Prospect: information for the patient

ANSIUM Hard Capsules

Sulpiride/Diazepam

1. What is Ansium and how it is used

2. What you need to know before starting to take Ansium

3. How to take Ansium

4. Possible adverse effects

5. Storage of Ansium

6. Contents of the package and additional information

Ansium contains two active substances, diazepam which belongs to a group of medicines called benzodiazepines and sulpiride which belongs to a group of medicines known as antipsychotics, also referred to as neuroleptics.

Doctors prescribe Ansium for sleep rhythm disorders and all forms of insomnia or anxiety, especially when there are difficulties in falling asleep, either initially or after a premature awakening.

This medicine will only be used for the treatment of a severe disorder that limits activity or puts the patient in a situation of significant stress.

Treatment should begin with the lowest dose. The maximum dose should not be exceeded.

Do not take Ansium

• If you are allergic to diazepam or sulpiride or to any of the other ingredients of this medication listed in section 6.
• If you are allergic to the benzodiazepine group in general.
• If you have respiratory difficulties related or unrelated to sleep for a long time.
• If you suffer from muscle problems.
• If you suffer from severe liver problems.
• If you have an increase in intraocular pressure.
• If you suffer from chronic severe hypercapnia.
• If you suffer from drug or alcohol dependencies unless your doctor indicates it formally.

If you have any doubts, consult your doctor.

Since it contains sulpiride, do not take Ansium capsules if:

• You have concomitant prolactin-dependent tumors, for example, pituitary prolactinomas and breast cancer,
• You have phaeochromocytoma (adrenal gland tumor),
• You are being treated with levodopa (See “Use of other medications”),
• You have low heart rate, with cardiac rhythm disturbances or with any other clinically important heart disease,
• You have acute porphyria, a metabolic disease that prevents the synthesis of certain components of red blood cells.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Ansium:

• If you have any liver or kidney disorders.

• If you suffer from muscle weakness.
• If you have other diseasesor someone in your family has a history of blood clots, these medications may be associated with the formation of the same.
• If you have allergies.
• Ifyou have drug or alcohol abuse problems.
• Ifyou are taking other medications.
• Ifyou are epileptic and are following a long-term treatment with Ansium, do not recommend the use of the benzodiazepine antagonist Anexate (flumazenil) to reverse the effect of diazepam as they may appear convulsions.
• If it is administered to patients with a clinical situation that may favor the appearance of cardiac rhythm disturbances, as sulpiride may potentiate the risk of severe cardiac rhythm disturbances.
• If you are at risk of having a stroke.
• If the medication is administered to the elderly, as there is a risk of sedation, decrease in blood pressure when standing up, or the appearance of dyskinesia (uncontrollable abnormal repetitive movements).
• If the medication is administered to children, as sulpiride has not been thoroughly investigated in this group of patients. Do not recommend its use in children.
• Ifyou have renal insufficiency (alteration of kidney function), as the dose must be reduced.
• Ifyou have or have had epilepsy as it may favor the appearance of seizures and convulsions.
• Ifyou suffer from Parkinson's disease, as it is contraindicated, except in exceptional cases, in patients taking antiparkinsonian medication.
• Ifyou appear with fever of unknown origin and muscle rigidity, as it could be the neuroléptico malignant syndrome, a potentially fatal complication characterized by elevated body temperature, muscle rigidity, and autonomic nervous system dysfunction (autonomic dysfunction). If you have an undiagnosed elevated body temperature, discontinue treatment with sulpiride (See “Possible adverse effects”).
• Ifyou have diabetes mellitus or have risk factors for developing diabetes.

If you appear with infection or fever of unknown origin, inform your doctor, as it could be a blood disorder (blood disorder) (see “Possible adverse effects”). Cases of leukopenia (decrease in white blood cell count), neutropenia (decrease in white blood cell count called neutrophils), and agranulocytosis (decrease in a type of white blood cell called granulocytes) have been reported with the use of antipsychotics, including Ansium.

• In elderly patients with dementia-related psychosis, who are being treated with antipsychotics (possibility of presenting a higher risk of death).
• In patients with risk factors for thromboembolism (See “Possible adverse effects”).

Consult your doctor or pharmacist if such symptoms appear.

It is not recommended to take this medication for the treatment of psychosis or anxiety associated with depression. Behavioral disorders may appear, mainly in children and the elderly, in this case, treatment will be discontinued.

