Largactil 100 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Largactil 100 mg film-coated tablets

chlorpromazine

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

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

Leaflet contents:

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

1. What Largactil is and what it is used for

It is an antipsychotic and neuroleptic drug belonging to the group of medicines known as phenothiazines. Its neuroleptic activity is manifested by its sedative effect, which is useful in states of agitation, aggressiveness, and mental distress in psychiatric patients. Chlorpromazine also has a marked antiemetic effect (stops or prevents vomiting) and reduces anxiety.

Always under a doctor's prescription, this medicine is indicated for the treatment of:

• Psychomotor agitation states: acute psychoses, manic crises, delirious episodes, confusional syndromes, psychogeriatric disorders, etc.
  • Psychotic disorders: schizophrenia, chronic delusional syndromes.
  • Sleep cures.

2. What you need to know before taking Largactil

Do not take Largactil

• if you are allergic (hypersensitive) to chlorpromazine, other phenothiazines, or any of the other components of this medicine (listed in section 6).
• if you are at risk of increased intraocular pressure (glaucoma).
• if you are at risk of urinary retention due to urethral or prostate problems.
• in case of coma caused by alcohol or barbiturate intoxication.
• if you have previously suffered from 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 the patient is under one year of age.
• if you are being treated with citalopram or escitalopram (see section “Taking Largactil with other medicines”).
• if you are being treated with dopaminergic medicines (see section “Taking Largactil with other medicines”).

Warnings and precautions

Talk to your doctor or pharmacist before taking Largactil:

• If your body temperature rises inexplicably, consult your doctor immediately due to the risk of developing a condition known as neuroleptic malignant syndrome, which has been reported during treatment with this type of medicine. Symptoms include muscle rigidity, increased body temperature, and disturbances of the nervous system.

• If you have risk factors for stroke.

• If you have Parkinson’s disease.

• If you have epilepsy. Treatment should be discontinued if seizures occur.

• If you have serious heart or circulatory problems.

• If you have liver or kidney disorders.

• If you have a history of liver disease.

• If you have intestinal obstruction (paralytic ileus).

• Ensure the absence of factors that may promote disturbances in heart rhythm (ventricular arrhythmia): heart rate below 55 beats per minute (bradycardia), low blood potassium levels, congenital prolonged QT interval, or concomitant use of medicines that may cause the conditions described above.

• If your treatment is prolonged, your doctor may recommend an eye examination and blood tests.

• If you develop fever, sore throat, infection, or mouth ulcers, your doctor will perform a blood test to rule out a possible decrease in a type of white blood cells (granulocytes) or an increase in white blood cell count (leukocytosis).

• If you suffer from epileptic seizures. The risk of seizures may increase, so your doctor may monitor you closely and perform an electroencephalogram (EEG).

• This type of medicine may increase the risk of disturbances in heart rhythm (prolonged QT interval), which can be serious (torsades de pointes) and potentially fatal. Therefore, your doctor will perform necessary checks to exclude possible risk factors before starting treatment and, if needed, during treatment.

• Elderly patients are more likely to experience sedation and low blood pressure (orthostatic hypotension). Elderly patients who are particularly susceptible to low blood pressure, sedation, extrapyramidal effects, chronic constipation, or prostate enlargement should be closely monitored.

• In elderly patients with dementia-related psychosis treated with antipsychotics (possible increased risk of death).

• If you have risk factors for thromboembolism (blood clot formation) (see section “4. Possible side effects”).

• If you or your caregiver notice:

• yellowing of the skin or eyes (jaundice) and darkening of the urine. These may be signs of liver damage.

• suspect any allergic reaction while taking chlorpromazine.

You must contact a doctor immediately if you experience symptoms such as fatigue (asthenia), loss of appetite, nausea, vomiting, or abdominal pain, due to the potential for severe liver toxicity from this medicine, which may occasionally be fatal. Your doctor should immediately initiate investigations, including clinical examination and biological assessment of liver function (see section “4. Possible side effects”).

• If you have diabetes mellitus or risk factors for it, since glucose levels (blood sugar) should be carefully monitored while taking Largactil.

• If you are being treated with lithium, other medicines that may prolong the QT interval, or dopaminergic anti-Parkinson medicines (see section “Taking Largactil with other medicines”).

• Alcohol consumption or medicines containing alcohol should be avoided (see sections “Taking Largactil with food, drinks, and alcohol” and “Taking Largactil with other medicines”).

• Use in children (see section “3. How to take Largactil”).

• Serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with the use of Largactil.

• DRESS initially presents with flu-like symptoms and a facial rash, followed by a more widespread rash, fever, elevated liver enzymes in blood tests, increased levels of a type of white blood cell (eosinophilia), and enlarged lymph nodes.

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

Taking Largactil with other medicines

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

Contraindicated combinations

• Quinagolide, cabergoline (medicines used to treat elevated prolactin hormone levels).
• Citalopram and escitalopram (medicines used to treat depression).

