LARGACTIL 5 mg/ml INJECTABLE SOLUTION

2. What you need to know before you use Largactil

Do not use Largactil

• if you are allergic (hypersensitive) to chlorpromazine, to other phenothiazines, or to 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.
  • if you are breastfeeding.
  • if you are under one year of age.
  • if you are being treated with citalopram or escitalopram (see section “Using Largactil with other medications”).
  • if you are being treated with dopaminergic medications (see section “Using 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 a syndrome called malignant neuroleptic syndrome, described during treatment with this type of medication, whose effects include muscle stiffness, 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 discontinued if seizures occur.
• If you have severe heart and/or blood circulation problems.

• If you have liver or kidney disorders.
• If you have a history of liver disease.
• If you have intestinal obstruction (paralytic ileus).
• It should be ensured that there are no factors that favor the appearance of cardiac rhythm disorders (ventricular arrhythmia): bradycardia <55 beats per minute, low potassium levels in the blood, congenital prolonged 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 disorders (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). Due to the risk of hypotension, you should remain in a supine position (lying on your back) for at least half an hour after injection. Elderly patients with a high susceptibility to decreased blood pressure, sedation, extrapyramidal effects, chronic constipation, or prostate hypertrophy should be monitored.
• When administered parenterally: your doctor must have everything necessary to quickly prepare an intravenous infusion, in order to prevent possible hypovolemia and place you in a dorsal decubitus position if you suffer from orthostatic hypotension. Position changes will be made with caution due to the risk of orthostatic hypotension.
• 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 color in 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 use 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 “Using Largactil with other medications”).
• Alcohol consumption should be avoided or medications that contain alcohol (see sections “Using Largactil with food, drinks, and alcohol” and “Using 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 is initially manifested 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 cells in the blood (eosinophilia) and enlarged lymph nodes.

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

Using Largactil with other medications

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

Contraindicated combinations

• Quinagolide, cabergoline (medications for treating high levels of the prolactin hormone).
• 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 movement disorders appear, your doctor will not prescribe it, 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 consumption 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 disorders 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 two hours apart.

• 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. 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

• 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 produce 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.

Using 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 an effective dose throughout the 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 stiffness and/or muscle weakness, somnolence, agitation, breathing problems, and feeding difficulties, decreased heart rate or rapid heart rate, abdominal distension, meconial ileus (a blockage of the small intestine by meconium), delayed meconium excretion. If your baby develops any of these symptoms, you should contact your doctor.

Breastfeeding:

If you are breastfeeding, you should not use Largactil, since chlorpromazine passes into breast milk. Your doctor will assess whether to substitute breastfeeding with formula feeding or discontinue treatment with Largactil.

Fertility:

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

Driving and using machines

Largactil can produce symptoms such as somnolence, dizziness, or changes in vision, 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.

Important information about some of the components of Largactil

This medication can produce severe allergic reactions and bronchospasm (sudden sensation of suffocation) because it contains sodium metabisulfite and anhydrous sodium sulfite.

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

3. How to use Largactil

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

In case of doubt, consult your doctor again if you are not sure of the dose to be used.

Remember to use your medication.

The normal dose is:

• In adults, it is administered parenterally: intramuscularly or intravenously by 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 doctor's discretion, 150 mg per day.

Patient over 65 years of age

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 one year of age.
• In children from 1 to 5 years, 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 action of Largactil is too strong or too weak, tell your doctor or pharmacist.

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

Method of administration

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

When Largactil is administered intravenously (IV), it should be administered by 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 a Largactil overdose can be: 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 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 administered or ingested.

If you forget to use Largactil

Do not administer 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 (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 coagulation) 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: unusual secretion of milk (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 in 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 moving, 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.

• Ocular 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 the 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: formation of blood clots (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 sensitivity of the skin 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. Conservation of Largactil

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 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 wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

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 metabisulfite, anhydrous sodium sulfite, and water for injectable preparations.

Appearance of the product and package contents

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

Marketing authorization holder and manufacturer

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 the last revision of this prospectus: May 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/