Active ingredients: Promazine
TALOFEN 4 g / 100 ml oral drops, solution
TALOFEN 25 mg / ml solution for injection
Why is Talofen used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antipsychotic drugs
THERAPEUTIC INDICATIONS
Treatment of psychomotor agitation or aggressive behavior. Schizophrenia and other psychotic disorders.
Contraindications When Talofen should not be used
- Hypersensitivity to the active substance, other phenothiazines or to any of the excipients
- State of coma
- Central nervous system depression
- Bone marrow depression
- Pheochromocytoma
- For the solution for injection: intra-arterial injection
Precautions for use What you need to know before taking Talofen
Parenteral Administration: Intravenous administration of promazine at concentrations above 25 mg / ml may cause localized thrombophlebitis or cellulitis.
Antiemetic effect: Promazine has an antiemetic effect that can mask the toxic effects of other drugs or the presence of concomitant pathologies. Therefore Talofen should be used with caution in combination with antineoplastic drugs (see "Interactions with other medicinal products and other forms of interaction").
Withdrawal symptoms: If discontinuation of therapy occurs abruptly, withdrawal symptoms (nausea, vomiting, dizziness, tremors and restlessness) may occur. Therefore it is advisable to gradually reduce the dosage of promazine (see "Dose, method and time of administration" and "Undesirable Effects").
Orthostatic hypotension: Transient orthostatic hypotension has been reported with the use of promazine, especially following the first parenteral administration (see "Undesirable effects"). The patient should remain supine and under observation for 30 minutes after the injection of Talofen. . Healing is usually spontaneous. In case of severe hypotension, norepinephrine should be administered (adrenaline can induce a further reduction in blood pressure). Talofen should be used with caution in patients with known cardiovascular and cerebrovascular diseases and conditions that may predispose to hypotension.
Seizures: Like other phenothiazines, promazine can reduce the seizure threshold (see "Undesirable Effects"): therefore Talofen should be used with caution in patients with a history of epilepsy or conditions that may reduce the seizure threshold.
Body temperature regulation: Impaired ability to lower body temperature has been attributed to antipsychotic drugs (see "Side Effects"). Appropriate caution should be exercised in prescribing Talofen to patients who may be in conditions of increased body temperature, such as intense physical activity, exposure to high temperatures, concomitant use of drugs with anticholinergic activity, or at risk of dehydration.
Dysphagia: Alterations in esophageal motility and inhalation have been associated with the use of antipsychotics (see "Undesirable Effects"). Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, particularly in those with stage Alzheimer's dementia. Talofen and other antipsychotics should be used with caution in patients at risk of aspiration pneumonia.
Photosensitivity: photosensitivity may appear during treatment with phenothiazines: patients should therefore be advised to avoid direct exposure to sunlight (see "Undesirable Effects"). Suicide: the possibility of attempted suicide is to be considered in psychosis , and careful monitoring of high-risk patients should be in place during therapy. The prescription of Talofen should include the minimum amount necessary for optimal patient management in order to reduce the risk of overdose (see "Overdose"). . Patients with depression or during a manic episode should be carefully monitored for any clinically relevant mood changes.
Liver disease: Jaundice or hepatic dysfunction have been reported following treatment with promazine (see "Undesirable effects"): therefore, caution should be exercised in patients with a history of liver disease. Patients who experience symptoms of liver dysfunction during Talofen therapy should have liver function tests immediately. If the increase in values is clinically relevant, treatment with Talofen should be discontinued.
Use in patients with concomitant conditions: An approximately 3-fold increased risk of cerebrovascular events was observed in placebo-controlled clinical trials in patients with dementia using some atypical antipsychotics. The mechanism behind this increased risk is unknown. An increased risk cannot be excluded with other antipsychotics or on other types of patients. Talofen should be used with caution in patients with stroke risk factors. Caution should be used in patients with cardiovascular disease or with a family history of QT prolongation. Avoid concomitant use of other neuroleptics. Since drugs of this type have been associated with blood clot formation, Talofen should be used with caution in patients with a history of blood clot formation or in patients who have family members with a blood clot. history of blood clots.
Due to its anticholinergic properties, promazine should be used with caution in patients with clinically relevant prostatic hypertrophy and narrow-angle glaucoma. Caution is needed in patients with a history of paralytic ileus, Parkinson's disease and myasthenia gravis.
During prolonged treatment with Talofen, it is advisable to carry out regular clinical evaluations and laboratory tests relating to the central nervous system, liver, bone marrow, eye and cardiovascular system.
Interactions Which drugs or foods can modify the effect of Talofen
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Concomitant use not recommended with the following drugs
Drugs that induce bone marrow depression: Talofen should not be used with other drugs with known potential to suppress bone marrow function (see "Contraindications" and "Special warnings").
QT-Prolonging Drugs: When neuroleptics are given together with QT-prolonging drugs, the risk of cardiac arrhythmias increases.
Drugs that cause changes in electrolytes: Do not administer concomitantly with drugs that cause changes in electrolytes.
Antibiotics: an increased risk of ventricular arrhythmias has been reported with the concomitant use of moxifloxacin and phenothiazines: therefore avoid concomitant use.
