ADT 25 mg

ADT 10 mg film-coated tablets ADT 25 mg film-coated tablets ADT 75 mg film-coated tablets Amitriptyline hydrochloride Read all of this leaflet carefully before you start taking this medicine. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor or pharmacist. - This medicine has been prescribed for you. You must not give it to others; the medicine can harm them even if they have the same symptoms. - If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist. In this leaflet: 1. What ADT is and what it is used for 2. Before you take ADT 3. How to take ADT 4. Possible side effects 5. How to store ADT 6. Further information

1. WHAT ADT IS AND WHAT IT IS USED FOR

Therapeutic indications The main therapeutic indication of ADT is the treatment of depressive states. Depression is characterized by a lack of response to the environment, events or personal relationships, as well as other symptoms such as loss of appetite, lack of energy, mental slowness, decreased productivity, sleep and motor activity changes. It is worth mentioning the particular importance of amitriptyline in anxious depressions and its effective anxiolytic action. ADT is also indicated in nocturnal enuresis in which organic pathology has been ruled out.

2. BEFORE YOU TAKE ADT

Do not take ADT - If you are allergic (hypersensitive) to the active substance or any of the other ingredients of ADT. - If you are taking tricyclic antidepressants or MAOIs: ADT should not be given simultaneously with monoamine oxidase inhibitors. Hyperpyretic attacks, severe convulsions and death have occurred in patients treated simultaneously with tricyclic antidepressants and MAOIs. -If you have had a myocardial infarction: you should not be taking ADT during the acute recovery phase after a myocardial infarction. Take special care with ADT When, in case of substitution of MAOI therapy, ADT treatment should only be started two weeks (14 days) after discontinuing the MAOI, in order to avoid a possible potentiating effect. Treatment with ADT should be initiated with caution in these patients, gradually increasing the dose until a satisfactory response is obtained (see section 2, "Taking ADT with other medicines" and "Taking ADT with food and drink"). If you have a history of seizures, urinary retention, prostatic hypertrophy, angle-closure glaucoma or intraocular hypertension: amitriptyline should be administered with caution to patients with a history of seizures, with liver function disorders and, due to its atropinic action, in patients with a history of urinary retention, prostatic hypertrophy, angle-closure glaucoma or intraocular hypertension. In patients with angle-closure glaucoma, even the usual therapeutic doses can precipitate an increase in intraocular pressure. If possible, treatment with amitriptyline should be stopped several days before surgery. However, if this is not possible, the anesthetist should be informed that the patient is receiving amitriptyline, as anesthesia may increase the risk of hypotension and arrhythmias. If you have cardiovascular disorders: Patients with cardiovascular disorders should be carefully monitored as amitriptyline can cause arrhythmias, sinus tachycardia and conductivity disorders as, due to a quinidine-like effect, an increase in conduction time may occur, but due to the anticholinergic action it may occur. the opposite. If you have hyperthyroidism or are being treated with thyroid drugs or anticholinergic agents: careful monitoring is required in these patients. When, in case of electroshock therapy: the dangers of electroshock therapy may be potentiated by the concomitant administration of amitriptyline. Therefore, this concomitant treatment should be limited to patients where it is considered absolutely essential. During treatment, the risk of suicide in depressed patients remains until significant remission is achieved, therefore these patients should be closely monitored. In manic-depressive states, depressed patients may transition to the manic phase if treated with a tricyclic antidepressant agent. Patients with paranoid symptoms may experience exacerbation of symptoms. In these cases, a tranquilizer may be administered concomitantly or the dose of amitriptyline may be reduced. Thoughts of suicide and worsening of your depression or anxiety disorder If you are depressed and/or have anxiety disorders you may sometimes have thoughts of harming or even killing yourself. These thoughts may increase at the beginning of treatment with antidepressants, as these medicines need time to work. Usually the therapeutic effects take about two weeks to be felt but sometimes it can take longer. You may be more likely to have these types of thoughts in the following situations: - If you have a history of having thoughts about committing suicide or harming yourself. -If you are a young adult. Information from clinical studies has shown an increased risk of suicidal behavior in adult subjects under age 25 with psychiatric conditions treated with antidepressants. If at any time you have thoughts of harming or killing yourself, you should contact your doctor or go to hospital immediately. It may be helpful for you to tell someone close to you or a family member that you are depressed or have anxiety disorders and give them this leaflet to read. You can also ask them to let you know if they notice a worsening of your depression or anxiety, or if they become concerned about changes in your behavior. A heart condition called “prolonged QT interval” (which is shown on your electrocardiogram, ECG) and heart rhythm disorders (rapid or irregular heartbeat) have been reported with ADT. Talk to your doctor if: you have a slow heart rate, have had or have a problem where your heart cannot pump blood around your body as well as it should (a condition called heart failure), are taking any other medication that can cause heart problems, or have a problem that determines a low level of potassium or magnesium or a high level of potassium in your blood. Use in children and adolescents below the age of 18 years: Amitriptyline hydrochloride should not