidental ingestion / intake of an excessive dose of SERENASE, notify your doctor immediately or go to the nearest hospital.
FOR ANY DOUBT ABOUT THE USE OF SERENASE, ASK YOUR DOCTOR OR PHARMACIST.
Side Effects What are the side effects of Serenase
Like all medicines, SERENASE can cause side effects, although not everybody gets them.
Side effects reported by patients taking SERENASE are listed below:
- Nervous system disorders: extrapyramidal disorders, hyperkinesia, tremor, hypertonia, dystonia, somnolence, bradykinesia, dizziness, akathisia, dyskinesia, hypokinesia, tardive dyskinesia, motor dysfunction, involuntary muscle contractions, neuroleptic malignant syndrome, nystagmus, parkinsonism, sedation headache.
- Eye disorders: vision disturbances, oculogyric crisis, blurred vision.
- Gastrointestinal disorders: constipation, dry mouth, salivary hypersecretion, vomiting, nausea.
- Vascular disorders: orthostatic hypotension, hypotension.
- Reproductive system and breast disorders: erectile dysfunction, amenorrhea, feeling of discomfort in the breast, breast pain, galactorrhea, dysmenorrhea, sexual dysfunction, menstrual disorders, menorrhagia, priapism, gynecomastia.
- Investigations: weight gain, prolonged QT electrocardiogram, weight decrease.
- Endocrine disorders: hyperprolactinaemia, inappropriate secretion of the antidiuretic hormone.
- Psychiatric disorders: decreased libido, loss of libido, agitation, psychotic disorders, confusional state, depression, insomnia.
- Cardiac disorders: tachycardia, torsade de pointes (torsade de pointes), ventricular fibrillation, ventricular tachycardia, extrasystole.
- Musculoskeletal and connective tissue disorders: trismus, stiff neck, muscle stiffness, muscle spasms, musculoskeletal pain, muscle contractions.
- General disorders and administration site conditions: gait disturbances, sudden death, face edema, edema, hyponatremia, hyperthermia.
- Blood and lymphatic system disorders: agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, neutropenia. Immune system disorders: anaphylactic reaction, hypersensitivity.
- Metabolism and nutrition disorders: hypoglycemia.
- Respiratory, thoracic and mediastinal disorders: bronchospasm, laryngospasm, laryngeal edema, dyspnoea.
- Hepatobiliary disorders: acute liver failure, hepatitis, cholestasis, jaundice, liver function test abnormalities.
- Skin and subcutaneous tissue disorders: leukocytoclastic vasculitis, exfoliative dermatitis, urticaria, photosensitivity reactions, rash, pruritus, hyperhidrosis.
- Pregnancy, puerperium and perinatal conditions: Tremor, muscle stiffness, weakness, drowsiness, agitation, breathing difficulties or feeding disturbances may occur in infants born to mothers who have used SERENASE during the last trimester of pregnancy.
Possible side effects
- Blood clots (thrombi) in the veins particularly in the legs (symptoms include swelling, pain and redness in the legs), which can travel through blood vessels in the lungs causing chest pain and difficulty breathing. If you notice any of these symptoms, please contact your doctor immediately.
Additional important information
- In older people with dementia, a small increase in the number of deaths has been reported for those patients taking antipsychotics compared with those not taking them.
- Elderly patients with dementia who require treatment with SERENASE to control their behavior may have an increased risk of death compared to not being treated.
- If you have had episodes of irregular heartbeat (palpitations, dizziness, fainting), high fever, muscle stiffness, fast breathing, abnormal sweating or decreased mental alertness, contact your doctor immediately. Your body may be reacting inappropriately to the medicine.
- Rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been observed with SERENASE and other drugs of the same class. Very rare cases of sudden death.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. Reporting of side effects If you get any side effects, including any side effects not listed in this leaflet, contact your doctor or pharmacist. Side effects can also be reported directly via the national reporting system at https: // www.aifa.gov.it/content/segnalazioni-reazioni-avverse ". By reporting side effects you can help provide more information on the safety of this medicine."
Expiry and Retention
Expiry: see the expiry date indicated on the package. WARNING: do not use the medicine after the expiry date indicated on the package. The expiry date refers to the product in intact packaging, correctly stored.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the sight and reach of children.
