Active ingredients: Perfenazine, Amitriptyline hydrochloride
Mutabon Mite 2 mg + 10 mg film-coated tablets
Indications Why is Mutabon Mite used? What is it for?
Mutabon Mite contains two active ingredients: perphenazine and amitriptyline hydrochloride.
Perphenazine belongs to a group of medicines called phenothiazines, which act on the central nervous system by reducing anxiety states (anxiolytic properties) and by carrying out therapeutic activity against psychotic symptoms (delusions and hallucinations).
Amitriptyline hydrochloride belongs to a group of medicines called 'tricyclic antidepressants' used to treat depression.
Mutabon Mite is therefore an antidepressant in combination with a psycholeptic, used for the treatment of some mental disorders, which may have genetic (endogenous) causes, or which may be triggered by an unpleasant life event (reactive type disorders), in which simple anxiety is associated with relatively few or mild symptoms of depression.
Mutabon Mite, due to the reduced content of its active ingredients, allows the dosage to be adapted according to the specific needs of the patient, with a reduction to a minimum of the doses of use. For this Mutabon Mite can also be used in maintenance treatments.
Mutabon Mite is also effective in cases of severe insomnia associated with anxiety and depression.
Contraindications When Mutabon Mite should not be used
Do not take Mutabon Mite if:
- you are allergic to the active substances (perphenazine and amitriptyline hydrochloride) or to other similar medicines, or to any of the other ingredients of this medicine (listed in section 6);
- you are taking or have taken within the last two weeks medicines for the treatment of depression known as monoamine oxidase inhibitors (iMAOs) (see section "Other medicines and Mutabon Mite");
- has an increase in pressure inside the eye;
- suffer from eye disease due to increased pressure in the eye (glaucoma);
- you have diseases affecting the urogenital system such as enlargement of the prostate (prostatic hypertrophy) or difficulty in emptying the bladder (urinary retention), suspected or known;
- have muscle disease characterized by loss of tone and strength (myasthenia gravis);
- have a blood disorder characterized by changes in the composition of the blood (blood dyscrasia);
- you have changes in the function of the bone marrow that cannot produce enough cells that are found in the blood (bone marrow depression);
- suffer from alterations in the production of blood cells (hematopoiesis disorders). The administration of medicines which can cause the reduction of white blood cells (leukopenizing drugs) should therefore be avoided;
- have liver disease;
- you are taking other medicines that reduce the activity of the central nervous system (such as barbiturates, ethyl alcohol, narcotics, analgesics, antihistamines; see section "Other medicines and Mutabon Mite");
- is in a state of decreased degree of consciousness (severe dulling) or in case of coma;
- suffer from severe depression;
- you have suffered suspected or confirmed brain damage (subcortical brain damage), as you may experience an increase in your body temperature up to a temperature of over 40 ° C, sometimes 14 or 16 hours after taking the medicine;
- you are pregnant or breast-feeding (see section "Pregnancy and breast-feeding");
- have recently had a heart attack (myocardial infarction).
Precautions for use What you need to know before taking Mutabon Mite
Talk to your doctor or pharmacist before taking Mutabon Mite.
Tell your doctor if:
- have or have had episodes of epilepsy or seizures (involuntary muscle contractions) or are being treated with medicines used to quell seizures. Your doctor will assess the need to increase the dose of these medicines when taken at the same time as Mutabon Mite;
- you are taking other medicines with similar action (neuroleptics);
- have a tumor of the adrenal glands (pheochromocytoma) or an alteration of the mitral valve of the heart (mitral insufficiency). In this case you will be subjected to greater control in the administration of perphenazine for the risks related to the lowering of blood pressure (hypotension).If you have pheochromocytoma you may experience hypertension after stopping treatment with Mutabon Mite (rebound hypertension);
- have breast cancer. In this case, perphenazine will be given to you with particular care, as it causes an increase in the concentration of a hormone (prolactin) which can worsen your disease;
- must undergo surgery. Your doctor will advise you on whether or not you need to stop taking Mutabon Mite a few days before the operation;
- is in the post-operative phase, since it could occur aspiration of vomit;
- you have had 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 generally exposed to temperatures that are too high or too low, as the perphenazine contained in Mutabon Mite can compromise the body's temperature regulation mechanisms;
- have severe kidney disease or reduced kidney function;
- is predisposed to or already suffering from Parkinson's disease or Parkinson-like forms, or other motor disorders, since perphenazine can increase the state of muscle rigidity;
- have ever had problems with emptying your bladder (urinary retention);
- have or have had difficulty emptying the stomach (pyloric stenosis) or have a blockage of intestinal transit (intestinal obstruction);
- suffer from thyroid disease (hyperthyroidism) or if you are taking thyroid hormone medicines. Your doctor will keep you under close control;
- have respiratory diseases caused by lung infections or chronic breathing disorders such as severe asthma or emphysema;
- take alcohol, as it may enhance the effects of the medicine, significantly lower your blood pressure (hypotension). If you abuse alcohol it may increase the risk of suicide or the danger of an overdose (see section "Mutabon Mite with alcohol);
- you are abstinent from alcohol;
- experience sudden onset of sore throat or other signs of infection, as Mutabon Mite can cause changes in the production of blood cells. Your doctor will carry out blood tests especially between the fourth and tenth week of therapy. If the tests show a significant decrease in white blood cells, your doctor will tell you to stop the treatment; while a slight drop in white blood cells is not in itself indicative of stopping treatment;
- have cognitive impairment (dementia) as treatment with Mutabon Mite may increase the risk of problems with the blood vessels of the brain (cerebrovascular events);
- suffer from diseases of the heart and blood vessels (cardiovascular disease), especially if you are elderly, or have a family history of abnormal heartbeat conduction (QT prolongation), or have risk factors for stroke (pathological vascular event at the level of brain), because antidepressant medicines, when given in high doses, can cause altered heart rhythms (arrhythmias, sinus tachycardia and prolonged conduction times) or more serious events such as myocardial infarction and stroke;
- have had diseases associated with blood clot formation or have a family history of such diseases;
- has a hardening, thickening and loss of elasticity of the arterial wall in the brain (cerebral arteriosclerosis);
- suffer from mental disorders such as manic-depressive psychosis (a disorder characterized by cyclic changes in mood, passing from excessive excitement to depression), or a personality disorder characterized by a persistent tendency to interpret the behavior of others with distrust and suspicion (disorder paranoid), since tricyclic antidepressants such as amitriptyline can accentuate the symptoms of these diseases. The tranquilizing action of Mutabon Mite, however, reduces the risk of these effects;
- you must undergo electroshock therapy, as the risks associated with this practice may increase in conjunction with the intake of amitriptyline; in this case the doctor will limit the intake of Mutabon Mite only to cases in which the therapy is absolutely essential.
Interactions Which drugs or foods can modify the effect of Mutabon Mite
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Do not take Mutabon Mite together with the following medicines:
- monoamine oxidase inhibitors (iMAO). Do not take Mutabon Mite at the same time or in the two weeks following the end of treatment with monoamine oxidase inhibitors as this may result in severe reactions, elevated temperature (hyperpyretic crisis) up to convulsions, coma and death (see section "Do not take Mutabon Mild if "). Once this time has elapsed, your doctor will start treatment with Mutabon Mite cautiously, gradually increasing the dose until a satisfactory response is achieved.