The use of benzodiazepines can lead to dependence. This occurs mainly after taking the medication continuously for a long time. To minimize the risk of dependence, the following precautions should be taken:

• The use of benzodiazepines should be made only under medical prescription (never because they have given results to other patients) and never recommend to others.
• Do not increase the prescribed doses, nor prolong the treatment more than recommended.
• Consult your doctor regularly to decide whether to continue treatment.

Children

Ansium should not be administered to children

Older patients

Older patients may be affected by Ansium more than young patients. If you are elderly, your doctor may prescribe a lower dose (for example, half the average dose) and check your response to treatment. Please follow your doctor's instructions carefully.

If you have any liver or kidney disorders, or suffer from muscle weakness, your doctor will decide whether to take a lower dose of Ansium or not to take it at all.

Taking Ansium with other medications

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

Your doctor should be informed if you are taking other medications (including those not prescribed). This is extremely important because the simultaneous use of more than one medication may increase or decrease its effect.

Therefore, do not take other medications at the same time as Ansium unless your doctor is informed and approves it in advance. For example, tranquilizers, sleep inducers, and similar medications act on the brain and nerves and may reinforce the effect of Ansium.

The cisapride, cimetidine, ketoconazole, fluvoxamine, fluoxetine, and omeprazole increase the sedative effect of Ansium temporarily, increasing the risk of drowsiness.

Similarly, the metabolism of phenytoin may be affected if you are taking Ansium, so if you are taking this medication, your doctor will adjust the doses of the same.

Patients with Parkinson's disease treated with levodopa cannot take this medication. Certain enzyme inhibitors may potentiate the activity of this medication.

Since it contains sulpiride, inform your doctor if you are taking any of the following medications:

• Antiarrhythmic agents such as quinidine, disopyramide, amiodarone, and sotalol.
• Other medications such as cisapride, thioridazine, intravenous erythromycin, vincamine, halofantrine, pentamidine, enoxacin, methadone, pimozide, haloperidol, and sultopride.
• Medications that induce bradycardia such as diltiazem and verapamil, clonidine, guanfacine; digitals.
• Medications that induce a decrease in potassium and magnesium levels.
• Depressants of the central nervous system including narcotics, analgesics, antihistamines H1 sedatives, barbiturates, benzodiazepines, and other anxiolytic drugs.
• Lithium salts (medications for the treatment of manic-depressive disorder or bipolar affective disorder).
• Sucralfate (medication for treating and preventing duodenal ulcers).
• Antacids.
• Medications to lower blood pressure.
• Lithium.

Take note that these instructions may also apply to medications that have been used before or may be used later.

Taking Ansium with medications, drinks, and alcohol

During treatment, avoid alcoholic beverages. The effect of alcohol may potentiate sedation and this may affect your ability to drive or operate machinery. If you need additional information on this point, consult your doctor.

Do not ingest grapefruit juice during treatment with Ansium.

Pregnancy and breastfeeding

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

Your doctor should be informed if you are pregnant or suspect you may be pregnant, or if you intend to become pregnant. The doctor will then decide whether to take Ansium.

Newborns of mothers who have used Ansium in the last trimester of pregnancy may present the following symptoms: tremors, muscle rigidity, and/or weakness, drowsiness, agitation, breathing problems, and feeding problems. If your newborn presents any of these symptoms, contact your doctor.

Benzodiazepines are excreted in breast milk, so you should consult your doctor about the advisability of taking Ansium while breastfeeding.

Driving and operating machinery

Diazepam may alter your ability to drive or operate machinery, as it may produce drowsiness, decrease your attention, or decrease your reaction time. The appearance of these effects is more likely at the beginning of treatment or when the dose is increased. Do not drive or operate machinery if you experience any of these effects.

Sulpiride may produce symptoms such as drowsiness, dizziness, or visual disturbances, and decrease your reaction time. These effects, as well as the disease itself, may make it difficult for you to drive vehicles or operate machinery. Therefore, do not drive or operate machinery, or practice other activities that require special attention, until your doctor evaluates your response to this medication.

Ansium contains lactose

If your doctor has indicated that you have a lactose intolerance, consult with him before taking this medication.

Follow exactly the medication administration instructions contained in this leaflet or those indicated by your doctor or pharmacist. Depending on the nature of your illness, your age and weight, your doctor will prescribe the appropriate dose.

Swallow Ansium capsules without chewing them, along with water or another non-alcoholic beverage.

The usual doses are as follows:

1 capsule (50 mg of sulpiride + 5 mg of diazepam) to 4 capsules (200 mg of sulpiride + 20 mg of diazepam) per day.

