Package Insert: Information for the User

Largactil 5 mg/ml Injectable Solution

Chlorpromazine

Read this package insert carefully before starting to use this medication, because it contains important information for you.

• Keep this package insert, as you may need to read 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 neurolptic medication belonging to the group of medications known as phenothiazines.Its neurolptic 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 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.

No use 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 developing 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 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 being treated with citalopram or escitalopram (see section “Use of Largactil with other medications”).
• if you are being treated with dopamine agonists (see section “Use of Largactil with other medications”).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Largactil:

• If your body temperature increases inexplicably, 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 any 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 their occurrence, so your doctor will perform a special control, 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). Due to the risk of hypotension, you should remain at least half an hour after injection in a supine position (lying on your back). You should be monitored by older patients with a high susceptibility to developing decreased blood pressure, sedation, extrapyramidal effects, chronic constipation, or prostate hypertrophy.
• When administered parenterally: your doctor should have everything necessary to prepare a rapid intravenous infusion, in order to prevent possible hypovolemia and place you in a dorsal decubitus position if you experience orthostatic hypotension. Changes in position should be made with caution due to the risk of developing orthostatic hypotension.
• In older patients with dementia-related psychosis and being treated with antipsychotics (possibility of presenting a higher risk of death).
• If you have risk factors for suffering thromboembolism (formation of blood clots) (see section “4. Possible adverse 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 should immediately inform your doctor if you experience symptoms such as fatigue (asthenia), anorexia, nausea, vomiting, abdominal pain, due to the severe toxicity of this medication to the liver, which can sometimes be fatal. Your doctor should immediately initiate investigations, including clinical examination and evaluation of liver function (see section “4. Possible adverse 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 being treated with lithium, other medications that may prolong the QT interval, dopamine agonist antiparkinsonian medications (see section “Use of Largactil with other medications”).
• Avoid consuming alcohol or medications containing alcohol (see sections “Use of Largactil with food, drinks, and alcohol” and “Use of Largactil with other medications”).
• Use in children (see section “3. How to use 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 medical attention immediately.

Use of 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 and cabergolina (medications for treating high 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 occur, 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 cardiac rhythm disorders that can be severe (torsades de pointes).

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

Combinations requiring caution

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

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

• Administering Largactil with CYP1A2 inhibitors increases chlorpromazine concentrations.

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

Combinations to be considered

• Administering Largactil with medications used to lower blood pressure (antihypertensives) increases their effect 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, clonidina and related substances, and metadona, enhance the effect of Largactil. They may cause changes in alertness that make it hazardous to drive or operate machinery.

• Medications for treating depression (type imipramina), 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.

Use of Largactil with food, drinks, and alcohol

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

Pregnancy, lactation, 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 estimates 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):shivering, muscle rigidity, or weakness, somnolence, agitation, breathing problems, and difficulty feeding, reduced heart rate, or rapid heart rate, abdominal distension,meconial ileus (it is a blockage of the small intestine by meconium), delayed meconium excretion. If your baby develops any of these symptoms, contact your doctor.

Lactation:

Do not use Largactil while breastfeeding, as chlorpromazine passes into breast milk. Your doctor should evaluate substituting breast milk with artificial feeding or interrupting treatment with Largactil.

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

This medication may cause severe allergic reactions and bronchospasm (sudden feeling of suffocation) because it containsmetabisulfito de sodio and sulfito de sodio anhidro.

This medication contains less than 23 mg of sodium (1 mmol) per 5 ml ampoule; it is essentially “sodium-free”.

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

In case of doubt, consult your doctor again if you are unsure of the dose to be used..

Remember to use your medication.

The normal dose is:

- In adults, it is administered parenterally: intramuscularly or intravenously via infusion, 25 to 50 mg of chlorpromazine (1-2 ampoules of 5 ml) several times a day, without exceeding, except in particular cases and always at the discretion of the doctor, 150 mg per day.

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..

- In children from 1 to 5 years old, the recommended dose is 1 mg of chlorpromazine per kilogram 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.

Administration form

When administered Largactil intramuscularly (IM), it must be injected deeply into the muscle. Since the solution is irritating, it should be avoided to administer intramuscularly superficially, in order to minimize local reactions.

When administered Largactil intravenously (IV), it must be administered via infusion to minimize local reactions.

If you use more Largactil than you should

Consult your doctor immediately or go to the nearest hospital.

The symptoms of Largactil overdose may 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 (gastric lavage and administration of antiparkinsonian and cardiac restorative drugs via intravenous and monitoring of respiratory and cardiac function).

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

If you forgot to use Largactil

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

Like all medications, 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 be:

• Blood and lymphatic system disorders

Unknown frequency:decreased white blood cell count in general (leucopenia), decreased granulocytes (agranulocytosis), eosinophilia, which is an increase in eosinophils (a type of white blood cell) found in a blood test, thrombocytopenia, which is a decrease in platelet count (a type of blood cell that helps with clotting) found in a blood test, which may lead to bleeding and hematomas (purpura thrombocytopenica).

• Immune system disorders

Unknown frequency:systemic, autoimmune, and chronic 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: increased levels of prolactin hormone in the blood,amenorrhea (lack of menstrual period).

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 antidiuretic hormone.

• Mental and behavioral 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), convulsion.

Unknown frequency: movement disorders such as acute dyskinesias (incoordination or difficulty with movements, characterized by muscle contractions in the neck, eye, and mouth), decreased or absence of voluntary movement (akinesia), syndrome characterized by hyperactivity, lack of attention (hyperkinesia), malignant neuroleptic 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 upon 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 dark 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: priapism (erection in the absence of sexual desire).

• 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 Vigilance 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.

Store in the original packaging to protect it from light.

Do not use this medication after the expiration date shown 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 at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medicines. By doing so, you will help protect the environment.

Composition of Largactil 5 mg/ml injectable solution

• The active ingredient is chlorpromazine. Each 5 ml ampoule contains 25 mg of chlorpromazine (in the form of hydrochloride).
• The other components are: ascorbic acid, sodium citrate, sodium chloride, sodium metabisulphite, anhydrous sodium sulphite, and water for injectable preparations.

Appearance of the product and contents of the packaging

Each package contains 5 ampoules..

Each ampoule contains 5 ml.

Other presentations:

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

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

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

Holder of the marketing authorization and responsible for manufacturing

Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69

08970 Sant Joan Despí

Barcelona - Spain

Responsible for manufacturing:

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

Avda. de Leganés, 62

28923 Alcorcón (Madrid)

Spain

Last review date of this leaflet: May 2023

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/