- opiates, barbiturates or other sedatives, antihistamines, anesthetics, tranquilizers and meperidine (and other opiate analgesics). Co-administration with Mutabon Mite may potentiate the central nervous system depressant effects of these medicinal products, including respiratory depression. Conversely, these medicines may potentiate the effects of Mutabon Mite. Therefore, you should not take Mutabon Mite together with these medicines (see section "Do not take Mutabon Mite if").
Talk to your doctor or pharmacist if you are taking:
- medicines that can cause reduction of white blood cells (leukopenizing drugs), as Mutabon Mite can cause changes in the production of blood cells (see sections "Do not take Mutabon Mite if:" and "Warnings and precautions");
- other psychotropic drugs, medicines with anticholinergic action (inhibiting action of acetylcholine, a substance that acts on the nervous system) or medicines that act on the autonomic nervous system (sympathomimetics), due to the possible occurrence of undesirable effects due to their interaction with Mutabon Mite ;
- medicines with anticholinergic action, such as atropine or similar medicines, or antihistamines, as it is possible that an increase in the effects on the cholinergic system may occur with the consequent risk of intestinal obstructions (paralytic ileus), blurred vision and possible alteration of ocular pressure in the presence of glaucoma;
- medicines that affect the autonomic nervous system (sympathomimetic amines) such as epinephrine combined with local anesthetics, as it is possible that an increase in the activity of these medicines or Mutabon Antidepessive may occur. Your doctor will monitor you closely and adjust your dose to avoid the onset of effects on blood pressure and heart function, which are sometimes fatal;
- reserpine, methyldopa, other medicines to treat high blood pressure (hypertension) such as guanethidine (concomitant use requires a dose adjustment by the doctor), beta-blockers that block adrenergic receptors such as propranolol or similar medicines, in how low blood pressure (hypotension) may occur; Concomitant use of Mutabon Mite and these medicines is therefore not recommended. Your doctor may ask you to have your blood pressure checked before starting treatment with Mutabon Mite and weekly checks in the first month of treatment;
- medicines to treat seizures (see section "Warnings and precautions");
- phenytoin, a medicine used to treat epilepsy as Mutabon Mite can alter its effectiveness;
- antipsychotic medicines; - sedative medicines such as diazepam;
- high doses of etcorvinol (sedative and hypnotic medicine), as transient delirium has been reported with this combination of medicines. The association with Mutabon Mite should be used with caution;
- medicines for the treatment of stomach hyperacidity based on aluminum salts as they can reduce the absorption of Mutabon Mite;
- 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 blood electrolytes;
- medicines based on cimetidine, as it can increase the concentrations of amitriptyline in the blood and its effects, with the possible occurrence of serious side effects;
- medicines that can inhibit cytochrome P450 2D6 (an enzyme present in the body, which is involved in the metabolism of medicines), such as quinidine, cimetidine, many other antidepressants, phenothiazines, propafenone and flecainide and all medicines called selective re-inhibitors serotonin uptake (SSRI), such as fluoxetine, sertraline and paroxetine. In this case your doctor may prescribe lower than recommended doses, both for these medicines and for Mutabon Mite. Your doctor will monitor you closely even if you switch from one drug to another, especially in the case of a switch from fluorexetine to Mutabon Mite;
- levodopa and phenylbutazone, as Mutabon Mite may interfere with the absorption of these medicines.
Mutabon Mite can interfere with the absorption of various other medications.
Tell your doctor if you are exposed to organic phosphorus insecticides.
Mutabon Mite and laboratory tests
Taking Mutabon Antidepressant can darken the urine and cause changes in the results of some laboratory tests:
- false-positive (non-real positive results) in the values of the following tests: urobilinogen, amylase, uroporphyrins, porphobilinogens and 5-hydroxy-indolacetic acid;
- changes in the electrocardiogram such as prolongation of the QT interval;
- abnormalities in the electroencephalogram;
- alteration (increase) in the levels of iodine bound to blood proteins;
- changes in the results of hypothalamic-pituitary function tests, as the medicine may cause a decrease in some hormones;
- false-positive and false-negative in the urine pregnancy test;
- possible rises and falls in blood sugar levels.
Mutabon Mite with alcohol
Mutabon Mite must not be administered simultaneously with alcohol (ethanol) due to a 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:
Suicide / Suicide idea
Depression is associated with an increased risk of thoughts associated with suicide, willingness to harm oneself (self-harm) and suicide. The risk of you experiencing these thoughts may increase in the early stages of improvement and persist until you experience a significant improvement in your symptoms. As improvement may not occur during the first weeks of treatment or in the weeks immediately following, you will be closely monitored by your doctor until improvement has occurred.
Other psychiatric mental disorders for which Mutabon Mite is prescribed may increase the risk of suicidal behavior and a depressive disorder characterized by alternating periods of well-being and phases of depression (major depressive disorder). major depressive, the doctor will observe the same precautions followed when treating patients with other psychiatric conditions.
You are more likely to have suicidal thoughts if:
- he has already thought in the past of taking his own life;
- is a young man under the age of 25, being treated with antidepressants.
Your doctor will monitor you closely, especially in the early stages of treatment and after any dose adjustments, and if you are a patient at high risk of having thoughts of suicide. Contact your doctor immediately if you experience any worsening of your symptoms, the onset of behavior or thoughts associated with suicide, or changes in behavior.
It is possible that during treatment with Mutabon Mite you may experience:
- appearance of involuntary movements of the muscles (tardive dyskinesia), especially if you are an elderly patient. Both the risk of developing dyskinesia and the possibility of it becoming irreversible increase with the duration of treatment and with the total dose of the drug taken, although, less frequently, it can also arise after short periods of treatment and at low doses. Discontinuation of treatment can lead to resolution of this disease. If you notice these symptoms, please inform your doctor who will consider adjusting the dose or stopping the treatment;
- increase or decrease in blood sugar levels;
- appearance of skin sensitivity reactions to light (photosensitivity). For this reason, avoid excessive exposure to sunlight while taking Mutabon Mite;
A heart problem, called "prolongation of the" QT interval "(seen on the" electrocardiogram, ECG) and heart rhythm disorders (fast or irregular heartbeat) have been reported in connection with taking Mutabon Mite. Talk to your doctor. self:
- have a slow heart rate,
- have or have had a problem where your heart has not been able to pump blood through your body as it should (a condition called heart failure),
- are taking other medicines that can cause heart problems or
- have a problem that causes too low a level of potassium or magnesium or too high a level of potassium in your blood.
Stop taking Mutabon Mite and tell your doctor if you experience:
- a significant increase in temperature not attributable to a specific cause. This increase in temperature could suggest a hypersensitivity to perphenazine and in this case your doctor will tell you to stop the therapy.
- a potentially fatal complex of symptoms called neuroleptic malignant syndrome, characterized by: increased body temperature, muscle stiffness, decreased or loss of the ability to spontaneously move (akinesia), vegetative disorders (irregular pulse and blood pressure, sweating, increased heart rate (tachycardia), changes in heart rhythm (arrhythmias), changes in consciousness which can progress to partial loss of consciousness (stupor) and coma. Your doctor will tell you to stop the therapy and will provide to initiate therapy for the treatment of these symptoms.
- abnormal blood urea values
During treatment with Mutabon Mite you will need to periodically check the red blood cell values and the function of the liver and kidneys. Should any abnormal results occur, the doctor will discontinue the therapy.
Taking Mutabon Mite may mask signs of overdose of other medicines, or make it more difficult to diagnose diseases such as intestinal obstruction, Reye's syndrome (acute disease usually found in patients under the age of 18, potentially fatal characterized by symptoms that mainly affect the brain and liver), brain tumors or other diseases that alter the structure and / or functions of the brain (encephalopathies).
