Active ingredients: Barnidipine (Barnidipine hydrochloride)
LIBRADIN 10 mg modified-release capsules
LIBRADIN 20 mg modified release capsules
Indications Why is Libradin used? What is it for?
The active substance in LIBRADIN belongs to a group of medicines called calcium channel blockers.
LIBRADIN causes blood vessels to dilate with consequent lowering of blood pressure. LIBRADIN capsules are "sustained release". This means that the active principle is absorbed by the body gradually and its effect is prolonged over time. For this reason, only one administration per day is sufficient.
LIBRADIN is used for the treatment of arterial hypertension.
Contraindications When Libradin should not be used
Do not take LIBRADIN
- if you are allergic to barnidipine or any of the LIBRADIN of the other ingredients of this medicine (listed in section 6)
- if you are allergic to dihydropyridines (substances found in medicines used to treat hypertension)
- if you suffer from liver disease
- if you have severe kidney disease
- if you have any of the following heart diseases: heart failure inadequately treated, some forms of chest pain (due to unstable angina pectoris) or acute cardiac arrest
- if you use any of the following medicines: protease inhibitors (medicines used to treat AIDS), ketoconazole or itraconazole (medicines used to treat fungal infections), erythromycin or clarithromycin (antibiotics).
Precautions for use What you need to know before taking Libradin
Talk to your doctor or pharmacist before taking LIBRADIN
- if you have kidney disease
- if you suffer from heart disease
Children and adolescents
LIBRADIN should not be given to children or adolescents under the age of 18.
Interactions Which drugs or foods can change the effect of Libradin
Other medicines and LIBRADIN
Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines.
This is especially important if you are using any of the following medicines, as they must not be taken together with LIBRADIN:
- protease inhibitors (drugs used to treat AIDS)
- ketoconazole or itraconazole (medicines used to treat fungal infections)
- erythromycin or clarithromycin (antibiotics)
Also tell your doctor if you are taking:
- other medicines to treat hypertension, which can cause blood pressure to drop further
- cimetidine (medicine used to treat stomach diseases) as it may increase the effect of LIBRADIN
- phenytoin or carbamazepine (medicines used to treat epilepsy) or rifampicin (an antibiotic), as you may need a higher dose of LIBRADIN. If you stop taking one of these medicines, your doctor may reduce your dose of LIBRADIN.
LIBRADIN with drinks and alcohol
Take special care when drinking alcohol or grapefruit juice, as these drinks can increase the effect of LIBRADIN.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
You should not use LIBRADIN if you are pregnant unless clearly necessary. Do not use LIBRADIN if you are breastfeeding. It can be excreted in breast milk.
Driving and using machines
There are no data suggesting that LIBRADIN may impair the ability to drive and use machines. However, LIBRADIN can cause dizziness, you should therefore be sure of the effect this medicine has on you before driving or using machines.
LIBRADIN capsules contain sucrose. If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Libradin: Dosage
Dosage
Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
The usual starting dose is 1 LIBRADIN 10 mg capsule once a day. Your doctor may increase this dose to 1 LIBRADIN 20 mg capsule once a day, or two 10 mg capsules once a day.
If you are elderly you can use the normal dosage. Your doctor is more likely to follow you more closely at the start of treatment.
Instructions for proper use
- Take the capsule once a day, in the morning. It is preferable to combine taking the capsule with a daily action, such as brushing your teeth or having breakfast.
- Swallow the capsules whole, preferably with a glass of water. You can take LIBRADIN before, during or after a meal, as you prefer.
- Even if you do not have any signs or symptoms of hypertension, it is important that you continue to take LIBRADIN every day to get the full benefits of lowering blood pressure.
Overdose What to do if you have taken too much Libradin
If you take more LIBRADIN than you should
If you have accidentally taken a large amount of capsules at one time, you should contact your doctor immediately or ask to be transported to a hospital emergency room. Symptoms that may arise following an overdose are weakness, decreased or increased heart rate, drowsiness, confusion, nausea, vomiting and convulsions.
