Active ingredients: Chlorpromazine
LARGACTIL 25 mg film-coated tablets
LARGACTIL 100 mg film-coated tablets
LARGACTIL 50 mg / 2 ml solution for injection
Why is Largactil used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
antipsychotics.
THERAPEUTIC INDICATIONS
Treatment of schizophrenias, paranoid states and mania. Toxic psychosis (amphetamines, LSD, cocaine etc.). Organic mental syndromes accompanied by delirium. Anxiety disorders if particularly severe and resistant to therapy with typical anxiolytics. Depression if accompanied by agitation and delirium, mostly in association with antidepressants. Vomiting and incoercible hiccups. Treatment of intense pain generally in association with narcotic analgesics. Pre-anesthetic medication.
Contraindications When Largactil should not be used
Hypersensitivity to the active substance, to any of the excipients or to other closely related substances from a chemical point of view. Comatose states, especially those caused by substances with a depressive action on the central nervous system (alcohol, barbiturates, opiates, etc.); patients with suspected or recognized subcortical brain damage; severe states of depression; blood dyscrasias; liver and kidney diseases. The product is not indicated in infancy. Pheochromocytoma, myasthenia gravis and untreated epilepsy. Breastfeeding. The risk of harmful effects on the fetus following administration of chlorpromazine is not excluded; therefore the use of Largactil in pregnancy is to be reserved, in the opinion of the doctor, for cases of absolute necessity.
Largactil ampoules contain potassium metabisulfite and sodium sulfite; these substances can cause in sog
Precautions for use What you need to know before taking Largactil
As with all neuroleptics, patients treated with chlorpromazine should be kept under direct medical supervision.
Due to its pharmacological properties, the product should be used with particular caution in the elderly, in subjects with cardiovascular diseases or with a family history of QT prolongation, acute and chronic lung diseases, glaucoma, prostatic hypertrophy and other stenosing diseases of the digestive and urinary tract. and Parkinson's disease In case of hypotension, do not use epinephrine, which can cause further lowering of blood pressure Avoid concomitant therapy with other neuroleptics.
Prolonged doses lead to an increase in the plasma level of prolactin with possible effects on target organs. Products containing phenothiazines must therefore be used with appropriate caution in women with breast cancer. During therapy, especially if prolonged or at high doses, it is always necessary to keep in mind the possibility of side effects affecting the CNS, liver, bone marrow, eye and cardiovascular system and it is therefore necessary to perform periodic clinical checks. and laboratory.
In particular, since changes in the blood count have been described with phenothiazine derivatives, it is advisable to periodically perform a blood count during chronic therapy with Largactil, as well as repeated checks of renal and hepatic function.
Patients treated with high doses of chlorpromazine and who must undergo surgical interventions require lower doses of anesthetics and central nervous system depressant drugs.
The effects on the blood count must be particularly followed between the fourth and the twelfth week. However, the onset of dyscrasia can be sudden and therefore the onset of inflammatory manifestations affecting the mouth and upper airways must be immediately followed by appropriate haematological checks.
Phenothiazines increase the state of muscle stiffness in individuals with Parkinson's disease or similar forms or other motor disorders; they can also lower the seizure threshold and facilitate the onset of epileptic seizures. Patients treated with phenothiazines must avoid excessive exposure to sunlight, resorting, if necessary, to the use of special protective creams. Use with caution in subjects exposed to particularly high or low temperatures as phenothiazines can compromise the ordinary mechanisms of thermoregulation.
Cases of prolongation of the QT interval have been reported very rarely with chlorpromazine as 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. Largactil should be used with caution in patients with stroke risk factors.
Interactions Which drugs or foods can modify the effect of Largactil
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The association with other psychotropic drugs requires special caution and vigilance on the part of the physician to avoid unexpected and unwanted effects of interaction.
When neuroleptics are given concomitantly with QT-prolonging drugs, the risk of developing cardiac arrhythmias increases.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Other combinations requiring special precautions or dosage adjustment:
Substances that depress the CNS: barbiturates, anxiolytics, hypnotics, anesthetics, antihistamines, opioid analgesics. In case of combination avoid high dosages and carefully monitor the patient to avoid excessive sedation or central depression.
AnticonvulsantsDue to the known effect of phenothiazines on the seizure threshold, an adjustment of specific therapy may be necessary in epileptic subjects. The respective dosage of the drugs in case of combination must be accurately determined since it is possible, among other things, that phenothiazines reduce the metabolism of phenylhydantoin, accentuating its toxicity, and that barbiturates, like other enzymatic inducers at the microsomal level, may accentuate the metabolism of phenothiazines.
Lithium: although rarely, the association with phenothiazines has resulted in acute encephalopathy. If fever of an undetermined nature is present together with side effects of an extrapyramidal nature, the administration of lithium and Largactil should be discontinued. Lithium may reduce the concentration of chlorpromazine in the plasma and may also increase the risk of extrapyramidal type reactions. One case of ventricular fibrillation has been reported following lithium withdrawal during combination therapy with chlorpromazine.
Antihypertensives: the interaction with antihypertensive drugs leads to an increase in the hypotensive effect; however phenothiazines may antagonize the effects of guanethidine and similar drugs.