Children and adolescents
Mutabon Mite is not recommended for use in children below 12 years of age due to a lack of data on safety and efficacy.
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.
Pregnancy
Mutabon Mite must not be used during pregnancy, whether known or suspected due to the risk of side effects in the newborn (see section "Do not take Mutabon Mite se" and section 4 "Side effects in children").
Feeding time
You should not use Mutabon Mite if you are breast-feeding (see section "Do not take Mutabon Mite se") as Mutabon Mite passes into breast milk and may cause side effects in the baby.
Driving and using machines
Mutabon Mite influences the ability to drive and use machines, as it can induce changes in the reaction time (time interval between the moment you perceive a danger and the moment you start to react to avoid it). Therefore, take due care when driving vehicles and using machines.
Mutabon Mite 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 Mutabon Mite: 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 Mutabon Mite must be established by the doctor, depending on the specific disorder to be treated, the duration and severity of the disease, and its response to therapy.
The recommended dose is 1 tablet, 1-3 times a day. It usually takes several days for Mutabon Mite to have an appreciable effect.
If you suffer from persistent insomnia, it may be advisable, especially in the first days of therapy, to take 1 or 2 tablets in the evening, half an hour before going to sleep; the remaining tablets prescribed by the doctor can be taken throughout the day.
To get a full effect you will have to continue the treatment for several weeks, according to the doctor's opinion. Once your symptoms are controlled, your doctor will gradually reduce your dose until the maintenance dose is most suitable for you. Your doctor will periodically evaluate the need to continue treatment with Mutabon Mite.
Use in children and adolescents
Mutabon Mite is not recommended for children below 12 years of age (see section "Children and adolescents").
Use in the elderly
The dose and frequency of administration of Mutabon Mite in elderly patients should be carefully determined by the physician, who will evaluate a possible reduction in the above dose based on individual needs.
If you forget to take Mutabon Mite
Do not take double the prescribed dose to make up for a forgotten tablet; continue therapy according to the usual schedule.
If you stop taking Mutabon Mite
Do not stop taking Mutabon Mite until you have consulted your doctor.
Generally phenothiazines (perphenazine) do not cause psychic dependence. However, following abrupt discontinuation of high-dose treatment, you may experience gastritis, nausea, vomiting, dizziness, tremors and motor hyperactivity. If you experience these symptoms, consult your doctor who will prescribe appropriate therapy.
Suddenly discontinuing high-dose tricyclic antidepressant therapy (amitriptyline hydrochloride) can cause symptoms such as: malaise, chills, cold, muscle pain, headache, nausea, vomiting, anxiety, unsteadiness, dizziness and a constant need to move ( akathisia) These symptoms are not indicative of addiction.
If you suddenly stop taking high dose Mutabon Mite, please inform your doctor and pay attention to any symptoms you may experience. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Mutabon Mite
If you have taken too much Mutabon Mite, contact your doctor or pharmacist immediately or go to the nearest hospital.
The signs and symptoms of an overdose come on quickly, therefore hospital check-up is required as soon as possible.
Overdose with Mutabon Mite, as with other medicines of the same category, can result in death.
Symptoms of overdose with Mutabon Mite may correspond to any of the side effects listed for the two active substances, perphenazine or amitriptyline hydrochloride (see section "Possible side effects").
Symptoms of perphenazine overdose are manifested by motor system abnormalities (extrapyramidal symptoms), such as involuntary muscle movements (dyskinesia) and abnormal muscle contractions (dystonia); however, they may be masked by the anticholinergic effects of amitriptyline. Other symptoms may include partial loss of consciousness (stupor) or coma; children may experience seizures.
Symptoms of an amitriptyline overdose are manifested by irregular heartbeat (cardiac arrhythmias), severe lowering of blood pressure (severe hypotension), involuntary muscle contractions (convulsions) and decreased nervous system activity (depression of the nervous system). central nervous system, including coma.
There have also been reported abnormalities in the conduction of the heartbeat detectable on the electrocardiogram.
Other symptoms of overdose include: confusion, disturbances in concentration, temporary visual hallucinations, dilated pupils, agitation, overactive reflexes, drowsiness, muscle stiffness, vomiting, low body temperature (hypothermia), fever or any of the symptoms listed among the effects unwanted.
Method of treatment in case of overdose of Mutabon Mite
There is no specific substance that can counteract the effect of an overdose of Mutabon Mite. In case of accidental or intentional overdose of Mutabon Mite, contact your doctor or pharmacist immediately or go to the nearest hospital.
Your doctor will subject you to appropriate emergency treatments, such as gastic lavage and electrocardiographic examination (ECG), and will closely observe you for any signs affecting the central nervous system, breathing difficulties, low blood pressure, rhythm abnormalities cardiac and / or conduction blockade of the heart and seizures.
The doctor may decide to contact the local poison control center.
Side Effects What are the side effects of Mutabon Mite
Like all medicines, Mutabon Mite can cause side effects, although not everybody gets them.
The side effects of Mutabon Mite are the same referable to the two active ingredients (perphenazine and amitriptyline), when taken individually. No undesirable effects have been reported due solely to their combination in Mutabon Mite.
In very rare cases, patients with hypersensitivity to phenothiazines (perphenazine) have experienced excessive accumulation of fluid in the brain (cerebral edema), circulatory collapse and death.
Occasionally, treatment with phenothiazines can cause blockage of the gut musculature with consequent arrest of the progression of the contents of the gut (adynamic ileus) which, if severe, can cause complications and death.
Stop taking Mutabon Mite and contact your doctor immediately if you experience:
- Neuroleptic Malignant Syndrome (NMS), a potentially fatal syndrome 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)), changes in consciousness which may progress to stupor and coma (see "Stop taking Mutabon Mite and tell your doctor if you get it" in section 2);
- persistent abnormalities in muscle contraction and movement, including abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (persistent late dyskinesia) (see "Stop taking Mutabon Mite and tell your doctor if it occurs" in section 2);
- swelling of the hands, feet, ankles, or also of the face, lips, tongue and / or throat resulting in difficulty in swallowing or breathing (angioedema);
- increased body temperature (hyperpyrexia);
- allergic reaction with skin rashes (hives), irritation and red spots on the skin (erythema), itchy inflammatory reactions on the skin (eczema), inflammation of the skin with formation of lesions and loss of the surface layer (exfoliative dermatitis), itching, sensitivity reactions of the skin to light (photosensitivity), asthma, fever, allergic reactions (anaphylactoids), swelling due to fluid accumulation in the upper airways (edema of the larynx), contact dermatitis;
- 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 (frequency of this side effect may not be defined on the basis of available data);
- worsening of your depressive state, including, rarely, thoughts or behavior related to suicide (see section "Warnings and precautions").
Undesirable effects related to perphenazine
The most common symptoms 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 "hyperextension of the neck, 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 cervical 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 an excess of motor activity (motor restlessness), alteration and deviations 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 changes in the tongue (color, pain, protrusion or rolling), sudden and involuntary contractions of the chewing muscles, constriction in the throat, difficulty in pronouncing words and swallowing (dysphagia), inability to sit up, a range of symptoms including tremor, muscle stiffness, slowing of movement speed and abnormalities posture (parkinsonism) and loss of muscle coordination (ataxia).
- The frequency and severity of these symptoms generally increases with increasing dosage of Mutabon Mite.