be used for the treatment of depression in children and adolescents below the age of 18 years. Efficacy of tricyclic antidepressants has not been demonstrated in studies of patients in this age group with depression. Studies with other groups of antidepressants, namely Selective Serotonin Reuptake Inhibitors, demonstrated that these drugs were related to suicidal ideation, self-aggression and hostility. The risk of occurrence of these reactions cannot be excluded for amitriptyline hydrochloride. Additionally, amitriptyline hydrochloride is associated with a risk of adverse cardiovascular events in all age groups. In addition to the above, long-term safety data for use in children and adolescents regarding growth, maturation and cognitive and behavioral development are not yet available (see also sections "Possible side effects" and "If you take more ADT than it should"). Taking other medicines Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. - CNS depressants (alcohol, barbiturates): amitriptyline may potentiate the depressant effect on the CNS, leading to respiratory depression. On the other hand, barbiturates may decrease the antidepressant effect of amitriptyline. -Other antidepressants: the concomitant administration of antidepressants with different modes of action should only be carried out with due knowledge of the possibility of potentiation and with complete mastery of the pharmacology of both drugs. - Anticholinergics and antihistamines: amitriptyline may potentiate the anticholinergic effects of these drugs. Increased anticholinergic activity can cause paralytic ileus, blurred vision and affect intraocular pressure in patients with glaucoma. -Clonidine and guanethidine: amitriptyline may antagonize the antihypertensive effect of these drugs, therefore their concomitant administration is not recommended. Tricyclic antidepressants block the absorption of guanethidine and other compounds with similar action, so it may be necessary to adjust the dose of these drugs. It is advisable to review antihypertensive therapy during treatment with tricyclic antidepressants. - Estrogens: lack of antidepressant response and tricyclic toxicity. -MAOIs: may potentiate the effects of tricyclic antidepressants, such as amitriptyline, and hyperpyrexia, severe convulsions and death may occur. - Sympathomimetic agents (adrenaline, ephedrine, isoprenaline, noradrenaline): there may be potentiation of the pressor and cardiac effects of sympathomimetics, which can be fatal. - Drugs that act on the thyroid: increases the possibility of arrhythmias. -Disulfiram: Delirium has been reported in patients treated concomitantly with disulfiram and amitriptyline. - Drugs metabolized by cytochrome P450 2D6: Concomitant use of tricyclic antidepressants with drugs that can inhibit CYP P450 2D6 (eg, quinidine, cimetidine) and drugs that are substrates for P450 2D6 (eg, amiptriptyline) may require doses lower than those normally prescribed for amitriptyline or the other drug. Dosage adjustment may be necessary. -Reserpine: amitriptyline may antagonize the effects of reserpine. - Ethcorvinol: The concomitant use of amitriptyline with high doses of ethcorvinol should be performed with caution. Transient delirium has been reported in patients treated with 1g ethorvinol and 75-100mg amitriptyline. -Anticonvulsants: reduced effectiveness in controlling seizures in epileptic patients. - Analgesics: amitriptyline may increase the risk of seizures in patients treated with tramadol. - Antipsychotics: may increase plasma concentrations of amitriptyline. - Serotonin-inducing drugs: “serotonin syndrome” may occur. Taking ADT with food and drink Alcohol is a CNS depressant. Amitriptyline may potentiate the depressant effect on the CNS, leading to respiratory depression. See also section Taking ADT with other medicines. Pregnancy and breast-feeding Consult your doctor or pharmacist before taking any medication. The safety of amitriptyline during pregnancy has not been established. The use of amitriptyline during pregnancy is not recommended unless, in the opinion of the doctor, the possible benefits justify the potential risks to the fetus. Amitriptyline and its major metabolite, nortriptyline, pass into breast milk at concentrations similar to plasma. Due to the possibility of serious adverse reactions in children, the mother should discontinue breast-feeding or discontinue the drug. Driving and using machines ADT can affect the mental abilities necessary to perform certain tasks, such as driving a vehicle or operating machinery. Important information about some of the ingredients of ADT ADT 25 mg and ADT 75 mg contain the dye tartarazine (E 102) which may cause allergic reactions. pass into breast milk in concentrations similar to plasma. Due to the possibility of serious adverse reactions in children, the mother should discontinue breast-feeding or discontinue the drug. Driving and using machines ADT can affect the mental abilities necessary to perform certain tasks, such as driving a vehicle or operating machinery. Important information about some of the ingredients of ADT ADT 25 mg and ADT 75 mg contain the dye tartarazine (E 102) which may cause allergic reactions. pass into breast milk in concentrations similar to plasma. Due to the possibility of serious adverse reactions in children, the mother should discontinue breast-feeding or discontinue the drug. Driving and using machines ADT can affect the mental abilities necessary to perform certain tasks, such as driving a vehicle or operating machinery. Important information about some of the ingredients of ADT ADT 25 mg and ADT 75 mg contain the dye tartarazine (E 102) which may cause allergic reactions. such as driving vehicles or handling machinery. Important information about some of the ingredients of ADT ADT 25 mg and ADT 75 mg contain the dye tartarazine (E 102) which may cause allergic reactions. such as driving vehicles or handling machinery. Important information about some of the ingredients of ADT ADT 25 mg and ADT 75 mg contain the dye tartarazine (E 102) which may cause allergic reactions.

