Active ingredients: Amitriptyline
Laroxyl 10 mg coated tablets
Laroxyl 25 mg coated tablets
Laroxyl 40 mg / ml oral drops solution
Why is Laroxyl used? What is it for?
Therapeutic category
Laroxyl belongs to the therapeutic class of tricyclic antidepressants.
Indications
Endogenous depression. Depressive phase of manic-depressive psychosis. Reactive depression. Masked depression. Neurotic depression. Depression in the course of schizophrenic psychosis. Involving Depressions. Severe depression in the course of neurological diseases or other organic affections.
Prophylaxis of migraine and chronic or recurrent headaches.
Contraindications When Laroxyl 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 gastro-enteric and genito-urinary system. Liver diseases. Heart failure. Disturbances of rhythm and myocardial conduction. Post-infarct recovery period.
Precautions for use What you need to know before taking Laroxyl
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 perform periodic electrocardiographic checks. Close clinical surveillance. and instrumental is also required in the elderly, in hyperthyroid patients or under treatment with thyroid hormones or in those taking 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. 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 diseases, etc ...) in whom an excessive parasympatholytic activity can be harmful.
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 shown efficacy for this class of drugs.
Suicidal 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 carefully monitored 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 Laroxyl is prescribed may also be associated with an increased risk of suicidal behavior. Furthermore, 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.
Pharmacological 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.
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.
Interactions Which drugs or foods can modify the effect of Laroxyl
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Monoamine oxidase inhibitors: tricyclic antidepressants must not be associated with irreversible MAOIs due to the possibility of serious side effects (hyperthermia, convulsions, coma, death); if it is essential to replace an irreversible 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. Patients who need to use nasal decongestants and products used in the treatment of asthma and pollinosis containing sympathomimetic substances will be carefully monitored and should, however, , strictly follow the recommended dosage schedules.
Anticholinergic drugs: attention requires the use of parasympatholytic drugs, especially those used in the treatment of Parkinson's disease.
Substances with depressive action on the CNS: tricyclic antidepressants can accentuate the action of such drugs as hypnotics, sedatives, anxiolytics and anesthetics. Antidepressant treatment should be suspended as soon as possible by the clinical situation before an elective surgery.
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.
Warnings It is important to know that:
Since the drug can cause orthostatic hypotension, changes in blood sugar, disturbances of hematopoiesis, liver and kidney, it is advisable to periodically check blood pressure, blood glucose, 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 photo-sensitization 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 neuro-psychic 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, in general, it should be the one that allows the assumption of the minimum effective dose.
Although amitriptyline exerts a sedative action, extreme caution still requires the use of antidepressants in outpatient treatment since these drugs can sometimes eliminate psycho-motor inhibition before having exerted an effect on the 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.
Suicidal ideation / behavior
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide / related events) (see Precautions for use). Patients under the influence of Laroxyl should refrain from drinking alcohol as the toxic effects of two substances can mutually enhance each other.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine. As sufficient data are not available to date on the use of tricyclic antidepressants in pregnant women, Laroxyl should only be used if the potential benefit to the mother justifies the potential risk to the fetus.
Epidemiological data have suggested that the use of a similar class of drugs (SSRI) in pregnancy, especially towards the end of pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases. every 1000 pregnancies In general, there are 1-2 cases of PPHN every 1000 pregnancies.
Effects on ability to drive and use machines
Laroxyl can induce vision disturbances, reduce the alertness of reflexes 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.
Important information about some of the ingredients
Laroxyl coated tablets contain lactose. 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 Laroxyl: Posology
Depression therapy
Outpatient treatment
Outpatient treatment involves the administration of an initial dose of 50 mg of Laroxyl per day which, according to the needs of the case, can be progressively reduced or increased until the optimal effect is achieved. Of this dose, 30 mg should be administered in the evening at the bedtime, 10 mg in the morning and 10 mg at noon. In elderly or young patients, weaker dosages are generally sufficient. The administration of the above doses is feasible with either the 25 mg or 10 mg Laroxyl coated tablets, either with the solution drops (one drop = 2 mg of amitriptyline).
