Trilafon - Package Leaflet
Active ingredients: Perfenazine
Trilafon 2 mg coated tablets
Trilafon 4 mg coated tablets
Trilafon 8 mg coated tablets
Why is Trilafon used? What is it for?
Trilafon contains the active substance perphenazine. Perphenazine belongs to a group of medicines called phenothiazines that act on the central nervous system by attenuating states of anxiety and anxiety (anxiolytic properties), carrying out therapeutic activity against psychotic symptoms (delusions and hallucinations) and is also able to prevent o eliminate vomiting and the feeling of nausea (antiemetic property).
Trilafon is indicated for the treatment of the following ailments and diseases:
- schizophrenia, mental disorder that manifests itself with various symptoms including hallucinations, delusions, tendency to isolation, difficulty in articulating thoughts;
- paranoid states, personality disorders characterized by a persistent tendency to interpret the behavior of others with distrust and suspicion;
- psychological states that manifest themselves with mood alterations associated with euphoria and excitability and characterized by obsessive ideas and behaviors (manias);
- toxic psychosis, psychiatric disorders induced by drug use (amphetamines, LSD, cocaine, etc.);
- mental disorders associated with organic causes and accompanied by delirium;
- severe anxiety disorders that do not show improvement with anxiolytic medications;
- depression, when accompanied by agitation and delirium, in association with antidepressants;
- for the reduction of vomiting and persistent and continuous hiccups;
- in the treatment of severe pain, usually in combination with analgesic medicines (painkillers).
Contraindications When Trilafon should not be used
Do not take Trilafon if:
- you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
- is in a state of decreased degree of consciousness (severe dullness) or in case of coma or severe depression;
- you are taking medicines that can slow down the normal activity of the brain (central nervous system depressants) such as alcohol, barbiturates, opiates, etc .; you are taking other medicines used to treat mental disorders (neuroleptics); in this case, tell your doctor ;
- have blood disorders (blood dyscrasias) or changes in the function of the bone marrow, which cannot produce enough cells that are found in the blood (bone marrow depression);
- have liver disease;
- has suffered presumed or ascertained brain damage (subcortical brain damage, with or without hypothalamic damage);
- are "under 12 years of age (see section" Children and adolescents ");
- are in the first trimester of pregnancy or are breast-feeding (see section "Pregnancy and breast-feeding").
Precautions for use What you need to know before you take Trilafon
Talk to your doctor or pharmacist before taking Trilafon if:
- is elderly;
- suffer from cardiovascular disease or have a family history of impaired heart function (QT prolongation);
- have a tumor of the adrenal glands (pheochromocytoma) or changes in the heart valves (mitral insufficiency). In this case he will be subjected to greater control in the administration of perphenazine for the risks related to the lowering of blood pressure (hypotension);
- have respiratory diseases caused by lung infections or chronic breathing disorders such as severe asthma or emphysema;
- have reduced kidney function;
- suffer from a disease that causes increased pressure in the eye (glaucoma);
- you have diseases affecting the urogenital system such as enlarged prostate (prostatic hypertrophy);
- has narrowing of the gastrointestinal and urinary tract (stenosing diseases of the digestive and urinary tract);
- suffer from mental disorders, as Trilafon may cause a worsening of the mood up to the onset of depression;
- have breast cancer. In this case, perphenazine will be given to you with particular care, as it induces an increase in the concentration of a hormone (prolactin) which can worsen your disease;
- suffer from Parkinson's disease or Parkinson-like forms, or other motor disorders, since perphenazine can increase the state of muscle stiffness;
- you are abstinent from alcohol;
- you have seizures and are taking anticonvulsant (antiepileptic) medicines. In such cases, if the doctor deems it appropriate, it may be necessary to increase the dose of medicines to treat seizures;
- is exposed to temperatures that are too high or too low, as Trilafon can compromise the body's temperature regulation mechanisms;
- you are undergoing surgery and are taking high doses of this medicine. In this case, your doctor will monitor you closely as there is a risk of a drop in blood pressure (hypotension). It may also be necessary to reduce the amount of anesthetics or sedatives you are taking;
- is in the post-operative phase, since aspiration of vomiting has occurred in a limited number of patients receiving phenothiazines;
- take alcohol, as it may potentiate the effects of the medicine, significantly lower blood pressure (hypotension) and increase the risk of suicide;
- suffer from dementia and are being treated with atypical antipsychotics, as an increased risk of cerebrovascular events (e.g. stroke, transient ischemic attack) has been observed in these cases;
- has risk factors for stroke;
- have had cardiovascular disease associated with blood clot formation (venous thromboembolism) or have risk factors for these diseases.
The use for the treatment of vomiting and nausea during pregnancy must take place only in cases for which an alternative intervention is not possible and not in the frequent and common cases of pregnancy nausea, much less in order to prevent it.
It is possible that during treatment with Trilafon you may experience:
- the appearance of inflammation of the mouth and upper airways. In this case it is advisable to undergo blood tests;
- alteration of organic functions. The safe and effective use of Trilafon requires adequate control of the dose of the medicine taken, and the performance of periodic checks to evaluate the values of blood cells, the function of the liver, kidneys and heart, especially if you are taking Trilafon. high doses or for prolonged periods of time. If abnormal results are found, your doctor may decide to stop the treatment;
- appearance of involuntary movements of the muscles (tardive dyskinesia). Both the risk of developing dyskinesia and the likelihood of it becoming irreversible increase with the duration of treatment and with the total dose of medication taken. Discontinuation of treatment may lead to resolution of these abnormalities. If you notice these symptoms, please inform your doctor who will consider adjusting the dose or stopping the treatment;
- the appearance of skin sensitivity reactions to light (photosensitivity). For this reason, avoid excessive exposure to sunlight or use specific protective creams during treatment with Trilafon;
- an increased risk of having thoughts associated with suicide if you have depression. This condition persists during treatment with Trilafon and until symptoms improve significantly. You will therefore be closely monitored to prevent access to excessive quantities of Trilafon.
