Package Insert: Information for the User

Largactil 100 mg Film-Coated Tablets

chlorpromazine

Read this entire package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

It is an antipsychotic and neuroleptic medication belonging to the group of medications known as phenothiazines. Its neuroleptic activity is manifested by its sedative effect, which is useful in states of agitation, aggression, and anxiety in mentally ill patients. Chlorpromazine also has marked antiemetic activity (prevents or stops vomiting) and reduces anxiety.

Under the prescription of your doctor, this medication is indicated for the treatment of:

-States of psychomotor agitation: acute psychoses, manic crises, delirious episodes, confusional syndromes, geriatric psychoprocesses, etc.

• Psychotic processes: schizophrenia, chronic delirious syndromes.
• Sleep cures.

Do not take Largactil

• if you are allergic (hypersensitive) to chlorpromazine, other phenothiazines, or any of the other components of this medication (listed in section 6).
• if you are at risk of developing increased intraocular pressure (glaucoma).
• if you are at risk of urinary retention due to problems with the urethra or prostate.
• in case of coma caused by alcohol or barbiturate intoxication.
• if you have had a disease characterized by a decrease in the number of granulocytes in the blood (agranulocytosis).
• if you are allergic or intolerant to gluten.
• if you are breastfeeding.
• if you are under one year old.
• if you are taking citalopram or escitalopram (see section "Taking Largactil with other medications").
• if you are taking dopaminergic medications (see section "Taking Largactil with other medications").

Warnings and precautions

Consult your doctor or pharmacist before starting to take Largactil:

• If your body temperature suddenly increases, consult your doctor immediately, due to the risk of developing a syndrome called malignant neuroleptic syndrome, described during treatment with this type of medication, whose effects include muscle rigidity, increased body temperature, and nervous system disorders.
• If you have risk factors for suffering a stroke.
• If you have Parkinson's disease.
• If you have epilepsy. Treatment should be interrupted if seizures occur.
• If you have severe heart and/or circulatory problems.
• If you have liver or kidney problems.
• If you have a history of liver disease.
• If you have intestinal obstruction (paralytic ileus).
• Ensure the absence of factors that favor the development of cardiac rhythm disorders (ventricular arrhythmia): bradycardia <55
• If your treatment is prolonged, your doctor may recommend an eye examination and blood test.
• In case of fever, sore throat, infection, or appearance of mouth ulcers, your doctor will perform a blood test to rule out a possible decrease in a type of white blood cell, granulocytes, or an increase in the number of leukocytes.
• If you suffer from seizures. It may increase the risk of developing them, so your doctor will monitor you closely, performing an electroencephalogram.
• This type of medication may potentiate the development of cardiac rhythm disorders (prolongation of the QT interval) that can be severe (torsades de pointes) and cause death. Therefore, your doctor will perform the necessary controls to exclude possible risk factors before starting treatment and if necessary during treatment.
• Older patients have a higher probability of experiencing sedation and decreased blood pressure (orthostatic hypotension). Monitor older patients with a high susceptibility to developing decreased blood pressure, sedation, extrapyramidal effects, chronic constipation, or prostate hypertrophy.
• In older patients with dementia-related psychosis and taking antipsychotics (possibility of presenting a higher risk of death).
• If you have risk factors for developing thromboembolism (blood clot formation) (see section "4. Possible side effects").
• If you or your caregiver:

• note a yellowish discoloration of the skin or eyes (jaundice) and darker urine. These may be signs of liver damage.
• suspect any allergic reaction while taking chlorpromazine.

You must immediately inform a doctor if you experience symptoms such as fatigue (asthenia), anorexia, nausea, vomiting, abdominal pain, due to severe liver toxicity of this medication, which can be sometimes fatal. Your doctor should immediately initiate investigations, including clinical examination and evaluation of liver function (see section "4. Possible side effects").

• If you have diabetes mellitus or risk factors for developing it, as you should control your blood glucose levels (blood sugar levels) properly while taking Largactil.
• If you are taking lithium, other medications that may prolong the QT interval, dopaminergic antiparkinsonian medications (see section "Taking Largactil with other medications").
• Avoid consuming alcohol or medications containing alcohol (see sections "Taking Largactil with food, drinks, and alcohol" and "Taking Largactil with other medications").
• Use in children (see section "3. How to take Largactil").
• Severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of Largactil.

