LARGACTIL 40mg/ml ORAL SOLUTION DROPS

Introduction

Package Leaflet: Information for the User

Largactil 40 mg/ml Oral Drops in Solution

Chlorpromazine

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• 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 only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information:

1. What is Largactil and what is it used for
2. What you need to know before you take Largactil
3. How to take Largactil
4. Possible side effects
5. Storing Largactil
6. Contents of the pack and other information

1. What is Largactil and what is it used for

It is an antipsychotic and neuroleptic medication belonging to the group of medications called phenothiazines. Its neuroleptic activity is manifested by its sedative capacity, 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 anxiety-reducing activity.

Always 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, psychogeriatric processes, etc.
  • Psychotic processes: schizophrenia, chronic delusional syndromes.
  • Sleep cures.

2. What you need to know before you take Largactil

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 have a risk of increased intraocular pressure (glaucoma).
• if you have a risk of urinary retention due to problems in the urethra or prostate.
  • in case of coma caused by alcoholic or barbituric 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, do not take Largactil in tablets.
  • if you are breastfeeding.
  • if you are under one year of age.
  • if you are being treated with citalopram or escitalopram (see section "Taking Largactil with other medications").
  • if you are being treated with 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 rises inexplicably, consult your doctor immediately, due to the risk of a syndrome called neuroleptic malignant 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 blood circulation problems.

• If you have any liver or kidney disorder.
• If you have a history of liver disease.
• If you have intestinal obstruction (paralytic ileus).
• It must be ensured that there are no factors that favor the appearance of cardiac rhythm alterations (arrhythmia): bradycardia <55 beats per minute, low potassium levels in the blood, prolonged congenital qt interval, being treated with medications that can produce situations described above.< li>
• If your treatment is prolonged, your doctor may recommend an eye examination and a blood test.

• In case of fever, sore throat, infection, or the appearance of ulcers in the mouth, 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 epileptic seizures. It can increase the risk of their appearance, so your doctor will subject you to special control, performing an electroencephalogram.
• This type of medication can potentiate the appearance of cardiac rhythm alterations (prolongation of the QT interval) that can be serious (torsades de pointes) and cause death. Therefore, your doctor will perform the necessary checks to exclude possible risk factors before starting treatment and, if necessary, during it.
• Elderly patients are more likely to suffer from sedation and decreased blood pressure (orthostatic hypotension). Elderly patients with a high susceptibility to suffer from decreased blood pressure, sedation, extrapyramidal effects, chronic constipation, or prostate hypertrophy should be monitored.
• In elderly patients with psychosis related to dementia and who are being treated with antipsychotics (possibility of presenting a higher risk of death).
• If you have risk factors for suffering from thromboembolism (blood clot formation) (see section "4. Possible side effects").

• If you or your caregiver:

• notice a yellowish coloration of the skin or eyes (jaundice) and the urine becomes darker. These could be signs of liver damage.
• suspect any allergic reaction while being treated with chlorpromazine.

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

• If you have diabetes mellitus or risk factors for it, since if you take Largactil, you should properly control your blood glucose levels.
• If you are being treated with lithium, other medications that can prolong the QT interval, dopaminergic antiparkinsonian medications (see section "Taking Largactil with other medications").
• Alcohol consumption should be avoided or medications that contain 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 manifests with symptoms similar to those of the flu and a rash on the face, then as a more widespread rash with an elevated body temperature, an increase in liver enzyme levels in blood tests, and an increase in a type of white blood cell in the blood (eosinophilia) and enlarged lymph nodes.

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

Taking Largactil with other medications

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medication.

Contraindicated combinations

• Quinagolide, cabergoline (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, cabergoline, levodopa, lisuride, pergolide, piribedil, ropinirole.

• Levodopa (medication for treating Parkinson's disease): in case extrapyramidal disorders appear, your doctor will not prescribe, or will substitute, levodopa with another medication.

• Medications that can 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 sultopride) and medications that can produce electrolyte imbalance.

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

• Guanethidine (medication for treating hypertension): concomitant administration with guanethidine produces a decrease in the antihypertensive effect of this medication.

• Sultopride (medication for treating psychosis): when Largactil is administered concomitantly with sultopride, cardiac rhythm alterations can occur that can be serious (torsades de pointes).

• Lithium (medication for treating bipolar disorder): concomitant administration of lithium and chlorpromazine can produce confusional syndrome, increased muscle tone, and increased reflexes.

Combinations that require caution

• Medications for treating diabetes: the administration of high doses of chlorpromazine (100 mg/day) together with antidiabetics can produce an increase in blood glucose levels. It may be necessary to adjust the dose of the antidiabetic medication.

• Concomitant administration with antacids (aluminum, magnesium, and calcium salts, oxides, and hydroxides) produces a decrease in the absorption of Largactil. Therefore, it is recommended to take them at least 2 hours apart.