Hospital treatment
Initial therapy: oral administration: starting with the dose of 25 mg to be repeated 2-4 times during the day (total dose / day 50-100 mg); if necessary, the total daily dose can be increased up to 200-250 mg. Once the optimal starting dose has been established, it can be maintained for 1 to 3 weeks, and then gradually decreased to the effective maintenance dose.
Maintenance therapy: the oral maintenance dose must be established on a case-by-case basis: generally it is 25 mg repeated 2-4 times a day. In young and elderly patients, lower doses are often sufficient. Laroxyl can be combined with other psychotropic drugs (neuroleptics, tranquilizers, hypnotics) as well as with physical therapy. 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.
Prophylaxis of migraine and chronic or recurrent headaches
The prophylactic treatment of migraine and chronic or recurrent headaches involves the administration of an initial dose of 30-50 mg of Laroxyl per day which, according to the needs of the case, can be reduced or progressively increased until the optimal effect is achieved.
Of this dose, the largest posological fraction should be administered in the evening at bedtime, a second in the morning and a third at noon. In elderly or young patients, weaker dosages are generally sufficient. The administration of the above doses is feasible both with the Laroxyl coated tablets, of 25 mg and 10 mg, and with the solution drops (one drop = 2 mg of amitriptyline).
Overdose What to do if you have taken an overdose of Laroxyl
In case of ingestion / intake of an excessive dose of Laroxyl notify your doctor immediately or go to the nearest hospital. If you have any questions about the use of Laroxyl, ask your doctor or pharmacist.
Overdose of amitriptyline hydrochloride can manifest itself with: dry mouth, mydriasis, 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 down its absorption.
Neostigmine (Prostigmine) can be administered 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.
Side Effects What are the side effects of Laroxyl
Like all medicines, Laroxyl can cause side effects, although not everybody gets them.
The following side effects have been reported with varying intensity and frequency during amitriptyline therapy:
Class Effects: An increased risk of bone fracture has been observed in patients taking this type of medication.
Anticholinergic effects: dry mouth, indistinct vision, mydriasis, ocular hypertonus, cycloplegia, constipation, dysuria, urinary retention
Cardiac disorders: orthostatic hypotension, tachycardia, hypertension, rhythm and conduction disturbances, cardiac arrest, flattening of the T wave and other changes in the E.C.G.trace; heart failure; myocardial infarction; stroke
Nervous system disorders: headache, changes in E.E.G .; dizziness, tremors, ataxia, dysarthria or other extrapyramidal signs, convulsions, paraesthesia in the extremities and peripheral neuropathies
Psychiatric disorders: sedation, drowsiness, asthenia or anxiety, agitation, confusional states with illusions and hallucinations especially in the elderly, euphoria, hypomanic reactions, change 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. Rare: Suicidal ideation / behavior (see Precautions for use and Special warnings).
Gastrointestinal disorders: anorexia, nausea, vomiting, diarrhea; stomatitis, sublingual and parotid adenitis; jaundice and modification of hepatic function indices (increase in transaminases, alkaline phosphatase, etc ...).
Endocrine disorders: gynecomastia, galactorrhea, libido changes, changes in glycemic rate, weight gain.
Blood and lymphatic system disorders: eosinophilia, bone marrow depression with agranulocytosis, thrombocytopenia and purpura.
Immune system disorders: itching, hives, erythema, petechiae, generalized or localized edema of the face and tongue. The appearance of important side effects always requires the interruption of the treatment; minor side effects, such as anticholinergic ones, can attenuate during therapy or be controlled with appropriate dosage adjustments. Hypersensitivity reactions may occur in predisposed subjects.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious or if you notice a side effect not listed in this leaflet, please inform your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact and correctly stored packaging.
Warning: do not use after the expiry date shown 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 this medicine out of the reach and sight of children.
Composition and pharmaceutical form
Composition
One Laroxyl 10 mg coated tablet contains 11.32 mg amitriptyline hydrochloride (equivalent to 10 mg amitriptyline base). Excipients: corn starch; lactose monohydrate; povidone; magnesium stearate; talc; gum arabic, dried spray; ethylcellulose; copolymer lacquer; rice starch, red iron oxide (E172); titanium dioxide; light liquid paraffin; solid paraffin; sucrose.