3. HOW TO TAKE ADT

Always take ADT exactly as your doctor has told you. Talk to your doctor or pharmacist if you are not sure. The usual/average dose of treatment is indicated in the dosage. The drug is administered orally. Dosage in depression: Initial dosage: The average dosage is 25 mg three times a day with meals. If necessary, it can be increased up to 150 mg daily. Increases should preferably be made in doses in the late afternoon or at bedtime. The effect of ADT manifests itself after a few days, with the full effect being reached after 2 to 3 weeks. There may be other alternative methods for initiating therapy: A dose of 50 to 100 mg of amitriptyline preferably in the afternoon or at bedtime may be increased up to 150 mg per day. A dose of 75 mg preferably in the afternoon or at bedtime, and increase if necessary to 150 mg at bedtime or 75 mg in the morning and 75 mg at night. For adolescent and elderly patients, lower doses of 50 mg daily are recommended, which can be administered in divided doses or as a single dose, preferably at the end of the day or at bedtime. Maintenance dosage: Maintenance doses are 50 to 100 mg daily, preferably in the late afternoon or at bedtime. As soon as possible, the dosage should be reduced until the minimum dose is reached that allows relief of symptoms. Maintenance therapy should be carried out for 3 months or longer to decrease the possibility of relapse. Children: ADT is not recommended for the treatment of depression in children and adolescents under 18 years of age. Dosage in enuresis: Children from 6 to 10 years: The dose should be adjusted according to weight and age, 10 to 20 mg daily can be given. Children 11 to 16 years: A dose of between 25 and 50 mg daily may be required. Most of these patients respond within the first few days of treatment and the tendency is for improvements to intensify and treatment should be continued to maintain the response until control is established. Treatment should not exceed 3 months. The doses of amitriptyline recommended in the treatment of enuresis are low compared to those used in the treatment of depression, even taking into account age and weight differences. The recommended dose should never be exceeded. Children: ADT is not recommended for the treatment of enuresis in children under 6 years of age. If you take more ADT than you should Overdose with tricyclic antidepressants can cause cardiac dysrhythmias, severe hypotension, seizures, CNS depression and coma. ECG changes, particularly in the QRS axis or amplitude, are clinically significant indicators of tricyclic antidepressant-induced toxicity. Other signs of overdose may include: confusion, disturbances in concentration, transient visual hallucinations, dilated pupils, agitation, hyperreflexia, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia or any of the adverse reactions listed in the Possible side effects section. Treatment is symptomatic and supportive. An ECG should be performed and careful monitoring of cardiac function immediately followed. Maintain a patent airway, establish an intravenous line, and initiate gastric decontamination. A minimum of 6 hours of observation is required with cardiac monitoring and observation of signs of CNS depression or respiratory depression: hypotension, cardiac dysrhythmias, conduction blocks and seizures. If signs of toxicity occur during this period, prolonged monitoring is necessary. There are case reports of patients with fatal arrhythmias following overdose; these patients had clinical evidence of significant poisoning before death, and most received inadequate gastrointestinal decontamination. Monitoring of drug plasma levels should not serve as a guide to patient management. Gastrointestinal decontamination: should be performed in all patients with suspected overdose. It should include large volume gastric lavage followed by administration of activated charcoal. If there is a disturbance in the state of consciousness, the airway must be kept clear. Emesis is contraindicated. Cardiovascular: A maximum duration of the QRS complex in the lower limb lead of 0.10 seconds may be the best indicator of the severity of the overdose. To maintain the serum pH between 7.45-7.55, IV sodium bicarbonate should be used. If the response is inadequate, hyperventilation can also be used. Their concomitant use must be carried out with extreme caution and frequent pH monitoring. A pH > 7.60 or a pCO2 < 20 mmHg is not desirable. Dysrhythmias that do not respond to this therapy may respond to lidocaine, bretylium, or phenytoin. Type 1A and 1C antiarrhythmics (eg, quinidine, disopyramide, procainamide) are generally contraindicated. In rare cases, hemoperfusion may be beneficial in refractory acute cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis have generally been reported to be ineffective in tricyclic antidepressant poisoning. CNS: In patients with CNS depression, early intubation is advisable because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines or, if these are ineffective, with other anticonvulsants (eg, phenobarbital, phenytoin). Physostigmine is only recommended in potentially fatal situations that do not respond to other therapies and after consultation with the CIAV. Psychiatric follow-up: given that overdose is often intentional, patients may attempt suicide by other means during the recovery phase, therefore psychiatric follow-up is advisable. If you forget to take ADT Do not take a double dose to make up for a forgotten dose. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, ADT can cause side effects, although not everybody gets them. Most of the undesirable effects of amitriptyline are similar to those of tricyclic antidepressants and result from its antimuscarinic action. Anticholinergics: xerostomia, constipation, paralytic ileus, urinary retention, blurred vision, accommodation disturbances, increased intraocular pressure and hyperthermia. Allergens: rash, urticaria, photosensitization, swelling of the face and tongue. Cardiovascular: hypotension, syncope, orthostatic hypotension, hypertension, tachycardia, palpitations, myocardial infarction, arrhythmias, heart block and stroke. Hematologic: Bone marrow depression, agranulocytosis, leukopenia, eosinophilia, purpura and thrombocytopenia. Gastrointestinal: nausea, epigastric discomfort, vomiting, anorexia, stomatitis, taste change, diarrhea, parotid swelling, black tongue. Rarely, cases of hepatitis, including changes in liver function and jaundice, have occurred. Endocrine: testicular swelling, gynecomastia, breast enlargement, galactorrhea, increased or decreased libido, impotence, sexual dysfunction, blood glucose changes and syndrome of inappropriate ADH secretion. Diagnostic work-ups Common (may affect up to 1 in 10 people) A heart problem called “prolonged QT interval” (which is shown on your electrocardiogram, ECG) CNS and neuromuscular: confusion, delirium, disturbances in concentration, disorientation, delusions, hallucinations, hypomania, mania, excitement, anxiety, agitation, insomnia, nightmares, insensitivity, tingling and paresthesias of the extremities; peripheral neuropathy, incoordination, ataxia, tremors, coma, seizures, changes in EEG patterns, extrapyramidal symptoms including abnormal involuntary movements and tardive dyskinesia; dysarthria and tinnitus. Cases of suicidal ideation/behavior have been reported during treatment with ADT or immediately after its discontinuation. The frequency is not known. An increased risk of bone fractures has been observed in patients taking these types of medicines. Other effects: dizziness, weakness, fatigue, headache, weight loss, increased sweating, urinary frequency, mydriasis, alopecia, drowsiness, increased appetite and weight gain. In enuresis: the most common side effects are drowsiness and anticholinergic effects. Other less frequent effects include moderate sweating and itching.