Composition and pharmaceutical form
COMPOSITION
SERENASE 1 mg tablets
Each tablet contains:
Active ingredient: haloperidol 1 mg
Excipients: lactose, corn starch, talc, hydrogenated vegetable oil.
SERENASE 5 mg tablets
Each tablet contains:
Active ingredient: haloperidol 5 mg
Excipients: lactose, corn starch, talc, hydrogenated vegetable oil.
SERENASE 10 mg tablets
Each tablet contains:
Active ingredient: haloperidol 10 mg
Excipients: lactose, corn starch, talc, hydrogenated vegetable oil.
SERENASE 2 mg / ml oral drops, solution
100 ml of oral solution contain:
Active ingredient: haloperidol 200 mg
Excipients: lactic acid, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, purified water.
SERENASE 10 mg / ml oral drops, solution
100 ml of oral solution contain:
Active ingredient: haloperidol 1 g
Excipients: lactic acid, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, purified water.
SERENASE 2 mg / 2 ml solution for injection for intramuscular use
Each vial contains:
Active ingredient: haloperidol 2 mg
Excipients: methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, lactic acid, water for injections.
SERENASE 5 mg / 2 ml solution for injection for intramuscular use
Each vial contains: Active ingredient: haloperidol 5 mg
Excipients: lactic acid, water for injections.
PHARMACEUTICAL FORM AND CONTENT
SERENASE 1 mg tablets: 20 tablets
SERENASE 5 mg tablets: 20 tablets
SERENASE 10 mg tablets: 20 tablets
SERENASE 2 mg / ml oral drops, solution: 15 ml oral drops, solution
SERENASE 10 mg / ml oral drops, solution: 15 ml oral drops, solution
SERENASE 2 mg / 2 ml solution for injection for intramuscular use: 5 ampoules for solution for injection
SERENASE 5 mg / 2 ml solution for injection for intramuscular use: 5 ampoules for solution for injection
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
SERENASE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
SERENASE 1 mg tablets
One tablet contains
Active principle: haloperidol 1 mg
Excipients with known effects: lactose
SERENASE 5 mg tablets
One tablet contains
Active principle: haloperidol 5 mg
Excipients with known effects: lactose
SERENASE 10 mg tablets
One tablet contains
Active principle: haloperidol 10 mg
Excipients with known effects: lactose
SERENASE 2 mg / ml oral drops, solution
100 ml of oral solution contain
Active ingredient: haloperidol 200 mg
Excipients with known effects: methyl p-hydroxybenzoate, propyl p-hydroxybenzoate
SERENASE 10 mg / ml oral drops, solution
100 ml of oral solution contain
Active ingredient: haloperidol 1 g
Excipients with known effects: methyl p-hydroxybenzoate, propyl p-hydroxybenzoate
SERENASE 2 mg / 2 ml solution for injection for intramuscular use
Each vial contains
Active ingredient: haloperidol 2 mg
Excipients with known effects: methyl p-hydroxybenzoate, propyl p-hydroxybenzoate
SERENASE 5 mg / 2 ml solution for injection for intramuscular use
Each vial contains
Active ingredient: haloperidol 5 mg
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Tablets
Oral drops, solution
Solution for injection for intramuscular use
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Oral tablets and drops, solution:
Psychomotor agitation in case of:
- manic states, dementia, oligophrenia, psychopathy, acute and chronic schizophrenia, alcoholism, compulsive, paranoid, histrionic personality disorders.
Delusions and hallucinations in case of:
- acute and chronic schizophrenia, paranoia, acute mental confusion, alcoholism (Korsakoff's Syndrome), hypochondriasis, personality disorders of the paranoid, schizoid, schizotypic, antisocial type, some cases of the borderline type.
- Choreiform movements.
- Agitation, aggression and flight reactions in elderly subjects.
- Tics and stuttering.
- He retched.
- Hiccup.
- Alcohol withdrawal syndromes.
Solution for injection for intramuscular use:
Resistant forms of psychomotor excitement, acute delusional and / or hallucinatory psychosis, chronic psychosis.