• DRESS initially presents with symptoms similar to the flu and a rash on the face, followed by a more widespread rash with increased body temperature, elevated liver enzymes in blood tests, and increased eosinophils and enlarged lymph nodes.

If you develop a severe rash or other skin symptoms, stop taking chlorpromazine and contact your doctor or seek immediate medical attention.

Taking Largactil with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Contraindicated combinations

• Quinagolida, cabergolina (medications for treating increased prolactin levels).
• Citalopram and escitalopram (medications for treating depression).

Not recommended combinations

• Medications for treating Parkinson's disease such as amantadine, bromocriptine, cabergolina, levodopa, lisurida, pergolida, piribedil, ropinirol.

• Levodopa (medication for treating Parkinson's disease): if movement disorders appear, your doctor will not prescribe or replace levodopa with another medication.

• Medications that may prolong the QT interval (heart disorder): there is an increased risk of arrhythmias when chlorpromazine is used simultaneously with medications that prolong the QT interval (including some antiarrhythmics and other antipsychotics, including sultoprida) and medications that may cause electrolyte imbalance.

• Alcohol: alcohol consumption potentiates the sedative effect of Largactil.

• Guanetidina (medication for treating hypertension): concurrent administration with guanetidina reduces the antihypertensive effect of this medication.

• Sultoprida (medication for treating psychosis): administering Largactil together with sultoprida may cause severe cardiac rhythm disorders (torsade de pointes).

• Litio (medication for treating bipolar disorder): concurrent administration of lithium and chlorpromazine may cause confusion syndrome, increased muscle tone, and increased reflexes.

Combinations requiring caution

• Medications for treating diabetes: concurrent administration of high doses of chlorpromazine (100 mg/day) with antidiabetic medications may increase blood glucose levels. The antidiabetic medication dose may need to be adjusted.

• Concurrent administration with antacids (aluminum, magnesium, and calcium salts, oxides, and hydroxides) reduces the absorption of Largactil. Therefore, it is recommended to take them at least two hours apart.

• Concurrent administration of Largactil with CYP1A2 inhibitors increases chlorpromazine concentrations.

• There may be an interaction between CYP2D6 inhibitors, such as phenothiazines (including chlorpromazine), and CYP2D6 substrates. Concurrent administration of Largactil with amitriptyline/amitriptylinoxide may increase amitriptyline/amitriptylinoxide plasma levels. Monitor for possible adverse reactions associated with amitriptyline/amitriptylinoxide treatment.

Combinations to be considered

• Concurrent administration of Largactil with medications used to lower blood pressure (anti-hypertensives) increases the effect of these medications and the risk of decreased blood pressure upon standing, which may cause dizziness.

• Medications that act on the brain, such as tranquilizers, morphine derivatives, barbiturates, medications for treating allergies, sleep inducers, medications for treating anxiety, benzodiazepines, other anxiolytics distinct from benzodiazepines, sedative antidepressants, medications for lowering blood pressure that act centrally, clonidine and related substances, and methadone, enhance the effect of Largactil and may cause changes in alertness that make it hazardous to drive or operate machinery.

• Medications for treating depression (type imipramine), medications for treating allergies that act on the brain, tranquilizers, medications for treating Parkinson's disease, for treating spasms, and disopiramida, when administered together with Largactil, increase the occurrence of the following adverse reactions: urinary retention, constipation, and dry mouth.

Taking Largactil with food, drinks, and alcohol

Avoid consuming alcoholic beverages during treatment. Alcohol potentiates the sedative effect.

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before using any medication.

Pregnancy:

Largactil is not recommended during pregnancy.

Consult your doctor before using this medication:

- if you are a fertile woman and are not using effective contraceptive methods, or

- if you are pregnant, think you may be pregnant, or intend to become pregnant.

If your doctor considers that treatment with Largactil is necessary to ensure the mother's mental balance, treatment should be initiated and maintained at the effective dose throughout pregnancy.

Notified symptoms in newborns of mothers treated with Largactil during the third trimester of pregnancy (last three months of pregnancy): tremors, muscle rigidity, or weakness, somnolence, agitation, respiratory problems, and feeding difficulties, reduced heart rate, or rapid heart rate, abdominal distension, meconium ileus (intestinal obstruction by meconium), delayed meconium excretion. If your baby develops any of these symptoms, contact your doctor.