Levodopa: phenothiazines may antagonize the effect of levodopa. The concomitant use of promazine and levodopa should be avoided.
Alcohol: An additive central nervous system depressant effect has been reported following concomitant administration of alcohol and phenothiazines. Avoid alcohol consumption during phenothiazine therapy.
Concomitant use requiring caution
Considering the effects of promazine on the central nervous system (CNS), caution should be exercised when using Talofen in combination with other centrally acting drugs.
Central nervous system depressants: concomitant use of Talofen and other CNS depressants, including barbiturates, anxiolytics, hypnotics, anesthetics, antihistamines, analgesics, opioids, may induce an additive depressant effect, including respiratory depression , CNS depression and hypotension.
Succinylcholine: Talofen should not be given to patients who have received succinylcholine during surgery due to possible prolongation of neuromuscular block.
Metrizamide: Concomitant administration of metrizamide and phenothiazines increases the risk of convulsions. Therefore, Talofen therapy must be stopped at least 48 hours before a myelography and can only be restarted 24 hours after the test is performed.
Lithium: Concomitant administration of lithium and antipsychotic drugs has resulted in a wide variety of symptoms of encephalopathy, brain damage, and extrapyramidal symptoms. Therefore patients on concomitant lithium therapy should be carefully monitored.
Anticonvulsant drugs: The concomitant use of phenothiazines and anticonvulsant drugs antagonizes the effects of the latter. Therefore the levels of anticonvulsant drugs should be monitored when a phenothiazine is added or removed from therapy: in fact, a dosage adjustment may be necessary. also be monitored for any signs of phenytoin toxicity.
Antineoplastic drugs: Promazine has an antiemetic effect which may mask the toxicity of antineoplastic drugs (see "Precautions for use").
Concomitant use to be considered
Anticholinergic drugs: Concomitant use of anticholinergic drugs may reduce the oral absorption of phenothiazines, antagonize the effects of the latter on behavioral and psychotic symptoms, and increase the occurrence of anticholinergic side effects (see "Precautions for use").
Antacids: Antacids can reduce the absorption of phenothiazines.
Antihypertensive drugs: phenothiazines may increase the hypotensive effects of antihypertensive drugs.
Interactions with laboratory tests: urinary metabolites of phenothiazines can cause the appearance of a dark color in the urine and give false positive responses to tests for amylase, urobilinogen, uroporphyrin, porphobilinogens and 5-hydroxy-indolacetic acid .
False positive pregnancy test results have been reported in women receiving phenothiazines.
Warnings It is important to know that:
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex called Neuroleptic Malignant Syndrome (see "Undesirable Effects") has been reported during treatment with antipsychotic drugs.
Clinical manifestations of this syndrome are: hyperpyrexia, muscle rigidity, altered mental status, vegetative disorders (irregular heart rate or blood pressure, tachycardia, profuse sweating, cardiac arrhythmias). Additional symptoms may include elevated creatine phosphokinase levels, rhabdomyolysis and acute renal failure. Treatment of NMS consists of immediately discontinuing the administration of antipsychotic and other non-essential drugs and instituting intensive symptomatic therapy. If treatment with antipsychotics is deemed essential after recovery from NMS, the patient should be carefully monitored.
Extrapyramidal symptoms: Extrapyramidal effects, such as parkinsonism, akathisia or dystonia have been associated with promazine, most commonly following use of high doses. Extrapyramidal symptoms include (see "Undesirable Effects"):
- akathisia (motor restlessness) usually appears after the first dose and can be confused with the underlying disease;
- dystonia (abnormal movements of the face and body), more common in children and young people and may appear after a few doses;
- parkinsonism (including tremor), more common in adults and the elderly, and appears gradually during treatment.
Extrapyramidal symptoms usually disappear after discontinuation of therapy or can be treated with anticholinergic drugs.
Tardive dyskinesia (DT): a potentially irreversible syndrome characterized by involuntary dyskinetic movements may appear in patients treated with antipsychotics (see "Undesirable effects"). Although the prevalence of DT appears to be higher among the elderly, especially women, it is impossible to predict which patients are most susceptible to developing DT. If symptoms of DT appear, treatment discontinuation should be considered.
Blood dyscrasia: Although rarely, agranulocytosis may occur during treatment with promazine, usually between the fourth and tenth week after initiation of therapy (see "Undesirable effects"). Leukopenia has also been reported. Patients should be monitored and periodically A complete blood count should be taken. Although it is not known whether the risk increases, it is prudent to avoid the use of Talofen, or use it with caution, in patients with a history of agranulocytosis induced by other drugs (see "Interactions with other medicines and other forms of interaction"). Although not specifically reported with promazine, phenothiazines have been associated with weight gain, urinary retention, ejaculation disturbances, galactorrhea, gynaecomastia, menstrual irregularities, corneal and lens changes, which do not normally affect vision (see "Effects retinal pigmentation has been reported with other phenothiazines, especially thioridazine and chlorpromazine.
Pregnancy and breastfeeding
Pregnancy
Ask your doctor or pharmacist for advice before taking any medicine. Studies are insufficient to highlight effects on pregnancy and / or embryonal / fetal development and / or postnatal development. The potential risk for humans is unknown. Talofen should not be used during pregnancy unless absolutely necessary.