Stop taking Trilafon and tell your doctor if you experience:
- a potentially fatal complex of symptoms called neuroleptic malignant syndrome, the symptoms of which are: increased body temperature, muscle stiffness, decreased movement (akinesia), vegetative disturbances (irregular pulse and blood pressure, sweating, increased frequency of heart beats (tachycardia), changes in heart rhythm (arrhythmias)), changes in consciousness which can progress to stupor and coma. The doctor will stop the therapy and start a therapy for the treatment of these symptoms;
- a significant increase in body temperature not attributable to a specific cause. This increase in temperature could suggest a "hypersensitivity to perphenazine and in this case the doctor will tell you to stop the therapy; abnormal liver or kidney function tests or blood dyscrasias, in which case the doctor will tell you to stop the therapy.
Perphenazine reduces the feeling of nausea and vomiting and therefore may mask the signs of overdose of other medicines or make it more difficult to diagnose diseases such as intestinal obstruction, Reye's syndrome and brain tumors.
Increased mortality in elderly patients with dementia
Elderly patients with dementia treated with antipsychotics have been observed to have a slightly increased risk of death compared to untreated patients. Trilafon is therefore not indicated for the treatment of dementia-related behavioral disorders.
Children and adolescents
The safety of Trilafon for use in children below 12 years of age has not been established, therefore its use in children is not recommended.
Interactions Which drugs or foods can change the effect of Trilafon
Other medicines and Trilafon
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Talk to your doctor or pharmacist if you are taking:
- other antipsychotic medicines because concomitant therapy with Trilafon should be avoided;
- barbiturates, anxiolytics, anesthetics, antihistamines, meperidine and other opiate analgesics;
- medicines to treat seizures, such as phenytoin, lithium, used to treat certain mood disorders;
- tricyclic antidepressants and selective serotonin re-uptake inhibitors (SSRIs);
- medicines to treat high blood pressure, such as guanethidine, methyldopa and beta blockers (for example propranolol);
- Quinidine, propafenone and flecainide (antiarrhythmics);
- Cimetidine (medicine used in the treatment of ulcer);
- medicines with anticholinergic action (inhibiting action of acetylcholine, a substance that acts on the nervous system), such as atropine;
- phenylbutazone (used for inflammation and muscle trauma), medicines that depress the production of thyroid hormones (thiouracyls) and other medicines that suppress the bone marrow (myelotoxic);
- metrizamide, a compound used as a contrast agent in some tests to diagnose blood disorders. Trilafon therapy should be discontinued at least 48 hours prior to testing due to the possibility of an increased risk of seizures. The administration of Trilafon should not be resumed for 24 hours after the examination;
- levodopa, a medicine used to treat Parkinson's disease;
- medicines used to reduce stomach acid, such as aluminum salts, as concomitant use with Trilafon may reduce its absorption;
- medicines that prolong the QT interval, as this increases the risk of developing changes in the heart beat (heart arrhythmias);
- medicines that cause changes in electrolytes, such as medicines used to treat high blood pressure (hypertension).
Tell your doctor if you are exposed to organic phosphorus insecticides.
Trilafon and laboratory tests
Taking Trilafon can darken the urine and cause changes in the results of some laboratory tests:
- false-positives in the values of the following tests: urobilinogen, amylase, uroporphyrins, porphobilinogens and 5-hydroxy-indolacetic acid;
- changes in the results of hypothalamus-pituitary function tests, as the medicine may cause a decrease in some hormones;
- false-positive and false-negative in the urine pregnancy test.
- changes in the electrocardiogram and specifically in the QT interval.
Trilafon with food, drink and alcohol
Do not take Trilafon at the same time as alcohol due to the possible increase in the effects of the medicine, including a decrease in blood pressure (hypotension). Furthermore, this combination may increase the risk of suicide and the danger of overdose.
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.
Trilafon should not be used in the first trimester of pregnancy. In the following months, your doctor will decide whether or not you need to take Trilafon.
Perphenazine is rapidly excreted in breast milk, therefore your doctor will decide whether to discontinue breastfeeding or Trilafon therapy, taking into account the importance of the therapy for you.
Driving and using machines
Trilafon can induce sedation and sleepiness. Take this into account when driving and using machines.
Trilafon contains lactose
If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Trilafon: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist. The optimal dose of Trilafon should be determined by your doctor, depending on the severity of the disease and your response to therapy.
It is always preferable to use the lowest effective dose, considering that the frequency and severity of undesirable effects is proportional to the dose increase. The need for continued treatment should be evaluated periodically by the physician.
The recommended dose for the treatment of outpatients is 4 - 8 mg of Trilafon three times a day or 8 - 16 mg twice a day. In hospitalized patients the recommended dose is 8-16 mg two / four times a day, or 8 - 32 mg twice a day. In any case, no more than 64 mg of perphenazine taken orally per day should be exceeded. The use of Trilafon for the reduction of vomiting requires dosages of 8 - 12 mg divided during the day.
Use in children and adolescents
Trilafon should not be used in children and adolescents under 12 years of age (see section "Children and adolescents"). For adolescents over 12 years of age, the same treatment schedule as for adults is applicable (see previous section).
Use in the elderly
The dose and frequency of administration of Trilafon in elderly patients should be carefully determined by the physician, who will evaluate a possible reduction in the above dose based on individual needs.
Overdose What to do if you have taken too much Trilafon
If you take more Trilafon than you should
If you have swallowed / taken too much Trilafon, contact your doctor immediately or go to the nearest hospital.
Symptoms of taking an excessive dose of perphenazine are manifested by abnormalities of the motor system (extrapyramidal symptoms). A progressive slowing of mental functions (depression of the central nervous system), from drowsiness to temporary detachment from external reality (stupor) may occur or coma with absence of reflexes. Children may experience seizures. Patients with moderate or early intoxication may experience restlessness, confusion and excitement. Other symptoms of overdose include: low blood pressure (hypotension), increased heart rate (tachycardia), decrease in body temperature (hypothermia), decrease in pupil size (miosis), tremors, muscle twitching, involuntary contractions (spasms), stiffness or decrease in muscle tone (hypotonia), seizures, difficulty in swallowing and breathing, bluish discoloration of the skin and mucous membranes (cyanosis), respiratory and / or collapse vasomotor, sometimes with sudden apnea.