Not recommended combinations

• Medicines used to treat Parkinson’s disease such as amantadine, bromocriptine, cabergoline, levodopa, lisuride, pergolide, piribedil, ropinirole.

• Levodopa (medicine used to treat Parkinson’s disease): if movement disorders occur, your doctor will either not prescribe levodopa or will switch you to another medicine.

• Medicines that may prolong the QT interval (heart disorder): the risk of arrhythmias increases when chlorpromazine is used simultaneously with medicines that prolong the QT interval (including some antiarrhythmics and other antipsychotics such as sultopride) and medicines that may cause electrolyte imbalances.

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

• Guanethidine (medicine used to treat hypertension): concomitant administration with guanethidine reduces its antihypertensive effect.

• Sultopride (medicine used to treat psychosis): co-administration of Largactil with sultopride may cause disturbances in heart rhythm that can be serious (torsades de pointes).

• Lithium (medicine used to treat bipolar disorder): concomitant administration of lithium and chlorpromazine may cause confusion, increased muscle tone, and increased reflexes.

Combinations requiring caution

• Medicines used to treat diabetes: administration of high doses of chlorpromazine (100 mg/day) together with antidiabetic medicines may increase blood glucose levels. A dose adjustment of the antidiabetic medicine may be necessary.
• Concomitant administration with antacids (salts, oxides, and hydroxides of aluminium, magnesium, and calcium) reduces the absorption of Largactil. Therefore, it is recommended to take them at least two hours apart.
• Concomitant administration of Largactil with CYP1A2 inhibitors leads to increased chlorpromazine concentrations.
• A possible interaction exists between CYP2D6 inhibitors, such as phenothiazines (including chlorpromazine), and CYP2D6 substrates. Administration of Largactil with amitriptyline / amitriptyline oxide may increase plasma levels of amitriptyline / amitriptyline oxide. Possible adverse reactions associated with amitriptyline / amitriptyline oxide treatment should be monitored.

Combinations to be aware of

• Administration of Largactil with medicines used to lower blood pressure (antihypertensives) increases their effect and the risk of low blood pressure upon standing, possibly causing dizziness.

• Medicines acting on the brain such as: tranquilizers, morphine derivatives, barbiturates, antihistamines, sleep-inducing medicines, medicines for anxiety, benzodiazepines, non-benzodiazepine anxiolytics, sedative antidepressants, centrally acting antihypertensives, clonidine and related substances, and methadone, enhance the effect of Largactil. These may cause changes in alertness, making driving or operating machinery dangerous.

• Medicines used to treat depression (e.g., imipramine), antihistamines acting on the brain, tranquilizers, anti-Parkinson medicines, antispasmodics, and disopyramide, when taken together with Largactil, increase the risk of adverse effects such as urinary retention, constipation, and dry mouth.

Taking Largactil with food, drinks, and alcohol

Avoid alcoholic drinks during treatment. Alcohol enhances sedation.

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before using any medicine.

Pregnancy:

Largactil is not recommended during pregnancy.

Consult your doctor before using this medicine:

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

If your doctor considers treatment with Largactil necessary to maintain the mother’s psychological stability, treatment should be initiated and maintained at the effective dose throughout pregnancy.

The following symptoms have been reported in newborns whose mothers received Largactil during the third trimester of pregnancy (last three months): tremors, muscle stiffness and/or muscle weakness, drowsiness, agitation, breathing difficulties, feeding problems, slow or rapid heartbeat, abdominal distension, meconium ileus (an obstruction of the small intestine by meconium), and delayed meconium excretion. If your baby develops any of these symptoms, contact your doctor immediately.

Breastfeeding:

You must not take Largactil if you are breastfeeding, as chlorpromazine passes into breast milk.

Your doctor should consider replacing breastfeeding with artificial feeding or discontinuing treatment with Largactil.

Fertility:

Largactil may increase the secretion of the hormone prolactin (hyperprolactinemia), which may be associated with fertility problems in women.

Driving and using machines

Largactil may cause symptoms such as drowsiness, dizziness, or visual disturbances, and may impair reaction ability. These effects, as well as the underlying illness, may impair your ability to drive or operate machinery. Therefore, do not drive, operate machinery, or engage in other activities requiring special attention until your doctor has assessed your response to this medicine.

Important information about some of the components of Largactil

Largactil contains gluten.

This medicine contains very low levels of gluten (from wheat starch), and it is very unlikely to cause problems if you have coeliac disease.

One tablet contains no more than 10.05 micrograms of gluten.

If you are allergic to wheat (other than coeliac disease), you must not take this medicine.

This medicine contains lactose and sucrose. If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

This medicine may cause allergic reactions as it contains the colouring agent orange yellow S (E-110). It may cause asthma, especially in patients allergic to acetylsalicylic acid.

3. How to take Largactil

Follow exactly the instructions for use of this medicine as given by your doctor.

If you are unsure, consult your doctor again if you are uncertain about the dose you should take.

Remember to take your medicine.