It can also occur:
- abnormalities in the composition of cerebrospinal fluid proteins, headache (headache), drowsiness;
- worsening of psychotic symptoms such as thought disturbances, delusions and hallucinations, motor, emotional and behavioral abnormalities (catatonic-like states), thought forms that deviate from reality (paranoid reactions), deep sleep (lethargy), excitement, restlessness and hyperactivity, nocturnal confusion, bizarre dreams, sleep disturbances (insomnia);
- abnormal breast milk secretion (galactorrhea), breast enlargement in women and men (gynaecomastia), menstrual cycle disturbances, prolonged absence of menstruation (amenorrhea), changes in sexual desire, ejaculation inhibition, false positives in pregnancy test, increased and decreased blood sugar concentration (hyperglycemia and hypoglycemia), presence of sugar in the urine (glycosuria), excessive release of an antidiuretic hormone (syndrome of inappropriate antidiuretic hormone secretion, SIADH);
- low blood pressure when rising from a sitting or lying position (postural hypotension), increased and decreased heart rate (tachycardia and bradycardia), cardiac arrest, fainting and dizziness;
- 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), involuntary muscle contractions (convulsions).
Occasionally it can occur:
- dry mouth and hypersalivation, nausea, vomiting and diarrhea, gastric retention, anorexia, constipation (constipation), stubborn constipation and hard mass of dehydrated stools in the bowel (fecaloma), difficulty emptying the bladder (urinary retention), frequent urge to pass urine 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 characterized by increased pressure in the eye (glaucoma), excessive sweating, increased blood pressure (hypertension), low blood pressure (hypotension), altered pulse rate;
Rarely have been observed:
- heart beat conduction abnormalities (QT prolongation), ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest;
- swelling of the salivary glands (parotid swelling).
Side effects related to long-term therapy:
- liver damage
- appearance of spots on the skin (skin pigmentation), changes in vision which consist in the deposit of fine particulate matter in the cornea and in the lens and which, in the most serious cases, lead to opacity of the star-shaped lens, inflammation of the cornea (epithelial keratopathies) changes in the retina, destruction of the retina up to loss of vision (pigmentary retinopathy);
- persistent abnormalities in the contraction of muscles and movements, such as abnormal, involuntary movements of the tongue, jaw, trunk, or limbs (persistent late dyskinesia) which may arise even after discontinuation of treatment.
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), syndrome similar to systemic lupus erythematosus (a 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.
In elderly patients with dementia, a small increase in the number of deaths has been reported in patients taking antipsychotics compared with patients not taking them.
Undesirable effects related to amitriptyline hydrochloride
Treatment with antidepressant medicines, including amitriptyline hydrochloride, can induce the onset of latent schizophrenia, which can be avoided, in some cases, thanks to the antipsychotic effect of the perphenazine contained in Mutabon Mite.
Cases of seizures (epileptic seizures) have been reported in chronic schizophrenia during treatment with amitriptyline hydrochloride.
Furthermore, the intake of amitriptyline hydrochloride may cause, in addition to some of the undesirable effects reported for perfanazine, the following undesirable effects:
- increased risk of bone fractures;
- skin rash (rash);
- changes in the pupil (accommodation disorders), difficulty emptying the bladder (urinary retention and dilation of the urinary tract);
- perception of heartbeat (palpitations), heart attack and stroke, altered heartbeat (arrhythmias), impaired conduction of electrical impulses of the heart which can lead to complete or partial arrest of the heart (heart block);
- confusional states, disturbances in concentration, disorientation, delusions and hallucinations, excitement, nervousness, anxiety and agitation, insomnia and nightmares, hearing loss, tingling and alterations in the perception of stimuli in the limbs (paraesthesia), disturbance of function at the level of the peripheral nervous system (peripheral neuropathy), tremors and convulsions, changes in the electroencephalogram, impaired hearing (tinnitus);
- increase in the size of the testicles;
- disorders of the gastrointestinal system (epigastric disorders and heartburn), inflammation of the oral cavity (stomatitis), taste disturbance, dark coloring of the tongue;
- inflammation of the liver (hepatitis) has rarely occurred;
- depression of the bone marrow (when the bone marrow cannot produce enough cells found in the blood), decrease in white blood cells (agranulocytosis, leukopenia), breakage of capillaries below the surface of the skin (purpura), increase of a particular type of white blood cells (eosinophilia), reduction in the number of platelets (thrombocytopenia); - a heart problem called "prolongation of the" QT interval "(seen on the" electrocardiogram, ECG) (common rate);
- dizziness, weakness and fatigue, weight gain or loss, hair loss (alopecia).
Abrupt discontinuation of treatment in long-term therapies can result in:
- nausea, headache (headache), malaise.
Undesirable effects in children
The following symptoms have been observed in newborns of mothers who have taken antipsychotics, including Mutabon Mite, during the last three months of pregnancy: muscle agitation, stiffness and / or weakness, overactive reflexes, tremor, motor system changes and abnormalities (extrapyramidal symptoms ), sleepiness, breathing problems, difficulty in food intake and neonatal withdrawal syndrome.
If your baby shows 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 the address www.agenziafarmaco.gov.it/it/responsabili.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 temperatures.
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.
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What Mutabon Mite contains
- The active ingredients are perphenazine and amitriptyline hydrochloride. Each film-coated tablet contains 2 mg of perphenazine and 10 mg of amitriptyline hydrochloride.
- The other ingredients are maize starch, lactose, magnesium stearate, pregelatinised starch, Opadry® white (hypromellose E-464, macrogol, titanium dioxide E-171, hydroxypropylcellulose E-463).
What Mutabon Mite looks like and contents of the pack
Mutabon Mite is available in packs of 30 film-coated tablets, contained in a blister.
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 -
MUTABON MITE 2 MG + 10 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each film-coated tablet contains:
Active ingredients: Perfenazine 2 mg + Amitriptyline hydrochloride 10 mg.
Excipient with known effects:
lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Film-coated tablets.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Mutabon Mite is indicated in the treatment of various mental disorders, both reactive and endogenous, in which simple anxiety is associated with relatively few or mild symptoms of depression as seen in daily medical practice.
Mutabon Mite, due to the reduced content of its components, allows the dosage to be adjusted according to individual needs, with a minimum of use doses. For these conditions Mutabon Mite can be advantageously used in maintenance treatments.
Mutabon Mite is shown to be effective in patients with severe insomnia associated with anxiety and depression.
04.2 Posology and method of administration -
Dosage
The dosage of Mutabon Mite should be individualized according to the particular disorder being treated, the duration and severity of the disease and the patient's response.
One Mutabon Mite tablet 1-3 times a day is usually sufficient; it generally takes several days of treatment to fully appreciate the therapeutic activity of the preparation.
Treatment will need to be continued for several weeks to achieve full effect, and once symptom control has been achieved, the doctor may gradually reduce the dosage until the individual maintenance dose is established. The need for continued treatment should be re-evaluated periodically.
In cases of persistent insomnia, it may be advisable, especially in the first days of therapy, to administer one or two Mutabon Mite tablets in the evening half an hour before bedtime and the remaining tablets during the day.
Pediatric population
The safety and efficacy of Mutabon Mite in children below 12 years of age have not been established and its use in children is not recommended.
Senior citizens
In the treatment of elderly patients the posology must be carefully established by the physician who will have to evaluate a possible reduction of the posology.
Method of administration
Oral use.
04.3 Contraindications -
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Cases of cross-allergenicity with other drugs with similar chemical structure have been reported.