5. HOW TO STORE ADT

Keep this medicine out of the sight and reach of children. Do not store above 25°C. Keep on original package for light protection. Do not use this medicine after the expiry date which is stated on the carton after "EXP". The validity period corresponds to the last day of the indicated month. Do not use ADT if you notice any visible signs of deterioration. Do not dispose of any medication down the drain or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.

6. OTHER INFORMATION

What ADT contains The active substance is amitriptyline hydrochloride. Each ADT 10 mg coated tablet contains 10 mg of amitriptyline hydrochloride, each ADT 25 mg coated tablet contains 25 mg of amitriptyline hydrochloride and each ADT 75 mg coated tablet contains 75 mg of amitriptyline hydrochloride. The other ingredients are: ADT 10 mg: calcium hydrogen phosphate dihydrate, sodium carboxymethyl starch, talc, macrogol 6000, magnesium stearate, opadry OY-30924 blue and indigotine (E 132) ADT 25 mg and 75 mg: calcium hydrogen phosphate di -hydrate, sodium carboxymethyl starch, talc, macrogol 6000, magnesium stearate, opadry yellow OY-22929 and tartarazine (E 102). What ADT looks like and contents of the pack Tablets packed in PVC/Aluminium blisters. packs of 10, 20 and 60 film-coated tablets (10 mg) and packs of 20 and 60 film-coated tablets (25 mg and 75 mg). It is possible that not all presentations are marketed. Marketing Authorization Holder and Manufacturer Marketing Authorization Holder Generis Farmacêutica, SA Rua João de Deus, 19 2700-487 Amadora Portugal Manufacturer Generis Farmacêutica, SA (Fab. Loures) Rua Comandante Carvalho Araújo, EN 374 - Sete Casas 2670-540 Loures (ADT 10 mg and ADT 25 mg) Sofarimex – Indústria Química e Farmacêutica, SA, Av. das Indústrias – Alto do Colaride, 2735-213 Cacém, Portugal Generis Farmacêutica, SA (Fab. Venda Nova) Rua João de Deus, 19 2700-487 Amadora, Portugal For any information about this medicine, please contact the Introduction Authorization Holder in the market.