Anticholinergics: caution requires the association of phenothiazines and parasympatholytic drugs which can favor the appearance of characteristic side effects. Anticholinergics can reduce the antipsychotic action of Largactil.
Drugs with leukopenizing activity: for the synergistic depressive effect on the blood crase, phenothiazines must not be associated with phenylbutazone, thiouracyl derivatives and other potentially myelotoxic drugs.
Metrizamide: this substance increases the risk of phenothiazine-induced convulsions. It is therefore necessary to suspend the therapy at least 48 hours before a myelographic examination and the administration must not be resumed before 24 hours from the execution of this.
AlcoholAlcohol intake during therapy is not recommended as it may facilitate the central side effects of phenothiazines.
Lisuride, Pergolide and Levodopa: the effects of these substances are specifically antagonized by phenothiazines; this is taken into account in subjects with Parkinson's disease.
Antacids: avoid ingestion of the product together with antacids or other substances that can reduce the absorption of phenothiazines.
Interaction with laboratory tests: the urinary metabolites of phenothiazines can impart a dark color to the urine and give false positive responses to tests for amylase, urobilinogen, uroporphyrins, porphobilinogens and 5-hydroxy-indolacetic acid. In women treated with phenothiazines they have been false positive pregnancy tests reported.
Antidiabetics: as chlorpromazine can cause hyperglycaemia, the dosage of oral hypoglycemic agents or insulin must be carefully determined.
Antiarrhythmics: neuroleptics can induce alterations in the E.C.G. such as Q.T.interval prolongation, should therefore be used with caution in patients taking medications such as antiarrhythmics that have similar effects.
Antidepressants: the combination of phenothiazines and tricyclic antidepressants accentuates the antimuscarinic effects.
Deferoxamine: the administration of deferoxamine and prochlorperazine resulted in a transient metabolic encephalopathy. It is possible that this situation may also occur with chlorpromazine, as it exhibits many of the pharmacological activities of prochlorperazine.
Warnings It is important to know that:
Special attention requires the use of this substance in children, especially during an infectious disease or in the case of surgery or vaccination, as in such conditions a higher incidence of extrapyramidal reactions has been found.
The antiemetic effect of phenothiazines can mask the signs of overdosing of other drugs or can make it more difficult to diagnose concomitant diseases, especially of the digestive tract or CNS such as intestinal obstruction, brain tumors, Reye's syndrome. for this reason these substances must be used with caution in association with antiblastics which, at toxic doses, can cause vomiting.
Since the risk of persistent delayed dyskinesias has been correlated with the duration of therapy, chronic treatment with neuroleptics should be reserved for those patients with conditions that respond to the drug and for whom an appropriate alternative therapy is not possible. The doses and duration of treatment should be the minimum in order to obtain a satisfactory clinical response. If signs or symptoms of tardive dyskinesia appear (see side effects) during the course of therapy, discontinue administration.
In general, phenothiazines do not produce psychic dependence. However, as a result of abrupt interruption, nausea, vomiting, dizziness, tremors, motor restlessness may appear. Special attention should be paid to patients with psychic depression or during the manic phase of cyclical psychosis due to the possibility of a rapid change in mood towards depression. A potentially fatal complex of symptoms has been reported during treatment with antipsychotic drugs , called Neuroleptic Malignant Syndrome. Clinical manifestations of this syndrome are: hyperpyrexia, muscle stiffness, akinesia, vegetative disorders (irregular pulse and blood pressure, sweating, tachycardia, arrhythmias); alterations in the state of consciousness that can progress to stupor and to coma. The treatment of NMS 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 in reducing hyperthermia and in correcting dehydration). the recovery considered essential d n treatment with antipsychotics, the patient should be carefully monitored.
Important information about some of the ingredients
The tablets contain lactose, therefore, if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
The vials contain sodium sulfite heptahydrate and potassium metabisulfite; these substances can rarely cause severe hypersensitivity reactions and bronchospasm.
Particular caution is required in treating patients who present, even at family level, a clinical history of thrombosis, since the drug is associated with the formation of thrombus.
PREGNANCY AND BREASTFEEDING
Ask your doctor or pharmacist for advice before taking any medicine.
During therapy, inform your doctor if you are pregnant; it is also necessary to consult it if you wish to proceed to breastfeeding or to become pregnant. In breastfeeding patients, it is necessary to decide whether to give up breastfeeding the infant and start the treatment or vice versa, continue breastfeeding avoiding the administration of the medicine.
The following symptoms have been observed in newborn babies of mothers who have taken conventional or atypical antipsychotics, including LARGACTIL, 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 THE ABILITY TO DRIVE VEHICLES AND ON THE USE OF MACHINERY
Since phenothiazines induce sedation and somnolence, this must be taken into account in those who drive vehicles or other machinery or who perform hazardous work.
Dosage and method of use How to use Largactil: Dosage
The dosage of chlorpromazine must be strictly individualized in relation to the age of the patient, the nature and severity of the disease, the therapeutic response and the tolerability of the drug. It is always advisable to start with low dosages, progressively increasing the doses. Usually the therapeutic interval is 6-8 hours. In parenteral use do not exceed 25 mg in the first 24 hours except in cases where this is strictly necessary in the opinion of the specialist. By way of example, the following general diagrams are provided.