Method of treatment in case of overdose of Trilafon
There is no specific substance that can counteract the effect of Trilafon overdose. In the hospital you will be immediately subjected to the appropriate emergency treatments (eg induction of vomiting or gastric lavage) and will be closely monitored by your doctor by monitoring your its state.
If you forget to take Trilafon
Do not take a double dose to make up for a forgotten dose.
If you stop taking Trilafon
Do not stop taking Trilafon until you have consulted your doctor. Phenothiazines are generally not addictive. However, if you stop suddenly, you may experience effects such as: gastritis, nausea, vomiting, dizziness, tremors and motor hyperactivity.
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 Trilafon
Like all medicines, Trilafon can cause side effects, although not everybody gets them.
Stop taking Trilafon and contact your doctor immediately if you experience:
- Neuroleptic Malignant Syndrome (NMS) which is characterized by the manifestation of symptoms such as increased body temperature, muscle stiffness, decreased movement (akinesia), vegetative disorders (irregular pulse and blood pressure, sweating, increased heart rate ( tachycardia), changes in heart rhythm (arrhythmias)), altered state of consciousness which can progress to stupor and coma;
- persistent abnormalities in muscle contraction and movement, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (late persistent dyskinesia);
- skin rash, similar to hives, accompanied by swelling of the hands, feet, ankles, or also of the face, lips, tongue and / or throat resulting in difficulty in swallowing or breathing (angioneurotic edema);
- increased body temperature (hyperpyrexia);
- excessive accumulation of fluid in the brain (cerebral edema), circulatory collapse and death due to hypersensitivity to phenothiazines (extremely rare side effects);
- swelling, pain and redness in the legs possibly accompanied by chest pain and difficulty in breathing.These symptoms are due to blood clots in the veins especially in the legs which can migrate through blood vessels to the lungs (the frequency of this side effect cannot be estimated from the available data).
The symptoms most commonly reported during treatment with perphenazine, as with all medicines belonging to the same pharmacological category as perphenazine, are alterations and abnormalities of the motor system (extrapyramidal reactions), such as:
- abnormal posture characterized by "excessive neck extension, stiffness and severe arching of the back (opisthotonus), abnormal contraction of the jaw muscles with difficulty opening the mouth (trismus), limited mobility or blockage of the neck accompanied by neck pain and contracture of the lateral muscles of the neck (torticollis), torticollis associated with a deviated posture of the head and in which sudden muscle spasms may occur, which cause sudden rotations of the head ("spastic" torticollis), pain and tingling in the limbs, state of agitation with excessive motor activity (motor restlessness), alteration and deviation of the eyes in one direction (oculogyric crisis), hyper-reactivity of reflexes characterized by abnormal muscle contractions (hyper-reflexia), movement disorder characterized by involuntary muscle contractions (dystonia) including deformation of the spine (protrusion), alteration to car ico of the tongue (color, pain and involuntary movements), sudden and involuntary contractions of the chewing muscles, a sense of constriction in the throat, difficulty in pronouncing words and swallowing (dysphagia), inability to sit, abnormal movements and contraction of the muscles (dyskinesia), muscle stiffness and slowing of movement speed (parkinsonism) and loss of muscle coordination (ataxia).
It can also occur:
- abnormalities in the protein composition of the fluid found in the central nervous system (cerebrospinal fluid), seizures, headache (headache), drowsiness;
- worsening of psychotic symptoms such as thought disturbances, delusions and hallucinations, motor, emotional and behavioral abnormalities (catatonic-like states), forms of thinking that deviate from reality (paranoid reactions), deep sleep (lethargy), worsening of symptoms for which it is treated (paradoxical excitement) restlessness and hyperactivity, nocturnal confusional states with bizarre dreams, sleep disturbances (insomnia);
- abnormal milk secretion (galactorrhea), enlarged breasts in women and men (gynecomastia), menstrual cycle disturbances, prolonged absence of menstruation (amenorrhea), changes in sexual desire, inhibition of ejaculation, increased and decreased concentration blood sugar (hyperglycemia and hypoglycemia), presence of sugar in the urine (glycosuria), excessive release of an antidiuretic hormone which can cause headache, nausea and malaise (syndrome of inappropriate antidiuretic hormone secretion, SIADH);
- false positivity in pregnancy tests;
- low blood pressure when rising from a sitting or lying position (postural hypotension), increased and decreased heart rate (tachycardia and bradycardia), cardiac arrest, momentary loss of consciousness and dizziness, non-specific changes in the electrocardiogram, abnormal heartbeat (QT prolongation, rarely seen), ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest;
- decrease in white blood cells (agranulocytosis, leukopenia), increase in a particular type of white blood cell (eosinophilia), decrease in the number of red blood cells (haemolytic anemia), abnormal destruction of platelets (thrombocytopenic purpura), decrease in the number of all blood cells blood (pancytopenia);
- inflammation and obstruction of particular channels that carry bile (biliary stasis), yellowing of the skin and whites of the eyes (jaundice).
Less frequent side effects:
- sedation, blood disorders (blood dyscrasia), loss of consciousness associated with involuntary muscle contractions (convulsions) and effects on the autonomic nervous system.