• The administration of Largactil with CYP1A2 inhibitor medications leads to an increase in chlorpromazine concentrations.

• There is a possible interaction between CYP2D6 inhibitors, such as phenothiazines (including chlorpromazine), and CYP2D6 substrates. The administration of Largactil with amitriptyline/amitriptylinoxide can lead to an increase in amitriptyline/amitriptylinoxide plasma levels. The possible appearance of adverse reactions associated with amitriptyline/amitriptylinoxide treatment should be monitored.

Combinations to be taken into account

• The administration of Largactil with medications used to decrease blood pressure (antihypertensives) increases their effect and the risk of decreased blood pressure when standing up, which can cause dizziness.

• Medications that act on the brain, such as: tranquilizers, morphine derivatives, barbiturics, medications for treating allergies, sleep inducers, medications for treating anxiety, benzodiazepines, other anxiolytics different from benzodiazepines, sedative antidepressants, medications for decreasing blood pressure that act centrally, clonidine, and related substances, and methadone, reinforce the effect of Largactil and can produce changes in the state of alertness that make it dangerous to drive or operate machines.

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

Taking Largactil with food, drinks, and alcohol

Avoid alcoholic beverages during treatment. The effect of alcohol potentiates sedation.

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 woman of childbearing age and are not using effective contraceptive methods, or
• if you are pregnant, think you may be pregnant, or plan to become pregnant.

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

The following symptoms have been reported in newborns of mothers treated with Largactil during the third trimester of pregnancy (last three months of pregnancy): tremors, muscle rigidity and/or muscle weakness, somnolence, agitation, breathing problems, and feeding problems, decreased heart rate or rapid heart rate, abdominal distension, meconial ileus (a small intestine obstruction caused by meconium). If your baby develops any of these symptoms, you should contact your doctor.

Breastfeeding:

If you are breastfeeding, you should not take Largactil, as chlorpromazine passes into breast milk.

Your doctor should assess whether to substitute breastfeeding with formula feeding or interrupt treatment with Largactil.

Fertility:

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

Driving and using machines

Largactil can produce symptoms such as somnolence, dizziness, or vision changes, and decrease reaction capacity. These effects, as well as the disease itself, can make it difficult for you to drive vehicles or operate machines. Therefore, do not drive, operate machines, or engage in other activities that require special attention until your doctor assesses your response to this medication.

Largactil 40 mg/ml Oral Drops in Solution contains alcohol

This medication contains 91.4 mg of alcohol (ethanol) in each ml of oral drops in solution, which is equivalent to 9.14% (p/v). The amount in one ml of oral drops in solution of this medication is equivalent to less than 2.3 ml of beer or 0.9 ml of wine.

The small amount of alcohol in this medication does not produce any noticeable effect.

Largactil 40 mg/ml Oral Drops in Solution contains sucrose

This medication contains sucrose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

It can cause cavities.

3. How to take Largactil

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

In case of doubt, consult your doctor again if you are not sure of the dose you should take.

In order to facilitate and obtain a correct dosage, the bottle has a built-in dropper.

The bottle should be inverted to obtain the indicated dose.

Remember to take your medication.

The normal dose is:

• In adults, 75 to 150 mg of chlorpromazine are usually administered, divided into 3 doses, every 24 hours, starting with low daily doses (25-50 mg) and progressively increasing until the useful dosage is found. The dose should not exceed 300 mg of chlorpromazine per day, except in particular cases and always at the discretion of your doctor.

Elderly patients ≥ 65 years

If you experience any side effects, consult your doctor, as your doctor will periodically review the dose.

Use in children

• Chlorpromazine should not be administered to children under 1 year of age.
• The administration of chlorpromazine in oral solution in children under 6 years of age is reserved for exceptional circumstances in a specialized unit.

• In children from 1 to 5 years of age, the recommended dose is 1 mg of chlorpromazine per kg of body weight and day.
• From this age on, the recommended dose is 1/3 or 1/2 of the adult dose, depending on the weight.

Never change the dose that your doctor has prescribed for you. If you think the effect 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 stop your treatment before.

If you take more Largactil than you should

Consult your doctor immediately or go to the nearest hospital.

The symptoms of a Largactil overdose can be: convulsions, 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 (stomach lavage and administration of antiparkinsonian medications and cardiac activity restorers, intravenously, and respiratory and cardiac monitoring will be performed).

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

If you forget to take Largactil

Do not take a double dose to make up for forgotten doses.

4. Possible Adverse Effects

Like all medicines, Largactil can cause adverse effects, although not all people suffer from them.