Psychiatric Disorders: in general, in outpatients and patients with symptoms of mild or medium severity, 25-75 mg orally is required over the course of the day. The dosage can then be increased until the desired therapeutic effect is obtained. Subsequently it can be gradually reduced until the maintenance dose is determined. If necessary, the treatment can be initiated by the IM route with 25 mg, which can be repeated if necessary. if necessary. Then switch to the oral route. In hospitalized patients, significantly higher doses may be necessary, both per os and im, depending on the judgment of the specialist. In children the recommended dosage is 1 mg / kg / day repeated, if necessary, 2-3 times a day.
He retched: 25-50 mg i.m. repeated, possibly, 2-3 times a day. Once the therapeutic effect has been obtained, the therapy, if necessary, must be continued orally.
Incoercible hiccups: 25-50 mg, 2-3 times a day.
In pre-anesthetic dressing: 25-50 mg orally or 12.5-25 mg by i.m. a few hours before the intervention.
In case of intramuscular administration, dilute the contents of a vial with sterile physiological solution to bring the solution to 5-6 ml.
For intravenous administration dilute the contents of a vial in the liquid used for intravenous infusion. In any case, switch to the oral route as soon as possible.
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 Largactil
In case of accidental ingestion / intake of an excessive dose of LARGACTIL, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of LARGACTIL, ask your doctor or pharmacist.
Enhancement of undesirable effects: establish suitable antiparkinsonian, muscle relaxant and / or antihistamine therapy.
In the absence of a specific antidote, gastric lavage must be performed: in case of severe hypotension, lay the patient in a supine position with the head tilted down and carefully administer plasma expanders; possibly phenylephrine or noradrenaline by slow venous infusion and with particular caution, as LARGACTIL can modify the normal response. Never use adrenaline.
Establish symptomatic treatment of nervous system depression such as in cases of acute barbiturate intoxication, including physiotherapy and antibiotic treatment to prevent bronchopneumonia. Hemodialysis is not effective. When the body temperature drops to particularly low levels, cardiac arrhythmias may appear. Particular surveillance must be exercised to control bowel and bladder distension phenomena.
Side Effects What are the side effects of Largactil
Like all medicines, LARGACTIL can cause side effects, although not everybody gets them
Nervous system disorders: with the use of phenothiazines, sedation and somnolence may occur, especially during the first weeks of therapy, which mostly disappear with continued treatment or with an appropriate dose reduction. Other behavioral effects that occurred with varying frequency are insomnia, restlessness, anxiety, euphoria, psychomotor agitation, mood depression or worsening of psychotic symptoms. The possible appearance of dry mouth, mydriasis, vision disturbances, constipation, constipation and even paralytic ileus, urinary retention, and other signs of reduced parasympathetic activity is due to the anticholinergic activity of phenothiazines. Convulsions and changes in body temperature are also possible. A significant and unexplained increase in body temperature may be due to intolerance towards the product; in this case it is necessary to interrupt the therapy. For depression of the cough center, ab ingestis affections can occur. Extrapyramidal-type reactions are common during treatment with phenothiazines. They are usually represented by muscular dystonias, akathisia, pseudo-parkinsonian syndromes and persistent late dyskinesias. Dystonias and akathisia are more frequent in children, while signs of parkinsonism prevail in the elderly, especially if they have organic brain lesions. Dystonias include spasms of the neck and trunk muscles up to stiff neck and opisthotonus, oculogyric crisis, trismus , protrusion of the tongue and carpal-breech spasms. These reactions appear very early and disappear within 24-48 hours of discontinuing therapy. Very rarely, dystonia can cause laryngospasm associated with cyanosis and asphyxia.
Akathisia is characterized by motor restlessness and sometimes by insomnia. More frequent in the first days of therapy, it can also appear late. The disorders often regress spontaneously; otherwise they can be well controlled by reducing the dosage or by combining an anti-parkinson anticholinergic. The pseudo-parkinsonian syndromes (akinesia, rigidity, tremor at rest, etc.) are mostly sensitive to specific drugs; in persistent cases it may be necessary to reduce the dosage or to suspend the treatment.
Late persistent dyskinesias occur mostly during long-term therapy and with high doses, even in the period following drug discontinuation.
The elderly and women are more frequently affected.
They manifest themselves with involuntary rhythmic movements of the tongue, lips and face, more rarely of the extremities and are generally preceded by fine vermicular movements of the tongue. Discontinuation of therapy can prevent the development of symptoms, for which a specific therapy is not known. Periodic reduction of neuroleptic dosage if clinically possible can help to recognize the onset of tardive dyskinesia early.
Very rarely, tardive dystonia, not associated with tardive dyskinesia, may occur. It is characterized by choreic movements or dystonic movements with delayed onset, often persistent and can potentially become irreversible.