The use of the product in high doses should be limited to the therapy of resistant forms of: psychomotor excitation syndromes, acute delusional and / or hallucinatory psychosis, chronic psychosis. In the treatment of intense pain generally in association with narcotic analgesics.
04.2 Posology and method of administration
The suggested posologies are only indicative as the dosage is strictly individual and varies according to the patient's response (age, condition of the patient, nature and severity of the ailments, therapeutic response, tolerability of the product). This means that in the acute phase a progressive increase in doses is often necessary, followed by a gradual reduction in the maintenance phase, in order to establish the minimum effective dose. High doses should only be given to patients who have responded poorly to lower doses.
SERENASE in ampoule formulation should be administered intramuscularly (see section 4.4. Special warnings and precautions for use).
ADULTS
1. As a neuroleptic
acute phase: acute episodes of schizophrenia, delirium tremens, paranoia, acute confusion, Korsakoff's syndrome, acute paranoia: 5 mg i.m. to be repeated every hour until adequate symptom control is achieved and in any case up to a maximum of 20 mg per day.
In oral administration, doses between 2 and 20 mg / day could be administered either as a single dose or as divided doses.
chronic phase: chronic schizophrenia, chronic alcoholism, chronic personality disorders: for oral administration: 1-3 mg three times a day, depending on the individual response.
However, the maximum daily dose should not exceed 20 mg.
2. In the control of psycho-motor agitation
acute phase: mania, dementia, alcoholism, personality and behavioral disorders, hiccups, choreiform movements, tics, stuttering: 5 mg i.m. to be repeated every hour until adequate symptom control is achieved and in any case up to a maximum of 20 mg per day
chronic phase: for oral administration: from 0.5-1 mg three times a day up to 2-3 mg three times a day, depending on the individual response.
3. As a hypnotic
for oral administration: 2-3 mg in a single dose, in the evening before bedtime.
4. As an antiemetic
in vomiting of central origin: 5 mg i.m.
In the prophylaxis of postoperative vomiting: 2.5-5 mg i.m. at the end of the intervention.
SENIOR CITIZENS
In the treatment of elderly patients the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
PEDIATRIC POPULATION
The safety and efficacy of haloperidol have not been established in the pediatric population.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Comatose states, patients strongly depressed by alcohol or other substances active on the central nervous system, endogenous depressions without agitation, Parkinson's disease.
Asthenia, neurosis and spastic states due to lesions of the basal ganglia (hemiplegia, multiple sclerosis, etc.).
Clinically significant heart disease (e.g. recent acute myocardial infarction, decompensated heart failure, arrhythmias treated with class IA and III antiarrhythmic drugs).
QTc interval prolongation.
Subjects with a family history of arrhythmia or torsades de pointes.
Uncorrected hypokalaemia.
Concomitant use of QTc prolonging drugs.
Known or suspected pregnancy, lactation and in children.
04.4 Special warnings and appropriate precautions for use
Perform a basic ECG before starting treatment (see section 4.3).
Monitor the ECG during therapy based on the patient's clinical condition.
During therapy, reduce dosage if QT prolongation is observed and discontinue if QTc is> 500ms.
Periodic checking of electrolytes is recommended.
Avoid concomitant therapy with other neuroleptics.
Rare cases of sudden death have been reported in psychiatric patients treated with antipsychotic drugs, including SERENASE.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Patients treated with antipsychotic drugs often have acquired risk factors for VTE; therefore all possible risk factors for VTE must be identified before and during therapy with SERENASE and preventive measures undertaken.
Increased mortality in older people with dementia
Data from two large observational studies have shown that the risk of death is slightly increased in older people with dementia treated with antipsychotics than in untreated people. There are insufficient data to accurately estimate the magnitude of the risk and the cause of the increased risk is not known.
SERENASE is not licensed for the treatment of dementia-related behavioral disorders.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs show an increased risk of death. Analysis of seventeen placebo-controlled clinical trials (10-week modal duration), predominantly in patients receiving atypical antipsychotic drugs, revealed a 1.6- to 1.7-fold increased risk of death in drug-treated patients. compared with placebo. In a 10-week controlled clinical trial with a typical drug, the mortality rate was approximately 4.5% in drug-treated patients compared to approximately 2.6% in the drug-treated group. placebo.