Feeding time
It is not known whether promazine is secreted in breast milk. Effects on infants are unknown but cannot be excluded. Sedation may appear. The decision whether to continue or discontinue breastfeeding or to continue or discontinue therapy with Talofen must be made taking into account the benefits of breastfeeding for the child and the benefits of Talofen therapy for the mother.
The following symptoms have been observed in newborn babies of mothers who have taken conventional or atypical antipsychotics, including Talofen, during the last trimester (last three months of pregnancy): shaking, muscle stiffness and / or weakness, sleepiness, agitation, breathing problems and difficulty in food intake. If your child shows any of these symptoms, contact your doctor.
Effects on ability to drive and use machines
Talofen can induce sedation and sleepiness. Caution is advised in patients driving vehicles or using machines.
Important information about some of the ingredients of Talofen
Talofen contains sodium sulfite and potassium metabisulfite which rarely can cause severe hypersensitivity reactions and bronchospasm.
Talofen oral drops, solution contains methyl p-hydroxybenzoate and propyl p-hydroxybenzoate which can cause allergic reactions (including delayed).
Talofen oral drops, solution contains sorbitol: if your doctor has diagnosed you with intolerance to some sugars, contact your doctor before taking this medicine. Talofen oral drops, solution contains small amounts of ethanol (alcohol) less than 100 mg per dose.
For those who practice sports (only for Talofen oral drops)
The use of medicines containing ethyl alcohol can determine positive doping tests in relation to the alcohol concentration limits indicated by some sports federations.
Dosage and method of use How to use Talofen: Dosage
Adults
In the patient with acute agitation, when rapid sedation is required, Talofen solution for injection should be administered intramuscularly. The starting dose is 50 mg intramuscularly. Intramuscular injection should be administered deeply and the needle should be slowly retracted. The injection should be performed with the patient supine and the patient observed for 30 minutes (see "Precautions for use"). If agitation persists 30 minutes after the first administration, the dose can be repeated, up to a maximum of 300 mg / day. Avoid direct intravenous injection of Talofen.
If intravenous administration is deemed necessary, Talofen solution for injection should be diluted in a 5% glucose solution or saline and administered slowly by drip. Intravenous administration should not exceed a promazine concentration of 25 mg / ml (see "Precautions for use").
Depending on the severity of the symptoms and the patient's characteristics, after a few days the parenteral administration can be replaced with oral treatment.
Talofen can be administered orally using the drops.
The drops must be diluted in water, with the possible addition of sugar.
The parenterally administered daily dose of promazine should be replaced with an equivalent oral daily dose.
One drop is equivalent to 2 mg of promazine.
It is recommended that a total daily dose greater than 50 mg (25 drops) is divided into 2-4 administrations. Dose adjustment should be made with caution based on individual patient characteristics in order to administer the lowest effective dose.
If the severity of symptoms and patient characteristics do not require acute treatment, 10-15 drops (20-30 mg) should be started as a single evening administration. If necessary, the dosage should be gradually increased in order to administer the lowest effective dose. The recommended oral dose is 15 drops 4 times a day (120 mg / day), up to a maximum of 50 drops 4 times a day (400 mg / day). It is recommended that a total daily dose greater than 25 drops be divided into 2-4 administrations.
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with promazine the dosage should be gradually reduced over a period of one to two weeks (see sections "Precautions for use" and "Undesirable effects"). intolerable symptoms reappear, the possibility of re-administering the previous prescribed dose may be considered. Thereafter the dose can be reduced, but more gradually.
Elderly patients:
the recommended oral dose in the elderly is 10-30 drops per day (20-60 mg / day), up to a maximum of 25 drops 4 times a day (200 mg / day). If parenteral administration is required, one or half ampoule of solution for injection can be administered intramuscularly. If a lower dose is required, the solution for injection can be diluted and administered slowly by drip.
Children:
Talofen should not be used in children below 12 years of age due to a lack of data on efficacy and safety. In children over 12 years of age and adolescents the recommended oral dose is 5-15 drops per day (10-30 mg / day), up to a maximum of 15 drops 4 times per day (120 mg / day). The parenteral dose is between 0.25 and 0.50 mg per kg of body weight.
Renal insufficiency: no dosage adjustment is necessary.
Hepatic insufficiency: Patients with hepatic insufficiency should start on a low dose and be carefully monitored.
Overdose What to do if you have taken too much Talofen
Symptoms
Symptoms include: respiratory depression, central nervous system depression, confusional state, apathy, cognitive impairment, hypotension, hypothermia, myocardial ischaemia, tachycardia, arrhythmia, dystonia, convulsions.
Treatment
There is no specific antidote for promazine. In the event of an overdose, gastric lavage should be performed as soon as possible and symptomatic treatment instituted.
In case of severe hypotension, lay the patient in a supine position and administer norepinephrine (adrenaline can further reduce blood pressure). Arrhythmia may respond to correction of hypoxia, acidosis or other biochemical changes. Dystonia can be eliminated by injection of diazepam. Hemodialysis is not effective. In case of accidental ingestion / intake of an excessive dose of Talofen, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Talofen, ask your doctor or pharmacist.
