Active ingredients: Amitriptyline
ADEPRIL 10 mg coated tablets
ADEPRIL25 mg coated tablets
Why is Adepril used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY: Antidepressants. ADEPRIL contains amitriptyline, an antidepressant belonging to the class of tricyclics.
THERAPEUTIC INDICATIONS: Endogenous depression - Depressive phase of manic-depressive psychosis - Reactive depression - Masked depression - Neurotic depression - Depression in the course of schizophrenic psychosis - Involutive depression - Severe depression in the course of neurological diseases or other organic affections.
Contraindications When Adepril should not be used
Hypersensitivity to the active substance or to any of the excipients. Glaucoma. Prostatic hypertrophy, pyloric stenosis and other stenosing affections of the gastrointestinal and genitourinary system. Liver diseases. Heart failure. Disturbances of myocardial rhythm and conduction. Post-infarct recovery period. Known or presumed pregnancy. Breastfeeding.
Precautions for use What you need to know before taking Adepril
Use in children and adolescents under 18 years.
Tricyclic antidepressants should not be used to treat children and adolescents under the age of 18. Studies conducted in depression in children of this age group have not demonstrated efficacy for this class of drugs. Studies with other antidepressants have highlighted the risk of suicide, self-harm and hostility related to these drugs. This risk may also occur with these drugs. tricyclic antidepressants.
Furthermore, tricyclic antidepressants are associated with a risk of adverse cardiovascular events in all age groups. It should be borne in mind that there are no long-term safety data available in children and adolescents regarding growth, maturation and cognitive and behavioral development.
Taking into account the pharmacological properties of the preparation, extreme caution requires its use in patients with cardiovascular diseases in which tachycardia, rhythm and conduction disturbances, myocardial insufficiency may occur. In these subjects it is therefore necessary to carry out periodic electrocardiographic checks. Close clinical surveillance. and instrumental is also required in the elderly, in hyperthyroid patients or in treatment with thyroid hormones or in those who take the antidepressant drug at high doses.
Tricyclic antidepressants can lower the seizure threshold. Their use, therefore, in epileptics and in patients with organic brain diseases or with predisposition to convulsions is allowed only under close medical supervision.
When amitriptyline is used to improve the depressive state during Parkinson's disease, particular attention requires the association with specific drugs (L-dopa and others). Due to its evident anticholinergic effects, the preparation must be administered with care in the elderly, and in all those patients (such as those with ocular, gastro-enteric affections, etc.), in which an excessive parasympatholytic activity can be harmful.
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 clinical experience in general that the risk of suicide may increase in the early stages of improvement.
Other psychiatric conditions for which ADEPRIL 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.
Since the drug can cause orthostatic hypotension, changes in blood sugar, disturbances of hematopoiesis, liver and kidney, it is advisable to carry out periodic checks of blood pressure, glycemia, blood count and liver and kidney function with special regard to hypertensive patients. to diabetics, to nephropaths and in subjects with current or previous affections of the haematopoietic system. In the event of fever, angina and other flu symptoms it is essential to check the blood count in order to reveal early the presence of agranulocytosis which has occasionally been reported during therapy with tricyclic antidepressants.
With the use of amitriptyline, allergic or photosensitization reactions may occur; cross-hypersensitivity between the various tricyclic compounds with antidepressant action is possible.
It should also be noted that the preparation can cause undesirable neuropsychic effects such as the appearance of hypomanic reactions and the activation of latent schizophrenic pictures; this must be taken into account, among other things, in the definition of the dosage scheme which, although strictly individual, must be in general the one that allows the assumption of the minimum effective dose.
Extreme caution requires the use of antidepressants in outpatient treatment since these drugs can eliminate psychomotor inhibition before having an effect on other symptoms.
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction (See INTERACTIONS).
Interactions Which drugs or foods can change the effect of Adepril
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
- Monoamine oxidase inhibitors (MAOIs): tricyclic antidepressants should not be combined with MAOIs due to the possibility of serious side effects (hyperthermia, convulsions, coma, death); if it is essential to replace an MAOI with a tricyclic one, an interval of at least two weeks must be allowed.
- Hypotensive drugs: tricyclic antidepressants block the synaptic recovery of guanethidine and other hypotensive drugs with a similar mechanism of action, reducing their therapeutic activity.