Although the causes of death varied, most deaths appeared to be cardiovascular (e.g. heart failure, sudden death) or infectious (e.g. pneumonia) in nature. Observational studies suggest that, like atypical antipsychotics, treatment with conventional antipsychotics can increase mortality.
In this context, it is not clear whether the increased mortality observed in observational studies can be attributed to antipsychotics or, conversely, to some characteristics of the patients.
Cardiovascular effects
Cases of QT interval prolongation and / or ventricular arrhythmias, in addition to rare cases of sudden death, have been reported very rarely with haloperidol and may occur more frequently with high drug doses and in predisposed patients.
Since QT interval prolongation has been observed during SERENASE therapy, caution is recommended in patients with conditions predisposing to QT prolongation (prolonged QT syndrome, hypokalaemia, electrolyte imbalance, drugs that cause QT prolongation. , cardiovascular disease, family history of QT prolongation) especially if SERENASE is administered parenterally (see section 4.5).
The risk of QT interval prolongation and / or ventricular arrhythmias may increase with high doses (see sections 4.8 and 4.9) or when the medicinal product is administered parenterally.
SERENASE should not be administered intravenously as intravenous administration of haloperidol has been associated with an increased risk of QT prolongation and Torsade de Pointes.
Tachycardia and hypotension have also been reported in occasional patients.
Neuroleptic malignant syndrome
Like other antipsychotic drugs, SERENASE has also been associated with neuroleptic malignant syndrome: a rare and idiosyncratic response characterized by hyperthermia, generalized muscle rigidity, autonomic instability, altered state of consciousness. Hyperthermia is often an early symptom of this syndrome. Antipsychotic treatment should be discontinued immediately and appropriate supportive care and careful monitoring instituted.
Tardive dyskinesia
As with all antipsychotic drugs, tardive dyskinesia may occur in some patients on long-term therapy or after discontinuation of therapy. This syndrome is mainly characterized by involuntary rhythmic movements of the tongue, face, mouth or jaw. Manifestations may be permanent in some patients. The syndrome may be masked by resuming treatment, increasing the dose or switching to another antipsychotic. Treatment should be stopped as soon as possible.
Extrapyramidal symptoms
As with all neuroleptics, extrapyramidal symptoms may arise, eg tremor, rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia.
Anticholinergic antiparkinsonian drugs may be prescribed if necessary, but should not be used routinely as a preventative measure. If concomitant treatment with antiparkinsonian drugs is necessary, it should be continued after the discontinuation of SERENASE, if their excretion is faster than that of SERENASE, in order to avoid the development or aggravation of extrapyramidal symptoms. The physician should consider what is possible. increased intraocular pressure due to anticholinergic drugs, including antiparkinsonian agents, when administered concomitantly with SERENASE.
Safety data available in the pediatric population indicate a risk of extrapyramidal symptoms, including tardive dyskinesia and sedation. No long-term safety data are available.
Seizures / Convulsions
Seizures triggered by SERENASE have been reported. Caution is recommended in patients with epilepsy and in conditions predisposing to seizures (eg alcohol withdrawal and brain damage).
Hepatobiliary effects
As SERENASE is metabolised by the liver, caution is recommended in patients with liver disease. There have been isolated reports of abnormal liver function or hepatitis, most often cholestatic.
Effects on the endocrine system
Thyroxine can facilitate the toxicity of SERENASE. Antipsychotic therapy in patients with hyperthyroidism should only be undertaken with great caution and should always be accompanied by therapy to achieve a euthyroid state.
The hormonal effects of neuroleptic antipsychotics include hyperprolactinaemia, which can cause galactorrhea, gynaecomastia, and oligo- or amenorrhea. Very rare cases of hypoglycaemia and ADH Inappropriate Secretion Syndrome have been reported.
Additional considerations
In schizophrenia, the response to antipsychotic drug treatment may be delayed. Even if the drugs are stopped, the resumption of symptoms may not appear visible for several weeks or months. Acute withdrawal symptoms including nausea, vomiting and insomnia have been described very rarely after abrupt withdrawal of high doses of antipsychotic drugs. Psychotic relapse can also occur, so a gradual withdrawal is recommended. As with all antipsychotics, SERENASE should not be used on its own in cases where depression is predominant. SERENASE can be combined with antidepressant drugs in conditions where depression and psychosis coexist.