Side Effects What are the side effects of Talofen
Like all medicines, Talofen can cause side effects, although not everybody gets them.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
The following side effects have been reported during marketing, which are temporally related to Talofen therapy (each single report may contain more than one sign or symptom):
Blood and lymphatic system disorders: agranulocytosis, disseminated intravascular coagulation, neutropenia
Endocrine disorders: increase in TSH
Psychiatric disorders: apathy, confusional state
Nervous system disorders: ataxia, cognitive disturbances, extrapyramidal symptoms, neuroleptic malignant syndrome, syncope
Cardiac disorders: T wave inversion, QT prolongation
Vascular disorders: hypovolemic shock
Respiratory, thoracic and mediastinal disorders: respiratory failure
Hepatobiliary disorders: hepatitis, increased transaminases, increased alkaline phosphatase
Skin and subcutaneous tissue disorders: erythema
Musculoskeletal and connective tissue disorders: creatine phosphokinase increased, rhabdomyolysis, muscle stiffness
Renal and urinary disorders: acute renal failure
General disorders and administration site conditions: hyperthermia, fever
Injury, poisoning and procedural complications: overdose, voluntary poisoning
Withdrawal symptoms: If discontinuation of therapy occurs abruptly, withdrawal symptoms (nausea, vomiting, dizziness, tremors and restlessness) may occur. Therefore it is advisable to gradually reduce the dosage of promazine (see "Dose, method and time of administration" and "Precautions for use").
The following side effects have been observed in patients receiving generic promazine or other phenothiazines:
Blood and lymphatic system disorders: aplastic anemia, haemolytic anemia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia
Immune system disorders: anaphylactic reactions, bronchospasm, laryngospasm, larynx edema
Metabolism and nutrition disorders: hyperglycemia, glycosuria
Psychiatric disorders: depression, euphoric mood, anxiety, insomnia, restlessness
Nervous system disorders: extrapyramidal symptoms (akathisia, dystonia, parkinsonism, tardive dyskinesia), neuroleptic malignant syndrome, convulsions, dizziness, sedation, somnolence
Eye disorders: blurred vision, deposits in the lens, corneal lesions, mydriasis, retinopathy
Cardiac disorders: The following side effects have been observed with other neuroleptics (see "Precautions for use"): rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest. Very rare cases of sudden death
Vascular disorders: orthostatic hypotension, syncope
Respiratory, thoracic and mediastinal disorders: aspiration pneumonia
Gastrointestinal disorders: constipation, dry mouth
Hepatobiliary disorders: jaundice
Skin and subcutaneous tissue disorders: exfoliative dermatitis, photosensitivity, eczema, erythema, urticaria, skin pigmentation, purpura
Musculoskeletal and connective tissue disorders: Systemic lupus erythematosus
Renal and urinary disorders: urinary retention
Reproductive system and breast disorders: amenorrhea, galactorrhea, gynaecomastia, erectile dysfunction, menstrual disorders
General disorders and administration site conditions: increased body temperature, decreased body temperature, peripheral edema, aggravation of psychotic symptoms
Investigations: weight gain
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 to 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 with 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 gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
EXPIRY: see expiry date indicated on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package.
SPECIAL STORAGE PRECAUTIONS:
Store at a temperature not exceeding 25 ºC in the original packaging, protected from light and humidity.
Talofen 4g / 100 ml oral drops, solution is valid for 2 months after first opening.
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.
Other_information "> Other information
Composition
Oral drops, solution:
100 ml of solution contain:
Active ingredient: Promazine HCl 4.51 g equivalent to 4 g of basic promazine
Excipients: non crystallizable liquid sorbitol, 96% ethanol, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, anhydrous sodium sulphite, potassium metabisulphite, purified water.
Injectable solution:
One vial of solution for injection contains:
Active ingredient: Promazine HCl 56.4 mg equivalent to 50 mg of promazine base
Excipients: anhydrous sodium sulphite, potassium metabisulfite, sodium chloride, sodium citrate, ascorbic acid, water for injections.
Pharmaceutical form and content
Oral drops, solution: dark glass bottle - solution 30 ml.
Solution for injection: dark glass ampoules - 6 ampoules of 2 ml.
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 -
TALOFEN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
TALOFEN 4 g / 100 ml oral drops, solution.
100 ml of solution contain:
Promazine HCl 4.51 g equivalent to 4 g of basic promazine
Excipients: non crystallizable liquid sorbitol, 96% ethanol, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, anhydrous sodium sulphite, potassium metabisulphite, purified water.
TALOFEN 25 mg / ml solution for injection.
One vial of solution for injection contains:
Promazine HCl 56.4 mg equivalent to 50 mg of promazine base.
Excipients: anhydrous sodium sulphite, potassium metabisulfite, sodium chloride, sodium citrate, ascorbic acid, water for injections.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Oral drops, solution.
Injectable solution.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Treatment of psychomotor agitation or aggressive behavior.