Breastfeeding:

Do not take Largactil while breastfeeding, as chlorpromazine passes into breast milk.

Your doctor should evaluate substituting breastfeeding with formula feeding or interrupting Largactil treatment.

Fertility:

Largactil may cause an increase in prolactin secretion (hyperprolactinemia) that may be associated with fertility problems in women.

Driving and operating machinery

Largactil may cause symptoms such as drowsiness, dizziness, or visual disturbances, and decrease your ability to react. These effects, as well as the underlying disease, may impair your ability to drive vehicles or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities that require special attention until your doctor evaluates your response to this medication.

Important information about some components of Largactil

Largactil contains gluten.

This medication contains very low levels of gluten (from wheat starch) and is unlikely to cause problems if you have celiac disease.

One tablet contains no more than 10.05 micrograms of gluten.

If you are allergic to wheat (other than celiac disease), do not take this medication.

This medication contains lactose and saccharose. If your doctor has indicated that you have a intolerance to certain sugars, consult with them before taking this medication.

This medication may cause allergic reactions because it contains yellow-orange S (E-110) dye. It may cause asthma, especially in patients allergic to aspirin.

Follow exactly the administration instructions for this medication as indicated by your doctor.

If in doubt, consult your doctor again if you are unsure of the dose you should take.

Remember to take your medication.

The usual dose is:

- In adults, 75 to 150 mg of chlorpromazine are usually administered in 3 doses, every 24 hours, starting with low daily doses (25-50 mg) and increasing progressively to find the useful dosage. Do not exceed 300 mg of chlorpromazine per day, except in special cases and always at the discretion of your doctor.

Patients aged 65 years or older

If you experience any adverse effect, consult your doctor as your doctor will review the dose periodically.

Use in children

-Chlorpromazine should not be administered to children under 1 year old.

- Chlorpromazine should not be administered in the form of tablets to children under 6 years old.

- The administration of chlorpromazine in the form of oral solution in children under 6 years old is reserved for exceptional circumstances in a specialized unit.

- In children aged 1 to 5 years, the recommended dose is 1 mg of chlorpromazine per kg of body weight per day.

- From this age, the recommended dose is 1/3 or 1/2 of the adult dose, according to weight.

Never change the dose prescribed by your doctor. If you estimate that the action of Largactil is too strong or too weak, inform your doctor or pharmacist.

Your doctor will indicate the duration of your treatment with Largactil. Do not discontinue your treatment before.

If you take more Largactil than you should

Consult your doctor immediately or go to the nearest hospital.

The symptoms of Largactil overdose may include seizures, severe parkinsonian syndrome, and even coma.

Although there is no specific antidote, in case of accidental overdose, specialized treatment will be performed in a hospital setting (gastric lavage and administration of antiparkinsonian and cardiac restorative drugs, intravenously, and respiratory and cardiac monitoring will be performed).

In case of overdose or accidental ingestion, consult the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to take Largactil

Do not take a double dose to compensate for the missed doses.

Like all medicines, Largactil may cause side effects, although not everyone will experience them.

The classification of possible side effects is based on the following frequency data:

Very common:may affect more than one in 10 people

Common:may affect up to one in 10 people

Uncommon:may affect up to one in 100 people

Rare:may affect up to one in 1,000 people

Very rare:may affect up to one in 10,000 people

Unknown frequency: cannot be estimated from available data

These may include:

• Blood and lymphatic system disorders

Unknown frequency:decreased white blood cell count in general (leucopenia), decreased granulocytes (agranulocytosis), eosinophilia, which is an increase in the number of eosinophils (a type of white blood cell) found in a blood test, thrombocytopenia, which is a decrease in the number of platelets (blood cells that help with clotting) found in a blood test, which may lead to bleeding and bruising (thrombotic purpura).

• Immune system disorders

Unknown frequency:systemic, autoimmune disease that can affect almost any part of the human body (systemic lupus erythematosus), antinuclear antibodies positive (may be seen without evidence of clinical disease).

• Endocrine disorders

Common:increase in prolactin hormone levels in the blood,amenorrhea.

Unknown frequency:inappropriate milk secretion (galactorrhea), excessive breast volume in men (gynecomastia),impotence, sexual excitement disorders in women.

