SINOGAN 25 mg FILM-COATED TABLETS

2. What you need to know before you take Sinogan

Read carefully the instructions provided in section 3 (see "How to take Sinogan").

Do not take Sinogan

• if you are allergic to levomepromazine or any of the other components of this medicine (listed in section 6),
• if you suffer from Parkinson's disease,
• if you have suffered from porphyria (blood disease),
• if you are being treated with levodopa,
• in combination with alcoholic beverages.

Warnings and precautions

Before and during chronic treatment, your doctor will ask you for blood tests to check your liver function.

Consult your doctor or pharmacist before starting to take Sinogan

• If your body temperature rises 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 altered consciousness. Sweating and irregular pulse or blood pressure may be early warning signs. Although this syndrome appears with this type of medication, it should be taken into account that there may be patients with some predisposition.
• 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 another type of white blood cell, leukocytes. If this happens, your doctor will suspend treatment.
• If you have risk factors for suffering a stroke.
• If you have heart and/or blood circulation problems.
• If you have liver and/or kidney disorders (hepatic and/or renal insufficiency).
• 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.
• If your treatment is prolonged, your doctor may recommend an eye exam and a blood test.
• 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.
• Older patients are more likely to suffer from drowsiness and dizziness when getting up due to a decrease in blood pressure. They may also be susceptible to chronic constipation and prostate problems.
• In older patients with psychosis related to dementia, who are being treated with antipsychotics (possibility of presenting a higher risk of death).
• If you have risk factors for suffering from venous thromboembolism (blood clot formation) (see "Possible side effects").

• Consult your doctor immediately if you suffer from abdominal distension and pain (risk of paralytic ileus).
• It should be used with caution in case of constipation, hypothyroidism, heart failure, pheochromocytoma (you have a tumor of the adrenal gland), myasthenia gravis (muscular disease that causes drooping eyelids, double vision, difficulty speaking and swallowing, and sometimes muscle weakness in arms or legs), and prostate hypertrophy.
• The risk of appearance of tardive dyskinesia (involuntary movements) should be taken into account, even at low doses, particularly in children and older patients.

• If you have diabetes mellitus or risk factors for it, since if you take Sinogan, you should properly control your blood glucose levels.
• At the start of treatment, liver function tests will be performed due to the risk of overdose. During chronic treatment, exams should be performed every 6-12 months.

Children and adolescents

Do not use in children under 3 years of age. Strict medical monitoring of adverse reactions, mainly neurological, is recommended in children over 3 years of age treated with Sinogan.

In this population, it is recommended to use Sinogan 40 mg/ml oral drops in solution.

Due to the impact on learning, a clinical examination is recommended once a year. The dose will be regularly adapted according to the child's clinical condition. Its use in children under 6 years of age will be carried out in a specialized environment.

Use of Sinogan with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Like other medicines used in the treatment of psychoses, if Sinogan and levodopa (a medicine used to treat Parkinson's disease) are administered together, the effect of these medicines may be canceled. In case of movement disorders, your doctor will not prescribe, or will substitute levodopa with another medicine.

The use of dopaminergic medications with Sinogan should be avoided. In case of needing to withdraw a dopaminergic medication, it should be gradually reduced (sudden interruption of dopaminergic agents exposes the patient to a risk of "malignant neuroleptic syndrome").

The use of cabergoline or quinagolide (medicines used to treat abnormal milk flow) should be avoided.

Tell your doctor if you are taking any of these medicines, as they may prolong the QT interval (produce changes in your electrocardiogram). There is a greater risk of arrhythmias when using Sinogan with medicines that prolong the QT interval (certain anti-arrhythmics, antidepressants, and other antipsychotics) and medicines that cause electrolyte imbalance.

Medicines that may prolong the QT interval:

• Anti-arrhythmics (medicines for heart rhythm): quinidine, procainamide, amiodarone, mibefradil.
• Antibiotics: erythromycin, cotrimoxazole, trimethoprim-sulfamethoxazole, azithromycin, ketoconazole, pentamidine.
• Medicines that act on gastrointestinal motility: cisapride.
• Antihistamines (medicines for allergies): terfenadine, astemizole.
• Lipid-lowering agents (medicines to lower cholesterol levels): probucol.
• Other psychotropic agents (medicines that improve your psychological state): tricyclic and tetracyclic antidepressants, haloperidol, and other phenothiazines.
• Other medicines: organophosphates and vasopressin.

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

The administration of Sinogan with medicines used to lower blood pressure (antihypertensives) increases the effect of these and the risk of decreased blood pressure when standing up, which can cause dizziness.