Cardiovascular pathologies: hypotension, tachycardia, dizziness, syncopal manifestations, are quite common in patients taking phenothiazines. Since they are more frequent and severe parenterally, the injection must be performed in the supine position keeping the patient in this position for 30 to 60 minutes. The hypotensive effects are more evident in subjects with pheochromocytoma and mitral insufficiency. Alterations of the trace are possible. Rare cases of QT prolongation, atrial arrhythmias, AV block, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been reported with Largactil or other drugs of the same class Very rare cases of sudden death.
Disorders of the blood and lymphatic system: effects on blood count are quite rare, but serious. They include leukopenia, agranulocytosis, thrombocytopenia, purpura, haemolytic anemia and aplastic anemia.
Skin and subcutaneous tissue disorders: hypersensitivity reactions (general or contact) and photosensitivity are possible, which are mostly represented by erythema, urticaria, eczema, exfoliative dermatitis. In long-term therapies, brown pigmentations have been reported, especially in the photo-exposed areas.
Metabolism and nutrition disorders: phenothiazines can cause hyperprolactinaemia, reduction of estrogen, progesterone and pituitary gonadotropins. As a consequence, breast enlargement and tenderness, abnormal lactation, amenorrhea may appear in women and gynecomastia and testicular volume reduction in men, impotence. Other possible effects are an increase in body weight, peripheral edema, hyperglycemia and glycosuria.
General disorders and administration site conditions: in addition to cutaneous and haematological ones, cholestatic jaundice can occur with varying frequency, clinically similar to infectious hepatitis and characterized by hyperbilirubinemia, hypertransaminasemia, increased alkaline phosphatase and eosinophilia. In case of signs or symptoms of hepatic distress, therapy should be discontinued immediately. Other hypersensitivity reactions are represented by laryngeal or angioneurotic edema, laryngospasm, bronchospasm, anaphylactic reactions, systemic lupus erythematosus-like syndromes.
Eye disorders: in the case of prolonged therapy, the appearance in the cornea and in the lens of particle material of an undetermined nature has been reported, which in some patients caused visual impairment. Pigmentary retinopathy. Since ocular damage appears to be related to dosage and duration of therapy, it is suggested that patients on high dose or long-term treatment should be monitored periodically.
Other:
Neuroleptic Malignant Syndrome (see "Special warnings").
Liver and kidney damage.
As with all phenothiazines, "silent pneumonia" may develop in patients on prolonged treatment with chlorpromazine.
Venous clots, especially in the legs (symptoms are swelling, pain and redness in the legs) can travel to the lungs through blood vessels and cause chest pain and difficulty breathing. If you notice any of these symptoms, see your doctor right away
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious or if you notice any side effects not described in this leaflet, please tell your doctor.
Expiry and Retention
Expiry: see the expiry date printed on the package
The expiry date refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package.
To be kept away from light.
Keep out of the reach and sight of children
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.
PHARMACEUTICAL FORM AND CONTENT
Largactil 25 mg coated tablets - box of 25 tablets Largactil 100 mg coated tablets - box of 20 tablets Largactil 50 mg / 2 ml solution for injection - box of 5 ampoules for intravenous (slow infusion) and intramuscular use
COMPOSITION
LARGACTIL 25 mg film-coated tablets
One tablet contains: active ingredient: chlorpromazine 25 mg (equivalent to 28 mg of hydrochloride)
LARGACTIL 100 mg film-coated tablets
One tablet contains: active ingredient: chlorpromazine 100 mg (equal to 112 mg of hydrochloride) Excipients: corn starch, lactose, microcrystalline cellulose, magnesium stearate, anhydrous colloidal silica, zein, castor oil, titanium dioxide, E 172.
LARGACTIL 50 mg / 2 ml solution for injection
One ampoule contains: active ingredient: chlorpromazine 50 mg (equal to 55.71 mg of hydrochloride) Excipients: sodium chloride; sodium sulfite heptahydrate; sodium citrate; potassium metabisulfite; water for injections
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
LARGACTIL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
LARGACTIL 25 mg film-coated tablets
One tablet contains active ingredient: chlorpromazine 25 mg (equivalent to 28 mg of hydrochloride)
LARGACTIL 100 mg film-coated tablets
One tablet contains active ingredient: chlorpromazine 100 mg (equivalent to 112 mg of hydrochloride)
LARGACTIL 50 mg / 2 ml solution for injection
One ampoule contains active ingredient: chlorpromazine 50 mg (equivalent to 55.71 mg of hydrochloride)
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets
Solution for injection for slow intravenous infusion and intramuscular administration
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of schizophrenias, paranoid states and mania. Toxic psychosis (amphetamines, LSD, cocaine etc.). Organic mental syndromes accompanied by delirium. Anxiety disorders if particularly severe and resistant to therapy with typical anxiolytics. Depression if accompanied by agitation and delirium, mostly in association with antidepressants. Vomiting and incoercible hiccups. Treatment of intense pain generally in association with narcotic analgesics. Pre-anesthetic medication.
04.2 Posology and method of administration
The dosage of chlorpromazine must be strictly individualized in relation to the age of the patient, the nature and severity of the disease, the therapeutic response and the tolerability of the drug. It is always advisable to start with low dosages, progressively increasing the doses. Usually the therapeutic interval is 6-8 hours. In parenteral use do not exceed 25 mg in the first 24 hours except in cases where this is strictly necessary in the opinion of the specialist. By way of example, the following general diagrams are provided.
