PROZIN - PACKAGE LEAFLET - LEAFLETS

Home / leaflets / 2021

Prozin - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Chlorpromazine (Chlorpromazine hydrochloride)

PROZIN 50 mg / 2 ml solution for injection
PROZIN 40 mg / ml oral drops, solution
PROZIN 25 mg coated tablets
PROZIN 100 mg coated tablets

Why is Prozin used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Antipsychotics, phenothiazines with aliphatic side chain.

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.

Contraindications When Prozin should not be used

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.

Severe states of depression; blood dyscrasias; liver and kidney diseases.

The product is not indicated in infancy.

Pheochromocytoma, myasthenia gravis and untreated epilepsy.

First trimester of pregnancy and during breastfeeding.

Precautions for use What you need to know before taking Prozin

As with all neuroleptics, patients treated with chlorpromazine should be under close medical supervision.

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. duration of treatment should be the minimum to achieve a satisfactory clinical response. If signs or symptoms of tardive dyskinesia appear (see side effects) during therapy, discontinue administration. In general, phenothiazines do not produce psychic dependence. However, following 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 (NMS) 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.

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. of hypotension do not use adrenaline which can lead to 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.

Because drugs of this type have been associated with the formation of blood clots, Prozin should be used with caution in patients with a history of blood clot formation or in patients who have family members with a history of blood clots.

Interactions Which drugs or foods can change the effect of Prozin

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, 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, hypnotics, anesthetics, antihistamines, opiate analgesics. In case of combination avoid high dosages and carefully monitor the patient to avoid excessive sedation or central depression.

Anticonvulsants: due 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 can 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 can 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 seizures. 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.

Alcohol: it is not advisable to drink alcohol during therapy as it can 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.

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 of amylase, urobilinogen, uroporphyrin, porphobilinogens and 5-hydroxy-indolacetic acid. False positive pregnancy tests have been reported in women receiving phenothiazines.

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. 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. taking substances such as antiarrhythmics that have similar effects.

Antidepressants: the combination of phenothiazines and tricyclic antidepressants accentuates the 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, mazindole, methamphetamine, phendimetrazine, phenmetrazine, phenylpropanolamine) and serotonergic stimulants (dexfenurfluramine with consequent their anorectic effect 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 can interact, enhancing their respective side effects.

Antivirals: Ritonavir may increase the area under the concentration-time curve (AUC) of chlorpromazine. Amantadine, an 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: Intense somnolence and lethargy have been reported after administration of naltrexone in patients treated with phenothiazines.

Tamoxifen: It has been shown that chlorpromazine, thanks to its antiproliferative 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.

Warnings It is important to know that:

Pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine. 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. The following symptoms have been observed in newborn babies of mothers who have taken conventional or atypical antipsychotics, including Prozin, 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. Since phenothiazines pass into breast milk, the drug is contraindicated (see Contraindications) during 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.

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. For those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positive anti-doping tests, in relation to the alcohol concentration limits indicated by some sports federations.

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 and the oral drops contain sucrose so if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. The oral drops contain para-hydroxy benzoates which can cause allergic reactions (including delayed ones).

Dosage and method of use How to use Prozin: 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, 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.

Vomiting: 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.

Overdose What to do if you have taken too much Prozin

In case of accidental ingestion / intake of an excessive dose of Prozin, notify your doctor immediately or go to the nearest hospital.

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.

IF YOU ARE IN ANY DOUBT ABOUT THE USE OF PROZIN, CONTACT YOUR DOCTOR OR PHARMACIST.

Side Effects What are the side effects of Prozin

As with all medicines, Prozin 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 they 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 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 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 disorders: 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.

Blood and lymphatic system disorders: 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 the photo areas exposed.

Endocrine disorders and disorders of metabolism and nutrition: phenothiazines can cause hyperprolactinemia, 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.

Immune system disorders and diagnostic tests: in addition to skin 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 protracted 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. dosage and duration of therapy it is suggested that patients on high dose or long-term treatment 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. Formation of blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in the legs), which can migrate through blood vessels into the lungs causing chest pain and difficulty in breathing. Patients who notice any of these symptoms should see their doctor immediately. In elderly patients with dementia, a small increase in the number of deaths has been reported in patients treated with antipsychotics compared to patients not treated with antipsychotics.

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.

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.

Keep the container tightly closed to protect from light.

Keep this medicine out of the reach and sight of children.

Medicines should not be disposed of 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

COMPOSITION

Prozin 50 mg / 2 ml solution for injection

Each vial contains:

Active ingredient: 50 mg chlorpromazine hydrochloride.

Excipients: hydroquinone, sodium metabisulfite, anhydrous sodium sulphite, sodium chloride, water for injections.

Prozin 40 mg / ml oral drops, solution

100 ml of solution contain:

Active ingredient: chlorpromazine hydrochloride g 4.

Excipients: color E 150, citric acid, sucrose, methyl p-hydroxybenzoate, propyl phydroxybenzoate, alcohol, purified water.

Prozin 25 mg coated tablets

Each coated tablet contains:

Active ingredient: chlorpromazine hydrochloride 25 mg

Excipients: lactose, corn starch, potato starch, precipitated silica, stearic acid, talc, color E 110, methacrylic acid copolymers, titanium dioxide, polyethylene glycol 6000, triethyl citrate.

Prozin 100 mg coated tablets

Each tablet contains:

Active ingredient: 100 mg chlorpromazine hydrochloride.

Excipients: lactose, corn starch, potato starch, precipitated silica, stearic acid, talc, methacrylic acid copolymers, titanium dioxide, polyethylene glycol 6000, triethyl citrate.

PHARMACEUTICAL FORM AND CONTENT

Prozin 50 mg / 2 ml solution for injection: 5 ampoules of 2 ml of solution for intramuscular and intravenous use in a lithographed cardboard box.

Prozin 40 mg / ml oral drops, solution: 10 ml bottle of solution for oral use in a lithographed cardboard box.

Prozin 25 mg coated tablets: 25 coated tablets of 25 mg for oral use in a lithographed cardboard box.

Prozin 100 mg coated tablets: 20 100 mg coated tablets for oral use in a lithographed cardboard box.

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.

More information about Prozin can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on the ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER 09 .0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS AND QUALITY CONTROLS

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

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 medicine 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. 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.

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.

Patients treated with high doses of chlorpromazine and who are undergoing surgical interventions require lower doses of anesthetics and central nervous system depressant drugs.

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.

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.

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.

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.

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.

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.

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 testicular volume reduction in men, impotence. Other possible effects are an increase in body weight, peripheral edema, hyperglycemia and glycosuria.

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.

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.