Glaucoma, increased intraocular pressure, prostatic hypertrophy, suspected or known urinary retention, myasthenia gravis, blood dyscrasia, bone marrow depression or liver damage.
The administration of Mutabon Mite is contraindicated in association with depressive drugs of the S.N.C. (barbiturates, ethyl alcohol, narcotics, analgesics, antihistamines).
In comatose states or in severe dullness and in severe states of depression.
Disorders of hematopoiesis (therefore avoid the simultaneous administration of potentially leukopenizing drugs).
In patients with suspected or known subcortical brain damage, with or without hypothalamic damage, as a hyperthermic reaction with temperatures above 40 ° C may arise in such patients, sometimes not until 14 or 16 hours after drug administration. Useful for the treatment of this reaction are the ice pack on the whole body and the administration of antipyretics.
Known or suspected pregnancy.
Feeding time.
In order to avoid even serious manifestations, hyperpyretic crises up to convulsions, coma and exitus, the product must not be administered in combination with MAOIs, nor before at least 2 weeks have elapsed from the interruption of a previous treatment with these drugs, to allow the disappearance of the effects of MAOIs and any possible enhancement.
Amitriptyline hydrochloride is not recommended during the acute recovery phase after myocardial infarction.
04.4 Special warnings and appropriate precautions for use -
Since phenothiazines and tricyclic antidepressants 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 a suspicion that the drug induces cardiovascular effects, an electrocardiogram should be done. If abnormal liver or kidney function tests appear, treatment with Mutabon Mite should be stopped.
The possibility of suicide in depressed patients continues during treatment until significant remission of symptoms occurs. Suicidal patients should not have access to large quantities of Mutabon Mite.
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.
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, pulse and blood pressure irregularities, sweating, tachycardia, arrhythmias; changes in consciousness which can progress to stupor and coma. The treatment of s.n.m. it consists in immediately suspending the administration of antipsychotic drugs and other non-essential drugs and in instituting intensive symptomatic therapy (particular care must be taken to reduce hyperthermia and correct dehydration). If the resumption of antipsychotic treatment is deemed essential, the patient should be carefully monitored.
In general, the same precautions that are followed during single administration of the two components should be observed.
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, the dose of these drugs may need to be increased when used together with Mutabon Mite.
Pediatric population
The safety and efficacy of Mutabon Mite in children below 12 years of age have not been established and its use in children is not recommended.
Perfenazine
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. Avoid concomitant therapy with other neuroleptics.
Particular attention should be paid to administering perphenazine to patients with pheochromocytoma or mitral insufficiency, due to any hypotensive effects that may occur, which can also be controlled with noradrenaline. The antiemetic effect of perphenazine can mask the signs of overdosing of other drugs or can make it more difficult to diagnose conditions such as intestinal obstruction, Reye's syndrome, brain tumors or other encephalopathies.
Since perphenazine causes an increase in the plasma level of prolactin, products containing phenothiazines should be used with appropriate caution in women with breast cancer.
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.
Patients undergoing surgery who receive high doses of perphenazine should be carefully monitored for the possible occurrence of hypotension phenomena. In addition, it may be necessary to reduce the amount of central nervous system (CNS) anesthetics or sedatives.
Use with caution in subjects exposed to too high or too low temperatures as phenothiazines can compromise the ordinary thermoregulation mechanisms.
A significant increase in body temperature, which cannot be explained otherwise, may suggest an "intolerance to perphenazine; in this case, discontinue therapy.
Since hypersensitivity reactions to phenothiazines have been reported, patients receiving these drugs should avoid excessive exposure to sunlight.
Red blood cell counts and liver and kidney function should be checked periodically. If blood dyscrasias or liver function abnormalities occur, treatment should be discontinued. If blood urea nitrogen (BUN) values become abnormal, treatment should be discontinued. The use of phenothiazine derivatives in patients with decreased renal function should be undertaken with caution.
Perphenazine can increase the state of muscle stiffness in individuals predisposed to or already suffering from Parkinson's disease or Parkinson-like forms, or other motor disorders.
The conduct of therapy must be characterized by particular caution in all the following cases, namely: in subjects with a history of epilepsy or convulsive events, in patients in alcohol withdrawal, in cardiac patients, especially if elderly, in cerebral arteriosclerosis, in patients with a history of urinary retention or intestinal obstruction or pyloric stenosis, in severe renal or hepatopatients, in hyperthyroid glands and in those undergoing treatment with thyroid hormones, in subjects exposed to high temperatures, in patients with respiratory damage, due to acute lung infections or chronic breathing disorders, such as severe asthma or emphysema.
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.
In patients on long-term therapy, the possible occurrence of liver damage, corneal or lenticular deposits, alterations to the retina and irreversible dyskinesia should be considered (see for the latter the specific section "4.8 Undesirable effects").
Patients should be carefully monitored for haematological effects, especially between the fourth and tenth week of therapy, for sudden onset of sore throat or other signs of infection. If the white blood cell count decreases and the differential count shows a significant decrease in granulocytes, the drug should be discontinued and appropriate therapy initiated. However, a slight decrease in white blood cells is not in itself indicative of discontinuation. of the treatment.
As cases of photosensitivity have been reported, sun exposure should be avoided during treatment with phenothiazines.
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. Mutabon Mite should be used with caution in patients with risk factors for stroke. Use with caution in patients with cardiovascular disease or with a family history of QT prolongation.
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 must be identified before and during treatment with "Mutabon Mite" 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.
"Mutabon Mite" is not licensed for the treatment of dementia-related behavioral disorders.
Amitriptyline hydrochloride
In patients undergoing treatment with a monoamine oxidase inhibitor, an interval of two weeks or more is recommended between stopping the administration of the MAO inhibitor and starting treatment with Mutabon Mite tablets in order to allow healing of the effects of the MAO inhibitor. MAO inhibitor and avoid a possible enhancement. Treatment with Mutabon Mite tablets should be initiated with caution in such patients with gradual dose escalation until a satisfactory response is achieved.
Carefully monitor patients with cardiovascular disorders during therapy with Mutabon Mite. Tricyclic antidepressant drugs act markedly on the cardiovascular system, even at therapeutic doses. These drugs, including amitriptyline hydrochloride, have caused arrhythmias, sinus tachycardia and prolonged conduction times, particularly when administered at high doses. Myocardial infarction and stroke have been reported with drugs in this category.
Due to the anticholinergic activity of amitriptyline hydrochloride, Mutabon Mite tablets should be used with caution in patients with glaucoma and increased intraocular pressure as well as in patients with present or anticipated urinary retention. Even usual doses can cause severe increases in intraocular pressure in patients with narrow-angle glaucoma.
Strict monitoring is necessary during the administration of amitriptyline hydrochloride to hyperthyroid patients or to subjects undergoing treatment with thyroid drugs.
In manic-depressive psychosis, depressed patients may progress to the manic phase when treated with a tricyclic antidepressant agent. Patients with paranoid symptoms may experience an excess of these symptoms. The tranquilizing action of Mutabon Mite tablets may reduce the possibility of this effect.
Both rises and falls in blood sugar levels have been reported.
The risk of electroshock therapy may be increased by the concomitant administration of amitriptyline hydrochloride. Such concomitant treatment should be limited to patients for whom it is considered absolutely essential.
If possible, stop taking Mutabon Mite tablets a few days before elective surgery.