Psychiatric disorders: in general, in outpatients and patients with symptoms of mild or medium severity, 25-75 mg orally is required divided over the day. The dosage can then be increased until the desired therapeutic effect is obtained. Subsequently it can be gradually reduced until the maintenance dose is determined. If necessary, the treatment can be initiated by the IM route with 25 mg, which can be repeated if necessary. if necessary. Then switch to the oral route. In hospitalized patients, significantly higher doses may be necessary, both per os and im, depending on the judgment of the specialist. In children the recommended dosage is 1 mg / kg / day repeated, if necessary, 2-3 times a day.
He retched: 25-50 mg i.m. repeated, possibly, 2-3 times a day. Once the therapeutic effect has been obtained, the therapy, if necessary, must be continued orally.
Incoercible hiccups: 25-50 mg, 2-3 times a day.
In pre-anesthetic dressing: 25-50 mg orally or 12.5-25 mg by i.m. a few hours before the intervention.
In case of intramuscular administration, dilute the contents of a vial with sterile physiological solution to bring the solution to 5-6 ml.
For intravenous administration dilute the contents of a vial in the liquid used for intravenous infusion. In any case, switch to the oral route as soon as possible.
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.
04.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients or to other closely related substances from a chemical point of view. Comatose states, especially those caused by substances with a depressive action on the central nervous system (alcohol, barbiturates, opiates, etc.); patients with suspected or recognized subcortical brain damage; severe states of depression; blood dyscrasias; liver and kidney diseases. The product is not indicated in infancy. Pheochromocytoma, myasthenia gravis and untreated epilepsy. Breastfeeding. The risk of harmful effects on the fetus following administration of chlorpromazine is not excluded; therefore the use of Largactil in pregnancy is to be reserved, in the opinion of the doctor, for cases of absolute necessity.
Largactil ampoules contain potassium metabisulfite and sodium sulfite; these substances can cause allergic reactions and severe asthmatic attacks in sensitive subjects and particularly in asthmatics.
04.4 Special warnings and appropriate precautions for use
Special attention requires the use of this substance in children, especially during an infectious disease or in the case of surgery or vaccination, as in such conditions a higher incidence of extrapyramidal reactions has been found.
Use with caution in patients with cardiovascular disease or a family history of QT prolongation.
Avoid concomitant therapy with other neuroleptics.
The antiemetic effect of phenothiazines can mask the signs of overdosing of other drugs or can make it more difficult to diagnose concomitant diseases, especially of the digestive tract or CNS such as intestinal obstruction, brain tumors, Reye's syndrome. for this reason these substances must be used with caution in association with antiblastics which, at toxic doses, can cause vomiting.
Since the risk of persistent delayed dyskinesias has been correlated with the duration of therapy, chronic treatment with neuroleptics should be reserved for those patients with conditions that respond to the drug and for whom an appropriate alternative therapy is not possible. The doses and duration of treatment should be the minimum in order to obtain a satisfactory clinical response. If signs or symptoms of tardive dyskinesia appear (see side effects) during the course of therapy, discontinue administration.
In general, phenothiazines do not produce psychic dependence. However, as a result of abrupt interruption, nausea, vomiting, dizziness, tremors, motor restlessness may appear. Special attention should be paid to patients with psychic depression or during the manic phase of cyclical psychosis due to the possibility of a rapid change in mood towards depression.
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 NMS 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 in reducing hyperthermia and in correcting dehydration). If the resumption of antipsychotic treatment is deemed essential, the patient should be carefully monitored.
During therapy, inform your doctor if you are pregnant; it is also necessary to consult it if you wish to proceed to breastfeeding or to become pregnant. In breastfeeding patients, it is necessary to decide whether to give up breastfeeding the infant and start the treatment or vice versa, continue breastfeeding avoiding the administration of the medicine.
As with all neuroleptics, patients treated with chlorpromazine should be kept under direct medical supervision.
Due to its pharmacological properties, the product should be used with particular caution in the elderly, in subjects with cardiovascular diseases, acute and chronic lung diseases, glaucoma, prostatic hypertrophy and other stenosing diseases of the digestive and urinary tract and Parkinson's disease. hypotension, do not use adrenaline, which can cause a further lowering of blood pressure.
Prolonged doses lead to an increase in the plasma level of prolactin with possible effects on target organs. Products containing phenothiazines must therefore be used with appropriate caution in women with breast cancer. During therapy, especially if prolonged or at high doses, it is always necessary to keep in mind the possibility of side effects affecting the CNS, liver, bone marrow, eye and cardiovascular system and it is therefore necessary to perform periodic clinical checks. and laboratory.
In particular, since changes in the blood count have been described with phenothiazine derivatives, it is advisable to periodically perform a blood count during chronic therapy with Largactil, as well as repeated checks of renal and hepatic function.
Patients treated with high doses of chlorpromazine and who must undergo surgical interventions require lower doses of anesthetics and central nervous system depressant drugs.