• Metabolism and nutrition disorders

Very common:weight gain.

Common: glucose intolerance.

Unknown frequency: high blood glucose levels (hyperglycemia), high triglyceride levels (hypertriglyceridemia), low sodium levels in the blood (hyponatremia), inappropriate secretion of the antidiuretic hormone.

• Mental and behavioural disorders

Common: anxiety.

Unknown frequency: somnolence (drowsiness), mood changes.

• Nervous system disorders

Very common:sedation and somnolence (particularly when starting treatment), movement disorders (dyskinesia, tardive dyskinesia),movement disorder characterized by inability to remain still (akathisia),extrapyramidal syndrome.

Common: increased muscle tone (hypertonia), convulsions.

Unknown frequency: movement disorders such as acute dyskinesias (incoordination or difficulty with movements, characterized by contraction of neck, eye, and mouth muscles), decreased or absence of voluntary movement (akinesia), syndrome characterized by hyperactivity, lack of attention (hyperkinesia), neuroléptico malignant syndrome characterized by muscle rigidity, increased body temperature, and nervous system alterations.

• Eye disorders

Unknown frequency: eye focusing disorder,pigment deposits in the anterior segment of the eye.

• Cardiac disorders

Common: prolonged QT interval on the electrocardiogram, which may trigger abnormal heart rhythm (ventricular arrhythmia).

Unknown frequency: abnormal heart rhythm such as ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia, torsades de pointes (a type of arrhythmia), cardiac arrest. There have been cases of sudden death associated with cardiac abnormalities or without apparent explanation in patients receiving this type of medication.

• Vascular disorders

Very common: decreased blood pressure when standing (orthostatic hypotension).

Unknown frequency: formation of blood clots (venous thromboembolism) that may affect the lungs (pulmonary embolism), sometimes fatal, and deep vein thrombosis.

• Gastrointestinal disorders

Very common: dry mouth, constipation.

Unknown frequency: intestinal obstruction and other gastrointestinal diseases such as paralytic ileus, ischemic colitis, gastrointestinal necrosis (sometimes fatal), necrotizing colitis (sometimes fatal), intestinal perforation (sometimes fatal).

• Hepatobiliary disorders

Unknown frequency:hepatic damage and cholestatic jaundice. Yellowing of the skin or eyes (jaundice) and darker urine may be signs of liver damage.

Cases of mixed, cholestatic, and hepatocellular liver damage have been reported, which sometimes may be fatal.

• Skin and subcutaneous tissue disorders

Unknown frequency: allergic dermatitis, increased skin sensitivity to the sun(erythema, pigmentation),swelling (angioedema), skin rash (urticaria).

• Renal and urinary disorders

Unknown frequency: urinary retention.

• Pregnancy, puerperium and perinatal conditions

Unknown frequency: withdrawal syndrome in newborns.

• Reproductive and breast disorders

Unknown frequency: prolonged erection in the absence of sexual desire (priapism).

• General disorders and administration site conditions

Unknown frequency: temperature regulation disorder.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep out of sight and reach of children.

Do not store at a temperature above 25°C.

Store in the original packaging to protect it from light.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and medicines you no longer need atthe SIGRE Drop-off Pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. By doing so, you will help protect the environment.

Composition of Largactil 100 mg film-coated tablets

• The active ingredient is chlorpromazine. Each tablet contains 100 mg of chlorpromazine (in the form of hydrochloride).
• The other components are: lactose monohydrate, wheat starch, sucrose, hydrated colloidal silica, magnesium stearate.

Coating: acetyl butyl ricinoleate, acetic anhydride, yellow-orange S (E-110) dye, zein varnish, 96% ethanol, and purified water.

Appearance of the product and content of the packaging

The film-coated tablets are round, orange in color, and scored on one face.

Each package contains 30 film-coated tablets.

Other presentations:

Largactil 25 mg film-coated tablets: package with 50 tablets

Largactil 40 mg/ml oral drops in solution: 30 ml bottle

Largactil 5 mg/ml injectable solution: package with 5 ampoules of 5 ml

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69

08970 Sant Joan Despí

Barcelona - Spain

Responsible manufacturer:

Famar Health Care Services Madrid, S.A.U.

Avda. de Leganés, 62

28923 Alcorcón (Madrid)

Spain

Last review date of this leaflet: May2023

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/