Mutabon Mite should not be administered concomitantly with guanethidine or similarly acting compounds, as amitriptyline, like other tricyclic antidepressants, may block the antihypertensive effect of these drugs. If hypotension occurs, epinephrine (adrenaline) should not be administered as its action is blocked and partially reversed by perphenazine. If a vasopressor is needed, norepinephrine can be used. Severe acute hypotension has occurred with the use of phenothiazines and particularly more easily in patients with mitral insufficiency or pheochromocytoma. Rebound hypertension may arise in patients with pheochromocytoma.
ABUSE AND DRUG DEPENDENCE: Generally, phenothiazines, including perphenazine, do not cause psychic dependence. However, gastritis, nausea, vomiting, dizziness, tremor and motor hyperactivity have been reported 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 thereafter. l "discontinuation of treatment with phenothiazines.
The usefulness of amitriptyline in the treatment of depression has been widely demonstrated; however, it should be understood that amitriptyline abuse among addicts is not uncommon.
Sudden discontinuation of high-dose tricyclic antidepressant therapy may cause cascading symptoms, including malaise, chills, shortness of breath, muscle pain, headache, nausea, vomiting, anxiety, unsteadiness, dizziness, and akathisia. These symptoms are not indicative of addiction. .
SUICIDARY IDEATION / BEHAVIOR
Suicide / Suicidal ideation
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide / related events). This risk persists until significant remission occurs. As improvement may not occur during the first or immediate weeks of treatment, patients should be monitored closely until improvement occurs. It is generally clinical experience that the risk of suicide may increase in the early stages of improvement.
Other psychiatric conditions for which Mutabon mite is prescribed may also be associated with an increased risk of suicidal behavior. Additionally, these conditions can be associated with major depressive disorder. Therefore, the same precautions followed when treating patients with other psychiatric disorders should be observed when treating patients with major depressive disorders.
Patients with a history of suicidal behavior or thoughts, or who exhibit a significant degree of suicidal ideation prior to initiation of treatment, are at increased risk of suicidal thoughts or suicidal thoughts, and should be closely monitored during treatment. of clinical trials conducted with antidepressant drugs in comparison with placebo in the therapy of psychiatric disorders, showed an increased risk of suicidal behavior in the age group below 25 years of patients treated with antidepressants compared to placebo.
Drug therapy with antidepressants should always be associated with close surveillance of patients, particularly those at high risk, especially in the initial stages of treatment and after dose changes. Patients (or caregivers) should be advised of the need to monitor and report immediately to their physician any clinical worsening, the onset of suicidal behavior or thoughts, or changes in behavior.
Prolongation of the QT interval
Cases of QT interval prolongation and arrhythmias have been reported in the post-marketing period. Caution is advised in patients with significant bradycardia, uncompensated heart failure or in patients taking concomitant QT interval prolonging medications. Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) are known as conditions that increase the proarrhythmic risk.
Important information about some of the excipients
The medicine contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose / galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction -
Perfenazine
Concomitant administration of phenothiazines may potentiate the central nervous system (CNS) depressant effects of opioids, barbiturates or other sedatives, antihistamines, anesthetics, tranquilizers, alcohol (ethanol) and meperidine (and other opioid analgesics), for which it may be necessary a reduction in the doses of these agents and overdose should be avoided. Similarly, concomitant use of these products can potentiate phenothiazines.
The association with other psychotropic drugs, with anticholinergics or sympathomimetics requires particular caution and vigilance on the part of the physician, in order to avoid undesirable effects of interaction.
Use with caution in patients treated with atropine or similar drugs due to additive anticholinergic effects and also in patients who will be exposed to high temperatures or organic phosphorus insecticides.
The use of alcohol should be avoided as it may have additive effects and hypotension. Patients should be advised that they may be more sensitive to alcohol when treated with Mutabon Mite. The risk of suicide and the danger of overdose may be increased in patients who consume excessive alcohol due to the potentiation of the drug's effects.
Mutabon Mite should be administered with caution in conjunction with antihypertensive therapy with reserpine, guanethidine, methyldopa, beta-blockers or similar compounds. The possible occurrence of hypotension can be controlled with noradrenaline (not adrenaline, as its activity is antagonized by perphenazine).
Co-administration of cimetidine may increase plasma concentrations of amitriptyline and related anticholinergic effects.
If the patient is being treated with anticonvulsants, a higher dose of these drugs may be required in conjunction with the administration of perphenazine.
Caution should be exercised in case of concomitant administration of perphenazine and phenytoin.
Antipsychotics can cause an increase or decrease in serum phenytoin levels.
Barbiturates can reduce plasma levels of phenothiazines and phenothiazines can reduce levels of barbiturates.
Plasma levels of propranolol (beta-adrenergic receptor blocking drug) and phenothiazines are both increased when the two drugs are administered simultaneously.
Aluminum salt antacids can inhibit the absorption of phenothiazines.
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.
Amitriptyline hydrochloride
Concomitant administration of tricyclic antidepressant drugs and monoamine oxidase inhibitors (MAOIs) has been reported to cause reactions similar to atropine poisoning resulting in hyperpyretic seizures, convulsions and death. These effects have usually occurred following overdose or parenteral administration of either drug. Non-fatal hyperpyrexia, hypertension, tachycardia, confusion and convulsions have been reported following oral administration of the two therapeutic doses.
Concomitant administration of cimetidine and tricyclic antidepressants may increase the plasma concentrations of the latter. Severe anticholinergic symptoms have been associated with elevated serum tricyclic antidepressant levels. When treatment with this component was introduced in patients already taking cimetidine, higher than expected steady-state serum concentrations were observed. Conversely, lower steady-state serum concentrations of tricyclic antidepressants have been reported upon discontinuation of cimetidine treatment. Dose adjustment may be required.
The concomitant use of amitriptyline and anticholinergics or sympathomimetic amines, including epinephrine combined with local anesthetics, may increase the activity of amitriptyline or sympathomimetic amine. Close patient monitoring and careful dosage adjustment are required. The pronounced pressure and cardiac effects of sympathomimetics can be fatal.
The combination with high doses of etcorvinol should be used with caution as transient delirium has been reported in patients treated with this combination of drugs.
The concomitant treatment with amitriptyline and electroshock therapy can increase the dangers of this treatment which must be limited only to patients for whom it is absolutely indispensable.
The combination of amitriptyline and guanethidine may antagonize the antihypertensive effect of guanethidine. Tricyclic drugs block the uptake of adrenergic neurons of guanethidine and compounds with similar effect. Dosage adjustment of guanethidine or tricyclic drug will be required. Concomitant administration of Mutabon tablets and guanethidine or compounds with similar effect is not recommended. Where possible, a check for hypertension is required before starting treatment with antidepressant drugs and blood pressure should be checked weekly during the first month of such treatment.
Concomitant use of amitriptyline, anticholinergics or antihistamines may potentiate their anticholinergic effects. The increased anticholinergic activity can cause paralytic ileus or blurred vision and may affect intraocular pressure in patients with glaucoma.
Concomitant use of amitriptyline and central nervous system (CNS) depressant agents, such as alcohol, barbiturates, sedatives or opioid analgesics, may potentiate CNS depressant effects, including respiratory depression.
The concomitant intake of amitriptyline and diazepam results in an increase in the half-life and constant plasma levels of amitriptyline. This interaction varies in a very important way between the various subjects.
Concomitant use of amitriptyline and reserpine may antagonize the effects of reserpine.
Concomitant use of amitriptyline and anticonvulsants may reduce effective control of seizures in epileptic patients.
It appears that tricyclic agents may act as weak inducers of drug metabolism.
