Package Insert: Information for the Patient

Sinogan 25 mg Film-Coated Tablets

levomepromazine, maleate

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

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed for you only, and you should not give it to others who 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.

Levomepromazine is an antipsychotic medication that belongs to the group of drugs known as phenothiazines, endowed with sedative properties, anxiety-reducing effects, and a great capacity to combat pain, as well as a significant ability to induce sleep.

This medication is indicated for treatment under the prescription of your doctor for:

• Schizophrenia, acute transient psychoses, and paranoid states, including manic psychoses, organic psychoses, and short-term treatment of prominent symptoms of psychosis as part of a personality disorder.

• Adjuvant treatment for relief of delirium, agitation, nervousness, and confusion associated with pain in the terminal phase.

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

Do not take Sinogan

• if you are allergic to levomepromazine, or to any of the other components of this medication (listed in section 6),
• if you have Parkinson's disease,
• if you have porphyria (a blood disorder),
• 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 to have blood tests to monitor your liver function.

Consult your doctor or pharmacist before starting to take Sinogan

• If your body temperature suddenly increases, 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 altered consciousness.Sweating and irregular pulse or blood pressure may be early warning signs.Although this syndrome appears with this type of medication, it is essential to note that some patients may have a predisposition.
• In case of fever, sore throat, infection, or 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 problems and/or circulatory disorders.
• If you have liver and/or kidney problems (hepatic and/or renal insufficiency).
• If you suffer from epilepsy. It may increase the risk of seizures, so your doctor will monitor you closely, performing an electroencephalogram.
• If your treatment is prolonged, your doctor may recommend an eye examination and a blood test.
• This type of medication may potentiate the appearance of cardiac rhythm disturbances (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 suffering from somnolence and dizziness when getting up due to decreased blood pressure.They may also be susceptible to chronic constipation and prostate problems.
• In older patients with dementia-related psychosis, who are being treated with antipsychotics (possibility of presenting a higher risk of death).
• If you have risk factors for suffering from venous thromboembolism (formation of blood clots) (see "Possible side effects").

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

• If you have diabetes mellitus or risk factors for developing it, as you will need to control your blood glucose levels properly while taking Sinogan.
• At the beginning of treatment, liver function tests will be performed due to the risk of overdose.During chronic treatment, blood tests should be performed every 6-12 months.

Children and adolescents

Do not use in children under 3 years old.

A strict medical monitoring of adverse reactions, particularly neurological, is recommended in children over 3 years old treated with Sinogan.

In this population, Sinogan 40 mg/ml oral drops in solution are recommended.

Due to the impact on learning, a clinical examination should be performed once a year.The dose should be adjusted regularly according to the child's clinical condition.Use in children under 6 years old should be done in a specialized environment.

Use of Sinogan with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Like other medications used to treat psychosis, if Sinogan and levodopa (a medication used to treat Parkinson's disease) are administered together, the effect of these medications may be cancelled out.In the case of movement disorders, your doctor will not prescribe or replace levodopa with another medication.

It is recommended to avoid using dopamine agonists with Sinogan.In case of needing to discontinue a dopamine agonist, it should be gradually reduced (sudden discontinuation of dopamine agonists exposes the patient to a risk of "malignant neuroleptic syndrome").

It is recommended to avoid using cabergoline or quinagolida (medications used to treat abnormal milk flow).

Inform your doctor if you are taking any of these medications, as they may prolong the QT interval (produce changes in your electrocardiogram).There is a higher risk of arrhythmias when Sinogan is used with medications that prolong the QT interval (certain antiarrhythmics, antidepressants, and other antipsychotics) and medications that cause electrolyte imbalance.

Medications that may prolong the QT interval:

• Antiarrhythmics (heart rhythm medications): quinidine, procainamide, amiodarone, mibefradil.
• Antibiotics: erythromycin, cotrimoxazole, trimethoprim-sulfamethoxazole, azithromycin, ketoconazole, pentamidine.
• Gastrointestinal motility medications: cisapride.
• Antihistamines (allergy medications): terfenadine, astemizole.
• Lipid-lowering medications: probucol.
• Other psychotropic agents (medications that improve your mental state): tricyclic and tetracyclic antidepressants, haloperidol, and other phenothiazines.
• Other medications: organophosphates and vasopressin.

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

Concomitant administration of Sinogan with blood pressure-lowering medications increases the effect of these medications and the risk of decreased blood pressure when getting up, which may cause dizziness.

Medications that act on the brain, such as tranquilizers, morphine derivatives (pain and cough medications), barbiturates, allergy medications, sleep inducers, anxiety medications, clonidine, and related substances, metadone, and talidomide, enhance the effect of Sinogan,which may cause respiratory depression.