If you forget to take LIBRADIN
If you forget to take LIBRADIN at the usual time of day, take the capsule as soon as possible on the same day. If you only remember the next day, do not take a double dose to make up for a forgotten capsule, but continue with your daily dose regularly.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Libradin
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you have a severe allergic reaction which causes difficulty in breathing or dizziness, you should inform your doctor or nurse immediately.
LIBRADIN can cause:
Very common: affects more than 1 in 10 patients
- headache
- redness of the face
- accumulation of fluid (edema) in the arms and legs
Common: affects up to 1 in 10 patients:
- dizziness
- palpitations
Not known: frequency cannot be estimated from the available data
- rapid heartbeat
- blood tests showing changes in liver function
- rash
These side effects usually reduce or disappear during the course of treatment (within one month for fluid accumulation and within two weeks for facial flushing, headache and palpitations).
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Store LIBRADIN capsules below 25 ° C.
Do not use LIBRADIN after the expiry date which is stated on the carton after "EXP." The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What LIBRADIN contains
- The active substance is 10 mg or 20 mg of barnidipine hydrochloride, equivalent to 9.3 mg and 18.6 mg of barnidipine respectively.
- The other ingredients are: Capsule contents: carboxymethylethylcellulose, polysorbate 80, sucrose, ethylcellulose and talc. Capsule shell: titanium dioxide (E 171), yellow iron oxide (E 172) and gelatin. Printing ink: shellac, propylene glycol (E 1520), black iron oxide (E 172) and ammonia.
What LIBRADIN looks like and contents of the pack
Yellow capsules.
LIBRADIN 10 mg capsules are marked with code 155 10
LIBRADIN 20 mg capsules are marked with code 155 20
LIBRADIN capsules are packaged in aluminum / aluminum blisters (with PVC and polyamide coating) contained in cardboard boxes of 10, 14, 20, 28, 30, 50, 56, 98 or 100 capsules. Not all pack sizes may be marketed.
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
PROZIN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Prozin 50 mg / 2 ml solution for injection
Each ampoule contains: 50 mg chlorpromazine hydrochloride
Prozin 40 mg / ml oral drops, solution
100 ml of solution contain: 4 g chlorpromazine hydrochloride (each drop corresponds to 2 mg of active ingredient)
Prozin 25 mg coated tablets
Each coated tablet contains: 25 mg chlorpromazine hydrochloride
Prozin 100 mg coated tablets
Each coated tablet contains: 100 mg chlorpromazine hydrochloride
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Solution for injection for intramuscular and intravenous use, oral drops, solution and tablets for oral use.
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 when accompanied by agitation and delirium, mostly in association with antidepressants.
Incoercible vomiting and hiccups.
Treatment of severe pain usually in combination with narcotic analgesics.
Pre-anesthetic dressing.
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, gradually 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 it is not strictly necessary in the opinion of the specialist.
As an example, the following general scheme is provided.
- In the treatment of psychiatric disorders the dosage is extremely varied. In general, in outpatients and patients with mild to moderate symptoms, 30-75 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. necessary, then move on 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. possibly repeated 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.
Pre-anesthetic dressing: 25-50 mg per os, 12.5-25 mg per 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 or to any of the excipients.
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.
Serious states of depression, blood dyscrasias, liver and kidney affections.
The product is not indicated in infancy.
Pheochromocytoma, myasthenia gravis and untreated epilepsy.
First trimester of pregnancy and during breastfeeding.
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.
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 late 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. duration of treatment should be the minimum 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 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.
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 drug 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.In case of hypotension, do not use adrenaline which can cause a further lowering of blood pressure.
Use with caution in patients with cardiovascular disease or a family history of QT prolongation.
Avoid concomitant therapy with other neuroleptics.