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

Very frequent: may affect more than 1 in 10 people

Frequent: may affect up to 1 in 10 people

Uncommon: may affect up to 1 in 100 people

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

Very rare: may affect up to 1 in 10,000 people

Frequency not known: cannot be estimated from the available data

These may be:

• Blood and lymphatic system disorders

Frequency not known: decrease in the number of white blood cells in general (leukopenia), decrease in a type of white blood cells, granulocytes (agranulocytosis), eosinophilia which is an increase in the number of eosinophils (a type of white blood cells) 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 can lead to bleeding and bruising (thrombocytopenic purpura).

• Immune system disorders

Frequency not known: a chronic, autoimmune, and systemic disease that can affect almost any part of the human body (systemic lupus erythematosus), positive antinuclear antibodies (may be seen without evidence of clinical disease).

• Endocrine disorders

Frequent: increase in prolactin hormone levels in blood, absence of menstrual period (amenorrhea).

Frequency not known: non-habitual milk secretion (galactorrhea), excessive breast volume in men (gynecomastia), impotence, sexual arousal disorders in women.

• Metabolic and nutritional disorders

Very frequent: weight gain.

Frequent: glucose intolerance.

Frequency not known: high blood glucose levels (hyperglycemia), high triglyceride levels (hypertriglyceridemia), low sodium concentration in blood (hyponatremia), inappropriate secretion of antidiuretic hormone.

• Psychiatric disorders

Frequent: anxiety.

Frequency not known: state of drowsiness (lethargy), mood changes.

• Nervous system disorders

Very frequent: sedation and drowsiness (particularly when starting treatment), alterations of voluntary movements (dyskinesia, tardive dyskinesia), movement disorder characterized by the inability to remain still (akathisia), extrapyramidal syndrome.

Frequent: increased muscle tone (hypertonia), convulsion.

Frequency not known: alteration of movements such as acute dyskinesias (incoordination or difficulty of movements, characterized by contraction of the neck, eye, or mouth muscles), decrease or absence of voluntary movement (akinesia), syndrome characterized by hyperactivity, lack of attention (hyperkinesia), malignant neuroleptic syndrome which is characterized by muscle rigidity, increased body temperature, and alterations of the nervous system.

• Eye disorders

Frequency not known: ocular accommodation disorder, pigment deposits in the anterior segment of the eye.

• Cardiac disorders

Frequent: prolonged QT interval on the electrocardiogram, which can trigger alteration of heart rhythm (ventricular arrhythmia).

Frequency not known: cardiac rhythm alterations 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 alterations or without apparent explanation in patients receiving this type of medication.

• Vascular disorders

Very frequent: decrease in blood pressure when standing up (orthostatic hypotension).

Frequency not known: blood clot formation (venous thromboembolism) that can affect the lungs (pulmonary embolism), sometimes fatal, and deep vein thrombosis.

• Gastrointestinal disorders

Very frequent: dry mouth, constipation.

Frequency not known: 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

Frequency not known: liver damage and cholestatic jaundice. Yellowing of the skin or eyes (jaundice) and the urine becomes darker. These could be signs of liver damage.

There have been reports of liver damage of the hepatocellular, cholestatic, and mixed type, which can sometimes be fatal.

• Skin and subcutaneous tissue disorders

Frequency not known: allergic dermatitis, increased skin sensitivity to the sun (erythema, pigmentation), swelling (angioedema), skin rash (urticaria).

• Renal and urinary disorders

Frequency not known: urinary retention.

• Pregnancy, puerperium, and perinatal disorders

Frequency not known: withdrawal syndrome in newborns.

• Reproductive system and breast disorders

Frequency not known: erection in the absence of sexual desire (priapism).

• General disorders and administration site conditions

Frequency not known: temperature regulation disorder.

Reporting of adverse effects

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

5. Storage of Largactil

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 thrown away through the drains or into the trash. Deposit the packaging and medications that you no longer need at the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications that you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Largactil 40 mg/ml oral drops in solution

• The active ingredient is chlorpromazine. Each ml of solution contains 40 mg of chlorpromazine (in the form of hydrochloride), taking into account that 1 drop of Largactil drops corresponds to 1 mg of chlorpromazine.
• The other components are: ethanol 96%, sucrose, citric acid monohydrate, glycerol, peppermint essence, ammonium glycyrrhizate, caramel color (E-150), and purified water.

Appearance of the product and package contents

Largactil 40 mg/ml oral drops in solution is an oral solution of brown color.

It is presented in glass bottles with 30 ml.

Other presentations:

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

Largactil 100 mg film-coated tablets: packaging with 30 tablets

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

Marketing authorization holder and manufacturer

Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69

08970 Sant Joan Despí

Barcelona - Spain

Manufacturer:

• Nattermann & Cie. GmbH

Nattermannallee 1

50829 Cologne

Germany

O

Manufacturer:

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

Avda. de Leganés, 62

28923 Alcorcón (Madrid)

Spain

Date of the last revision of this prospectus: September 2023

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/