The effects on the blood count must be particularly followed between the fourth and the twelfth week. However, the onset of dyscrasia can be sudden and therefore the onset of inflammatory manifestations affecting the mouth and upper airways must be immediately followed by appropriate haematological checks.
Phenothiazines increase the state of muscle stiffness in individuals with Parkinson's disease or similar forms or other motor disorders; they can also lower the seizure threshold and facilitate the onset of epileptic seizures. Patients treated with phenothiazines must avoid excessive exposure to sunlight, resorting, if necessary, to the use of special protective creams. Use with caution in subjects exposed to particularly high or low temperatures as phenothiazines can compromise the ordinary mechanisms of thermoregulation.
Cases of QT interval prolongation have been reported very rarely with chlorpromazine, as with other neuroleptics.
Important information about some of the ingredients
The tablets contain lactose so it is not suitable for people with lactase deficiency, galactosemia or glucose / galactose malabsorption syndrome.
Vials containing colored or non-clear solutions should be discarded.
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. Largactil should be used with caution in patients with stroke risk factors.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, these factors must be identified before and during treatment with Largactil and in order to take adequate preventive measures.
04.5 Interactions with other medicinal products and other forms of interaction
The association with other psychotropic drugs requires special caution and vigilance on the part of the physician to avoid unexpected and unwanted effects of interaction.
When neuroleptics are given concomitantly with QT-prolonging drugs, the risk of developing cardiac arrhythmias increases.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Other combinations requiring special precautions or dosage adjustment.
Substances that depress the CNS: barbiturates, anxiolytics, hypnotics, anesthetics, antihistamines, opioid analgesics. In case of combination avoid high dosages and carefully monitor the patient to avoid excessive sedation or central depression.
AnticonvulsantsDue to the known effect of phenothiazines on the seizure threshold, an adjustment of specific therapy may be necessary in epileptic subjects. The respective dosage of the drugs in case of combination must be accurately determined since it is possible, among other things, that phenothiazines reduce the metabolism of phenylhydantoin, accentuating its toxicity, and that barbiturates, like other enzymatic inducers at the microsomal level, may accentuate the metabolism of phenothiazines.
Lithium: although rarely, the association with phenothiazines has resulted in acute encephalopathy. If present, fever of an undetermined nature together with side effects of an extrapyramidal nature. administration of lithium and Largactil should be discontinued.
Lithium can reduce the concentration of chlorpromazine in the plasma and can also increase the risk of extrapyramidal type reactions. One case of ventricular fibrillation has been reported following lithium withdrawal during combination therapy with chlorpromazine.
Antihypertensives: the interaction with antihypertensive drugs leads to an increase in the hypotensive effect; however phenothiazines may antagonize the effects of guanethidine and similar drugs.
Anticholinergics: caution requires the association of phenothiazines and parasympatholytic drugs which can favor the appearance of characteristic side effects. Anticholinergics can reduce the antipsychotic action of Largactil.
Drugs with leukopenizing activity: for the synergistic depressive effect on the blood crase, phenothiazines must not be associated with phenylbutazone, thiouracyl derivatives and other potentially myelotoxic drugs.
Metrizamide: this substance increases the risk of phenothiazine-induced convulsions. It is therefore necessary to suspend the therapy at least 48 hours before a myelographic examination and the administration must not be resumed before 24 hours from the execution of this.
AlcoholAlcohol intake during therapy is not recommended as it may facilitate the central side effects of phenothiazines.
Lisuride, Pergolide and Levodopa: the effects of these substances are specifically antagonized by phenothiazines; this is taken into account in subjects with Parkinson's disease.
Antacids: avoid ingestion of the product together with antacids or other substances that can reduce the absorption of phenothiazines.
Interaction with laboratory tests: The urinary metabolites of phenothiazines can impart a dark color to the urine and give false positive responses to tests for amylase, urobilinogen, uroporphyrins, porphobilinogens and 5-hydroxy-indolacetic acid. In women treated with phenothiazines they are false positive pregnancy tests have been reported.
Antidiabetics: Since chlorpromazine can cause hyperglycaemia, the dosage of oral hypoglycaemics or insulin must be carefully determined.
Antiarrhythmics: Neuroleptics can induce ECG changes such as QT interval prolongation, therefore they should be used with caution in patients taking drugs such as antiarrhythmics that have similar effects (see above).
Antidepressants: the combination of phenothiazines and tricyclic antidepressants accentuates the antimuscarinic effects.
Deferoxamine: the administration of deferoxamine and prochlorperazine resulted in a transient metabolic encephalopathy. It is possible that this situation may also occur with chlorpromazine, as it exhibits many of the pharmacological activities of prochlorperazine.
04.6 Pregnancy and lactation
Do not administer in the first trimester of pregnancy or during lactation (see section 4.3): beyond this period, the product should be used only when considered essential and always under the direct supervision of the doctor.
When used as an antiemetic, the product should be used during pregnancy only in cases of overt symptoms for which an alternative intervention is not possible and not in the frequent and simple cases of emesis gravidarum and even less for its preventive purposes.
Infants exposed to conventional or atypical antipsychotics, including LARGACTIL, 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.