Occasionally it can occur:
- dry mouth and hypersalivation, feeling sick (nausea), vomiting and diarrhea, gastric retention, anorexia, constipation (constipation), stubborn constipation and hard lump of dehydrated stool (fecaloma), difficulty emptying the bladder (urinary retention) , frequent urination and involuntary passing of urine (incontinence), loss of bladder function (bladder paralysis), increased amount of urine passed (polyuria);
- stuffy nose (nasal congestion);
- paleness, increase (mydriasis) and decrease (miosis) in pupil size, blurred vision, eye disease resulting in increased pressure in the eye (glaucoma), excessive sweating, increased blood pressure (hypertension), low blood pressure (hypotension), altered pulse rate, alterations and blockages of the intestinal muscles (adynamic ileus) which in severe cases can cause complications and death;
- allergic reactions to the skin (hives), irritation and red spots on the skin (erythema), inflammatory reactions that itchy skin (eczema), inflammation of the skin with formation of lesions and loss of the superficial layer (exfoliative dermatitis), itching, reactions sensitivity of the skin to light (photosensitivity), asthma, fever, allergic reactions (anaphylactoids), accumulation of fluid in the upper airways (edema of the larynx), contact dermatitis.
Side effects related to long-term therapy:
- appearance of spots on the skin (skin pigmentation), changes in vision which, in severe cases, lead to opacity of the star-shaped lens, inflammation of the cornea (epithelial keratopathies), retinal changes, destruction of the retina up to loss of vision (retinopathy pigmentary).
Other side effects:
- fluid accumulation in the lower limbs (peripheral edema), state of sedation (reverse epinephrine effect), alteration in the amount of iodine-binding proteins (increase in PBI not attributable to an increase in thyroxine), swelling of the salivary glands (parotid swelling) , systemic lupus erythematosus-like syndrome (an inflammatory disease of the immune system affecting various organs and tissues of the body), increased appetite and weight, abnormal increase in food consumption (polyphagia), excessive sensitivity to light (photophobia), muscle weakness.
Sudden death has occasionally been reported in patients undergoing treatment with phenothiazines. In some patients it was not possible to determine the cause of death or to establish whether the death was attributable to phenothiazine.
Undesirable effects in children
Infants whose mothers have taken antipsychotics, including Trilafon, during the last three months of pregnancy are at risk for motor system disorders and abnormalities (extrapyramidal symptoms) and neonatal withdrawal syndrome. The following have also been reported: shaking, muscle stiffness and / or weakness, tremor, sleepiness, breathing problems, difficulty in eating and overactive reflexes. If your child displays any of these symptoms, contact your doctor immediately.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the package after "EXP". The expiry date refers to the last day of that month. The expiry date indicated refers to the product in intact packaging, correctly stored.
This medicinal product does not require any special storage conditions.
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 Trilafon contains
The active ingredient is perphenazine.
Each tablet of Trilafon 2 mg coated tablets contains 2 mg of perphenazine.
Each tablet of Trilafon 4 mg coated tablets contains 4 mg of perphenazine.
Each tablet of Trilafon 8 mg coated tablets contains 8 mg of perphenazine.
The other ingredients are Trilafon 2 mg coated tablets: maize starch, lactose, magnesium stearate, pregelatinised starch, hypromellose, macrogol, white opaspray, paraffin.
Trilafon 4 mg coated tablets and Trilafon 8 mg coated tablets: maize starch, lactose, magnesium stearate, pregelatinised starch, Opadry® white (hypromellose, macrogol, titanium dioxide, hydroxypropylcellulose).
Description of the appearance of Trilafon and contents of the packs
Trilafon comes in the form of coated tablets contained in a blister. Each pack contains 20 tablets.
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
TRILAFON COATED TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Trilafon 2 mg coated tablets
Each coated tablet contains:
Active ingredient: Perfenazine 2 mg.
Trilafon 4 mg coated tablets
Each coated tablet contains:
Active ingredient: Perfenazine 4 mg.
Trilafon 8 mg coated tablets
Each coated tablet contains:
Active ingredient: Perfenazine 8 mg.
Excipient with known effects:
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
In the treatment of schizophrenias, paranoid states and mania. In toxic psychoses (amphetamines, LSD, cocaine, etc.). In organic mental syndromes accompanied by delirium. In anxiety disorders if particularly severe and resistant to therapy with typical anxiolytics. In depression if accompanied by agitation and delirium, mostly in association with antidepressants. In vomiting and incoercible hiccups. In the treatment of intense pain generally in association with analgesics. narcotics.
04.2 Posology and method of administration
Trilafon dosage should be individualized according to the severity of the case and the response to the drug. However, it is always advisable to resort to the minimum effective dose, since the rare collateral manifestations present an increase in frequency and severity proportional to the increase in dosage.
The need for continued treatment should be reassessed periodically.
By way of example, the following scheme is proposed:
For the treatment of outpatient patients (adults and young people over 12 years of age) the average dosage is 4-8 mg three times a day or 8-16 mg twice a day.
In hospitalized patients the usual oral dose of perphenazine is 8-16 mg 2-4 times daily or 8-32 mg twice daily. In any case, you should not exceed 64 mg of perphenazine per day orally.
The antiemetic action is obtained with average dosages of 8-12 mg divided during the day.
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.
The safety of use of the product in subjects under the age of 12 has not been established, therefore its use in children is not recommended.
Method of administration
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Comatose states or with marked dullness and in subjects treated with high doses of substances with a depressive action on the central nervous system (alcohol, barbiturates, opiates, etc.) severe states of depression; blood dyscrasias; bone marrow depression or liver disease.
Trilafon is also contraindicated in patients with suspected or recognized subcortical brain damage, with or without hypothalamic damage, as a hyperthermic reaction can occur in such patients with temperatures above 40 ° C, sometimes not earlier than 14-16 hours after drug administration. . In such situations it is recommended to cover the body entirely with ice; antipyretics may also be helpful.
The safety of use of the product in subjects under the age of 12 has not been established, therefore its use in children is not recommended.
First trimester of pregnancy and during lactation.
04.4 Special warnings and appropriate precautions for use
Due to its pharmacological properties, the product should be used with caution in the elderly, in subjects with cardiovascular diseases, pheochromocytoma, acute and chronic lung diseases, kidney diseases, glaucoma, prostatic hypertrophy and other stenosing diseases of the digestive and urinary system.