- Sympathomimetic drugs: in general, sympathomimetic drugs should not be administered during treatment, the effects of which, especially those on the heart and circulation, can be significantly accentuated. The association between amitriptyline and L-DOPA facilitates the onset of hypotension and cardiac arrhythmias. The patient must also avoid the use of nasal decongestants and products used in the treatment of asthma and pollinosis containing sympathomimetic substances.
- Anticholinergic drugs: particular attention requires the use of parasympatholytic drugs, especially those used in the treatment of Parkinson's disease.
- Substances with depressive action on the central nervous system: tricyclic antidepressants can accentuate the action of such drugs as hypnotics, sedatives, anxiolytics and anesthetics. Antidepressant treatment should be discontinued as early as possible by the clinical situation before elective surgery It is recommended not to drink alcoholic beverages during treatment.
- Other drugs: tricyclic drugs, due to their anticholinergic action, can prolong the gastric emptying time; some substances, such as L-dopa and phenylbutazone, can be retained for a period long enough for them to be inactivated in the stomach. Barbiturates, due to their inductive effect on the microsomal systems of the liver, can stimulate drug metabolism while various phenothiazines, haloperidol and cimetidine can delay its elimination by increasing its blood concentration. The binding of amitriptyline to plasma proteins can be reduced by competition from phenytoin, phenylbutazone, aspirin, scopolamine and phenothiazines.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Not to be used in case of confirmed or presumed pregnancy and during lactation (see CONTRAINDICATIONS).
Effects on ability to drive and use machines
The product can induce vision disturbances, attenuate the alertness and interfere with the normal degree of alertness; this must be taken into account by those who drive motor vehicles or other machinery or carry out dangerous work.
Important information about some of the ingredients of ADEPRIL
ADEPRIL contains sucrose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Adepril: Posology
The daily dose is strictly individual; it will be established from time to time starting from lower quantities that can be progressively increased on the basis of clinical response and tolerability.
Lower doses are generally recommended in the elderly and outpatients.
The tablets should be swallowed whole without chewing.
As an example, the following diagram is provided:
Hospital treatment
Start with 100 mg per day in divided doses and progressively increase to 200-300 mg per day over a period of approximately 15 days.
Outpatient treatment
Adults: start with 75 mg / day in divided doses and increase to 150 mg / day. It is not recommended to exceed 200 mg / day.
Elderly subjects: 30-40 mg / day. It is generally not necessary to exceed 100 mg per day.
Once the clinical effect has been reached, the daily dosage should be gradually reduced until the individual maintenance dose is established, which is mostly between 50 and 150 mg per day.
In the treatment of elderly patients, the posology must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Overdose What to do if you have taken too much Adepril
In case of accidental ingestion / intake of an excessive dose of ADEPRIL, notify your doctor immediately or go to the nearest hospital.
Overdose with amitriptyline hydrochloride can manifest itself with: dry mouth, miosis, tachycardia and arrhythmia, hypotension, respiratory depression, urinary retention and, in cases of massive overdose, coma, convulsions and hallucinations.
Treatment is symptomatic. Gastric lavage can be useful as the anticholinergic properties of amitriptyline slow its absorption.
It is possible to administer pyridostigmine, by slow intravenous infusion, with continuous electrocardiographic monitoring, in order to counteract cardiac effects; this treatment can be repeated, if necessary, at half-hour intervals. Hypotension should be treated with metaraminol. Seizures can be controlled with diazepam or phenobarbital. If you have any questions about the use of ADEPRIL, ask your doctor or pharmacist.
Side Effects What are the side effects of Adepril
Like all medicines, ADEPRIL can cause side effects, although not everybody gets them.
The following side effects have been reported with varying intensity and frequency during amitriptyline therapy:
- Anticholinergic effects: headache, dry mouth, indistinct vision, mydriasis, ocular hypertonus, cycloplegia, tachycardia, constipation, dysuria, urinary retention.
- Cardio-vascular effects: orthostatic hypotension, hypertension, rhythm and conduction disturbances, cardiac arrest, flattening of the T wave and other modifications of the electrocardiogram (ECG) trace; heart failure; heart attack; stroke.
- Neurological effects: changes in the electroencephalogram (EEG); dizziness, tremors, ataxia, dysarthria or other extrapyramidal signs, convulsions, paraesthesia in the extremities and peripheral neuropathies.