04.7 Effects on ability to drive and use machines
Since phenothiazines induce sedation and somnolence, this must be taken into account in those who drive vehicles or other machinery or who perform hazardous work.
04.8 Undesirable effects
Nervous system disorders: with the use of phenothiazines, sedation and somnolence may occur, especially during the first weeks of therapy, which mostly disappear with continued treatment or with an appropriate dose reduction. Other behavioral effects that occurred with varying frequency are insomnia, restlessness, anxiety, euphoria, psychomotor agitation, mood depression or worsening of psychotic symptoms. The possible appearance of dry mouth, mydriasis, vision disturbances, constipation and even paralytic ileus, urinary retention, and other signs of reduced parasympathetic activity is due to the anticholinergic activity of phenothiazines. Convulsions and changes in body temperature are also possible. A significant and unexplained increase in body temperature may be due to intolerance towards the product; in this case it is necessary to interrupt the therapy. For depression of the cough center, ab ingestis affections can occur. Extrapyramidal-type reactions are common during treatment with phenothiazines. They are usually represented by muscular dystonias, akathisia, pseudo-parkinsonian syndromes and persistent late dyskinesias. Dystonias and akathisia are more frequent in children, while signs of parkinsonism prevail in the elderly, especially if they have organic brain lesions. Dystonias include spasms of the neck and trunk muscles up to stiff neck and opisthotonus, oculogyric crisis, trismus , protrusion of the tongue and carpal-breech spasms. These reactions appear very early and disappear within 24-48 hours of discontinuing therapy. Very rarely, dystonia can cause laryngospasm associated with cyanosis and asphyxia.
Akathisia is characterized by motor restlessness and sometimes by insomnia. More frequent in the first days of therapy, it can also appear late. The disorders often regress spontaneously; otherwise they can be well controlled by reducing the dosage or by associating an antiparkinsonian anticholinergic. pseudo-parkinsonian (akinesia, rigidity, tremor at rest, etc.) are mostly sensitive to specific drugs; in persistent cases it may be necessary to reduce the dosage or discontinue treatment.
Late persistent dyskinesias occur mostly during long-term therapy and with high doses, even in the period following drug discontinuation.
The elderly and women are more frequently affected.
They manifest themselves with rhythmic movements of the tongue, lips and face, more rarely of the extremities and are generally preceded by fine vermicular movements of the tongue. Discontinuation of therapy can prevent the development of symptoms, for which a specific therapy is not known. Periodic reduction of neuroleptic dosage if clinically possible can help to recognize the onset of tardive dyskinesia early.
Very rarely, tardive dystonia, not associated with tardive dyskinesia, may occur. It is characterized by choreic movements or dystonic movements with delayed onset, often persistent and can potentially become irreversible become irreversible.
Cardiovascular pathologies: hypotension, tachycardia, dizziness, syncopal manifestations, are quite common in patients taking phenothiazines. Since they are more frequent and severe by the parenteral route, the injection must be performed in the supine position keeping the patient in this position for 30 to 60 minutes. The hypotensive effects are more evident in subjects with pheochromocytoma and mitral insufficiency. Alterations of the trace are possible. Rare cases of QT prolongation, atrial arrhythmias, AV block, ventricular arrhythmias such as torsade de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been reported with Largactil or other drugs of the same class.
Disorders of the blood and lymphatic systemEffects on blood count are quite rare, but serious. They include leukopenia, agranulocytosis, thrombocytopenia, purpura, haemolytic anemia and aplastic anemia.
Skin and subcutaneous system disorders: hypersensitivity reactions (general or contact) and photosensitivity are possible, which are mostly represented by erythema, urticaria, eczema, exfoliative dermatitis. In long-term therapies, brown pigmentations have been reported, especially in the photo-exposed areas.
Metabolism and nutrition disorders: phenothiazines can cause hyperprolactinemia, reduction of estrogens, progesterone and pituitary gonadotropins. As a consequence, breast enlargement and tenderness, abnormal lactation, amenorrhea may appear in women and gynecomastia and testicular volume reduction in men, impotence. Other possible effects are an increase in body weight, peripheral edema, hyperglycemia and glycosuria.
General disorders and administration site conditions: in addition to cutaneous and haematological ones, cholestatic jaundice can occur with varying frequency, clinically similar to infectious hepatitis and characterized by hyperbilirubinemia, hypertransaminasemia, increased alkaline phosphatase and eosinophilia. In case of signs or symptoms of hepatic distress, therapy should be discontinued immediately. Other hypersensitivity reactions are represented by laryngeal or angioneurotic edema, laryngospasm, bronchospasm, anaphylactic reactions, systemic lupus erythematosus-like syndromes.
Eye disorders: in the case of prolonged therapy, the appearance in the cornea and in the lens of particle material of an undetermined nature has been reported, which in some patients caused visual impairment. Pigmentary retinopathy. Since ocular damage appears to be related to dosage and duration of therapy it is suggested that patients on high dose or long-term treatment should be monitored periodically.
Organic system class: pregnancy, puerperium and perinatal conditions:
Adverse reaction and frequency: neonatal withdrawal syndrome, frequency not known, extrapyramidal symptoms (See section 4.6).