Prolonged doses lead to an increase in the plasma level of prolactin with possible effects on target organs. Medicines containing phenothiazines should therefore be used with appropriate caution in women with breast cancer.
During therapy, especially if prolonged or at high doses, the possibility of undesirable effects affecting the CNS, liver, bone marrow, eye and cardiovascular system must always be kept in mind 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 Prozin. As well as repeated checks of renal and hepatic function are appropriate.
Patients treated with high doses of chlorpromazine and who are undergoing 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.
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. Prozin should be used with caution in patients with stroke risk factors.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients being treated with antipsychotics often present with acquired risk factors for VTE; all possible risk factors for VTE must be identified before and during treatment with Prozin and appropriate preventive measures undertaken.
Increased mortality in elderly patients with dementia
Data from two large observational studies showed that elderly patients with dementia treated with antipsychotics have a slightly increased risk of death compared to untreated patients. However, the available data are insufficient to be able to provide a precise estimate of the size of the risk. The cause of the increased risk is unknown.
Prozin is not licensed for the treatment of dementia-related behavior disorders.
Important information about some of the ingredients
Prozin ampoules contain potassium metabisulfite and sodium sulfite; these substances can cause allergic reactions and severe asthmatic attacks in sensitive subjects and particularly in asthmatics.
The 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.
The oral drops contain sucrose therefore patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency, should not take this medicine; they also contain para-hydroxy benzoates which can cause allergic reactions (even delayed).
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, unwanted effects of interaction.
Given their fundamental properties, phenothiazines can variously interfere with numerous groups of drugs. Between these:
Substances that depress the CNS: barbiturates, anxiolytics, anesthetics, antihistamines, analgesics, opiates. 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 association 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, can accentuate the metabolism of phenothiazines.
Lithium: lithium may reduce the concentration of chlorpromazine in the plasma and also increase the risk of extrapyramidal type reactions. One case of ventricular fibrillation has been reported following lithium withdrawal during combination therapy with chlorpromazine. Although rarely, the combination 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 Prozin should be discontinued.
Antihypertensives: Interaction with drugs used in the treatment of hypertension 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 Prozin.
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 medicine together with antacids or other substances that can reduce the absorption of phenothiazines.
Interactions with laboratory tests: The urinary metabolites of phenothiazines can impart a dark color to the urine and give false positive responses to the 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 may induce ECG changes such as QT interval prolongation. When neuroleptics are administered concomitantly with QT prolonging drugs the risk of developing cardiac arrhythmias increases. Therefore, they should be used with caution in patients who they take substances such as antiarrhythmics that have similar effects.
Antidepressants: the combination of phenothiazines and tricyclic antidepressants increases the risk of antimuscarinic effects.
It has been shown that the interaction between chlorpromazine and imipramine is responsible for the formation of stomatocytes, spherostomatocytes and spherocytes, due to an irreversible loss of erythrocyte area and volume, probably due to endo-vesiculation.
Deferoxamine: administration of deferoxamine and prochlorperazine resulted in a transient metabolic encephalopathy. It is possible that this situation could also occur with chlorpromazine, as it exhibits many of the pharmacological activities of prochlorperazine.
Antiepileptics: Chlorpromazine inhibits the metabolism of valproic acid and therefore increases its concentrations.
Anorectic drugs: Anorectic drugs, such as sympathomimetics (amphetamine, benzphetamine, dextroamphetamine, diethylpropion, mazindol, methamphetamine, phendimetrazine, phenmetrazine, phenylpropanolamine) and serotonergic stimulants (dexfenflurine, phenfluramine, with consequent anorexic and an increase in psychotic symptoms.
Antibiotics: Chlorpromazine may interact synergistically with antimicrobial agents such as streptomycin, erythromycin, oleandomycin, spectinomycin, azithromycin, amoxicillin-clavulanic acid and fluoroquinolones. The minimal inhibitory concentration of these antibiotics can be reduced up to 8,000 times in the presence of chlorpromazine. Antimicrobial agents that do not interact synergistically with chlorpromazine include gentamicin, amoxicillin and ampicillin.