Schizophrenia and other psychotic disorders
04.2 Posology and method of administration -
Adults
In the patient with acute agitation, when rapid sedation is required, Talofen solution for injection should be administered intramuscularly. The starting dose is 50 mg intramuscularly. Intramuscular injection should be administered deeply and the needle should be slowly retracted. The injection should be performed with the patient in the supine position and the patient observed for 30 minutes (see section 4.4). If agitation persists 30 minutes after the first administration, the dose can be repeated, up to a maximum of 30 minutes. maximum of 300 mg / day.
Avoid direct intravenous injection of Talofen.
If intravenous administration is deemed necessary, Talofen solution for injection should be diluted in a 5% glucose solution or saline and administered slowly by drip. Intravenous administration should not exceed a promazine concentration of 25 mg / ml (see section 4.4).
Depending on the severity of the symptoms and the patient's characteristics, after a few days the parenteral administration can be replaced with oral treatment.
Talofen can be administered orally using the drops.
The drops must be diluted in water, with the possible addition of sugar.
The parenterally administered daily dose of promazine should be replaced with an equivalent oral daily dose. One drop is equivalent to 2 mg of promazine.
It is recommended that a total daily dose greater than 50 mg (25 drops) is divided into 2-4 administrations. Dose adjustment should be made with caution based on individual patient characteristics in order to administer the lowest effective dose.
If the severity of symptoms and patient characteristics do not require acute treatment, 10-15 drops (20-30 mg) should be started as a single evening administration. If necessary, the dosage should be gradually increased in order to administer the lowest effective dose. The recommended oral dose is 15 drops 4 times a day (120 mg / day), up to a maximum of 50 drops 4 times a day (400 mg / day). It is recommended that a total daily dose greater than 25 drops be divided into 2-4 administrations.
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with promazine the dosage should be gradually reduced over a period of one to two weeks (see sections 4.4 and 4.8). If intolerable symptoms reappear following dose reduction or discontinuation of treatment, re-administering the previous prescribed dose may be considered. Thereafter the dose may be reduced, but more gradually.
Elderly patients: The recommended oral dose in the elderly is 10-30 drops per day (20-60 mg / day), up to a maximum of 25 drops 4 times a day (200 mg / day). If parenteral administration is required, one or half ampoule of solution for injection can be administered intramuscularly. If a lower dose is required, the solution for injection can be diluted and administered slowly by drip.
Children: Talofen should not be used in children below 12 years of age due to a lack of data on efficacy and safety.
In children over 12 years of age and adolescents the recommended oral dose is 5-15 drops per day (10-30 mg / day), up to a maximum of 15 drops 4 times per day (120 mg / day). The parenteral dose is between 0.25 and 0.50 mg per kg of body weight.
Kidney failure: No dosage adjustment is necessary.
Hepatic insufficiency: Patients with hepatic insufficiency should start on a low dose and be closely monitored.
04.3 Contraindications -
• hypersensitivity to the active substance, other phenothiazines or to any of the excipients;
- state of coma;
- central nervous system depression;
- bone marrow depression;
- pheochromocytoma
- for the solution for injection: intra-arterial injection
04.4 Special warnings and appropriate precautions for use -
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex called Neuroleptic Malignant Syndrome has been reported during treatment with antipsychotic drugs (see section 4.8).
Clinical manifestations of this syndrome are: hyperpyrexia, muscle rigidity, altered mental status, vegetative disorders (irregular heart rate or blood pressure, tachycardia, profuse sweating, cardiac arrhythmias). Additional symptoms may include elevated creatine phosphokinase levels, rhabdomyolysis and acute renal failure. Treatment of NMS consists of immediately discontinuing the administration of antipsychotic and other non-essential drugs and instituting intensive symptomatic therapy. If treatment with antipsychotics is deemed essential after recovery from NMS, the patient should be carefully monitored.
Extrapyramidal symptoms: Extrapyramidal effects, such as parkinsonism, akathisia or dystonia have been associated with promazine, most commonly following use of high doses. Extrapyramidal symptoms include (see section 4.8):
- akathisia (motor restlessness) usually appears after the first dose and can be confused with the underlying disease;
- dystonia (abnormal movements of the face and body), more common in children and young people and may appear after a few doses;
- parkinsonism (including tremor), more common in adults and the elderly, and appears gradually during treatment;
Extrapyramidal symptoms usually disappear after discontinuation of therapy or can be treated with anticholinergic drugs.
Tardive dyskinesia (DT): a potentially irreversible syndrome characterized by involuntary dyskinetic movements may appear in patients treated with antipsychotics (see section 4.8). Although the prevalence of DT appears to be higher among the elderly, especially women, it is impossible to predict which patients are most susceptible to developing DT. If symptoms of DT appear, treatment discontinuation should be considered.
Blood dyscrasia: Although rarely, agranulocytosis may occur during treatment with promazine, usually between the fourth and tenth week after initiation of therapy (see section 4.8). Leukopenia has also been reported. Patients should be monitored and periodically a blood count.Although it is not known whether the risk increases, it is prudent to avoid the use of Talofen, or use it with caution, in patients with a history of other drug-induced agranulocytosis (see section 4.5).
Venous thromboembolism
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients being treated with antipsychotics often have acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Talofen and appropriate preventive measures should be taken.