The anticholinergic effects of tricyclic antidepressants can slow gastrointestinal motility in such a way that it interferes with the absorption of various other drugs. In addition, delayed transit from the stomach can result in the inactivation of drugs such as levodopa and phenylbutazone.
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 small or quite large (8 times the increase in plasma AUC of the tricyclic antidepressant). In a study of 45 patients elderly with dementia and treated with perphenazine, the 5 patients prospectively identified as "poor metabolisers" of P450 2D6 had significantly greater side effects during the first 10 days of treatment than the 40 "heavy metabolisers"; after this period, the groups tended to converge Perspective phenotyping of patients The elderly before neuroleptic treatment allows to identify subjects at risk of adverse events.
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 administered together with another drug known to be a P450 2D6 inhibitor (see also Clinical Pharmacology).
INTERACTIONS BETWEEN DRUG AND LABORATORY TESTS: Urinary metabolites of phenothiazines can darken urine, giving false positive results for urobilinogen, amylase, uroporphyrins, porphobilinogens and 5-hydroxy-indolacetic acid.
Patients receiving therapeutic doses of phenothiazines may present with electrocardiographic changes, such as a lengthening of the QT interval accompanied by a widening, smoothing and incision of the T wave. At higher doses, a lowering and inversion of the wave may occur. T.
The main electrocardiographic alteration observed with amitriptyline is "flattening or" inversion of T waves. QRS complex enlargement, QT interval prolongation, as well as abnormal ST segments and T waves are observed following overdose.
Tricyclic antidepressants can lower the seizure threshold and produce abnormal electroencephalographic pictures.
Perphenazine can increase plasma protein-bound iodine levels without causing clinical thyrotoxicosis.
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.
04.6 Pregnancy and breastfeeding -
Mutabon Mite tablets should be used during established or suspected pregnancy and during lactation only if the potential benefits to the mother justify the potential risk to the fetus or baby.
Pregnancy
Infants exposed to conventional or atypical antipsychotics including Mutabon Mite 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.Therefore infants should be carefully monitored.
Feeding time
Perphenazine is rapidly excreted in breast milk and may cause side effects in the breastfed infant. Amitriptyline has been measured in human milk. The safe use of Mutabon Mite during breastfeeding has not been established; therefore, in administering the drug to nursing mothers it is necessary to evaluate the possible benefits with respect to the possible risks for the mother and the child.
04.7 Effects on ability to drive and use machines -
During therapy with Mutabon Mite, people who use machines or who drive vehicles should use caution, as the product may induce changes in the reaction time.
04.8 Undesirable effects -
The side effects of Mutabon Mite are the same as its components, perphenazine and amitriptyline hydrochloride. No effects have been reported due solely to their combination in Mutabon Mite.
Perfenazine
Not all adverse events listed below have been reported with the use of perphenazine; 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).
Nervous system disorders
Extrapyramidal reactions: opisthotonus, trismus, torticollis, spastic torticollis, pain and numbness in the 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 develop such symptoms. Extrapyramidal symptoms can usually be controlled with concomitant use of anti-parkinsonian agents, such as benzatropine mesylate. , and / or by reducing the dosage. 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 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 disorders, including cardiovascular effects (irregular pulse, tachycardia). There is no specific treatment; administration of the neuroleptic drug should be discontinued immediately and appropriate intensive supportive treatment initiated. If treatment with antipsychotic drugs is required for the patient after recovery from NMS, cautionary 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.
General disorders and administration site conditions
Urticaria, erythema, eczema, exfoliative dermatitis, pruritus, photosensitivity, asthma, fever, anaphylactoid reactions and laryngeal edema may 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.
Endocrine pathologies
Lactation, galactorrhea, moderate breast enlargement in women and gynecomastia in men after high doses, menstrual cycle disturbances, amenorrhea, libido changes, ejaculation inhibition, false positive pregnancy tests, hyperglycemia, hypoglycemia, glucosuria, inappropriate secretion syndrome of the antidiuretic hormone (ADH).
Cardiovascular pathologies
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).
Disorders of the blood and lymphatic system
Agranulocytosis, eosinophilia, leukopenia, haemolytic anemia, thrombocytopenic purpura and pancytopenia. Most cases of agranulocytosis occurred between the fourth and tenth week of therapy.
Liver disorders
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).
Other effects
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.
Amitriptyline hydrochloride
Although the activation of latent schizophrenia has been reported with antidepressant drugs, including amitriptyline hydrochloride, it can be avoided in some cases with Mutabon Mite, thanks to the antipsychotic effect of perphenazine. Some examples of epileptic seizures have been reported. in chronic schizophrenic patients during treatment with amitriptyline hydrochloride.
When using a tricyclic antidepressant, the following adverse reactions should be considered:
General disorders and administration site conditions
Rash, itching, hives, photosensitization, edema of the face and tongue.
Anticholinergic effects
Dry mouth, blurred vision, accommodation disorders, constipation, paralytic ileus, urinary retention, dilation of the urinary tract.
Cardiovascular pathologies
Hypotension, hypertension, tachycardia, palpitations, myocardial infarction, arrhythmias, heart block, stroke.
Nervous system disorders
Confusional states, disturbances in concentration, disorientation, delusions, hallucinations, excitement, nervousness, anxiety, agitation, insomnia, nightmares, deafness, tingling and paraesthesia in the extremities, peripheral neuropathy, lack of coordination, ataxia, tremors, convulsions, alterations in the " EEG, extrapyramidal symptoms, tinnitus.
Rare: suicidal ideation / behavior (see section 4.4 Special warnings and precautions for use).
Endocrine pathologies
Swelling of the testicles and gynecomastia in the male, breast enlargement and galactorrhea in the female, increased or decreased libido, raised and lowered blood sugar levels, syndrome of inappropriate ADH secretion.
Gastrointestinal disorders
Nausea, epigastric disorders, heartburn, vomiting, anorexia, stomatitis, taste disturbance, diarrhea, jaundice, parotid swelling, dark tongue. Hepatitis (including impaired liver function and jaundice) has occurred rarely.
Disorders of the blood and lymphatic system
Bone marrow depression, including agranulocytosis, leukopenia, eosinophilia, purpura, thrombocytopenia.
Effects related to the therapeutic class
Epidemiological studies, mainly conducted in patients aged 50 or over, show an increased risk of bone fractures in patients being treated with SSRIs and TCAs. The mechanism leading to this increased risk is unknown.
Diagnostic tests
QT interval prolongation on ECG (common rate).
Others
Dizziness, weakness, fatigue, headache, weight gain or loss, increased sweating, urination frequency, mydriasis, somnolence, alopecia.
Withdrawal Symptoms: Abrupt discontinuation of treatment after prolonged administration may produce nausea, headache and malaise. These are not indicative of addiction.
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 www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
With this category of drugs, overdose can result in patient death. The ingestion of multiple drugs (including alcohol) is common in deliberate overdose. As the treatment of overdose is complex and changing, it is recommended that the physician contact a poison control center for up-to-date information. The signs and symptoms of overdose. toxicities develop rapidly after an overdose; hospital screening is therefore required as soon as possible.
Symptoms :
Overdose of Mutabon Mite can result in any of the adverse events listed for perphenazine or amitriptyline hydrochloride.
Overdose of perphenazine usually produces extrapyramidal symptoms, such as dyskinesia and dystonia, as described among adverse events; however, they may be masked by the anticholinergic effects of amitriptyline. Other symptoms may include stupor or coma; children may have seizures.