Anticoagulants: Concomitant administration of warfarin inhibits the metabolism of chlorpromazine
Anti-migraine drugs: Derivatives of ergot and eletriptan may interact, potentiating their respective side effects.
Antivirals: Ritonavir may increase the area under the concentration-time curve (AUC, area under curve) of chlorpromazine. Amantadine, antiviral and antiparkinsonian drug, antagonizes the effect of chlorpromazine on motility.
Cholinesterase inhibitors: The action of chlorpromazine can be antagonized by these drugs (donepezil, galantamine, rivastigmine), which are centrally reversible acetylcholinesterase inhibitors, used in the treatment of Alzheimer's disease.
Naltrexone: In patients treated with phenothiazines, intense somnolence and lethargy have been reported following administration of naltrexone.
Tamoxifen: It has been shown that chlorpromazine, due to its anti-proliferative properties, can enhance the effect of tamoxifen through an estrogen receptor mediated mechanism.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Studies on the metabolism of chlorpromazine have identified two isoenzymes CYP2D6 and CYP1A2 involved in the metabolism from chlorpromazine to 7-hydroxy-chlorpromazine.
They are inhibitors of CYP2D6 (main isoenzyme involved in the metabolism of chlorpromazine): antidepressants, methadone, quinidine, H2 blockers, codeine, alprenolol, antimalarials. They are inhibitors of CYP1A2: 5HT reuptake inhibitors, fluoroquinolones, methylated xanthines, warfarin.
04.6 Pregnancy and lactation
Do not administer in the first trimester of pregnancy. In the second and third trimester of pregnancy the medicine should be used only when considered essential and always under the direct supervision of the doctor as the risk of harmful effects on the fetus, following the administration of chlorpromazine, is not excluded.
Infants exposed to conventional or atypical antipsychotics including Prozin 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.
As phenothiazines pass into breast milk, women on treatment should be advised not to engage in breastfeeding.
When used as an antiemetic, the medicine must 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.
04.7 Effects on ability to drive and use machines
Since phenothiazines induce sedation and drowsiness, this must be taken into account in subjects who drive vehicles or other machinery, or who perform dangerous 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 have 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, 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 drug; 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-parkinsonians (akinesia, rigidity, tremor at rest, etc.) are mostly sensitive to specific drugs; in persistent cases, dose reduction or discontinuation of treatment may be necessary.
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 consist of 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 the dosage of neuroleptics, 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 has the potential to become irreversible.
Cardiac 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. electrocardiographic tracing.
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 observed with Prozin or other drugs of the same class.
Very rare cases of sudden death.
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 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 exposed areas.
Endocrine disorders and disorders of metabolism and nutrition: 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 reduction of testicular volume in men, impotence.Other possible effects are weight gain, peripheral edema, hyperglycemia and glucosuria.
Immune system disorders and diagnostic tests: 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 type 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.
Pregnancy, puerperium and perinatal conditions: neonatal withdrawal syndrome, frequency not known, extrapyramidal symptoms (See section 4.6.).
Other:
Neuroleptic Malignant Syndrome: (see Special warnings and precautions for use).
Hepatic and renal damage: As with all phenothiazines, "silent pneumonia" may develop in patients on prolonged treatment with chlorpromazine.
Cases of venous thromboembolism, including cases of pulmonary embolism and deep vein thrombosis, have been reported with antipsychotic drugs (frequency not known).
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 should 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 Prozin can modify the normal response. Never use adrenaline.