Medicines that act on the brain, such as tranquilizers, morphine derivatives (medicines for pain and cough treatment), barbiturates, medicines for allergy treatment, sleep inducers, medicines for anxiety treatment, clonidine, and related substances, methadone, and thalidomide, reinforce the effect of Sinogan, which can lead to respiratory depression.

Medicines for depression treatment (such as imipramine), medicines for allergy treatment that act on the brain, sedatives, some medicines for Parkinson's disease treatment, and spasm, and disopyramide, when administered together with Sinogan, increase the appearance of atropine-like adverse reactions, such as urinary retention, constipation, dry mouth, etc.

There is a possibility of interaction between CYP2D6 inhibitors, such as phenothiazines (including levomepromazine), and CYP2D6 substrates. Therefore, if you take Sinogan with any of the following medicines:

• Some antidepressants: amitriptyline/amitriptylinoxide, clomipramine, desipramine, imipramine, fluoxetine, fluvoxamine, sertraline, paroxetine.
• • Some medicines used to treat cardiac arrhythmias: encainide, flecainide, propafenone.
  • Some medicines used to treat hypertension: metoprolol, propranolol.
  • Some medicines used to treat cough: codeine, dextromethorphan.
  • Other medicines used to treat psychosis: perphenazine.

You may need to adjust the dose of these medicines as a result of an increase in their blood levels.

Sinogan inhibits the antihypertensive effect of guanethidine.

Lithium: there is a risk of developing symptoms suggestive of malignant neuroleptic syndrome or lithium poisoning.

The combined use of pro-convulsant medicines or those that decrease the epileptic threshold with Sinogan should be carefully weighed due to the severity of the risk of seizure appearance.

Taking Sinogan with food, drinks, and alcohol

Do not drink alcoholic beverages during treatment with Sinogan, as the effect of alcohol potentiates sedation.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Sinogan is not recommended during pregnancy. Consult your doctor before taking this medicine:

• if you are a woman of childbearing age and are not using effective contraception
• if you are pregnant, might be pregnant, or think you may be pregnant.

The following symptoms have been reported in newborns of mothers treated with Sinogan during the third trimester of pregnancy (last three months of pregnancy): tremors, muscle stiffness and/or weakness, drowsiness, agitation, breathing and feeding problems at the start, slow or fast heartbeat, abdominal distension, meconial ileus, delayed meconium elimination, and constipation. If your baby develops any of these symptoms, you should contact your doctor.

Breastfeeding

If you are breastfeeding, you should not take Sinogan, as Sinogan passes into breast milk in small amounts.

A decision should be made whether to discontinue breastfeeding or discontinue treatment, considering the benefit of breastfeeding for the child and the benefit of treatment for the mother.

A risk to breastfed children cannot be excluded.

Fertility

In humans, levomepromazine may cause an increase in prolactin levels in the blood (hyperprolactinemia) that may be associated with fertility problems in women.

Some data suggest that levomepromazine treatment is associated with fertility problems in men.

Driving and using machines

Sinogan can cause symptoms such as drowsiness, dizziness, or vision changes, disorientation, and confusion, and may reduce your reaction ability. These effects, as well as the disease itself, may impair your ability 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 medicine.

Sinogan contains gluten and lactose:

Gluten

This medicine contains very low levels of gluten (from wheat starch) and is very unlikely to cause problems if you have celiac disease. One tablet does not contain more than 5.87 micrograms of gluten.

If you have a wheat allergy (different from celiac disease), you should not take this medicine.

Lactose: This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Sinogan

Follow exactly the administration instructions of this medicine indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

When starting to take Sinogan, you should remain lying down for the next hour after each intake. If your dose is high, it is important to monitor your blood pressure due to the risk of it dropping when standing up.

Remember to take your medicine.

The recommended doses are as follows:

• in psychotic patients: the recommended dose is 4 to 8 tablets (100 to 200 mg of levomepromazine) per day, sometimes more, divided into 2 or 3 intakes.
• in non-psychotic patients: the recommended dose is 1 to 3 tablets (25 to 75 mg of levomepromazine) per day, divided into 2 or 3 intakes.

Never change the dose that your doctor has prescribed for you. If you think the action of Sinogan is too strong or too weak, tell your doctor or pharmacist.

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

If you take more Sinogan than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount ingested.

Consult your doctor immediately or go to the nearest hospital. The symptoms of a Sinogan intoxication can be convulsions, severe parkinsonian syndrome, and even coma. Although there is no specific antidote, in case of acute intoxication, it is recommended to treat the symptoms and administer cardiac activity-restoring medications intravenously.