Important information about some of the ingredients
SERENASE tablets contain lactose therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
SERENASE oral drops contain parahydroxybenzoates. They can cause allergic reactions (even delayed).
SERENASE injectable solutions contain parahydroxybenzoates. They can cause allergic reactions (even delayed) and, exceptionally, bronchospasm.
04.5 Interactions with other medicinal products and other forms of interaction
As with other antipsychotics, use caution when prescribing haloperidol along with other drugs that induce QT interval prolongation.
Haloperidol follows several metabolic pathways including glucuronidation and the cytochrome P450 system (particularly CYP 3A4 or CYP 2D6). Inhibition of these metabolic pathways by another drug or a decrease in the enzymatic activity of CYP 2D6 it can cause increased haloperidol concentration and an increased risk of adverse events including QT prolongation.
Mild to moderate increases in haloperidol concentration have been reported in pharmacokinetic studies when co-administered with substrates or inhibitors of CYP 3A4 or CYP 2D6 isoenzymes such as itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, serthal chlorpromazine and promethazine. A decrease in CYP 2D6 enzyme activity may cause increased concentrations of haloperidol. Increases in QTc have been observed when haloperidol was administered with a combination of the metabolic inhibitors ketoconazole (400 mg / day) and paroxetine (20 mg / day). die). In this case it may be necessary to reduce the haloperidol dose. Caution should be used when administering haloperidol in combination with drugs that can cause electrolyte imbalance.
Effects of other drugs on haloperidol
When prolonged treatment with enzyme inducers such as carbamazepine, phenobarbital, rifampicin is added to SERENASE therapy, a significant decrease in plasma haloperidol levels may occur. Therefore, during the combined treatment, the dose of SERENASE should be adjusted if necessary. It may be necessary to reduce the dosage of SERENASE after stopping such drugs.
Sodium valproate, a drug known as a glucuronidation inhibitor, does not affect the plasma levels of haloperidol.
Effects of haloperidol on other drugs
Like all neuroleptics, SERENASE may enhance the CNS depressant action of other drugs including alcohol, hypnotics, sedatives, or strong analgesics.
An enhancement of these effects has also been reported when combined with methyldopa. SERENASE can antagonize the action of adrenaline and other sympathomimetic agents and reverse the hypotensive effect of adrenergic blocking agents, such as eg guanethidine.
SERENASE may decrease the antiparkinsonian effects of levodopa.
Haloperidol is a CYP 2D6 inhibitor.
Do not administer concomitantly with QT prolonging drugs such as some class IA antiarrhythmics (e.g. quinidine, disopyramide and procainamide) and class III (e.g. amiodarone, sotalol), some antihistamines, other antipsychotics and some antimalarials (e.g. quinine and mefloquine) and also moxifloxacin. This list is to be considered only indicative and not exhaustive.
Do not administer concomitantly with drugs that cause alteration of electrolytes.
Concomitant use of diuretics, particularly those that can cause hypokalaemia, should be avoided.
SERENASE inhibits the metabolism of tricyclic antidepressants, thereby increasing their plasma levels.
Other forms of interaction
In rare cases, the following symptoms have been reported during concomitant use of lithium and SERENASE: encephalopathy, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, brain stem disorders, acute brain syndrome and coma. Most of these symptoms were Reversible. It remains controversial whether these symptoms are related to co-administration or whether they are the manifestation of a distinct clinical episode. Nevertheless, it is recommended that, in patients treated concomitantly with SERENASE and lithium, therapy is immediately discontinued if these appear. symptoms.
An "antagonistic action on" the effect of the anticoagulant phenindione has been reported.
04.6 Pregnancy and lactation
Studies in animals have shown a teratogenic effect of haloperidol (see section 5.3).
Infants exposed to conventional or atypical antipsychotics including SERENASE during the third trimester of pregnancy are at risk for side effects including extrapyramidal or withdrawal symptoms which may vary in severity and duration after birth. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, food intake disturbances. Infants should therefore be closely monitored.