- Psychological effects: sedation, drowsiness, asthenia or anxiety, agitation, confusional states with illusions and hallucinations especially in the elderly, euphoria, hypomanic reactions, turning towards the manic phase in subjects with bipolar psychosis, exacerbation of psychotic states. Psychotic manifestations can be treated by reducing the dosage or by combining a phenothiazine with antidepressant therapy. Rarely, suicidal ideation / behavior may occur (see Precautions for use).
- Gastro-intestinal reactions: anorexia, nausea, vomiting, diarrhea, stomatitis, sublingual and parotid adenitis; jaundice and modification of hepatic function indices (increase in transaminases, alkaline phosphatase etc.).
- Endocrine effects: gynecomastia, galactorrhea, libido changes, changes in blood glucose, weight gain.
- Haematological reactions: eosinophilia, bone marrow depression with agranulocytosis, thrombocytopenia and purpura.
- Allergic reactions: itching, hives, erythema, petechiae, generalized or localized edema on the face and tongue. The onset of major side effects always requires discontinuation of treatment; minor side effects, such as anticholinergic ones, may lessen during therapy or be controlled with appropriate dosage adjustments.
An increased risk of bone fractures has been observed in patients using this type of medicine.
Compliance with the instructions in the package leaflet reduces the risk of side effects, although not everybody gets them.
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 the expiry date indicated on the package.
The expiry date refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.
Other Information
ADEPRIL 10 mg coated tablets
Each coated tablet contains:
Active ingredient: 11.4 mg amitriptyline hydrochloride (equivalent to 10 mg amitriptyline). Excipients: Tribasic calcium phosphate; Microcrystalline cellulose; Cornstarch; Povidone; Magnesium stearate; Rosin; Sandracca gum; Shellac; Turpentine; Sodium dioctyl sulfosuccinate; Talc; Light magnesium carbonate; Titanium dioxide (E 171); Kaolin; Jelly; Sucrose.
ADEPRIL 25 mg coated tablets
Each coated tablet contains:
Active ingredient: Amitriptyline hydrochloride 28.5 mg (equivalent to Amitriptyline 25 mg).
Excipients: Tribasic calcium phosphate; Microcrystalline cellulose; Cornstarch; Povidone; Magnesium stearate; Rosin; Sandracca gum; Shellac; Turpentine; Sodium dioctyl sulfosuccinate; Talc; Light magnesium carbonate; Titanium dioxide (E 171); Kaolin; Jelly; Sucrose. PHARMACEUTICAL FORM AND CONTENTS 10 mg coated tablets - Box of 30 coated tablets in blister packs.
Coated tablets 25 mg - Box of 30 coated tablets in blister packs.
ADEPRIL contains amitriptyline, an antidepressant belonging to the class of tricyclics.
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
ADEPRIL COATED TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Coated tablets 10 mg - Active ingredient: 11.4 mg Amitriptyline hydrochloride (equivalent to 10 mg Amitriptyline). Excipients: sucrose
Coated tablets 25 mg - Active ingredient: Amitriptyline hydrochloride 28.5 mg (equivalent to Amitriptyline 25 mg). Excipients: sucrose
For the full list of excipients see section 6.1
03.0 PHARMACEUTICAL FORM
Coated tablets
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Endogenous depression - Depressive phase of manic-depressive psychosis - Reactive depression - Masked depression - Neurotic depression - Depression in the course of schizophrenic psychosis - Involutive depression - Severe depression in the course of neurological diseases or other organic affections.
04.2 Posology and method of administration
Adults and children over 12 years of age.
The daily dose is strictly individual; it will be established from time to time starting from lower quantities that can be progressively increased on the basis of clinical response and tolerability.
Lower doses are usually recommended in the elderly, young people and outpatients.
The tablets should be swallowed whole without chewing
As an example, the following diagram is provided:
Hospital treatment
Start with 100 mg per day in divided doses and progressively increase to 200-300 mg per day over a period of approximately 15 days.
Outpatient treatment
Adults: start with 75 mg / day in divided doses and increase up to 150 mg / day. It is not recommended to exceed 200 mg / day.
Young and old subjects: 30-40 mg / day. It is generally not necessary to exceed 100 mg per day.