One Laroxyl 25 mg coated tablet contains 28.3 mg amitriptyline hydrochloride (equivalent to 25 mg amitriptyline base). Excipients: corn starch; lactose monohydrate; povidone; magnesium stearate; talc; gum arabic, dried spray; ethylcellulose; copolymer lacquer; rice starch, red iron oxide (E172); titanium dioxide; light liquid paraffin; solid paraffin; sucrose.
One ml of Laroxyl oral drops solution contains 45.28 mg amitriptyline hydrochloride (equivalent to 40 mg amitriptyline base). Excipients: purified water, hydrochloric acid.
Composition
Laroxyl 10 mg coated tablets: 30 tablets 10 mg.
Laroxyl 25 mg coated tablets: 25 tablets 25 mg.
Laroxyl 40 mg / ml oral drops solution: Bottle 20 ml.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
LAROXYL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One Laroxyl 10 mg coated tablet contains:
amitriptyline hydrochloride 11.32 mg (equivalent to amitriptyline base 10 mg).
One Laroxyl 25 mg coated tablet contains:
amitriptyline hydrochloride 28.3 mg (equivalent to amitriptyline base 25 mg).
One ml of Laroxyl oral drops solution contains:
amitriptyline hydrochloride 45.28 mg (equal to amitriptyline base 40 mg).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Coated tablets and oral drops solution.
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.
Involving Depressions.
Severe depression in the course of neurological diseases or other organic affections.
Prophylaxis of migraine and chronic or recurrent headaches.
Treatment of adult peripheral neuropathic pain.
04.2 Posology and method of administration
Depression therapy
Outpatient treatment
Outpatient treatment involves the administration of an initial dose of 50 mg of Laroxyl per day which, according to the needs of the case, can be progressively reduced or increased until the optimal effect is achieved. Of this dose, 30 mg should be administered in the evening at the bedtime, 10 mg in the morning and 10 mg at noon. In elderly or young patients, weaker dosages are generally sufficient. The administration of the above doses is feasible with either the 25 mg or 10 mg Laroxyl coated tablets, either with the solution drops (one drop = 2 mg of amitriptyline).
Hospital treatment
Initial therapy: starting with the dose of 25 mg to be repeated 2-4 times during the day (total dose / day 50-100 mg); if necessary, the total daily dose can be increased up to 200-250 mg. Once the optimal starting dose has been established, it can be maintained for 1 to 3 weeks, and then gradually decreased to the effective maintenance dose.
Maintenance therapy: the maintenance dose must be established on a case-by-case basis: generally it is 25 mg repeated 2-4 times a day. In young and elderly patients, lower doses are often sufficient.
Laroxyl can be combined with other psychotropic drugs (neuroleptics, tranquilizers, hypnotics) as well as with physical therapy.
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.
Prophylaxis of migraine and chronic or recurrent headaches
The prophylactic treatment of migraine and chronic or recurrent headaches involves the administration of an initial dose of 30-50 mg of Laroxyl per day which, according to the needs of the case, can be reduced or progressively increased until the optimal effect is achieved.
Of this dose, the largest posological fraction should be administered in the evening at bedtime, a second in the morning and a third at noon. In elderly or young patients, weaker dosages are generally sufficient. The administration of the above doses is feasible both with the Laroxyl coated tablets, of 25 mg and 10 mg, and with the solution drops (one drop = 2 mg of amitriptyline).
Treatment of neuropathic pain
Treatment should begin at low doses: 12.5 mg to 25 mg per day for one week. The dose is then increased weekly in gradual increments from 12.5 mg to 25 mg depending on tolerability.
The dosage is individual and varies from 50 mg to 150 mg per day and must take into account any associated analgesic treatments.
Maintenance therapy should be conducted at the lowest effective dose, periodically evaluating the advisability of interrupting treatment.
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 disease.
Heart failure.
Myocardial rhythm and conduction disturbances.