Other:
Neuroleptic Malignant Syndrome (see section 4.4)
Liver and kidney damage.
As with all phenothiazines, "silent pneumonia" may develop in patients on prolonged treatment with chlorpromazine.
Cases of venous thromboembolism (VTE) have been reported, including cases of pulmonary embolism (PE) and deep vein thrombosis (VTE). The frequency of these events is unknown
04.9 Overdose
Enhancement of undesirable effects: establish suitable antiparkinsonian, muscle relaxant and / or antihistamine therapy.
In the absence of a specific antidote, gastric lavage must be performed: in case of severe hypotension, lay the patient in a supine position with the head tilted down and carefully administer plasma expanders; possibly phenylephrine or noradrenaline by slow venous infusion and with particular caution, as LARGACTIL can modify the normal response. Never use adrenaline.
Establish symptomatic treatment of nervous system depression such as in cases of acute barbiturate intoxication, including physiotherapy and antibiotic treatment to prevent bronchopneumonia. Hemodialysis is not effective. When the body temperature drops to particularly low levels, cardiac arrhythmias may appear. Particular surveillance must be exercised to control bowel and bladder distension phenomena.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antipsychotics. ATC code: N05AA01.
LARGACTIL contains as the active ingredient chlorpromazine, a phenothiazine neuroleptic that acts mainly at the level of the basal ganglia, the limbic system and the hypothalamus. At the level of the CNS the most important effect is that of blocking dopaminergic receptors.
Chlorpromazine also possesses an alpha-adrenergic blocking action and anticholinergic and adrenergic properties, the latter by reducing the recovery of sympathetic-mimetic amines at the level of pre-synaptic neuronal membranes. The exact mechanism by which phenothiazines perform their antipsychotic effect is not known. The pharmacological properties, however, well explain the extrapyramidal, cardiovascular, endocrine and autonomic nervous system effects that usually accompany the therapeutic use of these drugs.
05.2 Pharmacokinetic properties
Chlorpromazine administered orally is rapidly absorbed; its relative bioavailability in relation to the i.m. route is about 50%. Chlorpromazine is distributed throughout the body, its binding to plasma proteins is high. Chlorpromazine crosses the blood brain barrier, reaching concentrations in brain tissue higher than those in plasma, is found in the placenta and is excreted in breast milk.
The half-life of chlorpromazine is short (a few hours) but its elimination is slow and prolonged (4 weeks or more). Individual variations are very large.
Chlorpromazine undergoes first pass metabolism in the gastrointestinal tract; an intense hepatic metabolism with the formation of both active and inactive metabolites; there is also an enterohepatic circle. Elimination occurs through urine and faeces.
05.3 Preclinical safety data
Acute toxicity was 25 mg / kg in rats by the i.v route; 75 mg / kg and 50 mg / kg in mice orally and i.v. respectively; 15 mg / kg in rabbits intravenously.
Subacute toxicity studies in dogs treated by the SC route and oral for one month at doses of 2 and 20 mg / kg and by s.c. and e.v. for 12 days at doses of 5 mg / kg have shown a good tolerability of the drug, as well as chronic toxicity studies in rats treated 13 months orally.
Chlorpromazine showed no adverse effects on the reproductive cycle of the rat, and was not teratogenic. In vivo and in vitro studies on human chromosomes have shown the non-mutagenicity of chlorpromazine.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablets
Corn starch, Lactose, Microcrystalline cellulose, Magnesium stearate, Silica, colloidal anhydrous, Zeine, Titanium dioxide, E 172, Castor oil.
Injectable solution
Sodium chloride, Sodium sulphite heptahydrate, Sodium citrate, Potassium metabisulfite, Water for injections.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
- Tablets: 4 years.
- solution for injection: 3 years
06.4 Special precautions for storage
Keep away from light.
06.5 Nature of the immediate packaging and contents of the package
Tablets: Carton of 25 film-coated tablets of 25 mg in opaque blister.
carton of 20 film-coated tablets of 100 mg in opaque blister.
Solution for injection: box of 5 glass vials of 2 ml dosed at 50 mg.
06.6 Instructions for use and handling
None
07.0 MARKETING AUTHORIZATION HOLDER
TEOFARMA S.r.l.
Via F.lli Cervi, 8
27010 Salimbene Valley (PV)
08.0 MARKETING AUTHORIZATION NUMBER
LARGACTIL 25 mg film-coated tablets - 25 tablets AIC n °. 007899026
LARGACTIL 100 mg film-coated tablets - 20 tablets AIC n °. 007899038
LARGACTIL 50 mg / 2 ml solution for injection - 5 ampoules 50 mg 2 ml AIC n °. 007899014
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
LARGACTIL 25 mg film-coated tablets - 25 tablets 21.02.1955 / 31.05.2010
LARGACTIL 100 mg film-coated tablets - 20 tablets 02.02.1956 / 31.05.2010
LARGACTIL 50 mg / 2 ml solution for injection - 5 ampoules 50 mg 2 ml 12.06.1953 / 31.05.2010
10.0 DATE OF REVISION OF THE TEXT
April 2012