Effects on blood count must be particularly followed between the fourth and twelfth week of treatment.
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.
In general, phenothiazines do not produce psychic dependence. However, gastritis, nausea, vomiting, dizziness, tremors, motor restlessness may appear following abrupt discontinuation of high-dose therapy. Studies suggest that these symptoms may be reduced with continued administration of antiparkinsonian agents for a few weeks after discontinuation of phenothiazine treatment.
Special attention should be paid to patients with psychic depression, ie during the manic phase of cyclical psychosis, due to the possibility of a rapid change in mood towards depression.
The antiemetic effect of phenothiazines can mask the signs of overdosing of other drugs or can make it more difficult to diagnose concomitant diseases of the digestive tract or central nervous system 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.
When used as an antiemetic, the product must be used during pregnancy only in cases of overt symptoms for which an intervention is not possible and not in the frequent and simple cases of emesis gravidarum and even less with preventive purposes of it.
Neuroleptics cause an increase in the plasma level of prolactin with possible effects on target organs. Products containing phenothiazines should therefore be used with appropriate caution in women with breast cancer.
During therapy, especially if prolonged or at high doses, it is necessary to always keep in mind the possibility of side effects affecting the central nervous system, liver, bone marrow, eye and cardiovascular system and it is therefore necessary to perform periodic clinical and laboratory checks.
Tardive dyskinesia may develop in patients treated with neuroleptics. Older patients are at greater risk of the disease. Both the risk of developing the syndrome and the possibility of it becoming irreversible increase with the duration of treatment and with the cumulative total dose of neuroleptics administered to the patient. However, although less frequently, the syndrome can develop even after relatively short periods of low dose therapy.
If neuroleptic treatment is eliminated, tardive dyskinesia can have a partial or complete remission. Neuroleptic treatment itself can, however, suppress (or partially eliminate) the signs and symptoms of the syndrome, and therefore mask the progression of the disease. In patients requiring chronic treatment, the lowest dose and shortest duration should be provided. to produce a satisfactory clinical response The need to continue with treatment should be periodically evaluated.
If signs and symptoms of tardive dyskinesia appear in a patient, consideration should be given to discontinuing the drug. However, some patients may need treatment even in the presence of the syndrome.
Phenothiazines increase the state of muscle stiffness in individuals with Parkinson's disease or similar forms or other motor disorders. Perphenazine can lower the seizure threshold in predisposed individuals. It must be used with caution in situations of alcohol withdrawal and in subjects with convulsive pathology. If the patient is being treated with anticonvulsant drugs, an increase in the dose of these drugs may be necessary when used together with Trilafon.
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. If hypotension occurs, epinephrine should not be administered as its action is blocked and partially reversed by perphenazine. If a vasopressor is needed, use norepinephrine.
Acute and severe hypotension has occurred with the use of phenothiazines, particularly in patients with mitral insufficiency or pheochromocytoma.
As with all phenothiazine derivatives, perphenazine should not be used indiscriminately. Some of the side effects of perphenazine tend to occur more frequently when high doses are given. However, as with other phenothiazines, patients treated with perphenazine should be closely monitored.
Patients treated with phenothiazines must avoid excessive exposure to sunlight by resorting, if necessary, to the use of special protective creams.
Use with caution in subjects exposed to too high or too low temperatures as phenothiazines can compromise the ordinary thermoregulation mechanisms.
An increase in body temperature, which cannot be explained otherwise, may suggest the existence of intolerance to perphenazine, in which case the product must be discontinued.
The association with other psychotropic drugs requires special caution and vigilance to avoid unexpected, unwanted effects of interaction.
Patients, close to surgery, treated with high doses of phenothiazines, must be carefully monitored for possible hypotensive phenomena. However, a small amount of anesthetics or central nervous system depressant drugs may be needed. Since phenothiazines and central nervous system depressant drugs (opioids, analgesics, antihistamines, barbiturates) can potentiate each other, it is recommended that the added drug be given in quantities below the normal dosage and that caution is used. Avoid concomitant therapy with other neuroleptics.
Aspiration of vomiting occurred in a few patients receiving phenothiazines during the postoperative phase. Even if a causal relationship has not been established, this possible occurrence must be taken into consideration during post-operative management.
Use with caution in patients treated with atropine or similar due to additive anticholinergic effects and also in patients who will be exposed to particularly high temperatures or phosphorus-organic insecticides.
The use of alcohol should be avoided, as it may potentiate the effects of the drug, including hypotension. The risk of suicide and the danger of overdose may increase in patients who abuse alcohol.
Since phenothiazines affect many organic functions, their safe and effective use requires pre-treatment and periodic laboratory tests, especially during high-dose or prolonged treatments. Red blood cell counts and liver and kidney function should be checked periodically. If there is suspicion that the drug induces cardiovascular effects, an electrocardiogram should be done. Use with caution in patients with cardiovascular disease or a family history of QT prolongation. If liver or kidney function test abnormalities or blood dyscrasias appear, the treatment with phenothiazines should be discontinued. The use of phenothiazines in patients with impaired renal function requires caution.
Use with caution in patients with respiratory failure due to lung infections, or with chronic respiratory conditions such as severe asthma or emphysema.
The possibility of liver damage, corneal and lenticular deposits and irreversible dyskinesia should be kept in mind.
The possibility of suicide in depressed patients persists during treatment and until significant remission of symptoms. Therefore this type of patient should not have access to large quantities of Trilafon.
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. Trilafon should be used with caution in patients with stroke risk factors.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. As patients being treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Trilafon 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.
Trilafon is not licensed for the treatment of dementia-related behavioral disorders.
Important information about some of the excipients
Trilafon tablets contain lactose are therefore not suitable for people with lactase deficiency, galactosemia or glucose / galactose malabsorption syndrome.
04.5 Interactions with other medicinal products and other forms of interaction
Given their fundamental properties, phenothiazines can variously interfere with numerous groups of drugs.