Establish symptomatic treatment of nervous system depression such as acute barbiturate intoxication, including physiotherapy and antibiotic treatment to prevent bronchopneumonia. Hemodialysis is not effective. When the body temperature drops to particularly low levels, heart arrhythmias can appear. Particular surveillance must be exercised to control bowel and bladder distension phenomena.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Drug therapeutic category: Antipsychotics, phenothiazines with aliphatic side chain
ATC code: N05AA01
Chlorpromazine is a phenothiazine-derived neuroleptic characterized by multiple pharmacodynamic activities: sedative, vagolytic, sympatholytic, antiemetic, anticonvulsant, hypothermic, ganglionic, and enhancing the effects of some CNS depressants. including hypnotics, analgesics and anesthetics. At low doses in the experimental animal it causes a typical sedative effect with increased sociability, while at increasing doses it induces a progressive decay of spontaneous motility up to immobility and catatonic state. Pharmacologically it has a broad spectrum of activity, characterized by adrenolytic, antiacetylcholinic, antihistamine, antiserotonin, spasmolytic and anesthetic effects.
05.2 "Pharmacokinetic properties
Chlorpromazine is rapidly and completely absorbed from the gastrointestinal tract. After oral administration the drug reaches high concentrations in the liver, myocardium, lungs and brain. Plasma concentration is subject to considerable individual variability; after oral administration the blood concentration reaches the peak within 2-3 hours with a half-life time of approximately 6 hours.
50-60% of the drug is eliminated via the kidney mostly as glucuronide and only 1% as active substance.
05.3 Preclinical safety data
DL50: via i.v. 28 mg / kg (mouse), 25 mg / kg (rat), 30 mg / kg (dog); per os 135 mg / kg (mouse), 492 mg / kg (rat); via s.c. 160-200 mg / kg (mouse), 540 mg / kg (rat). Chronic toxicity was studied in the rat and dog; up to doses of 81 mg / kg (rat) for 1 month of oral administration and 30 mg / kg for 3 months (dog) no toxic effects were noted. Pregnancy and fetal toxicity did not reveal any teratogenic effects.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Injectable solution: hydroquinone, sodium metabisulfite, anhydrous sodium sulphite, sodium chloride, water for injections.
Oral drops, solution: E150 dye, citric acid, sucrose, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, alcohol, purified water.
25 mg coated tablets: lactose, corn starch, potato starch, precipitated silica, stearic acid, talc, color E110, methacrylic acid copolymers, titanium dioxide, polyethylene glycol 6000, triethyl citrate.
100 mg coated tablets: lactose, corn starch, potato starch, precipitated silica, stearic acid, talc, methacrylic acid copolymers, titanium dioxide, polyethylene glycol 6000, triethyl citrate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 years
06.4 Special precautions for storage
Keep the container tightly closed to protect from light.
06.5 Nature of the immediate packaging and contents of the package
Solution for injection: cardboard box containing 5 ampoules of 2 ml
Oral drops, solution: cardboard box containing glass bottle and built-in dropper with 10 ml of oral solution
25 mg coated tablets: carton box containing 25 tablets packed in opaque blisters
100 mg coated tablets1: carton box containing 20 tablets packed in opaque blisters
1 hospital pack only
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
LUSOFARMACO
Luso Farmaco Institute of Italy S.p.A.
Via W. Tobagi, 8 - Peschiera Borromeo (MI)
08.0 MARKETING AUTHORIZATION NUMBER
Prozin 50 mg / 2 ml solution for injection: A.I.C. n. 010852010
Prozin 40 mg / ml oral drops, solution: A.I.C. n. 010852034
Prozin 25 mg coated tablets: A.I.C. n. 010852022
Prozin 100 mg coated tablets: A.I.C. n. 010852046
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Prozin 50 mg / 2 ml solution for injection: 10.02.56 / 1.06.10
Prozin 40 mg / ml oral drops, solution: 10.02.56 / 1.06.10
Prozin 25 mg coated tablets: 10.02.56 / 1.06.10
Prozin 100 mg coated tablets: 21.01.57 / 1.06.10
10.0 DATE OF REVISION OF THE TEXT
February 2012