Post-infarct recovery period.
04.4 Special warnings and appropriate precautions for use
Since the drug can cause orthostatic hypotension, changes in blood sugar, disturbances of hematopoiesis, liver and kidney, it is advisable to periodically check blood pressure, blood glucose, 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 photo-sensitization 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 neuro-psychic 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, in general, it should be the one that allows the assumption of the minimum effective dose.
Although amitriptyline exerts a sedative action, extreme caution still requires the use of antidepressants in outpatient treatment since these drugs can sometimes eliminate psycho-motor inhibition before having exerted an effect on the 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.
Patients under the influence of Laroxyl must refrain from drinking alcoholic beverages as the toxic effects of the two substances can mutually potentiate.
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 perform periodic electrocardiographic checks. Close clinical surveillance. and instrumental is also required in the elderly, in hyperthyroid patients or under treatment with thyroid hormones or in those taking 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.
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 diseases, etc ...) in whom an excessive parasympatholytic activity can be harmful.
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 shown efficacy for this class of drugs.
Suicidal 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 carefully monitored 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 Laroxyl is prescribed may also be associated with an increased risk of suicidal behavior. Furthermore, 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.
Pharmacological 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.
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.
Important information about some of the ingredients
Laroxyl coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Laroxyl coated tablets contain 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 irreversible MAOIs due to the possibility of serious side effects (hyperthermia, convulsions, coma, exitus); if it is essential to replace an irreversible 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. Patients who need to use nasal decongestants and products used in the treatment of asthma and pollinosis containing sympathomimetic substances will be carefully monitored and should, however, , strictly follow the recommended dosage schedules.
- Anticholinergic drugs: attention requires the use of parasympatholytic drugs, especially those used in the treatment of Parkinson's disease.
- Substances with depressive action on the CNS: tricyclic antidepressants can accentuate the action of such drugs as hypnotics, sedatives, anxiolytics and anesthetics. The antidepressant treatment should be suspended as early as allowed by the clinical situation before an elective surgery.
• 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.
• The 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.
04.6 Pregnancy and lactation
As sufficient data are not available to date on the use of tricyclic antidepressants in pregnant women, Laroxyl should only be used if the potential benefit to the mother justifies the potential risk to the fetus.
Epidemiological data have suggested that the use of SSRIs in pregnancy, especially towards the end of pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 in 1000 pregnancies. there are 1-2 cases of PPHN per 1000 pregnancies.
04.7 Effects on ability to drive and use machines
The product can induce vision disturbances, attenuate the alertness of reflexes 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
Undesirable effects related to the drug class
Epidemiological studies, mainly conducted in patients aged 50 and over treated with SSRIs and tricyclic antidepressants, have shown an increased risk of bone fractures in these patients. The mechanism associated with this risk is not known.
The following side effects have been reported with varying intensity and frequency during amitriptyline therapy:
- Anticholinergic effects: dry mouth, indistinct vision, mydriasis, ocular hypertonia, cycloplegia, constipation, dysuria, urinary retention
- Cardiac disorders: orthostatic hypotension, tachycardia, hypertension, rhythm and conduction disturbances, cardiac arrest, flattening of the T wave and other modifications of the E.C.G. trace; heart failure; myocardial infarction; stroke
- Nervous system disorders: headache, changes in E.E.G .; dizziness, tremors, ataxia, dysarthria or other extrapyramidal signs, convulsions, paraesthesia in the extremities and peripheral neuropathies
- Psychiatric disorders: sedation, drowsiness, asthenia or anxiety, agitation, confusional states with illusions and hallucinations especially in the elderly, euphoria, hypomanic reactions, change 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.
Rare: suicidal ideation / behavior (see section 4.4 "Special warnings and precautions for use").
- Gastrointestinal disorders: anorexia, nausea, vomiting, diarrhea; stomatitis, sublingual and parotid adenitis; jaundice and modification of hepatic function indices (increase in transaminases, alkaline phosphatase, etc ...)