• Substances that depress the central nervous system: barbiturates, anxiolytics, anesthetics, antihistamines, meperidine and other opiate analgesics. In case of combination use caution to avoid overdose 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 to accentuate the metabolism of phenothiazines Caution should be exercised in case of concomitant administration of perphenazine and phenytoin.
Antipsychotics can cause an increase or decrease in serum phenytoin levels.
• Lithium: rarely the association with phenothiazines has determined an acute encephalopathy.
• Antihypertensives: taking into account the effects of phenothiazines on the autonomic nervous system and on blood pressure, the interaction with drugs used in the treatment of hypertension can be variable. In particular, phenothiazines can antagonize the effects of guanethidine and similar drugs. This interaction may be less severe with perphenazine than with other phenothiazines. If antagonism with guanethidine is known, it may be appropriate to increase the dose of guanethidine or replace it with another antihypertensive drug. On the other hand, the concomitant use of phenothiazines with methyldopa and beta-blockers, used in hypertension, may potentiate the hypotensive effect, so phenothiazines should be administered with caution in patients treated with these drugs to avoid excessive hypotension. The concomitant use of phenothiazines with propranolol (beta-blocker) can lead to increased plasma levels of both medications.
• Anticholinergics: the association of phenothiazines and parasympatholytic drugs requires caution as it can favor the appearance of characteristic side effects.
• Drugs with leukopenizing activity: phenothiazines must not be associated with phenylbutazone, thiouracil derivatives and other potentially myelotoxic drugs due to the synergistic depressive effect on the blood crase.
• 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.
• Levodopa: the effects of this substance are specifically antagonized by phenothiazines; for this reason phenothiazines should be avoided or used with caution in individuals with Parkinson's disease.
• Antacids: avoid ingestion of the product together with antacids (including aluminum salts) or other substances that can reduce the absorption of phenothiazines.
See also section 4.4 "Special warnings and precautions for use".
Other types of interactions
The urinary metabolites of phenothiazines can impart a dark color to the urine and give false positive responses to tests for urobilinogen, amylase, uroporphyrin, porphobilinogens and 5-hydroxy-indolacetic acid.
Since phenothiazines can cause decreased adrenocorticoid secretion as a consequence of decreased corticotropin release, perphenazine can interfere with the metyrapone test of hypothalamic-pituitary function.
In patients being treated with phenothiazines, the urine pregnancy test can give both false positive and false negative results.
Patients treated with therapeutic doses of phenothiazines may show changes in the electrocardiographic trace, such as lengthening of the QT interval, accompanied by extension, reduction and depression of the T wave. At higher doses, a lowering and a "reversal of the T wave" may occur. .
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.
Drugs metabolised by Cytochrome P450 2D6
The biochemical activity of the isoenzyme cytochrome P450 2D6 (debrisoquine hydroxylase) which metabolizes the drug is reduced in a subgroup of the Caucasian population (about 7-10% of the Caucasian population is composed of subjects called "poor metabolisers"); however, no reliable estimates are available on the prevalence of reduced P450 2D6 isoenzyme activity in Asian, African and other populations. The "poor metabolisers" have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) after administration of Usual dosages. Depending on the fraction of the drug metabolised by P450 2D6, the increase in plasma concentration may be minimal or quite high (equal to 8 times the increase in plasma AUC of the tricyclic antidepressant).
Furthermore, some drugs inhibit the activity of this isoenzyme and make normal metabolisers similar to poor metabolisers. An individual stable at a given dosage of TCA can develop very strong toxicity if he is subjected to concomitant therapy with one of these inhibitory drugs. Cytochrome P450 2D6 inhibitor drugs include some that are not metabolised by the enzyme (quinidine, cimetidine) and many that are substrates of P450 2D6 (many other antidepressants, phenothiazines and type 1C antiarrhythmics propafenone and flecainide). All selective serotonin re-uptake inhibitors (SSRIs), such as fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, but the extent of this inhibition may vary. The extent to which the interactions of TCAs with SSRIs may pose clinical problems depends on the degree of inhibition and pharmacokinetics of the SSRIs involved. Nevertheless, caution should be exercised in the combined administration of TCA and any SSRI and also in switching from one drug category to another.
It is particularly important that sufficient time must elapse before starting TCA treatment in a patient who has stopped taking fluoxetine: this is due to the long half-life of the parent and active metabolite (this may take at least 5 weeks).
The concomitant use of tricyclic antidepressants and drugs that can inhibit cytochrome P450 2D6 may require lower than commonly prescribed doses for both tricyclic antidepressants and the other drugs. In addition, where one of these other drugs is eliminated from the therapeutic combination, it may a higher dose of tricyclic antidepressant may be required. It is desirable to monitor plasma TCA levels when these are co-administered with another drug known to be a P450 2D6 inhibitor.
04.6 Pregnancy and breastfeeding
Do not administer during the first trimester of pregnancy. In the further period, the product must be administered only when considered essential and in any case always under the direct supervision of the doctor.
Infants exposed to conventional or atypical antipsychotics including Trilafon 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.
Since phenothiazines are rapidly excreted in breast milk, a decision must be made whether to discontinue breastfeeding or the drug, taking into account the importance of the therapy to the mother.
04.7 Effects on ability to drive and use machines
Since phenothiazines induce sedation and drowsiness, this must be taken into account in those who drive vehicles or other machinery or who perform dangerous work.
04.8 Undesirable effects
Not all adverse events reported below have been reported with the use of Trilafon; however, due to the pharmacological similarities between the various phenothiazine derivatives it is necessary to consider them individually. With the piperazine group (to which perphenazine belongs) the symptoms extrapyramidal ones are more common while others are less frequent (for example, sedation, jaundice, blood dyscrasia, convulsions and effects on the autonomic nervous system).