The usual dose is:

• In adults, 75 to 150 mg of chlorpromazine divided into 3 doses every 24 hours, starting with low daily doses (25–50 mg) and gradually increasing until the effective dose is reached. The daily dose of chlorpromazine should not exceed 300 mg, except in special cases and always at the discretion of your doctor.

Elderly patients ≥ 65 years of age

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

Use in children

• Chlorpromazine must not be given to children under 1 year of age.

• Chlorpromazine tablets must not be given to children under 6 years of age.

• Administration of chlorpromazine oral solution in children under 6 years of age 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 onwards, the recommended dose is 1/3 or 1/2 of the adult dose, depending on body weight.

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

Your doctor will advise you on how long your treatment with Largactil should last. Do not stop your treatment prematurely.

If you take more Largactil than you should

Seek immediate medical advice or go to the nearest hospital.

Symptoms of Largactil overdose may include: seizures, severe parkinsonism, and even coma.

Although there is no specific antidote, in case of accidental overdose, specialized treatment should be administered in a hospital setting (gastric lavage and intravenous administration of antiparkinsonian drugs and agents to restore cardiac function), along with respiratory and cardiac monitoring).

In case of overdose or accidental ingestion, contact the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Largactil

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

4. Possible adverse effects

Like all medicines, Largactil may produce adverse effects, although not everyone experiences them.

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

Very common: may affect more than 1 in 10 people
Common: 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 available data

These may include:

• Blood and lymphatic system disorders

Frequency not known: decrease in overall white blood cell count (leucopenia), 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 may 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 (which may be observed without evidence of clinical disease).

• Endocrine disorders

Common: increased levels of prolactin hormone in blood, absence of menstrual periods (amenorrhea).
Frequency not known: unusual milk secretion (galactorrhea), excessive breast development in men (gynecomastia), impotence, sexual arousal disorders in women.

• Metabolism and nutrition disorders

Very common: weight gain.
Common: 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

Common: anxiety.
Frequency not known: drowsy state (lethargy), mood changes.

• Nervous system disorders

Very common: sedation and drowsiness (particularly at the start of treatment), disturbances in voluntary movements (dyskinesia, tardive dyskinesia), movement disorder characterized by inability to remain still (akathisia), extrapyramidal syndrome.
Common: increased muscle tone (hypertonia), seizure.
Frequency not known: movement disturbances such as acute dyskinesias (incoordination or difficulty in movement, characterized by contraction of neck, eye, or mouth muscles), reduction or absence of voluntary movement (akinesia), syndrome characterized by hyperactivity and lack of attention (hyperkinesia), neuroleptic malignant syndrome characterized by muscle rigidity, elevated body temperature, and nervous system disturbances.

• Eye disorders

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

• Cardiac disorders

Common: prolonged QT interval on electrocardiogram, which may trigger heart rhythm disturbances (ventricular arrhythmia).
Frequency not known: heart rhythm disturbances such as ventricular arrhythmias, ventricular fibrillation, ventricular tachycardia, torsade de pointes (a type of arrhythmia), cardiac arrest. Cases of sudden death associated with cardiac disturbances or without apparent explanation have been reported in patients receiving this type of medication.

• Vascular disorders

Very common: drop in blood pressure upon standing (orthostatic hypotension).
Frequency not known: blood clot formation (venous thromboembolism) which may affect the lungs (pulmonary embolism), sometimes fatal, and deep vein thrombosis.

• Gastrointestinal disorders

Very common: dry mouth, constipation.
Frequency not known: intestinal obstruction and other gastrointestinal disorders 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 darkening of the urine. These could be signs of liver damage.
Cases of hepatocellular, cholestatic, and mixed-type liver injury have been reported, which in some cases may be fatal.

• Skin and subcutaneous tissue disorders

Frequency not known: allergic dermatitis, increased sensitivity of the skin to sunlight (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 not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Largactil

Keep out of the sight and reach of children.

Do not store above 25°C.

Keep in the original packaging to protect from light.

Do not use this medicine after the expiry date stated on the container after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. If you are unsure how to dispose of containers and unused medicines, ask your pharmacist. This will help protect the environment.

6. Contents of the pack and other information

Composition of Largactil 100 mg film-coated tablets

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

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

Appearance of the product and contents of the pack

The film-coated tablets are round, orange in colour, and scored on one side.

Each pack contains 30 film-coated tablets.

Other pack sizes:

Largactil 25 mg film-coated tablets: pack containing 50 tablets
Largactil 40 mg/ml oral drops solution: 30 ml bottle
Largactil 5 mg/ml injectable solution: pack containing 5 vials of 5 ml each

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Neuraxpharm Spain, S.L.U.
Avda. Barcelona, 69
08970 Sant Joan Despí
Barcelona - Spain

Manufacturer:

Famar Health Care Services Madrid, S.A.U.
Avda. de Leganés, 62
28923 Alcorcón (Madrid)
Spain

Date of latest revision of this leaflet: May 2023

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