Not to be used in case of confirmed or presumed pregnancy, nor during breastfeeding.
04.7 Effects on ability to drive and use machines
SERENASE can cause sedation and reduced attention, especially with higher doses and at the beginning of treatment; these effects can be enhanced by alcohol. Patients should be advised not to drive or operate machinery during treatment until their reactivity to the drug is ascertained.
04.8 Undesirable effects
Clinical trial data
Data from double blind placebo controlled studies - Adverse drug reactions reported at incidence ≥ 1%
The safety of SERENASE (2-20 mg / day) was evaluated in 566 subjects (including 284 treated with SERENASE and 282 with placebo) participating in 3 double-blind placebo-controlled clinical trials, two in the treatment of schizophrenia and the third in the treatment of bipolar disorder.
Adverse drug reactions (ADRs) reported by ≥ 1% of subjects treated with SERENASE in these studies are shown in Table 1.
Table 1. Adverse drug reactions reported by ≥ 1% of SERENASE-treated subjects participating in 3 clinical trials of SERENASE in parallel with placebo.
Data from active controlled clinical trials - Adverse drug reactions reported at incidence ≥ 1%
Sixteen double-blind, active-controlled clinical trials were selected to determine the incidence of ADRs. In these 16 studies 1295 subjects were treated with SERENASE at a dose of 1-45 mg / day for the treatment of schizophrenia.
The ADRs reported by ≥ 1% of subjects treated with SERENASE observed in these studies are shown in Table 2.
Table 2. Adverse drug reactions reported by ≥ 1% of subjects treated with SERENASE in 16 double-blind controlled clinical studies involving SERENASE
Data from placebo and active controlled clinical trials - Adverse drug reactions reported at incidence
Additional ADRs that occurred in
Table 3. Adverse drug reactions reported by
Endocrine pathologies
Hyperprolactinemia
Psychiatric disorders
Decreased libido
Loss of libido
Agitation
Nervous system disorders
Motor dysfunction
Involuntary muscle contractions
Neuroleptic malignant syndrome
Nystagmus
Parkinsonism
Sedation
Eye disorders
Blurred vision
Cardiac pathologies
Tachycardia
Musculoskeletal and connective tissue disorders
Trismus
Stiff neck
Muscle stiffness
Muscle spasms
Musculoskeletal soreness
Muscle contractions
Diseases of the reproductive system and breast
Amenorrhea
Breast discomfort
Breast pain
Galactorrhea
Dysmenorrhea
Sexual dysfunction
Menstrual disturbances
Menorrhagia
General disorders and administration site conditions
Gait disturbances
Postmarketing data
The first adverse events identified as ADRs during the post-marketing experience with haloperidol are included in Table 4. The post-marketing review is based on the review of all cases in which the active part of haloperidol (SERENASE) was administered. In each table the frequencies are provided in accordance with the following convention:
Very common ≥ 1/10
Common ≥ 1/100 e
Uncommon ≥ 1/1000 e
Rare ≥ 1/10000 e
Very rare
In Table 4 ADRs are shown by frequency class based on spontaneous reporting rate.
Table 4. Adverse drug reactions in postmarketing experience with haloperidol (oral, solution) reported by frequency category estimated from spontaneous reporting rates
Disorders of the blood and lymphatic system
Very rare Agranulocytosis, pancytopenia, thrombocytopenia, leukopenia, neutropenia
Disorders of the immune system
Very rare Anaphylactic reaction, hypersensitivity
Endocrine pathologies
Very rare Inappropriate antidiuretic hormone secretion
Metabolism and nutrition disorders
Very rare Hypoglycemia
Psychiatric disorders
Very rare Psychotic disorders, agitation, confusion, depression, insomnia
Nervous system disorders
Very rare Convulsions, headaches
Cardiac pathologies
Very rare Torsade de pointes (torsade de pointes), ventricular fibrillation, ventricular tachycardia, extrasystole
Respiratory, thoracic and mediastinal disorders
Very rare Bronchospasm, laryngospasm, laryngeal edema, dyspnoea
Gastrointestinal disorders
Very rare Vomiting, nausea
Hepatobiliary disorders
Very rare Acute liver failure, hepatitis, cholestasis, jaundice, liver function test abnormalities
Skin and subcutaneous tissue disorders
Very rare Leukocytoclastic vasculitis, exfoliative dermatitis, urticaria, photosensitivity reactions, rash, pruritus, hyperhidrosis
Renal and urinary disorders
Very rare Urinary retention
Pregnancy, puerperium and perinatal conditions
Not known Neonatal withdrawal syndrome
Extrapyramidal symptoms (see section 4.6)
Diseases of the reproductive system and breast
Very rare Priapism, gynecomastia
General disorders and administration site conditions
Very rare Sudden death, face edema, edema, hyponatremia, hyperthermia
Diagnostic tests
Very rare Electrocardiogram with prolonged QT, weight decrease
Rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been observed with SERENASE and other drugs of the same class.