Although not specifically reported with promazine, phenothiazines have been associated with weight gain, urinary retention, ejaculation disturbances, galactorrhea, gynaecomastia, menstrual irregularities, corneal and lens changes, which do not normally impair vision (see section 4.8. Retinal pigmentation has been reported with other phenothiazines, especially thioridazine and chlorpromazine.
Parenteral administration: Intravenous administration of promazine at concentrations above 25 mg / ml may cause localized thrombophlebitis or cellulitis.
Antiemetic effect: Promazine has an antiemetic effect that can mask the toxic effects of other drugs or the presence of concomitant diseases. Therefore Talofen should be used with caution in combination with antineoblastic drugs (see section 4.5).
Withdrawal symptoms: If treatment is stopped abruptly, withdrawal symptoms (nausea, vomiting, dizziness, tremors and restlessness) may appear.
Therefore it is advisable to gradually reduce the dosage of promazine (see sections 4.2 and 4.8).
Orthostatic hypotension: Transient orthostatic hypotension has been reported with the use of promazine, especially following the first parenteral administration (see section 4.8). The patient should remain in the supine position and under observation for 30 minutes after the injection of Talofen. Healing is usually spontaneous. In case of severe hypotension, norepinephrine should be administered (adrenaline can induce a further reduction in blood pressure). Talofen should be used with caution in patients with known cardiovascular and cerebrovascular diseases and conditions that may predispose to hypotension.
Convulsions: Like other phenothiazines, promazine may reduce the seizure threshold (see section 4.8): therefore Talofen should be used with caution in patients with a history of epilepsy or conditions that may reduce the seizure threshold. Body temperature regulation: Impaired ability to reduce body temperature has been attributed to antipsychotic drugs (see section 4.8). Appropriate care should be exercised in prescribing Talofen to patients who may be in conditions of increased body temperature, for example due to intense physical activity, exposure to elevated temperatures, concomitant use of drugs with anticholinergic activity, or at risk of dehydration.
Dysphagia: Alterations in esophageal motility and inhalation have been associated with the use of antipsychotics (see section 4.8). Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, particularly those with advanced Alzheimer's dementia. Talofen and other antipsychotics should be used with caution in patients at risk of aspiration pneumonia.
Photosensitivity: photosensitivity may appear during treatment with phenothiazines: therefore patients should be advised to avoid direct exposure to sunlight (see section 4.8).
Suicide: the possibility of suicide attempt is to be taken into consideration in psychosis, and careful monitoring of high-risk patients must be implemented during therapy. The prescription of Talofen should include the minimum amount necessary for optimal patient management in order to reduce the risk of overdose (see section 4.9).
Patients with depression or during a manic episode should be carefully monitored for any clinically relevant mood changes. Hepatopathy: Jaundice or hepatic dysfunction have been reported following treatment with promazine (see section 4.8): therefore caution should be exercised in patients with a history of liver disease. Patients who experience symptoms of liver dysfunction during Talofen therapy should have liver function tests immediately. If the increase in values is clinically relevant, treatment with Talofen should be discontinued.
Use in patients with concomitant pathologies:
An approximately 3-fold increased risk of cerebrovascular events was observed in placebo-controlled clinical trials in patients with dementia using some atypical antipsychotics. The mechanism behind this increased risk is unknown. An increased risk cannot be excluded with other antipsychotics or on other types of patients. Talofen should be used with caution in patients with stroke risk factors.
Increased mortality in elderly patients with dementia:
Data from two large-scale observational studies showed that older adults with dementia being treated with antipsychotics have a slightly increased risk of death compared with those not treated. The data are insufficient to provide a reliable estimate of the order of magnitude of the risk and the cause of the increase in this risk is not known.
Caution should be used in patients with cardiovascular disease or with a family history of QT prolongation. Avoid concomitant use of other neuroleptics.
Due to its anticholinergic properties, promazine should be used with caution in patients with clinically relevant prostatic hypertrophy and narrow-angle glaucoma. Caution is needed in patients with a history of paralytic ileus, Parkinson's disease and myasthenia gravis.
During prolonged treatment with Talofen, it is advisable to carry out regular clinical evaluations and laboratory tests relating to the central nervous system, liver, bone marrow, eye and cardiovascular system.
Sodium sulphite and potassium metabisulfite: Talofen contains these excipients, which can rarely cause serious hypersensitivity reactions and bronchospasm.
Talofen 4g / 100ml oral drops, solution contains sorbitol. Patients with rare problems of fructose intolerance should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
Concomitant use not recommended with the following drugs
Drugs that induce bone marrow depression: Talofen should not be used with other drugs with known potential to suppress bone marrow function (see sections 4.3 and 4.4).
Drugs that prolong the QT stretch: when neuroleptics are given together with drugs that prolong the QT tract, the risk of cardiac arrhythmias increases
Drugs that cause changes in electrolytes: do not administer concomitantly with drugs that cause alterations in electrolytes.
AntibioticsAn increased risk of ventricular arrhythmias has been reported with the concomitant use of moxifloxacin and phenothiazines: therefore avoid concomitant use.
Levodopa: phenothiazines may antagonize the effect of levodopa. The concomitant use of promazine and levodopa should be avoided.