Clinical manifestations of tricyclic antidepressant overdose include: cardiac dysrhythmias, severe hypotension, seizures and CNS depression, including coma. Electrocardiographic changes, particularly in the QRS axis or depth, are clinically significant indicators of the toxicity of tricyclic antidepressants. Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, overactive reflexes, stupor, sleepiness, muscle stiffness, vomiting, hypothermia, hyperpyrexia or any of the symptoms listed as adverse events.
Treatment :
Generic: Take an ECG and begin cardiac monitoring immediately. Maintain a patent airway for the patient, establish an intravenous line and initiate gastric disinfection. At least 6 hours of cardiac monitoring and observation for signs of the CNS or respiratory depression, hypotension, cardiac dysrhythmias and / or conduction block and seizures are required. Should signs of toxicity occur within this time period, prolongation of monitoring is required. There have been reports of patients dying from fatal dysrhythmias occurring long after overdose; these patients had clinical evidence of significant poisoning prior to death and most of them had undergone inadequate gastrointestinal disinfection. Monitoring of plasma drug levels should not guide patient management. There are no specific antidotes.
Gastrointestinal Disinfection: All patients suspected of overdose with tricyclic antidepressants should undergo gastrointestinal disinfection. It should include large volume gastric lavage followed by the administration of activated charcoal. In the event of an altered state of consciousness, ensure that the airways are clear before lavender. Emesis is contraindicated due to the possibility of convulsions, central nervous system depression, or a dystonic reaction of the head or neck with subsequent aspiration.
Cardiovascular system: A maximum duration of the QRS trace of the extremities? 0.10 seconds may be the best indication of the severity of the overdose. Intravenous sodium bicarbonate should be administered to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, it is possible resort to hyperventilation. The concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. PH values> 7.60 or pCO2 lidocaine, bretylium or phenytoin are not desirable. Type 1A and 1C antiarrhythmic agents are generally contraindicated. (for example, quinidine, disopyramide and procainamide).
In rare cases, hemoperfusion may be beneficial in refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, transfusions and forced diuresis have generally been reported as ineffective in tricyclic antidepressant poisoning.
Central nervous system (CNS): In patients with CNS depression, early intubation is advised due to the potential for rapid deterioration of the condition. Seizures can be controlled with benzodiazepines or, if these are ineffective, with other anticonvulsants (eg, phenobarbital, phenytoin) Physostigmine is not recommended except for the treatment of life-threatening symptoms that have not reacted to other therapies, and only after consultation with a poison control center.
Psychiatric Follow-up: Because overdose is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric support will be appropriate.
Pediatric population: The principles of managing overdose in children and adults are similar. It is strongly recommended that the physician contact the local poison center for specific treatment in children. Although Mutabon Mite is not indicated for children, accidental ingestion can occur.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Antidepressants in combination with psycholeptics, ATC code: N06CA01.
Mutabon Mite combines the anxiolytic, antipsychotic and antiemetic properties of perphenazine with the antidepressant activity of amitriptyline.
Perphenazine carries out actions at all levels of the central nervous system, particularly at the level of the hypothalamus and demonstrates anxiolytic, antipsychotic and antiemetic properties.
Amitriptyline hydrochloride has 3 major pharmacological actions: sedation, anticholinergic activity, and blocking the re-uptake of sympathomimetic amines released into the synaptic space.
The latter action is considered most relevant in the relief of depression, although the precise mechanism of clinical antidepressant activity is not known.
05.2 "Pharmacokinetic properties -
Perfenazine:
Absorption
Phenothiazines are readily absorbed from the gastrointestinal tract and parenteral sites.
60% to 70% of an orally administered dose is rapidly removed from the portal circulation and the enterohepatic circulation is very active.
This results in less unchanged drug in the circulation, compared to what happens after parenteral administration.
Distribution
After absorption, phenothiazines are rapidly distributed into tissues. The drugs are highly lipophilic and highly bound to membranes and proteins.
High concentrations of unchanged drug are found in the brain, while metabolites predominate in the lungs, liver, kidney and spleen.
Biotransformation
Phenothiazines are mainly metabolised in the liver, through mechanisms of oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid. The pharmacokinetics of perphenazine varies with the hydroxylation of debrisoquine which is mediated by cytochrome P450 2D6 (CYP 2D6) and is therefore prone to polymorphism - that is, 7-10% of the Caucasian population and a low percentage of Asians have little or no activity. and are referred to as “poor metabolisers.” CYP 2D6 “poor metabolisers” metabolize perphenazine more slowly and will have higher concentrations of this substance than normal or “strong” metabolisers.
Elimination from plasma may be more rapid than from high-lipid and highly bound sites, particularly in the central nervous system.
Amitriptyline hydrochloride:
Absorption
Following oral administration, tricyclic antidepressants are absorbed relatively rapidly with peak plasma levels observed within 2-4 hours.
The amount of unchanged drug available is affected by hepatic "first-pass" metabolism.
Steady-state plasma levels are generally reached within 7-21 days and remain relatively constant thereafter.
The elimination half-life of amitriptyline after a single oral dose ranges from 10 to 43 hours. At usual therapeutic concentrations, plasma concentrations of tricyclic antidepressants are low.
Biotransformation
Amitriptyline, a tertiary amine is metabolized to nortriptyline, a secondary amine, its derivative. The N-demethylation process is mediated by cytochrome P450 3A4, -2C9, -2D6 and an unidentified enzyme. Both amitriptyline and nortriptyline undergo CYP 2D6-mediated hydroxylation. Subjects with reduced cytochrome P450 2D6 activity ("poor metabolisers") may have higher than expected plasma concentrations of amitriptyline.
Subsequent oxidation, followed by glucuronidation, leads to the formation of metabolites that are less pharmacologically active.
Elimination
The active ingredients and their metabolites are excreted in the urine and via the bile, in the faeces.
05.3 Preclinical safety data -
Experimental animals tolerate, without showing toxic symptoms, doses of Mutabon Mite much higher than those recommended in humans, even for 2-3 months of administration.
Perphenazine, like most neuroleptics, in low doses reduces the exploratory behavior of the animals, without eliminating their discriminatory capacities and inhibits nutrition.
At high doses it causes the characteristic catatonic immobility of the animals, which maintain the position in which they are placed, even if uncomfortable, with an increase in muscle tone and indifference to most of the stimuli.
Even at very high doses, perphenazine does not cause coma and the lethal dose is extremely high.
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.
Amitriptyline hydrochloride causes cerebral intoxication with antimuscarinic but also cardiotoxic effects.
The LD50 is 800-900 mg / kg in rats and 322 mg / kg in rabbits. Rat and rabbit tolerated, respectively, 6-18 mg / kg and 10 mg / kg for 5 days a week, for 6 and 4 weeks both in behavioral and laboratory terms.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Maize starch, Lactose, Magnesium stearate, Pregelatinised starch, Opadry white (Hypromellose E-464, Macrogol, Titanium dioxide E-171, Hydroxypropylcellulose E-463).
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
3 years.
06.4 Special precautions for storage -
No particular precautions for storage.
06.5 Nature of the immediate packaging and contents of the package -
Carton containing blister packs of 30 film-coated tablets of 2 mg + 10 mg.
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Neopharmed Gentili S.r.l.
Via San Giuseppe Cottolengo, 15
20143 Milan
08.0 MARKETING AUTHORIZATION NUMBER -
Mutabon Mite 2 mg + 10 mg film-coated tablets
30 tablets
AIC: 021460074
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: December 1984
Date of most recent renewal: 01 June 2010
10.0 DATE OF REVISION OF THE TEXT -
July 2016.