Central nervous system
Extrapyramidal reactions - opisthotonus, trismus, torticollis, spastic torticollis, pain and numbness in limbs, motor restlessness, oculogyric crisis, hyperreflexia, dystonia, including protrusion, discolouration, pain and rolling of the tongue, tonic spasm of the chewing muscles, constriction throat, confused diction, dysphagia, inability to sit, dyskinesia, parkinsonism and ataxia. Their incidence and severity usually increases with increasing dosage, but there is considerable individual variation in the tendency to exhibit these symptoms.Extrapyramidal symptoms can usually be controlled with concomitant use of anti-parkinsonian agents, such as benzatropine mesylate, and / or dose reduction. However, in some cases, extrapyramidal reactions may persist after discontinuation of perphenazine treatment.
Late persistent dyskinesia
As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may arise after discontinuation of treatment. Although the risk appears to be greater in the elderly, especially in women treated with high doses of the drug, this This phenomenon can also occur in patients of both sexes and in children. Symptoms are persistent and in some patients seem irreversible. There are no known effective therapies for tardive dyskinesia: anti-parkinson drugs do not normally relieve symptoms of this syndrome. much less commonly than with prolonged use, this syndrome may develop after relatively short, low-dose treatment periods. Should these symptoms occur, it is suggested that treatment with all antipsychotic agents be discontinued. The syndrome may be hidden if it is necessary to re-institute treatment, increase the dosage or switch to another antipsychotic agent. Mild vermicular movements of the tongue can be an early sign of the syndrome. If you stop treatment at this time, the complete syndrome may not develop.
Other effects on the central nervous system
Cerebral edema; abnormalities of cerebrospinal fluid proteins; seizures, particularly in patients with EEG abnormalities or with a history of such disorders, and headache.
Neuroleptic malignant syndrome (NMS) has been reported in patients treated with neuroleptic drugs. It is a relatively uncommon, life-threatening syndrome characterized by severe extrapyramidal dysfunction, accompanied by rigidity and possibly stupor or coma, hyperthermia and autonomic disturbances, including cardiovascular effects. There is no specific treatment; administration of the neuroleptic drug should be discontinued. and appropriate intensive supportive treatment should be initiated.If treatment with antipsychotic drugs is required for the patient after recovery from NMS, precautionary monitoring is advised, as NMS may recur.
Somnolence may occur, especially during the first or second week of treatment; after which this disorder usually disappears. Hypnotic effects appear to be minimal, especially in patients who are allowed to remain active.
Behavioral Adverse Events
Paradoxical aggravation of psychotic symptoms, catatonic-like states, paranoid reactions, lethargy, paradoxical excitement, restlessness, hyperactivity, nocturnal confusion, bizarre dreams and insomnia. Hyperreflexia has been reported in the newborn when a phenothiazine was administered during pregnancy.
Effects of the autonomous system
Occasionally dry mouth or salivation, nausea, vomiting, gastric retention, diarrhea, anorexia, constipation, obstinate constipation, fecaloma, urinary retention, frequent urination or incontinence, bladder paralysis, polyuria, nasal congestion, pallor, myosis, mydriasis, blurred vision, glaucoma, sweating, hypertension, hypotension and an altered pulse rate.
Significant autonomic effects were infrequent in patients treated with less than 24 mg of perphenazine per day.
Adynamic ileus may occasionally occur following phenothiazine therapy and, if severe, can cause complications and death. This is of particular concern in psychiatric patients who may not spontaneously request treatment for this condition.
Urticaria, erythema, eczema, exfoliative dermatitis, pruritus, photosensitivity, asthma, fever, anaphylactoid reactions and larynx edema may occasionally occur. Angioneurotic edema and contact dermatitis have been reported in nurses who administered phenothiazines. In extremely rare cases, individual idiosyncrasy or hypersensitivity to phenothiazines have caused cerebral edema, circulatory collapse and death.
Lactation, galactorrhea, moderate breast enlargement in women and gynecomastia in men after high doses, menstrual disturbances, amenorrhea, libido changes, ejaculation inhibition, hyperglycaemia, hypoglycemia, glucosuria, syndrome of inappropriate secretion of antidiuretic hormone (ADH) , false positivity of pregnancy tests.
Postural hypotension, tachycardia (especially with sudden marked increase in dosage), bradycardia, cardiac arrest, fainting and dizziness. Sometimes the hypotensive effect can cause a shock-like condition. Non-specific (quinidine-like effect), usually reversible, ECG changes have been observed in some patients undergoing treatment with phenothiazine tranquilizers.
The following side effects have been observed with other drugs of the same class: rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest.
Sudden death has occasionally been reported in patients undergoing treatment with phenothiazines. In some cases, death was apparently due to cardiac arrest; in others, the cause appeared to be asphyxiation due to insufficient cough reflex. In some patients it was not possible to determine the cause of death or to establish whether the death was attributable to phenothiazine.
Cases of venous thromboembolism, including cases of pulmonary embolism and deep vein thrombosis, have been reported with antipsychotic drugs (frequency not known).
Agranulocytosis, eosinophilia, leukopenia, haemolytic anemia, thrombocytopenic purpura and pancytopenia. Most cases of agranulocytosis occurred between the fourth and tenth week of therapy.
Liver damage (biliary stasis) can occur. Jaundice - which usually appears between the second and fourth week of treatment - is considered to be a hypersensitivity reaction. The incidence is low. The clinical picture resembles that of infectious hepatitis but with the laboratory characteristics of obstructive jaundice. It is usually reversible; however, chronic jaundice has been reported.
Pregnancy, puerperium and perinatal conditions: neonatal withdrawal syndrome, extrapyramidal symptoms (frequency not known. See section 4.6).
Particular factors related to long-term therapy include: skin pigmentation, especially in exposed areas; ocular alterations which consist in the deposit of fine particle substance in the cornea and in the lens and which, in the most serious cases, lead to opacity of the star-shaped lens; epithelial keratopathies; retinal changes; pigmentary retinopathy.
Furthermore: peripheral edema; reverse epinephrine effect; increase in PBI not attributable to an increase in thyroxine; parotid swelling (rare); hyperpyrexia; systemic lupus erythematosus-like syndrome; increased appetite and weight; polyphagia; photophobia; muscle weakness.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Emergency treatment must be instituted immediately and the patient must be hospitalized as soon as possible. It should also be borne in mind that the patient may have taken alcohol or other drugs at the same time.