Alcohol: An additive central nervous system depressant effect has been reported following concomitant administration of alcohol and phenothiazines. Avoid alcohol consumption during phenothiazine therapy.
Concomitant use requiring caution
Considering the effects of promazine on the central nervous system (CNS), caution should be exercised when using Talofen in combination with other centrally acting drugs.
Drugs that depress the Central Nervous System : Concomitant use of Talofen and other CNS depressants, including barbiturates, anxiolytics, hypnotics, anesthetics, antihistamines, analgesics, opioids, may induce an additive depressant effect, including respiratory depression, CNS depression and hypotension.
Succinylcholine: Talofen should not be given to patients who have received succinylcholine during surgery due to possible prolongation of neuromuscular block
Metrizamide: Concomitant administration of metrizamide and phenothiazines increases the risk of convulsions. Therefore, Talofen therapy must be stopped at least 48 hours before a myelography and can only be restarted 24 hours after the test is performed.
Lithium: Concomitant administration of lithium and antipsychotic drugs has resulted in a wide variety of symptoms of encephalopathy, brain damage, and extrapyramidal symptoms. Therefore patients on concomitant lithium therapy should be carefully monitored.
Anticonvulsant drugs: Concomitant use of phenothiazines and anticonvulsant drugs antagonizes the effects of the latter. Therefore the levels of anticonvulsant drugs should be monitored when a phenothiazine is added or removed from therapy: in fact, a dosage adjustment may be necessary. Patients should also be monitored for any signs of fentoin toxicity.
Antineoblastic drugs: promazine has an antiemetic effect which may mask the toxicity of antineoblastic drugs (see section 4.4).
Concomitant use to be considered
Anticholinergic drugs: Concomitant use of anticholinergic drugs may reduce the oral absorption of phenothiazines, antagonize their effects on behavioral and psychotic symptoms, and increase the occurrence of anticholinergic side effects (see section 4.4).
Antacids: antacids can reduce the absorption of phenothiazines.
Antihypertensive drugs: phenothiazines may increase the hypotensive effects of antihypertensive drugs.
Interactions with laboratory tests : urinary metabolites of phenothiazines can cause the appearance of a dark color in the urine and give false positive responses to the tests of amylase, urobilinogen, uroporphyrins, porphobilinogens and 5-hydroxy-indolacetic acid. In women being treated with Phenothiazines have been reported false positive pregnancy test results.
04.6 Pregnancy and breastfeeding -
Pregnancy
Studies are insufficient to highlight effects on pregnancy and / or embryonal / fetal development and / or postnatal development. The potential risk for humans is unknown. Talofen should not be used during pregnancy unless absolutely necessary.
Feeding time
It is not known whether promazine is secreted in breast milk. Effects on infants are unknown but cannot be excluded. Sedation may appear. The decision whether to continue or discontinue breastfeeding or to continue or discontinue therapy with Talofen must be made taking into account the benefits of breastfeeding for the child and the benefits of Talofen therapy for the mother.
Infants exposed to conventional and atypical antipsychotics including Talofen during the third trimester of pregnancy are at risk for side effects including extrapyramidal or withdrawal symptoms which may vary in severity and duration after birth. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, food intake disturbances. Infants should therefore be closely monitored.
04.7 Effects on ability to drive and use machines -
Talofen can induce sedation and sleepiness. Caution is advised in patients driving vehicles or using machines.
04.8 Undesirable effects -
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
The following side effects have been reported during marketing, which are temporally related to Talofen therapy (each single report may contain more than one sign or symptom):
Disorders of the blood and lymphatic system: agranulocytosis, disseminated intravascular coagulation, neutropenia
Endocrine pathologies: increase in TSH
Psychiatric disorders: apathy, confusional state
Nervous system disorders: ataxia, cognitive disorders, extrapyramidal symptoms, neuroleptic malignant syndrome, syncope
Cardiac pathologies: inversion of the T wave, prolongation of the QT segment
Vascular pathologies: hypovolemic shock
Respiratory, thoracic and mediastinal disorders: Respiratory failure
Hepatobiliary disorders: hepatitis, increased transaminases, increased alkaline phosphatase
Skin and subcutaneous tissue disorders: erythema
Musculoskeletal and connective tissue disorders: increased creatine phosphokinase, rhabdomyolysis, muscle rigidity
Renal and urinary disorders: acute renal failure
General disorders and administration site conditions: hyperthermia, fever
Injury, poisoning and procedural complications: overdose, voluntary poisoning
Withdrawal symptoms: If discontinuation of therapy occurs abruptly, withdrawal symptoms (nausea, vomiting, dizziness, tremor and restlessness) may occur. Therefore, it is advisable to gradually reduce the dosage of promazine (see sections 4.2 and 4.4).
Organic system class: pregnancy, puerperium and perinatal conditions:
Adverse reactions and frequency: neonatal withdrawal syndrome, frequency not known, extrapyramidal symptoms (see section 4.6).