Once the clinical effect has been reached, the daily dosage should be gradually reduced until the individual maintenance dose is established, which is mostly between 50 and 150 mg per day. In the treatment of elderly patients, the dosage should be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Glaucoma. Prostatic hypertrophy, pyloric stenosis and other stenosing affections of the gastro-enteric and genito-urinary system. Liver diseases. Heart failure. Disturbances of rhythm and myocardial conduction. Post-infarct recovery period. Subjects under the age of 12 years.
04.4 Special warnings and appropriate precautions for use
Use in children and adolescents under 18 years.
Tricyclic antidepressants should not be used to treat children and adolescents under the age of 18. Studies conducted in depression in children of this age group have not demonstrated efficacy for this class of drugs. Studies with other antidepressants have highlighted the risk of suicide, self-harm and hostility related to these drugs. This risk may also occur with these drugs. tricyclic antidepressants.
Furthermore, tricyclic antidepressants are associated with a risk of adverse cardiovascular events in all age groups. It should be borne in mind that there are no long-term safety data available in children and adolescents regarding growth, maturation and cognitive and behavioral development.
Taking into account the pharmacological properties of the preparation, extreme caution requires its use in patients with cardio-vascular diseases in which tachycardia, rhythm and conduction disturbances, myocardial insufficiency may occur.
In these subjects it is therefore necessary to carry out periodic electrocardiographic checks. Close clinical and instrumental surveillance is also required in the elderly, in hyperthyroid patients or in patients treated with thyroid hormones or in those taking the antidepressant drug in high doses.
Tricyclic antidepressants can lower the seizure threshold. Their use, therefore, in epileptics and in patients with organic brain diseases or with predisposition to convulsions is allowed only under close medical supervision.
When amitriptyline is used to improve the depressive state during Parkinson's disease, particular attention requires the association with specific drugs (L-dopa and others). Due to its evident anticholinergic effects, the preparation must be administered with care in the elderly and in all those patients (such as those with ocular, gastrointestinal affections, etc.) in which an excessive parasympatholytic activity can be harmful.
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 Adepril 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.
Since the drug can cause orthostatic hypotension, changes in blood sugar, disturbances of hematopoiesis, liver and kidney, it is advisable to carry out periodic checks of blood pressure, glycemia, blood count and liver and kidney function with special regard to hypertensive patients. to diabetics, to nephropaths and in subjects with current or previous affections of the haematopoietic system. In the event of fever, angina and other flu symptoms it is essential to check the blood count in order to reveal early the presence of agranulocytosis which has occasionally been reported during therapy with tricyclic antidepressants.
With the use of amitriptyline, allergic or photosensitization reactions may occur; cross hypersensitivity is possible between the various tricyclic compounds with antidepressant action. It should also be noted that the preparation can cause undesirable neuropsychic effects such as the onset of hypomanic reactions and the activation of latent schizophrenic pictures; this must be kept in mind, among other things, in the definition of the dosage scheme which, although strictly individual, must in general be the one that allows the assumption of the minimum effective dose.
Extreme caution requires the use of antidepressants in outpatient treatment since these drugs can eliminate psychomotor inhibition before having an effect on other symptoms.
Important information about some of the ingredients of Adepril
Adepril contains sucrose: patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency, should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Monoamine oxidase inhibitors: tricyclic antidepressants must not be associated with MAOIs due to the possibility of serious side effects (hyperthermia, convulsions, coma, death); if it is necessary to replace an MAOI with a tricyclic one, an interval of at least two weeks must be allowed.
Hypotensive drugs: tricyclic antidepressants block the synaptic recovery of guanethidine and other hypotensive drugs with a similar mechanism of action, reducing their therapeutic activity.
Sympathomimetic drugs: in general, sympathomimetic drugs should not be administered during treatment, the effects of which, especially those on the heart and circulation, may be significantly accentuated. The association between amitriptyline and L-DOPA facilitates the onset of hypotension and cardiac arrhythmias. The patient must also avoid the use of nasal decongestants and products used in the treatment of asthma and pollinosis containing sympathomimetic substances.
Anticholinergic drugs: particular attention requires the use of parasympatholytic drugs, especially those used in the treatment of Parkinson's disease.
CNS depressant substances: tricyclic antidepressants can accentuate the action of such drugs as hypnotics, sedatives, anxiolytics and anesthetics. Antidepressant treatment should be discontinued as early as the clinical situation allows before an elective surgical interval.