Perphenazine overdose primarily involves the extrapyramidal system.
Overdose symptoms are generally an exaltation of the multiple pharmacological effects of perphenazine.
Progressive depression of the CNS may occur. from drowsiness to stupor or coma with areflexia; children can have seizures. Patients with moderate or early stage intoxication may experience restlessness, confusion and excitement. Other symptoms include hypotension, tachycardia, hypothermia, myosis, tremors, muscle twitching, spasms, stiffness or hypotonia, convulsions, difficulty swallowing and breathing, cyanosis, and respiratory and / or vasomotor collapse, sometimes with sudden apnea.
Treatment is symptomatic and supportive. There is no specific antidote.
If the patient is conscious, vomiting must be induced even if the emesis has already occurred spontaneously.
Pharmacological stimulation using syrup of ipecacuana is to be preferred.
However, it must be borne in mind that ipecac has a central action in addition to the local irritative action at the gastric level, which can be blocked by the antiemetic effect of perphenazine. The action of ipecac is facilitated by physical activity and the simultaneous administration of 240-360 ml of water. If the emesis does not occur within 15 ", it is necessary to repeat the dose of ipecac. Take the necessary precautions to avoid aspiration. vomiting especially in children and infants. Once vomiting has been induced, the drug residue in the stomach can be absorbed on activated charcoal administered in an aqueous suspension. In cases where vomiting was contraindicated or did not occur, especially in children, perform gastric lavage with physiological saline solution.
In adults, running water can be used, however, as much as possible should be removed before the next administration. The saline purgatives, recalling water in the intestine by osmosis, can be useful as with their action they rapidly dilute the contents of the intestine.
Standard measures (oxygen, intravenous fluids, corticosteroids) should be used to treat circulatory shock or metabolic acidosis.
Maintain good lung ventilation and adequate fluid intake and regulate body temperature. Hypothermia may arise, but severe hyperthermia may also occur which must be promptly and adequately treated.
Perform an electrocardiogram and monitor cardiac function for not less than 5 days. Cardiac arrhythmias can be treated with neostigmine, pyridostigmine or propranolol.
Vasoconstrictors such as norepinephrine and phenylephrine can be used to treat hypotension, but epinephrine should not be used. Anticonvulsants such as inhalation anesthetics, diazepam or paraldehyde are indicated to control seizures. On the other hand, barbiturates of which perphenazine increases the central depressive activity, but not the anticonvulsant action, are not indicated. Since phenothiazines lower the seizure threshold, stimulants with central seizure action such as picrotoxin or pentetrazole should not be administered. If acute parkinsonian symptoms occur, benzatropine mesylate, trihexyphenidyl or diphenhydramine can be administered.
Following a toxic overdose, the patient may not awaken for 48 hours, despite the support or attack measures implemented. Dialysis is of no use given the low plasma concentrations of the drug. Since overdose is often deliberate, the patient may otherwise attempt suicide during the hospitalization phase.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Phenothiazines with piperazine structure.
ATC code: N05AB03
Mechanism of action:
Perfenazine exhibits actions at all levels of the central nervous system, particularly at the hypothalamic level and demonstrates anxiolytic, antipsychotic and antiemetic properties.
05.2 "Pharmacokinetic properties
Phenothiazines are readily absorbed from the gastrointestinal tract and parenteral sites.
50-70% of an orally administered dose is rapidly removed from the portal circulation and the enterohepatic circulation is very active.
As a result of this, less unchanged drug enters the circulation when phenothiazines are administered parenterally.
After absorption, phenothiazines are rapidly distributed to all body tissues.
These drugs are highly lipophilic and highly bound to membranes and proteins.
High concentrations of unchanged drug are detectable in the brain, metabolites predominate in the lungs, liver, kidneys, spleen.
Phenothiazines are mainly metabolised in the liver via oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid.
Elimination from plasma may be more rapid than from high-fat, highly bound sites, particularly from the central nervous system.
05.3 Preclinical safety data
The toxicological profile of perphenazine was evaluated after acute administration in mice, rats and dogs, while subacute and chronic toxicities were evaluated in rats and dogs.
When administered orally, the LD50 values were 37 mg / kg in mice, 38 mg / kg in rats and 51 mg / kg in dogs.
Prolonged treatments with oral perphenazine in rats and dogs were well tolerated.
There is published evidence indicating that chlorinated phenothiazine drugs, such as perphenazine, potentially induce photogotoxicity in vitro upon light activation. Post marketing experience has not identified any increased risk of photomutagenesis and / or carcinogenesis due to light exposure in more than 40 years of marketing.
06.0 PHARMACEUTICAL INFORMATION
Trilafon 2 mg coated tablets
Corn starch, lactose, magnesium stearate, pregelatinised starch, hypromellose, macrogol, white Opaspray, paraffin.
Trilafon 4 mg coated tablets
Corn starch, lactose, magnesium stearate, pregelatinised starch, Opadry white (hypromellose, macrogol, titanium dioxide, hydroxypropylcellulose).
Trilafon 8 mg coated tablets
Corn starch, lactose, magnesium stearate, pregelatinised starch, Opadry white (hypromellose, macrogol, titanium dioxide, hydroxypropylcellulose).
06.3 Period of validity
Coated tablets: 3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Trilafon 2 mg coated tablets - 20 tablets
Trilafon 4 mg coated tablets - 20 tablets
Trilafon 8 mg coated tablets - 20 tablets
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
NEOPHARMED GENTILI S.r.l.
Via S.G. Cottolengo, 15 - 20143 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Trilafon 2 mg coated tablets AIC: 013403023
Trilafon 4 mg coated tablets AIC: 013403035
Trilafon 8 mg coated tablets AIC: 013403011
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
26 August 1963 / June 2010.
10.0 DATE OF REVISION OF THE TEXT