The following side effects have been observed in patients receiving generic promazine or other phenothiazines:
Disorders of the blood and lymphatic system: aplastic anemia, haemolytic anemia, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia
Disorders of the immune system: anaphylactic reactions, bronchospasm, laryngospasm, larynx edema
Metabolism and nutrition disorders: hyperglycemia, glycosuria
Psychiatric disorders: depression, euphoric mood, anxiety, insomnia, restlessness
Nervous system disorders: extrapyramidal symptoms (akathisia, dystonia, parkinsonism, tardive dyskinesia), Neuroleptic Malignant Syndrome, convulsions, dizziness, sedation, somnolence
Eye disorders: blurred vision, deposits in the lens, corneal lesions, mydriasis, retinopathy
Cardiac pathologies: The following undesirable effects have been observed with other neuroleptics (see section 4.4): rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest. Very rare cases of sudden death
Vascular pathologies: orthostatic hypotension, syncope
Respiratory, thoracic and mediastinal disorders: aspiration pneumonia
Gastrointestinal disorders: constipation, dry mouth
Hepatobiliary disorders: jaundice
Skin and subcutaneous tissue disorders: exfoliative dermatitis, photosensitivity, eczema, erythema, urticaria, skin pigmentation, purpura
Musculoskeletal and connective tissue disorders: systemic lupus erythematosus
Renal and urinary disorders: urinary retention
Diseases of the reproductive system and breast: amenorrhea, galactorrhea, gynaecomastia, erectile dysfunction, menstrual disorders
General disorders and administration site conditions: increase in body temperature, decrease in body temperature, peripheral edema, aggravation of psychotic symptoms
Diagnostic tests: weight gain
Cases of venous thromboembolism, including cases of pulmonary embolism and deep vein thrombosis, have been reported with antipsychotic drugs with an unknown frequency.
04.9 Overdose -
Symptoms
Symptoms include: respiratory depression, central nervous system depression, confusional state, apathy, cognitive impairment, hypotension, hypothermia, myocardial ischaemia, tachycardia, arrhythmia, dystonia, convulsions.
Treatment
There is no specific antidote for promazine. In the event of an overdose, gastric lavage should be performed as soon as possible and symptomatic treatment instituted. In case of severe hypotension, lay the patient in a supine position and administer norepinephrine (adrenaline can further reduce blood pressure). Arrhythmia may respond to correction of hypoxia, acidosis or other biochemical changes. Dystonia can be eliminated by injection of diazepam. Hemodialysis is not effective.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: antipsychotic drugs. ATC code: N05AA03
Promazine is an aliphatic phenothiazine neuroleptic.
Promazine possesses a "high affinity for histaminergic H1 receptors, which may explain its potent sedative effect.
In contrast, promazine has low affinity for dopaminergic D2, serotonergic 5-HT, alpha1-adrenergic and muscarinic receptors.
05.2 "Pharmacokinetic properties -
Absorption: the effect of the intravenous and intramuscular injection occurs, respectively, after a few minutes and 20 minutes after administration; the oral solution in drops is rapidly absorbed and the effect becomes evident 30 minutes to 1 hour after administration.
Distribution: plasma concentrations of promazine are very low: it is widely distributed, especially in the brain.
Metabolism: promazine is extensively metabolised in the liver, into various metabolites;
Elimination: plasma half-life is approximately 6 hours; excretion is urinary.
05.3 Preclinical safety data -
In non-clinical acute and chronic toxicity studies, effects were observed only at dosages sufficiently above the maximum human dose to indicate minimal relevance to clinical use.
Non-clinical data based on conventional reproductive toxicity studies indicate no risk for humans.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Oral drops, solution:
non-crystallizable liquid sorbitol, ethanol 96%, methyl p-hydroxybenzoate, propyl p-hydroxybenzoate, anhydrous sodium sulphite, potassium metabisulphite, purified water. Injectable solution:
sodium sulphite anhydrous, potassium metabisulfite, sodium chloride, sodium citrate, ascorbic acid, water for injections.
06.2 Incompatibility "-
Talofen solution for injection must not be administered together with: aminophylline, fibrinogen, heparin sodium, prednisolone, sodium bicarbonate, thiopental
06.3 Period of validity "-
Oral drops: 18 months
Oral drops: validity after first opening 2 months. Solution for injection: 5 years
06.4 Special precautions for storage -
Store at a temperature not exceeding 25 ° C in the original packaging, protected from light and humidity.
06.5 Nature of the immediate packaging and contents of the package -
Solution for injection: dark glass ampoules - 6 ampoules of 2 ml
Oral drops, solution: dark glass bottle - solution 30 ml
06.6 Instructions for use and handling -
How to use the dropper bottle
To make the drops come out, turn the bottle upside down and hold it vertically with the opening downwards.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
BGP PRODUCTS S.r.l. - Viale Giorgio Ribotta 11 - 00144 Rome
08.0 MARKETING AUTHORIZATION NUMBER -
Talofen 25 mg / ml solution for injection - 6 ampoules 2 ml - A.I.C. n. 012611101
Talofen 4 g / 100 ml oral drops, solution - bottle 30 ml - A.I.C. n. 012611125
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Talofen 25 mg / ml solution for injection: 23.07.1957 / 31-05-2010
Talofen 4 g / 100 ml oral drops, solution: 29.04.1958 / 31-05-2010