Never change the dose that has been prescribed for you. If you believe the medication's effect is too strong or too weak, consult your doctor.

No individual dose should exceed the indicated limits, and the total daily dose should not either, unless your doctor prescribes a higher dose.

For the treatment of anxiety, the treatment duration will be 8 to 12 weeks, including the gradual withdrawal period. For the treatment of insomnia, the treatment duration will be a few days to two weeks, with a maximum duration of four weeks including the gradual withdrawal period.

To avoid withdrawal symptoms, do not stop taking Ansium abruptly, especially if you have been taking it for a long time.

Ansium should be taken at least two hours before taking antacids and sucralfate.

In elderly patients or those with liver or kidney disorders, or muscle weakness, the doctor will prescribe a lower initial dose and a more gradual dose adjustment.In cases of severe renal insufficiency, treatment will be suspended.

Taking more Ansium than you should

In case of overdose, with Sulpiride, muscle spasms of the face, neck, and tongue may appear. Some patients may develop parkinsonian manifestations (tremor, rigidity) with vital risk and coma.

There is no specific antidote for Sulpiride, the treatment is only symptomatic and hemodialysis is partially effective for eliminating the drug. In case of overdose, implement the appropriate supportive measures, recommending close monitoring of vital functions and cardiac function control until the patient recovers.

In case of severe extrapyramidal symptoms (tremor, increased muscle tone, decreased movement, hypersalivation, etc.), anticholinergic agents should be administered.

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 taken.

Missing a dose of Ansium

If you forget to take a dose, do not try to correct it by taking a double dose the next time, but rather continue with the normal dose.

Stopping treatment with Ansium

Upon cessation of administration, restlessness, anxiety, insomnia, lack of concentration, headache, and hot flashes may appear. It is not generally recommended to stop medication abruptly without gradually reducing the dose, according to the doctor's instructions.

If you have any other doubts about the use of the medication, ask your doctor or pharmacist.

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

DIAZEPAM

In addition to the beneficial effects of Ansium, undesirable effects may occur, even when the medicine is used properly.

Most patients tolerate Ansium well, but some, especially at the beginning of treatment, may feel a bit tired or drowsy during the day.

Occasionally, other side effects of the type of confusion, decreased alertness, numbness, constipation, depression, diplopia (double vision), ataxia (inability to coordinate voluntary muscle movements), difficulty articulating words, digestive alterations, heart rhythm alterations, headache, hypotension, circulatory alterations, increased or decreased libido, nausea, dry mouth or hypersalivation (excessive salivation), incontinence or urinary retention, skin eruptions, stuttering, tremor, dizziness, and blurred vision have been described.The most common skin reactions are inflammation (skin inflammation), urticaria (red rashes), and pruritus (uncomfortable skin itching that causes the desire to scratch the affected area.

Very rarely, an increase in transaminases and alkaline phosphatase has been reported, as well as jaundice(yellowish discoloration of the skin and eyes), and cardiac arrest.

An increase in the risk of falls and fractures has been observed in elderly patients and in patients taking other sedatives (including alcoholic beverages) at the same time.It is known that when benzodiazepines are used, adverse effects on behavior such as restlessness, agitation, irritability, delirium (incoherence of ideas), nightmares, hallucinations, psychosis, or inappropriate behavior can occur. These reactions are more common in the elderly and in children. If these effects occur, you should discontinue treatment and contact your doctor immediately.

On the other hand, the use of benzodiazepines can lead to dependence, mainly when the medicine is taken continuously for a long time. It is not generally recommended to stop treatment abruptly, always following the doctor's instructions.

Amnesia (memory loss) may appear at normal doses, and the risk increases with increased doses. Amnestic effects can be associated with behavioral alterations.

The use of benzodiazepines can unmask an existing depression.

SULPIRIDA

The following side effects due to Sulpirida may be:

Blood and lymphatic system disorders

• Rare (may affect up to 1 in 100 patients): leukopenia (decrease in the numberof white blood cells) (see “Warnings and precautions”).

• Unknown frequency: neutropenia (decrease in the number of white blood cells called

neutrophils) and agranulocytosis (decrease in a type of white blood cell, granulocytes) (see

“Warnings and precautions”).

Immune system disorders

• Unknown frequency: anaphylactic reactions (severe allergic reaction), urticaria, respiratory difficulty (dyspnea), decreased blood pressure, and anaphylactic shock (severe allergic reactionthat can put your life at risk).

Endocrine disorders

• Common (may affect up to 1 in 10 patients): increase in normal levels of prolactin hormone.