- Endocrine disorders: gynaecomastia, galactorrhea, libido changes, blood sugar changes, weight gain
- Blood and lymphatic system disorders: eosinophilia, bone marrow depression with agranulocytosis, thrombocytopenia and purpura
- Immune system disorders: itching, hives, erythema, petechiae, generalized or localized edema of 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.
Hypersensitivity reactions may occur in predisposed subjects.
04.9 Overdose
Overdose of amitriptyline hydrochloride can manifest itself with: dry mouth, mydriasis, 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 down its absorption.
Neostigmine (Prostigmine) can be administered 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
Pharmacotherapeutic group: antidepressant.
ATC code: N06AA09.
Medicinal specialty containing amitriptyline, an antidepressant belonging to the group of tricyclics; this substance is characterized from a pharmacological point of view by an "evident anticholinergic activity and by an" action inhibiting the reuptake of various neurotransmitters at the presynaptic level. Amitriptyline also exerts an adrenolytic effect on the periphery by blocking the alpha-1-receptors.
The exact antidepressant mechanism of this drug is not fully understood although it is believed that it is mostly related to the increased concentration of brain amines (noradrenaline, serotonin) in the synaptic spaces.
Amitriptyline has its main clinical indication in the treatment of endogenous depression, but it has also been found to be effective in depressive syndromes of another nature and in the treatment of psychiatric, neurological or internal diseases, the course of which is accompanied or complicated by depression. maximum therapeutic effect usually occurs within two weeks or more of starting therapy. Laroxyl is also indicated in the prophylactic treatment of migraine and chronic or recurrent headaches.
05.2 Pharmacokinetic properties
Amitriptyline is well absorbed orally, binds in high percentage to plasma proteins and undergoes the action of microsomal enzymes of the liver. Eight metabolites were identified: demethylated, hydroxylated, conjugated or N-oxidized derivatives; the demethylated metabolite, nortriptyline, is therapeutically active. The mean half-life of a single dose is 16 hours. 95% of the administered dose is eliminated by the kidney and this process (pH dependent) is faster in acidic urine. In normal subjects treated with repeated doses, the drug is inactivated and excreted within one week of the end of therapy. As with most antidepressants, amitriptyline is metabolized more slowly in the elderly.
05.3 Preclinical safety data
Acute toxicity of amitriptyline:
- LD50 per os in the male rat equal to 900 mg / kg
- LD50 per os in the female rat equal to 825 mg / kg
- LD50 per os in rabbits equal to 322 mg / kg
Subacute toxicity of amitriptyline:
after administration of 10 mg / kg per esophageal tube in rabbits, five times a week, for four weeks, no noteworthy side effects appeared.
Chronic toxicity of amitriptyline:
after administration from 6 to 18 mg / kg in rats, for 6 weeks, no effects appeared on motility, on weight gain, on various laboratory parameters (SGOT and SGPT), on the mortality rate in the animals considered.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Laroxyl 10 mg coated tablets:
cornstarch; lactose monohydrate; povidone; magnesium stearate; talc; gum arabic, dried spray; ethylcellulose; copolymer lacquer; rice starch, red iron oxide (E172); titanium dioxide; light liquid paraffin; solid paraffin; sucrose.
Laroxyl 25 mg coated tablets:
cornstarch; lactose monohydrate; povidone; magnesium stearate; talc; gum arabic, dried spray; ethylcellulose; copolymer lacquer; rice starch, red iron oxide (E172); titanium dioxide; light liquid paraffin; solid paraffin; sucrose.
Laroxyl 40 mg / ml oral drops solution:
purified water, hydrochloric acid.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Coated tablets: 5 years.
Oral drops solution: 3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Coated tablets
blisters made of thermoformed plastic material coupled with aluminum tape. The blisters are contained in a cardboard box, together with the package leaflet.
Oral drops solution
bottle of dark glass (amber yellow), III hydrolytic class, with dropper and screw cap in thermoplastic material. The bottle is contained in a cardboard box, together with the package leaflet.
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
25 coated tablets 25 mg AIC n ° 019906015
30 coated tablets 10 mg AIC n ° 019906027
Oral drops solution 20 ml bottle AIC n ° 019906054
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: June 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination October 2013
