Package Insert: Information for the Patient

Sinogan 25 mg/ml Injectable Solution

Levomepromazine Hydrochloride

Read this entire package insert carefully before starting to use 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 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.

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

Under the prescription of your doctor, this medication is indicated for the treatment of:

• 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 use Sinogan”).

Do not use 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 use 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 occurs with this type of medication, it is essential to note that some patients may be predisposed.
• If you have risk factors for suffering a stroke.
• 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 heart problems and/or circulatory disorders.
• If you have liver and/or kidney disorders (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 drowsiness 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 (blood clot formation) (see “Possible side effects”).

• Consult your doctor immediately if you experience abdominal distension and pain (risk of paralytic ileus).
• Use with caution in case of constipation, hypothyroidism, heart failure, phaeochromocytoma (has an adrenal gland tumor), myasthenia gravis (a muscle disorder that causes drooping eyelids, double vision, difficulty speaking and swallowing, and sometimes weakness in the arms or legs), and prostate hypertrophy.
• Be aware of the 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, examinations should be performed every 6-12 months.
• Warn patients who experience postural hypotension not to get up quickly and to ask for help when needed.

Children and adolescents

Do not use in children under 3 years old. Strict medical supervision of adverse reactions, particularly neurological, is recommended in children over 3 years old 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 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 using, have used recently, or may need to use any other medication.

Like other medications used in the treatment of psychosis, if Sinogan is administered together with levodopa (a medication used to treat Parkinson's disease), the effect of these medications may be canceled. If movement disorders appear, your doctor will not prescribe or replace levodopa with another medication.

Avoid using dopamine agonists together with Sinogan. If you need 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).

Avoid using cabergoline or quinagolide (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.
• Medications that act on gastrointestinal motility: 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

(anti-hypertensives) 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, methadone, 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, somemedications for Parkinson's disease and spasms, and disopyramide, when administered together with Sinogan, increase the appearance of atropinic side effects 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, so if you take 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 increased blood levels.

Sinogan inhibits the anti-hypertensive effect of guanetidine.

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

The combined use of proconvulsant medications or those that decrease the seizure threshold with Sinogan should be carefully weighed due to the severity of the risk of seizures.

Use of 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 stiffness and/or weakness, drowsiness, agitation, breathing difficulties, and feeding difficulties at the beginning, slow or fast heart rate, abdominal distension, meconium ileus, delayed meconium passage, and constipation. If your baby develops any of these symptoms, contact your doctor.

Breastfeeding

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

Decide whether to interrupt breastfeeding or interrupt treatment after considering the benefits of breastfeeding for the baby and the benefits of treatment for the mother.

It cannot be ruled out that there is a risk for the baby.

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 operating machines

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

Sinogan contains sodium sulfite:

• Sodium sulfite. This medication may cause severe allergic reactions and bronchospasm (sudden sensation of suffocation) because it contains sodium sulfite.

• Sodium. This medication contains less than1 mmol of sodium (23 mg)per ampoule; this is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again. When starting treatment, you must be closely monitored, and it is recommended that you remain lying down to avoid a decrease in blood pressure, dizziness, and fainting.

Generally, the recommended dose is 75 to 100 mg of levomepromazine per day, divided into 3 or 4 injections of 25 mg, administered intramuscularly. In some cases, higher doses may be needed. The maximum recommended dose is 200 mg.

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.

If you use 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 administered.

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

If you forgot to use Sinogan

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

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

Rare(may affect up to 1 in 100 people)

Nervous system disorders:

• convulsions

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 toamenorrhea, galactorrhea, gynecomastia, and impotence.

Metabolism and nutrition disorders:

• glucose intolerance
• high blood glucose levels (hyperglycemia)
• low sodium levels in the blood (hyponatremia)
• syndrome of inappropriate antidiuretic hormone secretion (SIADH), leading to 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)
• drowsiness or somnolence, especially at the start of treatment,
• early discinesia (incoordination or difficulty with movements, characterized by muscle contractions in the neck, eye, mouth, etc.)
• late discinesia (involuntary movements)
• extrapyramidal 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, both physically and mentally).

• sudden onset of neuroleptic malignant syndrome (see “Warnings and precautions”) anticholinergic effects such as paralytic ileus, risk of urinary retention, 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 seen 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).

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

• Dermatological disorders:
• increased sensitivity to sunlight
• skin allergic reactions.

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

• Ocular 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 and lymphatic system disorders:

• decreased white blood cell count (leucopenia)
• decreased granulocyte count (agranulocytosis)
• thrombocytopenia, a decrease in platelet count, which may lead to bleeding and bruising (thrombocytopenic purpura)
• eosinophilia, an increase in eosinophil count.

- Gastrointestinal disorders:

• inflammatory bowel disease (necrotizing enterocolitis) that can be fatal
• constipation
• intestinal obstruction (paralytic ileus).

• Pregnancy, puerperium, and perinatal conditions:
• withdrawal symptoms in newborns (see “Pregnancy, lactation, and fertility”).

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly to the Spanish System for the Pharmacovigilance of Medicinal Products for Human Use:https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

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

Do not store at a temperature above 25°C. Store in the original packaging to protect it from light.

Expiration Date

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 your pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Sinogan 25 mg/ml injectable solution

Appearance of the product and contents of the packaging

Each package contains 10 ampoules. Each ampoule contains 1 ml of injectable solution.

Holder of the marketing authorization and manufacturer responsible

Holder:

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69

08970 Sant Joan Despí

Barcelona - Spain

Manufacturer responsible:

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/