Mental disorders

• Common (may affect up to 1 in 10 patients): insomnia (difficulty sleeping).

Nervous system disorders

• Common (may affect up to 1 in 10 patients): sedation or somnolence, extrapyramidal disorder (these symptoms are generally reversible if antiparkinsonian medication is administered), parkinsonism, tremor, akathisia (inability of the person to sit or remain seated).

• Rare (may affect up to 1 in 100 patients): increased muscle tone, dyskinesia (abnormal and involuntary movements), dystonia (muscle contractions).

• Unknown frequency: oculogyric crisis (involuntary deviation of the gaze).

• Unknown frequency: convulsions, neuroleptic malignant syndrome (see “Warnings and precautions”), a complication characterized by elevated body temperature, muscle rigidity, which can even lead to death, decreased or slowed involuntary movements (hypokinesia), tardive dyskinesia (characterized by rhythmic and involuntary movements mainly of the tongue and/or face, as has been reported with all neuroleptics, after administration for more than 3 months. Antiparkinsonian medication is ineffective or may worsen symptoms).

Cardiac disorders

• Rare (may affect up to 1 in 1000 patients): ventricular arrhythmia (change in heart rhythm), ventricular tachycardia (rapid succession of heartbeats whose cause resides in the ventricles), ventricular fibrillation.
• Unknown frequency: prolonged QT interval (problems with heart conduction), cardiac arrest, torsades de pointes (alteration of heart rhythm), sudden death (see “Warnings and precautions”).

Vascular disorders

• Rare (may affect up to 1 in 100 patients): orthostatic hypotension (decrease in blood pressure when standing up).
• Unknown frequency: increased blood pressure, venous thrombosis, especially in the legs (symptoms include swelling, pain, and redness in the leg), these clots can move through the blood vessels, to the lungs, causing chest pain and difficulty breathing. If you experience any of these symptoms, go to your doctor immediately.

Gastrointestinal disorders

• Rare (may affect up to 1 in 100 patients): increased salivation.

Hepatobiliary disorders

• Common (may affect up to 1 in 10 patients): increase in liver enzymes.

Skin and subcutaneous tissue disorders

• Common (may affect up to 1 in 10 patients): maculopapular rash (appearance of red patches and papules on the skin).

Musculoskeletal and connective tissue disorders

• Unknown frequency: torticollis, trismus (muscle contraction of the jaw).

Pregnancy, puerperium, and perinatal diseases

• Unknown frequency: extrapyramidal symptoms (involuntary movements), withdrawal syndrome in newborns (see “Pregnancy and lactation”).

Reproductive and breast disorders

• Common (may affect up to 1 in 10 patients): chest pain, milk secretion by the breasts outside the pregnancy period.
• Rare (may affect up to 1 in 100 patients): absence of menstruation in a fertile woman, breast enlargement, abnormal orgasm, impotence.
• Unknown frequency: breast enlargement in men.

General disorders and administration site conditions

• Common (may affect up to 1 in 10 patients): weight gain.

A small increase in the number of deaths in elderly patients with dementia treated with antipsychotics has been reported, compared to those who do not receive this treatment.

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 prospectus. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use, Website:www.notificaRAM.es. By reporting adverse reactions, 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 30°C.

No use this medication after the expiration date that appears in the box after CAD. La expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medicines at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and unused medicines. By doing so, you will help protect the environment.

Composition of Ansium

• The active principles are diazepam and sulpiride.
• The other components are pregelatinized cornstarch, lactose monohydrate, hydrated colloidal silica, talc (E-553b), magnesium stearate (E-572). Gelatin capsule: gelatin, titanium dioxide (E-171), yellow iron oxide (E-172), black iron oxide (E-172) and indigo carmine (E-132).

Appearance of the product and contents of the packaging

The hard capsules are opaque, with a white body and a blue head.

It is marketed in packaging of 30 hard capsules.

Holder of the marketing authorization and responsible for manufacturing

Holder of marketing authorization

Neuraxpharm Spain, S.L.U.

Avda. Barcelona, 69

08970 Sant Joan Despí (Barcelona)

Spain

Responsible for manufacturing

Neuraxpharm Pharmaceuticals, S.L.

Avda. Barcelona, 69

08970 Sant Joan Despí (Barcelona)

Spain

Last review date of this leaflet: October 2021

The detailed and updated information on this medicine is available on the website of the Spanish Agency of Medicines and Medical Products (AEMPS)www.aemps.gob.es