Other drugs: tricyclic drugs, due to their anticholinergic action, can prolong the gastric emptying time; some substances, such as L-dopa and phenylbutazone, can be retained for a period sufficient for their inactivation in the stomach.
Barbiturates, due to their inductive effect on the microsomal systems of the liver, can stimulate drug metabolism while various phenothiazines, haloperidol and cimetidine can delay its elimination by increasing its blood concentration. The binding of amitriptyline to plasma proteins can be reduced by competition from phenytoin, phenylbutazone, aspirin, scopolamine and phenothiazines.
It is recommended not to drink alcoholic beverages during treatment.
04.6 Pregnancy and breastfeeding
Not to be used in case of confirmed or presumed pregnancy and during breastfeeding.
04.7 Effects on ability to drive and use machines
The product can induce vision disturbances, attenuate the alertness and interfere with the normal degree of alertness; those who drive motor vehicles or other machinery or carry out dangerous work must be warned of this.
04.8 Undesirable effects
The following side effects have been reported with varying intensity and frequency during amitriptyline therapy:
anticholinergic effects: headache, dry mouth, indistinct vision, mydriasis, ocular hypertonus, cycloplegia, tachycardia, constipation, dysuria, urinary retention;
cardio-vascular effects: orthostatic hypotension, hypertension, rhythm and conduction disturbances, cardiac arrest, flattening of the T wave and other anomalies of the ECG trace, heart failure, myocardial infarction, stroke;
neurological effects: EEG changes, dizziness, tremors, ataxia, dysarthria or other extrapyramidal signs, convulsions, paraesthesia in the extremities and peripheral neuropathies;
psychological effects: sedation, drowsiness, asthenia or anxiety, agitation, confusional states with illusions and hallucinations especially in the elderly, euphoria, hypomanic reactions, turning towards the manic phase in subjects with bipolar psychosis, exacerbation of psychotic states. Psychotic manifestations can be treated by reducing the dosage or by combining a phenothiazine with antidepressant therapy. Rarely, suicidal ideation / behavior may occur (see section 4.4 Special warnings and special precautions for use).
gastro-intestinal reactions: anorexia, nausea, vomiting, diarrhea, stomatitis, sublingual and parathyroid adenitis, jaundice and modification of liver function indices (increase in transaminases, alkaline phosphatase, etc.);
endocrine effects: gynecomastia, galactorea, changes in libido, changes in glycemic rate, weight gain;
haematological reactions: eosinophilia, bone marrow depression with agranulocytosis, thrombocytopenia and purpura;
allergic reactions: itching, hives, erythema, petechiae, generalized or localized edema on the face and tongue.
The appearance of important side effects always requires the interruption of treatment; minor side effects, such as anticholinergic ones, can be attenuated during therapy or be controlled with appropriate dosage adjustments.
Epidemiological studies, mainly conducted on patients aged 50 or over, show an increased risk of bone fractures in patients using SSRIs and TCAs. The mechanism leading to this risk is unknown.
04.9 Overdose
Overdose of amitriptyline hydrochloride can manifest itself with: dry mouth, miosis, tachycardia and arrhythmia, hypotension, respiratory depression, urinary retention and in cases of massive overdose, coma, convulsions and hallucinations.
Treatment is symptomatic. Gastric lavage can be useful as the anticholinergic properties of amitriptyline slow its absorption.
It is possible to administer pyridostigmine, by slow intravenous infusion, with continuous electrocardiographic monitoring, in order to counteract cardiac effects; this treatment can be repeated, if necessary, at half-hour intervals. Hypotension should be treated with metaraminol. Seizures can be controlled with diazepam or phenobarbital.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Medicinal product category: antidepressants, non-selective monoamine reuptake inhibitors.
ATC code: N06AA09
Amitriptyline is an antidepressant drug, belonging to the group of tricyclics, with a remarkable tranquilizing activity. Pharmacodynamic studies, aimed at demonstrating the antidepressant action of amitriptyline and verifying its effects on different systems and apparatuses, have allowed us to highlight a pharmacological profile of the drug characterized by an evident anticholinergic activity, by an adrenolytic effect through the blocking of delta 1 receptors, by an "action that inhibits the reuptake of various neurotransmitters at the presynaptic level and by an" efficacy that, against imipramine compounds, it is more marked in the sedative component. From the experimental point of view, there is evidence that "amitriptyline, like the other tricyclic compounds, can exert an" antagonistic action on sedation induced by tetrabenazine, exert an "antireserpinic activity, enhance the effects of sympathomimetic amines, influence the autonomic nervous system and the structures innervated by them and determine effects on behavior, motor activity and electroencephalogram.