Very rare cases of sudden death.
Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis, have been reported with antipsychotic drugs - Frequency not known.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse".
04.9 Overdose
Symptoms:
The manifestations of overdose are those deriving from an exaltation of the known pharmacological effects and adverse reactions. The main symptoms are: intense extrapyramidal reactions, hypotension and sedation. An extrapyramidal reaction manifests itself with muscle stiffness and generalized or localized tremor.
In extreme cases, the patient may manifest a comatose state with respiratory depression and severe arterial hypotension, leading to a shock-like state. The risk of ventricular arrhythmias possibly associated with prolongation of the QT interval of the electrocardiogram should also be considered.
Treatment:
There is no specific antidote. Treatment is primarily supportive. Activated charcoal can be given.
In comatose patients, a patent airway should be established by tracheostomy or intubation. Respiratory depression may require artificial respiration. The ECG and vital signs should be monitored until the ECG is restored to normal.
Severe arrhythmias should be treated with appropriate antiarrhythmic measures.
Hypotension and circulatory collapse can be treated by intravenous infusion of fluids, plasma or concentrated albumin or the use of vasopressor agents such as dopamine or noradrenaline. Adrenaline should not be used as it may cause severe hypotension in the presence of SERENASE.
In case of severe extrapyramidal reactions, anti-parkinson drugs (eg benztropine mesylate: 1-2 mg im or iv) should be administered parenterally.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antipsychotic, derivative of butyrophenone.
ATC code: N05AD01
Haloperidol is a neuroleptic belonging to the group of butyrophenones. Haloperidol is a potent dopamine antagonist; it has similar affinity for all dopamine receptor subtypes: it is therefore a non-selective dopaminergic antagonist. The drug also has antagonistic activity towards a-adrenergic receptors, while it does not exhibit antihistaminergic or anticholinergic activity.
The drug's effect on delirium and hallucinations is believed to be linked to dopaminergic antagonism in the mesocortical and limbic regions.
Antagonism in the basal ganglia is probably the cause of the extrapyramidal motor side effects (dystonia, akathisia and parkinsonism).
Haloperidol has an effective psychomotor sedative effect which contributes to the favorable action on mania and other agitation syndromes.
Haloperidol has also been shown to be useful in the treatment of chronic pain, an effect possibly due to limbic action.
The more peripheral anti-dopaminergic effects explain the activity against nausea and vomiting (antagonism at the level of chemoreceptor trigger zone, CTZ), the increased release of prolactin (through the antagonism towards the inhibition activity, mediated by dopamine, of the release of prolactin by the adenohypophysis) and the relaxation of the gastrointestinal sphincters.
05.2 Pharmacokinetic properties
Absorption
After oral administration, the bioavailability of the drug is 60-70% of the administered dose; maximum plasma concentrations are reached between 2 and 6 hours.
After intramuscular administration, the peak concentration is reached after 20 minutes.
Distribution
Haloperidol easily crosses the blood-brain barrier. The drug is 92% bound to plasma proteins. The steady-state volume of distribution (Vdss) is high (7.9 + 2.5 L / kg).
Metabolism
Haloperidol is metabolised by several pathways, including the cytochrome P450 enzyme system (particularly CYP 3A4 or CYP 2D6) and glucuronidation.