Medications for depression (such as imipramine), allergy medications that act on the brain, sedatives, some medications for Parkinson's disease and spasms, and disopyramide, when administered together with Sinogan, increase the appearance of adverse reactions of the atropinic type, 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.If you are taking Sinogan together with any of the following medications:

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

You may need to adjust the dose of these medications due to 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 anticonvulsants or medications that lower the seizure threshold with Sinogan should be carefully weighed due to the severity of the risk of seizures.

Taking Sinogan with food, drinks, and alcohol

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

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

• if you are a fertile woman who does not use effective contraception
• if you are pregnant, may become 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 rigidity, and/or muscle weakness, drowsiness, agitation, breathing difficulties, and feeding difficulties, slow or rapid heart rate, abdominal distension, meconium ileus, delayed meconium passage, and constipation.If your baby develops any of these symptoms, you should contact your doctor.

Breastfeeding

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

You should decide whether to stop breastfeeding or stop treatment after considering the benefits of breastfeeding for the baby and the benefits of treatment for the mother.

You cannot rule out a risk for the baby.

Fertility

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

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

Driving and operating machinery

Sinogan may cause symptoms such as drowsiness, dizziness, or visual disturbances, disorientation, and confusion, which 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 assesses your response to this medication.

Sinogan contains gluten and lactose:

Gluten

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

If you are allergic to wheat (other than celiac disease), do not take this medication.

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

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

When starting to take Sinogan, remain lying down for the hour following each dose. If your dose is high, it is essential to monitor your blood pressure due to the risk of it dropping upon rising.

Remember to take your medication.

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 doses.
• 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 doses.

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

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

If you take more Sinogan than you should

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

Consult your doctor immediately, or go to the nearest hospital. The symptoms of Sinogan intoxication may include seizures, 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 forgot to take Sinogan

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

Like all medicines, Sinogan can cause side effects, although not everyone will experience them.

Rare(may affect up to 1 in 100 people)

Central nervous system disorders:

• seizures

Vascular disorders:

• blood clot formation (venous thromboembolism)

Frequency not known(cannot be estimated from available data)

Endocrine disorders:

• difficulty regulating body temperature
• increased levels of a hormone called prolactin (hyperprolactinemia) that may lead toabsence of menstruation (amenorrhea), unusual milk secretion (galactorrhea), excessive breast volume in men (gynecomastia) andimpotence.

Metabolism and nutrition disorders:

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

Psychiatric disorders:

• anxiety reactions
• mood changes
• confusion
• delirium.

Central nervous system disorders:

• parkinsonism (with high and prolonged doses)
• drowsiness or somnolence, especially at the beginning of treatment
• early dyskinesia (incoordination or difficulty with movements, characterized by contraction of muscles in the neck, eye, mouth, etc.)
• late dyskinesia (involuntary movements)
• sextrapyramidal syndrome:
• • akinesia with or without hypertonia (loss of movement with or without muscle rigidity),
  • hyperkinesia – hypertonic movements (movements with muscle rigidity),motor excitement.
  • akathisia (sensation of restlessness at both physical and mental levels)
• neuroleptic malignant syndrome (see “Warnings and precautions”).
• 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 that include prolongation of the QT interval, as occurs with other neuroleptics
• cardiac arrhythmias that may lead to ventricular fibrillation or cardiac arrest possibly related to the dose.

Vascular disorders:

• blood clots that may affect the lungs (pulmonary embolism), which can be fatal
• deep vein thrombosis (see “Warnings and precautions”)
• postural hypotension (decreased blood pressure when standing up after sitting or lying down).

Liver disorders:

• yellowing of the eyes and skin (cholestasis)
• hepatic damage (hepatocellular, cholestatic, and mixed).

Skin disorders:

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

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 drug and generally without effect on vision.

Complementary examinations:

• 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 (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 coagulation) found in a blood test, which can lead to bleeding and hematomas (thrombocytopenic purpura).
• eosinophilia, which is an increase in the number of eosinophils (a type of white blood cell) found in a blood test.

Digestive disorders:

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

Pregnancy, puerperium, and perinatal diseases:

• withdrawal symptoms in newborns (see “Pregnancy, lactation, 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 does not appear in this prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use:https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

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

Do not store at a temperature above 25°C.

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.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Sinogan

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

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

Appearance of the product and content of the packaging

The tablets are white, round, with a groove on one of the faces and engraved ‘Sinogan 25’ and the other face is smooth.

Each package contains 20 tablets.

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 nº 62

28923 Alcorcón (Madrid)

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/