If you forget to take Sinogan

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

4. Possible Adverse Effects

Like all medicines, Sinogan can produce adverse effects, although not all people suffer from them.

Uncommon(may affect up to 1 in 100 people)

Nervous System Disorders:

• seizures

Vascular Disorders:

• blood clot formation (venous thromboembolism)

Frequency Not Known(frequency cannot be estimated from available data)

Endocrine Disorders:

• difficulty regulating body temperature
• increased levels of a hormone called prolactin in the blood (hyperprolactinemia) that could lead to absence of menstrual period (amenorrhea), unusual milk secretion (galactorrhea), excessive breast volume in men (gynecomastia), and impotence.

Metabolic and Nutritional Disorders:

• glucose intolerance
• high blood glucose levels (hyperglycemia)
• low blood sodium levels (hyponatremia)
• inadequate secretion of antidiuretic hormone syndrome (fluid retention and decreased levels of certain electrolytes in the blood).

Psychiatric Disorders:

• anxiety reactions
• mood changes
• confusion
• delirium.

Nervous System Disorders:

• parkinsonism (with high and prolonged doses)
• sedation or somnolence, especially at the start of treatment
• early dyskinesia (incoordination or difficulty moving, characterized by contraction of neck, eye, mouth, etc. muscles)
• late dyskinesia (involuntary movements)
• extrapyramidal syndrome:
• • akinesia with or without hypertonia (loss of movement with or without muscle stiffness),
  • hyperkinetic - hypertonic movements (movements with muscle stiffness), motor excitement.
  • akathisia (feeling of restlessness, both physical and mental)
• malignant neuroleptic syndrome (see "Warnings and Precautions" section).
• anticholinergic effects such as paralytic ileus, risk of urinary retention, and dry mouth, constipation, eye accommodation problems,

Cardiac Disorders:

• Torsades de Pointes (a type of arrhythmia)
• changes in the electrocardiogram, including prolongation of the QT interval, as with other neuroleptics
• cardiac arrhythmias that can lead to ventricular fibrillation or cardiac arrest, possibly related to the dose.

Vascular Disorders:

• blood clot formation that can affect the lungs (pulmonary embolism), which can sometimes be fatal
• deep vein thrombosis (see "Warnings and Precautions")
• decrease in blood pressure when standing up from sitting or lying down (postural hypotension).

Hepatic Disorders:

• yellowing of the eyes and skin (cholestatic jaundice)
• liver damage (hepatocellular, cholestatic, and mixed).

Skin Disorders:

• increased sensitivity of the skin to the sun
• allergic reactions on the skin.

Genital Disorders:

• erection in the absence of sexual desire (priapism).

Eye Disorders:

• decreased tension of the eye muscles
• brown deposits in the anterior segment of the eye caused by the accumulation of the medication, generally without effect on vision.

Investigations:

• weight gain

General Disorders and Administration Site Conditions

• sudden death with possible cardiac causes (see "Warnings and Precautions")
• sudden unexplained death in patients receiving phenothiazine neuroleptics.

Blood Disorders:

• decrease in the number of white blood cells in general (leukopenia)
• decrease in a type of white blood cell, granulocytes (agranulocytosis)
• 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).
• eosinophilia, which is an increase in the number of eosinophils (a type of white blood cell) found in a blood test.

Gastrointestinal Disorders:

• inflammation of the small intestine and colon that can be fatal (necrotizing enterocolitis)
• constipation
• intestinal obstruction (paralytic ileus).

Pregnancy, Puerperium, and Perinatal Conditions:

• withdrawal symptoms in newborns (see "Pregnancy, Breastfeeding, and Fertility").

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 is not listed 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 medicine.

5. Storage of Sinogan

Keep this medicine out of the sight and reach of children.

Do not store above 25°C.

Do not use this medicine after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medicines at the pharmacy's SIGRE point. In case of doubt, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Packaging Contents and Additional Information

Sinogan Composition

• The active ingredient is levomepromazine. Each tablet contains 25 mg of levomepromazine (in the form of maleate).

• The other components are: wheat starch (contains gluten), lactose, levilite, dextrin, magnesium stearate. Coating: hypromellose, polyethylene glycol, demineralized water, and ethanol.

Product Appearance and Packaging Contents

The tablets are white, round, with a notch on one side and engraved 'Sinogan 25' and the other side is smooth.

Each package contains 20 tablets.

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 nº 62

28923 Alcorcón (Madrid)

Date of the Last Revision of this Prospectus: May 2023

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