Elimination
The terminal plasma half-life (terminal elimination) is on average 24 hours (12 ÷ 38 hours) after oral administration and 21 hours (13 ÷ 36 hours) after intramuscular administration. Excretion occurs via faecal (60%) and urine (40%). Approximately 1% of the ingested dose is excreted as unchanged drug in the urine.
Therapeutic concentrations
It has been suggested that the therapeutic response is achieved with a range of haloperidol plasma concentrations between 4 mcg / l and 20-25 mcg / l.
05.3 Preclinical safety data
Non-clinical data based on conventional studies of repeated dose toxicity, genotoxicity and carcinogenicity did not reveal any particular hazard for humans.
In rodents the administration of haloperidol has shown a decrease in fertility and limited teratogenic and embryotoxic effects.
In several published studies in vitro, haloperidol has shown the ability to block the cardiac hERG channel.
In some studies conducted in vivo In animal models, intravenous haloperidol administration caused significant QTc prolongation, at doses equal to 0.3 mg / kg iv, showing a peak blood concentration Cmax 3 to 7 times higher than the effective plasma concentration of 4- 20 ng / ml obtained in man.
These intravenously administered doses that cause QTc interval prolongation did not cause arrhythmias. In some studies a higher dose of 1 to 5 mg / kg administered intravenously caused QTc prolongation and / or ventricular cardiac arrhythmias. a peak plasma concentration Cmax 19 to 68 times greater than the effective plasma concentrations in humans.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablets
lactose, corn starch, talc, hydrogenated vegetable oil
Oral drops, solution
lactic acid, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, purified water
SERENASE 2 mg / 2ml solution for injection for intramuscular use
methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, lactic acid, water for
injectable preparations
SERENASE 5 mg / 2ml solution for injection for intramuscular use
lactic acid, water for injections
06.2 Incompatibility
None known.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
SERENASE 2 mg / 2 ml solution for injection for intramuscular use: carton box containing 5 ampoules of 2 mg in 2 ml
SERENASE 5 mg / 2 ml solution for injection for intramuscular use: carton box containing 5 ampoules of 5 mg in 2 ml
SERENASE 2 mg / ml oral drops, solution: cardboard box containing 15 ml plastic bottle with dropper (20 drops = 1 ml = 2 mg)
SERENASE 10 mg / ml oral drops, solution: cardboard box containing 15 ml plastic bottle with dropper (20 drops = 1 ml = 10 mg)
SERENASE 1 mg tablets: carton box containing 20 tablets of 1 mg packed in opaque blisters
SERENASE 5 mg tablets: cardboard box containing 20 tablets of 5 mg packed in blisters
SERENASE 10 mg tablets: cardboard box containing 20 tablets packed in blisters
06.6 Instructions for use and handling
Oral drops, solution:
SERENASE is available in 15ml bottles with dropper device and child resistant closure. To open, push the plastic cap down firmly, then unscrew.
After removing the cap, pour the required number of drops using the dropper.
07.0 MARKETING AUTHORIZATION HOLDER
LUSOFARMACO
Luso Farmaco Institute of Italy S.p.A.
Milanofiori - Road 6 - Building L - Rozzano (MI)
08.0 MARKETING AUTHORIZATION NUMBER
SERENASE 1 mg tablets: 016805032
SERENASE 5 mg tablets: 016805044
SERENASE 10 mg tablets: 016805057
SERENASE 2 mg / ml oral drops, solution: 016805095
SERENASE 10 mg / ml oral drops, solution: 016805107
SERENASE 2 mg / 2 ml solution for injection for intramuscular use: 016805018
SERENASE 5 mg / 2 ml solution for injection for intramuscular use: 016805020
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
SERENASE 1 mg tablets: 10.02.87 / 1.06.2010
SERENASE 5 mg tablets: 13.04.83 / 1.06.2010
SERENASE 10 mg tablets: 13.04.83 / 1.06.2010
SERENASE 2 mg / ml oral drops, solution: 13.02.86 / 1.06.2010
SERENASE 10 mg / ml oral drops, solution: 13.02.86 / 1.06.2010
SERENASE 2 mg / 2 ml solution for injection for intramuscular use: 24.03.60 / 1.06.2010
SERENASE 5 mg / 2 ml solution for injection for intramuscular use: 13.04.83 / 1.06.2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of 15 July 2014