Amitriptyline is involved in interaction processes with different substances, some of which are of considerable clinical interest, such as the enhancement of the toxic effects of alcohol and interactions with monoamine oxidase inhibitors, with biogenic amines, with antiparkinsonian agents, antipsychotic drugs and compounds with antimuscarinic action. The antidepressant mechanism of action of amitriptyline has not yet been clarified; however, it appears to involve the concentration of brain amines (noradrenaline, serotonin) in the synaptic spaces, rather than the inhibition of monoamine oxidase.
05.2 Pharmacokinetic properties
Amitriptyline is well absorbed orally and spreads rapidly in tissues and organs, binding in a high percentage to plasma proteins and tissue constituents; in laboratory animals the highest concentrations are found in the adrenal, pituitary and lungs and the average concentrations in the brain, liver, spleen and kidneys.
The mean half-life of a single dose is approximately 16 hours.
The most important metabolic pathways of amitriptyline, like the rest of the other tricyclic antidepressants, involve processes of oxidative demethylation, hydroxylation, N-oxidation and conjugation with glucuronic acid. The demethylated metabolite nortriptyline is therapeutically active and against amitriptyline it exerts a greater activity in behavioral tests and against noradrenaline, but less efficacy against serotonin.
Amitriptyline is oxidized by hepatic microsomal enzymes which are followed by conjugation processes with glucuronic acid, with the formation of compounds that are eliminated in the urine. The amount excreted in the urine (unchanged compound plus metabolites) is about 90-95% of the dose administered within one week of the end of therapy (approximately 30-40% in the first 24 hours). No metabolites are detected in the faeces while the excreted amitriptyline is estimated at around 8%. As with most antidepressants, amitriptyline is metabolised more slowly in the elderly.
05.3 Preclinical safety data
The toxicity for single administration of amitriptyline is relatively low, as deduced from the numerous experiences carried out in various animal species and for different routes of administration.
In mice, the LD50 values are between 140-405 mg / kg orally, 56-109 mg / kg intravenously, 13-26 mg / kg intravenously and 120-140 mg / kg subcutaneously. In rats, the LD50 varies from 257 to 320 mg / kg by the oral route and is 105 mg / kg by the endoperitoneal route; in the rabbit, values of about 9 mg / kg were obtained intravenously, while in the guinea pig the minimum lethal dose was 52 mg / kg.
Amitriptyline was satisfactorily tolerated in repeated oral administration tests for 12 weeks in the rat (15 mg / kg / day) and 12 months in the dog (scalar doses up to 100 mg / kg / day. In the fetal toxicity tests performed in the rat (up to 25 mg / kg / day) no malformations of the product of conception were highlighted, as well as no effect was observed in the mutagenesis tests performed with the Ames test in presence or absence of metabolic activation.
Toxicological studies conducted with nortriptyline, considered the active metabolite of amitriptyline, have provided comparable results with respect to acute and chronic toxicity tests and reproductive experiences.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Coated tablets 10 mg - 25 mg
Tribasic calcium phosphate; microcrystalline cellulose; cornstarch; povidone; magnesium stearate; rosin; sandracca; shellac; turpentine; sodium dioctyl sulfosuccinate; talc; light magnesium carbonate; titanium dioxide (E 171); kaolin; jelly; sucrose.
06.2 Incompatibility
The association with other psychotropic drugs requires particular caution and vigilance on the part of the physician to avoid unexpected undesirable effects from interaction.
It is recommended not to drink alcoholic beverages during treatment.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Carton of 30 coated tablets of 10 mg, in blister packs (white opaque PVC)
Carton of 30 coated tablets of 25 mg, in blister packs (white opaque PVC)
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
TEOFARMA S.r.l. via F.lli Cervi, 8 - 27010 Valle Salimbene (PV)
08.0 MARKETING AUTHORIZATION NUMBER
30 coated tablets of 10 mg: A.I.C .: 020019016
30 coated tablets of 25 mg: A.I.C .: 020019028
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
10.07.1962/01/06/2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of September 2010
